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Lin W, Ruishi X, Caijiao X, Haoming L, Xuefeng H, Jiyou Y, Minqiang L, Shuo Z, Ming Z, Dongyang L, Xiaoxue F. Potential applications and mechanisms of natural products in mucosal-related diseases. Front Immunol 2025; 16:1594224. [PMID: 40370438 PMCID: PMC12075308 DOI: 10.3389/fimmu.2025.1594224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2025] [Accepted: 04/09/2025] [Indexed: 05/16/2025] Open
Abstract
The mucosal barrier serves as a crucial defense against external pathogens and allergens, being widely distributed across the respiratory, gastrointestinal, urogenital tracts, and oral cavity. Its disruption can lead to various diseases, including inflammatory bowel disease, asthma, urinary tract infections, and oral inflammation. Current mainstream treatments for mucosa-associated diseases primarily involve glucocorticoids and immunosuppressants, but their long-term use may cause adverse effects. Therefore, the development of safer and more effective therapeutic strategies has become a focus of research. Natural products, with their multi-target and multi-system regulatory advantages, offer a promising avenue for the treatment of mucosal diseases. This review summarizes the potential applications of natural products in diseases of mucosal barrier dysfunction through mechanisms such as immune modulation, inflammation inhibition, tight junction protein restoration, and gut microbiota regulation, with the aim of providing insights for the exploration of novel therapeutic strategies.
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Affiliation(s)
- Wang Lin
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Xie Ruishi
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Xu Caijiao
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Luo Haoming
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Hua Xuefeng
- The First People’s Hospital of Guangzhou, Department of Hepatobiliary and Pancreatic Surgery, Guangzhou, China
| | - Yao Jiyou
- The First People’s Hospital of Guangzhou, Department of Hepatobiliary and Pancreatic Surgery, Guangzhou, China
| | - Lu Minqiang
- The First People’s Hospital of Guangzhou, Department of Hepatobiliary and Pancreatic Surgery, Guangzhou, China
| | - Zhou Shuo
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Zhu Ming
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Li Dongyang
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Fang Xiaoxue
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
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Zheng Y, Li Y, Yu B, Luo Y, Huang Z, Zheng P, Mao X, Dai Z, Yu J, Yan H, Luo J, He J. Dietary supplementation of grape seed proanthocyanidins improves growth performance, carcass traits, and meat quality in growing-finishing pigs. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2025; 20:200-210. [PMID: 39967699 PMCID: PMC11833782 DOI: 10.1016/j.aninu.2024.10.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 10/01/2024] [Accepted: 10/21/2024] [Indexed: 02/20/2025]
Abstract
Grape seed proanthocyanidin (GSP) is a type of plant polyphenol with a wide variety of biological activities, such as antioxidant properties. This study investigated the effects of GSP supplementation on growth performance and meat quality in growing-finishing pigs. A total of 180 pigs (with an initial average body weight of 30.37 ± 0.66 kg) were randomly assigned to five treatments: a control diet or a control diet supplemented with GSP at 15, 30, 60, and 120 mg/kg. Each treatment group comprised six replicate pens (6 pigs per pen). Results showed that GSP supplementation linearly increased the average daily gain (P = 0.048) and quadratically decreased the feed intake to gain ratio (P = 0.049) with the lowest values at 30 and 60 mg/kg GSP. Serum concentrations of immunoglobulins (Ig) (IgA, IgG, IgM), total antioxidative capacity, catalase, and total superoxide dismutase were elevated with the peak levels at 30 mg/kg GSP (P < 0.05). Serum glutathione peroxidase increased and malondialdehyde decreased quadratically (P < 0.05), with peak and trough levels at 120 and 60 mg/kg GSP, respectively. The GSP also improved dressing percentage and muscle redness (a∗45 min) with optimal levels at 30 and 60 mg/kg (P < 0.05). Additionally, GSP supplementation quadratically reduced the muscle yellowness (b∗24 h) and shear force (P < 0.05), with the lowest values at 120 mg/kg. The expression level of myosin heavy chain I in muscle was quadratically increased with maximum expression at 30 and 60 mg/kg (P = 0.015). Furthermore, the expression levels of fatty acid synthase, phosphoenolpyruvate carboxykinase (PEPCK), and glucokinase in the muscle were decreased quadratically (P < 0.05) with the lowest values at 120 mg/kg. Additionally, GSP supplementation at 60 mg/kg upregulated the expression of hepatic hormone-sensitive triglyceride lipase and PEPCK (P < 0.05). These results suggest that GSP enhances carcass characteristics and meat quality in growing-finishing pigs, potentially through improved antioxidative capacity, modified muscle fiber type distribution, and altered glucose-lipid metabolism in muscle and liver.
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Affiliation(s)
- Yuyang Zheng
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Yan Li
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Bing Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Yuheng Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Zhingqing Huang
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Ping Zheng
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Xiangbing Mao
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Zhaolai Dai
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Jie Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Hui Yan
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Junqiu Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Jun He
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
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Yu L, Liu S, Liu J, Li J, Zhang W, Lin L, Yang L, Zheng G. Smilaxchina L. polyphenols inhibit LPS-induced macrophage M1 polarization to alleviate inflammation through NF-κB signaling pathway in vitro and in vivo. JOURNAL OF ETHNOPHARMACOLOGY 2025; 342:119355. [PMID: 39800244 DOI: 10.1016/j.jep.2025.119355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 01/09/2025] [Accepted: 01/10/2025] [Indexed: 01/15/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE As an important component of the cell wall of Gram-negative bacteria, lipopolysaccharide (LPS) is an important inducer of inflammation in humans. Smilax china L. is known for its diverse bioactive functions, particularly its anti-inflammatory effects. AIM OF THE STUDY This study aimed to investigate the bioactive function of Smilax china L. polyphenols (SCLP) on LPS-induced inflammation. MATERIALS AND METHODS Inflammation in RAW264.7 macrophages and mice were induced using LPS. The cytotoxicity of SCLP was investigated by MTT assay. Inflammatory factors were detected by ELISA and RT-PCR. The expression of NF-κB pathway-related proteins was analyzed by Western Blotting. RESULTS The results demonstrated that SCLP significantly reduced the levels of pro-inflammatory factors (TNF-α, IL-1β, and IL-6) and inhibited M1 polarization of macrophages in both RAW264.7 macrophages and mice (p < 0.05). Western Blotting analysis revealed that the levels of NF-κB signaling pathway-associated proteins (p-p65, p-IKB, p-IKK) were significantly reduced (p < 0.05). Notably, SCLP significantly downregulated the expression of pro-apoptotic proteins, while upregulating the expression of anti-apoptotic proteins in RAW264.7 macrophages (p < 0.05). Additionally, the levels of antioxidant enzymes were enhanced in mice, suggesting a potential reduction in the inflammatory response. CONCLUSIONS These findings indicated that SCLP might inhibit LPS-induced M1 polarization through the NF-κB signaling pathway, thereby reducing inflammation. Consequently, SCLP might serve as a promising bioactive substance for preventing inflammation-related injury.
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Affiliation(s)
- Longhui Yu
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, 330045, China
| | - Shanshan Liu
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, 330045, China
| | - Jiluan Liu
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, 330045, China
| | - Jingen Li
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, 330045, China
| | - Wenkai Zhang
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, 330045, China
| | - Lezhen Lin
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, 330045, China
| | - Licong Yang
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350108, China.
| | - Guodong Zheng
- Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, 330045, China.
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Waly DA, Abou Zeid AH, Mohammed RS, Moustafa SF, El-Halawany AM, Ahmed KA, Sleem AA, El-Kashoury ESA. UPLC/HR-ESI-MS/MS and GC/MS profiling of Eriobotrya japonica L. fruit in correlation to its antioxidant, anti-inflammatory, and anti-arthritic effects. J Food Sci 2024; 89:9879-9900. [PMID: 39455243 DOI: 10.1111/1750-3841.17468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 09/09/2024] [Accepted: 09/25/2024] [Indexed: 10/28/2024]
Abstract
Eriobotrya japonica Lindl. (Loquat) fruit is a subtropical edible fruit originally from China. It grows well in Egypt, but it is not widely known. In the current study, the fruit was extracted with 80% ethanol to get the total ethanol extract (TEE). A part of which was fractionated by dichloromethane to yield polar and nonpolar fractions (PF and NPF). The antioxidant and anti-inflammatory activities of the TEE were in vitro evaluated. The complete Freund's adjuvant (CFA) arthritis model was used to explore the in vivo biological assessment of the anti-arthritic properties in vivo of the TEE, PF, and NPF of the fruit. Additionally, the inspected limbs detached from all animals were subjected to histological inspection. Moreover, GC/MS analysis of the unsaponifiable (USF) and saponifiable (SF) fractions of the NPF was performed. Furthermore, 64 metabolites from various chemical classes were identified using UHPLC/HR-MS/MS analysis of the TEE of the fruit in both positive and negative ionization modes. The positive ionization mode of loquat fruit allowed for the first time the detection of two kinds of lyso-glycerophospholipids (Lyso-GPLs): lyso-glycerophosphoethanolamines (Lyso-PtdEtn) and lyso-glycerophosphocholines (Lyso-PtdCho). The fruit extracts exhibited a notable in vivo anti-arthritic activity by decreasing paw thickness in the treated rats and adjusting the inflammatory mediators. The TEE showed the highest anti-arthritic activity, followed by the PF that showed an observed activity, while the NPF exhibited the lowest activity. Histopathological findings showed a marked improvement in the arthritic condition of the excised limbs. Thus, E. japonica fruit may be considered as a promising natural antioxidant and anti-arthritic agent.
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Affiliation(s)
- Dina Atef Waly
- Department of Pharmacognosy, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Giza, Egypt
| | - Aisha Hussein Abou Zeid
- Department of Pharmacognosy, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Giza, Egypt
| | - Reda Sayed Mohammed
- Department of Pharmacognosy, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Giza, Egypt
| | | | | | - Kawkab A Ahmed
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Amany Ameen Sleem
- Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt
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Kim SM, Joh JH, Jung IM, Kim MJ, Lee SS, Hwang HP, Kang JM, Jung HJ, Yang SS, Min SK, Yoo YS, Gwon JG, Park HS, Lee T. Vitis Vinifera Seed Extract Versus Micronized Purified Flavonoid Fraction for Patients with Chronic Venous Disease: A Randomized Noninferiority Trial. Ann Vasc Surg 2024; 109:177-186. [PMID: 39009117 DOI: 10.1016/j.avsg.2024.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 06/17/2024] [Accepted: 06/17/2024] [Indexed: 07/17/2024]
Abstract
BACKGROUND Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was noninferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease. METHODS In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score at 4 and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline. RESULTS In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant intergroup difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval -1.65 to 5.72). The lower limit of the 95% confidence interval was within the predefined noninferiority margin of 6.9. Furthermore, the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score scores significantly decreased at 4 and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract. CONCLUSIONS Vitis vinifera seed extract was noninferior to MPFF in relieving venous symptoms and improving the quality of life in patients with chronic venous disease.
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Affiliation(s)
- Suh Min Kim
- Department of Surgery, Chung-Ang University College of Medicine, Chung-Ang University Hospital, Seoul, Korea
| | - Jin Hyun Joh
- Department of Surgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - In Mok Jung
- Division of Vascular and Transplantation Surgery, Department of Surgery, SMG-SNU Seoul Boramae Medical Center, Seoul, Korea
| | - Mi Jin Kim
- Department of Surgery, Jeonbuk National University Medical School and Hospital, Jeonju, Korea
| | - Sang Su Lee
- Research Institute for Convergence of Biomedical Science and Technology, Division of Vascular and Endovascular Surgery, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Pusan, Korea
| | - Hong Pil Hwang
- Department of Surgery, Jeonbuk National University Medical School and Hospital, Jeonju, Korea
| | - Jin Mo Kang
- Division of Vascular Surgery, Department of Surgery, Gachon University of Medicine and Science, Incheon, Korea
| | - Hyuk Jae Jung
- Endovascular and Vascular and Transplantation Division, Department of Surgery, Pusan National University School of Medicine, Pusan, Korea
| | - Shin-Seok Yang
- Division of Vascular Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung-Kee Min
- Division of Vascular Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Young Sun Yoo
- Department of Surgery, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea
| | - Jun Gyo Gwon
- Division of Vascular Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Hyung Sub Park
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Taeseung Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
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Nazdar N, Imani A, Abtahi Froushani SM, Farzaneh M, Sarvi Moghanlou K. Antioxidative properties, phenolic compounds, and in vitro protective efficacy of multi-herbal hydro-alcoholic extracts of ginger, turmeric, and thyme against the toxicity of aflatoxin B 1 on mouse macrophage RAW264.7 cell line. Food Sci Nutr 2024; 12:8013-8029. [PMID: 39479629 PMCID: PMC11521708 DOI: 10.1002/fsn3.4257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 05/14/2024] [Accepted: 05/20/2024] [Indexed: 11/02/2024] Open
Abstract
Aflatoxin B1 (AFB1), the most potent toxic and carcinogenic secondary fungal metabolite, has frequently been reported in food/feed. Nowadays, herbal extracts are considered safe dietary additives to reduce the toxicity of such compounds. The protective capability of various combinations of hydro-alcoholic extracts (HAEs) of ginger, turmeric, and Shirazi thyme, against the toxicity of AFB1 on the RAW264.7 cell line was investigated. The RAW264.7 cells were exposed to six different concentrations of AFB1 (0.09, 0.18, 0.37, 0.75, 1.5, and 3 μg mL-1) for 48 h to determine the IC50 of AFB1. AFB1 was estimated to have an IC50 of 1.5 μg mL-1 for RAW264.7 cells. Then, the cells were simultaneously incubated with 1.5 μg mL-1 AFB1 and the HAEs for 24 h. The HAEs significantly reduced the toxicity of AFB1 in RAW264.7 cells. HAE of Shirazi thyme showed the highest amount of total phenol content (TPC) and the highest DPPH• activity. In addition, a combination of ginger, turmeric, and Shirazi thyme extract showed the highest antioxidant activity. Rutin, quercetin, and apigenin were the main phenolic components of ginger HAE. A significantly positive correlation was observed between TPC of hydro-alcoholic extract with ferric reducing antioxidant power (FRAP) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) values. Consequently, the simultaneous consumption of such extracts is recommended to protect the cells against dietary toxins.
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Affiliation(s)
- Nina Nazdar
- Department of Fisheries, Faculty of Natural ResourcesUrmia UniversityUrmiaIran
| | - Ahmad Imani
- Department of Fisheries, Faculty of Natural ResourcesUrmia UniversityUrmiaIran
| | | | - Mohsen Farzaneh
- Department of AgricultureMedicinal Plants and Drugs Research Institute, Shahid Beheshti UniversityTehranIran
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Shan Q, Wang X, Yang H, Zhu Y, Wang J, Yang G. Bacillus cereus CwpFM induces colonic tissue damage and inflammatory responses through oxidative stress and the NLRP3/NF-κB pathway. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 933:173079. [PMID: 38735331 DOI: 10.1016/j.scitotenv.2024.173079] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 03/30/2024] [Accepted: 05/07/2024] [Indexed: 05/14/2024]
Abstract
Bacillus cereus (B. cereus) from cow milk poses a threat to public health, causing food poisoning and gastrointestinal disorders in humans. We identified CwpFM, an enterotoxin from B. cereus, caused oxidative stress and inflammatory responses in mouse colon and colonic epithelial cells. Colon proteomics revealed that CwpFM elevated proteins associated with inflammation and oxidative stress. Notably, CwpFM induced activation of the NLRP3/NF-κB signaling, but suppressed antioxidant NFE2L2/HO-1 expression in the intestine and epithelial cells. Consistently, CwpFM exposure led to cytotoxicity and ROS accumulation in Caco-2 cells in a dose-dependent manner. Further, NAC (ROS inhibitor) treatment abolished NLRP3/NF-κB activation due to CwpFM. Moreover, overexpression of Nfe2l2 or activation of NFE2L2 by NK-252 reduced ROS production and inhibited activation of the NLRP3/NF-κB pathway. Inhibition of NF-κB by ADPC and/or suppression of NLRP3 by MCC950 attenuated CwpFM-induced inflammatory responses in Caco-2 cells. Collectively, CwpFM induced oxidative stress and NLRP3/NF-κB activation by inhibiting the NFE2L2/HO-1 signaling and ROS accumulation, leading to the development of intestinal inflammation. Our data elucidate the role of oxidative stress and innate immunity in CwpFM enterotoxicity and contribute to developing diagnostic and therapeutic products for B. cereus-related food safety issues.
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Affiliation(s)
- Qiang Shan
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Sanya Institute of China Agricultural University, Sanya 572025, China
| | - Xue Wang
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Sanya Institute of China Agricultural University, Sanya 572025, China
| | - Hao Yang
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Sanya Institute of China Agricultural University, Sanya 572025, China
| | - Yaohong Zhu
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Sanya Institute of China Agricultural University, Sanya 572025, China
| | - Jiufeng Wang
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Sanya Institute of China Agricultural University, Sanya 572025, China.
| | - Guiyan Yang
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
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Chu C, Ru H, Chen Y, Xu J, Wang C, Jin Y. Gallic acid attenuates LPS-induced inflammation in Caco-2 cells by suppressing the activation of the NF-κB/MAPK signaling pathway. Acta Biochim Biophys Sin (Shanghai) 2024; 56:905-915. [PMID: 38516705 PMCID: PMC11214974 DOI: 10.3724/abbs.2024008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 12/20/2023] [Indexed: 03/23/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by intestinal barrier dysfunction, inflammatory synergistic effects and excessive tissue injury. Gallic acid (GA) is renowned for its remarkable biological activity, encompassing anti-inflammatory and antioxidant properties. However, the underlying mechanisms by which GA protects against intestinal inflammation have not been fully elucidated. The aim of this study is to investigate the effect of GA on the inflammation of a lipopolysaccharide (LPS)-stimulated human colon carcinoma cell line (Caco-2) and on the intestinal barrier dysfunction, and explore the underlying molecular mechanism involved. Our findings demonstrate that 5 μg/mL GA restores the downregulation of the mRNA and protein levels of Claudin-1, Occludin, and ZO-1 and decreases the expressions of inflammatory factors such as IL-6, IL-1β and TNF-α induced by LPS. In addition, GA exhibits a protective effect by reducing the LPS-enhanced early and late apoptotic ratios, downregulating the mRNA levels of pro-apoptotic factors ( Bax, Bad, Caspase-3, Caspase-8, and Caspase-9), and upregulating the mRNA levels of anti-apoptotic factor Bcl-2 in Caco-2 cells. GA also reduces the levels of reactive oxygen species increased by LPS and restores the activity of antioxidant enzymes, namely, superoxide dismutase and catalase, as well as the level of glutathione. More importantly, GA exerts its anti-inflammatory effects by inhibiting the LPS-induced phosphorylation of key signaling molecules in the NF-κB/MAPK pathway, including p65, IκB-α, p38, JNK, and ERK, in Caco-2 cells. Overall, our findings show that GA increases the expressions of tight junction proteins, reduces cell apoptosis, relieves oxidative stress and suppresses the activation of the NF-κB/MAPK pathway to reduce LPS-induced intestinal inflammation in Caco-2 cells, indicating that GA has potential as a therapeutic agent for intestinal inflammation.
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Affiliation(s)
- Chu Chu
- />College of Biotechnology and BioengineeringZhejiang University of TechnologyHangzhou310032China
| | - Huan Ru
- />College of Biotechnology and BioengineeringZhejiang University of TechnologyHangzhou310032China
| | - Yuyan Chen
- />College of Biotechnology and BioengineeringZhejiang University of TechnologyHangzhou310032China
| | - Jinhua Xu
- />College of Biotechnology and BioengineeringZhejiang University of TechnologyHangzhou310032China
| | - Caihong Wang
- />College of Biotechnology and BioengineeringZhejiang University of TechnologyHangzhou310032China
| | - Yuanxiang Jin
- />College of Biotechnology and BioengineeringZhejiang University of TechnologyHangzhou310032China
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Zeng J, Weng Y, Lai T, Chen L, Li Y, Huang Q, Zhong S, Wan S, Luo L. Procyanidin alleviates ferroptosis and inflammation of LPS-induced RAW264.7 cell via the Nrf2/HO-1 pathway. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:4055-4067. [PMID: 38010399 DOI: 10.1007/s00210-023-02854-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 11/12/2023] [Indexed: 11/29/2023]
Abstract
Inflammation is a common occurrence in many medical conditions and is a natural defense mechanism of the human body. Ferroptosis, an iron-dependent form of cell death related to lipid peroxide build-up, has been found to be involved in inflammation. The anti-inflammatory effects of procyanidin, however, are not yet fully understood. Through network pharmacology and bioinformatics analysis, it was suggested that procyanidin could modulate ferroptosis and cause anti-inflammatory effects on RAW264.7 cells. This was further evidenced through molecular docking, molecular dynamics, and in vitro experiments. The results indicated that procyanidin could diminish inflammation in LPS-induced RAW264.7 cells by regulating ferroptosis via the Nrf2/HO-1/Keap-1 pathway. In conclusion, procyanidin supplementation might be an effective way to reduce inflammation by decreasing the release of inflammatory cytokines and suppressing ferroptosis.
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Affiliation(s)
- Jiayan Zeng
- The First Clinical College, Guangdong Medical University, Zhanjiang, 524023, Guangdong, China
| | - Yanmin Weng
- The First Clinical College, Guangdong Medical University, Zhanjiang, 524023, Guangdong, China
| | - Tianli Lai
- The First Clinical College, Guangdong Medical University, Zhanjiang, 524023, Guangdong, China
| | - Lan Chen
- The First Clinical College, Guangdong Medical University, Zhanjiang, 524023, Guangdong, China
| | - Ying Li
- The First Clinical College, Guangdong Medical University, Zhanjiang, 524023, Guangdong, China
| | - Qiqi Huang
- The First Clinical College, Guangdong Medical University, Zhanjiang, 524023, Guangdong, China
| | - Saiyi Zhong
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Seafood, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, 524088, China
| | - Shibiao Wan
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
| | - Lianxiang Luo
- The Marine Biomedical Research Institute, Guangdong Medical University, No. 2 Wenming East Road, Xiashan District, Zhanjiang, 524023, Guangdong, China.
- The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong, 524023, China.
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10
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Amarowicz R, Pegg RB. Condensed tannins-Their content in plant foods, changes during processing, antioxidant and biological activities. ADVANCES IN FOOD AND NUTRITION RESEARCH 2024; 110:327-398. [PMID: 38906590 DOI: 10.1016/bs.afnr.2024.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/23/2024]
Abstract
Condensed tannins are considered nutritionally undesirable, because they precipitate proteins, inhibit digestive enzymes, and can affect the absorption of vitamins and minerals. From the consumer's point of view, they impart astringency to foods. Yet, they are viewed as a double-edged sword, since they possess antioxidant and anti-inflammatory activities. Intake of a small quantity of the right kind of tannins may in fact be beneficial to human health. This chapter reports on the chemical structure of condensed tannins, their content in plants and food of plant origin, how they are extracted, and methods for their determination. A description of the effects of processing on condensed tannins is discussed and includes soaking, dehulling, thermal processing (i.e., cooking, boiling, autoclaving, extrusion), and germination. The astringency of condensed tannins is described in relation to their interactions with proteins. Finally, details about the biological properties of condensed tannins, including their antimicrobial, anti-inflammatory, anticancer, anti-diabetic, and anti-obesity activities, are reviewed.
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Affiliation(s)
- Ryszard Amarowicz
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
| | - Ronald B Pegg
- Department of Food Science & Technology, The University of Georgia, Athens, GA, United States
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11
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Li XW, Qiu F, Liu Y, Yang JZ, Chen LJ, Li JH, Liu JL, Hsu C, Chen L, Zeng JH, Xie XL, Wang Q. Inulin alleviates perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure-induced intestinal toxicity by reshaping the gut microbiota and suppressing the enteric-origin LPS/TLR4/NF-κb pathway in dams and pups. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 346:123659. [PMID: 38417603 DOI: 10.1016/j.envpol.2024.123659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/18/2024] [Accepted: 02/24/2024] [Indexed: 03/01/2024]
Abstract
Organophosphorus flame retardants (OPFRs), such as 2-ethylhexyl diphenyl phosphate (EHDPHP), are ubiquitously used, leading to pervasive environmental contamination and human health risks. While associations between EHDPHP and health issues such as disruption of hormones, neurotoxic effects, and toxicity to reproduction have been recognized, exposure to EHDPHP during perinatal life and its implications for the intestinal health of dams and their pups have largely been unexplored. This study investigated the intestinal toxicity of EHDPHP and the potential for which inulin was effective. Dams were administered either an EHDPHP solution or a corn oil control from gestation day 7 (GD7) to postnatal day 21 (PND21), with inulin provided in their drinking water. Our results indicate that inulin supplementation mitigates damage to the intestinal epithelium caused by EHDPHP, restores mucus-secreting cells, suppresses intestinal hyperpermeability, and abates intestinal inflammation by curtailing lipopolysaccharide leakage through reshaping of the gut microbiota. A reduction in LPS levels concurrently inhibited the inflammation-associated TLR4/NF-κB pathway. In conclusion, inulin administration may ameliorate intestinal toxicity caused by EHDPHP in dams and pups by reshaping the gut microbiota and suppressing the LPS/TLR4/NF-κB pathway. These findings underscore the efficacy of inulin as a therapeutic agent for managing health risks linked to EHDPHP exposure.
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Affiliation(s)
- Xiu-Wen Li
- Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Feng Qiu
- Department of Laboratory Medicine, The Seventh Affiliated Hospital of Southern Medical University, Foshan, Guangdong 528244, China
| | - Yi Liu
- Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Jian-Zheng Yang
- Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Li-Jian Chen
- Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Jia-Hao Li
- Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Jia-Li Liu
- Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Clare Hsu
- Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Long Chen
- Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Jia-Hao Zeng
- Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Xiao-Li Xie
- Department of Toxicology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, Guangdong 510515, China
| | - Qi Wang
- Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
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12
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Alomair MK, Alobaid AA, Almajed MAA, Alabduladheem LS, Alkhalifah EA, Mohamed ME, Younis NS. Grape Seed Extract and Urolithiasis: Protection Against Oxidative Stress and Inflammation. Pharmacogn Mag 2023. [DOI: 10.1177/09731296221145069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2023] Open
Abstract
Background Grape seed extract (GSE) has demonstrated various pharmacological actions. Urolithiasis is the occurrence of calculus in the renal system. The present study evaluated the anti-urolithic effect of GSE on ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Materials and Methods Rats were assigned into six groups; Normal control and Normal + GSE, in which rats received standard drinking water and GSE orally daily, respectively; Urolithiatic animals received EG with AC in drinking water for 28 days; Urolithiatic animals + GSE, in which rats were administered EG with AC in drinking water and GSE 100 and 200 mg/kg orally; and Urolithiatic + cystone, where rats received EG with AC in drinking water and 750 g/kg of cystone as a standard drug orally. Results Urolithiatic animals showed a significant decrease in excreted magnesium and citrate and antioxidant enzymes, whereas they exhibited amplified oxalate crystal numbers, urinary excreted calcium, phosphate, oxalate ions, uric acid, intensified renal function parameters, lipid peroxidation, and inflammatory mediators. Management with GSE and cystone significantly augmented urolithiasis inhibitors (excreted magnesium and citrate) and amplified the antioxidant enzymes’ activities. GSE reduced oxalate crystal numbers and urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid excretion, lessened renal function parameters, and declined lipid peroxidation and the inflammatory mediators. Conclusion GSE could protect against EG-induced renal stones as evidenced by mitigated kidney dysfunction, histological alterations, and oxalate crystal formation. This action may be related to the antioxidant as well as anti-inflammatory activities of the extracts.
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Affiliation(s)
- Manar Khalid Alomair
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Amjad Abdullah Alobaid
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Marwah Abdulaziz Ali Almajed
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Lama Salman Alabduladheem
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | | | - Maged Elsayed Mohamed
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Nancy Safwat Younis
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
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13
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Cuevas-Cianca SI, Romero-Castillo C, Gálvez-Romero JL, Juárez ZN, Hernández LR. Antioxidant and Anti-Inflammatory Compounds from Edible Plants with Anti-Cancer Activity and Their Potential Use as Drugs. Molecules 2023; 28:molecules28031488. [PMID: 36771154 PMCID: PMC9920972 DOI: 10.3390/molecules28031488] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/28/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023] Open
Abstract
Food is our daily companion, performing numerous beneficial functions for our bodies. Many of them can help to alleviate or prevent ailments and diseases. In this review, an extensive bibliographic search is conducted in various databases to update information on unprocessed foods with anti-inflammatory and antioxidant properties that can aid in treating diseases such as cancer. The current state of knowledge on inflammatory processes involving some interleukins and tumor necrosis factor-alpha (TNF-α) is reviewed. As well as unprocessed foods, which may help reduce inflammation and oxidative stress, both of which are important factors in cancer development. Many studies are still needed to take full advantage of the food products we use daily.
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Affiliation(s)
- Sofía Isabel Cuevas-Cianca
- Department of Chemical Biological Sciences, Universidad de las Américas Puebla, Ex Hacienda Sta. Catarina Mártir S/N, San Andrés Cholula 72810, Mexico
| | - Cristian Romero-Castillo
- Biotechnology Faculty, Deanship of Biological Sciences, Universidad Popular Autónoma del Estado de Puebla, 21 Sur 1103 Barrio Santiago, Puebla 72410, Mexico
- Chemistry Area, Deanship of Biological Sciences, Universidad Popular Autónoma del Estado de Puebla, 21 Sur 1103 Barrio Santiago, Puebla 72410, Mexico
| | - José Luis Gálvez-Romero
- ISSTE Puebla Hospital Regional, Boulevard 14 Sur 4336, Colonia Jardines de San Manuel, Puebla 72570, Mexico
| | - Zaida Nelly Juárez
- Chemistry Area, Deanship of Biological Sciences, Universidad Popular Autónoma del Estado de Puebla, 21 Sur 1103 Barrio Santiago, Puebla 72410, Mexico
- Correspondence: (Z.N.J.); (L.R.H.)
| | - Luis Ricardo Hernández
- Department of Chemical Biological Sciences, Universidad de las Américas Puebla, Ex Hacienda Sta. Catarina Mártir S/N, San Andrés Cholula 72810, Mexico
- Correspondence: (Z.N.J.); (L.R.H.)
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14
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Zamani M, Ashtary-Larky D, Hafizi N, Naeini F, Rezaei Kelishadi M, Clark CCT, Davoodi SH, Asbaghi O. The effect of grape products on liver enzymes: A systematic review and meta-analysis of randomized controlled trials. Phytother Res 2022; 36:4491-4503. [PMID: 36264051 DOI: 10.1002/ptr.7653] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 08/12/2022] [Accepted: 08/20/2022] [Indexed: 12/13/2022]
Abstract
The favorable influence of grape consumption on metabolic diseases has previously been shown in studies. We sought to assess the effects of grape intake on liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), in adults. We performed literature search in online databases, to find eligible randomized controlled trials (RCTs). we considered RCTs that met the following criteria: RCTs consisted of use of grape products on ALT, AST, and ALP in adults (≥18 years) with at least 2 weeks intervention duration. Pooling data from 11 trials showed that grape products intake significantly reduced ALP (p = .010), without any significant changes in ALT (p = .234) and AST (p = .300). In subgroup analysis, we found a significant reduction in ALP, ALT, and AST when the duration of intervention was ≥12 weeks, and when grape seed extract (GSE) was administered. The variable duration and dosage of intervention was one of the sources of bias in our meta-analysis. Additionally, participants involved in included studies had different physiological status and various age groups. Grape products administration may significantly improve ALT, AST, and ALP in adults in long-term interventions and/or when GSE is administered. It should be noted that the favorable effects of grape consumption were small and may not reach clinical importance.
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Affiliation(s)
- Mohammad Zamani
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Damoon Ashtary-Larky
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nadia Hafizi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatemeh Naeini
- Department of Clinical Nutrition, School of Nutritional Science, Tehran University of Medical Science, Tehran, Iran
| | - Mahnaz Rezaei Kelishadi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Cain C T Clark
- Centre for Intelligent Healthcare, Coventry University, Coventry, UK
| | - Sayed Hosein Davoodi
- National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Cancer Research Center, Shahid Beheshti University of Medical sciences, Tehran, Iran
| | - Omid Asbaghi
- Cancer Research Center, Shahid Beheshti University of Medical sciences, Tehran, Iran
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15
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Avocado (Persea americana Mill.) seeds compounds affect Helicobacter pylori infection and gastric adenocarcinoma cells growth. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
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16
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Metabolomic Profiling and Assessment of Phenolic Compounds Derived from Vitis davidii Foex Cane and Stem Extracts. Int J Mol Sci 2022; 23:ijms232314873. [PMID: 36499201 PMCID: PMC9735678 DOI: 10.3390/ijms232314873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/23/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Phenolic extracts from berry seeds have been extensively studied for their health benefits. However, few studies have been conducted on the effects of phenolic extracts from Vitis L. canes and berry stems. The Chinese spine grape (V. davidii Foex) is an important and widely distributed wild species of Vitis L. The present study explored the metabolomic profile and evaluated the antioxidant activity of phenolic compounds in extracts from V. davidii Foex. canes and stems, with a focus on their role in preventing DNA damage caused by free radicals and inhibiting the growth of breast (MCF-7) and cervical (HeLa) cancer cells. Total phenolic compounds in the dried berry stems of spine grapes were higher than that in vine canes. Analysis of the extracts showed that proanthocyanins, epicatechin, catechin, and phenolic acid were the main phenolic compounds in V. davidii Foex, but in higher quantities in berry stems than in vine canes. However, trans-resveratrol and kaempferol 3-O-glucoside were present in the vine canes but not in the berry stems. Antioxidant analysis by FRAP and ABTS showed that extracts from berry stems and vine canes had a higher antioxidant activity than thinned young fruit shoots before flowering, leaves, peel, pulp, and seeds in V. davidii Foex. Moreover, the antioxidant activity of extracts from berry stems was higher than that in other grape species, except for muscadine. In vitro analyses further showed that the extracts significantly increased H2O2 scavenging ability and conferred a protective effect against DNA damage. Furthermore, a low concentration of phenolic compounds in extracts from the vine canes and berry stems of spine grapes inhibited the proliferation of the MCF-7 and Hela cancer cells. These research results provided some important useful information for the exploitation of V. davidii Foex canes and berry stems and indicated that canes and stems of V. davidii Foex had good antioxidant properties, anticancer activity and prevented DNA damage, providing evidence for medical utilization of V. davidii Foex.
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17
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Ryyti R, Hämäläinen M, Leppänen T, Peltola R, Moilanen E. Phenolic Compounds Known to Be Present in Lingonberry ( Vaccinium vitis-idaea L.) Enhance Macrophage Polarization towards the Anti-Inflammatory M2 Phenotype. Biomedicines 2022; 10:3045. [PMID: 36551801 PMCID: PMC9776286 DOI: 10.3390/biomedicines10123045] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 11/10/2022] [Accepted: 11/15/2022] [Indexed: 11/29/2022] Open
Abstract
Macrophages are pleiotropic immune cells whose phenotype can polarize towards the pro-inflammatory M1 or anti-inflammatory M2 direction as a response to environmental changes. In obesity, the number of macrophages in adipose tissue is enhanced, and they shift towards the M1 phenotype. Activated M1 macrophages secrete pro-inflammatory cytokines and adipokines involved in the development of systemic low-grade inflammation, complicating obesity. Polyphenols are widely found in the vegetable kingdom and have anti-inflammatory properties. We and others have recently found that lingonberry (Vaccinium vitis-idaea L.) supplementation is able to prevent the development of low-grade inflammation and its metabolic consequences in experimentally induced obesity. In the present study, we investigated the effects of twelve phenolic compounds known to be present in lingonberry (resveratrol, piceid, quercetin, kaempferol, proanthocyanidins, delphinidin, cyanidin, benzoic acid, cinnamic acid, coumaric acid, caffeic acid, and ferulic acid) on macrophage polarization, which is a meaningful mechanism determining the low-grade inflammation in obesity. Mouse J774 and human U937 macrophages and commercially available phenolic compounds were used in the studies. Three of the twelve compounds investigated showed an effect on macrophage polarization. Resveratrol, kaempferol, and proanthocyanidins enhanced anti-inflammatory M2-type activation, evidenced as increased expression of Arg-1 and MRC-1 in murine macrophages and CCL-17 and MRC-1 in human macrophages. Resveratrol and kaempferol also inhibited pro-inflammatory M1-type activation, shown as decreased expression of IL-6, NO, and MCP-1 in murine macrophages and TNF-α and IL-6 in human macrophages. In the further mechanistic studies, the effects of the three active compounds were investigated on two transcription factors important in M2 activation, namely on PPARγ and STAT6. Resveratrol and kaempferol were found to enhance PPARγ expression, while proanthocyanidins increased the phosphorylation of STAT6. The results suggest proanthocyanidins, resveratrol, and kaempferol as active constituents that may be responsible for the positive anti-inflammatory effects of lingonberry supplementation in obesity models. These data also extend the previous knowledge on the anti-inflammatory effects of lingonberry and encourage further studies to support the use of lingonberry and lingonberry-based products as a part of a healthy diet.
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Affiliation(s)
- Riitta Ryyti
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, 33014 Tampere, Finland
| | - Mari Hämäläinen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, 33014 Tampere, Finland
| | - Tiina Leppänen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, 33014 Tampere, Finland
| | - Rainer Peltola
- Bioeconomy and Environment, Natural Resources Institute Finland, 96200 Rovaniemi, Finland
| | - Eeva Moilanen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, 33014 Tampere, Finland
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18
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Chauhan S, Saini D, Madan K. Screening of Phytoconstituents from Traditional Plants against SARSCoV-
2 using Molecular Docking Approach. LETT DRUG DES DISCOV 2022. [DOI: 10.2174/1570180819666220307163058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
The emergence of COVID-19 as a fatal viral disease encourages researchers to
develop effective and efficient therapeutic agents. The intervention of in silico studies has led to revolutionary
changes in the conventional method of testing the bioactivity of plant constituents.
Objective:
The current study deals with the investigation of some traditional immunomodulators of plant
origin to combat this ailment.
Materials and Methods:
A total of 151 phytomolecules of 12 immunomodulatory plants were evaluated
for their inhibitory action against the main protease (PDB ID: 7D1M) and NSP15 endoribonuclease (PDB
ID: 6WLC) by structure-based virtual screening. In addition, the promising molecules with ligand efficiency
of more than -0.3(kcal/mol)/heavy atoms were further predicted for pharmacokinetic properties
and druggability using the SwissADME web server, and their toxicity was also evaluated using Protox-II.
Result:
Myricetin-3-O-arabinofuranoside of cranberry plant was found to be the most potential candidate
against both enzymes: main protease (–14.2 kcal/mol) and NSP15 endoribonuclease (–12.2 kcal/mol).
Conclusion:
The promising outcomes of the current study may be implemented in future drug development
against coronavirus. The findings also help in the development of lead candidates of plant origin
with a better ADMET profile in the future.
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Affiliation(s)
- Shilpi Chauhan
- Department of Pharmacy, Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-I1, Greater
Noida, Uttar Pradesh 201306, India
| | - Deepika Saini
- Department of Pharmacy, Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-I1, Greater
Noida, Uttar Pradesh 201306, India
| | - Kumud Madan
- Department of Pharmacy, Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-I1, Greater
Noida, Uttar Pradesh 201306, India
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19
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Christofoletti CR, Fernandes AC, Gandra RL, Martins IM, Gambero A, Macedo GA, Macedo JA. “Wine residues extracts modulating in vitro metabolic syndrome”. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.101957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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20
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Pharmacological Effects of Polyphenol Phytochemicals on the Intestinal Inflammation via Targeting TLR4/NF-κB Signaling Pathway. Int J Mol Sci 2022; 23:ijms23136939. [PMID: 35805952 PMCID: PMC9266441 DOI: 10.3390/ijms23136939] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/20/2022] [Accepted: 06/21/2022] [Indexed: 02/05/2023] Open
Abstract
TLR4/NF-κB is a key inflammatory signaling transduction pathway, closely involved in cell differentiation, proliferation, apoptosis, and pro-inflammatory response. Toll like receptor 4 (TLR4), the first mammalian TLR to be characterized, is the innate immune receptor that plays a key role in inflammatory signal transductions. Nuclear factor kappa B (NF-κB), the TLR4 downstream, is the key to accounting for the expression of multiple genes involved in inflammatory responses, such as pro-inflammatory cytokines. Inflammatory bowel disease (IBD) in humans is a chronic inflammatory disease with high incidence and prevalence worldwide. Targeting the TLR4/NF-κB signaling pathway might be an effective strategy to alleviate intestinal inflammation. Polyphenol phytochemicals have shown noticeable alleviative effects by acting on the TLR4/NF-κB signaling pathway in intestinal inflammation. This review summarizes the pharmacological effects of more than 20 kinds of polyphenols on intestinal inflammation via targeting the TLR4/NF-κB signaling pathway. We expected that polyphenol phytochemicals targeting the TLR4/NF-κB signaling pathway might be an effective approach to treat IBD in future clinical research applications.
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21
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Chen Y, Wang J, Zou L, Cao H, Ni X, Xiao J. Dietary proanthocyanidins on gastrointestinal health and the interactions with gut microbiota. Crit Rev Food Sci Nutr 2022; 63:6285-6308. [PMID: 35114875 DOI: 10.1080/10408398.2022.2030296] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Many epidemiological and experimental studies have consistently reported the beneficial effects of dietary proanthocyanidins (PAC) on improving gastrointestinal physiological functions. This review aims to present a comprehensive perspective by focusing on structural properties, interactions and gastrointestinal protection of PAC. In brief, the main findings of this review are summarized as follows: (1) Structural features are critical factors in determining the bioavailability and subsequent pharmacology of PAC; (2) PAC and/or their bacterial metabolites can play a direct role in the gastrointestinal tract through their antioxidant, antibacterial, anti-inflammatory, and anti-proliferative properties; (3) PAC can reduce the digestion, absorption, and bioavailability of carbohydrates, proteins, and lipids by interacting with them or their according enzymes and transporters in the gastrointestinal tract; (4). PAC showed a prebiotic-like effect by interacting with the microflora in the intestinal tract, and the enhancement of PAC on a variety of probiotics, such as Bifidobacterium spp. and Lactobacillus spp. could be associated with potential benefits to human health. In conclusion, the potential effects of PAC in prevention and alleviation of gastrointestinal diseases are remarkable but clinical evidence is urgently needed.
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Affiliation(s)
- Yong Chen
- Laboratory of Food Oral Processing, School of Food Science & Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jing Wang
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, Zhejiang, China
- Ningbo Research Institute, Zhejiang University, Ningbo, Zhejiang, China
| | - Liang Zou
- Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Sichuan Engineering & Technology Research Center of Coarse Cereal Industralization, School of Food and Biological Engineering, Chengdu University, Chengdu, Sichuan, China
| | - Hui Cao
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Sciences, Universidade de Vigo, Ourense, Spain
| | - Xiaoling Ni
- Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jianbo Xiao
- Institute of Food Safety and Nutrition, Jinan University, Guangzhou, China
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22
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Procyanidin A1 alleviates DSS-induced ulcerative colitis via regulating AMPK/mTOR/p70S6K-mediated autophagy. J Physiol Biochem 2022; 78:213-227. [PMID: 35001346 DOI: 10.1007/s13105-021-00854-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 10/21/2021] [Indexed: 01/08/2023]
Abstract
Ulcerative colitis (UC) is a recurrent chronic inflammatory disease. The symptom of UC is mainly diarrhea including bloody stools. Increasing evidence has suggested that procyanidin A1 (PCA1) exerts an anti-inflammatory effect in several diseases. However, the role of PCA1 in UC is still a mystery. In our study, we explored the effect of PCA1 in dextran sulfate sodium (DSS)-induced UC mice and lipopolysaccharide (LPS)-stimulated HT-29 and IEC-6 cells. Then, cell proliferation, apoptosis, the production of proinflammatory cytokines, and autophagy-related markers were determined. Furthermore, the AMPK/mTOR/p70S6K signaling pathway was assayed by Western blot assay. In in vivo study, we found that PCA1 administration alleviated DSS-induced UC, as evidenced by reducing weight loss, clinical scores, colon weight/length ratio, histological damage, proinflammatory cytokines, and apoptosis. Moreover, we showed that the expression of Beclin-1 and LC3II/I ratio was increased, whereas the level of p62 was decreased after PCA1 treatment in vivo. Meanwhile, the reduced AMP/ATP ratio, enhanced expression of p-AMPK, and decreased p-p70S6K and p-mTOR levels indicate the activation of AMPK/mTOR/p70S6K signaling pathway. In in vitro study, PCA1 promoted cell proliferation and inhibited cell apoptosis in LPS-stimulated HT-29 and IEC-6 cells. Pro-inflammatory cytokines and autophagy-related factors exhibited the same trend as in in vivo results. Mechanically, PCA1 activated the AMPK/mTOR/p70S6K signaling pathway. The treatment with an AMPK inhibitor compound C significantly reversed the anti-inflammatory effect of PCA1 in LPS-stimulated cells. Taken together, these data indicated that PCA1 alleviated UC through induction of AMPK/mTOR/p70S6K-mediated autophagy.
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Mu C, Hao X, Zhang X, Zhao J, Zhang J. Effects of high-concentrate diet supplemented with grape seed procyanidins on the colonic fermentation, colonic morphology, and inflammatory response in lambs. Anim Feed Sci Technol 2021. [DOI: 10.1016/j.anifeedsci.2021.115118] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Das NC, Labala RK, Patra R, Chattoraj A, Mukherjee S. In silico identification of new anti-SARS-CoV-2 agents from bioactive phytocompounds targeting the viral spike glycoprotein and human TLR4. LETT DRUG DES DISCOV 2021. [DOI: 10.2174/1570180818666210901125519] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
The recent outbreak of novel coronavirus disease (COVID-19) pandemic caused by SARS-CoV-2 has posed a tremendous threat to mankind. The unavailability of a specific drug or vaccine has been the major concern to date. Spike (S) glycoprotein of SARS-CoV-2 plays the most crucial role in the viral infection and immunopathogenesis, and hence this protein appears to be an efficacious target for drug discovery.
Objective:
Identifying potent bioactive phytocompound that can target viral spike (S) glycoprotein and human TLR4 to reduce immunopathological manifestations of COVID-19.
Method:
A series of thirty (30) bioactive phytocompounds, previously documented for antiviral activity, were theoretically screened for their binding efficacy against key proteins related to pathogenesis of SARSCoV-2 namely viral spike (S) glycoprotein and human TLR4. MD simulation was employed to verify the postulations of molecular docking study and further ADME analysis was performed to predict the most effective one.
Results:
Studies hypothesized that two new phytochemicals viz. cajaninstilbene acid (-8.83 kcal/mol) and papaverine (-5.81 kcal/mol) might be the potent inhibitors of spike glycoprotein with stout binding affinity and favourable ADME attributes. MD simulation further ratified the stability of the docked complexes between the phytochemicals and S protein through strong hydrogen bonding. Our in silico data also indicated that cajaninstilbene acid and papaverine might block human TLR4 which could be useful to mitigate SARS-CoV-2-induced lethal proinflammatory responses.
Conclusion:
Experimental data collectively predict cajaninstilbene acid as the potential blocker of S protein which may be used as anti-viral against COVID-19 in the future. However, further experimental validations alongside toxicological detailing are needed for claiming the candidature of these molecules as future anti-corona therapeutics.
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Affiliation(s)
- Nabarun Chandra Das
- Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol-713 340, West Bengal, India
| | - Rajendra Kumar Labala
- Biological Rhythm Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol-713 340, West Bengal, India
| | - Ritwik Patra
- Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol-713 340, West Bengal, India
| | - Asamanja Chattoraj
- Biological Rhythm Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol-713 340, West Bengal, India
| | - Suprabhat Mukherjee
- Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol-713 340, West Bengal, India
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25
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Andersen-Civil AIS, Leppä MM, Thamsborg SM, Salminen JP, Williams AR. Structure-function analysis of purified proanthocyanidins reveals a role for polymer size in suppressing inflammatory responses. Commun Biol 2021; 4:896. [PMID: 34290357 PMCID: PMC8295316 DOI: 10.1038/s42003-021-02408-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 06/30/2021] [Indexed: 02/06/2023] Open
Abstract
Proanthocyanidins (PAC) are dietary compounds that have been extensively studied for beneficial health effects due to their anti-inflammatory properties. However, the structure-function relationships of PAC and their mode-of-action remain obscure. Here, we isolated a wide range of diverse PAC polymer mixtures of high purity from plant material. Polymer size was a key factor in determining the ability of PAC to regulate inflammatory cytokine responses in murine macrophages. PAC polymers with a medium (9.1) mean degree of polymerization (mDP) induced substantial transcriptomic changes, whereas PAC with either low (2.6) or high (12.3) mDP were significantly less active. Short-term oral treatment of mice with PAC modulated gene pathways connected to nutrient metabolism and inflammation in ileal tissue in a polymerization-dependent manner. Mechanistically, the bioactive PAC polymers modulated autophagic flux and inhibited lipopolysaccharide-induced autophagy in macrophages. Collectively, our results highlight the importance of defined structural features in the health-promoting effects of PAC-rich foods.
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Affiliation(s)
| | - Milla Marleena Leppä
- Natural Chemistry Research Group, Department of Chemistry, University of Turku, Turku, Finland
| | - Stig M Thamsborg
- Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark
| | - Juha-Pekka Salminen
- Natural Chemistry Research Group, Department of Chemistry, University of Turku, Turku, Finland
| | - Andrew R Williams
- Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
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26
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de Souza Silva AP, Rosalen PL, de Camargo AC, Lazarini JG, Rocha G, Shahidi F, Franchin M, de Alencar SM. Inajá oil processing by-product: A novel source of bioactive catechins and procyanidins from a Brazilian native fruit. Food Res Int 2021; 144:110353. [PMID: 34053546 DOI: 10.1016/j.foodres.2021.110353] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 03/20/2021] [Accepted: 03/23/2021] [Indexed: 12/30/2022]
Abstract
Agro-industrial activities generate large amounts of solid residues, which are generally discarded or used as animal feed. Interestingly, some of these by-products could serve as natural sources of bioactive compounds with great potential for industrial exploitation. This study aimed to optimize the extraction of phenolic antioxidants from the pulp residue (oil processing by-product) of inajá (Maximiliana maripa, a native species found in the Brazilian Amazon). The antioxidant properties of the optimized extract and its phenolic profile by high-resolution mass spectrometry (LC-ESI-QTOF-MS) were further determined. Central composite rotatable design and statistical analysis demonstrated that the temperature of 70 °C and 50% (v/v) ethanol concentration improved the extraction of phenolic compounds with antioxidant properties. The optimized extract also showed scavenging activity against the ABTS radical cation and reactive oxygen species (ROS; peroxyl and superoxide radical, and hypochlorous acid). Moreover, the optimized extract was able to reduce NF-κB activation and TNF-α release, which are modulated by ROS. Flavan-3-ols were the major phenolics present in the optimized extract. Collectively, our findings support the use of inajá cake as a new source of bioactive catechins and procyanidins. This innovative approach adds value to this agro-industrial by-product in the functional food, nutraceutical, pharmaceutical, and/or cosmetic industries and complies with the circular economy agenda.
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Affiliation(s)
- Anna Paula de Souza Silva
- Agri-food Industry, Food and Nutrition Department, Luiz de Queiroz College of Agriculture, University of São Paulo, ESALQ/USP, Piracicaba, São Paulo, Brazil
| | - Pedro Luiz Rosalen
- Department of Biosciences, Piracicaba Dental School, University of Campinas, UNICAMP, São Paulo, Brazil; Federal University of Alfenas, Alfenas, Minas Gerais, Brazil
| | - Adriano Costa de Camargo
- Laboratory of Antioxidants, Nutrition and Food Technology Institute, University of Chile, Santiago, Chile
| | - Josy Goldoni Lazarini
- Department of Biosciences, Piracicaba Dental School, University of Campinas, UNICAMP, São Paulo, Brazil
| | - Gabriela Rocha
- Citróleo Industry and Commerce of Essential Oils, LTDA, Research, Development and Innovation Department, Torrinha, São Paulo, Brazil
| | - Fereidoon Shahidi
- Department of Biochemistry, Memorial University of Newfoundland, NL A1B 3X9, Canada
| | - Marcelo Franchin
- Department of Biosciences, Piracicaba Dental School, University of Campinas, UNICAMP, São Paulo, Brazil; Federal University of Alfenas, Alfenas, Minas Gerais, Brazil
| | - Severino Matias de Alencar
- Agri-food Industry, Food and Nutrition Department, Luiz de Queiroz College of Agriculture, University of São Paulo, ESALQ/USP, Piracicaba, São Paulo, Brazil.
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27
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Andersen-Civil AIS, Arora P, Williams AR. Regulation of Enteric Infection and Immunity by Dietary Proanthocyanidins. Front Immunol 2021; 12:637603. [PMID: 33717185 PMCID: PMC7943737 DOI: 10.3389/fimmu.2021.637603] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 01/14/2021] [Indexed: 12/11/2022] Open
Abstract
The role of dietary components in immune function has acquired considerable attention in recent years. An important focus area is to unravel the role of bioactive dietary compounds in relation to enteric disease and their impact on gut mucosal immunity. Proanthocyanidins (PAC) are among the most common and most consumed dietary polyphenols, and are characterised by their variable molecular structures and diverse bioactivities. In particular, their anti-oxidative effects and ability to modulate gut microbiota have been widely described. However, there is limited evidence on the mechanism of action of PAC on the immune system, nor is it clearly established how PAC may influence susceptibility to enteric infections. Establishing the sites of action of PAC and their metabolites within the gut environment is fundamental to determine the applicability of PAC against enteric pathogens. Some mechanistic studies have shown that PAC have direct modulatory effects on immune cell signalling, isolated pathogens, and gut mucosal barrier integrity. Boosting the recruitment of immune cells and suppressing the amount of pro-inflammatory cytokines are modulating factors regulated by PAC, and can either be beneficial or detrimental in the course of re-establishing gut homeostasis. Herein, we review how PAC may alter distinct immune responses towards enteric bacterial, viral and parasitic infections, and how the modulation of gut microbiota may act as a mediating factor. Furthermore, we discuss how future studies could help unravel the role of PAC in preventing and/or alleviating intestinal inflammation and dysbiosis caused by enteric disease.
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Affiliation(s)
- Audrey I S Andersen-Civil
- Department of Veterinary and Animal Sciences, University of Copenhagen, Faculty of Health and Medical Sciences, Frederiksberg, Denmark
| | - Pankaj Arora
- Department of Veterinary and Animal Sciences, University of Copenhagen, Faculty of Health and Medical Sciences, Frederiksberg, Denmark
| | - Andrew R Williams
- Department of Veterinary and Animal Sciences, University of Copenhagen, Faculty of Health and Medical Sciences, Frederiksberg, Denmark
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28
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Butkevičiūtė A, Liaudanskas M, Ramanauskienė K, Janulis V. Biopharmaceutical Evaluation of Capsules with Lyophilized Apple Powder. Molecules 2021; 26:1095. [PMID: 33669650 PMCID: PMC7922082 DOI: 10.3390/molecules26041095] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/17/2021] [Accepted: 02/17/2021] [Indexed: 11/16/2022] Open
Abstract
Apples are an important source of biologically active compounds. Consequently, we decided to model hard gelatin capsules with lyophilized apple powder by using different excipients and to evaluate the release kinetics of phenolic compounds. The apple slices of "Ligol" cultivar were immediately frozen in a freezer (at -35°C) with air circulation and were lyophilized with a sublimator at the pressure of 0.01 mbar (condenser temperature, -85°C). Lyophilized apple powder was used as an active substance filled into hard gelatin capsules. We conducted capsule disintegration and dissolution tests to evaluate the quality of apple lyophilizate-containing capsules of different encapsulating content. Individual phenolic compounds can be arranged in the following descending order according to the amount released from the capsules of different compositions: chlorogenic acid > rutin > avicularin > hyperoside > phloridzin > quercitrin > (-)-epicatechin > isoquercitrin. Chlorogenic acid was the compound that was released in the highest amounts from capsules of different encapsulating content: its released amounts ranged from 68.4 to 640.3 μg/mL. According to the obtained data, when hypromellose content ranged from 29% to 41% of the capsule mass, the capsules disintegrated within less than 30 min, and such amounts of hypromellose did not prolong the release of phenolic compounds. Based on the results of the dissolution test, the capsules can be classified as fast-dissolving preparations, as more than 85% of the active substances were released within 30 min.
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Affiliation(s)
- Aurita Butkevičiūtė
- Department of Pharmacognosy, Lithuanian University of Health Sciences, Sukileliu av. 13, LT-50162 Kaunas, Lithuania; (M.L.); (V.J.)
| | - Mindaugas Liaudanskas
- Department of Pharmacognosy, Lithuanian University of Health Sciences, Sukileliu av. 13, LT-50162 Kaunas, Lithuania; (M.L.); (V.J.)
| | - Kristina Ramanauskienė
- Department of Clinical Pharmacy, Lithuanian University of Health Sciences, Sukileliu av. 13, LT-50162 Kaunas, Lithuania;
| | - Valdimaras Janulis
- Department of Pharmacognosy, Lithuanian University of Health Sciences, Sukileliu av. 13, LT-50162 Kaunas, Lithuania; (M.L.); (V.J.)
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29
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Ibraheem S, Idris Y, Elghali Mustafa S, Kabeir B, Abas F, Maulidiani M, Hamid N. Phytochemical profile and biological activities of Sudanese baobab (Adansonia digitata L.) fruit pulp extract. INTERNATIONAL FOOD RESEARCH JOURNAL 2021. [DOI: 10.47836/ifrj.28.1.03] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The present work aimed to investigate the phytochemical profile and biological activities of Sudanese baobab (Adansonia digitata L.) fruit pulp extract. Baobab fruit pulp serves as food, and has been used in traditional medicine in Africa for the treatment of several diseases, and believed to possess many biological activities. The sample of baobab fruit was collected from Blue Nile State in Sudan. The fruit pulp was obtained from baobab pods, sieved, extracted with methanol (80%), and analysed for its antioxidant activity, and alpha-glucosidase and nitric oxide (NO) inhibitory activities. The phytochemical constituents of the pulp were determined by LC-MS and 1H-NMR techniques. The results for antioxidant activity evaluated by DPPH and FRAP for methanolic extract were 232.70 mg Ascorbic Acid Equivalent Antioxidant Capacity (AEAC)/g and 222.28 mmol/g of Fe2+, respectively. Baobab pulp extract showed greater capability in inhibiting the generation of NO from the stimulated RAW264.7 cells at 98.45% inhibition and IC50 of 36.55 µg/mL; and α-glucosidase enzyme activity at 97.94% inhibition and IC50 of 58.59 µg/mL. The LC-MS/MS analysis of the baobab extract showed that 52 compounds were found in the baobab pulp, including 19 flavonoids, ten phenolic acids, four lipids (glycero-3-phosphocholine derivative, 1,2-didodecanoyl-sn-glycero-3-phospho-(1'-sn-glycerol), 1-pentadecanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphate, and glycero-3-hosphocholine derivative), sugars, organic acid, iridoids, adenosine, scopoletin, and taraxerone. The NMR detected 21 metabolites from baobab pulp extract including carbohydrates, organic acids, vitamin, amino acids, phenolic compounds, alkaloids, and fatty acids. The present work is the first of its kind in comprehensively analysing the Sudanese baobab fruit pulp, combined with qualitative characterisation of chemical components using NMR, LC-MS, α-glucosidase, and NO inhibitors. Baobab fruit pulp contains several beneficial phytochemicals and biological activities, and it has potential positive effect on general human’s health.
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30
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Zhang L, Chen J, Liao H, Li C, Chen M. Anti-inflammatory effect of lipophilic grape seed proanthocyanidin in RAW 264.7 cells and a zebrafish model. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104217] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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31
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Saraswati, Giriwono PE, Iskandriati D, Tan CP, Andarwulan N. In-vitro anti-inflammatory activity, free radical (DPPH) scavenging, and ferric reducing ability (FRAP) of Sargassum cristaefolium lipid-soluble fraction and putative identification of bioactive compounds using UHPLC-ESI-ORBITRAP-MS/MS. Food Res Int 2020; 137:109702. [PMID: 33233276 DOI: 10.1016/j.foodres.2020.109702] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 08/10/2020] [Accepted: 09/06/2020] [Indexed: 10/23/2022]
Abstract
Sargassum brown seaweed is well-known to contain several bioactive compounds which exhibit various biological activities, including anti-inflammatory and antioxidant activity. Lipophilic extracts and fractions of Sargassum were reported to possess promising anti-inflammatory activity. This study, therefore, aims to evaluate the anti-inflammatory and antioxidant activity of Sargassum cristaefolium crude lipid extract and its fractions. The brown seaweed was obtained from Awur Bay, Jepara - Indonesia. Crude lipid fractionation was performed using normal phase column chromatography, and three different fractions (dichloromethane, acetone, methanol) were produced. The results showed that treatment of acetone fraction exerted strongest nitric oxide inhibition in lipopolysaccharide-induced RAW 264.7 cells, both in pre-incubated and co-incubated cell culture models. This outcome was in accordance with its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and ferric reducing antioxidant power (FRAP). Metabolite profiling of lipid fractions was performed by ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry, while the orthogonal projection to latent structures analysis was conducted to determine some features with significant correlation to the bioactivity. There were 14 feature candidates considered from both positive and negative ionization mode datasets. Seven out of them were putatively identified as pheophytin a (1), all-trans fucoxanthin (2), 132-hydroxy-pheophytin a (3), pheophorbide a (4), 1-hexadecanoyl-2-(9Z-octadecenoyl)-3-O-β-D-galactosyl-sn-glycerol (6), 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-3-O-β-D-galactosyl-sn-glycerol (10), and 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-3-O-β-D-galactosyl-sn glycerol (12).
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Affiliation(s)
- Saraswati
- Department of Food Science and Technology, Faculty of Agricultural Engineering and Technology, Bogor Agricultural University 16680, Indonesia.
| | - Puspo Edi Giriwono
- Department of Food Science and Technology, Faculty of Agricultural Engineering and Technology, Bogor Agricultural University 16680, Indonesia; Southeast Asian Food and Agricultural Science Technology (SEAFAST) Center, Bogor Agricultural University 16680, Indonesia
| | - Diah Iskandriati
- Primate Research Center, Bogor Agricultural University 16151, Indonesia
| | - Chin Ping Tan
- Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - Nuri Andarwulan
- Department of Food Science and Technology, Faculty of Agricultural Engineering and Technology, Bogor Agricultural University 16680, Indonesia; Southeast Asian Food and Agricultural Science Technology (SEAFAST) Center, Bogor Agricultural University 16680, Indonesia.
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Yousefi R, Parandoosh M, Khorsandi H, Hosseinzadeh N, Madani Tonekaboni M, Saidpour A, Babaei H, Ghorbani A. Grape seed extract supplementation along with a restricted-calorie diet improves cardiovascular risk factors in obese or overweight adult individuals: A randomized, placebo-controlled trial. Phytother Res 2020; 35:987-995. [PMID: 33044768 DOI: 10.1002/ptr.6859] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 06/13/2020] [Accepted: 07/18/2020] [Indexed: 12/21/2022]
Abstract
Grape seed extract (GSE) is a flavonoid-rich supplement, recently discussed as a potential moderator of inflammation and obesity. In this study, we aimed to investigate the effects of GSE supplementation along with a restricted-calorie diet (RCD), on changes in blood lipid profile, visceral adiposity index (VAI), and atherogenic index of plasma (AIP). We designed a randomized, double-blinded, placebo-controlled clinical trial. Forty obese or overweight individuals (25 ≤ body mass index < 40 kg/m2 ) were randomly assigned to receive GSE (300 mg/day) or placebo, plus RCD, for 12 weeks. We studied the anthropometric measures, biochemical biomarkers and dietary intake within the study timelines. Levels of high-density lipoprotein cholesterol (HDL-C) and HDL-C/low-density lipoprotein cholesterol (LDL-C) significantly increased in the GSE group as compared with the placebo group at week 12 (p = .03 and .008, respectively, adjusted for age, sex, energy and saturated fatty acid intake). We also observed a significant reduction in LDL-C following GSE supplementation in comparison to placebo (adjusted for age, sex and energy intake, p = .04). VAI, AIP, total cholesterol and triglyceride significantly decreased in the GSE group compared with the baseline (p = .04, .02, .01, and .02, respectively). GSE supplementation may have a modulatory role in improving blood lipid profile in obese or overweight individuals, when accompanied by RCD.
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Affiliation(s)
- Reyhaneh Yousefi
- Department of Health, Kinesiology, and Applied Physiology, Concordia University, and Montréal Behavioural Medicine Centre, CIUSSS-NIM, Hôpital du Sacré-Coeur de Montréal, Montréal, Quebec, Canada
| | - Maryam Parandoosh
- Faculty of Nutrition Sciences and Food Technology, Department of Clinical Nutrition & Dietetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hoda Khorsandi
- Faculty of Nutrition Sciences and Food Technology, Department of Clinical Nutrition & Dietetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nima Hosseinzadeh
- Faculty of Biostatistics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Atoosa Saidpour
- Faculty of Nutrition Sciences and Food Technology, Department of Clinical Nutrition & Dietetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Babaei
- Drug Applied Research Center, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Arman Ghorbani
- Faculty of Nutrition Science and Food Technology, Department of Cellular and Molecular Nutrition, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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The effect of grape products containing polyphenols on C-reactive protein levels: a systematic review and meta-analysis of randomised controlled trials. Br J Nutr 2020; 125:1230-1245. [DOI: 10.1017/s0007114520003591] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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34
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Yan F, Zhao L, Chen W, Lu Q, Tang C, Wang C, Liu R. Comparison of the inhibitory effects of procyanidins with different structures and their digestion products against acrylamide-induced cytotoxicity in IPEC-J2 cells. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104073] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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35
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Kamalian A, Sohrabi Asl M, Dolatshahi M, Afshari K, Shamshiri S, Momeni Roudsari N, Momtaz S, Rahimi R, Abdollahi M, Abdolghaffari AH. Interventions of natural and synthetic agents in inflammatory bowel disease, modulation of nitric oxide pathways. World J Gastroenterol 2020; 26:3365-3400. [PMID: 32655263 PMCID: PMC7327787 DOI: 10.3748/wjg.v26.i24.3365] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/09/2020] [Accepted: 06/04/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) refers to a group of disorders characterized by chronic inflammation of the gastrointestinal (GI) tract. The elevated levels of nitric oxide (NO) in serum and affected tissues; mainly synthesized by the inducible nitric oxide synthase (iNOS) enzyme; can exacerbate GI inflammation and is one of the major biomarkers of GI inflammation. Various natural and synthetic agents are able to ameliorate GI inflammation and decrease iNOS expression to the extent comparable with some IBD drugs. Thereby, the purpose of this study was to gather a list of natural or synthetic mediators capable of modulating IBD through the NO pathway. Electronic databases including Google Scholar and PubMed were searched from 1980 to May 2018. We found that polyphenols and particularly flavonoids are able to markedly attenuate NO production and iNOS expression through the nuclear factor κB (NF-κB) and JAK/STAT signaling pathways. Prebiotics and probiotics can also alter the GI microbiota and reduce NO expression in IBD models through a broad array of mechanisms. A number of synthetic molecules have been found to suppress NO expression either dependent on the NF-κB signaling pathway (i.e., dexamethasone, pioglitazone, tropisetron) or independent from this pathway (i.e., nicotine, prednisolone, celecoxib, β-adrenoceptor antagonists). Co-administration of natural and synthetic agents can affect the tissue level of NO and may improve IBD symptoms mainly by modulating the Toll like receptor-4 and NF-κB signaling pathways.
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Affiliation(s)
- Aida Kamalian
- Department of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Masoud Sohrabi Asl
- Department of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Mahsa Dolatshahi
- Department of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Khashayar Afshari
- Department of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Shiva Shamshiri
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Nazanin Momeni Roudsari
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran 1941933111, Iran
| | - Saeideh Momtaz
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Tehran 1417614411, Iran
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
- Gastrointestinal Pharmacology Interest Group, Universal Scientific Education and Research Network, Tehran 1417614411, Iran
| | - Roja Rahimi
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Mohammad Abdollahi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Amir Hossein Abdolghaffari
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran 1941933111, Iran
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Tehran 1417614411, Iran
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
- Gastrointestinal Pharmacology Interest Group, Universal Scientific Education and Research Network, Tehran 1417614411, Iran
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
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Williams AR, Andersen-Civil AIS, Zhu L, Blanchard A. Dietary phytonutrients and animal health: regulation of immune function during gastrointestinal infections. J Anim Sci 2020; 98:5718206. [PMID: 31999321 DOI: 10.1093/jas/skaa030] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 01/26/2020] [Indexed: 12/13/2022] Open
Abstract
The composition of dietary macronutrients (proteins, carbohydrates, and fibers) and micronutrients (vitamins, phytochemicals) can markedly influence the development of immune responses to enteric infection. This has important implications for livestock production, where a significant challenge exists to ensure healthy and productive animals in an era of increasing drug resistance and concerns about the sector's environmental footprint. Nutritional intervention may ultimately be a sustainable method to prevent disease and improve efficiency of livestock enterprises, and it is now well established that certain phytonutrients can significantly improve animal performance during challenge with infectious pathogens. However, many questions remain unanswered concerning the complex interplay between diet, immunity, and infection. In this review, we examine the role of phytonutrients in regulating immune and inflammatory responses during enteric bacterial and parasitic infections in livestock, with a specific focus on some increasingly well-studied phytochemical classes-polyphenols (especially proanthocyanidins), essential oil components (cinnamaldehyde, eugenol, and carvacrol), and curcumin. Despite the contrasting chemical structures of these molecules, they appear to induce a number of similar immunological responses. These include promotion of mucosal antibody and antimicrobial peptide production, coupled with a strong suppression of inflammatory cytokines and reactive oxygen species. Although there have been some recent advances in our understanding of the mechanisms underlying their bioactivity, how these phytonutrients modulate immune responses in the intestine remains mostly unknown. We discuss the complex inter-relationships between metabolism of dietary phytonutrients, the gut microbiota, and the mucosal immune system, and propose that an increased understanding of the basic immunological mechanisms involved will allow the rational development of novel dietary additives to promote intestinal health in farmed animals.
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Affiliation(s)
- Andrew R Williams
- Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark
| | | | - Ling Zhu
- Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark
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Ethnopharmacological Potential of Aspilia africana for the Treatment of Inflammatory Diseases. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:8091047. [PMID: 32733588 PMCID: PMC7321516 DOI: 10.1155/2020/8091047] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 05/23/2020] [Indexed: 02/07/2023]
Abstract
Inflammatory diseases are major health concerns affecting millions of people worldwide. Aspilia africana has been used for centuries by many African communities in the treatment of a wide range of health conditions, including inflammatory diseases, osteoporosis, rheumatic pains, and wounds. Analysis of the phytochemical composition of A. africana indicated that the plant is rich in a broad range of secondary metabolites, including flavonoids, alkaloids, tannins, saponins, terpenoids, sterols, phenolic compounds, and glycosides. This explains the efficacy of the plant in treating inflammation-related diseases, as well as several other health conditions affecting different African communities. The mechanisms of action of the anti-inflammatory phytochemical compounds in A. africana include inhibition of a number of physiological processes involved in the inflammatory process and synthesis or action of proinflammatory enzymes. The phytochemicals enhance anti-inflammatory biological responses such as inhibition of a number of chemical mediators including histamine, prostanoids and kinins, 5-lipoxygenase. and cyclooxygenase and activation of phosphodiesterase and transcriptase. Currently used anti-inflammatory medications are associated with several disadvantages such as drug toxicity and iatrogenic reactions, thereby complicating the treatment process. The adverse effects related to the use of these conventional synthetic drugs have been the driving force behind consideration of natural remedies, and efforts are being made toward the development of anti-inflammatory agents based on natural extracts. A. africana is rich in secondary metabolites, and its use as a traditional medicine for treating inflammatory diseases has been validated through in vitro and in vivo studies. Therefore, the plant could be further explored for potential development of novel anti-inflammatory therapeutics.
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González-Quilen C, Grau-Bové C, Jorba-Martín R, Caro-Tarragó A, Pinent M, Ardévol A, Beltrán-Debón R, Terra X, Blay MT. Protective properties of grape-seed proanthocyanidins in human ex vivo acute colonic dysfunction induced by dextran sodium sulfate. Eur J Nutr 2020; 60:79-88. [PMID: 32189068 DOI: 10.1007/s00394-020-02222-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 03/04/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE Anti-inflammatory and barrier-protective properties have been attributed to proanthocyanidins in the context of intestinal dysfunction, however little information is available about the impact of these phytochemicals on intestinal barrier integrity and immune response in the human. Here we assessed the putative protective properties of a grape-seed proanthocyanidin extract (GSPE) against dextran sodium sulfate (DSS)-induced acute dysfunction of the human colon in an Ussing chamber system. METHODS Human proximal and distal colon tissues from colectomized patients were submitted ex vivo for a 30-min preventive GSPE treatment (50 or 200 µg mL-1) followed by 1-h incubation with DSS (12% w v-1). Transepithelial electrical resistance (TEER), permeation of a fluorescently-labeled dextran (FD4) and proinflammatory cytokine release [tumor necrosis factor (TNF)-α and interleukin (IL)-1β] of colonic tissues were determined. RESULTS DSS reduced TEER (45-52%) in both the proximal and distal colon; however, significant increments in FD4 permeation (fourfold) and TNF-α release (61%) were observed only in the proximal colon. The preventive GSPE treatment decreased DSS-induced TEER loss (20-32%), FD4 permeation (66-73%) and TNF-α release (22-33%) of the proximal colon dose-dependently. The distal colon was not responsive to the preventive treatment but showed a reduction in IL-1β release below basal levels with the highest GSPE concentration. CONCLUSIONS Our results demonstrate potential preventive effects of GSPE on human colon dysfunction. Further studies are required to test whether administering GSPE could be a complementary therapeutic approach in colonic dysfunction associated with metabolic disorders and inflammatory bowel disease.
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Affiliation(s)
- Carlos González-Quilen
- Departament de Bioquímica i Biotecnologia, MoBioFood Research Group, Universitat Rovira I Virgili, 43007, Tarragona, Spain
| | - Carme Grau-Bové
- Departament de Bioquímica i Biotecnologia, MoBioFood Research Group, Universitat Rovira I Virgili, 43007, Tarragona, Spain
| | - Rosa Jorba-Martín
- Servei de Cirurgia General i de l'Aparell Digestiu, Hospital Universitari Joan XXIII, Tarragona, Spain
| | - Aleidis Caro-Tarragó
- Servei de Cirurgia General i de l'Aparell Digestiu, Hospital Universitari Joan XXIII, Tarragona, Spain
| | - Montserrat Pinent
- Departament de Bioquímica i Biotecnologia, MoBioFood Research Group, Universitat Rovira I Virgili, 43007, Tarragona, Spain
| | - Anna Ardévol
- Departament de Bioquímica i Biotecnologia, MoBioFood Research Group, Universitat Rovira I Virgili, 43007, Tarragona, Spain
| | - Raúl Beltrán-Debón
- Departament de Bioquímica i Biotecnologia, MoBioFood Research Group, Universitat Rovira I Virgili, 43007, Tarragona, Spain.
| | - Ximena Terra
- Departament de Bioquímica i Biotecnologia, MoBioFood Research Group, Universitat Rovira I Virgili, 43007, Tarragona, Spain
| | - M Teresa Blay
- Departament de Bioquímica i Biotecnologia, MoBioFood Research Group, Universitat Rovira I Virgili, 43007, Tarragona, Spain
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González-Quilen C, Rodríguez-Gallego E, Beltrán-Debón R, Pinent M, Ardévol A, Blay MT, Terra X. Health-Promoting Properties of Proanthocyanidins for Intestinal Dysfunction. Nutrients 2020; 12:E130. [PMID: 31906505 PMCID: PMC7019584 DOI: 10.3390/nu12010130] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 12/20/2019] [Accepted: 12/31/2019] [Indexed: 12/22/2022] Open
Abstract
The intestinal barrier is constantly exposed to potentially harmful environmental factors, including food components and bacterial endotoxins. When intestinal barrier function and immune homeostasis are compromised (intestinal dysfunction), inflammatory conditions may develop and impact overall health. Evidence from experimental animal and cell culture studies suggests that exposure of intestinal mucosa to proanthocyanidin (PAC)-rich plant products, such as grape seeds, may contribute to maintaining the barrier function and to ameliorating the pathological inflammation present in diet-induced obesity and inflammatory bowel disease. In this review, we aim to update the current knowledge on the bioactivity of PACs in experimental models of intestinal dysfunction and in humans, and to provide insights into the underlying biochemical and molecular mechanisms.
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Affiliation(s)
| | | | | | | | | | - M Teresa Blay
- MoBioFood Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, 43007 Tarragona, Spain; (C.G.-Q.); (E.R.-G.); (R.B.-D.); (M.P.); (A.A.); (X.T.)
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40
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Yan H, Gao W, Li Q, Li H, Hao R. Effect of grapeseed procyanidins on small intestinal mucosa morphology and small intestinal development in weaned piglets. ANIMAL PRODUCTION SCIENCE 2020. [DOI: 10.1071/an18638] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Context
Grapeseed procyanidins (GSP) are widely recognised to have potential biological properties, and dietary supplementation with GSP could reduce diarrhoea incidence in weaned piglets.
Aims
This trial was conducted to investigate the effect of GSP on small intestinal mucosa morphology and small intestinal development in weaned piglets.
Methods
Seventy-two weaned piglets were randomly allocated into four dietary groups with three replicate pens per group and six piglets per pen. Each group received one of the following diets: a basal maize–soybean meal diet; or basal diet supplemented with 50, 100 or 150 mg GSP/kg. Small intestinal mucosa morphology and the expression of genes involved in improving small intestinal development were determined.
Key results
Morphological observations obtained by optical microscopy showed that the villus height of the duodenum and ileum increased in all groups receiving GSP, significantly (P < 0.05) so in the group receiving 100 mg GSP/kg compared with the control group. Crypt depth of the duodenum and ileum in the groups receiving 100 and 150 mg GSP/kg decreased compared with the control group. Similarly, the crypt depth of the jejunum in the group receiving 100 mg GSP/kg was significantly (P < 0.05) lowered. Moreover, the villus height/crypt depth ratio of each small intestinal segment in the group receiving 100 mg GSP/kg increased significantly (P < 0.01). Morphological observations obtained by scanning electron microscopy indicated that dietary supplementation with GSP was favourable for growth of small intestinal villi. Specifically, the villi of the small intestine in the group receiving 100 mg GSP/kg were most closely aligned, most uniform in size and clearest in structure. Furthermore, dietary supplementation with GSP increased the expression of genes encoding epidermal growth factor receptor, insulin-like growth factor 1 (IGF-1) and IGF-1 receptor in the duodenum, the group receiving 100 mg GSP/kg showing a significant (P < 0.05) increase.
Conclusions
Dietary supplementation with GSP could improve small intestinal mucosa morphology and promote small intestinal development. Dietary supplementation of 100 mg GSP/kg could be recommended for weaned piglets.
Implications
Dietary supplementation with GSP generated a beneficial role in small intestinal health in weaned piglets.
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Weng CL, Chen CC, Tsou HH, Liu TY, Wang HT. Areca nut procyanidins prevent ultraviolet light B-induced photoaging via suppression of cyclooxygenase-2 and matrix metalloproteinases in mouse skin. Drug Chem Toxicol 2019; 45:353-359. [PMID: 31790610 DOI: 10.1080/01480545.2019.1696813] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Chronic exposure to solar ultraviolet (UV) light induces photoaging in human skin. Our previous results have shown that areca nut procyanidins (ANPs) have antioxidant capacity and possess potential anti-inflammatory effects. Here, we aimed to investigate the effect of ANPs on UVB-induced photoaging. In the present study, dorsal skin of CD-1 mice was exposed to UVB at a minimal erythema dose (130 mJ/cm2) throughout a 3-week period. The effects of ANPs and epigallocatechin-3-gallate (EGCG), a polyphenolic constituent of green tea, on UVB-induced photoaging were compared. The results show that oral administration of ANP prevented UVB-induced photoaging, indicated by epidermal thickness and collagen disorientation, and inhibited UVB-induced expression of cyclooxygenase-2 and matrix metalloproteinases (MMPs), such as MMP-2, MMP-9, and TIMP1. The protective potential of ANP on UVB-induced photodamage was comparable to that of EGCG. These data suggest that ANP could be useful as a dietary supplement to attenuate solar UVB-induced premature skin aging.
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Affiliation(s)
- Chia-Ling Weng
- Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan
| | - Chih-Chiang Chen
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Dermatology, National Yang-Ming University, Taipei, Taiwan.,Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Han-Hsing Tsou
- Institute of Environmental and Occupational Health Sciences, National Yang-Ming University, Taipei, Taiwan
| | - Tsung-Yun Liu
- Institute of Environmental and Occupational Health Sciences, National Yang-Ming University, Taipei, Taiwan.,Institute of Food Safety and Health Risk Assessment, National Yang-Ming University, Taipei, Taiwan
| | - Hsiang-Tsui Wang
- Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan
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Arie H, Nozu T, Miyagishi S, Ida M, Izumo T, Shibata H. Grape Seed Extract Eliminates Visceral Allodynia and Colonic Hyperpermeability Induced by Repeated Water Avoidance Stress in Rats. Nutrients 2019; 11:E2646. [PMID: 31689935 PMCID: PMC6893525 DOI: 10.3390/nu11112646] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 10/17/2019] [Accepted: 10/28/2019] [Indexed: 12/12/2022] Open
Abstract
Grape seed extract (GSE) is rich in polyphenols composed mainly of proanthocyanidins, which are known to attenuate proinflammatory cytokine production. Repeated water avoidance stress (WAS) induces visceral allodynia and colonic hyperpermeability via toll-like receptor 4 (TLR4) and proinflammatory cytokine pathways, which is a rat irritable bowel syndrome (IBS) model. Thus, we explored the effects of GSE on repeated WAS (1 h for 3 days)-induced visceral allodynia and colonic hyperpermeability in Sprague-Dawley rats. Paracellular permeability, as evaluated by transepithelial electrical resistance and flux of carboxyfluorescein, was analyzed in Caco-2 cell monolayers treated with interleukin-6 (IL-6) and IL-1β. WAS caused visceral allodynia and colonic hyperpermeability, and intragastric administration of GSE (100 mg/kg, once daily for 11 days) inhibited these changes. Furthermore, GSE also suppressed the elevated colonic levels of IL-6, TLR4, and claudin-2 caused by WAS. Paracellular permeability was increased in Caco-2 cell monolayers in the presence of IL-6 and IL-1β, which was inhibited by GSE. Additionally, GSE suppressed the claudin-2 expression elevated by cytokine stimulation. The effects of GSE on visceral changes appear to be evoked by suppressing colonic TLR4-cytokine signaling and maintaining tight junction integrity. GSE may be useful for treating IBS.
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Affiliation(s)
- Hideyuki Arie
- Institute for Health Care Science, Suntory Wellness Limited, Seikadai 8-1-1, Seika-cho, Soraku-gun, Kyoto 619-0284, Japan.
| | - Tsukasa Nozu
- Department of Regional Medicine and Education, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
| | - Saori Miyagishi
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
| | - Masayuki Ida
- Institute for Health Care Science, Suntory Wellness Limited, Seikadai 8-1-1, Seika-cho, Soraku-gun, Kyoto 619-0284, Japan.
| | - Takayuki Izumo
- Institute for Health Care Science, Suntory Wellness Limited, Seikadai 8-1-1, Seika-cho, Soraku-gun, Kyoto 619-0284, Japan.
| | - Hiroshi Shibata
- Institute for Health Care Science, Suntory Wellness Limited, Seikadai 8-1-1, Seika-cho, Soraku-gun, Kyoto 619-0284, Japan.
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Tannins, novel inhibitors of the volume regulation and the volume-sensitive anion channel. EUROPEAN PHARMACEUTICAL JOURNAL 2019. [DOI: 10.2478/afpuc-2019-0016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Abstract
The volume-sensitive outwardly rectifying anion channel (VSOR) is a key component of volume regulation system critical for cell survival in non-isosmotic conditions. The aim of the present study was to test the effects of four tannin extracts with defined compositions on cell volume regulation and VSOR. Preparation I (98% of hydrolysable tannins isolated from leaves of sumac Rhus typhina L.) and Preparation II (100% of hydrolysable tannins isolated from leaves of broadleaf plantain Plantago major L) completely and irreversibly abolished swelling-activated VSOR currents in HCT116 cells. Both preparations profoundly suppressed the volume regulation in thymocytes with half-maximal effects of 40.9 μg/ml and 12.3 μg/ml, respectively. The inhibition was more efficient at lower concentrations but reverted at higher doses due to possible non-specific membrane-permeabilizing activity. Preparations III and IV (54,7% and 54.3% of hydrolysable tannins isolated, respectively, from roots and aboveground parts of Fergana spurge Euphorbia ferganensis B.Fedtch) inhibited VSOR activity in a partially reversible manner and suppressed the volume regulation with substantially higher half-maximal doses of 270 and 278 μg/ml, respectively, with no secondary reversion at higher doses. Hydrolysable tannins represent a novel class of VSOR channel inhibitors with the capacity to suppress the cell volume regulation machinery.
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Kawahara SI, Ishihara C, Matsumoto K, Senga S, Kawaguchi K, Yamamoto A, Suwannachot J, Hamauzu Y, Makabe H, Fujii H. Identification and characterization of oligomeric proanthocyanidins with significant anti-cancer activity in adzuki beans ( Vigna angularis). Heliyon 2019; 5:e02610. [PMID: 31687492 PMCID: PMC6820087 DOI: 10.1016/j.heliyon.2019.e02610] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 09/11/2019] [Accepted: 10/03/2019] [Indexed: 11/05/2022] Open
Abstract
The aim of the present study was to characterize and evaluate the anti-cancer activity of proanthocyanidin-enriched fractions from adzuki beans. For this purpose, we concentrated proanthocyanidins from adzuki beans (Vigna angularis) into five fractions using Amberlite XAD-1180N, Toyopearl HW40F, and Sepacore C-18 reverse-phase flash column chromatography. Proanthocyanidin-enriched fractions were characterized as (epi)catechin hexamer, heptamer, and octamer, epigallocatechin-(epi)catechin pentamer, and epigallocatechin-(epi)catechin hexamer using electrospray ionization time-of-flight mass spectrometry and thiolytic degradation. These fractions showed significant anti-cancer activity against the human PC-3 prostate cancer cell line. They also significantly suppressed the expression of the fatty acid-binding protein 5 gene, which plays critical roles in cell growth and metastasis in prostate cancer.
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Affiliation(s)
- Sei-Ichi Kawahara
- Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan
| | - Chisato Ishihara
- Graduate School of Science and Technology, Department of Biomedical Engineering, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan
| | - Kiriko Matsumoto
- Department of Bioscience and Biotechnology, Faculty of Agriculture, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan
| | - Shogo Senga
- Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan
| | - Koichiro Kawaguchi
- Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan
| | - Ayaka Yamamoto
- Graduate School of Science and Technology, Department of Biomedical Engineering, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan
| | - Jutalak Suwannachot
- Graduate School of Science and Technology, Department of Agriculture, Division of Food Science and Biotechnology, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan
| | - Yasunori Hamauzu
- Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan.,Graduate School of Science and Technology, Department of Agriculture, Division of Food Science and Biotechnology, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan
| | - Hidefumi Makabe
- Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan.,Graduate School of Science and Technology, Department of Agriculture, Division of Food Science and Biotechnology, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan.,Department of Biomolecular Innovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan
| | - Hiroshi Fujii
- Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan.,Graduate School of Science and Technology, Department of Biomedical Engineering, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano, 399-4598, Japan.,Department of Biomolecular Innovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Minami-minowa, Kami-ina, Nagano, 399-4598, Japan
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Han S, Gao H, Chen S, Wang Q, Li X, Du LJ, Li J, Luo YY, Li JX, Zhao LC, Feng J, Yang S. Procyanidin A1 Alleviates Inflammatory Response induced by LPS through NF-κB, MAPK, and Nrf2/HO-1 Pathways in RAW264.7 cells. Sci Rep 2019; 9:15087. [PMID: 31636354 PMCID: PMC6803657 DOI: 10.1038/s41598-019-51614-x] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 10/03/2019] [Indexed: 12/16/2022] Open
Abstract
Inflammation is a complex physiological process that poses a serious threat to people’s health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/β and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.
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Affiliation(s)
- Shan Han
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020, China
| | - Hongwei Gao
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020, China
| | - Shaoru Chen
- Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, 44272, USA
| | - Qinqin Wang
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020, China
| | - Xinxing Li
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020, China
| | - Li-Jun Du
- School of Life Sciences, Tsinghua University, Beijing, 100084, China
| | - Jun Li
- State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China
| | - Ying-Ying Luo
- State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China
| | - Jun-Xiu Li
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020, China
| | - Li-Chun Zhao
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China. .,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020, China.
| | - Jianfang Feng
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China. .,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020, China.
| | - Shilin Yang
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020, China
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Lohani M, Majrashi M, Govindarajulu M, Patel M, Ramesh S, Bhattacharya D, Joshi S, Fadan M, Nadar R, Darien B, Maurice DV, Kemppainen B, Dhanasekaran M. Immunomodulatory actions of a Polynesian herb Noni (Morinda citrifolia) and its clinical applications. Complement Ther Med 2019; 47:102206. [PMID: 31780035 DOI: 10.1016/j.ctim.2019.102206] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/25/2019] [Accepted: 09/30/2019] [Indexed: 12/24/2022] Open
Abstract
Morinda citrifolia (Noni) is a popular traditional medicinal plant consumed in various forms in several countries around the world as a complementary and alternative treatment due to its established health benefits. Noni is rich in bioactive substances and has significantly exhibited pro-oxidant and immunomodulatory effects. In this review, we highlight the pharmacological basis related to the phytochemicals and polysaccharides present in Noni and its potential therapeutic effects. We screened electronic databases such as PubMed, Google Scholar, Scopus for scientific literature. Our results indicate that Noni is beneficial for various diseases with its crude extracts showing therapeutic benefit for a wide range of pathological diseases. We believe that further pharmacological and toxicological studies in addition to well-designed controlled clinical trials can validate Noni to be an effective and novel natural product for prophylactic and therapeutic use of several diseases.
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Affiliation(s)
- Madhukar Lohani
- Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn, AL 36830, USA
| | - Mohammed Majrashi
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA; Department of Pharmacology, Faculty of Medicine, University of Jeddah, Jeddah, 23881, Saudi Arabia
| | - Manoj Govindarajulu
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA
| | - Mansi Patel
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA
| | - Sindhu Ramesh
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA
| | - Dwipayan Bhattacharya
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA
| | - Sneha Joshi
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA
| | - Maali Fadan
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA
| | - Rishi Nadar
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA
| | - Benjamin Darien
- Department of Medical Sciences, College of Veterinary Medicine, University of Wisconsin-Madison, WI, 53706, USA
| | - Denzil V Maurice
- Animal and Veterinary Sciences, College of Agriculture, Clemson University, Clemson, 29634, USA
| | - Barbara Kemppainen
- Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn, AL 36830, USA
| | - Muralikrishnan Dhanasekaran
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
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Khan H, Ullah H, Castilho PCMF, Gomila AS, D'Onofrio G, Filosa R, Wang F, Nabavi SM, Daglia M, Silva AS, Rengasamy KRR, Ou J, Zou X, Xiao J, Cao H. Targeting NF-κB signaling pathway in cancer by dietary polyphenols. Crit Rev Food Sci Nutr 2019; 60:2790-2800. [PMID: 31512490 DOI: 10.1080/10408398.2019.1661827] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Being a transcription factor, NF-κB regulates gene expressions involving cell survival and proliferation, drug resistance, metastasis, and angiogenesis. The activation of NF-κB plays a central role in the development of inflammation and cancer. Thus, the down-regulation of NF-κB may be an exciting target in prevention and treatment of cancer. NF-κB could act as a tumor activator or tumor suppressant decided by the site of action (organ). Polyphenols are widely distributed in plant species, consumption of which have been documented to negatively regulate the NF-κB signaling pathway. They depress the phosphorylation of kinases, inhibit NF-κB translocate into the nucleus as well as interfere interactions between NF-κB and DNA. Through inhibition of NF-κB, polyphenols downregulate inflammatory cascade, induce apoptosis and decrease cell proliferation and metastasis. This review highlights the anticancer effects of polyphenols on the basis of NF-κB signaling pathway regulation.
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Affiliation(s)
- Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan
| | - Hammad Ullah
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan
| | | | - Antoni Sureda Gomila
- Research Group on Community Nutrition and Oxidative Stress, University of the Balearic Islands, Palma de Mallorca, Spain
- CIBEROBN (Physiopathology of Obesity and Nutrition, CB12/03/30038), Instituto de Salud Carlos III, Madrid, Spain
| | - Grazia D'Onofrio
- Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza", Complex Unit of Geriatrics, San Giovanni Rotondo, Italy
| | - Rosanna Filosa
- Department of Experimental Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy
- Consorzio Sannio Tech, Apollosa, Italy
| | - Fang Wang
- College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, China
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Maria Daglia
- Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Pavia, Italy
| | - Ana Sanches Silva
- National Institute for Agricultural and Veterinary Research, Vairão, Vila do Conde, Portugal
- Center for Study in Animal Science (CECA), ICETA, University of Oporto, Oporto, Portugal
| | - Kannan R R Rengasamy
- Department of Bio-resources and Food Science, Konkuk University, Seoul, South Korea
| | - Juanying Ou
- Institute of Food Safety and Nutrition, Jinan University, Guangzhou, China
| | - Xiaobo Zou
- Institute of Food Safety and Nutrition, Jiangsu University, Zhenjiang, China
| | - Jianbo Xiao
- Institute of Food Safety and Nutrition, Jinan University, Guangzhou, China
- Institute of Food Safety and Nutrition, Jiangsu University, Zhenjiang, China
| | - Hui Cao
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China
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48
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Isolation and characterization of a novel oligomeric proanthocyanidin with significant anti-cancer activities from grape stems (Vitis vinifera). Sci Rep 2019; 9:12046. [PMID: 31427660 PMCID: PMC6700121 DOI: 10.1038/s41598-019-48603-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 08/08/2019] [Indexed: 11/13/2022] Open
Abstract
Novel proanthocyanidin fractions from grape stem extracts were purified using Amberlite XAD-1180N, Sephadex-LH-20, Toyopearl HW40F and reverse phase high-performance liquid chromatography. Two key compounds were estimated as epigallocatechin-(epicatechin)7 gallate using electron-spray ionization time-of-flight mass spectrometry. Epigallocatechin-(epicatechin)7 gallate (compound 1) showed significant anti-cancer activity in PC-3 prostate cancer cells. In particular, compound 1 suppressed the gene expression of fatty acid-binding protein 5 (FABP5), which is involved in promoting cell proliferation and metastasis in prostate cancer cells.
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49
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Tian Y, Yang C, Yao Q, Qian L, Liu J, Xie X, Ma W, Nie X, Lai B, Xiao L, Wang N. Procyanidin B2 Activates PPARγ to Induce M2 Polarization in Mouse Macrophages. Front Immunol 2019; 10:1895. [PMID: 31440258 PMCID: PMC6693435 DOI: 10.3389/fimmu.2019.01895] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 07/26/2019] [Indexed: 11/13/2022] Open
Abstract
Procyanidins, a subclass of flavonoids found in commonly consumed foods, possess potential anti-inflammatory activity. Manipulation of M1/M2 macrophage homeostasis is an effective strategy for the treatment of metabolic inflammatory diseases. The objective of this study was to determine the effect of procyanidins on macrophage polarization. Procyanidin B2 (PCB2), the most widely distributed natural procyanidins, enhanced the expressions of M2 macrophage markers (Arg1, Ym1, and Fizz1). PCB2 activated peroxisome proliferator-activated receptor γ (PPARγ) activity and increased the expressions of PPARγ target genes (CD36 and ABCG1) in macrophages. Inhibition of PPARγ using siRNA or antagonist GW9662 attenuated the PCB2-induced expressions of M2 macrophage markers. In addition, we identified cognate PPAR-responsive elements (PPREs) within the 5'-flanking regions of the mouse Arg1, Ym1, and Fizz1 genes. Furthermore, macrophages isolated from db/db diabetic mice showed lower expressions of M2 markers. PCB2 effectively restored the Arg1, Ym1, and Fizz1 expressions in a PPARγ-dependent manner. These findings support the notion that PCB2 regulated macrophage M2 polarization via the activation of PPARγ. Our results provide a new mechanism by which procyanidins exert their beneficial anti-inflammatory effects.
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Affiliation(s)
- Ying Tian
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Chunmiao Yang
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Qinyu Yao
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Lei Qian
- The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China
| | - Jia Liu
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Xinya Xie
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Wen Ma
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Xin Nie
- The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China
| | - Baochang Lai
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Lei Xiao
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Nanping Wang
- The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China.,College of Basic Medical Sciences, Dalian Medical University, Dalian, China
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50
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Zhang L, Virgous C, Si H. Synergistic anti-inflammatory effects and mechanisms of combined phytochemicals. J Nutr Biochem 2019; 69:19-30. [DOI: 10.1016/j.jnutbio.2019.03.009] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 02/22/2019] [Accepted: 03/14/2019] [Indexed: 12/31/2022]
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