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Ren Y, Li Z, Li W, Fan X, Han F, Huang Y, Yu Y, Qian L, Xiong Y. Arginase: Biological and Therapeutic Implications in Diabetes Mellitus and Its Complications. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:2419412. [PMID: 36338341 PMCID: PMC9629921 DOI: 10.1155/2022/2419412] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 10/18/2022] [Indexed: 09/21/2023]
Abstract
Arginase is a ubiquitous enzyme in the urea cycle (UC) that hydrolyzes L-arginine to urea and L-ornithine. Two mammalian arginase isoforms, arginase1 (ARG1) and arginase2 (ARG2), play a vital role in the regulation of β-cell functions, insulin resistance (IR), and vascular complications via modulating L-arginine metabolism, nitric oxide (NO) production, and inflammatory responses as well as oxidative stress. Basic and clinical studies reveal that abnormal alterations of arginase expression and activity are strongly associated with the onset and development of diabetes mellitus (DM) and its complications. As a result, targeting arginase may be a novel and promising approach for DM treatment. An increasing number of arginase inhibitors, including chemical and natural inhibitors, have been developed and shown to protect against the development of DM and its complications. In this review, we discuss the fundamental features of arginase. Next, the regulatory roles and underlying mechanisms of arginase in the pathogenesis and progression of DM and its complications are explored. Furthermore, we review the development and discuss the challenges of arginase inhibitors in treating DM and its related pathologies.
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Affiliation(s)
- Yuanyuan Ren
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Zhuozhuo Li
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Wenqing Li
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Xiaobin Fan
- Department of Obstetrics and Gynecology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, China
| | - Feifei Han
- Department of Endocrinology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, China
| | - Yaoyao Huang
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Yi Yu
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Lu Qian
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China
- Department of Obstetrics and Gynecology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, China
| | - Yuyan Xiong
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China
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Park I, Yang S, Choi G, Moon BC, Song JH. An Integrated Approach for Efficient and Accurate Medicinal Cuscutae Semen Identification. PLANTS (BASEL, SWITZERLAND) 2020; 9:E1410. [PMID: 33105814 PMCID: PMC7690581 DOI: 10.3390/plants9111410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 10/11/2020] [Accepted: 10/20/2020] [Indexed: 11/16/2022]
Abstract
To guarantee the safety and efficacy of herbal medicines, accurate identification and quality evaluation are crucial. The ripe dried seeds of Cuscuta australis R.Br. and C. chinensis Lam. are known as Cuscutae Semen (CS) and are widely consumed in Northeast Asia; however, the seeds of other species can be misidentified as CS owing to morphological similarities, leading to misuse. In this report, we propose a multilateral strategy combining microscopic techniques with statistical analysis and DNA barcoding using a genus-specific primer to facilitate the identification and authentication of CS. Morphology-based identification using microscopy revealed that the useful diagnostic characteristics included general shape, embryo exudation, hairiness, and testa ornamentation, which were used to develop an effective identification key. In addition, we conducted DNA barcoding-based identification to ensure accurate authentication. A novel DNA barcode primer was produced from the chloroplast rbcL gene by comparative analysis using Cuscuta chloroplast genome sequences, which allowed four Cuscuta species and adulterants to be discriminated completely. Therefore, this investigation overcame the limitations of universal DNA barcodes for Cuscuta species with high variability. We believe that this integrated approach will enable CS to be differentiated from other species, thereby improving its quality control and product safety in medicinal markets.
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Affiliation(s)
| | | | | | - Byeong Cheol Moon
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju 58245, Korea; (I.P.); (S.Y.); (G.C.)
| | - Jun-Ho Song
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju 58245, Korea; (I.P.); (S.Y.); (G.C.)
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l-Theanine attenuates liver aging by inhibiting advanced glycation end products in d-galactose-induced rats and reversing an imbalance of oxidative stress and inflammation. Exp Gerontol 2020; 131:110823. [DOI: 10.1016/j.exger.2019.110823] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 12/07/2019] [Accepted: 12/29/2019] [Indexed: 12/31/2022]
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Semen Cuscutae Administration Improves Hepatic Lipid Metabolism and Adiposity in High Fat Diet-Induced Obese Mice. Nutrients 2019; 11:nu11123035. [PMID: 31842363 PMCID: PMC6950589 DOI: 10.3390/nu11123035] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 12/05/2019] [Accepted: 12/10/2019] [Indexed: 12/29/2022] Open
Abstract
Since arginase has been shown to compete with nitric oxide (NO) synthase, emerging evidence has reported that arginase inhibition improves obesity by increasing NO production. Semen cuscutae (SC), which is a well-known Chinese medicine, has multiple biological functions such as anti-oxidant function and immune regulation. In this study, we investigated whether the SC as a natural arginase inhibitor influences hepatic lipid abnormalities and whole-body adiposity in high-fat diet (HFD)-induced obese mice. The lipid accumulation was significantly reduced by SC treatment in oleic acid-induced hepatic steatosis in vitro. Additionally, SC supplementation substantially lowered HFD-induced increases in arginase activity and weights of liver and visceral fat tissue, while increasing hepatic NO. Furthermore, elevated mRNA expressions of sterol regulatory element-binding transcription factor 1 (SREBP-1c), fatty-acid synthase (FAS), peroxisome proliferator-activated receptor-gamma (PPAR-γ)1, and PPAR-γ2 in HFD-fed mice were significantly attenuated by SC supplementation. Taken together, SC, as a novel natural arginase inhibitor, showed anti-obesity properties by modulating hepatic arginase and NO production and metabolic pathways related to hepatic triglyceride (TG) metabolism.
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Tang C, Feng W, Qin L, Bao Y. Chinese Herbal Medicine, Jian Pi Li Gan Decoction, Improved Survival of Nonresectable Hepatocellular Cancer After Radiofrequency Ablation: A Retrospective Study. Integr Cancer Ther 2018; 17:431-436. [PMID: 28745082 PMCID: PMC6041913 DOI: 10.1177/1534735417722223] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2016] [Revised: 05/22/2017] [Accepted: 06/14/2017] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE To observe the effect of Jian Pi Li Gan Decoction (JPLGD) on long-term survival of nonresectable hepatocellular cancer (HCC) after radiofrequency ablation (RFA). METHODS Between January 2010 and February 2013, 95 patients with nonresectable HCC treated by RFA in our hospital were enrolled, of whom 47 patients received JPLGD accompanying RFA (JPLGD group), and 48 patients received RFA alone (control group). Medical records of these patients were retrospectively analyzed. Long-term survival, complication, and treatment event were compared. RESULTS Baseline characteristics did not differ between the 2 groups. No significant adverse effects or toxicities related to herbal medicine were found. The JPLGD group had significantly less liver failure (3/47 vs 10/48, P = .0405) and a higher treatment success rate than the control group (44/47 vs 37/48, P = .0230). The 3-year overall survival probability was significantly higher in the JPLGD group ( P = .0175). CONCLUSION JPLGD has the potential to effectively and safely improve long-term survival of nonresectable HCC by increasing treatment success of RFA.
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Affiliation(s)
- Chengwu Tang
- First People’s Hospital Affiliated to Huzhou Normal College, Huzhou, Zhejiang Province, People’s Republic of China
| | - Wenming Feng
- First People’s Hospital Affiliated to Huzhou Normal College, Huzhou, Zhejiang Province, People’s Republic of China
| | - Lianjin Qin
- First People’s Hospital Affiliated to Huzhou Normal College, Huzhou, Zhejiang Province, People’s Republic of China
| | - Ying Bao
- First People’s Hospital Affiliated to Huzhou Normal College, Huzhou, Zhejiang Province, People’s Republic of China
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Neuroprotective effects of cuscutae semen in a mouse model of Parkinson's disease. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 2014:150153. [PMID: 25140184 PMCID: PMC4129928 DOI: 10.1155/2014/150153] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Revised: 06/15/2014] [Accepted: 07/03/2014] [Indexed: 11/18/2022]
Abstract
Parkinson's disease (PD) is a neurodegenerative movement disorder that is characterized by the progressive degeneration of the dopaminergic (DA) pathway. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes damage to the DA neurons, and 1-4-methyl-4-phenylpyridinium (MPP(+)) causes cell death in differentiated PC12 cells that is similar to the degeneration that occurs in PD. Moreover, MPTP treatment increases the activity of the brain's immune cells, reactive oxygen species- (ROS-) generating processes, and glutathione peroxidase. We recently reported that Cuscutae Semen (CS), a widely used traditional herbal medicine, increases cell viability in a yeast model of PD. In the present study, we examined the inhibitory effect of CS on the neurotoxicity of MPTP in mice and on the MPP+-induced cell death in differentiated PC12 cells. The MPTP-induced loss of nigral DA neurons was partly inhibited by CS-mediated decreases in ROS generation. The activation of microglia was slightly inhibited by CS, although this effect did not reach statistical significance. Furthermore, CS may reduce the MPP+ toxicity in PC12 cells by suppressing glutathione peroxidase activation. These results suggest that CS may be beneficial for the treatment of neurodegenerative diseases such as PD.
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Su KY, Yu CY, Chen YP, Hua KF, Chen YLS. 3,4-Dihydroxytoluene, a metabolite of rutin, inhibits inflammatory responses in lipopolysaccharide-activated macrophages by reducing the activation of NF-κB signaling. Altern Ther Health Med 2014. [PMID: 24417898 DOI: 10.1186/1472-6882-14-21.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND Saussurea involucrata (Kar. et Kir.) (S. involucrate), is a rare traditional Chinese medicinal herb. Rutin and hispidulin as well as their metabolites are flavonoids of the flavonol type that abound in S. involucrata, which has been reported to inhibit nonoxidative advanced glycation end products which was involved in physiological inflammation. This study aims to investigate the role of 3,4-dihydroxytoluene (DHT), a metabolite of rutin, in inflammatory inhibition and its involved mechanism. METHODS This study utilized lipopolysaccharide (LPS) stimulated murine macrophage cell line RAW 264.7 as inflammatory model. The inhibitory effects of DHT were evaluated by the expression level of several inflammation markers such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 after LPS treatment. In addition, underlying mechanisms, the activation of mitogen-activated protein kinases (MAPKs) and NF-κB, were also investigated. RESULTS Our results showed that DHT significantly suppressed the LPS-induced production of nitric oxide (NO), iNOS, and COX-2 in a dose-dependent manner without cytotoxicity. DHT also reduced the generation of proinflammatory cytokines majorly in tumor necrosis factor (TNF)-α and minor in interleukin (IL)-1β and IL-6. In addition, LPS-stimulated I-κBα phosphorylation and degradation followed by translocation of the nuclear factor κB (NF-kB)-p65 from the cytoplasm to the nucleus were attenuated after DHT treatment. CONCLUSIONS Combined, the results suggest that DHT might exert anti-inflammatory effects in vitro in LPS stimulated RAW 264.7 macrophages and is potential in adjuvant treatment in inflammation disease.
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Affiliation(s)
| | | | | | | | - Yi-Lin Sophia Chen
- Department of Biotechnology and Animal Science, National Ilan University, Shen-Lung Road, Ilan 260, Taiwan.
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Su KY, Yu CY, Chen YP, Hua KF, Chen YLS. 3,4-Dihydroxytoluene, a metabolite of rutin, inhibits inflammatory responses in lipopolysaccharide-activated macrophages by reducing the activation of NF-κB signaling. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 14:21. [PMID: 24417898 PMCID: PMC3900474 DOI: 10.1186/1472-6882-14-21] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2013] [Accepted: 01/10/2014] [Indexed: 01/01/2023]
Abstract
Background Saussurea involucrata (Kar. et Kir.) (S. involucrate), is a rare traditional Chinese medicinal herb. Rutin and hispidulin as well as their metabolites are flavonoids of the flavonol type that abound in S. involucrata, which has been reported to inhibit nonoxidative advanced glycation end products which was involved in physiological inflammation. This study aims to investigate the role of 3,4-dihydroxytoluene (DHT), a metabolite of rutin, in inflammatory inhibition and its involved mechanism. Methods This study utilized lipopolysaccharide (LPS) stimulated murine macrophage cell line RAW 264.7 as inflammatory model. The inhibitory effects of DHT were evaluated by the expression level of several inflammation markers such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 after LPS treatment. In addition, underlying mechanisms, the activation of mitogen-activated protein kinases (MAPKs) and NF-κB, were also investigated. Results Our results showed that DHT significantly suppressed the LPS-induced production of nitric oxide (NO), iNOS, and COX-2 in a dose-dependent manner without cytotoxicity. DHT also reduced the generation of proinflammatory cytokines majorly in tumor necrosis factor (TNF)-α and minor in interleukin (IL)-1β and IL-6. In addition, LPS-stimulated I-κBα phosphorylation and degradation followed by translocation of the nuclear factor κB (NF-kB)-p65 from the cytoplasm to the nucleus were attenuated after DHT treatment. Conclusions Combined, the results suggest that DHT might exert anti-inflammatory effects in vitro in LPS stimulated RAW 264.7 macrophages and is potential in adjuvant treatment in inflammation disease.
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Evaluation on Anti-Inflammatory, Analgesic, Antitumor, and Antioxidant Potential of Total Saponins from Nigella glandulifera Seeds. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:827230. [PMID: 23533525 PMCID: PMC3590790 DOI: 10.1155/2013/827230] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/12/2012] [Revised: 12/15/2012] [Accepted: 01/16/2013] [Indexed: 01/11/2023]
Abstract
Nigella glandulifera seeds are used as a spice or remedy for the treatment of various inflammatory diseases. This study aimed to investigate analgesic (writhing test), anti-inflammatory (ear-induced edema, vascular permeability test), antioxidant, and antitumor activities of total saponins from this plant (TSN). TSN (6, 12, and 24 mg/kg) were exhibited analgesic and anti-inflammatory activities in a dose-dependent manner (P < 0.05). In D-galactose-induced ageing model, TSN significantly increased the plasma superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities (P < 0.05) and decreased the malondialdehyde (MDA) level compared to control group (P < 0.05). DPPH radical scavenging effect of TSN was also found. Moreover, TSN (20 mg/mL) showed 86.75% and 88.26% inhibition of the growth on Bel-7402 and Hela cells, respectively. Five compounds were further isolated and identified from TSN as Nigella A, B, C, D, and nigeglanoside, of which the content of Nigella A was 60.36 ± 1.25 g/100 g TSN by HPLC-ELSD method. Altogether, these results suggest that TSN could be considered as a potential analgesic, anti-inflammatory, antitumor, and antioxidant agent.
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Rutin, a Flavonoid That Is a Main Component of Saussurea involucrata, Attenuates the Senescence Effect in D-Galactose Aging Mouse Model. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 2012:980276. [PMID: 22952557 PMCID: PMC3431096 DOI: 10.1155/2012/980276] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2012] [Accepted: 06/19/2012] [Indexed: 12/31/2022]
Abstract
Saussurea involucrata (Kar. et Kir.), known as the snow lotus, grows in the Tian Shan and A'er Tai areas of China. It has recently been reported that the ethyl acetate extract of S. involucrata (SI-2) can inhibit proliferation and induce apoptosis in PC-3 human prostate cancer cells. This study investigated the protective effect of ethyl acetate extract of S. involucrata (SI-2) or rutin, a flavonoid extracted from ethyl acetate extract of S. involucrata (SI-2), on D-galactose- (D-gal-) induced brain injury in mice. Administering SI-2 or rutin (30 mg/kg/d and 30 mg/kg/d) for 6 weeks, concomitant with D-gal injection, significantly increased superoxide dismutase and glutathione peroxidase activities and decreased the MDA level in plasma. Furthermore, the result showed that the percentages of cleaved caspase-3 and PARP in the D-gal-treated mice were much higher than those in the control. Pretreatment using SI-2 or rutin decreased the expression of cyclooxygenase-2 via downregulation of NF-kappaB, resulting in a decrease in lipid peroxidation. Furthermore, our results also showed that oral administration of rutin to these mice significantly improved behavioral performance in a step-through passive avoidance task and these results suggest that SI-2 or rutin exerts potent antiaging effects on D-gal in mice via antioxidative mechanisms.
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Szeto YT, Wong SCY, Wong JWM, Kalle W, Pak SC. In vitro antioxidation activity and genoprotective effect of selected Chinese medicinal herbs. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2011; 39:827-38. [PMID: 21721160 DOI: 10.1142/s0192415x11009238] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Some traditional Chinese medicinal seeds and fruits are well known for their antioxidant properties. This research aims to investigate whether Fructus Lycii, Fructus Schisandrae Chinensis, Fructus Ligustri Lucidi and Semen Cuscutae protect DNA from oxidant challenge by hydrogen peroxide (H(2)O(2)). The standard comet assay was used to assess the genoprotective effect of these medicinal herbs. Blood was taken from three healthy adults, aged from 36 to 42. Lymphocytes were isolated and treated with different concentrations of aqueous herbal extracts, while controls were treated with phosphate buffered saline. The lymphocytes were stressed with 50 μM H(2)O(2). Treated cells were embedded in agarose and layered on slides. These sandwiched lymphocytes were lysed and afterwards subjected to an electric field in an alkaline environment. Damaged DNA was pulled out from the nucleus towards the positive electrode as a comet tail; its density was related to the degree of DNA damage. Finally, the slides were stained with fluorescence dye and tails were visually scored for 100 cells. The experiment was repeated three times and DNA damage in treated cells was compared to the controls. There was no statistical difference in DNA damage among the herb treated cells and untreated cells in the comet assay. Our data demonstrated that the selected medicinal herbs did not show in vitro DNA protection in the comet assay against oxidant challenge.
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Affiliation(s)
- Yim Tong Szeto
- Department of Applied Science, Hong Kong Institute of Vocational Education (Shatin), Sha Tin, New Territories, Hong Kong.
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Antioxidative and hepatoprotective effects of fructo-oligosaccharide ind-galactose-treated Balb/cJ mice. Br J Nutr 2010; 105:805-9. [DOI: 10.1017/s000711451000437x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Chronic subcutaneous (s.c.) administration ofd-galactose (DG) to BL/6J mice has been shown to induce oxidative stress and is considered a model to mimic accelerated ageing. Fructo-oligosaccharide (FO) is a well-defined prebiotic and its fermentation by lactic acid bacteria has been shown to exert antioxidative capacity. The present study was aimed to determine whether FO attenuated DG-induced oxidative stress and hepatopathy in Balb/cJ mice. Mice (12 weeks of age,n40) were divided into control (s.c. saline), DG (s.c. 1·2 g/kg body weight), DG+FO (5 %, w/w) and DG+vitamin E (0·2 %, w/w) groups and were killed after 52 d of treatment. Results indicated that DG significantly decreased the hepatic superoxide dismutase and glutathione peroxidase activities. These alterations were ameliorated both by FO and vitamin E. DG increased the hepatic TAG content approximately by 7·2 % compared with the vehicle control, which was in agreement with the histological alteration. FO, similar to vitamin E, almost normalised the hepatic TAG content and ameliorated the histological characteristics of fatty liver. Similarly, the increased plasma alanine aminotransferase activity induced by DG was normalised by FO and vitamin E, respectively. Faecal bifidobacteria counts were greater in the DG+FO and DG+vitamin E groups compared with the DG group, respectively. In conclusion, the present study indicated that FO diminished the altered hepatic antioxidative enzyme activities and morphology caused by chronic DG administration in Balb/cJ mice, partially associated with its prebiotic role in the colon.
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Yu SL, Lin SB, Yu YL, Chien MH, Su KJ, Lin CJ, Way TD, Yiang GT, Lin CC, Chan DC, Harn HJ, Chen YLS. Isochaihulactone protects PC12 cell against H(2)O(2) induced oxidative stress and exerts the potent anti-aging effects in D-galactose aging mouse model. Acta Pharmacol Sin 2010; 31:1532-40. [PMID: 21042289 DOI: 10.1038/aps.2010.152] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
AIM to investigate the effect of isochaihulactone (also known as K8), a lignan compound of Bupleurum scorzonerifolium, on H(2)O(2)-induced cytotoxicity in neuronally differentiated PC12 cells (nPC12). METHODS viability of neuronal PC12 cells was measured using MTT assay. Protein expression was determined by Western blot. Apoptotic cells was determined using TUNEL assay. D-galactose aging mice were used as a model system to study the anti-oxidant effects of isochaihulactone in vivo. RESULTS pretreatment with isochaihulactone (5-10 micromol/L) increased cell viability and decreased membrane damage, generation of reactive oxygen species and degradation of poly (ADP-ribose) polymerase in H(2)O(2)-treated nPC12 cells and also decreased the expression of cyclooxygenase-2, via downregulation of NF-kappaB, resulting in a decrease in lipid peroxidation. The results suggest that isochaihulactone is a potential antioxidant agent. In a murine aging model, in which chronic systemic exposure to D-galactose (D-gal) causes the acceleration of senescence, administration of isochaihulactone (10 mgxkg(-1)xd(-1), sc) for 7 weeks concomitant with D-gal injection significantly increased superoxide dismutase and glutathione peroxidase activities and decreased the MDA level in plasma. Furthermore, H&E staining to quantify cell death within hippocampus showed that percentage of pyknotic nuclei in the D-gal-treated mice were much higher than in control. CONCLUSION the results suggest that isochaihulactone exerts potent anti-aging effects against D-gal in mice possibly via antioxidative mechanisms.
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Ku SK, Seo BI, Park JH, Park GY, Seo YB, Kim JS, Lee HS, Roh SS. Effect of Lonicerae Flos extracts on reflux esophagitis with antioxidant activity. World J Gastroenterol 2009; 15:4799-805. [PMID: 19824114 PMCID: PMC2761558 DOI: 10.3748/wjg.15.4799] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To observe the effects of traditional antiinflammatory medicine Lonicerae Flos (LF) on rat reflux esophagitis (RE) induced by pylorus and forestomach ligation compared with the well-known proton antioxidant, α-tocopherol.
METHODS: Rats were pretreated with three different dosages of LF (500, 250 and 125 mg/kg) orally, once a day for 14 d before pylorus and forestomach ligation. Nine hours after pylorus and forestomach ligation, changes to the stomach and esophagus lesion areas, gastric volumes, acid and pepsin outputs, antioxidant effects, esophageal lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), myeloperoxidase and glutathione (GSH) levels, and collagen contents (marker of flexibility) were observed on the esophageal and fundic histopathology. The results were compared with an α-tocopherol (once orally, 1 h before operation, 30 mg/kg) treated group in which the effects on RE were already confirmed.
RESULTS: Pylorus and forestomach ligations caused marked increases of gross esophageal and gastric mucosa lesion areas, which corresponded with histopathological changes. In addition, increases of esophageal lipid peroxidation, decreases of SOD, CAT, and GSH-free radical scavengers, increases of collagen were observed. However, these pylorus and forestomach ligation induced RE were dose-dependently inhibited by treatment of 500, 250 and 125 mg/kg of LF extract, mediated by antioxidant effects. RE at 250 mg/kg showed similar effects α-tocopherol.
CONCLUSION: The results suggest that antioxidant effects of LF could attenuate the severity of RE and prevent the esophageal mucosal damage, and validate its therapeutic use in esophageal reflux disease.
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Extraction, characterization of Angelica sinensis polysaccharides and modulatory effect of the polysaccharides and Tai Chi exercise on oxidative injury in middle-aged women subjects. Carbohydr Polym 2009. [DOI: 10.1016/j.carbpol.2009.01.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Tempest HG, Homa ST, Routledge EJ, Garner A, Zhai XP, Griffin DK. Plants used in Chinese medicine for the treatment of male infertility possess antioxidant and anti-oestrogenic activity. Syst Biol Reprod Med 2008; 54:185-95. [PMID: 18942026 DOI: 10.1080/19396360802379073] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
In this study Chinese herbs commonly used in the treatment of male infertility were investigated for relevant biochemical activity. Male factor infertility predominantly arises via barriers to, or defects in, spermatogenesis. The process of spermatogenesis is under strict endocrine control; in addition oxidative stress has been implicated in male infertility with significant levels of reactive oxygen species detected in 25% of infertile males. A total of 37 individual herbs and seven herb decoctions used in the treatment of male factor infertility were therefore tested for endocrine activity using a recombinant yeast based assay and antioxidant activity using the FRAP (ferric reducing antioxidant potential) assay. Individual herbs tested did not show androgenic properties, 20 showed strong and 10 weak anti-oestrogenic activity (per g of dried herb tamoxifen equivalents ranged from 1.18-1280.66 mg and 0.06-0.98 mg, respectively). Oestrogenic responses were elicited for two herbs (85.30-550 microg oestradiol equivalents/g dried herb), with seven and three herbs exhibiting a strong or weak anti-androgenic response (per g of dried herb DHT equivalents ranged from 1.54-66.78 mg and 0.17-0.32 mg), respectively. Of these 37 herbs, strong (15 herbs), intermediate (7 herbs) and weak/no (15 herbs) antioxidant activity was detected (ranging from 0.912-1.26; 0.6-0.88 and 0-0.468 microg ascorbate equivalent/mg dried herb, respectively). The seven decoctions (previously used to treat patients) tested elicited strong (5 herbs) and weak (2 herbs) anti-oestrogenic responses (per g of dried herb tamoxifen equivalents ranged from 1.14-13.23 mg and 0.22-0.26 mg, respectively), but not oestrogenic, androgenic nor anti-androgenic, consistent with their individual composition. With regard to antioxidant activity the following responses were recorded: three strong, three intermediate and one weak (ranging from 1.02-1.2; 0.72-0.76 and 0.44 microg ascorbate equivalent/mg dried herb, respectively). The prospects for introducing Chinese herbal treatments into the Western-based medicine are discussed.
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Affiliation(s)
- Helen G Tempest
- Department of Biosciences, Canterbury, Kent, University of Kent, UK.
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Thangthaeng N, Sumien N, Forster MJ. Dissociation of functional status from accrual of CML and RAGE in the aged mouse brain. Exp Gerontol 2008; 43:1077-85. [PMID: 18783731 PMCID: PMC2698668 DOI: 10.1016/j.exger.2008.08.045] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2007] [Revised: 08/18/2008] [Accepted: 08/19/2008] [Indexed: 11/25/2022]
Abstract
The objectives of this study were: (i) to identify regions of the aged mouse brain in which advanced glycation end-products (AGEs) were increased, and (ii) assess the functional significance of AGEs by determining the extent to which they could predict age-related brain dysfunction. Densitometric analyses of immunoblots for N epsilon-(carboxymethyl)lysine (CML), a predominant AGE, and receptor for AGE (RAGE), were performed in different brain regions of mice aged 8 or 25 months. The 25-month-old mice were tested for ability to perform on tests of cognitive and psychomotor function prior to assessment of CML or RAGE, to determine if immunostaining results could predict functional impairment among the older mice. The amounts of CML increased with age in cortex, hippocampus, striatum, and midbrain, but were unchanged in the brainstem and cerebellum. Increases in RAGE were evident in all brain regions but the hippocampus, and were not linked to increased amounts of CML. Different statistical approaches each failed to reveal any strong association between the degree of age-related functional impairment among individual mice and amounts of CML or RAGE in any particular region of the brain. The findings from this study suggest that accrual of CML and expression of RAGE in different brain regions are time-related phenomena that do not account for individual differences in brain aging or cognitive decline.
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Affiliation(s)
- Nopporn Thangthaeng
- Department of Pharmacology and Neuroscience, Department of Psychology, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107
| | - Nathalie Sumien
- Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107
| | - Michael J. Forster
- Department of Pharmacology and Neuroscience, Department of Psychology, Institute for Aging and Alzheimer’s Disease Research, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107
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Tong Y, Wang Q, Hou H. Protection by Chinese Herbs Against Doxorubicin-Induced Focal and Segmental Glomerulosclerosis in Rats. Drug Dev Ind Pharm 2008; 34:663-7. [DOI: 10.1080/03639040701836537] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Wu YF, Cao MF, Gao YP, Chen F, Wang T, Zumbika EP, Qian KX. Down-modulation of heat shock protein 70 and up-modulation of Caspase-3 during schisandrin B-induced apoptosis in human hepatoma SMMC-7721 cells. World J Gastroenterol 2004; 10:2944-8. [PMID: 15378770 PMCID: PMC4576249 DOI: 10.3748/wjg.v10.i20.2944] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To investigate the effect of schisandrin B (Sch B) on proliferation and apoptosis of human hepatoma SMMC-7721 cells in vitro and regulation of Hsp70 and Caspases-3, 7, 9 expression by Sch B.
METHODS: Human hepatoma cell line SMMC-7721 was cultured and treated with Sch B at various concentrations. Growth suppression was detected with MTT colorimetric assay. Cell apoptosis was confirmed by DNA ladder detection and flow cytometric analysis. The expression of Hsp70, Caspases-3, 7, 9 were analyzed by Western blot analysis.
RESULTS: Sch B inhibited the growth of hepatoma SMMC-7721 cells in a dose-dependent manner, leading to a 50% decrease in cell number (LC50) value of 23.50 mg/L. Treatment with Sch B resulted in degradation of chromosomal DNA into small internucleosomal fragments, evidenced by the formation of a 180-200 bp DNA ladder on agarose gels. FCM analysis showed the peak areas of subdiploid at the increased concentration of Sch B. The results of Western bolt analysis showed that Hsp70 was down-regulated and Caspase-3 was up-regulated, while the activity of Caspases-7, -9 had no significant change.
CONCLUSION: Sch B is able to inhibit the proliferation of human hepatoma SMMC-7721 cells and induce apoptosis, which goes through Caspase-3-dependent and Caspase-9-independent pathway accompanied with the down-regulation of Hsp70 protein expression at an early event.
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Affiliation(s)
- Yi-Feng Wu
- College of Life Sciences, Zhejiang University, Hangzhou 310027, Zhejiang Province, China
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