|
1
|
Regmi D, Haque S, Karim MRU, Stanic A, Du D. Inhibition of amyloid formation of prion fragment (106-128) by polyphenolic compounds. Biochim Biophys Acta Gen Subj 2025; 1869:130778. [PMID: 39988109 DOI: 10.1016/j.bbagen.2025.130778] [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: 07/12/2024] [Revised: 02/14/2025] [Accepted: 02/18/2025] [Indexed: 02/25/2025]
Abstract
Prion diseases are characterized by the self-association and amyloid formation of misfolded prion proteins. Developing effective inhibitors of protein aggregation is critical for therapeutic intervention. In this study, we systematically evaluated a range of polyphenolic compounds as potential inhibitors of amyloid fibril formation of PrP(106-128), a prion fragment crucially involved in prion aggregation and propagation. Our findings demonstrate that the basic aromatic backbone structure of flavone alone is insufficient to inhibit PrP(106-128) amyloid formation. Remarkably, flavone molecules containing adjacent hydroxyl groups on the phenolic B or A ring efficiently inhibited PrP(106-128) fibrillization, whereas compounds lacking vicinal hydroxyl groups were less effective in inhibiting amyloid formation. Epigallocatechin-3-gallate (EGCG) was one of the most potent inhibitors found in this study, with the gallate moiety playing an active role in the inhibitory function. Our findings indicate a structure-dependent inhibition activity of the phenolic small molecules, where the number and positioning of hydroxyl groups on the phenyl ring play a pivotal role in inhibiting the aggregation of the peptide. The auto-oxidation of the catechol or pyrogallol moieties to form quinone structures, followed by their reaction with amino acid side chains of the peptide to form covalent adducts, likely account for the inhibitory activity of these phenolic compounds on PrP(106-128) amyloidogenesis. These results will help the design of novel polyphenolic molecules with optimized structural features as potent inhibitors of amyloid formation of both PrP(106-128) and the full-length prion proteins.
Collapse
Affiliation(s)
- Deepika Regmi
- Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - Seymour Haque
- Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - Md Raza Ul Karim
- Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - Aleksander Stanic
- Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - Deguo Du
- Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA.
| |
Collapse
|
|
2
|
Xu SY, Yin SS, Wang L, Zhong H, Wang H, Yu HY. Insights into emerging mechanisms of ferroptosis: new regulators for cancer therapeutics. Cell Biol Toxicol 2025; 41:63. [PMID: 40131564 PMCID: PMC11937073 DOI: 10.1007/s10565-025-10010-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 03/10/2025] [Indexed: 03/27/2025]
Abstract
Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxides, which has been implicated in the pathogenesis of various diseases, and therapeutic agents targeting ferroptosis are emerging as promising tools for cancer treatment. Current research reveals that ferroptosis-targeted therapies can effectively inhibit tumor progression or delay cancer development. Notably, natural product-derived compounds-such as artemisinin, baicalin, puerarin, quercetin, kaempferol, and apigenin-have demonstrated the ability to modulate ferroptosis, offering potential anti-cancer benefits. Mechanistically, ferroptosis exhibits negative glutathione peroxidase 4 (GPX4) regulation and demonstrates a positive correlation with plasma membrane polyunsaturated fatty acid (PUFA) abundance. Moreover, the labile iron pool (LIP) serves as the redox engine of ferroptosis. This review systematically analyzes the hallmarks, signaling pathways, and molecular mechanisms of ferroptosis, with a focus on how natural product-derived small molecules regulate this process. It further evaluates their potential as ferroptosis inducers or inhibitors in anti-tumor therapy, providing a foundation for future clinical translation.
Collapse
Affiliation(s)
- Si-Yi Xu
- National Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
- Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China
- School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Shuang-Shuang Yin
- National Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
- Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China
| | - Lei Wang
- National Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
- Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China
| | - Hao Zhong
- National Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
- Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China
| | - Hong Wang
- School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Hai-Yang Yu
- National Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
- Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China.
| |
Collapse
|
|
3
|
Hu H, Lu F, Guan X, Jiang X, Wen C, Wang L. Baicalein Ameliorates Experimental Ulcerative Colitis Recurrency by Downregulating Neonatal Fc Receptor via the NF-κB Signaling Pathway. ACS OMEGA 2025; 10:10701-10712. [PMID: 40124052 PMCID: PMC11923634 DOI: 10.1021/acsomega.5c00243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 02/27/2025] [Accepted: 03/04/2025] [Indexed: 03/25/2025]
Abstract
Ulcerative colitis (UC) is a chronic autoimmune disease (AID) that causes mild to moderate unpredictable symptoms, including diarrhea and abdominal pain. Against neonatal Fc receptor (FcRn) has been proven to be a unique AID treatment strategy by decreasing the effects of pathogenic autoantibody. Our previous study revealed that FcRn inhibition is beneficial in UC treatment through reducing colonic neutrophil extracellular trap (NET) formation via accelerating serum antineutrophil cytoplasm antibodies (ANCA) clearance. In this study, we initially confirmed the specific impact of downregulating FcRn in preventing UC relapse by injecting rAAV, which is carrying Fcgrt-shRNA, in mice. Next, we investigated the inhibition effects and regulation mechanisms of baicalein (BCL) on FcRn and assessed its capacity to withstand UC recurrence using NCM460 cells and dextran sodium sulfate-induced mice models by determining the expression of FcRn and its related transcription factors. We also measured colonic NET-associated protein (NAP) expression and serum concentrations of IgG, ANCA, TNF-α, IL-1β, and c-reactive protein (CRP). UC inflammation severity was determined by using the disease activity index (DAI) and histopathological score (HS). BCL treatment remarkably decreased the mRNA and protein contents of FcRn, p50, and p65 but did not impact STAT1 expression or the phosphorylation of IκB and STAT1. Long-term BCL administration inhibited colonic FcRn expression and reduced serum ANCA levels, colonic NAP expression, serum inflammation-related indexes (including TNF-α, IL-1β, and CRP), and DAI and HS scores in UC mice during inflammation relapse better than salazosulfapyridine. Our study indicates that BCL ameliorates UC recurrency by inhibiting FcRn expression via p50/p65 heterodimer-mediated NF-κB signaling.
Collapse
Affiliation(s)
- Haoyang Hu
- Department
of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of
Drug-Targeting and Drug Delivery System of the Education Ministry,
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
- National
Key Laboratory of Diagnosis and Treatment of Severe Infectious Disease,
National Clinical Research Center for Infectious Diseases, Collaborative
Innovation Center for Diagnosis and Treatment of Infectious Diseases,
The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China
| | - Fuliang Lu
- Department
of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of
Drug-Targeting and Drug Delivery System of the Education Ministry,
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Xudong Guan
- Department
of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of
Drug-Targeting and Drug Delivery System of the Education Ministry,
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Xuehua Jiang
- Department
of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of
Drug-Targeting and Drug Delivery System of the Education Ministry,
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Chengming Wen
- Department
of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of
Drug-Targeting and Drug Delivery System of the Education Ministry,
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
- School
of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China
| | - Ling Wang
- Department
of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of
Drug-Targeting and Drug Delivery System of the Education Ministry,
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| |
Collapse
|
|
4
|
Zuo X, Li P, Ren G, Bai Z, Jiang D, Liu C. Functional Characterization of β-Glucuronidase Genes Involved in Baicalein Biosynthesis from Scutellaria baicalensis Based on Transcriptome Analysis. Int J Mol Sci 2025; 26:1793. [PMID: 40076421 PMCID: PMC11898752 DOI: 10.3390/ijms26051793] [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: 01/02/2025] [Revised: 02/11/2025] [Accepted: 02/16/2025] [Indexed: 03/14/2025] Open
Abstract
Baicalein is a unique flavonoid compound with important pharmacological activities, derived from Scutellaria baicalensis Georgi. Baicalein, as the aglycone of baicalin, is a key form for exerting pharmacological activity in vivo. β-glucuronidases (GUSs) are the enzymes involved in the conversion of baicalin to baicalein. In this study, the content of baicalein in S. baicalensis was significantly increased by 20.44% after treatment with 5% PEG6000. Seven GUSs from the glycoside hydrolase 79 family were identified through comparative transcriptome analysis. Among them, GUS1 and GUS2 were confirmed to have catalytic activity in converting baicalin to baicalein in prokaryotic and eukaryotic systems. The correlation analysis further revealed a significant positive correlation of 0.962 (p < 0.01) between the expression of GUS2 and baicalein content in six different sources of S. baicalensis. Interestingly, the presence of variable sites in the GUS1 and GUS2 genes significantly affected their catalytic efficiency in the S. baicalensis samples from the six geographic origins. These findings also provide valuable GUS biological enzyme resources for the effective synthesis of baicalein and offer new insights into the accumulation pattern of baicalein in S. baicalensis.
Collapse
Affiliation(s)
| | | | | | | | - Dan Jiang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Chunsheng Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| |
Collapse
|
|
5
|
Tian D, Zheng XY, Hou SL, Yu ZW, Wu Y, Liu PZ, Liu LX, Chen YX, Zhao Y, Li Y, Tang HT, Chen WY, Liu YL, Zhang CF, Wang Y, Wen HY, Pu Q, Sato M, Liu LX. Baicalein relieves lung graft ischemia-reperfusion injury by reducing advanced glycation endproducts: From screens to mechanisms. J Heart Lung Transplant 2025:S1053-2498(25)00073-7. [PMID: 39954833 DOI: 10.1016/j.healun.2025.01.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 01/27/2025] [Accepted: 01/30/2025] [Indexed: 02/17/2025] Open
Abstract
BACKGROUND The lack of effective drugs for treating ischemia-reperfusion injury (IRI) in lung transplants (LTx) remains an issue. Traditional Chinese medicine (TCM) ingredients are promising but poorly studied in LTx. This study aimed to identify potential ingredients and elucidate their mechanisms. METHODS Ten TCM ingredients, including (-)-epigallocatechin-3-gallate, quercetin, wogonin, triptolide, berberine, fisetin, coumestrol, luteolin, nobiletin, and baicalein, were identified as promising candidates using a network pharmacology approach. All the candidates were tested for their ability to improve clamp-induced IRI. Multiple-dose validation was conducted in LTx models, with a focus on baicalein. The pharmacological efficacy of baicalin was verified in an ex-vivo rat lung perfusion model. RESULTS All ten TCM ingredients improved clamp-induced IRI. Multiple-dose validation confirmed that baicalein mitigated IRI-induced graft damage and dysfunction. Baicalein reduced the elevated levels of advanced glycation endproducts (AGEs) and their downstream pathogenic effects induced by IRI. Exogenous AGEs counteracted the therapeutic effect of baicalein. Baicalein inhibited AGE formation by modulating glucose oxidation rather than polyol metabolism. CONCLUSIONS This study provides a laboratory foundation for the use of TCM ingredients in the treatment of IRI in LTx.
Collapse
Affiliation(s)
- Dong Tian
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Lung Transplant Research Laboratory, Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Xiang-Yun Zheng
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Lung Transplant Research Laboratory, Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Sen-Lin Hou
- Lung Transplant Research Laboratory, Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Zeng-Wei Yu
- Lung Transplant Research Laboratory, Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Ye Wu
- Heart and Lung Transplant Research Laboratory, North Sichuan Medical College, Nanchong 637000, China
| | - Pei-Zhi Liu
- Heart and Lung Transplant Research Laboratory, North Sichuan Medical College, Nanchong 637000, China
| | - Lin-Xi Liu
- Heart and Lung Transplant Research Laboratory, North Sichuan Medical College, Nanchong 637000, China
| | - Yu-Xuan Chen
- Heart and Lung Transplant Research Laboratory, North Sichuan Medical College, Nanchong 637000, China
| | - Yang Zhao
- Heart and Lung Transplant Research Laboratory, North Sichuan Medical College, Nanchong 637000, China
| | - Yang Li
- Heart and Lung Transplant Research Laboratory, North Sichuan Medical College, Nanchong 637000, China
| | - Hong-Tao Tang
- Lung Transplant Research Laboratory, Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wei-Yang Chen
- Lung Transplant Research Laboratory, Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang 110002, China
| | - Ya-Ling Liu
- Lung Transplant Research Laboratory, Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chuan-Fen Zhang
- Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yun Wang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Hong-Ying Wen
- Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Qiang Pu
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Masaaki Sato
- Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Lun-Xu Liu
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Lung Transplant Research Laboratory, Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China; Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China.
| |
Collapse
|
|
6
|
Song P, Shen N, Wu Z, He S. Baicalein Inhibits Tumor Property of Hepatocellular Carcinoma Cells Through the Inactivation of the E2F Transcription Factor 1/Mediator Complex Subunit 7 Axis. Chem Biol Drug Des 2025; 105:e70063. [PMID: 39935236 DOI: 10.1111/cbdd.70063] [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: 04/17/2024] [Revised: 01/16/2025] [Accepted: 01/28/2025] [Indexed: 02/13/2025]
Abstract
Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis. Baicalein, a natural compound, can regulate multiple cellular processes in various cancer types. In this study, we investigated the role of baicalein in regulating HCC and explored its potential mechanism. The expression of mediator complex subunit 7 (MED7) and E2F transcription factor 1 (E2F1) was analyzed by quantitative real-time polymerase chain reaction or Western blotting assay. Cell proliferation was assessed by cell colony formation assay and 5-ethynyl-2'-deoxyuridine assay. Cell migration was analyzed by transwell assay and wound-healing assay. Cell invasion was analyzed by transwell assay. Angiogenic ability of HCC cells was assessed by tube formation assay. Dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to validate the association between E2F1 and MED7. The xenograft mouse model assay was conducted to determine the effects of baicalein and E2F1 overexpression on tumor formation. Immunohistochemistry assay was used to determine positive expression rates of proteins. Upregulation of MED7 and E2F1 expression was observed in both HCC tissues and cells. Knockdown of MED7 suppressed HCC cell proliferation, migration, invasion, and tube formation. Transcriptional activation of MED7 by E2F1 was demonstrated in HCC cells. Overexpression of MED7 mitigated the effects induced by E2F1 depletion in HCC cells. Additionally, baicalein treatment effectively inhibited the tumor property of HCC cells by decreasing E2F1 expression in both in vitro and in vivo models. Baicalein inhibited the tumor property of HCC cells through the inactivation of the E2F1/MED7 axis, highlighting its potential clinical application in the treatment of HCC.
Collapse
Affiliation(s)
- Pinghui Song
- Department of General Surgery, Shaanxi 215 Hospital of Nuclear Industry, Xianyang City, Shaanxi, China
| | - Naiying Shen
- Department of General Surgery, Shaanxi 215 Hospital of Nuclear Industry, Xianyang City, Shaanxi, China
| | - Zhongkun Wu
- Department of General Surgery, Shaanxi 215 Hospital of Nuclear Industry, Xianyang City, Shaanxi, China
| | - Sha He
- Department of Interventional, Shaanxi 215 Hospital of Nuclear Industry, Xianyang City, Shaanxi, China
| |
Collapse
|
|
7
|
Le S, Wu X, Dou Y, Song T, Fu H, Luo H, Zhang F, Cao Y. Promising strategies in natural products treatments of psoriasis-update. Front Med (Lausanne) 2024; 11:1386783. [PMID: 39296901 PMCID: PMC11408484 DOI: 10.3389/fmed.2024.1386783] [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: 02/16/2024] [Accepted: 07/31/2024] [Indexed: 09/21/2024] Open
Abstract
Psoriasis is a chronic, relapsing, inflammatory skin disease and has been increasing year by year. It is linked to other serious illnesses, such as psoriatic arthritis, cardiometabolic syndrome, and depression, resulting in a notable decrease in the quality of life for patients. Existing therapies merely alleviate symptoms, rather than providing a cure. An in-depth under-standing of the pathogenesis of psoriasis is helpful to discover new therapeutic targets and develop effective novel therapeutic agents, so it has important clinical significance. This article reviews the new progress in the study of pathogenesis and natural products of psoriasis in recent years. These natural products were summarized, mainly classified as terpenoids, polyphenols and alkaloids. However, the translation of experimental results to the clinic takes a long way to go.
Collapse
Affiliation(s)
- Sihua Le
- Ningbo Medical Center LiHuiLi Hosptial, Ningbo, China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xuan Wu
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuan Dou
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Tianhao Song
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Hongyang Fu
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Hongbin Luo
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Fan Zhang
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Yi Cao
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| |
Collapse
|
|
8
|
Zhou X, Alimu A, Zhao J, Xu X, Li X, Lin H, Lin Z. Paeonia genus: a systematic review of active ingredients, pharmacological effects and mechanisms, and clinical applications for the treatment of cancer. Arch Pharm Res 2024; 47:677-695. [PMID: 39306813 DOI: 10.1007/s12272-024-01512-2] [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: 03/19/2024] [Accepted: 09/12/2024] [Indexed: 10/11/2024]
Abstract
The main active constituents of plants of the Paeonia genus are known to have antitumor activity. Hundreds of compounds with a wide range of pharmacological activities, including monoterpene glycosides, flavonoids, tannins, stilbenes, triterpenoids, steroids, and phenolic compounds have been isolated. Among them, monoterpenes and their glycosides, flavonoids, phenolic acids, and other constituents have been shown to have good therapeutic effects on various cancers, with the main mechanisms including the induction of apoptosis; the inhibition of tumor cell proliferation, migration, and invasion; and the modulation of immunity. In this study, many citations related to the traditional uses, phytochemical constituents, antitumor effects, and clinical applications of the Paeonia genus were retrieved from popular and widely used databases such as Web of Science, Science Direct, Google Scholar, and PubMed using different search strings. A systematic review of the antitumor constituents of the Paeonia genus and their therapeutic effects on various cancers was conducted and the mechanisms of action and pathways of these phytochemicals were summarised to provide a further basis for antitumor research.
Collapse
Affiliation(s)
- Xinrui Zhou
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - Aikebaier Alimu
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - Jiarui Zhao
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - Xinyi Xu
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - Xiaowen Li
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, China
| | - He Lin
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, China.
| | - Zhe Lin
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, China.
| |
Collapse
|
|
9
|
Lv S, Yang N, Lu Y, Zhang G, Zhong X, Cui Y, Huang Y, Teng J, Sai Y. The therapeutic potential of traditional Chinese medicine in depression: focused on the modulation of neuroplasticity. Front Pharmacol 2024; 15:1426769. [PMID: 39253375 PMCID: PMC11381291 DOI: 10.3389/fphar.2024.1426769] [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: 05/03/2024] [Accepted: 08/06/2024] [Indexed: 09/11/2024] Open
Abstract
Depression, a mood disorder characterized by a persistent low mood and lack of enjoyment, is considered the leading cause of non-fatal health losses worldwide. Neuroplasticity refers to the brain's ability to adapt to external or internal stimuli, resulting in functional and structural changes. This process plays a crucial role in the development of depression. Traditional Chinese Medicine (TCM) shows significant potential as a complementary and alternative therapy for neurological diseases, including depression. However, there has been no systematic summary of the role of neuroplasticity in the pathological development of depression and TCM Interventions currently. This review systematically summarized recent literature on changes in neuroplasticity in depression and analyzed the regulatory mechanisms of active metabolites in TCM and TCM formulas on neuroplasticity in antidepressant treatment. Additionally, this review discussed the limitations of current research and the application prospects of TCM in regulating neuroplasticity in antidepressant research.
Collapse
Affiliation(s)
- Shimeng Lv
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ni Yang
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yitong Lu
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Guangheng Zhang
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xia Zhong
- Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China
| | - Yaru Cui
- Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yufei Huang
- Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jing Teng
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yanyan Sai
- University Town Hospital, Afiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| |
Collapse
|
|
10
|
Chen T, Zhang P, Cong XF, Wang YY, Li S, Wang H, Zhao SR, Sun XJ. Synergistic antitumor activity of baicalein combined with almonertinib in almonertinib-resistant non-small cell lung cancer cells through the reactive oxygen species-mediated PI3K/Akt pathway. Front Pharmacol 2024; 15:1405521. [PMID: 39144617 PMCID: PMC11322074 DOI: 10.3389/fphar.2024.1405521] [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: 03/23/2024] [Accepted: 07/01/2024] [Indexed: 08/16/2024] Open
Abstract
Introduction Almonertinib is an important third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) exhibiting high selectivity to EGFR-sensitizing and T790M-resistant mutations. Almonertinib resistance is a major obstacle in clinical use. Baicalein possesses antitumor properties, but its mechanism of antitumor action against almonertinib-resistant non-small cell lung cancer (NSCLC) remains unelucidated. Methods CCK-8 assay was used to examine the survival rate of H1975/AR and HCC827/AR cells following treatment for 24 h with different concentrations of baicalein, almonertinib or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/Akt signaling pathway were observed in baicalein- and/or almonertinib-treated cells. A nude mouse model bearing subcutaneous HCC827/AR cell xenograft were treated with baicalein (20 mg/kg) or almonertinib (15 mg/kg), and the tumor volume and body mass changes was measured. Results Both baicalein and almonertinib represses the viability of HCC827/AR and H1975/AR cells in a concentration-dependent manner. Compared with baicalein or almonertinib alone, the combined application of the two drugs dramatically attenuates cell proliferation; triggers apoptosis; causes cleavage of Caspase-3, PARP, and Caspase-9; downregulates the protein expressions of p-PI3K and p-Akt; and significantly inhibits tumor growth in nude mice. Furthermore, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS) and preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction, with partial recovery of the decline of p-PI3K and p-Akt. Discussion The combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.
Collapse
Affiliation(s)
- Teng Chen
- School of Pharmacy, Bengbu Medical University, Bengbu, China
| | - Pei Zhang
- School of Pharmacy, Bengbu Medical University, Bengbu, China
- Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, China
| | - Xiao-Fan Cong
- School of Pharmacy, Bengbu Medical University, Bengbu, China
| | - Yuan-Yuan Wang
- School of Pharmacy, Bengbu Medical University, Bengbu, China
| | - Shuo Li
- School of Pharmacy, Bengbu Medical University, Bengbu, China
| | - Hao Wang
- School of Pharmacy, Bengbu Medical University, Bengbu, China
| | - Su-Rong Zhao
- School of Pharmacy, Bengbu Medical University, Bengbu, China
- Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, China
| | - Xiao-Jin Sun
- School of Pharmacy, Bengbu Medical University, Bengbu, China
- Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, China
| |
Collapse
|
|
11
|
Saadh MJ, Mustafa MA, Malathi H, Ahluwalia G, Kaur S, Al-Dulaimi MAAH, Alubiady MHS, Zain Al-Abdeen SH, Shakier HG, Ali MS, Ahmad I, Abosaoda MK. Targeting the pancreatic tumor microenvironment by plant-derived products and their nanoformulations. Med Oncol 2024; 41:201. [PMID: 39001987 DOI: 10.1007/s12032-024-02443-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 06/27/2024] [Indexed: 07/15/2024]
Abstract
Pancreatic cancer remains a significant health issue with limited treatment options. The tumor stroma, a complex environment made up of different cells and proteins, plays a crucial role in tumor growth and chemoresistance. Targeting tumor stroma, consisting of diverse non-tumor cells such as fibroblasts, extracellular matrix (ECM), immune cells, and also pre-vascular cells is encouraging for remodeling solid cancers, such as pancreatic cancer. Remodeling the stroma of pancreas tumors can be suggested as a strategy for reducing resistance to chemo/immunotherapy. Several studies have shown that phytochemicals from plants can affect the tumor environment and have anti-cancer properties. By targeting key pathways involved in stromal activation, phytochemicals may disrupt communication between the tumor and stroma and make tumor cells more sensitive to different treatments. Additionally, phytochemicals have immunomodulatory and anti-angiogenic properties, all of which contribute to their potential in treating pancreatic cancer. This review will provide a detailed look at how phytochemicals impact the tumor stroma and their effects on pancreatic tumor growth, spread, and response to treatment. It will also explore the potential of combining phytochemicals with other treatment options like chemotherapy, immunotherapy, and radiation.
Collapse
Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | - Mohammed Ahmed Mustafa
- Department of Medical Laboratory Technology, University of Imam Jaafar AL-Sadiq, Baghdad, Iraq
| | - H Malathi
- Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to Be University), Bangalore, Karnataka, India
| | - Gunveen Ahluwalia
- Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, 303012, Rajasthan, India
| | - Sumeet Kaur
- Department of Applied Sciences, Chandigarh Engineering Colleges, Chandigarh Group of Colleges, Jhanjeri, 140307, Mohali, Punjab, India
| | | | | | | | | | | | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
| | - Munther Kadhim Abosaoda
- College of Pharmacy, The Islamic University, Najaf, Iraq
- College of Pharmacy, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- College of Pharmacy, The Islamic University of Babylon, Babylon, Iraq
| |
Collapse
|
|
12
|
Qin P, Li Q, Zu Q, Dong R, Qi Y. Natural products targeting autophagy and apoptosis in NSCLC: a novel therapeutic strategy. Front Oncol 2024; 14:1379698. [PMID: 38628670 PMCID: PMC11019012 DOI: 10.3389/fonc.2024.1379698] [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: 01/31/2024] [Accepted: 03/18/2024] [Indexed: 04/19/2024] Open
Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the predominant type. The roles of autophagy and apoptosis in NSCLC present a dual and intricate nature. Additionally, autophagy and apoptosis interconnect through diverse crosstalk molecules. Owing to their multitargeting nature, safety, and efficacy, natural products have emerged as principal sources for NSCLC therapeutic candidates. This review begins with an exploration of the mechanisms of autophagy and apoptosis, proceeds to examine the crosstalk molecules between these processes, and outlines their implications and interactions in NSCLC. Finally, the paper reviews natural products that have been intensively studied against NSCLC targeting autophagy and apoptosis, and summarizes in detail the four most retrieved representative drugs. This paper clarifies good therapeutic effects of natural products in NSCLC by targeting autophagy and apoptosis and aims to promote greater consideration by researchers of natural products as candidates for anti-NSCLC drug discovery.
Collapse
Affiliation(s)
- Peiyi Qin
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
- Shandong College of Traditional Chinese Medicine, Yantai, Shandong, China
| | - Qingchen Li
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qi Zu
- Shandong College of Traditional Chinese Medicine, Yantai, Shandong, China
| | - Ruxue Dong
- Shandong College of Traditional Chinese Medicine, Yantai, Shandong, China
| | - Yuanfu Qi
- Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| |
Collapse
|
|
13
|
Lee K, Choi YJ, Lim HI, Cho KJ, Kang N, Ko SG. Network pharmacology study to explore the multiple molecular mechanism of SH003 in the treatment of non-small cell lung cancer. BMC Complement Med Ther 2024; 24:70. [PMID: 38303001 PMCID: PMC10832243 DOI: 10.1186/s12906-024-04347-y] [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: 02/23/2023] [Accepted: 01/11/2024] [Indexed: 02/03/2024] Open
Abstract
BACKGROUND Non-small cell lung cancer (NSCLC) is one of the leading causes of human death worldwide. Herbal prescription SH003 has been developed to treat several cancers including NSCLC. Due to the multi-component nature of SH003 with multiple targets and pathways, a network pharmacology study was conducted to analyze its active compounds, potential targets, and pathways for the treatment of NSCLC. METHODS We systematically identified oral active compounds within SH003, employing ADME criteria-based screening from TM-MC, OASIS, and TCMSP databases. Concurrently, SH003-related and NSCLC-associated targets were amalgamated from various databases. Overlapping targets were deemed anti-NSCLC entities of SH003. Protein-protein interaction networks were constructed using the STRING database, allowing the identification of pivotal proteins through node centrality measures. Empirical validation was pursued through LC-MS analysis of active compounds. Additionally, in vitro experiments, such as MTT cell viability assays and western blot analyses, were conducted to corroborate network pharmacology findings. RESULTS We discerned 20 oral active compounds within SH003 and identified 239 core targets shared between SH003 and NSCLC-related genes. Network analyses spotlighted 79 hub genes, including TP53, JUN, AKT1, STAT3, and MAPK3, crucial in NSCLC treatment. GO and KEGG analyses underscored SH003's multifaceted anti-NSCLC effects from a genetic perspective. Experimental validations verified SH003's impact on NSCLC cell viability and the downregulation of hub genes. LC-MS analysis confirmed the presence of four active compounds, namely hispidulin, luteolin, baicalein, and chrysoeriol, among the eight compounds with a median of > 10 degrees in the herb-compounds-targets network in SH003. Previously unidentified targets like CASP9, MAPK9, and MCL1 were unveiled, supported by existing NSCLC literature, enhancing the pivotal role of empirical validation in network pharmacology. CONCLUSION Our study pioneers the harmonization of theoretical predictions with practical validations. Empirical validation illuminates specific SH003 compounds within NSCLC, simultaneously uncovering novel targets for NSCLC treatment. This integrated strategy, accentuating empirical validation, establishes a paradigm for in-depth herbal medicine exploration. Furthermore, our network pharmacology study unveils fresh insights into SH003's multifaceted molecular mechanisms combating NSCLC. Through this approach, we delineate active compounds of SH003 and target pathways, reshaping our understanding of its therapeutic mechanisms in NSCLC treatment.
Collapse
Affiliation(s)
- Kangwook Lee
- Department of Food and Biotechnology, Korea University, Sejong, 30019, South Korea
- Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, 02447, South Korea
| | - Yu-Jeong Choi
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, South Korea
| | - Hae-In Lim
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, South Korea
| | - Kwang Jin Cho
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, South Korea
| | - Nuri Kang
- Department of Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, South Korea
| | - Seong-Gyu Ko
- Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, 02447, South Korea.
| |
Collapse
|
|
14
|
Bailly C. Efficacy and safety of the traditional herbal medication Chai-Ling-Tang (in China), Siryung-tang (in Republic of Korea) or Sairei-To (in Japan). JOURNAL OF ETHNOPHARMACOLOGY 2024; 319:117127. [PMID: 37683930 DOI: 10.1016/j.jep.2023.117127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 08/18/2023] [Accepted: 09/03/2023] [Indexed: 09/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The herbal medicine designated Chai-Ling-Tang in China, Siryung-tang in South Korea, and Sairei-To (or Tsumura Saireito extract granules, TJ-114) in Japan is a complex polyherbal formulations with 12 plant components. It is used historically to treat Shaoyang syndrome, recorded in an ancient Chinese medical text "Treatise on Cold Damage Disorder" (Shanghan Lun). Chai-Ling-Tang formula combines two traditional Chinese herbal medicine prescriptions: Xiao-Chai-Hu-Tang and Wu-Ling-San (known as Sho-Saiko-To and Goreisan in Japan, and So Shi Ho Tang and Oreonsang in Korea, respectively). These traditional Chinese/Korean medicines and Kampo medicine have been used for more than 2000 years in East Asia, notably as regulators of body fluid homeostasis. AIM OF THE STUDY This study aims to evaluate clinical uses, pharmacological effects and unwanted effects of Sairei-To through a narrative literature survey. The main active phytoconstituents and their mechanism of actions are also collated based on the literature. METHODS Several databases including SciFinder and PubMed were searched in sourcing information using keywords corresponding to the medicinal treatment names and the corresponding plants and phytochemicals. Relevant textbooks, reviews, and digital documents (mostly in English) were consulted to collate all available scientific literature and to provide a complete science-based survey of the topic. RESULTS Sairei-To derives from ten plants and two fungi. The three major components are Bupleuri radix (Saiko), Pinelliae rhizoma (Hange), and Alismatis rhizoma (Takusha). The rest includes the species Scutellariae radix, Zizyphi fructus, Ginseng radix, Glycyrrhizae radix, Zingiberis rhizoma, Cinnamomi cortex, Atractylodis lanceae rhizoma, Poria sclerotium, and Polyporus sclerotium. The therapeutic uses of Sairei-To are very diversified, ranging from the treatment of autoimmune diseases, intestinal inflammatory disorders, edema, intestinal and kidney diseases, cancers, inflammatory skin pathologies, and other conditions such as reproductive failure. Sairei-To is considered as a safe and efficient medication, with potential rare unwanted side effects, notably lung injuries (pneumonitis essentially). Marked anti-inflammatory and immune-modulatory effects of Sairei-To have been reported, generally associated to the action of saponins (saikosaponins, glycyrrhizin), terpenoids (alisols) and flavonoids (baicalin, oroxylin A). CONCLUSION Sairei-To is commonly used to treat inflammatory diseases and appears efficient to decrease the side effects of corticosteroids. Its immune-regulatory action is well recognized and exploited to treat certain skin lesions and chemotherapy-related toxic effects. The activity of the Sairei-To product relies on the synergistic action of its individual ingredients. Further studies are warranted to quantify the synergy of action inherent to this interesting botanical medication.
Collapse
Affiliation(s)
- Christian Bailly
- OncoWitan, Consulting Scientific Office, Lille, Wasquehal, 59290, France; University of Lille, Faculty of Pharmacy, Institut de Chimie Pharmaceutique Albert Lespagnol (ICPAL), 3 rue du Professeur Laguesse, 59000, Lille, France; University of Lille, CNRS, Inserm, CHU Lille, UMR9020 - UMR1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000, Lille, France.
| |
Collapse
|
|
15
|
Alkan AH, Ensoy M, Cansaran-Duman D. Strategic and Innovative Roles of lncRNAs Regulated by Naturally-derived Small Molecules in Cancer Therapy. Curr Med Chem 2024; 31:6672-6691. [PMID: 37921177 DOI: 10.2174/0109298673264372230919102758] [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: 05/27/2023] [Revised: 07/22/2023] [Accepted: 08/17/2023] [Indexed: 11/04/2023]
Abstract
In the field of precision and personalized medicine, the next generation sequencing method has begun to take an active place as genome-wide screening applications in the diagnosis and treatment of diseases. Studies based on the determination of the therapeutic efficacy of personalized drug use in cancer treatment in the size of the transcriptome and its extension, lncRNA, have been increasing rapidly in recent years. Targeting and/or regulating noncoding RNAs (ncRNAs) consisting of long noncoding RNAs (lncRNAs) are promising strategies for cancer treatment. Within the scope of rapidly increasing studies in recent years, it has been shown that many natural agents obtained from biological organisms can potentially alter the expression of many lncRNAs associated with oncogenic functions. Natural agents include effective small molecules that provide anti-cancer effects and have been used as chemotherapy drugs or in combination with standard anti-cancer drugs used in routine treatment. In this review, it was aimed to provide detailed information about the potential of natural agents to regulate and/or target non-coding RNAs and their mechanisms of action to provide an approach for cancer therapy. The discovery of novel anti-cancer targets and subsequent development of effective drugs or combination strategies that are still needed for most cancers will be promising for cancer treatment.
Collapse
Affiliation(s)
- Ayşe Hale Alkan
- Biotechnology Institute, Ankara University, Keçiören, Ankara, Turkey
- Department of Molecular Biology and Genetics, Faculty of Science, Bartın University, Bartın, Turkey
| | - Mine Ensoy
- Biotechnology Institute, Ankara University, Keçiören, Ankara, Turkey
| | | |
Collapse
|
|
16
|
Mazurakova A, Koklesova L, Csizmár SH, Samec M, Brockmueller A, Šudomová M, Biringer K, Kudela E, Pec M, Samuel SM, Kassayova M, Hassan STS, Smejkal K, Shakibaei M, Büsselberg D, Saso L, Kubatka P, Golubnitschaja O. Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine. J Adv Res 2024; 55:103-118. [PMID: 36871616 PMCID: PMC10770105 DOI: 10.1016/j.jare.2023.02.015] [Citation(s) in RCA: 26] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 02/26/2023] [Indexed: 03/06/2023] Open
Abstract
BACKGROUND Cancer management faces multiple obstacles, including resistance to current therapeutic approaches. In the face of challenging microenvironments, cancer cells adapt metabolically to maintain their supply of energy and precursor molecules for biosynthesis and thus sustain rapid proliferation and tumor growth. Among the various metabolic adaptations observed in cancer cells, the altered glucose metabolism is the most widely studied. The aberrant glycolytic modification in cancer cells has been associated with rapid cell division, tumor growth, cancer progression, and drug resistance. The higher rates of glycolysis in cancer cells, as a hallmark of cancer progression, is modulated by the transcription factor hypoxia inducible factor 1 alpha (HIF-1α), a downstream target of the PI3K/Akt signaling, the most deregulated pathway in cancer. AIM OF REVIEW We provide a detailed overview of current, primarily experimental, evidence on the potential effectiveness of flavonoids to combat aberrant glycolysis-induced resistance of cancer cells to conventional and targeted therapies. The manuscript focuses primarily on flavonoids reducing cancer resistance via affecting PI3K/Akt, HIF-1α (as the transcription factor critical for glucose metabolism of cancer cells that is regulated by PI3K/Akt pathway), and key glycolytic mediators downstream of PI3K/Akt/HIF-1α signaling (glucose transporters and key glycolytic enzymes). KEY SCIENTIFIC CONCEPTS OF REVIEW The working hypothesis of the manuscript proposes HIF-1α - the transcription factor critical for glucose metabolism of cancer cells regulated by PI3K/Akt pathway as an attractive target for application of flavonoids to mitigate cancer resistance. Phytochemicals represent a source of promising substances for cancer management applicable to primary, secondary, and tertiary care. However, accurate patient stratification and individualized patient profiling represent crucial steps in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM / 3PM). The article is focused on targeting molecular patterns by natural substances and provides evidence-based recommendations for the 3PM relevant implementation.
Collapse
Affiliation(s)
- Alena Mazurakova
- Department of Anatomy, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01, Martin, Slovakia.
| | - Lenka Koklesova
- Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01, Martin, Slovakia
| | - Sandra Hurta Csizmár
- Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01, Martin, Slovakia
| | - Marek Samec
- Department of Pathological Physiology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia
| | - Aranka Brockmueller
- Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University Munich, Pettenkoferstr. 11, D-80336 Munich, Germany
| | - Miroslava Šudomová
- Museum of Literature in Moravia, Klášter 1, 66461 Rajhrad, Czech Republic
| | - Kamil Biringer
- Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01, Martin, Slovakia
| | - Erik Kudela
- Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01, Martin, Slovakia
| | - Martin Pec
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01, Martin, Slovakia
| | - Samson Mathews Samuel
- Department of Physiology and Biophysics, Weill Cornell Medicine in Qatar, Education City, Qatar Foundation, 24144, Doha, Qatar
| | - Monika Kassayova
- Department of Animal Physiology, Institute of Biology and Ecology, Faculty of Science, P. J. Safarik University, 04001 Kosice, Slovakia
| | - Sherif T S Hassan
- Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 00 Prague, Czech Republic
| | - Karel Smejkal
- Department of Natural Drugs, Faculty of Pharmacy, Masaryk University, 61242 Brno, Czech Republic
| | - Mehdi Shakibaei
- Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University Munich, Pettenkoferstr. 11, D-80336 Munich, Germany
| | - Dietrich Büsselberg
- Department of Physiology and Biophysics, Weill Cornell Medicine in Qatar, Education City, Qatar Foundation, 24144, Doha, Qatar
| | - Luciano Saso
- Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University, P.le Aldo Moro 5, 00185, Rome, Italy
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01, Martin, Slovakia.
| | - Olga Golubnitschaja
- Predictive, Preventive and Personalised (3P) Medicine, Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127, Bonn, Germany.
| |
Collapse
|
|
17
|
Li Z, Li J, Liu X, Sun Z, Sun X. Ethyl Acetate Fraction from Hedyotis Diffusa Plus Scutellaria Barbata Inhibits the Progression of Breast Cancer via Targeting LMO1 and AKT/Mtor Signaling Pathway. Comb Chem High Throughput Screen 2024; 27:1735-1744. [PMID: 37711008 DOI: 10.2174/1386207326666230913105858] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/20/2023] [Accepted: 07/11/2023] [Indexed: 09/16/2023]
Abstract
BACKGROUND Traditional Chinese medicines are widely used in cancer treatment. Scutellaria barbata and Hedyotis diffusa herb pair (SH) has an anticancer effects in various tumors. However, the specific mechanism of SH in breast cancer remains unclear. METHODS In the present research, we investigated the effect and regulatory network of SH in in breast cancer. CCK8, colony formation, transwell, wound healing and flow cytometry analysis were used for the detection of cell function. RESULTS Ethyl acetate fraction from SH at an equal weight ratio (EA11) could inhibit the proliferation, migration and invasion of MCF7 and MDA-MB-231 cells. It also induced apoptosis in these two cell lines by downregulating Bcl2 and upregulating Bax and Cleaved-Caspase3. SH reduced the activation of the AKT/mTOR signaling pathway and the expression of p70S6K. Sequencing results showed that LMO1 was significantly downregulated in SH-treated cells compared with control cells. Importantly, overexpression of LMO1 attenuated the inhibitory effect of SH on cell proliferation and invasion and induced inflammatory tumor microenvironment. CONCLUSION In conclusion, the SH herb pair inhibited the proliferation and metastasis through downregulating LMO1 expression and reducing the activation of the AKT/mTOR signaling pathway. LMO1 has the potential as a new target in the treatment of breast cancer.
Collapse
Affiliation(s)
- Zhiyuan Li
- Health Care Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
- Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Shadong, Jinan, China
| | - Jingwei Li
- Department of Breast Thyroid Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiaofei Liu
- Department of Breast Thyroid Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ziyuan Sun
- Department of Breast Thyroid Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiaohui Sun
- Department of Breast Thyroid Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| |
Collapse
|
|
18
|
Bao T, Zhang X, Xie W, Wang Y, Li X, Tang C, Yang Y, Sun J, Gao J, Yu T, Zhao L, Tong X. Natural compounds efficacy in complicated diabetes: A new twist impacting ferroptosis. Biomed Pharmacother 2023; 168:115544. [PMID: 37820566 DOI: 10.1016/j.biopha.2023.115544] [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: 03/28/2023] [Revised: 09/13/2023] [Accepted: 09/18/2023] [Indexed: 10/13/2023] Open
Abstract
Ferroptosis, as a way of cell death, participates in the body's normal physiological and pathological regulation. Recent studies have shown that ferroptosis may damage glucose-stimulated islets β Insulin secretion and programmed cell death of T2DM target organs are involved in the pathogenesis of T2DM and its complications. Targeting suppression of ferroptosis with specific inhibitors may provide new therapeutic opportunities for previously untreated T2DM and its target organs. Current studies suggest that natural bioactive compounds, which are abundantly available in drugs, foods, and medicinal plants for the treatment of T2DM and its target organs, have recently received significant attention for their various biological activities and minimal toxicity, and that many natural compounds appear to have a significant role in the regulation of ferroptosis in T2DM and its target organs. Therefore, this review summarized the potential treatment strategies of natural compounds as ferroptosis inhibitors to treat T2DM and its complications, providing potential lead compounds and natural phytochemical molecular nuclei for future drug research and development to intervene in ferroptosis in T2DM.
Collapse
Affiliation(s)
- Tingting Bao
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 BeiXianGe Street, Xicheng District, Beijing 100053, China; Graduate school, Beijing University of Traditional Chinese Medicine, Beijing 100029, China
| | - Xiangyuan Zhang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 BeiXianGe Street, Xicheng District, Beijing 100053, China; Graduate school, Beijing University of Traditional Chinese Medicine, Beijing 100029, China
| | - Weinan Xie
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 BeiXianGe Street, Xicheng District, Beijing 100053, China; Graduate school, Beijing University of Traditional Chinese Medicine, Beijing 100029, China
| | - Ying Wang
- Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Jingyue National High-tech Industrial Development Zone, Changchun 130117, China
| | - Xiuyang Li
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 BeiXianGe Street, Xicheng District, Beijing 100053, China
| | - Cheng Tang
- Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Jingyue National High-tech Industrial Development Zone, Changchun 130117, China
| | - Yingying Yang
- National Center for Integrated Traditional and Western Medicine, China-Japan Friendship Hospital, Beijing 100029, China
| | - Jun Sun
- Affiliated Hospital of Changchun University of Traditional Chinese Medicine, No. 1478, Gongnong Road, Chaoyang District, Changchun 130021, China
| | - Jiaqi Gao
- School of Qi-Huang Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North 3rd Ring East Roa, Chaoyang Distric, Beijing 10010, China
| | - Tongyue Yu
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 BeiXianGe Street, Xicheng District, Beijing 100053, China
| | - Linhua Zhao
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 BeiXianGe Street, Xicheng District, Beijing 100053, China.
| | - Xiaolin Tong
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 BeiXianGe Street, Xicheng District, Beijing 100053, China.
| |
Collapse
|
|
19
|
Yang K, Zeng L, Zeng J, Deng Y, Wang S, Xu H, He Q, Yuan M, Luo Y, Ge A, Ge J. Research progress in the molecular mechanism of ferroptosis in Parkinson's disease and regulation by natural plant products. Ageing Res Rev 2023; 91:102063. [PMID: 37673132 DOI: 10.1016/j.arr.2023.102063] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Revised: 08/25/2023] [Accepted: 09/01/2023] [Indexed: 09/08/2023]
Abstract
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder of the central nervous system after Alzheimer's disease. The current understanding of PD focuses mainly on the loss of dopamine neurons in the substantia nigra region of the midbrain, which is attributed to factors such as oxidative stress, alpha-synuclein aggregation, neuroinflammation, and mitochondrial dysfunction. These factors together contribute to the PD phenotype. Recent studies on PD pathology have introduced a new form of cell death known as ferroptosis. Pathological changes closely linked with ferroptosis have been seen in the brain tissues of PD patients, including alterations in iron metabolism, lipid peroxidation, and increased levels of reactive oxygen species. Preclinical research has demonstrated the neuroprotective qualities of certain iron chelators, antioxidants, Fer-1, and conditioners in Parkinson's disease. Natural plant products have shown significant potential in balancing ferroptosis-related factors and adjusting their expression levels. Therefore, it is vital to understand the mechanisms by which natural plant products inhibit ferroptosis and relieve PD symptoms. This review provides a comprehensive look at ferroptosis, its role in PD pathology, and the mechanisms underlying the therapeutic effects of natural plant products focused on ferroptosis. The insights from this review can serve as useful references for future research on novel ferroptosis inhibitors and lead compounds for PD treatment.
Collapse
Affiliation(s)
- Kailin Yang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China; Hunan Academy of Chinese Medicine, Changsha, Hunan, China.
| | - Liuting Zeng
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China.
| | - Jinsong Zeng
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Ying Deng
- People's Hospital of Ningxiang City, Ningxiang, China
| | - Shanshan Wang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Hao Xu
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Qi He
- People's Hospital of Ningxiang City, Ningxiang, China
| | - Mengxia Yuan
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou University Medical College, Shantou, China
| | - Yanfang Luo
- The Central Hospital of Shaoyang, Shaoyang, China
| | - Anqi Ge
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Jinwen Ge
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China; Hunan Academy of Chinese Medicine, Changsha, Hunan, China.
| |
Collapse
|
|
20
|
Zhang T, Deng W, Deng Y, Liu Y, Xiao S, Luo Y, Xiang W, He Q. Mechanisms of ferroptosis regulating oxidative stress and energy metabolism in myocardial ischemia-reperfusion injury and a novel perspective of natural plant active ingredients for its treatment. Biomed Pharmacother 2023; 165:114706. [PMID: 37400352 DOI: 10.1016/j.biopha.2023.114706] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/11/2023] [Accepted: 04/12/2023] [Indexed: 07/05/2023] Open
Abstract
Acute myocardial infarction remains the leading cause of death in humans. Timely restoration of blood perfusion to ischemic myocardium remains the most effective strategy in the treatment of acute myocardial infarction, which can significantly reduce morbidity and mortality. However, after restoration of blood flow and reperfusion, myocardial injury will aggravate and induce apoptosis of cardiomyocytes, a process called myocardial ischemia-reperfusion injury. Studies have shown that the loss and death of cardiomyocytes caused by oxidative stress, iron load, increased lipid peroxidation, inflammation and mitochondrial dysfunction, etc., are involved in myocardial ischemia-reperfusion injury. In recent years, with the in-depth research on the pathology of myocardial ischemia-reperfusion injury, people have gradually realized that there is a new form of cell death in the pathological process of myocardial ischemia-reperfusion injury, namely ferroptosis. A number of studies have found that in the myocardial tissue of patients with acute myocardial infarction, there are pathological changes closely related to ferroptosis, such as iron metabolism disorder, lipid peroxidation, and increased reactive oxygen species free radicals. Natural plant products such as resveratrol, baicalin, cyanidin-3-O-glucoside, naringenin, and astragaloside IV can also exert therapeutic effects by correcting the imbalance of these ferroptosis-related factors and expression levels. Combining with our previous studies, this review summarizes the regulatory mechanism of natural plant products intervening ferroptosis in myocardial ischemia-reperfusion injury in recent years, in order to provide reference information for the development of targeted ferroptosis inhibitor drugs for the treatment of cardiovascular diseases.
Collapse
Affiliation(s)
- Tianqing Zhang
- Department of Cardiology, The First People's Hospital of Changde City, Changde 415003, Hunan, China
| | - Wenxu Deng
- The Central Hospital of Hengyang, Hengyang, Hunan 421001, China
| | - Ying Deng
- People's Hospital of Ningxiang City, Ningxiang, Hunan, China
| | - Yao Liu
- The Second Affiliated Hospital, Department of Cardiovascular Medicine, Hengyang Medcial School, University of South China, Hunan 421001, China.
| | - Sijie Xiao
- Department of Ultrasound, The First People's Hospital of Changde City, Changde 415003, China
| | - Yanfang Luo
- Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Wang Xiang
- Department of Immunology and Rheumatology, The First People's Hospital of Changde City, Changde 415003, China
| | - Qi He
- People's Hospital of Ningxiang City, Ningxiang, Hunan, China
| |
Collapse
|
|
21
|
Morshed AKMH, Paul S, Hossain A, Basak T, Hossain MS, Hasan MM, Hasibuzzaman MA, Rahaman TI, Mia MAR, Shing P, Sohel M, Bibi S, Dey D, Biswas P, Hasan MN, Ming LC, Tan CS. Baicalein as Promising Anticancer Agent: A Comprehensive Analysis on Molecular Mechanisms and Therapeutic Perspectives. Cancers (Basel) 2023; 15:2128. [PMID: 37046789 PMCID: PMC10093079 DOI: 10.3390/cancers15072128] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 03/07/2023] [Accepted: 03/10/2023] [Indexed: 04/05/2023] Open
Abstract
Despite significant therapeutic advancements for cancer, an atrocious global burden (for example, health and economic) and radio- and chemo-resistance limit their effectiveness and result in unfavorable health consequences. Natural compounds are generally considered safer than synthetic drugs, and their use in cancer treatment alone, or in combination with conventional therapies, is increasingly becoming accepted. Interesting outcomes from pre-clinical trials using Baicalein in combination with conventional medicines have been reported, and some of them have also undergone clinical trials in later stages. As a result, we investigated the prospects of Baicalein, a naturally occurring substance extracted from the stems of Scutellaria baicalensis Georgi and Oroxylum indicum Kurz, which targets a wide range of molecular changes that are involved in cancer development. In other words, this review is primarily driven by the findings from studies of Baicalein therapy in several cancer cell populations based on promising pre-clinical research. The modifications of numerous signal transduction mechanisms and transcriptional agents have been highlighted as the major players for Baicalein's anti-malignant properties at the micro level. These include AKT serine/threonine protein kinase B (AKT) as well as PI3K/Akt/mTOR, matrix metalloproteinases-2 & 9 (MMP-2 & 9), Wnt/-catenin, Poly(ADP-ribose) polymerase (PARP), Mitogen-activated protein kinase (MAPK), NF-κB, Caspase-3/8/9, Smad4, Notch 1/Hes, Signal transducer and activator of transcription 3 (STAT3), Nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap 1), Adenosine monophosphate-activated protein kinase (AMPK), Src/Id1, ROS signaling, miR 183/ezrin, and Sonic hedgehog (Shh) signaling cascades. The promise of Baicalein as an anti-inflammatory to anti-apoptotic/anti-angiogenic/anti-metastatic medicinal element for treating various malignancies and its capability to inhibit malignant stem cells, evidence of synergistic effects, and design of nanomedicine-based drugs are altogether well supported by the data presented in this review study.
Collapse
Affiliation(s)
- A K M Helal Morshed
- Pathology and Pathophysiology, Academy of Medical Science, Zhengzhou University, No. 100 Science Avenue, Zhengzhou 450001, China
| | - Supti Paul
- Department of Chemistry, University of Dhaka, Dhaka 1000, Bangladesh
| | - Arafat Hossain
- Biochemistry and Molecular Biology Department, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Tuli Basak
- Department of Genetic Engineering and Biotechnology, Faculty of Science and Engineering, East West University, Dhaka 1212, Bangladesh
| | - Md. Sanower Hossain
- Centre for Sustainability of Ecosystem and Earth Resources (Pusat ALAM), Universiti Malaysia Pahang, Gambang, Kuantan 26300, Malaysia
| | - Md. Mehedi Hasan
- Biochemistry and Molecular Biology Department, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Md. Al Hasibuzzaman
- Institute of Nutrition and Food Science, University of Dhaka, Dhaka 1000, Bangladesh
| | - Tanjim Ishraq Rahaman
- Department of Biotechnology and Genetic Engineering, Faculty of Life Science, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Md. Abdur Rashid Mia
- Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Malaysia
| | - Pollob Shing
- Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Md Sohel
- Department of Biochemistry and Molecular Biology, Primeasia University, Banani, Dhaka 1213, Bangladesh
| | - Shabana Bibi
- Department of Bioscience, Shifa Tameer-e-Millat University, Islamabad 44000, Pakistan
- Yunnan Herbal Laboratory, College of Ecology and Environmental Sciences, Yunnan University, Kunming 650091, China
| | - Dipta Dey
- Biochemistry and Molecular Biology Department, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Partha Biswas
- Laboratory of Pharmaceutical Biotechnology and Bioinformatics, Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Md. Nazmul Hasan
- Laboratory of Pharmaceutical Biotechnology and Bioinformatics, Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Long Chiau Ming
- School of Medical and Life Sciences, Sunway University, Sunway City 47500, Malaysia;
| | - Ching Siang Tan
- School of Pharmacy, KPJ Healthcare University College, Nilai 71800, Malaysia
| |
Collapse
|
|
22
|
Lai HC, Lin HJ, Jeng LB, Huang ST. Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma. World J Gastrointest Oncol 2023; 15:19-35. [PMID: 36684056 PMCID: PMC9850766 DOI: 10.4251/wjgo.v15.i1.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/03/2022] [Accepted: 12/07/2022] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the fourth leading cause of cancer-related deaths in the world. HCC has a reported recurrence rate of 70%-80% after 5 years of follow-up. Controlling tumor recurrence is the most critical factor associated with HCC mortality. Conventional salvage therapies for recurrent HCC include re-hepatectomy or liver transplantation, transcatheter arterial chemoembolization, Y-90, target therapy, and immunotherapy; however, these conventional treatment modalities have yet to achieve consistently favorable outcomes. Meanwhile, previous studies have demonstrated that conventional therapies in combination with traditional Chinese medicine (TCM), acupuncture, moxibustion or dietary supplements could notably benefit patients with HCC recurrence by strengthening and augmenting the overall management strategy. However, systemic reviews related to the interactions between complementary therapies and conventional therapy in recurrent HCC are limited. In this review, we discuss the molecular mechanisms underlying the functions of complementary therapies for recurrent HCC, which include augmenting the local control to improve the congestion status of primary tumors and reducing multicentric tumor occurrence via inducing autophagy, apoptosis or cell cycle arrest. TCM and its derivatives may play important roles in helping to control HCC recurrence by inhibiting epithelial-mesenchymal transition, migration, invasion, and metastasis, inhibiting cancer stem cells, and ameliorating drug resistance.
Collapse
Affiliation(s)
- Hsiang-Chun Lai
- Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40447, Taiwan
- Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan
| | - Hung-Jen Lin
- Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan
| | - Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung 40447, Taiwan
| | - Sheng-Teng Huang
- Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan
- School of Chinese Medicine, China Medical University, Taichung 40447, Taiwan
- Cancer Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan
- An-Nan Hospital, China Medical University, Tainan 709204, Taiwan
| |
Collapse
|
|
23
|
Kim S, Lim SW, Choi J. Drug discovery inspired by bioactive small molecules from nature. Anim Cells Syst (Seoul) 2022; 26:254-265. [PMID: 36605590 PMCID: PMC9809404 DOI: 10.1080/19768354.2022.2157480] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Natural products (NPs) have greatly contributed to the development of novel treatments for human diseases such as cancer, metabolic disorders, and infections. Compared to synthetic chemical compounds, primary and secondary metabolites from medicinal plants, fungi, microorganisms, and our bodies are promising resources with immense chemical diversity and favorable properties for drug development. In addition to the well-validated significance of secondary metabolites, endogenous small molecules derived from central metabolism and signaling events have shown great potential as drug candidates due to their unique metabolite-protein interactions. In this short review, we highlight the values of NPs, discuss recent scientific and technological advances including metabolomics tools, chemoproteomics approaches, and artificial intelligence-based computation platforms, and explore potential strategies to overcome the current challenges in NP-driven drug discovery.
Collapse
Affiliation(s)
- Seyun Kim
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea, Seyun Kim
| | - Seol-Wa Lim
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
| | - Jiyeon Choi
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
| |
Collapse
|
|
24
|
Natural Polyphenols as SERCA Activators: Role in the Endoplasmic Reticulum Stress-Related Diseases. Molecules 2022; 27:molecules27165095. [PMID: 36014327 PMCID: PMC9415898 DOI: 10.3390/molecules27165095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/05/2022] [Accepted: 08/08/2022] [Indexed: 11/17/2022] Open
Abstract
Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) is a key protein responsible for transporting Ca2+ ions from the cytosol into the lumen of the sarco/endoplasmic reticulum (SR/ER), thus maintaining Ca2+ homeostasis within cells. Accumulating evidence suggests that impaired SERCA function is associated with disruption of intracellular Ca2+ homeostasis and induction of ER stress, leading to different chronic pathological conditions. Therefore, appropriate strategies to control Ca2+ homeostasis via modulation of either SERCA pump activity/expression or relevant signaling pathways may represent a useful approach to combat pathological states associated with ER stress. Natural dietary polyphenolic compounds, such as resveratrol, gingerol, ellagic acid, luteolin, or green tea polyphenols, with a number of health-promoting properties, have been described either to increase SERCA activity/expression directly or to affect Ca2+ signaling pathways. In this review, potential Ca2+-mediated effects of the most studied polyphenols on SERCA pumps or related Ca2+ signaling pathways are summarized, and relevant mechanisms of their action on Ca2+ regulation with respect to various ER stress-related states are depicted. All data were collected using scientific search tools (i.e., Science Direct, PubMed, Scopus, and Google Scholar).
Collapse
|
|
25
|
Farooqi AA, Kapanova G, Kalmakhanov S, Tanbayeva G, Zhakipbekov KS, Rakhmetova VS, Syzdykbayev MK. Regulation of Cell Signaling Pathways and Non-Coding RNAs by Baicalein in Different Cancers. Int J Mol Sci 2022; 23:ijms23158377. [PMID: 35955525 PMCID: PMC9368823 DOI: 10.3390/ijms23158377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 07/24/2022] [Accepted: 07/26/2022] [Indexed: 11/16/2022] Open
Abstract
Landmark discoveries in molecular oncology have provided a wide-angle overview of the heterogenous and therapeutically challenging nature of cancer. The power of modern ‘omics’ technologies has enabled researchers to deeply and comprehensively characterize molecular mechanisms underlying cellular functions. Interestingly, high-throughput technologies have opened new horizons for the design and scientific fool-proof evaluation of the pharmacological properties of targeted chemical compounds to tactfully control the activities of the oncogenic protein networks. Groundbreaking discoveries have galvanized the expansion of the repertoire of available pharmacopoeia to therapeutically target a myriad of deregulated oncogenic pathways. Natural product research has undergone substantial broadening, and many of the drugs which constitute the backbone of modern pharmaceuticals have been derived from the natural cornucopia. Baicalein has gradually gained attention because of its unique ability to target different oncogenic signal transduction cascades in various cancers. We have partitioned this review into different sub-sections to provide a broader snapshot of the oncogenic pathways regulated by baicalein. In this review, we summarize baicalein-mediated targeting of WNT/β-catenin, AKT/mTOR, JAK/STAT, MAPK, and NOTCH pathways. We also critically analyze how baicalein regulates non-coding RNAs (microRNAs and long non-coding RNAs) in different cancers. Finally, we conceptually interpret baicalein-mediated inhibition of primary and secondary growths in xenografted mice.
Collapse
Affiliation(s)
- Ammad Ahmad Farooqi
- Department of Molecular Oncology, Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 44000, Pakistan
- Correspondence:
| | - Gulnara Kapanova
- Scientific Center of Anti-Infectious Drugs, 75 al-Faraby Ave, Almaty 050040, Kazakhstan;
- Al-Farabi Kazakh National University, 71 al-Farabi Ave, Almaty 050040, Kazakhstan; (S.K.); (G.T.)
| | - Sundetgali Kalmakhanov
- Al-Farabi Kazakh National University, 71 al-Farabi Ave, Almaty 050040, Kazakhstan; (S.K.); (G.T.)
| | - Gulnur Tanbayeva
- Al-Farabi Kazakh National University, 71 al-Farabi Ave, Almaty 050040, Kazakhstan; (S.K.); (G.T.)
| | - Kairat S. Zhakipbekov
- Department of Organization and Management and Economics of Pharmacy and Clinical Pharmacy, Asfendiyarov Kazakh National Medical University KazNMU, Tole Bi St. 94, Almaty 050000, Kazakhstan;
| | - Venera S. Rakhmetova
- Department Internal Diseases, Astana Medical University, Nur-Sultan 010000, Kazakhstan;
| | - Marat K. Syzdykbayev
- Department of Anesthesiology, Reanimatology and Narcology, Semey Medical University, Semey 071400, Kazakhstan;
| |
Collapse
|