Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.
{"title":"Quercetin Limits Tumor Immune Escape through PDK1/CD47 Axis in Melanoma.","authors":"Xin Li, Xue He, Bing Lin, Li Li, Qifeng Deng, Chengzhi Wang, Jing Zhang, Ying Chen, Jingyi Zhao, Xinrui Li, Yan Li, Qing Xi, Rongxin Zhang","doi":"10.1142/S0192415X2450023X","DOIUrl":"10.1142/S0192415X2450023X","url":null,"abstract":"<p><p>Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both <i>in vivo</i> and <i>in vitro</i> methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-05-08DOI: 10.1142/S0192415X24500265
Danping Pan, Yilei Guo, Yongfu Fan, Haitong Wan
Traditional Chinese medicine (TCM) has been used for thousands of years and has been proven to be effective at treating many complicated illnesses with minimal side effects. The application and advancement of TCM are, however, constrained by the absence of objective measuring standards due to its relatively abstract diagnostic methods and syndrome differentiation theories. Ongoing developments in machine learning (ML) and deep learning (DL), specifically in computer vision (CV) and natural language processing (NLP), offer novel opportunities to modernize TCM by exploring the profound connotations of its theory. This review begins with an overview of the ML and DL methods employed in TCM; this is followed by practical instances of these applications. Furthermore, extensive discussions emphasize the mature integration of ML and DL in TCM, such as tongue diagnosis, pulse diagnosis, and syndrome differentiation treatment, highlighting their early successful application in the TCM field. Finally, this study validates the accomplishments and addresses the problems and challenges posed by the application and development of TCM powered by ML and DL. As ML and DL techniques continue to evolve, modern technology will spark new advances in TCM.
传统中医药(TCM)已有数千年的历史,被证明能有效治疗多种疑难杂症,且副作用极小。然而,由于中医的诊断方法和辨证理论相对抽象,缺乏客观的衡量标准,制约了中医的应用和发展。机器学习(ML)和深度学习(DL),特别是计算机视觉(CV)和自然语言处理(NLP)的不断发展,为探索中医理论的深刻内涵,实现中医现代化提供了新的机遇。本综述首先概述了中医中采用的 ML 和 DL 方法,然后介绍了这些应用的实际案例。此外,大量的论述强调了 ML 和 DL 在中医中的成熟整合,如舌诊、脉诊和辨证论治,突出了它们在中医领域的早期成功应用。最后,本研究验证了这些成就,并探讨了以 ML 和 DL 为动力的中医药应用与发展所面临的问题和挑战。随着 ML 和 DL 技术的不断发展,现代技术将为中医药带来新的进步。
{"title":"Development and Application of Traditional Chinese Medicine Using AI Machine Learning and Deep Learning Strategies.","authors":"Danping Pan, Yilei Guo, Yongfu Fan, Haitong Wan","doi":"10.1142/S0192415X24500265","DOIUrl":"10.1142/S0192415X24500265","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) has been used for thousands of years and has been proven to be effective at treating many complicated illnesses with minimal side effects. The application and advancement of TCM are, however, constrained by the absence of objective measuring standards due to its relatively abstract diagnostic methods and syndrome differentiation theories. Ongoing developments in machine learning (ML) and deep learning (DL), specifically in computer vision (CV) and natural language processing (NLP), offer novel opportunities to modernize TCM by exploring the profound connotations of its theory. This review begins with an overview of the ML and DL methods employed in TCM; this is followed by practical instances of these applications. Furthermore, extensive discussions emphasize the mature integration of ML and DL in TCM, such as tongue diagnosis, pulse diagnosis, and syndrome differentiation treatment, highlighting their early successful application in the TCM field. Finally, this study validates the accomplishments and addresses the problems and challenges posed by the application and development of TCM powered by ML and DL. As ML and DL techniques continue to evolve, modern technology will spark new advances in TCM.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteoporosis (OP) represents a substantial public health issue and is associated with increasing rates of morbidity and mortality. It is characterized by reduced bone mineral density, deterioration of bone tissue quality, disruption of the microarchitecture of bones, and compromised bone strength. These changes may be attributed to the following factors: intercellular communication between osteoblasts and osteoclasts; imbalanced bone remodeling; imbalances between osteogenesis and adipogenesis; imbalances in hormonal regulation; angiogenesis; chronic inflammation; oxidative stress; and intestinal microbiota imbalances. Treating a single aspect of the disease is insufficient to address its multifaceted nature. In recent decades, traditional Chinese medicine (TCM) has shown great potential in the treatment of OP, and the therapeutic effects of Chinese patent drugs and Chinese medicinal herbs have been scientifically proven. TCMs, which contain multiple components, can target the diverse pathogeneses of OP through a multitargeted approach. Herbs such as XLGB, JTG, GSB, Yinyanghuo, Gusuibu, Buguzhi, and Nvzhenzi are among the TCMs that can be used to treat OP and have demonstrated promising effects in this context. They exert their therapeutic effects by targeting various pathways involved in bone metabolism. These TCMs balance the activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells), and they exhibit anti-inflammatory, immunomodulatory, anti-oxidative, and estrogen-like functions. These multifaceted mechanisms underlie the efficacy of these herbs in the management and treatment of OP. Herein, we examine the efficacy of various Chinese herbs and Chinese patent drugs in treating OP by reviewing previous clinical trials and basic experiments, and we examine the potential mechanism of these therapies to provide evidence regarding the use of TCM for treating OP.
骨质疏松症(Osteoporosis,OP)是一个重大的公共卫生问题,其发病率和死亡率与日俱增。骨质疏松症的特点是骨矿物质密度降低、骨组织质量恶化、骨骼微结构破坏和骨强度受损。这些变化可归因于以下因素:成骨细胞和破骨细胞之间的细胞间交流、骨重塑失衡、成骨和脂肪生成失衡、激素调节失衡、血管生成、慢性炎症、氧化应激和肠道微生物群失衡。治疗疾病的单一方面不足以解决其多面性。近几十年来,传统中医药在治疗 OP 方面显示出巨大潜力,中成药和中草药的治疗效果已得到科学证实。中药含有多种成分,可通过多靶点方法针对 OP 的多种病原体。XLGB、JTG、GSB、Yinyanghuo、Gusuibu、Buguzhi 和 Nvzhenzi 等中草药可用于治疗 OP,并已显示出良好的效果。这些中药通过靶向参与骨代谢的各种途径发挥治疗作用。这些中药可平衡成骨细胞(骨形成细胞)和破骨细胞(骨吸收细胞)的活性,并具有抗炎、免疫调节、抗氧化和类似雌激素的功能。这些多方面的机制是这些草药在管理和治疗 OP 方面具有疗效的基础。在此,我们通过回顾以往的临床试验和基础实验,研究各种中草药和中成药在治疗 OP 方面的疗效,并探讨这些疗法的潜在机制,为使用中医药治疗 OP 提供证据。
{"title":"The Role of Traditional Chinese Medicines in the Treatment of Osteoporosis.","authors":"Liang Wang, Xinyi Huang, Jinran Qin, Baoyu Qi, Chuanrui Sun, Xiangyun Guo, Qingqing Liu, Yichen Liu, Yong Ma, Xu Wei, Yili Zhang","doi":"10.1142/S0192415X24500393","DOIUrl":"10.1142/S0192415X24500393","url":null,"abstract":"<p><p>Osteoporosis (OP) represents a substantial public health issue and is associated with increasing rates of morbidity and mortality. It is characterized by reduced bone mineral density, deterioration of bone tissue quality, disruption of the microarchitecture of bones, and compromised bone strength. These changes may be attributed to the following factors: intercellular communication between osteoblasts and osteoclasts; imbalanced bone remodeling; imbalances between osteogenesis and adipogenesis; imbalances in hormonal regulation; angiogenesis; chronic inflammation; oxidative stress; and intestinal microbiota imbalances. Treating a single aspect of the disease is insufficient to address its multifaceted nature. In recent decades, traditional Chinese medicine (TCM) has shown great potential in the treatment of OP, and the therapeutic effects of Chinese patent drugs and Chinese medicinal herbs have been scientifically proven. TCMs, which contain multiple components, can target the diverse pathogeneses of OP through a multitargeted approach. Herbs such as XLGB, JTG, GSB, Yinyanghuo, Gusuibu, Buguzhi, and Nvzhenzi are among the TCMs that can be used to treat OP and have demonstrated promising effects in this context. They exert their therapeutic effects by targeting various pathways involved in bone metabolism. These TCMs balance the activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells), and they exhibit anti-inflammatory, immunomodulatory, anti-oxidative, and estrogen-like functions. These multifaceted mechanisms underlie the efficacy of these herbs in the management and treatment of OP. Herein, we examine the efficacy of various Chinese herbs and Chinese patent drugs in treating OP by reviewing previous clinical trials and basic experiments, and we examine the potential mechanism of these therapies to provide evidence regarding the use of TCM for treating OP.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-06-14DOI: 10.1142/S0192415X24500423
Shaohua Wu, Yaya Zhou, Yang Wang, Zuping Zhang
The use of medicinal leeches in clinical therapy has been employed for a long time, as it was originally recognized for exerting antithrombin effects. These effects were due to the ability of the leech to continuously suck blood while attached to human skin. According to Chinese Pharmacopoei, leeches used in traditional Chinese medicine mainly consist of Whitmania pigra Whitman, Hirudo nipponia Whitman, and Whitmania acranulata, but the latter two species are relatively scarce. The main constituents of leeches are protein and peptide macromolecules. They can be categorized into two categories based on their pharmacological effects. One group consists of active ingredients that directly target the coagulation system, such as hirudin, heparin, and histamine, which are widely known. The other group comprises protease inhibitor components like Decorsin and Hementin. Among these, hirudin secreted by the salivary glands of the leech is the most potent thrombin inhibitor and served as the sole remedy for preventing blood clotting until the discovery of heparin. Additionally, leeches play a significant role in various traditional Chinese medicine formulations. In recent decades, medicinal leeches have been applied in fields including anti-inflammatory treatment, cardiovascular disease management, antitumor treatment, and many other medical conditions. In this review, we present a comprehensive overview of the historical journey and medicinal applications of leeches in various medical conditions, emphasizing their pharmaceutical significance within traditional Chinese medicine. This review offers valuable insights for exploring additional therapeutic opportunities involving the use of leeches in various diseases and elucidating their underlying mechanisms for future research.
{"title":"Therapeutic Potentials of Medicinal Leech in Chinese Medicine.","authors":"Shaohua Wu, Yaya Zhou, Yang Wang, Zuping Zhang","doi":"10.1142/S0192415X24500423","DOIUrl":"10.1142/S0192415X24500423","url":null,"abstract":"<p><p>The use of medicinal leeches in clinical therapy has been employed for a long time, as it was originally recognized for exerting antithrombin effects. These effects were due to the ability of the leech to continuously suck blood while attached to human skin. According to <i>Chinese Pharmacopoei</i>, leeches used in traditional Chinese medicine mainly consist of <i>Whitmania pigra</i> Whitman, <i>Hirudo nipponia</i> Whitman, and <i>Whitmania acranulata</i>, but the latter two species are relatively scarce. The main constituents of leeches are protein and peptide macromolecules. They can be categorized into two categories based on their pharmacological effects. One group consists of active ingredients that directly target the coagulation system, such as hirudin, heparin, and histamine, which are widely known. The other group comprises protease inhibitor components like Decorsin and Hementin. Among these, hirudin secreted by the salivary glands of the leech is the most potent thrombin inhibitor and served as the sole remedy for preventing blood clotting until the discovery of heparin. Additionally, leeches play a significant role in various traditional Chinese medicine formulations. In recent decades, medicinal leeches have been applied in fields including anti-inflammatory treatment, cardiovascular disease management, antitumor treatment, and many other medical conditions. In this review, we present a comprehensive overview of the historical journey and medicinal applications of leeches in various medical conditions, emphasizing their pharmaceutical significance within traditional Chinese medicine. This review offers valuable insights for exploring additional therapeutic opportunities involving the use of leeches in various diseases and elucidating their underlying mechanisms for future research.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recommendations on the use of acupuncture in managing low back pain (LBP) vary across different guidelines. The methodological quality of existing systematic reviews and meta-analyses on this topic also demonstrates considerable diversity, potentially leading to biased conclusions. Therefore, we comprehensively searched PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Chinese National Knowledge Infrastructure (CNKI) databases and conducted an umbrella review. Scrutiny was performed to ascertain whether primary studies within the systematic reviews and meta-analyses adhered to our inclusion criteria, followed by a meticulous reanalysis of pertinent data. Participant numbers, heterogeneity, publication bias, and excessive significance were taken into account when assessing the credibility of the evidence. For robustness, sensitivity analysis was performed using the leave-one-out method. The results of the umbrella review yielded highly suggestive evidence in favor of the immediate and short-term analgesic effects of acupuncture, with suggestive evidence supporting intermediate-term analgesic effects. However, the effectiveness of acupuncture on disability improvement has demonstrated weak to suggestive evidence. Evidence supporting the enhancement of quality of life by acupuncture is limited. The leave-one-out analysis corroborated the robustness of the meta-analysis, further confirming the credibility of the findings. This umbrella review indicated that the most significant advantage of acupuncture for LBP is its capacity to reduce pain.
不同的指南对使用针灸治疗腰背痛(LBP)的建议各不相同。现有的相关系统综述和荟萃分析的方法学质量也存在很大差异,可能导致结论有失偏颇。因此,我们全面检索了 PubMed、EMBASE、Web of Science、Cochrane 系统综述数据库和中国国家知识基础设施(CNKI)数据库,并进行了总体综述。为了确定系统综述和荟萃分析中的主要研究是否符合我们的纳入标准,我们对相关数据进行了仔细的再分析。在评估证据可信度时,我们考虑了参与者人数、异质性、发表偏差和过度显著性等因素。为确保稳健性,我们采用了 "留一剔除法 "进行了敏感性分析。综述结果显示,有高度提示性证据支持针灸的即时和短期镇痛效果,并有提示性证据支持中期镇痛效果。然而,针灸对改善残疾状况的有效性证据不足,仅为提示性证据。支持针灸提高生活质量的证据有限。剔除分析证实了荟萃分析的稳健性,进一步证实了研究结果的可信度。本综述表明,针灸治疗腰椎间盘突出症的最大优势在于其减轻疼痛的能力。
{"title":"The Effectiveness of Acupuncture for Low Back Pain: An Umbrella Review and Meta-Analysis.","authors":"Mengjiao Wu, Cheng Fan, Hong Liu, Xiaolin Chen, Zhen Gao, Xin Zhao, Jianhao Zhou, Zheng Jiang","doi":"10.1142/S0192415X2450037X","DOIUrl":"10.1142/S0192415X2450037X","url":null,"abstract":"<p><p>Recommendations on the use of acupuncture in managing low back pain (LBP) vary across different guidelines. The methodological quality of existing systematic reviews and meta-analyses on this topic also demonstrates considerable diversity, potentially leading to biased conclusions. Therefore, we comprehensively searched PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Chinese National Knowledge Infrastructure (CNKI) databases and conducted an umbrella review. Scrutiny was performed to ascertain whether primary studies within the systematic reviews and meta-analyses adhered to our inclusion criteria, followed by a meticulous reanalysis of pertinent data. Participant numbers, heterogeneity, publication bias, and excessive significance were taken into account when assessing the credibility of the evidence. For robustness, sensitivity analysis was performed using the leave-one-out method. The results of the umbrella review yielded highly suggestive evidence in favor of the immediate and short-term analgesic effects of acupuncture, with suggestive evidence supporting intermediate-term analgesic effects. However, the effectiveness of acupuncture on disability improvement has demonstrated weak to suggestive evidence. Evidence supporting the enhancement of quality of life by acupuncture is limited. The leave-one-out analysis corroborated the robustness of the meta-analysis, further confirming the credibility of the findings. This umbrella review indicated that the most significant advantage of acupuncture for LBP is its capacity to reduce pain.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-05-27DOI: 10.1142/S0192415X24500484
Chi Teng Vong, Dechao Tan, Fengyun Liao, Zhejie Chen, Zhangmei Chen, Hisa Hui Ling Tseng, Wai San Cheang, Shengpeng Wang, Yitao Wang
Hyperglycemia induces chronic stresses, such as oxidative stress and endoplasmic reticulum (ER) stress, which can result in [Formula: see text]-cell dysfunction and development of Type 2 Diabetes Mellitus (T2DM). Ginsenoside Rk1 is a minor ginsenoside isolated from Ginseng. It has been shown to exert anti-cancer, anti-inflammatory, anti-oxidant, and neuroprotective effects; however, its effects on pancreatic cells in T2DM have never been studied. This study aims to examine the novel effects of Ginsenoside Rk1 on ER stress-induced apoptosis in a pancreatic [Formula: see text]-cell line MIN6 and HFD-induced diabetic pancreas, and their underlying mechanisms. We demonstrated that Ginsenoside Rk1 alleviated ER stress-induced apoptosis in MIN6 cells, which was accomplished by directly targeting and activating insulin-like growth factor 1 receptor (IGF-1R), thus activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2-associated agonist of cell death (Bad)-B-cell lymphoma-2 (Bcl-2) pathway. This pathway was also confirmed in an HFD-induced diabetic pancreas. Meanwhile, the use of the IGF-1R inhibitor PQ401 abolished this anti-apoptotic effect, confirming the role of IGF-1R in mediating anti-apoptosis effects exerted by Ginsenoside Rk1. Besides, Ginsenoside Rk1 reduced pancreas weights and increased pancreatic insulin contents, suggesting that it could protect the pancreas from HFD-induced diabetes. Taken together, our study provided novel protective effects of Ginsenoside Rk1 on ER stress-induced [Formula: see text]-cell apoptosis and HFD-induced diabetic pancreases, as well as its direct target with IGF-1R, indicating that Ginsenoside Rk1 could be a potential drug for the treatment of T2DM.
{"title":"Ginsenoside Rk1 Ameliorates ER Stress-Induced Apoptosis through Directly Activating IGF-1R in Mouse Pancreatic [Formula: see text]-Cells and Diabetic Pancreas.","authors":"Chi Teng Vong, Dechao Tan, Fengyun Liao, Zhejie Chen, Zhangmei Chen, Hisa Hui Ling Tseng, Wai San Cheang, Shengpeng Wang, Yitao Wang","doi":"10.1142/S0192415X24500484","DOIUrl":"10.1142/S0192415X24500484","url":null,"abstract":"<p><p>Hyperglycemia induces chronic stresses, such as oxidative stress and endoplasmic reticulum (ER) stress, which can result in [Formula: see text]-cell dysfunction and development of Type 2 Diabetes Mellitus (T2DM). Ginsenoside Rk1 is a minor ginsenoside isolated from Ginseng. It has been shown to exert anti-cancer, anti-inflammatory, anti-oxidant, and neuroprotective effects; however, its effects on pancreatic cells in T2DM have never been studied. This study aims to examine the novel effects of Ginsenoside Rk1 on ER stress-induced apoptosis in a pancreatic [Formula: see text]-cell line MIN6 and HFD-induced diabetic pancreas, and their underlying mechanisms. We demonstrated that Ginsenoside Rk1 alleviated ER stress-induced apoptosis in MIN6 cells, which was accomplished by directly targeting and activating insulin-like growth factor 1 receptor (IGF-1R), thus activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2-associated agonist of cell death (Bad)-B-cell lymphoma-2 (Bcl-2) pathway. This pathway was also confirmed in an HFD-induced diabetic pancreas. Meanwhile, the use of the IGF-1R inhibitor PQ401 abolished this anti-apoptotic effect, confirming the role of IGF-1R in mediating anti-apoptosis effects exerted by Ginsenoside Rk1. Besides, Ginsenoside Rk1 reduced pancreas weights and increased pancreatic insulin contents, suggesting that it could protect the pancreas from HFD-induced diabetes. Taken together, our study provided novel protective effects of Ginsenoside Rk1 on ER stress-induced [Formula: see text]-cell apoptosis and HFD-induced diabetic pancreases, as well as its direct target with IGF-1R, indicating that Ginsenoside Rk1 could be a potential drug for the treatment of T2DM.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-05-08DOI: 10.1142/S0192415X24500344
Yong-Feng Chen, Qi Qiu, Lei Wang, Xiao-Rong Li, Shun Zhou, Heng Wang, Wen-Di Jiang, Jia-Yi Geng, Qin-Gao, Bi Tang, Hong-Ju Wang, Pin-Fang Kang
A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet in vivo. Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group in vitro and in vivo. Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.
{"title":"Quercetin Ameliorates Myocardial Injury in Diabetic Rats by Regulating Autophagy and Apoptosis through AMPK/mTOR Signaling Pathway.","authors":"Yong-Feng Chen, Qi Qiu, Lei Wang, Xiao-Rong Li, Shun Zhou, Heng Wang, Wen-Di Jiang, Jia-Yi Geng, Qin-Gao, Bi Tang, Hong-Ju Wang, Pin-Fang Kang","doi":"10.1142/S0192415X24500344","DOIUrl":"10.1142/S0192415X24500344","url":null,"abstract":"<p><p>A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet <i>in vivo</i>. Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group <i>in vitro</i> and <i>in vivo</i>. Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-03-14DOI: 10.1142/S0192415X24500216
Jun-Jie Huang, Yue-Min Feng, Shu-Mei Zheng, Cheng-Long Yu, Rui-Gang Zhou, Ming-Jiang Liu, Ruo-Nan Bo, Jie Yu, Jin-Gui Li
Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.
{"title":"Eugenol Possesses Colitis Protective Effects: Impacts on the TLR4/MyD88/NF-[Formula: see text]B Pathway, Intestinal Epithelial Barrier, and Macrophage Polarization.","authors":"Jun-Jie Huang, Yue-Min Feng, Shu-Mei Zheng, Cheng-Long Yu, Rui-Gang Zhou, Ming-Jiang Liu, Ruo-Nan Bo, Jie Yu, Jin-Gui Li","doi":"10.1142/S0192415X24500216","DOIUrl":"10.1142/S0192415X24500216","url":null,"abstract":"<p><p>Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated <i>in vitro.</i> The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liver diseases and their related complications endanger the health of millions of people worldwide. The prevention and treatment of liver diseases are still serious challenges both in China and globally. With the improvement of living standards, the prevalence of metabolic liver diseases, including non-alcoholic fatty liver disease and alcoholic liver disease, has increased at an alarming rate, resulting in more cases of end-stage liver disease. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently needed. Glycyrrhizin (GL), a triterpene glycoside from the roots of licorice plants, possesses a wide range of pharmacological and biological activities. Currently, GL preparations (GLPs) have certain advantages in the treatment of liver diseases, with good clinical effects and fewer adverse reactions, and have shown broad application prospects through multitargeting therapeutic mechanisms, including antisteatotic, anti-oxidative stress, anti-inflammatory, immunoregulatory, antifibrotic, anticancer, and drug interaction activities. This review summarizes the currently known biological activities of GLPs and their medical applications in the treatment of liver diseases, and highlights the potential of these preparations as promising therapeutic options and their alluring prospects for the treatment of liver diseases.
{"title":"Glycyrrhizin and the Related Preparations: An Inspiring Resource for the Treatment of Liver Diseases.","authors":"Yu Mou, Wenhao Liao, Yuchen Li, Lina Wan, Jingwen Liu, Xialing Luo, Hongping Shen, Qin Sun, Jing Wang, Jianyuan Tang, Zhilei Wang","doi":"10.1142/S0192415X24500149","DOIUrl":"10.1142/S0192415X24500149","url":null,"abstract":"<p><p>Liver diseases and their related complications endanger the health of millions of people worldwide. The prevention and treatment of liver diseases are still serious challenges both in China and globally. With the improvement of living standards, the prevalence of metabolic liver diseases, including non-alcoholic fatty liver disease and alcoholic liver disease, has increased at an alarming rate, resulting in more cases of end-stage liver disease. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently needed. Glycyrrhizin (GL), a triterpene glycoside from the roots of licorice plants, possesses a wide range of pharmacological and biological activities. Currently, GL preparations (GLPs) have certain advantages in the treatment of liver diseases, with good clinical effects and fewer adverse reactions, and have shown broad application prospects through multitargeting therapeutic mechanisms, including antisteatotic, anti-oxidative stress, anti-inflammatory, immunoregulatory, antifibrotic, anticancer, and drug interaction activities. This review summarizes the currently known biological activities of GLPs and their medical applications in the treatment of liver diseases, and highlights the potential of these preparations as promising therapeutic options and their alluring prospects for the treatment of liver diseases.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-05-08DOI: 10.1142/S0192415X24500307
Rongmao Gao, Yuanyu Lu, Wei Zhang, Zhao Zhang
The formation of fibrotic tissue, characterized by the excessive accumulation of extracellular matrix (ECM) components such as collagen and fibronectin, is a normal and crucial stage of tissue repair in all organs. The over-synthesis, deposition, and remodeling of ECM components lead to organ dysfunction, posing a significant medical burden. Berberine, an isoquinoline alkaloid, is commonly used in the treatment of gastrointestinal diseases. With the deepening of scientific research, it has been gradually discovered that berberine also plays an important role in fibrotic diseases. In this review, we systematically introduce the effective role of berberine in fibrosis-related diseases. Specifically, this paper aims to provide a comprehensive review of the therapeutic role of berberine in treating fibrosis in organs such as the heart, liver, lungs, and kidneys. By summarizing its various pathways and mechanisms of action, including the inhibition of the transforming growth factor-[Formula: see text]/Smad signaling pathway, PI3K/Akt signaling pathway, MAPK signaling pathway, RhoA/ROCK signaling, and mTOR/p70S6K signaling pathway, as well as its activation of the Nrf2-ARE signaling pathway, AMPK signaling pathway, phosphorylated Smad 2/3 and Smad 7, and other signaling pathways, this review offers additional evidence to support the treatment of fibrotic diseases.
{"title":"The Application of Berberine in Fibrosis and the Related Diseases.","authors":"Rongmao Gao, Yuanyu Lu, Wei Zhang, Zhao Zhang","doi":"10.1142/S0192415X24500307","DOIUrl":"10.1142/S0192415X24500307","url":null,"abstract":"<p><p>The formation of fibrotic tissue, characterized by the excessive accumulation of extracellular matrix (ECM) components such as collagen and fibronectin, is a normal and crucial stage of tissue repair in all organs. The over-synthesis, deposition, and remodeling of ECM components lead to organ dysfunction, posing a significant medical burden. Berberine, an isoquinoline alkaloid, is commonly used in the treatment of gastrointestinal diseases. With the deepening of scientific research, it has been gradually discovered that berberine also plays an important role in fibrotic diseases. In this review, we systematically introduce the effective role of berberine in fibrosis-related diseases. Specifically, this paper aims to provide a comprehensive review of the therapeutic role of berberine in treating fibrosis in organs such as the heart, liver, lungs, and kidneys. By summarizing its various pathways and mechanisms of action, including the inhibition of the transforming growth factor-[Formula: see text]/Smad signaling pathway, PI3K/Akt signaling pathway, MAPK signaling pathway, RhoA/ROCK signaling, and mTOR/p70S6K signaling pathway, as well as its activation of the Nrf2-ARE signaling pathway, AMPK signaling pathway, phosphorylated Smad 2/3 and Smad 7, and other signaling pathways, this review offers additional evidence to support the treatment of fibrotic diseases.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}