Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.
{"title":"Calycosin Enhances Heat Shock Related-Proteins in H9c2 Cells to Modulate Survival and Apoptosis against Heat Shock.","authors":"Pei-Fang Lai, Ramasamy Mahendran, Bruce Chi-Kang Tsai, Cheng-You Lu, Chia-Hua Kuo, Kuan-Ho Lin, Shang-Yeh Lu, Yu-Ling Wu, Yung-Ming Chang, Wei-Wen Kuo, Chih-Yang Huang","doi":"10.1142/S0192415X24500472","DOIUrl":"10.1142/S0192415X24500472","url":null,"abstract":"<p><p>Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1173-1193"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474131","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: 2024-02-07DOI: 10.1142/S0192415X2450006X
Jingya Fu, Xiaoxia Xie, Huimin Yao, Haijuan Xiao, Zhuoqun Li, Zhenzhi Wang, Ran Ju, Yan Zhao, Zhijun Liu, Nana Zhang
Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.
{"title":"The Effectiveness of Traditional Chinese Medicine in Treating Malignancies via Regulatory Cell Death Pathways and the Tumor Immune Microenvironment: A Review of Recent Advances.","authors":"Jingya Fu, Xiaoxia Xie, Huimin Yao, Haijuan Xiao, Zhuoqun Li, Zhenzhi Wang, Ran Ju, Yan Zhao, Zhijun Liu, Nana Zhang","doi":"10.1142/S0192415X2450006X","DOIUrl":"10.1142/S0192415X2450006X","url":null,"abstract":"<p><p>Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"137-160"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704314","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: 2024-02-07DOI: 10.1142/S0192415X24500071
Youke Wang, Xiang Yuan, Min Ren, Zhiyu Wang
Ferroptosis, an iron-dependent cell death mechanism driven by an accumulation of lipid peroxides on cellular membranes, has emerged as a promising strategy to treat various diseases, including cancer. Ferroptosis inducers not only exhibit cytotoxic effects on multiple cancer cells, including drug-resistant cancer variants, but also hold potential as adjuncts to enhance the efficacy of other anti-cancer therapies, such as immunotherapy. In addition to synthetic inducers, natural compounds, such as artemisinin, can be considered ferroptosis inducers. Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug. For clinical applications, researchers have synthesized various water-soluble artemisinin derivatives such as dihydroartemisinin, artesunate, and artemether. Artemisinin and artemisinin derivatives (ARTEs) upregulate intracellular free iron levels and promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects in vitro and in vivo. In this review, we introduce the mechanisms of ferroptosis, summarize the research on ARTEs-induced ferroptosis in cancer cells, and discuss the clinical research progress and current challenges of ARTEs in anti-cancer treatment. This review deepens the current understanding of the relationship between ARTEs and ferroptosis and provides a theoretical basis for the clinical anti-cancer application of ARTEs in the future.
铁中毒是一种由细胞膜上脂质过氧化物积累驱动的铁依赖性细胞死亡机制,已成为治疗包括癌症在内的各种疾病的一种有前途的策略。铁氧化诱导剂不仅对多种癌细胞(包括耐药性癌症变种)具有细胞毒性作用,而且还具有作为辅助药物提高免疫疗法等其他抗癌疗法疗效的潜力。除合成诱导剂外,青蒿素等天然化合物也可被视为铁突变诱导剂。青蒿素提取自黄花蒿,是一种水溶性很差的抗疟药物。为了临床应用,研究人员合成了各种水溶性青蒿素衍生物,如双氢青蒿素、青蒿琥酯和蒿甲醚。青蒿素和青蒿素衍生物(ARTEs)可上调细胞内游离铁水平,促进细胞内脂质过氧化物的积累,从而诱导癌细胞铁变态反应,缓解癌症的发展,在体外和体内产生强大的抗癌作用。在这篇综述中,我们介绍了铁突变的机制,总结了 ARTEs 诱导癌细胞铁突变的研究,并讨论了 ARTEs 在抗癌治疗中的临床研究进展和目前面临的挑战。这篇综述加深了目前人们对 ARTEs 与铁突变之间关系的理解,并为 ARTEs 未来的临床抗癌应用提供了理论依据。
{"title":"Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment.","authors":"Youke Wang, Xiang Yuan, Min Ren, Zhiyu Wang","doi":"10.1142/S0192415X24500071","DOIUrl":"10.1142/S0192415X24500071","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent cell death mechanism driven by an accumulation of lipid peroxides on cellular membranes, has emerged as a promising strategy to treat various diseases, including cancer. Ferroptosis inducers not only exhibit cytotoxic effects on multiple cancer cells, including drug-resistant cancer variants, but also hold potential as adjuncts to enhance the efficacy of other anti-cancer therapies, such as immunotherapy. In addition to synthetic inducers, natural compounds, such as artemisinin, can be considered ferroptosis inducers. Artemisinin, extracted from <i>Artemisia annua L.</i>, is a poorly water-soluble antimalarial drug. For clinical applications, researchers have synthesized various water-soluble artemisinin derivatives such as dihydroartemisinin, artesunate, and artemether. Artemisinin and artemisinin derivatives (ARTEs) upregulate intracellular free iron levels and promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects <i>in vitro</i> and <i>in vivo</i>. In this review, we introduce the mechanisms of ferroptosis, summarize the research on ARTEs-induced ferroptosis in cancer cells, and discuss the clinical research progress and current challenges of ARTEs in anti-cancer treatment. This review deepens the current understanding of the relationship between ARTEs and ferroptosis and provides a theoretical basis for the clinical anti-cancer application of ARTEs in the future.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"161-181"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704366","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: 2024-11-19DOI: 10.1142/S0192415X24500733
Yafei Liu, Kaifeng Zheng, Huanhuan Wang, Hong Liu, Kunyang Zheng, Junjun Zhang, Liang Han, Shenghao Tu, Yaoxian Wang
Hyperuricemia is a crucial feature of metabolic syndrome, characterized by elevated uric acid that causes urate crystal deposits in joints, kidneys, and subcutaneous tissues, resulting in gout and hyperuricemic nephropathy. The primary causes of uric acid metabolism disorder include overproduction and reduced excretion. The majority of uric acid in human body is derived from the breakdown of purine nucleotides. Overproduction of uric acid can result from increased concentration or activity of xanthine oxidase, the key enzyme responsible for uric acid synthesis. Alterations in the activity of proteins responsible for uric acid reabsorption and excretion can also affect serum uric acid. Many bioactive compounds derived from natural plants have been shown to inhibit xanthine oxidase activity to reduce uric acid production, modulate the activity of transport proteins to promote uric acid excretion, or alleviate oxidative stress and inflammation through various signaling pathways. These properties have garnered significant attention from researchers. In this paper, we first introduce the pathophysiological mechanisms of hyperuricemia, then summarize bioactive compounds with urate-lowering effects, and discuss their potential applications in treating hyperuricemia and its complications.
{"title":"Natural Bioactive Compounds: Emerging Therapies for Hyperuricemia.","authors":"Yafei Liu, Kaifeng Zheng, Huanhuan Wang, Hong Liu, Kunyang Zheng, Junjun Zhang, Liang Han, Shenghao Tu, Yaoxian Wang","doi":"10.1142/S0192415X24500733","DOIUrl":"10.1142/S0192415X24500733","url":null,"abstract":"<p><p>Hyperuricemia is a crucial feature of metabolic syndrome, characterized by elevated uric acid that causes urate crystal deposits in joints, kidneys, and subcutaneous tissues, resulting in gout and hyperuricemic nephropathy. The primary causes of uric acid metabolism disorder include overproduction and reduced excretion. The majority of uric acid in human body is derived from the breakdown of purine nucleotides. Overproduction of uric acid can result from increased concentration or activity of xanthine oxidase, the key enzyme responsible for uric acid synthesis. Alterations in the activity of proteins responsible for uric acid reabsorption and excretion can also affect serum uric acid. Many bioactive compounds derived from natural plants have been shown to inhibit xanthine oxidase activity to reduce uric acid production, modulate the activity of transport proteins to promote uric acid excretion, or alleviate oxidative stress and inflammation through various signaling pathways. These properties have garnered significant attention from researchers. In this paper, we first introduce the pathophysiological mechanisms of hyperuricemia, then summarize bioactive compounds with urate-lowering effects, and discuss their potential applications in treating hyperuricemia and its complications.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1863-1885"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669752","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}
Acupuncture is widely accepted as a therapeutic treatment by patients and healthcare providers globally. The safety record has been well established in acupuncture practice although some rare adverse events (AEs) were reported in the literature. While acupuncture-related AEs are generally defined as any undesirable event that occurs in patients during acupuncture treatment that may or may not be associated with the treatment, acupuncture-related adverse reactions (ARs) are defined as any undesirable or harmful reaction induced by trained practitioners practicing acupuncture treatment with standard doses. In this review, we clarify the relationship between AEs and ARs. Furthermore, we compile a list of acupuncture-related AEs reported in systematic reviews and meta-analysis articles. We find that serious acupuncture-related AEs are rare, with serious AEs occurring at a rate of approximately 0.04-0.08 per 10,000 treatments. The most likely serious AEs are pneumothorax, central and peripheral nerve injuries, heart injuries, abdominal organ injuries, infections, and needle breakage. Commonly reported minor AEs include bruising, hematoma, or bleeding at the needling site, as well as vasovagal reactions such as tiredness, dizziness, fainting, or residual pain at insertion points. The analysis identifies contributing factors for serious AEs being deep needle penetration, incorrect acupoint selection, and improper needle manipulation. It also addresses infections caused by contaminated needles, environmental factors, and inadequate skin disinfection. Moreover, other serious AEs, like needle breakage, are mostly due to aggressive manipulation and repeated reheating. Importantly, most acupuncture-related AEs are preventable. To avoid such AEs, acupuncturists in clinical practice should carefully select needling areas, be aware of cautions and contraindications of acupuncture, maintain safe acupuncture depth and hygiene, and strictly adhere to standard operating procedures.
{"title":"Acupuncture: A Review of the Safety and Adverse Events and the Strategy of Potential Risk Prevention.","authors":"Chien-Chen Huang, Peddanna Kotha, Cheng-Hao Tu, Ming-Cheng Huang, Yi-Hung Chen, Jaung-Geng Lin","doi":"10.1142/S0192415X24500617","DOIUrl":"10.1142/S0192415X24500617","url":null,"abstract":"<p><p>Acupuncture is widely accepted as a therapeutic treatment by patients and healthcare providers globally. The safety record has been well established in acupuncture practice although some rare adverse events (AEs) were reported in the literature. While acupuncture-related AEs are generally defined as any undesirable event that occurs in patients during acupuncture treatment that may or may not be associated with the treatment, acupuncture-related adverse reactions (ARs) are defined as any undesirable or harmful reaction induced by trained practitioners practicing acupuncture treatment with standard doses. In this review, we clarify the relationship between AEs and ARs. Furthermore, we compile a list of acupuncture-related AEs reported in systematic reviews and meta-analysis articles. We find that serious acupuncture-related AEs are rare, with serious AEs occurring at a rate of approximately 0.04-0.08 per 10,000 treatments. The most likely serious AEs are pneumothorax, central and peripheral nerve injuries, heart injuries, abdominal organ injuries, infections, and needle breakage. Commonly reported minor AEs include bruising, hematoma, or bleeding at the needling site, as well as vasovagal reactions such as tiredness, dizziness, fainting, or residual pain at insertion points. The analysis identifies contributing factors for serious AEs being deep needle penetration, incorrect acupoint selection, and improper needle manipulation. It also addresses infections caused by contaminated needles, environmental factors, and inadequate skin disinfection. Moreover, other serious AEs, like needle breakage, are mostly due to aggressive manipulation and repeated reheating. Importantly, most acupuncture-related AEs are preventable. To avoid such AEs, acupuncturists in clinical practice should carefully select needling areas, be aware of cautions and contraindications of acupuncture, maintain safe acupuncture depth and hygiene, and strictly adhere to standard operating procedures.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1555-1587"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515657","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: 2024-11-25DOI: 10.1142/S0192415X24500812
Meng'en Zhou, Yan Chen, Wenqi Jin, Peng Li, Jie Hu, Xiutian Guo
Intestinal fibrosis, a common complication of inflammatory bowel disease, in particular in Crohn's disease, arises from chronic inflammation, leading to intestinal narrowing, structural damage, and functional impairment that significantly impact patients' quality of life. Current treatment options for intestinal fibrosis are limited, with surgery being the primary intervention. Traditional Chinese Medicine (TCM) has emerged as a promising approach in preventing and treating intestinal fibrosis. However, there is a scarcity of literature summarizing the mechanisms underlying TCM's efficacy in this context. To address this gap, we conducted a comprehensive review, uncovering multiple mechanisms through which TCM mitigates intestinal fibrosis. These mechanisms include immune cell balance regulation, suppression of inflammatory responses, reduction of inflammatory mediators, alleviation of colon tissue damage, restoration of intestinal function, modulation of growth factors to inhibit fibroblast activation, dynamic regulation of TIMPs and MMPs to reduce extracellular matrix deposition, inhibition of epithelial-mesenchymal transition and endothelial-mesenchymal transition, autophagy modulation, maintenance of the intestinal mucosal barrier, prevention of tissue damage by harmful factors, and regulation of cell proliferation and apoptosis. This study aims to bridge existing knowledge gaps by presenting recent evidence supporting the utilization of TCM in both clinical and experimental research settings.
{"title":"Traditional Chinese Medicine: A Promising Treatment Option for Intestinal Fibrosis.","authors":"Meng'en Zhou, Yan Chen, Wenqi Jin, Peng Li, Jie Hu, Xiutian Guo","doi":"10.1142/S0192415X24500812","DOIUrl":"10.1142/S0192415X24500812","url":null,"abstract":"<p><p>Intestinal fibrosis, a common complication of inflammatory bowel disease, in particular in Crohn's disease, arises from chronic inflammation, leading to intestinal narrowing, structural damage, and functional impairment that significantly impact patients' quality of life. Current treatment options for intestinal fibrosis are limited, with surgery being the primary intervention. Traditional Chinese Medicine (TCM) has emerged as a promising approach in preventing and treating intestinal fibrosis. However, there is a scarcity of literature summarizing the mechanisms underlying TCM's efficacy in this context. To address this gap, we conducted a comprehensive review, uncovering multiple mechanisms through which TCM mitigates intestinal fibrosis. These mechanisms include immune cell balance regulation, suppression of inflammatory responses, reduction of inflammatory mediators, alleviation of colon tissue damage, restoration of intestinal function, modulation of growth factors to inhibit fibroblast activation, dynamic regulation of TIMPs and MMPs to reduce extracellular matrix deposition, inhibition of epithelial-mesenchymal transition and endothelial-mesenchymal transition, autophagy modulation, maintenance of the intestinal mucosal barrier, prevention of tissue damage by harmful factors, and regulation of cell proliferation and apoptosis. This study aims to bridge existing knowledge gaps by presenting recent evidence supporting the utilization of TCM in both clinical and experimental research settings.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"2107-2129"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712292","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 : 2024-01-01DOI: 10.1142/S0192415X24500678
Hao Lin, Qiang You, Xing Wei, Zongjun Chen, Xianwei Wang
Osthole, a coumarin compound mainly derived from Cnidium monnieri (L.), has attracted much interest from the scientific community owing to its multiple therapeutic properties. However, its pharmacological mechanism, pharmacokinetics, and toxicological effects are far from clear. Furthermore, the potential drug delivery platforms of osthole remain to be comprehensively delineated. The present review aimed to systematically summarize the most up-to-date information related to pharmacology, pharmacokinetics, and safety issues related to osthole, and discuss the investigations of novel drug delivery platforms. The information herein discussed was retrieved from authoritative databases, including PubMed, Web of Science, Google Scholar, Chinese National Knowledge Infrastructure (CNKI) and so on, reviewing information published up until February of 2024. New evidence shows that osthole induces a sequence of therapeutic actions and has a moderate absorption rate and rapid metabolic characteristics. In addition, this phytoconstituent possesses potential hepatotoxicity, and caution should be exercised against the risk of the drug combination. Furthermore, given its needy solubility in aqueous medium and non-organizational targeting, novel drug delivery methods have been designed to overcome these shortcomings. Given the properties of osthole, its therapeutic benefits ought to be elucidated in a greater array of comprehensive research studies, and the molecular mechanisms underlying these benefits should be explored.
Osthole 是一种香豆素化合物,主要提取自 Cnidium monnieri(L.),因其具有多种治疗特性而备受科学界关注。然而,它的药理机制、药代动力学和毒理效应还很不清楚。此外,奥司孔的潜在给药平台仍有待全面界定。本综述旨在系统总结与奥司孔相关的药理学、药代动力学和安全性问题的最新信息,并讨论新型给药平台的研究。本文讨论的信息来自权威数据库,包括PubMed、Web of Science、Google Scholar、中国国家知识基础设施(CNKI)等,查阅了截至2024年2月发表的信息。新证据表明,奥司孔可诱导一系列治疗作用,并具有吸收率适中、代谢迅速的特点。此外,这种植物成分还具有潜在的肝毒性,因此应谨慎对待联合用药的风险。此外,鉴于其在水介质中的溶解度较低,且不具有组织靶向性,人们设计了新型给药方法来克服这些缺点。鉴于奥司孔的特性,应在更多的综合研究中阐明其治疗功效,并探索这些功效的分子机制。
{"title":"Osthole, a Coumarin from <i>Cnidium monnieri</i>: A Review on Its Pharmacology, Pharmacokinetics, Safety, and Innovative Drug Delivery Platforms.","authors":"Hao Lin, Qiang You, Xing Wei, Zongjun Chen, Xianwei Wang","doi":"10.1142/S0192415X24500678","DOIUrl":"10.1142/S0192415X24500678","url":null,"abstract":"<p><p>Osthole, a coumarin compound mainly derived from <i>Cnidium monnieri</i> (L.), has attracted much interest from the scientific community owing to its multiple therapeutic properties. However, its pharmacological mechanism, pharmacokinetics, and toxicological effects are far from clear. Furthermore, the potential drug delivery platforms of osthole remain to be comprehensively delineated. The present review aimed to systematically summarize the most up-to-date information related to pharmacology, pharmacokinetics, and safety issues related to osthole, and discuss the investigations of novel drug delivery platforms. The information herein discussed was retrieved from authoritative databases, including PubMed, Web of Science, Google Scholar, Chinese National Knowledge Infrastructure (CNKI) and so on, reviewing information published up until February of 2024. New evidence shows that osthole induces a sequence of therapeutic actions and has a moderate absorption rate and rapid metabolic characteristics. In addition, this phytoconstituent possesses potential hepatotoxicity, and caution should be exercised against the risk of the drug combination. Furthermore, given its needy solubility in aqueous medium and non-organizational targeting, novel drug delivery methods have been designed to overcome these shortcomings. Given the properties of osthole, its therapeutic benefits ought to be elucidated in a greater array of comprehensive research studies, and the molecular mechanisms underlying these benefits should be explored.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"52 5","pages":"1397-1425"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335551","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}
Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction.
{"title":"<i>Astragalus membranaceus</i> Polysaccharide Regulates Small Intestinal Microbes and Activates IL-22 Signal Pathway to Promote Intestinal Stem Cell Regeneration in Aging Mice.","authors":"Jia-Ting Yin, Ming-Ruo Zhang, Shu Zhang, Shu-Hui Yang, Jian-Ping Li, Yun Liu, Jin-Ao Duan, Jian-Ming Guo","doi":"10.1142/S0192415X24500228","DOIUrl":"10.1142/S0192415X24500228","url":null,"abstract":"<p><p>Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of <i>Astragalus membranaceus</i> polysaccharide (APS) and <i>Astragalus membranaceus</i> ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of <i>Lactobacillus</i>, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"513-539"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295763","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: 2024-01-30DOI: 10.1142/S0192415X24500125
Chao Liu, Jian Ji, Chenglin Li
This study intends to explore the effects of Cucurbitacin B (CuB) and KIF20A on esophageal carcinoma (ESCA). Data were downloaded from the Cancer Genome Atlas (TCGA) database. The expression properties of KIF20A have been confirmed by GEPIA and ualcan from TCGA. The expression of KIF20A was determined using western blotting in ECA109 and KYSE150 cells after transfection with KIF20A, KIF20A siRNA, or numerical control siRNA (si-NC). Then, different concentrations of CuB were used to treat ECA109 and KYSE150 cells. CCK-8 and colony formation assays were used to measure cell viability, and a Transwell assay was utilized to assess cell migration and invasion ability. N-cadherin, E-cadherin, snail, p-Janus kinase 2 (JAK2), JAK2, p-signal transducer and activator of transcription 3 (STAT3), and STAT3 expression levels were evaluated using western blot. KIF20A was higher expressed in ESCA than in normal cells, and its overexpression was associated with squamous cell carcinoma, TNM stage, and lymph nodal metastasis of ESCA patients. In ECA109 and KYSE150 cells, increased KIF20A facilitated cell proliferation, migration, and invasion, whereas the knockdown of KIF20A can reverse these effects with N-cadherin. Snail expression diminished and E-cadherin increased. Similarly, CuB treatment could inhibit cell proliferation, migration, and invasion concentration dependently. Furthermore, KIF20A accelerated the expression of p-JAK2 and p-STAT3, while the application of CuB inhibited KIF20A expression and attenuated the activation of the JAK/STAT3 pathway. These findings revealed that CuB could inhibit the growth, migration, and invasion of ESCA through downregulating the KIF20A/JAK/STAT3 signaling pathway, and CuB could serve as an essential medicine for therapeutic intervention.
{"title":"Cucurbitacin B Inhibits the Malignancy of Esophageal Carcinoma through the KIF20A/JAK/STAT3 Signaling Pathway.","authors":"Chao Liu, Jian Ji, Chenglin Li","doi":"10.1142/S0192415X24500125","DOIUrl":"10.1142/S0192415X24500125","url":null,"abstract":"<p><p>This study intends to explore the effects of Cucurbitacin B (CuB) and KIF20A on esophageal carcinoma (ESCA). Data were downloaded from the Cancer Genome Atlas (TCGA) database. The expression properties of KIF20A have been confirmed by GEPIA and ualcan from TCGA. The expression of KIF20A was determined using western blotting in ECA109 and KYSE150 cells after transfection with KIF20A, KIF20A siRNA, or numerical control siRNA (si-NC). Then, different concentrations of CuB were used to treat ECA109 and KYSE150 cells. CCK-8 and colony formation assays were used to measure cell viability, and a Transwell assay was utilized to assess cell migration and invasion ability. N-cadherin, E-cadherin, snail, p-Janus kinase 2 (JAK2), JAK2, p-signal transducer and activator of transcription 3 (STAT3), and STAT3 expression levels were evaluated using western blot. KIF20A was higher expressed in ESCA than in normal cells, and its overexpression was associated with squamous cell carcinoma, TNM stage, and lymph nodal metastasis of ESCA patients. In ECA109 and KYSE150 cells, increased KIF20A facilitated cell proliferation, migration, and invasion, whereas the knockdown of KIF20A can reverse these effects with N-cadherin. Snail expression diminished and E-cadherin increased. Similarly, CuB treatment could inhibit cell proliferation, migration, and invasion concentration dependently. Furthermore, KIF20A accelerated the expression of p-JAK2 and p-STAT3, while the application of CuB inhibited KIF20A expression and attenuated the activation of the JAK/STAT3 pathway. These findings revealed that CuB could inhibit the growth, migration, and invasion of ESCA through downregulating the KIF20A/JAK/STAT3 signaling pathway, and CuB could serve as an essential medicine for therapeutic intervention.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"275-289"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643736","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}
Flavonol and flavonoid compounds are important natural compounds with various biomedical activities. Therefore, it is of great significance to develop a strategy for the specific extraction of flavonol and flavonoid compounds. Quercetin is a well-studied flavonoid possessing many health benefits. This compound is a versatile antioxidant known to possess protective abilities against body tissue injury induced by pathological situations and various drug toxicities. Although quercetin is widely distributed in many plants, its content generally is not very high. Therefore, the specific extraction of quercetin as well as other flavonol and flavonoid compounds has profound significance. In this work, the quercetin molecularly imprinting polymer (QMIP) was successfully prepared, in which a typical flavonol quercetin was selected as the template molecule. QMIP was synthesized by performing the surface molecular imprinting technology on the surface of NH2-MIL-101(Fe). Our study results showed that QMIP exhibited quick binding kinetic behavior, a high adsorption capacity (57.04[Formula: see text]mg/g), and the specific recognition ability toward quercetin compared with structurally distinct compounds (selective [Formula: see text]). The specific adsorption ability of quercetin by QMIP was further explained using computation simulation that molecules with non-planar 3D conformations hardly entered the molecularly imprinted cavities on QMIP. Finally, QMIP was successfully used for the specific extraction of quercetin and five other flavonol and flavonoid compounds in the crude extracts from Sapium sebiferum. This study proposes a new strategy to synthesize the molecularly imprinted polymer based on a single template for enriching and loading a certain class of active ingredients with similar core structures from variable botanicals.
{"title":"Using Quercetin to Construct Molecularly Imprinting Polymer in the Preparation and Enrichment of Flavonol and Flavonoid Compounds.","authors":"Dan-Dan Yang, Shu-Yi Li, Xiao-Wei Xu, Qing-Yao Li, Jia-Yuan He, Lian-Di Zhou, Qi-Hui Zhang","doi":"10.1142/S0192415X24500459","DOIUrl":"10.1142/S0192415X24500459","url":null,"abstract":"<p><p>Flavonol and flavonoid compounds are important natural compounds with various biomedical activities. Therefore, it is of great significance to develop a strategy for the specific extraction of flavonol and flavonoid compounds. Quercetin is a well-studied flavonoid possessing many health benefits. This compound is a versatile antioxidant known to possess protective abilities against body tissue injury induced by pathological situations and various drug toxicities. Although quercetin is widely distributed in many plants, its content generally is not very high. Therefore, the specific extraction of quercetin as well as other flavonol and flavonoid compounds has profound significance. In this work, the quercetin molecularly imprinting polymer (QMIP) was successfully prepared, in which a typical flavonol quercetin was selected as the template molecule. QMIP was synthesized by performing the surface molecular imprinting technology on the surface of NH<sub>2</sub>-MIL-101(Fe). Our study results showed that QMIP exhibited quick binding kinetic behavior, a high adsorption capacity (57.04[Formula: see text]mg/g), and the specific recognition ability toward quercetin compared with structurally distinct compounds (selective [Formula: see text]). The specific adsorption ability of quercetin by QMIP was further explained using computation simulation that molecules with non-planar 3D conformations hardly entered the molecularly imprinted cavities on QMIP. Finally, QMIP was successfully used for the specific extraction of quercetin and five other flavonol and flavonoid compounds in the crude extracts from <i>Sapium sebiferum</i>. This study proposes a new strategy to synthesize the molecularly imprinted polymer based on a single template for enriching and loading a certain class of active ingredients with similar core structures from variable botanicals.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1137-1154"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328217","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}