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Obakulactone Alleviates Rheumatoid Arthritis by Promotion of ACOT1 Degradation via the Ubiquitin‒Proteasome Pathway and Restoration of Unsaturated Fatty Acid Homeostasis 认领 引用
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作者 Hongda Liu Le Yang +12 位作者 Yu Yang Huan Tang Junling Ren Hui Sun Xin Sun Songyuan Tang Chong Qiu Ye Sun Jigang Wang Guangli Yan Ling Kong Ying Han Xijun Wang 《Engineering》 SCIE EI CSCD 2026年第1期341-360,共20页
Rheumatoid arthritis(RA)remains a therapeutic challenge because of the suboptimal efficacy and significant adverse effects of current treatments.Obakulactone(OL),a natural tetracyclic triterpenoid isolated from Phello... Rheumatoid arthritis(RA)remains a therapeutic challenge because of the suboptimal efficacy and significant adverse effects of current treatments.Obakulactone(OL),a natural tetracyclic triterpenoid isolated from Phellodendri cortex,has emerged as a promising candidate for RA intervention.However,its underlying mechanism remains poorly understood.In this study,we investigated the therapeutic effects of OL and its molecular mechanisms in RA using a multifaceted approach.A complete Freund's adjuvant(CFA)-induced RA rat model revealed that OL significantly alleviated joint swelling and restored the expression of CD3+T cells and CD68+macrophages in joints,and the polarization state of macrophages shifted from proinflammatory M1(CD86)to anti-inflammatory M2(CD206)dominant.In addition,OL alleviated pathological changes in lymphoid organs(thymus and spleen),effectively inhibited the differentiation of CD4+T cells into T helper 17(Th17)cells,and normalized serum levels of inflammatory cytokines(e.g.,interleukin(IL)-6 and tumor necrosis factor-α(TNF-α))and RA diagnostic markers(e.g.,creactive protein(CRP)and rheumatoid factor(RF)).Multiomics profiling revealed that OL corrected the dysregulated biosynthesis and metabolism of unsaturated fatty acids(e.g.,arachidonic acid and linolenic acid)in RA rats,with acyl coenzyme A(CoA)thioesterase 1(ACOT1)identified as a critical regulator.In vitro studies have shown that OL significantly inhibits cell proliferation and inflammatory cytokine secretion and promotes the apoptosis of RA synovial fibroblasts(SFs).It inhibited the M1 polarization of Raw264.7 macrophages and promoted M2 polarization.Mechanistically,cellular thermal shift assays(CETSA),microscale thermo phoresis(MST),surface plasmon resonance(SPR),and short hairpin RNA(shRNA)experiments revealed ACOT1 as the direct target of OL.OL enhanced ACOT1 ubiquitinationmediated proteasomal degradation,thereby reducing downstream stearoyl-CoA desaturase-1 expression and inhibiting the Janus kinase(JAK)-signal transducer and activator of transcription(STAT)and phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT)signaling pathways,thus suppressing inflammation and fibrosis in SFs.This study establishes OL as a potential RA therapeutic agent and highlights ACOT1 as a novel target for RA intervention,offering insights into fatty acid metabolism reprogramming as a therapeutic strategy. 展开更多
关键词 Obakulactone Rheumatoid arthritis Unsaturated fatty acids Acyl coenzyme A thioesterase 1 Synovial fibroblasts Multiomics Ubiquitin-proteasome pathway
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Research progress on the hepatoprotective effect,pharmacokinetic properties,and hepatotoxicity of geniposide 认领 引用 被引量：2
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作者 Songyuan Tang Guangli Yan +4 位作者 Ling Kong Hui Sun Chang Liu Ying Han Xijun Wang 《Acupuncture and Herbal Medicine》 CAS CSCD 2025年第2期136-146,共11页
Liver disease(LD)is a global health problem caused by multiple factors.At present,there are still obvious problems with limited efficacy and strong side effects of drugs used in the clinical treatment of LD.Therefore,... Liver disease(LD)is a global health problem caused by multiple factors.At present,there are still obvious problems with limited efficacy and strong side effects of drugs used in the clinical treatment of LD.Therefore,it is of great significance to search for effective hepatoprotective drugs from natural products.Geniposide(GS)is a cyclic ether terpenoid compound and a key component in the traditional Chinese medicine Gardenia jasminoides.It has a significant inhibitory effect on LD.However,there is currently no literature systematically analyzing its mechanism of action.To adapt to the environment of new drug research and the need for precision medication,this article summarizes the pathways and possible mechanisms of action discovered by GS in the treatment of LD,based on recent research literature:regulating bile stasis,antioxidant and anti-apoptosis,improving amino acid metabolism,improving energy metabolism,regulating lipid metabolism,anti-inflammatory and analgesic effects,etc.It also summarizes the pharmacokinetics of GS in vivo and discusses the liver toxicity of GS that is positively correlated with dosage.In addition,the existing problems in current research and possible future development directions were also discussed,to lay the foundation for the clinical development of natural product GS. 展开更多
关键词 Geniposide Hepatotoxicity Liver disease Molecular mechanism Pharmacokinetics
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基于药效物质基础的中药药物发现策略及其迭代发展 认领 引用 被引量：19
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作者 葛楠 闫广利 +7 位作者 孙晖 杨乐 孔玲 孙野 韩莹 赵琦琦 康舒宇 王喜军 《Acupuncture and Herbal Medicine》 2023年第3期158-179,共22页
中药药效物质基础发现是中药新药创制的重要途径,青蒿素、黄连素和麻黄碱等国际知名药物均是由此途径陆续被发现及开发出来。然而,由于中医药理论及实践的复杂性,中药药效物质基础发现技术仍然不能完全满足创新药物的需要,仍然是制约中... 中药药效物质基础发现是中药新药创制的重要途径,青蒿素、黄连素和麻黄碱等国际知名药物均是由此途径陆续被发现及开发出来。然而,由于中医药理论及实践的复杂性,中药药效物质基础发现技术仍然不能完全满足创新药物的需要,仍然是制约中药创新药物的关键科学问题。中医临床是以多味中药组成方剂作为药物针对证候而表达临床疗效,而方剂的复杂性和证候的模糊性使得与临床疗效相关的中药体内药效物质基础发现充满挑战性。几十年来,中医药研究人员不断地建立及发展多项交叉学科的技术和方法,努力去发现发挥疗效的中药药效物质基础。本文回顾总结了中药药效物质基础发现的策略及其迭代发展历史,主要包括植物化学方法,即经典的系统分离筛选法(提取、分离、纯化、结构鉴定和药理活性测试);生物活性导向分离;中药血清药物化学方法;以及将体内成分与证候生物标志物关联分析的中医方证代谢组学方法。而中医方证代谢组学是近年来出现的一种符合中医药理论与特点的药效物质基础发现策略,该方法基于证候标记物与方剂体内显效成分关联分析,揭示方剂发挥疗效的体内药效物质及作用靶点与通路,推动基于临床疗效的创新药物研发及先导化合物的发现,促进中医药的现代化及产业化发展。 展开更多
关键词 中医方证代谢组学 中药药效物质基础 新药开发策略 中药血清药物化学 中医药现代化
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中医理论视域下创新中药发现策略和实践 认领 引用 被引量：14
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作者 刘鸿达 孙晖 +3 位作者 闫广利 孔玲 韩莹 王喜军 《中国科学基金》 CSSCI CSCD 北大核心 2024年第3期483-491,共9页
在现代科学技术飞速发展的新形势下,源于中医临床的中药创新药物发现在应对新发疾病、重大疾病具有鲜明的中医药特色和优势,探索合理的创新中药发现策略、研究路径是我国中医药创新发展的关键问题。中医药具有完整独特的理论体系和丰富... 在现代科学技术飞速发展的新形势下,源于中医临床的中药创新药物发现在应对新发疾病、重大疾病具有鲜明的中医药特色和优势,探索合理的创新中药发现策略、研究路径是我国中医药创新发展的关键问题。中医药具有完整独特的理论体系和丰富的临床实践积累,在中医理论指导下,临床驱动、主动创新、中西医结合,是我国具有中医药特色的药物发现的重要途径。本文就中医理论指导下的中药创新药物发现研究思路进行阐述,列举了近年来基于中药的药物发现研究成果和相关新兴研究策略,为现代中药创新药物研发提供一定的思路和参考。 展开更多
关键词 中医理论 中药创新药物 中西医结合
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Drug innovation via integration of traditional Chinese and Western medicine 认领 引用 被引量：1
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作者 Zhineng Li Le Yang +6 位作者 Ling Kong Hui Sun Ye Sun Xiangmei Chen Fengting Yin Guangli Yan Xijun Wang 《Science of Traditional Chinese Medicine》 CSCD 2025年第2期97-112,共16页
Innovative drugs are defined as new chemical entities that play a vital role in the treatment and maintenance of human health.While single-target innovative drugs have achieved notable success,they face limitations in... Innovative drugs are defined as new chemical entities that play a vital role in the treatment and maintenance of human health.While single-target innovative drugs have achieved notable success,they face limitations in addressing the increasingly complex and precise spectra of diseases.The advent of multi-target innovative drugs offers new opportunities,supported by a growing body of pharmaco-logical evidence.Herbal medicines are recognized as valuable sources of multi-target therapeutics due to their proven efficacy in treating complex diseases.However,the identification and validation of such drugs from herbal sources continue to pose significant challenges.This paper presents a comprehensive review of the literature on traditional Chinese medicine,integrated medicine,chemistry,and biol-ogy from 2015 to 2025.It summarizes the strategies employed in integrating traditional Chinese and Western medicine for innovative drug development,along with successful application cases.We believe these efforts will deepen understanding of the current land-scape,accelerate the discovery of multi-target innovative drugs from herbal medicine,and contribute to addressing major human health challenges. 展开更多
关键词 Drug innovation Traditional Chinese medicine Western medicine Research strategy Multitarget drugs
Cancer chemoprevention:signaling pathways and strategic approaches 认领 引用
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作者 Junling Ren Guangli Yan +7 位作者 Le Yang Ling Kong Yu Guan Hui Sun Chang Liu Lei Liu Ying Han Xijun Wang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2025年第5期2702-2745,共44页
Although cancer chemopreventive agents have been confirmed to effectively protect high-risk populations from cancer invasion or recurrence,only over ten drugs have been approved by the U.S.Food and Drug Administration... Although cancer chemopreventive agents have been confirmed to effectively protect high-risk populations from cancer invasion or recurrence,only over ten drugs have been approved by the U.S.Food and Drug Administration.Therefore,screening potent cancer chemopreventive agents is crucial to reduce the constantly increasing incidence and mortality rate of cancer.Considering the lengthy prevention process,an ideal chemopreventive agent should be nontoxic,inexpensive,and oral.Natural compounds have become a natural treasure reservoir for cancer chemoprevention because of their superior ease of availability,cost-effectiveness,and safety.The benefits of natural compounds as chemopreventive agents in cancer prevention have been confirmed in various studies.In light of this,the present review is intended to fully delineate the entire scope of cancer chemoprevention,and primarily focuses on various aspects of cancer chemoprevention based on natural compounds,specifically focusing on the mechanism of action of natural compounds in cancer prevention,and discussing in detail how they exert cancer prevention effects by affecting classical signaling pathways,immune checkpoints,and gut microbiome.We also introduce novel cancer chemoprevention strategies and summarize the role of natural compounds in improving chemotherapy regimens.Furthermore,we describe strategies for discovering anticancer compounds with low abundance and high activity,revealing the broad prospects of natural compounds in drug discovery for cancer chemoprevention.Moreover,we associate cancer chemoprevention with precision medicine,and discuss the challenges encountered in cancer chemoprevention.Finally,we emphasize the transformative potential of natural compounds in advancing the field of cancer chemoprevention and their ability to introduce more effective and less toxic preventive options for oncology. 展开更多
关键词 chemopreventive agent drug discovery immune checkpoints gut microbiome signaling pathways cancer chemoprevention cancer chemopreventive agents natural compounds
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Chinmedomics facilitated quality-marker discovery of Sijunzi decoction to treat spleen qi deficiency syndrome 认领 引用 被引量：19
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作者 Qiqi Zhao Xin Gao +6 位作者 Guangli Yan Aihua Zhang Hui Sun Ying Han Wenxiu Li Liang Liu Xijun Wang 《Frontiers of Medicine》 SCIE CSCD 2020年第3期335-356,共22页
Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years.However,the quality control (QC) standards of SJZD are insufficient... Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years.However,the quality control (QC) standards of SJZD are insufficient.Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formularapidly.In this study,we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC.A total of 56 compounds in SJZD were characterized in vitro,and 23 compounds were discovered in vivo.A total of 58 biomarkers were related to SQDS,and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status.A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy.We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng;dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria;glycyrrhizic acid,isoglabrolide,and glycyrrhetnic acid as the q-markers of licorice;and 2-atractylenolide as the q-marker of macrocephala.According to the discovery of the SJZD q-markers,we can establish the quality standard that is related to efficacy. 展开更多
关键词 traditional Chinese medicine Sijunzi decoction spleen qi deficiency syndrome Chinmedomics quality-marker
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