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Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice

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Chinese Journal of Integrative Medicine 2024年第7期30卷 608-615页

作者： WEI Ya-ru HOU Yun-long YIN Yu-jie LI Zhen LIU Yi HAN Ning-xin WANG Zi-xuan LIU Lu WANG Xiao-qi HAO Yuan-jie MA Kun GU Jiao-jiao JIA Zhen-hua Graduate School Hebei University of Chinese MedicineShijiazhuang050090China shijiazhuang yiling pharmaceutical new drug evaluation center Shijiazhuang050035China Hebei Institute of Integrated Traditional and Western Medicine Shijiazhuang050035China National Key Laboratory for Innovation and Transformation of Luobing Theory Shijiazhuang050035China Department of Cardiology Hebei Yiling HospitalShijiazhuang050091China Graduate School Hebei Medical UniversityShijiazhuang050017China

Objective To investigate the potential role of Tongxinluo(TXL)in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI)in *** A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 *** to a random number table,66 mice were randomly divided into 6 groups(n=11 per group):the sham group,the model group,the LY-294002 group,the TXL group,the TXL+LY-294002 group and the benazepril(BNPL)*** day after modeling,TXL and BNPL were administered by *** injection of LY-294002 was performed twice a week for 4 consecutive *** was used to measure cardiac function in *** staining was used to evaluate the degree of myocardial fibrosis in *** and quantitative analysis of endothelial mesenchymal transition(EndMT)after MIRI was performed by immunohistochemistry,immunofluorescence staining and flow cytometry,*** protein expressions of platelet endothelial cell adhesion molecule-1(CD31),α-smoth muscle actin(α-SMA),phosphatidylinositol-3-kinase(PI3K)and phospho protein kinase B(p-AKT)were assessed using Western *** TXL improved cardiac function in MIRI mice,reduced the degree of myocardial fibrosis,increased the expression of CD31 and inhibited the expression ofα-SMA,thus inhibited the occurrence of EndMT(P0.05).In addition,the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention,eliminated the protective effect of TXL,further supporting the protective effect of *** TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

关键词： myocardial fibrosis endothelial mesenchymal transition myocardial ischemia-reperfusion injury phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway

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Antifungal variant bis(bibenzyl)s from the liverwort Asterella angusta

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Chinese Chemical Letters 2013年第9期24卷 801-803页

作者： Jian-Bo Qu Ling-Mei Sun Hong-Xiang Lou School of pharmaceutical Sciences Shandong University center for drug evaluation SFDA

Bioassay-guided fractionation of the diethyl ether extract of the liverwort Asterella angusta led to the isolation of two antifungal bis（bibenzyl）s, riccardin I （1）, and angustatin A （2）. Their structures were established by spectroscopic analysis （1D NMR and 2D NMR, IR, MS）. Compound I is a novel variant riccardin-type bis（bibenzyl）, while compound 2 is the first nonheteratom-containing variant bis（bibenzyl） possessing a bibenzyl-phenanthrene skeleton.

关键词： Variant bis(bibenzyl)s Asterella angusta Antifungal activity

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Synthesis and evaluation of nitrate derivatives of colchicine as anticancer agents

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Chinese Chemical Letters 2011年第7期22卷 768-770页

作者： Li Hong Shen Ya Li Da Hai Zhang Yi Sheng Lai Li Jie Liu Department of Chemistry Handan College Handan 056005 China center of drug Discover China Pharmaceutical University Nanjing 210009 China Hebei yiling Medicine Corporation Ltd. Shijiazhuang 050035 China

To search for more potent antitumor agent, a series of novel nitric oxide-donating colchicine （Col） derivatives （6a-f, 8a and b） were synthesized by coupling nitrates with N-methyl colchiceinamide. Their cytotoxicity against four human cancer cell lines in vitro were evaluated by MTT assay. It was found that many of the derivatives displayed significant activity, particularly, compounds 6c, 8a and 8b showed more potent cytotoxic activities than Col.

关键词： Colchicine N-methyl colchiceinamide Nitrates Cytotoxicity

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A novel norsesquiterpene alkaloid from the mushroom-forming fungus Flammulina velutipes

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Chinese Chemical Letters 2013年第1期24卷 57-58页

作者： Zhen-Yu Xu Zhi-Ang Wu Kai-Shun Bi School of Business Administration Shenyang Pharmaceutical University center for drug evaluation SFDA

A new norsesquiterpe alkaloid （1） was isolated from the solid culture of mushroom-forming fungus Flammulina velutipes fermented on rice. The structure of I was elucidated by spectroscopic methods. The absolute confi... 详细信息

关键词： MushroomNorsesquiterpeneFlammulina velutipesCytotoxicity

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Inhibitory effects of Tripterygium wilfordii multiglycoside on benign prostatic hyperplasia in rats

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Chinese Journal of Natural Medicines 2015年第6期13卷 421-427页

作者： SHEN Hai-Nan XU Yuan JIANG Zhen-Zhou HUANG Xin ZHANG Lu-Yong WANG Tao Jiangsu center of drug Screening China Pharmaceutical University Key Laboratory of drug Quality Control and Pharmacovigilance (China pharmaceutical University) Ministry of Education Jiangsu center for Pharmacodynamics Research and evaluation China Pharmaceutical University

The present study was designed to evaluate the inhibitory effects of Tripterygium wilfordii multiglycoside(GTW) against testosterone-induced benign prostatic hyperplasia(BPH) in rats. A total of 45 rats were randomly divided into five groups: Group I, vehicle control group(sham-operated and treated with vehicle); Group II, BPH group; Group III, BPH rats treated with finasteride at a dose of 5 mg·kg-1; and Groups IV and V, BPH rats treated with GTW at dose levels of 10 and 20 mg·kg-1, respectively. The drugs were administered orally once a day for 14 days. Prostate weight, prostatic index, and the testosterone and dihydrotestosterone(DHT) levels in serum and prostate, and the serum prostate specific antigen(PSA) levels were measured; prostate tissues were taken for histopathological examination; and serum biochemical analysis was also performed. The BPH rats displayed an increase in prostate weight, prostatic index with increased testosterone and DHT levels in both the serum and prostate, and increased serum PSA levels. GTW treatment at both doses resulted in significant reductions in prostate weight, prostatic index, testosterone and DHT levels in both the serum and prostate, and serum PSA levels, compared with BPH group. Histopathological examination also indicated that GTW treatment at both doses inhibited testosterone-induced prostatic hyperplasia. Serum biochemical analysis showed that the liver and renal functions were normal. In conclusion, GTW inhibited testosterone-induced prostatic hyperplasia in rats, without host toxicity, providing a basis for the development of GTW as a novel therapy for BPH.

关键词： Tripterygium wilfordii Multiglycoside Benign prostatic hyperplasia Testosterone Dihydrotestosterone

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Jujuboside A ameliorates tubulointerstitial fibrosis in diabetic mice through down-regulating the YY1/TGF-β1 signaling pathway

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Chinese Journal of Natural Medicines 2022年第9期20卷 656-668页

作者： LIU Yang-Yang LI Lin JI Bei HAO Shi-Long KUANG Xiao-Feng CAO Xin-Yun YUAN Jia-Yu JIANG Zhen-Zhou QIAN Si-Tong WEI Chu-Jing XU Jing YIN Xiao-Xing LU Qian YANG Ting-Ting Jiangsu Key Laboratory of new drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China new drug Screening center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing 210009China

Diabetic nephropathy(DN)is one of the most common complications of diabetes mellitus,which is characterized in renal tubulointerstitial fibrosis(TIF).The current study was designed to investigate the protective effect of Jujuboside A(Ju A)on TIF in type 2 diabetes(T2DM)mice,and explore its underlying anti-fibrosis mechanism.A mouse T2DM model was established using high fat diet(HFD)feeding combined with intraperitoneal injection of streptozotocin(STZ).Then,diabetic mice were treated with Ju A(10,20 and 40 mg·kg^(−1)·d^(−1),i.g.)for 12 *** showed that administration of Ju A not only down-regulated fasting blood glucose(FBG)levels,but also improved hyperlipidemia and renal function in diabetic ***,the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice,while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition(EMT)of renal tubular epithelial cells(RTECs).Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1(YY1)in the renal cortex of diabetic mice,and reduced the levels of transforming growth factor-β1(TGF-β1)in the serum and renal cortex of Ju A treated *** to in vitro studies,the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose(HG)cultured HK-2 *** together,these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway.

关键词： Diabetic nephropathy Jujuboside A Tubulointerstitial fibrosis Extracellular matrix YY1/TGF-β1 signaling pathway

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Exploration of 5-cyano-6-phenylpyrimidin derivatives containing an 1,2,3-triazole moiety as potent FAD-based LSD1 inhibitors

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Acta Pharmaceutica Sinica B 2020年第9期10卷 1658-1668页

作者： Liying May Haojie Wangy Yinghua You Chaoya Ma Yuejiao Liu Feifei Yang Yichao Zheng Hongmin Liu Collaborative Innovation center of new drug Research and Safety evaluation Henan ProvinceKey Laboratory of Technology of Drug Preparation(Zhengzhou University)Ministry of Education of ChinaKey Laboratory of Henan Province for Drug Quality and EvaluationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China

Histone lysine specific demethylase 1(LSD1)has become a potential therapeutic target for the treatment of *** and develop novel and potent LSD1 inhibitors is a challenge,although several of them have already entered into clinical ***,for the first time,we reported the discovery of a series of 5-cyano-6-phenylpyrimidine derivatives as LSD1 inhibitors using flavin adenine dinucleotide(FAD)similarity-based designing strategy,of which compound 14 q was finally identified to repress LSD1 with IC50=183 nmol/*** analysis suggested that compound 14 q fitted well into the FAD-binding *** mechanism studies showed that compound 14 q may inhibit LSD1 activity competitively by occupying the FAD binding sites of LSD1 and inhibit cell migration and invasion by reversing epithelial to mesenchymal transition(EMT).Overall,these findings showed that compound14 q is a suitable candidate for further development of novel FAD similarity-based LSD1 inhibitors.

关键词： LSD1 inhibitors Pyrimidine Anticancer Flavin adenine dinucleotide(FAD) Gastric cancer

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Organic anion transporter 1 and 3 contribute to traditional Chinese medicine-induced nephrotoxicity

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Chinese Journal of Natural Medicines 2020年第3期18卷 196-205页

作者： SHEN Qing-Qing WANG Jing-Jing ROY Debmalya SUN Li-Xin JIANG Zhen-Zhou ZHANG Lu-Yong HUANG Xin Jiangsu Key Laboratory of drug Screening China Pharmaceutical UniversityNanjing 210009China Jiangsu center for Pharmacodynamics Research and evaluation China Pharmaceutical UniversityNanjing 210009China Key Laboratory of drug Quality Control and Pharmacovigilance Ministry of EducationChina Pharmaceutical UniversityNanjing 210009China center for drug Screening and Pharmacodynamics evaluation School of PharmacyGuangdong Pharmaceutical UniversityGuangzhou 510006China

With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to ***-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.

关键词： Traditional Chinese medicine Nephrotoxicity Renal tubular epithelial cell Organic anion transporter Aristolochic acid Tripterygium wilfordii Hook.f. Rheum officinale Baill

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Commentary:brain endothelial GSDMD as a novel target for brain disorders associated with BBB damage

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Chinese Journal of Natural Medicines 2024年第7期22卷 580-581页

作者： LIU Kui PANG Tao State Key Laboratory of Natural Medicines New Drug Screening and Pharmacodynamics Evaluation CenterChina Pharmaceutical UniversityNanjing 210009China

The blood-brain barrier(BBB)is a highly selective and critical interface between the blood and the central nervous system(CNS),essential for maintaining the microenvironment necessary for normal brain function and homeostasis[1].The BBB is primarily formed by brain endothelial cells(bECs),pericytes,and astrocytes,and it operates in concert with microglia/macrophages and neurons[2,3]to constitute the neurovascular unit(Fig.1).Disruption of the BBB or the presence of systemic inflammation can precipitate or exacerbate various CNS pathologies,including Alzheimer’s disease[4],amyotrophic lateral sclerosis[5],Huntington’s disease[6]and multiple sclerosis.

关键词： Brain endothelial cells GSDMD Blood-brain barrier Natural products Neuroinflammation Brain disorders

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Total glucosides of Rhizoma Smilacis Glabrae:a therapeutic approach for psoriasis by regulating Th17/Treg balance

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Chinese Journal of Natural Medicines 2023年第8期21卷 589-598页

作者： TANG Yingzhan YU Jingyi ZHAO Wen LIU Juyan PENG Hongying ZHANG Haoran JIANG Zhenzhou YU Qinwei ZHANG Luyong new drug screening center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing 210009China Guangzhou Baiyunshan Jingxiutang pharmaceutical Co. Ltd.Guangzhou 510130China Guangzhou pharmaceutical Holdings Co. Ltd.Guangzhou 510103China center for drug Research and Development Guangdong Pharmaceutical UniversityGuangzhou 510006China

Total glucosides of Rhizoma Smilacis Glabrae(RSG)are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T *** this study,we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material *** findings revealed significant improvements upon administration of RSG in an imiquimod(IMQ)-induced psoriasis *** improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema,ulceration,and *** transcriptome sequencing and T-cell flow sorting assay,we identified notable effects of RSG on the modulation of various cellular ***,RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G2 phase ***,RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial *** particular interest,we discovered thatβ-sitosterol,sitostenone,stigmasterol,smiglanin,and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT *** summary,our study highlights the therapeutic potential of RSG in the treatment of psoriasis,attributed to its ability to regulate the Th17/Treg *** findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.

关键词： Psoriasis Rhizoma Smilacis Glabrae Th17/Treg balance Inflammation Epithelium development

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