Journal of Natural Medicines最新文献

{"title":"Cycloartane-type triterpenoids from the leaves of Sandoricum koetjape and their efficacy on α-glucosidase inhibition activity","authors":"Tai-Xuan-Hoa Hang,&nbsp;Suekanya Jarupinthusophon,&nbsp;Rita Hairani,&nbsp;Van-Kieu Nguyen,&nbsp;Warinthorn Chavasiri","doi":"10.1007/s11418-023-01778-8","DOIUrl":"10.1007/s11418-023-01778-8","url":null,"abstract":"<div><p>The preliminary α-glucosidase inhibitory activity of the methanol extract of the leaves of <i>Sandoricum koetjape</i> Merr. exhibited promising results. The leaves was extracted with methanol to obtain\u0000the methanol extract that was continuedly partitioned with hexane and ethyl acetate. Those fractions were further purified by various chromatographic techniques. The isolation of the potent fractions furnished two new cycloartane-type triterpenoids (<b>1</b> and <b>2</b>) along with ten known compounds (<b>3</b>–<b>12</b>). Their chemical structures were unambiguously established by interpretation of NMR (1 D &amp; 2 D) and high-resolution electrospray ionization mass spectrometry (HRESIMS) data. Furthermore, the configurations of two new compounds were determined by using NOESY spectrum as well as comparing their NMR data to the reference. These compounds were evaluated against α-glucosidase. All tested compounds revealed potent activity with IC₅₀ value in the range of 2.17–49.2 µM compared to that of acarbose (IC₅₀ 100.6 µM). Compound <b>10</b> showed the lowest IC₅₀ value. This compound was reported as a mixed-type inhibitor. Compound <b>3</b> possessed the second strong activity with an IC₅₀ value of 14.0 μM and was further investigated on kinetic analysis which revealed as a mixed-type inhibitor with K_i and K_i′ values of 59.1 and 155.2 μM, respectively.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 3","pages":"655 - 663"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-023-01778-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140011933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Angelica acutiloba, A. sinensis, and other Chinese medicinal Apiaceae plants by DNA barcoding","authors":"Motoyasu Minami,&nbsp;Ryusaku Tanaka,&nbsp;Takako Mori,&nbsp;Taichi Fujii,&nbsp;Takashi Tsuchida","doi":"10.1007/s11418-024-01796-0","DOIUrl":"10.1007/s11418-024-01796-0","url":null,"abstract":"<div><p>Crude drug Angelicae acutilobae radix is one of the most important crude drugs in Japanese traditional medicine and is used mainly for the treatment of gynecological disorders. In the listing in the Japanese Pharmacopoeia XVIII, Angelicae acutilobae radix is defined as the root of <i>Angelica acutiloba</i> (Apiaceae), which has long been produced on an industrial scale in Japan. With the aging of farmers and depopulation of production areas, the domestic supply has recently declined and the majority of the supply is now imported from China. Due to having only slightly different morphological and chemical characteristics for the Apiaceae roots used to produce dried roots for Chinese medicines, the plant species originating the crude drug Apiaceae roots may be incorrectly identified. In particular, Angelicae sinensis radix, which is widely used in China, and Angelicae acutilobae radix are difficult to accurately identify by morphology and chemical profiles. Thus, in order to differentiate among Angelicae acutilobae radix and other radixes originated from Chinese medicinal Apiaceae plants, we established DNA markers. Using DNA sequences for the chloroplast <i>psb</i>A–<i>trn</i>H intergenic spacer and nuclear internal transcribed spacer regions, Angelicae acutilobae radix and other Chinese Apiaceae roots, including Angelicae sinensis radix<i>,</i> can be definitively identified.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 3","pages":"792 - 798"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paeoniflorin attenuates cuproptosis and ameliorates left ventricular remodeling after AMI in hypobaric hypoxia environments","authors":"Xin Fang,&nbsp;Yaoxuan Ji,&nbsp;Shuang Li,&nbsp;Lei Wang,&nbsp;Bo He,&nbsp;Bo li,&nbsp;Boshen Liang,&nbsp;Hongke Yin,&nbsp;Haotian Chen,&nbsp;Duojie Dingda,&nbsp;Bing Wu,&nbsp;Fabao Gao","doi":"10.1007/s11418-024-01781-7","DOIUrl":"10.1007/s11418-024-01781-7","url":null,"abstract":"<div><p>This study investigates the cardioprotective effects of Paeoniflorin (PF) on left ventricular remodeling following acute myocardial infarction (AMI) under conditions of hypobaric hypoxia. Left ventricular remodeling post-AMI plays a pivotal role in exacerbating heart failure, especially at high altitudes. Using a rat model of AMI, the study aimed to evaluate the cardioprotective potential of PF under hypobaric hypoxia. Ninety male rats were divided into four groups: sham-operated controls under normoxia/hypobaria, an AMI model group, and a PF treatment group. PF was administered for 4 weeks after AMI induction. Left ventricular function was assessed using cardiac magnetic resonance imaging. Biochemical assays of cuproptosis, oxidative stress, apoptosis, inflammation, and fibrosis were performed. Results demonstrated PF significantly improved left ventricular function and remodeling after AMI under hypobaric hypoxia. Mechanistically, PF decreased FDX1/DLAT expression and serum copper while increasing pyruvate. It also attenuated apoptosis, inflammation, and fibrosis by modulating Bcl-2, Bax, NLRP3, and oxidative stress markers. Thus, PF exhibits therapeutic potential for left ventricular remodeling post-AMI at high altitude by inhibiting cuproptosis, inflammation, apoptosis and fibrosis. Further studies are warranted to optimize dosage and duration and elucidate PF’s mechanisms of action.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 3","pages":"664 - 676"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of growth inhibitors for epithelial–mesenchymal transition-induced cells by TGF-β from plant-based sources identified the active compound hydroxychavicol from Piper bitle","authors":"Hirotaka Matsuo,&nbsp;Hitomi Kawakami,&nbsp;Naoko Anjiki,&nbsp;Noriaki Kawano,&nbsp;Hiroyuki Fuchino,&nbsp;Nobuo Kawahara,&nbsp;Kayo Yoshimatsu","doi":"10.1007/s11418-024-01785-3","DOIUrl":"10.1007/s11418-024-01785-3","url":null,"abstract":"<div><p>Epithelial–mesenchymal transition (EMT) has recently been associated with cancer invasion, metastasis, and resistance. In our previous study, we discovered nanaomycin K, a natural growth inhibitor for EMT-induced Madin Darby canine kidney (MDCK) cells, from the cultured broth of actinomycetes. However, the screening method was undeveloped, because the activity of nanaomycin K was discovered accidentally. In this study, we established a screening method by analyzing the characteristics of nanaomycin K in MDCK cells. Nanaomycin K showed the characteristic growth inhibitory activity on MDCK cells cultured under four conditions: medium containing dimethyl sulfoxide, SB431542, TGF-β, and a mixture of SB431542 and TGF-β. The activity was stronger in TGF-β-treated cells than in DMSO-treated cells. In the mixture of SB431542 and TGF-β-treated cells, the activity of nanaomycin K was suppressed. The anti-cancer agents, mitomycin C, cisplatin, and staurosporine, lacked the characteristics as that of nanaomycin K for these four treatment conditions. Since these four conditions distinguish between the effects of nanaomycin K and other anti-cancer agents in EMT-induced cells, the screening method was established. Among the 13,427 plant extracts tested, <i>Piper betle</i> leaf extract displayed growth inhibitory activity against EMT-induced cells. Through the purification of the extract via bio-guided fractionation, hydroxychavicol was isolated as an active compound. The cytotoxic activity of hydroxychavicol was stronger in EMT-induced MDCK cells than in control cells. However, its cytotoxic activity was suppressed in EMT-inhibited cells. Furthermore, hydroxychavicol exhibited same activity against SAS cells (human squamous cell carcinoma of the tongue). Thus, we have successfully established a screening method for growth inhibitors of EMT-induced cells and have discovered an inhibitor from plant-based sources.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 3","pages":"774 - 783"},"PeriodicalIF":2.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-024-01785-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139988926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new linear peptide, higapeptin, isolated from the mud flat-derived fungus Acremonium persicinum inhibits mitochondrial energy metabolism","authors":"Ahmed H. El-Desoky,&nbsp;Yuki Hitora,&nbsp;Yoshitomo Nishime,&nbsp;Yusaku Sadahiro,&nbsp;Teppei Kawahara,&nbsp;Sachiko Tsukamoto","doi":"10.1007/s11418-024-01784-4","DOIUrl":"10.1007/s11418-024-01784-4","url":null,"abstract":"<div><p>A combination of LC–MS/MS and feature-based molecular networking analyses led to the isolation of a new adenopeptin analog, higapeptin (<b>1</b>), and four known peptides, adenopeptin (<b>2</b>), adenopeptins B and C (<b>3</b> and <b>4</b>), and acremopeptin (<b>5</b>), from the rice culture of the fungus <i>Acremonium persicinum</i> (18F04103) isolated from a mud flat of the Ariake Sea in Kyushu, Japan. The structure of <b>1</b> was determined by NMR and MS/MS fragmentation analyses. The absolute configuration of the constituent amino acids was determined by Marfey’s analysis after acid hydrolysis. The C-terminal residue was synthesized, and its absolute configuration was established by Marfey’s analysis. Compounds <b>1</b> and <b>2</b> were found to inhibit mitochondrial energy metabolism, similar to efrapeptin D (<b>6</b>), a known mitochondrial ATPase inhibitor.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 3","pages":"505 - 513"},"PeriodicalIF":2.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139988925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating network pharmacology and experimental models to identify notoginsenoside R1 ameliorates atherosclerosis by inhibiting macrophage NLRP3 inflammasome activation","authors":"Jingyue Yu,&nbsp;Jinyu Hu,&nbsp;Margaret Baldini,&nbsp;Huan Lei,&nbsp;Lei Li,&nbsp;Shanshan Luo,&nbsp;Jielian Wu,&nbsp;Xupin Liu,&nbsp;Dan Shan,&nbsp;Yanfei Xie,&nbsp;Haihong Fang,&nbsp;Jun Yu","doi":"10.1007/s11418-023-01776-w","DOIUrl":"10.1007/s11418-023-01776-w","url":null,"abstract":"<div><p>Atherosclerosis is a cardiovascular disease, accounting for the most common mortality cause worldwide. Notoginsenoside R1 (NGR1) is a characteristic saponin of Radix notoginseng that exhibits anti-inflammatory and antioxidant effects while modulating lipid metabolism. Evidence suggests that NGR1 exerts cardioprotective, neuroprotective, and anti-atherosclerosis effects. However, underlying NGR1 mechanisms alleviating atherosclerosis (AS) have not been examined. This study used a network pharmacology approach to construct the drug-target-disease correlation and protein–protein interaction (PPI) network of NGR1 and AS. Moreover, functional annotation and pathway enrichment analyses deciphered the critical biological processes and signaling pathways potentially regulated by NGR1. The protective effect of NGR1 against AS and the underlying mechanism(s) was assessed in an atherogenic apolipoprotein E-deficient (ApoE^−/−) mice in vivo and an oxidized low-density lipoprotein (ox-LDL)-induced macrophage model in vitro. The network pharmacology and molecular docking analyses revealed that NGR1 protects against AS by targeting the NLRP3/caspase-1/IL-1β pathway. NGR1 reduced foam cell formation in ox-LDL-induced macrophages and decreased atherosclerotic lesion formation, serum lipid metabolism, and inflammatory cytokines in AS mice in vivo. Therefore, NGR1 downregulates the NLRP3 inflammasome complex gene expression of NLRP3, caspase-1, ASC, IL-1β, and IL-18, in vivo and in vitro.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 3","pages":"644 - 654"},"PeriodicalIF":2.5,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-023-01776-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Betulinic acid induces apoptosis of HeLa cells via ROS-dependent ER stress and autophagy in vitro and in vivo","authors":"Ping Chen,&nbsp;Xueer Zhang,&nbsp;Qiaomiao Fang,&nbsp;Zhongxiang Zhao,&nbsp;Chaozhan Lin,&nbsp;Yuan Zhou,&nbsp;Fangle Liu,&nbsp;Chenchen Zhu,&nbsp;Aizhi Wu","doi":"10.1007/s11418-024-01782-6","DOIUrl":"10.1007/s11418-024-01782-6","url":null,"abstract":"<div><p>Betulinic acid (BA), a naturally occurring lupane-type triterpenoid, possesses a wide range of potential activities against different types of cancer. However, the molecular mechanisms involved in anti-cervical cancer about BA were rarely investigated. Herein, the role of BA in cervical cancer suppression by ROS-mediated endoplasmic reticulum stress (ERS) and autophagy was deeply discussed. The findings revealed that BA activated Keap1/Nrf2 pathway and triggered mitochondria-dependent apoptosis due to ROS production. Furthermore, BA increased the intracellular Ca²⁺ levels, inhibited the expression of Beclin1 and promoted the expression of GRP78, LC3-II, and p62 associated with ERS and autophagy. Besides, BA initiated the formation of autophagosomes and inhibited autophagic flux by the co-administration of BA with 3-methyladenine (3-MA) and chloroquine (CQ), respectively. The in vivo experiment manifested that hydroxychloroquine (HCQ) enhanced the apoptosis induced by BA. For the first time, we demonstrated that BA could initiate early autophagy, inhibit autophagy flux, and induce protective autophagy in HeLa cells. Thus, BA could be a potential chemotherapy drug for cervical cancer, and inhibition of autophagy could enhance the anti-tumor effect of BA. However, the interactions of signaling factors between ERS-mediated and autophagy-mediated apoptosis deserve further attention.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 3","pages":"677 - 692"},"PeriodicalIF":2.5,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-024-01782-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139967510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydroartemisinin abolishes cisplatin-induced nephrotoxicity in vivo","authors":"Yan Luo,&nbsp;Jiaxing Zhang,&nbsp;Yue Jiao,&nbsp;Hao Huang,&nbsp;Liangshan Ming,&nbsp;Yunlei Song,&nbsp;Yanlong Niu,&nbsp;Xiaolu Tang,&nbsp;Liwei Liu,&nbsp;Yi Li,&nbsp;Yumao Jiang","doi":"10.1007/s11418-024-01783-5","DOIUrl":"10.1007/s11418-024-01783-5","url":null,"abstract":"<div><p>Dihydroartemisinin (DHA), a derivative of artemisinin which is primarily used to treat malaria in clinic, also confers protective effect on lipopolysaccharide-induced nephrotoxicity. While, the activities of DHA in cisplatin (CDDP)-caused nephrotoxicity are elusive. To investigate the role and underlying mechanism of DHA in CDDP-induced nephrotoxicity. Mice were randomly separated into four groups: normal, CDDP, and DHA (25 and 50 mg/kg were orally injected 1 h before CDDP for consecutive 10 days). All mice except the normal were single injected intraperitoneally with CDDP (22 mg/kg) for once on the 7th day. Combined with quantitative proteomics and bioinformatics analysis, the impact of DHA on renal cell apoptosis, oxidative stress, biochemical indexes, and inflammation in mice were investigated. Moreover, a human hepatocellular carcinoma cells xenograft model was established to elucidate the impact of DHA on tumor-related effects of CDDP. DHA reduced the levels of creatinine (CREA) (<i>p</i> &lt; 0.01) and blood urea nitrogen (BUN) (<i>p</i> &lt; 0.01), reversed CDDP-induced oxidative, inflammatory, and apoptosis indexes (<i>p</i> &lt; 0.01). Mechanistically, DHA attenuated CDDP-induced inflammation by inhibiting nuclear factor κB p65 (NFκB p65) expression, and suppressed CDDP-induced renal cell apoptosis by inhibiting p63-mediated endogenous and exogenous apoptosis pathways. Additionally, DHA alone significantly decreased the tumor weight and did not destroy the antitumor effect of CDDP, and did not impact AST and ALT. In conclusion, DHA prevents CDDP-triggered nephrotoxicity via reducing inflammation, oxidative stress, and apoptosis. The mechanisms refer to inhibiting NFκB p65-regulated inflammation and alleviating p63-mediated mitochondrial endogenous and Fas death receptor exogenous apoptosis pathway.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 2","pages":"439 - 454"},"PeriodicalIF":2.5,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139728700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vincazalidine A, a unique bisindole alkaloid from Catharanthus roseus","authors":"Yusuke Hirasawa,&nbsp;Ayaka Kase,&nbsp;Akie Okamoto,&nbsp;Keigo Suzuki,&nbsp;Mizuki Hiroki,&nbsp;Toshio Kaneda,&nbsp;Nahoko Uchiyama,&nbsp;Hiroshi Morita","doi":"10.1007/s11418-023-01775-x","DOIUrl":"10.1007/s11418-023-01775-x","url":null,"abstract":"<div><p>A new dimeric indole alkaloid, vincazalidine A consisting of an aspidosperma type and a modified iboga type with 1-azatricyclo ring system consisting of one azepane and two piperidine rings coupled with an oxazolidine ring was isolated from <i>Catharanthus roseus</i>, and the structure including absolute stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Vincazalidine A induced G2 arrest and subsequent apoptosis in human lung carcinoma cell line, A549 cells.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 2","pages":"382 - 392"},"PeriodicalIF":2.5,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angelica dahurica extract and its effective component bergapten alleviated hepatic fibrosis by activating FXR signaling pathway","authors":"Chong Gao,&nbsp;Zhong-He Hu,&nbsp;Zhen-Yu Cui,&nbsp;Yu-Chen Jiang,&nbsp;Jia-Yi Dou,&nbsp;Zhao-Xu Li,&nbsp;Li-Hua Lian,&nbsp;Ji-Xing Nan,&nbsp;Yan-Ling Wu","doi":"10.1007/s11418-024-01780-8","DOIUrl":"10.1007/s11418-024-01780-8","url":null,"abstract":"<div><p><i>Angelica dahurica (A. dahurica)</i> has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of <i>A. dahurica</i> extract (AD) and its effective component bergapten (BG) on hepatic fibrosis and potential mechanisms. Hepatic fibrosis was induced by intraperitoneal injection with carbon tetrachloride (CCl₄) for 1 week, and mice were administrated with AD or BG by gavage for 1 week before CCl₄ injection. Hepatic stellate cells (HSCs) were stimulated by transforming growth factor-β (TGF-β) and cultured with AD, BG, GW4064 (FXR agonist) or Guggulsterone (FXR inhibitor). In CCl₄-induced mice, AD significantly decreased serum aminotransferase, reduced excess accumulation of extracellular matrix (ECM), inhibited caspase-1 and IL-1β, and increased FXR expressions. In activated HSCs, AD suppressed the expressions of α-SMA, collagen I, and TIMP-1/MMP-13 ratio and inflammatory factors, functioning as FXR agonist. In CCl₄-induced mice, BG significantly improved serum transaminase and histopathological changes, reduced ECM excessive deposition, inflammatory response, and activated FXR expression. BG increased FXR expression and inhibited α-SMA and IL-1β expressions in activated HSCs, functioning as GW4064. FXR deficiency significantly attenuated the decreasing effect of BG on α-SMA and IL-1β expressions in LX-2 cells. In conclusion, AD could regulate hepatic fibrosis by regulating ECM excessive deposition and inflammation. Activating FXR signaling by BG might be the potential mechanism of AD against hepatic fibrosis.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 2","pages":"427 - 438"},"PeriodicalIF":2.5,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139705744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}