Chinese Journal of Natural Medicines最新文献

{"title":"Pure drug nanomedicines - where we are?","authors":"Yaoyao Lai,&nbsp;Bing Xie,&nbsp;Wanting Zhang,&nbsp;Wei He","doi":"10.1016/S1875-5364(25)60851-X","DOIUrl":"10.1016/S1875-5364(25)60851-X","url":null,"abstract":"<div><div>Pure drug nanomedicines (PDNs) encompass active pharmaceutical ingredients (APIs), including macromolecules, biological compounds, and functional components. They overcome research barriers and conversion thresholds associated with nanocarriers, offering advantages such as high drug loading capacity, synergistic treatment effects, and environmentally friendly production methods. This review provides a comprehensive overview of the latest advancements in PDNs, focusing on their essential components, design theories, and manufacturing techniques. The physicochemical properties and <em>in vivo</em> behaviors of PDNs are thoroughly analyzed to gain an in-depth understanding of their systematic characteristics. The review introduces currently approved PDN products and further explores the opportunities and challenges in expanding their depth and breadth of application. Drug nanocrystals, drug-drug cocrystals (DDCs), antibody-drug conjugates (ADCs), and nanobodies represent the successful commercialization and widespread utilization of PDNs across various disease domains. Self-assembled pure drug nanoparticles (SAPDNPs), a next-generation product, still require extensive translational research. Challenges persist in transitioning from laboratory-scale production to mass manufacturing and overcoming the conversion threshold from laboratory findings to clinical applications.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 385-409"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel araucarene diterpenes from Agathis dammara exert hypoglycemic activity by promoting pancreatic β cell regeneration and glucose uptake","authors":"Zhewei Yu ,&nbsp;Yi Zhang ,&nbsp;Wenhui Wang ,&nbsp;XinYi Wu ,&nbsp;Shunzhi Liu ,&nbsp;Yanlin Bin ,&nbsp;Hongsheng Li ,&nbsp;Bangping Cai ,&nbsp;Zheng Wang ,&nbsp;Meijuan Fang ,&nbsp;Rong Qi ,&nbsp;Mingyu Li ,&nbsp;Yingkun Qiu","doi":"10.1016/S1875-5364(25)60856-9","DOIUrl":"10.1016/S1875-5364(25)60856-9","url":null,"abstract":"<div><div>In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of <em>Agathis dammara</em>, including 11 previously unreported compounds: dammaradione (<strong>1</strong>), dammarones D−G (<strong>2</strong>, <strong>5</strong>, <strong>14</strong>, <strong>15</strong>), dammaric acids B−F (<strong>8</strong>−<strong>12</strong>), and dammarol (<strong>16</strong>). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure–activity relationship (SAR) analysis was conducted. Araucarone (<strong>3</strong>) and dammaric acid C (<strong>9</strong>), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic <em>β</em> cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into <em>β</em> cells in zebrafish.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 492-503"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structurally diverse sesquiterpenoids with anti-MDR cancer activity from Penicillium roqueforti","authors":"Shuyuan Mo ,&nbsp;Nanjin Ding ,&nbsp;Zhihong Huang ,&nbsp;Jun Yao ,&nbsp;Weiguang Sun ,&nbsp;Jianping Wang ,&nbsp;Yonghui Zhang ,&nbsp;Zhengxi Hu","doi":"10.1016/S1875-5364(25)60857-0","DOIUrl":"10.1016/S1875-5364(25)60857-0","url":null,"abstract":"<div><div>Five novel <em>nor</em>-eremophilane-type sesquiterpenoids, peniroqueforins E–H and J (<strong>1</strong>–<strong>4</strong> and <strong>7</strong>), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (<strong>5</strong> and <strong>8</strong>), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (<strong>9</strong>), along with four known compounds (<strong>6</strong> and <strong>10</strong>–<strong>12</strong>), were isolated and characterized from fungus <em>Penicillium roqueforti</em> (<em>P. roqueforti</em>). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with <strong>1</strong> in SW620/Ad300 cells was 50.36 nmol·L⁻¹, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L⁻¹). Subsequent molecular docking studies revealed an affinity between compound <strong>1</strong> and P-glycoprotein (P-gp), suggesting that this <em>nor</em>-eremophilane-type sesquiterpenoid (<strong>1</strong>) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 504-512"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Andrographolide sulfonate alleviates rheumatoid arthritis by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation","authors":"Chunhong Jiang ,&nbsp;Xi Zeng ,&nbsp;Jia Wang ,&nbsp;Xiaoqian Wu ,&nbsp;Lijuan Song ,&nbsp;Ling Yang ,&nbsp;Ze Li ,&nbsp;Ning Xie ,&nbsp;Xiaomei Yuan ,&nbsp;Zhifeng Wei ,&nbsp;Yi Guan","doi":"10.1016/S1875-5364(25)60855-7","DOIUrl":"10.1016/S1875-5364(25)60855-7","url":null,"abstract":"<div><div>Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from <em>Andrographis paniculata</em> (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. <em>In vitro</em>, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals <em>in vivo</em> and <em>in vitro</em>, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 480-491"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xiaohuang Qudan decoction alleviates ANIT-induced cholestatic liver injury by inhibiting the JAK2/STAT3 pathway and regulating TH17/Treg","authors":"Zhangkui Tan ,&nbsp;Lifeng Chen ,&nbsp;Zhiqin Ye ,&nbsp;Qiping Lu","doi":"10.1016/S1875-5364(25)60854-5","DOIUrl":"10.1016/S1875-5364(25)60854-5","url":null,"abstract":"<div><div>Xiaohuang Qudan decoction (XHQDD) is a classical traditional Chinese medicine (TCM) formula widely used in the treatment of cholestatic liver injury. Despite its widespread use, the protective mechanism of XHQDD against cholestatic liver injury remains incompletely understood. The aim of this study was to investigate whether XHQDD mediates its beneficial effects by inhibiting the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway and regulating TH17/Treg balance. To this end, the researchers used Sprague-Dawley (SD) rats and established a cholestatic liver injury model by oral administration of alpha-naphthylisothiocyanate (ANIT). The experimental group was divided into six groups: Control (CON), ANIT, ursodeoxycholic acid (UDCA), XHQDD-low dose (XHQDD-L) group, XHQDD-medium dose (XHQDD-M) group, and XHQDD-high dose (XHQDD-H) groups. Then, after 7 d of treatment, various tests were performed to verify the results. Firstly, XHQDD and its drug-containing serum were analyzed by ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), and 14 blood-entry components were identified. Then, bile flow was monitored and found to be significantly reduced in the model group, which was significantly reversed in the UDCA and XHQDD groups. To further assess ANIT-induced liver injury, hematoxylin and eosin (H&amp;E) and Sirius red staining, alongside transmission electron microscopy (TEM), were employed to observe liver tissues, revealing hepatocellular injury, cholestasis, and hepatic fibrotic changes. Serum inflammatory factors and liver injury indicators were assessed using enzyme-linked immunosorbent assay (ELISA), indicating an inflammatory state in ANIT-induced liver injury rats. The expression levels of JAK2/STAT3-related genes and proteins in liver and intestinal tissues were measured <em>via</em> quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, immunofluorescence (IF) staining, and Western blottting (WB) assays. These studies revealed that the inflammatory state of liver-injured rats was inextricably linked to the inflammatory cascade associated with the JAK2/STAT3 pathway and that XHQDD may exert anti-inflammatory efficacy by inhibiting the JAK2/STAT3 pathway. Flow cytometry was used to determine the percentage of T helper 17 (Th17)/regulatory T (Treg) cells in serum and hepatocytes, and it was further found that XHQDD was able to regulate Th17/Treg immune homeostasis in liver-injured rats. The findings suggest that XHQDD markedly alleviates inflammation in ANIT rats, potentially treating cholestasis and liver injury through JAK2/STAT3 inhibition and Th17/Treg balance regulation.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 457-470"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total alkaloids from Thesium chinense inhibit lipopolysaccharide-induced respiratory inflammation by modulating Nrf2/NF-κB/NLRP3 signaling pathway","authors":"Guohui Li ,&nbsp;Yueqin Guan ,&nbsp;Lintao Xu ,&nbsp;Guangcheng Peng ,&nbsp;Qingtong Han ,&nbsp;Tian Wang ,&nbsp;Zhenpeng Xu ,&nbsp;Xuesen Wen ,&nbsp;Hongxiang Lou ,&nbsp;Tao Shen","doi":"10.1016/S1875-5364(25)60834-X","DOIUrl":"10.1016/S1875-5364(25)60834-X","url":null,"abstract":"<div><div>Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of <em>Thesium chinense</em> Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of <em>T. chinense</em> (BC-Alk) are potent active substances underlying the traditional and clinical applications of <em>T. chinense</em> and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice <em>in vivo</em>. Mechanistic studies <em>in vitro</em> revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-<em>κ</em>B phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-<em>κ</em>B, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of <em>T. chinense</em> and Bairui Granules.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 421-430"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shionone protects cerebral ischemic injury through alleviating microglia-mediated neuroinflammation","authors":"Lushan Xu ,&nbsp;Chenggang Li ,&nbsp;ChenChen Zhao ,&nbsp;Zibu Wang ,&nbsp;Zhi Zhang ,&nbsp;Xin Shu ,&nbsp;Xiang Cao ,&nbsp;Shengnan Xia ,&nbsp;Xinyu Bao ,&nbsp;Pengfei Shao ,&nbsp;Yun Xu","doi":"10.1016/S1875-5364(25)60812-0","DOIUrl":"10.1016/S1875-5364(25)60812-0","url":null,"abstract":"<div><div>Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus <em>Aster</em> (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in <em>vitro</em>. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 4","pages":"Pages 471-479"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zishen Huoxue decoction (ZSHX) alleviates ischemic myocardial injury (MI) via Sirt5-β-tubulin mediated synergistic mechanism of “mitophagy-unfolded protein response” and mitophagy","authors":"Xing Chang ,&nbsp;Siyuan Zhou ,&nbsp;Yu Huang ,&nbsp;Jinfeng Liu,&nbsp;Yanli Wang,&nbsp;Xuanke Guan,&nbsp;Qiaomin Wu,&nbsp;Zhiming Liu,&nbsp;Ruxiu Liu","doi":"10.1016/S1875-5364(25)60838-7","DOIUrl":"10.1016/S1875-5364(25)60838-7","url":null,"abstract":"<div><div>Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. <em>In vitro</em>, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPR^mt) <em>via</em> the SIRT5 and -<em>β</em>-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury <em>via</em> the SIRT5-<em>β</em>-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-<em>β</em>-tubulin axis-related mitophagy and UPR^mt on cardiomyocytes.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 3","pages":"Pages 311-321"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saponins from Aralia taibaiensis protect against brain ischemia/reperfusion injuries by regulating the apelin/AMPK pathway","authors":"Zhengrong Li ,&nbsp;Yuwen Liu ,&nbsp;Kedi Liu ,&nbsp;Xingru Tao ,&nbsp;Naping Hu ,&nbsp;Wangting Li ,&nbsp;Jialin Duan","doi":"10.1016/S1875-5364(25)60841-7","DOIUrl":"10.1016/S1875-5364(25)60841-7","url":null,"abstract":"<div><div><em>Aralia taibaiensi</em>, widely distributed in western China, particularly in the Qinba Mountains, has been utilized as a folk medicine for treating diabetes, gastropathy, rheumatism, and cardiovascular diseases. Saponins from <em>A. taibaiensis</em> (sAT) have demonstrated protective effects against oxidative stress and mitochondrial dysfunction induced by ischemia/reperfusion (I/R). However, the underlying mechanisms remain unclear. <em>In vivo</em>, middle cerebral artery occlusion/reperfusion (MCAO/R) induced inflammatory infiltration, neuronal injury, cell apoptosis, mitochondrial dysfunction, and oxidative stress in the ischaemic penumbra, which were effectively mitigated by sAT. sAT increased the mRNA and protein expression levels of apelin and its receptor apelin/apelin receptors (ARs) both <em>in vivo</em> and <em>in vitro</em>. (Ala13)-Apelin-13 (F13A) and small interfering RNA (siRNA) abolished the regulatory effects of sAT on neuroprotection mediated by adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/protein kinase B (Akt). Furthermore, sAT induced apelin/AR expression by simultaneously inhibiting P38 mitogen-activated protein kinase (P38 MAPK)/activating transcription factor 4 (ATF4) and upregulating hypoxia-inducible factor-1α (HIF-1α). Our findings indicate that sAT regulates apelin/AR/AMPK by inhibiting P38 MAPK/ATF4 and upregulating HIF-1a, thereby suppressing oxidative stress and mitochondrial dysfunction.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 3","pages":"Pages 299-310"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ziyuglycoside II suppressed the progression of osteosarcoma by coordinating estrogen-related receptor gamma and p53 signaling pathway","authors":"Hang Du ,&nbsp;Dongjin Wu ,&nbsp;Tianyu Zhang ,&nbsp;Ying Zhong ,&nbsp;Kaiyi Wu ,&nbsp;Xin Guo ,&nbsp;Lisong Sheng ,&nbsp;Nana Huang ,&nbsp;Chunzheng Gao ,&nbsp;Rong Sun","doi":"10.1016/S1875-5364(25)60847-8","DOIUrl":"10.1016/S1875-5364(25)60847-8","url":null,"abstract":"<div><div>Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs <em>in vitro</em> experiments using multiple established osteosarcoma cell lines, as well as <em>in vivo</em> studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 3","pages":"Pages 354-367"},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}