Journal of ethnopharmacology最新文献

{"title":"Palmatine, an isoquinoline alkaloid from Phellodendron amurense Rupr., ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome","authors":"Yin-Jing Jiang ,&nbsp;Yong-Hong Cheng ,&nbsp;Hao-Qing Zhu ,&nbsp;Yan-Ling Wu ,&nbsp;Ji-Xing Nan ,&nbsp;Li-Hua Lian","doi":"10.1016/j.jep.2024.119231","DOIUrl":"10.1016/j.jep.2024.119231","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Palmatine (Pal), derived from <em>Daemonorops margaritae</em> (Hance) Becc and <em>Phellodendron amurense Rupr.</em> is a natural isoquinoline alkaloid widely used in clearing heat and drying dampness, purging the pathogenic fire and removing symptoms, detoxifying toxins and healing sores.</div></div><div><h3>Aim of the study</h3><div>Gout is a common metabolic inflammatory disease caused by the deposition of MSU crystals (MSU) in joints and non-articulation structures. Given the multiple toxic side effects of clinical anti-gout medications, there is a need to find a safe and effective alternative. We investigated the therapeutic effects of Pal on MSU crystal-induced acute gouty inflammation, targeting the NLRP3 inflammasome mediated pyroptosis.</div></div><div><h3>Materials and methods</h3><div><em>In vitro</em>, mouse peritoneal macrophages (MPM) and rat articular chondrocytes were stimulated with LPS plus MSU in the presence or absence of Palmatine. <em>In vivo</em>, arthritis models include the acute gouty arthritis model by injecting MSU crystals in the paws of mice and the air pouch acute gout model by injecting MSU crystals into the mouse subcutaneous tissue of the back. Expression of NLRP3 inflammasome activation and NETosis formation was determined by Western blot, ELISA kit, immunohistochemistry, and immunofluorescence. In addition, the anti-cartilage damage of Palmatine on MSU-induced arthritis mice were also evaluated.</div></div><div><h3>Results</h3><div>Pal dose-dependently decreased levels of NLRP3 inflammasome activation related proteins NLRP3, ASC, caspase-1, IL-1β, HMGB1 and Cathepsin B. The NETosis protein levels of caspase-11, histone3, PR3 and PAD4 were remarkably reduced by Pal. Pal effectively blocked the activation of NLRP3 inflammasome, attenuated the caspase-11 mediated noncanonical NLRP3 inflammasome activation and intervened the formation of NETs, thereby inhibiting the pyroptosis. <em>In vivo</em>, Pal attenuated MSU-induced inflammation in gouty arthritis and protect the articular cartilage through inhibiting the pyroptosis of proteins NLRP3, ASC, caspase-1, IL-1β, HMGB1 and Cathepsin B, reducing levels of NETosis relevant proteins caspase-11, histone3, PR3 and PAD4 and up-regulating expression of protein MMP-3.</div></div><div><h3>Conclusion</h3><div>Palmatine ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119231"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864400","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":"Kouqiangjie formula alleviates diabetic periodontitis by regulating alveolar bone homeostasis via miR-29a-3p-mediated Dkk-1/Wnt/β-catenin signaling pathway","authors":"Yeke Wu ,&nbsp;Min Liu ,&nbsp;Jiawei Li ,&nbsp;Ranran Gao ,&nbsp;Qiongying Hu ,&nbsp;Yunfei Xie ,&nbsp;Hongling Zhou ,&nbsp;Huijing Li ,&nbsp;Xiang He ,&nbsp;Li Li","doi":"10.1016/j.jep.2024.119270","DOIUrl":"10.1016/j.jep.2024.119270","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Diabetic periodontitis (DP) is a commonly co-occurring complication in diabetes patients characterized by advanced gum disease and bone resorption. Conventional treatment modalities often fail to adequately address the underlying biological disruptions caused by diabetes. The use of traditional medicinal formulas Kouqiangjie Formula (KQJF) potentially offers novel therapeutic approaches for DP, but its detailed regulatory mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the impacts of KQJF on osteoblastic activity and inflammatory responses in a rat model and <em>in vitro</em> pre-osteoblast cultures under conditions mimicking DP, focusing on the involvement of the miR-29a-3p-Dkk-1/Wnt/β-catenin signaling pathway.</div></div><div><h3>Materials and methods</h3><div>Using network pharmacological analysis, micro-CT, histological staining, and an array of molecular biology methodologies including Western blotting, RT-qPCR, and immunofluorescence, we investigated the systemic and cellular responses to KQJF treatment. Both <em>in vivo</em> (rat model) and <em>in vitro</em> (MC3T3-E1 pre-osteoblasts) models subjected to high glucose and lipopolysaccharide (HG + LPS) stress were used to simulate DP conditions.</div></div><div><h3>Results</h3><div>Network pharmacological analyses, incorporating protein-protein interactions and pathway enrichment, disclosed that KQJF interacts with pathways crucial for inflammation and bone metabolism. Experimentally, KQJF significantly preserved alveolar bone architecture, reduced osteoclast activity, and dampened inflammatory cytokine production in DP rats. In pre-osteoblasts, KQJF enhanced cell viability, promoted cell cycle progression, and decreased apoptosis. At the molecular level, KQJF treatment upregulated miR-29a-3p and downregulated Dkk-1, thereby activating the Wnt/β-catenin pathway. The interventional studies with miR-29a-3p antagonists and Dkk-1 knockdown further confirmed the regulatory role of the miR-29a-3p/Dkk-1 axis in mediating the effects of KQJF.</div></div><div><h3>Conclusion</h3><div>KQJF mitigates the deleterious effects of DP by enhancing osteoblastic activity and reducing inflammatory responses, predominantly through the modulation of the miR-29a-3p-Dkk-1/Wnt/β-catenin signaling pathway. These discoveries underscore the therapeutic promise of KQJF in managing bone and inflammatory complications of DP, offering insights into its mechanism, and supporting its use in clinical settings.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119270"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872233","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":"Myristica fragrans water extract modulates multiple biological processes to pre-protect anhydrous ethanol-induced gastric ulcers via Akt/JNK/Nrf2 pathway activation","authors":"Xinzhong Li ,&nbsp;Junchi Wang ,&nbsp;Jiahui Zhou ,&nbsp;Haiyan Xiao ,&nbsp;Lina Liu ,&nbsp;Zheng Zhang ,&nbsp;Jianyong Si ,&nbsp;Chengmin Yang ,&nbsp;Ming Wang ,&nbsp;Jingxue Ye ,&nbsp;Guibo Sun","doi":"10.1016/j.jep.2024.119258","DOIUrl":"10.1016/j.jep.2024.119258","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Myristica fragrans&lt;/em&gt; (Nutmeg) is a commonly used Chinese herbal medicine and edible spice. According to &lt;em&gt;Pharmacopoeia of People's Republic of China&lt;/em&gt;, it has the effects of warming the middle and promoting qi, astringent intestines, and antidiarrheal. In the record of &lt;em&gt;Compendium of Materia Medica&lt;/em&gt;, it is the myristica fragrans water extract (MFWE) that is utilized for therapeutic purposes of gastrointestinal disorders frequently.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Research purpose&lt;/h3&gt;&lt;div&gt;This study is to investigate the pharmacodynamic material foundation and molecular mechanism of myristica fragrans on gastric ulcers using UHPLC-Q-Orbitrap-MS/MS with network pharmacology and experimental verification. This may provide theoretical guidance for the clinical use of myristica fragrans, and support a theoretical foundation for its future advancement into natural functional products that can relieve acute gastric ulcers.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;Using UHPLC/MS technology and network pharmacology, we identified possible active chemicals molecules, screened out core targets and core pathways, and simulated drug target binding through molecular docking situations. Acute gastric ulcer was caused by intragastric administration of absolute ethanol (0.075 ml/10g). Myristica fragrans water extract (182 mg/kg and 364 mg/kg) was administered orally 14 days in advance. The same method was used to distribute 0.5% carboxymethyl cellulose solution into the Model and Control group. The mice were murdered on the 15th day. Following the sacrifice, the gastric tissue was removed for histological analysis. The tissue needs to detect levels of IL-1β, TNF-α, IL-10, and IL-6 as well as the activity of SOD, GSH-Px, MDA, and MPO. In addition, H&amp;E staining and the TUNEL method were used to observe the effect on the gastric mucosa of mice. Western blot was used to detect apoptosis, ferroptosis, and antioxidation-related proteins.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 10 chemical constituents were identified from MFWE using UHPLC-Q-Orbitrap MS/MS and TCMSP database. Through the network pharmacological analysis of these identified components, it was discovered that the protective effect is mainly carried out by six compounds, they are: Myristicin, Myrisligna, Ferulaldehyde, Dehydrodiisoeugenol, 7-Methoxy-4-methylcoumarin, 1,5-Bis(2,5-dimethoxyphenyl) pentane-1,5-dione. Furthermore, MFWE was found to significantly reduce TNF-α, IL-1β, and IL-6, increase IL-10, and alleviate the inflammation caused by alcoholic gastric ulcers. It can lower MDA and MPO, raise SOD and GSH-Px to relieve oxidative stress. Results from network pharmacology indicated that the Akt, JNK, and apoptosis signaling pathways were essential for the therapeutic effects of MFWE on gastric ulcers. Further literature research revealed that Nrf2 and ferroptosis signaling pathways may be related to the role of MFWE. Mole","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119258"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872240","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":"Xiaoxuming decoction enhanced neuroprotection after cerebral ischemia/reperfusion via the JAK2/STAT3 signaling pathway based on UPLC/HRMS, network pharmacology and experimental validation","authors":"Manman Wang ,&nbsp;Yong Zhang ,&nbsp;Xueqin Fu ,&nbsp;Xuhuan Zou ,&nbsp;Jun Xiang ,&nbsp;Rui Lan","doi":"10.1016/j.jep.2024.119279","DOIUrl":"10.1016/j.jep.2024.119279","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Xiao-xu-ming decoction (XXMD), a prominent traditional Chinese medicinal formula historically revered for stroke treatment, demonstrates pronounced efficacy in ameliorating ischemic stroke injury.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the effects and mechanisms of XXMD on neuroprotection subsequent to cerebral ischemia/reperfusion in vivo and in vitro.</div></div><div><h3>Materials and methods</h3><div><em>N</em>eurobehavioral test, TTC staining, HE staining and nissl staining were used to examine the neuroprotective effect of XXMD on cerebral ischemia-reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats. Additionally, we assessed cell viability and injury with CCK8 and lactate dehydrogenase (LDH) assays. The changes in neuronal ultra-structure were observed after oxygen-glucose deprivation and reoxygenation (OGD/R) by transmission electron microscopy (TEM). Network analysis combined with ultrahighperformance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) predicted the mechanism of XXMD on ischemic stroke injury. Furthermore, the expression of neuroplasticity-related proteins neurofilament 200 (NF200), microtubule-associated protein 2 (MAP2), postsynaptic density protein 95 (PSD95), synaptophysin (SYN), phosphorylated Janus kinase2 (p-JAK2), and phosphorylated signal transduction and activator of transcription 3 (p-STAT3) was evaluated by immunofluorescence staining and Western blot analyses.</div></div><div><h3>Results</h3><div>XXMD significantly improved Ethology, infarct area and pathological changes after MCAO and reperfusion, reducing morphological and ultrastructural alterations and decreased cell viability in HT22 cells induced by OGD/R. Network pharmacology showed that 1153 compounds of XXMD were matched. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that XXMD treated ischemia stroke mainly regulating inflammation reaction-related signaling pathways, atherosclerosish-related signaling pathways. Molecular docking results showed that TP53, AKT1, STAT3, and IL6 are closely bound to the corresponding active ingredients. XXMD treatment significantly reversed the above alternations. XXMD or AG490 up-regulated the expression of neuroplasticity-associated proteins, and reduced phosphorylation of JAK2, STAT3 expression following OGD/R.</div></div><div><h3>Conclusion</h3><div>XXMD exerts neuroprotective effects by promoting neural plasticity via regulating the JAK2/STAT3 pathway, indicating a promising alternative therapeutic strategy for ischemic stroke.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119279"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895005","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":"Danggui Liuhuang Decoction ameliorates endothelial dysfunction by inhibiting the JAK2/STAT3 mediated inflammation","authors":"Yuanying Xu ,&nbsp;Wenjun Sha ,&nbsp;Jun Lu ,&nbsp;Shanshan Yu ,&nbsp;Xinyan Jin ,&nbsp;Cheng Chen ,&nbsp;Guangbo Ge ,&nbsp;Tao Lei","doi":"10.1016/j.jep.2024.119170","DOIUrl":"10.1016/j.jep.2024.119170","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Vascular endothelial dysfunction (VED) is recognized as a key triggering diabetic vascular complications. Danggui Liuhuang Decoction (DGLHD) has shown potential in mitigating these complications. However, the clinical efficacy of DGLHD in enhancing endothelial function, as well as the molecular mechanisms underlying its alleviation of Type 2 Diabetes-Related Vascular Endothelial Dysfunction (T2DM-VED), remains insufficiently understood.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;This study aims to validate the therapeutic efficacy of DGLHD in ameliorating T2DM-VED through clinical research. Furthermore it seeks to analyze the pharmacodynamic basis and molecular mechanisms of DGLHD, elucidating the biological processes through which DGLHD alleviates VED in type 2 diabetes mellitus (T2DM).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;Patients diagnosed with “Yin deficiency with hyperactive fire syndrome”, who are at a high risk for atherosclerotic cardiovascular disease (ASCVD) associated with T2DM, were recruited for this study. The effect of DGLHD on vascular endothelial function in T2DM was assessed by measuring the levels of pro-inflammatory factors through enzyme-linked immunosorbent assay (ELISA) and flow-mediated dilation (FMD). The primary components of DGLHD were analyzed using the UHPLC-Q-Exactive Orbitrap system. Potential therapeutic targets of DGLHD were predicted using network pharmacology and molecular docking analysis. To validate the mechanism of DGLHD on T2DM-VED, endothelial injury and inflammation cell models were established using human umbilical vein endothelial cells (HUVECs). A mouse model of diabetic endothelial injury was also developed to observe the effects of DGLHD on pro-inflammatory factors and vascular endothelial factors were observed through immunohistochemistry. Additionally, the effects on the janus kinase 2 (JAK2) / signal transducer and activator of transcription 3 (STAT3) signaling pathway were observed through Western blot experiments.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;DGLHD was found to contain 201 active components. Network pharmacology analysis indicated that the treatment of T2DM-VED with DGLHD is associated with modulation of the JAK2/STAT3 signaling pathway. Molecular docking analysis demonstrated that small molecules in DGLHD interact with JAK2 and STAT3. Our clinical study demonstrated that DGLHD significantly reduces the levels of pro-inflammatory factors and improves FMD readings in diabetic patients, thereby alleviating T2DM-VED. DGLHD was shown to inhibit the phosphorylation of JAK2 and STAT3, which blocks the JAK2/STAT3 signaling pathway transmission, reducing the release of pro-inflammatory and vascular endothelial growth factors, and preventing the inflammatory response &lt;em&gt;in vivo&lt;/em&gt; and &lt;em&gt;in vitro&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study demonstrates the potential efficacy of DGLHD in improving endothelial functi","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119170"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768108","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":"Anti-hyperuricemic effects of the seeds of Hovenia acerba in hyperuricemia mice","authors":"Ya Wang ,&nbsp;Xingjiang Liao ,&nbsp;Jinjuan Zhang ,&nbsp;Yaxin Yang ,&nbsp;Yanyan Gao ,&nbsp;Chunlei Zhang ,&nbsp;Xiaoli Guo ,&nbsp;Qinfeng Zhu ,&nbsp;Jing Li ,&nbsp;Lingling Yu ,&nbsp;Guobo Xu ,&nbsp;Xiang Fang ,&nbsp;Shang-Gao Liao","doi":"10.1016/j.jep.2024.119215","DOIUrl":"10.1016/j.jep.2024.119215","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The seeds of <em>Hovenia acerba</em> water extract (HAW) are used as an edible traditional Chinese medicine to treat diseases related to hyperuricemia (HUA).</div></div><div><h3>Aim of the study</h3><div>To evaluate HAW for its anti-HUA effect and to figure out their underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>The anti-HUA effects were evaluated on a mouse model by testing HAW's effects on the levels of serum uric acid (SUA), the biochemical indicators of liver and kidney function, and the histology of liver and kidney. Body weight and organ coefficients were determined for safety evaluation. RT-qPCR, Western blot and transcriptomic analysis was applied to investigate key mRNAs, proteins and signaling pathways.</div></div><div><h3>Results</h3><div>HAW significantly reduced the serum levels of UA, ALT, AST, and xanthine oxidase (XOD) and histologically alleviated the liver damage in HUA mice with no negative effect on body weight and organ coefficients. HAW markedly inhibited hepatic XOD activity and protein expression, significantly down-regulated mRNA and protein expressions of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), and up-regulated those of ATP transporter G2 (ABCG2) and renal organic anion transporter 1 (OAT1). RNA-seq analysis showed that 248 HUA-induced differential expression genes (DEGs) were reversed by HAW in the kidney. qRT-PCR analysis showed that regulation of the expressions of HUA-related inflammatory genes were involved.</div></div><div><h3>Conclusion</h3><div>HAW possessed remarkable anti-HUA effect. The mechanism involved XOD inhibition to reduce uric acid production, up-regulation of ABCG2 and OAT1 to increase uric acid excretion, and down-regulation of GLUT9 and URAT1 to inhibit uric acid reabsorption, and regulation of HUA-related inflammatory genes.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119215"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792009","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":"Carob leaves: Phytochemistry, antioxidant properties, vasorelaxant effect and mechanism of action","authors":"Widad Dahmani ,&nbsp;Zachée Louis Evariste Akissi ,&nbsp;Nabia Elaouni ,&nbsp;Nour Elhouda Bouanani ,&nbsp;Hassane Mekhfi ,&nbsp;Mohamed Bnouham ,&nbsp;Abdelkhaleq Legssyer ,&nbsp;Sevser Sahpaz ,&nbsp;Abderrahim Ziyyat","doi":"10.1016/j.jep.2024.119226","DOIUrl":"10.1016/j.jep.2024.119226","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Ceratonia siliqua</em> L., is a species of significant nutritional and industrial interest with extensive traditional uses. This fabaceae is renowned for its medicinal properties, including the treatment of high blood pressure. Due to its chemical composition, carob exhibits several valuable therapeutic functions such as antioxidant, antidiarrheal, antidiabetic, and antibacterial actions.</div></div><div><h3>Aim of the review</h3><div>This study investigates the chemical composition of <em>Ceratonia siliqua</em> L. leaves aqueous extract (CsAE) and explores the vasorelaxant effect and its underlying mechanisms. Acute toxicity and antioxidant activity of CsAE were also examined.</div></div><div><h3>Methods</h3><div>The phytochemical profile was elucidated using TLC and UHPLC-MS. The vasorelaxant effect and mechanisms were studied on thoracic aortic rings from normotensive rats, using various antagonists. Acute toxicity was assessed by orally administering the extract to mice. Antioxidant activity was evaluated using β-carotene bleaching and DPPH.</div></div><div><h3>Results</h3><div>TLC analysis of CsAE reveals flavonoids and hydrolysable tannins. Gallic acid, myricitrin, quercitrin as well as galloylglucopyranoside derivatives were identified by UHPLC-MS. CsAE relaxed phenylephrine-precontracted aorta in a concentration-dependent manner. This response was reduced when the aorta was denuded or pretreated with L-NAME, hydroxocobalamin, ODQ, 4-AP, TEA, calmidazolium chloride, and thapsigargin. CsAE showed significant antioxidant activity with no observed toxicity in the experimental animals.</div></div><div><h3>Conclusion</h3><div>CsAE has a significant vasodilatory effect, mediated through the CaM/eNOS/sGC pathway, activation of Kc_a and K_v, and intracellular calcium mobilization into SERCA. It also exhibits strong antioxidant activity, with no observed toxicity in the experimental animals. These findings represent the first evidence of the vasorelaxant effect of <em>Ceratonia siliqua</em> L. leaves from Eastern Morocco.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119226"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801075","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":"Osteoking inhibits apoptosis of BMSCs in osteoporotic rats via PI3K/AKT signaling pathway","authors":"Guijiang Huang ,&nbsp;Wenjie Yin ,&nbsp;Xin Zhao ,&nbsp;Muli Xu ,&nbsp;Peijin Wang ,&nbsp;Rong Li ,&nbsp;Li Zhou ,&nbsp;Wei Tang ,&nbsp;Jianlin Jiao","doi":"10.1016/j.jep.2024.118961","DOIUrl":"10.1016/j.jep.2024.118961","url":null,"abstract":"&lt;div&gt;&lt;div&gt;In China, Osteoking is a commonly used treatment and preventive measure for osteoporosis. The pathophysiology of osteoporosis is closely associated with apoptosis; however, it remains unclear whether the role of Osteoking in promoting bone formation is linked to apoptosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of study&lt;/h3&gt;&lt;div&gt;This study aims to investigate whether Osteoking inhibits apoptosis of BMSCs in osteoporotic rats via the PI3K/AKT signaling pathway and to conduct a detailed exploration of this mechanism. The goal is to provide a theoretical basis for the clinical application of Osteoking in osteoporosis treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A rat model of osteoporosis was established through bilateral ovariectomy (OVX), followed by treatment with Osteoking. After ten weeks of therapy, BMD was evaluated. The biomechanics of the left tibia were measured, the left femur was sequenced, and the right tibia was stained using histomorphometric and Masson's staining methods. Peripheral serum was collected to measure bone-related markers, including E2, PINP, and CTX. RNA-Seq results were verified using the remaining bone samples. Comparative analysis demonstrated the efficacy of Osteoking in treating osteoporosis and provided preliminary insights into the underlying mechanisms. Primary BMSCs were cultured using bone marrow apposition. CCK8 assays were conducted to screen the intervention conditions of Osteoking and LY294002. Various concentrations of Osteoking-containing serum and LY294002 were tested separately to determine the optimal intervention concentration for drug delivery. The impact of Osteoking on lipid formation was also evaluated. Following treatment of BMSCs from OVX rats with Sham serum, OVX serum, OVX + LY294002 serum, and Osteoking + LY294002 serum, the expression of PI3K/AKT/mTOR, osteogenesis-related regulatory factors, and apoptosis-related regulatory factors was assessed. Flow cytometry was employed to evaluate apoptosis in BMSCs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Osteoking significantly improved whole-body BMD and bone biomechanical indices in OVX rats. It also significantly elevated the serum levels of E2 and PINP while reducing the level of CTX, which significantly improved bone microstructure and promoted new bone formation. RNA-seq analysis indicated that the therapeutic mechanism involved the PI3K/AKT signaling pathway. Osteoking increased the expression of RUNX2 and decreased the expression of PPAR-γ, a marker of lipogenesis, in OVX rats. Extraction of BMSCs for subsequent studies revealed a significant reduction in proliferation and osteogenic differentiation, along with an increase in lipogenic differentiation, in the OVX group. Osteoking treatment inhibited the expression of PPAR-γ and increased the expression of RUNX2 in BMSCs. Additionally, Osteoking reversed the LY294002-mediated inhibition of PI3K/AKT/mTOR signaling pathway activation, increased the expression of the apoptosis-protecting protein Bcl2, ","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 118961"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801080","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":"Chemical diversity of the herbal decoction of Plectranthus ornatus and its anti-nociceptive and anti-inflammatory activities in zebrafish models","authors":"Joana Deyse Lima Agostinho ,&nbsp;Taynara Simão Matos ,&nbsp;Francisco das Chagas Lima Pinto ,&nbsp;Jéssica Bezerra Maciel ,&nbsp;Maria Kueirislene Amâncio Ferreira ,&nbsp;Jane Eire Silva Alencar de Menezes ,&nbsp;Edilberto Rocha Silveira ,&nbsp;Otília Deusdênia Loiola Pessoa","doi":"10.1016/j.jep.2024.119235","DOIUrl":"10.1016/j.jep.2024.119235","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Plectranthus ornatus&lt;/em&gt; is a medicinal plant originally from Africa but adapted to Brazil's climate conditions. It is recognized for its therapeutic properties, particularly for treating liver and stomach diseases, gastritis control, heartburn, and hangover. Therefore, studies on its chemical composition and pharmacological evaluation are important for the safe use of the plant.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;To investigate the chemical composition and pharmacological activity of leaf decoction of &lt;em&gt;P. ornatus&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;The lyophilized herbal decoction from &lt;em&gt;P. ornatus&lt;/em&gt; leaves was extracted with MeOH (methodology A), and CHCl&lt;sub&gt;3&lt;/sub&gt; and &lt;em&gt;n&lt;/em&gt;-BuOH (methodology B). The compounds were isolated using chromatographic techniques. Their structures were determined using spectroscopic methods (&lt;sup&gt;1&lt;/sup&gt;H and &lt;sup&gt;13&lt;/sup&gt;C NMR, IR, and HRESIMS) and comparison with published data. The lyophilized herbal decoctions DPO A (decoction from methodology A) and DPO B (methodology B), and compounds &lt;strong&gt;8&lt;/strong&gt;, &lt;strong&gt;9&lt;/strong&gt;, &lt;strong&gt;15&lt;/strong&gt;, and &lt;strong&gt;16&lt;/strong&gt; (4, 20, and 40 mg/kg) were evaluated for their toxicity, anti-nociceptive, and anti-inflammatory effects in experimental adult zebrafish (&lt;em&gt;Danio rerio&lt;/em&gt;) models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The present study focused on the CHCl&lt;sub&gt;3&lt;/sub&gt; and MeOH soluble fractions from the lyophilized leaf decoction leading to the isolation of five new diterpenes (&lt;strong&gt;1&lt;/strong&gt;, &lt;strong&gt;4-7&lt;/strong&gt;) and two new glucuronide flavonoid derivatives (&lt;strong&gt;2&lt;/strong&gt; and &lt;strong&gt;3&lt;/strong&gt;). In addition, four diterpenes (&lt;strong&gt;14&lt;/strong&gt;–&lt;strong&gt;17&lt;/strong&gt;), two glucuronide flavonoid derivatives (&lt;strong&gt;10&lt;/strong&gt; and &lt;strong&gt;11&lt;/strong&gt;), three phenolics (&lt;strong&gt;8&lt;/strong&gt;, &lt;strong&gt;12&lt;/strong&gt;, and &lt;strong&gt;13&lt;/strong&gt;), and one disaccharide (&lt;strong&gt;9&lt;/strong&gt;) previously reported were also isolated. In zebrafish essays, all samples showed no toxicity and exhibited an anti-nociceptive effect in at least one of the tested doses: &lt;strong&gt;9&lt;/strong&gt;, &lt;strong&gt;15&lt;/strong&gt;, &lt;strong&gt;16&lt;/strong&gt;, and DPO B (4 mg/kg), &lt;strong&gt;8&lt;/strong&gt; (20 mg/kg), and DPO A (40 mg/kg). Moreover, the compounds &lt;strong&gt;15&lt;/strong&gt; (4, 20, and 40 mg/kg) and &lt;strong&gt;16&lt;/strong&gt; (4, 20, and 40 mg/kg) exhibited anti-inflammatory effects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The lyophilized decoctions (DPO A and DPO B) including the compounds &lt;strong&gt;8&lt;/strong&gt;, &lt;strong&gt;9&lt;/strong&gt;, &lt;strong&gt;15&lt;/strong&gt;, and &lt;strong&gt;16&lt;/strong&gt; exhibited significant anti-nociceptive effects in adult zebrafish and showed no toxicity. Since pain can be a symptom of liver, stomach, and gastrointestinal disorders, and all the samples proved to be non-toxic, the herbal decoction of &lt;em&gt;P. ornatus&lt;/em&gt; leaf could be considered a potential therapeutic option in pain management, supporting the","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119235"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818250","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":"Discovering the Q-marker of scutellaria baicalensis against viral pneumonia integrated chemical profile identification, pharmacokinetic, metabolomics and network pharmacology","authors":"Xiaoyan Wang ,&nbsp;Yujun Xie ,&nbsp;Alamusi Bayoude ,&nbsp;Boli Zhang ,&nbsp;Boyang Yu","doi":"10.1016/j.jep.2024.119232","DOIUrl":"10.1016/j.jep.2024.119232","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Scutellaria baicalensis (SR), an ancient antiviral herbal medicine, is widely used in treating viral pneumonia and its active constituents, baicalin and baicalein, have been reported to have antiviral activity.</div></div><div><h3>Aim of the study</h3><div>However, reports on Q-markers of SR for antiviral pneumonia are still scarce. This study aims to screen for Q-markers using a comprehensive strategy that integrates identification of chemical profiles, in vivo absorption, metabolic regulation and predicted target.</div></div><div><h3>Materials and methods</h3><div>First, the markers were screened by chemical profile identification and pharmacokinetics using HPLC-MS/MS. Then, the therapeutic effects and differential metabolites of SR on viral pneumonia rats were evaluated by HE staining, assessment of inflammation levels and metabolomics analysis. Finally, the mechanisms of action between Q-markers and metabolites were exploited based on network pharmacology.</div></div><div><h3>Conclusion</h3><div>A total of 139 compounds were identified in SR, of which 35 and 41 were found in rat plasma and urine, respectively. Pharmacokinetic screening identified baicalin, baicalein, wogonin, wogonoside and oroxylin A as potential markers of SR. Furthermore, SR significantly improved interstitial and alveolar oedema, hemorrhage and alveolar collapse after modelling, while reducing the expression of inflammatory factors. Metabolomics revealed that SR significantly regulated the expression of 37 metabolites, mainly involving phenylalanine, tyrosine and tryptophan biosynthesis pathways. Network pharmacology showed that these five biomarkers can regulate the expression of metabolites through the key target SRC, ESR1, HSP90AA1, EGFR, thereby exerting antiviral effects against pneumonia. The study results suggest that baicalin, baicalein, wogonin, wogonoside and oroxylin A serve as primary Q-markers of SR in the treatment of viral pneumonia.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119232"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813290","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}