Journal of ethnopharmacology最新文献

{"title":"Inhibition of Bcl-2/Bax/cleaved caspase-3 pathway activity by rare ginsenosides ameliorates cyclophosphamide-induced oligoasthenospermia (OA) in male mice.","authors":"Fei Yan, Jiamin Li, Murong Zhu, Ke Zhao, Jiasheng Han, Yan Wang, Lei Fang, Peng Xue","doi":"10.1016/j.jep.2025.120378","DOIUrl":"10.1016/j.jep.2025.120378","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Oligoasthenozoospermia (OA) is the main factor leading to male infertility. According to traditional Chinese medicine, ginseng and its derivatives can improve male sperm quality by nourishing the kidneys and replenishing qi. Ginsenosides have been recognized as the principal pharmacologically active constituents of Panax ginseng, and are generally categorized into highly polar and rare ginsenosides. Rare ginsenosides can be generated through thermal transformation of the highly polar forms, yielding structurally related compounds collectively referred to as heat-transformed saponins (HTS). HTS comprising Rg6, F4, Rg3, Rk1, and Rg5-demonstrate substantial bioactivity at a dose of 50 mg/kg without observable toxicity. However, their effects on oligoasthenospermia (OA) and the associated molecular mechanisms remain poorly defined.</p><p><strong>Aim of this study: </strong>To determine whether HTS can mitigate sperm damage caused by cyclophosphamide (CP) and elucidate their potential mechanism of action.</p><p><strong>Materials and methods: </strong>Rare ginsenosides (HTS) were prepared in our laboratory. CP was used to construct an OA model. HTS were either administered prior to CP modelling to create a prevention group (HTS-CP) or after CP modelling to create a treatment group (CP-HTS). The intervention effect of HTS was evaluated using indicators such as sperm quality, hormone levels, and the degree of inflammation.</p><p><strong>Results: </strong>In this study, HTS significantly increased the sperm count, improved sperm motility, and ameliorated testicular tissue damage. HTS decreased the elevation in follicle-stimulating hormone (FSH), lactate dehydrogenase (LDH), malondialdehyde (MDA), and inflammatory factor levels caused by CP and increased the levels of testosterone (T), luteinizing hormone (LH), acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase (SOD), and glutathione peroxidase (GSH) in the model group. HTS significantly increased the gene and protein expression levels of PUMA and Bcl-2 in testicular tissue and significantly decreased the gene and protein expression levels of Bax and caspase-3.</p><p><strong>Conclusion: </strong>This study revealed that HTS can effectively ameliorate CP-induced damage to male sperm by inhibiting apoptosis via the Bcl-2/Bax/cleaved caspase-3 pathway.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120378"},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794670","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":"Unveiling the dark side of Moringa: High doses of Moringa oleifera Lam. Leaf extract increase the risk of adenocarcinoma in obesity-induced prostate hyperplasia through hyperhomocysteinemia/miR-155/STAT3 cascade.","authors":"Sylvia E Shaker, Wessam M Aziz, Olfat A Hammam, Noha E Ibrahim, Heba Shawky","doi":"10.1016/j.jep.2025.120373","DOIUrl":"10.1016/j.jep.2025.120373","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Moringa oleifera Lam., known as the \"miracle tree\", has been applauded as a complementary medicine, owing to its broad-spectrum health benefits.</p><p><strong>Aim: </strong>This study provides novel insights into the unrecognized risk associated with the use of high-dose M. oleifera Lam. leaf extract (MLE) in an obesity-induced prostate hyperplasia (BPH) rat model.</p><p><strong>Methods: </strong>Dry M. oleifera leaves were water-extracted, and the phytocomposition was determined using HPLC and GC-MS. Obesity-related BPH symptoms were induced in male Sprague Dawley rats receiving a high-fat diet (HFD) for 12 weeks, plus testosterone propionate injected subcutaneously (10 mg/kg/day in corn oil) for 4 weeks. BPH animals received different MLE doses, a reference drug (Prostride), and a combination of MLE + Prostride for 30 days. The therapeutic efficacy of different treatments was assessed in terms of their modulatory effect on obesity-related markers, including body weight, lipid profile, plasma homocysteine (Hcy), and BPH-related markers, including prostate index, androgenic hormones, and prostatic transcriptome of inflammatory/oncogenic/apoptotic mediators.</p><p><strong>Results: </strong>the MLE treatment presented a dose-dependent effect in BPH animals, where the low and medium doses alleviated the BPH symptoms, as indicated by the restoration of redox homeostasis and nearly normalizing the inflammatory, oncogenic, and apoptotic transcriptome in treated prostates, reflected by the reversal of histopathological alterations. Conversely, the high-dose MLE aggravated BPH symptoms and further promoted a protumorigenic milieu through elevating plasma Hcy, which simultaneously upregulated a miR-155/STAT3-mediated oncogenic cascade.</p><p><strong>Conclusion: </strong>These findings emphasize the need for cautious dose optimization in future translational applications of MLE and reinforce the importance of context-specific phytotherapy.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120373"},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799297","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-inflammatory activity of flavanones isolated from the roots of Pronephrium penangianum.","authors":"Feibing Huang, Muhammad Aamer, Jara Muhdin Aliye, Yong Yang, Yu Mao, Qingling Xie, Hanwen Yuan, Yuqing Jian, Wei Wang","doi":"10.1016/j.jep.2025.120360","DOIUrl":"10.1016/j.jep.2025.120360","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Pronephrium penangianum, a traditional Chinese Tujia Ethnomedicine, is commonly used to treat various inflammatory conditions, including strains, dysentery, and traumatic injuries.</p><p><strong>Aim of the study: </strong>The study aimed to examine the anti-inflammatory activity of flavanones isolated from the roots of P. penangianum.</p><p><strong>Material and methods: </strong>Extensive spectrometric and spectroscopic techniques, including HRESI-MS, 1D and 2D-NMR spectra, and CD experiments, were used to elucidate the structures of the compounds. RAW264.7 cells were used for the anti-inflammatory assay. Griess reagent method, CCK-8 cell viability assay, Enzyme-linked immunosorbent assay (ELISA), molecular docking, and Western blot experiments to assess the related mechanism.</p><p><strong>Results: </strong>Five new flavanone glycosides, jixueqisus G-K (1-5), and seven known flavonoid derivatives (6-12), were purified from the roots of P. penangianum. Activity screening of these compounds indicated that 6 significantly inhibited the release of NO, TNF-α, and IL-6. The in-silico study of 6, examining its interactions with IL-6 and p65.</p><p><strong>Conclusion: </strong>The phytochemical analysis of P. penangianum's roots resulted in five new flavanone glycosides, jixueqisus G-K (1-5), and seven known flavonoid derivatives (6-12). The structures of the compounds were elucidated using spectroscopic and spectrometric analysis. Compound 6 exhibited potent anti-inflammatory effects associated with NF-κB activation by inhibiting IKBα phosphorylation and p65 degradation. To predict key interactions, compound 6 was also examined using molecular docking studies.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120360"},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784407","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":"Essential oil of Saposhnikovia divaricata mitigates Cutibacterium acnes-induced inflammatory acne via Nrf2 pathway activation and NF-κB pathway inhibition.","authors":"Song-Xue Yang, Wei-Lie Xiao, Xing-Jie Zhang","doi":"10.1016/j.jep.2025.120647","DOIUrl":"10.1016/j.jep.2025.120647","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>The root of Saposhnikovia divaricata has been traditionally used in Chinese medicine to treat inflammation and immune related skin diseases, such as skin allergy and itchy rash. However, scientific research supporting its efficacy, particularly in curing inflammation from acne, is still scarce.</p><p><strong>Aim of the study: </strong>To evaluate the therapeutic effects of essential oil of Saposhnikovia divaricata (EOSD) on Cutibacterium acnes (C. acnes)-induced acne and investigate its mechanisms.</p><p><strong>Materials and methods: </strong>An acute acne model was established by injecting C. acnes into mouse ears, followed by topical EOSD treatment (0.25 %, 0.5 % and 1 %). Ear tissues were analyzed 24 h post-treatment. In vitro, C. acnes-stimulated J774A.1 macrophages were treated with EOSD (3, 10 and 30 μg/ml) to assess mitochondrial damage, oxidative stress, and inflammatory responses. Key markers were analyzed using transmission electron microscopy, real-time PCR, immunoblotting, ELISA, and immunofluorescence. Nrf2 knockdown was achieved via siRNA transfection.</p><p><strong>Results: </strong>In vivo, C. acnes suppressed Nrf2 activation, increased ROS levels, and triggered NLRP3 inflammasome activation, leading to inflammation. EOSD restored Nrf2 activity, reduced ROS levels, and inhibited NLRP3 activation. In vitro, EOSD disrupted Nrf2/Keap1 interaction, enhanced Nrf2 nuclear translocation, reduced mitochondrial damage, and suppressed pyroptosis by downregulating IL-1β, Caspase-1, GSDMD, and NF-κB signaling. These effects were reversed by Nrf2 knockdown.</p><p><strong>Conclusion: </strong>EOSD alleviates oxidative stress and modulates NLRP3 inflammasome activation through upregulating Nrf2 pathway and inhibiting NF-κB pathway, as well as improving mitochondrial homeostasis and inflammatory responses in acne. These findings suggest that EOSD may be a promising therapeutic agent for the treatment of acne vulgaris.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120647"},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182142","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":"Ganoderma lucidum sporoderm-broken spore powder alleviates kidney aging by modulating gut microbiota.","authors":"Xiaojing Liu, Jiamin Zhao, Jia Liu, Wei Deng, Luwen Yan, Yan Huang, Liao Zhang, Zhihong Liu, Ming Cui, Huiwen Xiao, Xingzhong Liu","doi":"10.1016/j.jep.2025.120344","DOIUrl":"10.1016/j.jep.2025.120344","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Ganoderma lucidum (G. lucidum), a revered medicinal mushroom in traditional Chinese medicine (TCM), has been historically documented for its anti-aging properties and nephroprotective effects. Nevertheless, its mechanism of action through gut microbiota modulation to attenuate renal and systemic aging remains incompletely understood.</p><p><strong>Aim of the study: </strong>To elucidate the gut microbiota-dependent anti-aging mechanisms of G. lucidum on renal and systemic senescence using integrative multi-omics approaches.</p><p><strong>Materials and methods: </strong>We systematically evaluated the anti-aging efficacy of G. lucidum sporoderm-broken spore powder (Gl-SBSP) via the gut-kidney axis in naturally aged and radiation-induced premature senescence mouse models. Renal aging phenotypes were assessed using histopathological analyses (hematoxylin-eosin and Masson staining), immunofluorescence (IF), complete blood counts, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time PCR (RT-qPCR). Gut microbiota involvement was confirmed via antibiotic-treated mice and fecal microbiota transplantation (FMT). Multi-omics integration of 16S rRNA sequencing and metabolomic profiling identified microbiota-derived metabolites, functionally validated in HK-2 cells and aged mice. Mechanistic pathways were elucidated via transcriptomic analysis.</p><p><strong>Results: </strong>Gl-SBSP attenuated kidney aging phenotypes in both natural aging and irradiation models. It selectively enriched Lachnospiraceae, whose metabolite nicotinamide riboside (NR) elevated renal NAD⁺ levels (in vitro and in vivo), rejuvenated senescent kidneys, and improved renal function through steroid metabolism regulation.</p><p><strong>Conclusion: </strong>Gl-SBSP counters renal aging through Lachnospiraceae-driven gut microbiota remodeling, where NR serves as the core rejuvenating metabolite. By activating NAD⁺ biosynthesis and modulating steroid metabolism via the gut-kidney axis, this mechanism offers a novel therapeutic strategy against age-related renal decline and validates Ganoderma lucidum's ethnopharmacological relevance.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120344"},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775488","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":"Protecting the brain from stroke: Huoxue Rongluo formula (HXRLF) targets ferroptosis for neuroprotection.","authors":"Qiang Ma, Lei Luo, Yuanchen Liao, Renyi Yang, Xinyi Ouyang, Yuxing Zhang, Siyang Yan, Cuilan Gong, Lijuan Liu, Desheng Zhou","doi":"10.1016/j.jep.2025.120329","DOIUrl":"10.1016/j.jep.2025.120329","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Ethnopharmacological significance: &lt;/strong&gt;Huoxue Rongluo Formula (HXRLF) is a traditional Chinese medicine prescription widely used to treat ischemic stroke (IS), based on the classical therapeutic principles of nourishing yin and activating blood circulation. Preliminary clinical studies have demonstrated its effectiveness in improving neurological function and prognosis. However, the precise mechanisms by which HXRLF confers neuroprotection, especially its role in modulating ferroptosis after cerebral ischemia-reperfusion injury (CIRI), remain unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim of the study: &lt;/strong&gt;This study aimed to investigate whether HXRLF ameliorates cerebral I/R injury by inhibiting neuronal ferroptosis through NR4A1-mediated activation of the xCT/GPX4 antioxidant axis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Active components of HXRLF were identified by UPLC-Q-TOF-MS. UPLC-Q-TOF-MS analysis revealed several representative active constituents of HXRLF, including catalpol, chebulic acid, didymin, armepavine, harpagoside, atractylenolide III, poncirin, and coclaurine, which together represent the diverse chemical basis underlying its pharmacological actions. Potential anti-ferroptosis targets were screened using network pharmacology and GEO transcriptomic data. A transient middle cerebral artery occlusion (tMCAO) model in mice and an OGD/R model in HT22 cells were used to evaluate the neuroprotective effects of HXRLF. Biochemical assays, immunofluorescence, transmission electron microscopy (TEM), and Western blotting were employed to detect ferroptosis-related indicators. The role of NR4A1 was further examined using its antagonist DIM-C-pPhOH, and the downstream involvement of ferroptosis was confirmed by the ferroptosis inhibitor Fer-1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HXRLF significantly improved neurobehavioral outcomes, reduced infarct volume, and alleviated pathological damage in tMCAO mice in a dose-dependent manner. Biochemical assays revealed that HXRLF reduced Fe&lt;sup&gt;2+&lt;/sup&gt; and MDA levels while increasing GSH content in brain tissue. HXRLF treatment also restored GPX4 expression and mitochondrial structure. In HT22 cells, HXRLF-containing serum improved cell viability, reversed lipid peroxidation, reduced iron accumulation, and restored mitochondrial membrane potential. Mechanistically, HXRLF upregulated NR4A1 and enhanced the expression of xCT and GPX4. Importantly, the neuroprotective and anti-ferroptotic effects of HXRLF were diminished by NR4A1 inhibition and partially rescued by Fer-1, confirming the involvement of the NR4A1-xCT-GPX4 axis in ferroptosis regulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;HXRLF ameliorates cerebral I/R injury by inhibiting neuronal ferroptosis through NR4A1-mediated activation of the xCT/GPX4 antioxidant axis. These findings provide mechanistic insights into the neuroprotective effects of traditional Chinese medicine and offer a scientific foundation for developing ferroptosis-targeted","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120329"},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760255","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":"The therapeutic mechanisms of Compound Kushen Injection in relieving cancer-induced bone pain by targeting Nav1.7 and microglial activation.","authors":"Li Gao, Qian-Wen Li, Xin-Yue Zhang, Rong-Li You, Xue-Mei Qin, Wen-Jie Qin","doi":"10.1016/j.jep.2025.120367","DOIUrl":"10.1016/j.jep.2025.120367","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>In traditional Chinese medicine (TCM) theory, Compound Kushen Injection (CKI) possesses multiple therapeutic effects, including heat-clearing, detoxification, blood-cooling, dampness-resolving, and pain relief. CKI has been used clinically for 30 years as an adjunctive drug alongside chemotherapy and radiotherapy for cancer treatment. However, the effects of CKI on cancer-induced bone pain (CIBP) and potential mechanisms remain poorly understood.</p><p><strong>Aim of the study: </strong>To investigate the therapeutic effects of CKI on CIBP and elucidate its mechanisms based on Nav1.7 and microglial activation.</p><p><strong>Methods: </strong>The therapeutic effect of CKI in CIBP was systematically evaluated using behavioral tests, X-ray, HE staining, Micro-CT and TRAP staining. The mechanisms of CKI were explored by examining Nav1.7 expression and microglial activation both in vivo and in vitro. We further examined the effects of CKI on the blood-spinal cord barrier (BSCB) damage in CIBP rats. Inspired by the mechanisms of CKI, we further investigated whether inhibition of Nav1.7 could inhibit microglial activation and attenuates BSCB damage, thereby alleviating CIBP.</p><p><strong>Results: </strong>In CIBP rats, CKI significantly alleviated pain hypersensitivity. Furthermore, CKI enhanced trabecular bone quantity and continuity, reduced trabecular separation, and decreased the number of TRAP-positive cells, thereby preserving tibial structural integrity. Notably, CKI significantly reduced Nav1.7 expression in the spinal cord and DRG. Meanwhile, CKI and its primary active ingredients, matrine and oxymatrine, dose-dependently suppressed Nav1.7 expression in vitro. Additionally, CKI attenuated microglial hyperactivation, restored the expression of spinal barrier proteins (Claudin1 and Occludin) in the spinal cord, and disrupted the vicious cycle between microglial activation and BSCB damage. In LPS-activated BV-2 microglial cells, CKI, matrine and oxymatrine inhibited the release of NO, and restored the balance of anti-inflammatory and pro-inflammatory (IL-4/TNF-α), thereby inhibiting BV-2 cell activation. Moreover, PF05089771 relieved CIBP by significantly decreasing osteoclasts number, suppressing microglial activation in the spinal cord, and attenuating BSCB damage.</p><p><strong>Conclusion: </strong>CKI significantly alleviated CIBP likely through downregulating Nav1.7, thereby suppressing microglial activation and attenuating BSCB damage. Overall, this study not only uncovered the novel mechanisms of CKI in combating CIBP, but also unveiled Nav1.7 as a promising pharmacological target for CIBP therapy.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120367"},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794676","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":"Sijunzi Decoction treatment improved depression with qi deficiency/fatigue in the strain-dependent manner, involved in anti-inflammation in the hippocampus and muscles.","authors":"Jingwen Tan, Zhenzhen Fu, Mingzhi Han, Nga-Lee Wong, Chenghao Song, Yin Chen, Wenjia Li, Maria A Deli, Hailou Zhang, Gang Chen","doi":"10.1016/j.jep.2025.120380","DOIUrl":"10.1016/j.jep.2025.120380","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Ethnopharmacological relevance: &lt;/strong&gt;In the traditional Chinese medicine (TCM) clinic, qi deficiency is a common syndrome pattern in major depressive disorder (MDD). Sijunzi decoction (SJZD), a classic muti-herbal formula to replenish qi and nourish blood, is widely used to treat qi deficiency syndrome. The symptoms of qi deficiency are very similar to fatigue. Currently the mainstream antidepressant treatment outcome for depression with fatigue remains unsatisfying. SJZD has potential for improvement in the treatment of depression with qi deficiency, which has not been scientifically characterized previously.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim of the study: &lt;/strong&gt;The study aimed to test the effects of SJZD in a mouse model of depression with qi deficiency/fatigue and to investigate the associated mechanisms, focusing on inflammation in the hippocampus and muscles.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Balb/c and 129S1/SvImJ (129/S1) strains of mice were compared for depression-like and qi deficiency-like behaviors following receiving the same procedure of chronic unpredictable mild stress (CUMS). Qi deficiency behavior was assessed using grip strength test (GST), exhaustive swimming test (EST) and degree of redness (DOR). Depressive behavior was assessed using sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST). SJZD was administrated for 1 week in CUMS-exposed mice in both strains. The conventional antidepressant fluoxetine (FLX), ineffective to fatigue/qi deficiency, was used to compared with SJZD, qPCR was used to detect gene expressions of inflammatory factors in the hippocampus and muscles in both strains.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Balb/c and 129/S1 mice both showed depressive symptoms comparably after exposed to CUMS. However, qi deficiency symptoms were only shown in Balb/c mice, with decreased grip strength in GST, reduced swimming times in EST and decreased degree of redness in DOR. SJZD was able to reverse both depressive deficits and qi deficiency in Balb/c mice, without influencing 129/S1 mice. Consistent with the depression-phenotype, the expressions of the inflammatory factors including IL-1β, TNF-α, NF-kB and CD8 in the hippocampus were upregulated in both Balb/c and 129/S1 mice, which were reversed by SJZD only in Balb/c mice. Consistent with the qi deficiency-phenotype, the expressions of these inflammatory factors were up-regulated in the muscles only in Balb/c mice, which were reversed by SJZD. In contrast, FLX elicited antidepressant effects without changing qi deficiency in Balb/c mice, consistent with its improvement of inflammation in the hippocampus, but not muscles.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Balb/c strain mice showed co-susceptibility to depression and qi deficiency/fatigue following CUMS, both of which were alleviated by SJZD. These effects were associated with the suppression of inflammation in the hippocampus and muscles respectively, suggesting that the a","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120380"},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794673","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":"Platycodon grandiflorum: A promising medicinal and food homologous plant for cigarette smoke-induced chronic bronchitis.","authors":"Jianwen Sun, Xinrui Wang, Xiangwei Chang, Yuzhe Huang, Liangping Zha, Nannan Zhi, Jutao Wang, Daiyin Peng, Qijun Xia, Jingjing Hu, Xingyuan Pang, Xiao Liang, Cheng Jin, Shuangying Gui","doi":"10.1016/j.jep.2025.120381","DOIUrl":"10.1016/j.jep.2025.120381","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Platycodon grandiflorum (PG), a medicinal food homologous plant, has demonstrated efficacy in the treatment of airway diseases. However, the bioactive compounds and mechanisms of PG against chronic bronchitis (CB) remain poorly characterized. This study is the first to combine in vivo/in vitro component analysis, network pharmacology, and experimental validation to identify PG compounds with anti-CB activity.</p><p><strong>Aim of the study: </strong>This study established an LPS-induced inflammation model in RAW264.7 cells and a cigarette smoke-induced CB rat model. The therapeutic effects of the 70 % ethanol elution fraction of PG (PG-E_70 %) on CB were evaluated through histopathological examination, assessment of oxidative stress markers, and analysis of inflammatory factor expression. Using a multi-faceted strategy integrating in vivo and in vitro component analysis with network pharmacology data mining, we predicted potential bioactive compounds and mechanisms of PG-E_70 % in CB therapy. Subsequently, a cigarette smoke extract (CSE)-induced 16HBE cell injury model was developed to validate the bioactivity of candidate compounds. Potential therapeutic mechanisms were confirmed via western blotting.</p><p><strong>Results: </strong>PG-E_70 % significantly alleviated pathological lung tissue damage, oxidative stress, and inflammation. Using UPLC-Q-Exactive-Orbitrap-MS, we identified 104 chemical compounds in PG-E_70 % and 40 blood-entry compounds. In combination with network pharmacology, eight potential bioactive compounds were identified: Platycodin D₃ (PD₃), Platycoside E (PE), Platycoside G₁ (PG₁), Platycodin D (PD), Platyconic acid A (Pa-A), Deapio-platycodin D₃ (DeaP-D₃), Polygalacin D₂ (PolyG-D₂), and Polygalacin D (PolyG-D). These compounds significantly reduced oxidative stress and inflammation and exhibited strong binding affinities for TLR4, MyD88, and NF-κB proteins in molecular docking assays. Western blotting confirmed PG-E70 % downregulated expression of these three proteins.</p><p><strong>Conclusion: </strong>The results indicate that the active compounds of PG in the treatment of CB are PD₃, PE, PG₁, PD, Pa-A, DeaP-D₃, PolyG-D₂, and PolyG-D. PG mitigates the progression of CB inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. This study provides important evidence supporting the use of PG to treat and prevent cigarette smoke-induced CB.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120381"},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794672","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":"Shaoyao decoction promotes ISCs proliferation by activating Wnt/β-catenin and YAP1/TAZ signaling to enhance epithelial regeneration in damp-heat colitis.","authors":"Rong Yang, Luoxia Han, Yahui Zhang, Jiaqi Dong, Qian Ma, Yongli Hua, Peng Ji, Wanling Yao, Ziwen Yuan, Yanming Wei","doi":"10.1016/j.jep.2025.120641","DOIUrl":"10.1016/j.jep.2025.120641","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Shaoyao decoction (SYD) is a classic traditional Chinese medicine formulation that presented a significant therapeutic effect on damp-heat colitis. However, its potential pharmacological mechanisms remain not fully elucidated.</p><p><strong>Aim of the study: </strong>This study aimed to investigate the effect of SYD on intestinal epithelial regeneration by analyzing the activity of intestinal stem cells (ISCs) in a mouse model of damp-heat colitis.</p><p><strong>Materials and methods: </strong>LC-MS/MS was employed to identify the main compounds in SYD extract. A damp-heat colitis mouse model was established by combining three factors: the high-sugar and high-fat diet, high heat (33 ± 1 °C) and high damp (90 ± 2 %) environment, and DSS treatment. SYD was given orally to evaluate its therapeutic efficacy. The therapeutic efficacy of SYD was assessed via clinical indicators and histopathological observation. ELISA and RT-qPCR were performed to measure cytokine levels (IL-18, IL-21, IL-22, IL-33 and EGF) in distal colon tissue. Western blotting and RT-qPCR were applied to detect the expression levels of proteins (Lgr5, EpCAM, Wnt3a, LRP6, β-catenin, TCF4, FZD1, Gα13, YAP1, TAZ, α-catenin and Muc2) and mRNA (Lgr5, Ki67, TCF4, Fzd1, Ereg, Egfr) in colon. Additionally, immunofluorescence and immunohistochemistry were used to observe the localization of key proteins (EpCAM, Wnt3a, β-catenin, YAP1, Muc2, Hes1) in colon.</p><p><strong>Results: </strong>91 compounds were identified in SYD extract. SYD significantly alleviated clinical symptoms and reduced histopathological damage of mice with damp-heat colitis. SYD downregulated the levels of pro-inflammatory cytokines (IL-18 and IL-21), and upregulated levels of epithelial regeneration-associated cytokines (IL-22, IL-33 and EGF). Mechanistically, SYD promoted ISC activation and epithelial proliferation by increasing expressions of Lgr5, Ki67 and EpCAM. Concurrently, SYD upregulated protein expressions in canonical Wnt/β-catenin pathway (Wnt3a, LRP6, β-catenin and TCF4) and alternative Wnt-YAP1/TAZ signaling axis (FZD1, Gα13, YAP1 and TAZ). Finally, SYD promoted mucus barrier repair by increasing Muc2 expression.</p><p><strong>Conclusions: </strong>This study suggested that SYD exerts significantly therapeutic efficacy on damp-heat colitis. Mechanistically, SYD enhances ISC proliferation and differentiation by activating both the canonical Wnt/β-catenin pathway and alternative Wnt-YAP1/TAZ signaling axis, thereby promoting injury-induced intestinal epithelial regeneration.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120641"},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182130","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}