Yu Xiao , Tianfeng Luo , Changsong Duan , Xinhui Wang , Yixi Yang , Rui Li , Jinpeng Deng , Qi Zhao
{"title":"Ethyl acetate extract from Herpetospermun cardigerum wall. Ameliorated concanavalin A-induced autoimmune hepatitis in mice by reprofiling gut microenvironment to modulate IDO1/KYN and PI3K/AKT/NF-κB pathways","authors":"Yu Xiao , Tianfeng Luo , Changsong Duan , Xinhui Wang , Yixi Yang , Rui Li , Jinpeng Deng , Qi Zhao","doi":"10.1016/j.jep.2025.119578","DOIUrl":"10.1016/j.jep.2025.119578","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune hepatitis (AIH) is an immunoinflammatory chronic liver disease with increasing prevalence worldwidely, lacking of effective medicine. <em>Herpetospermum caudigerum</em> Wall. (HC) is a traditional Tibetan medicine used to treat liver diseases for thousands of years. However, investigation into the effects of HC in AIH remains scarce.</div></div><div><h3>Purpose</h3><div>Our study aimed to explore the effects and mechanisms of ethyl acetate extract from the seeds of HC (HCDEAE) against concanavalin A (Con A)-induced liver impairment in mouse.</div></div><div><h3>Study design and methods</h3><div>HCDEAE was extracted from the seeds of HC, then characterized by UPLC-Q-TOF/MS. Con A-induced AIH mice were used to investigate the impacts of HCDEAE on liver impairment, T cells differentiation, gut microbiota and its derived metabolites, intestinal barrier impairment and inflammation, as well as the mechanisms of HCDEAE in liver in AIH.</div></div><div><h3>Results</h3><div>HCDEAE (90 mg/kg, i.g.) effectively alleviated Con A-induced hepatic pathological damage, suppressed elevation of serum ALT, AST, IFN-γ, and TNF-α; in spleen, HCDEAE attenuated spleen impairment, elevated the percentage of CD4<sup>+</sup>CD25<sup>+</sup> cells and FOXP3 gene expression, inhibited up-regulation of RORγt gene expression and IL-17; in liver, HCDEAE down-regulated IL-17, elevated FOXP3 gene expression and IL-10, increased the protein and gene expression of TGF-β1; in colon, HCDEAE attenuated intestinal barrier impairment, inhibited down-regulation of Occludin and ZO-1, and relieved elevation of IL-1β, as well as re-profiled the gut microenvironment. Furthermore, HCDEAE demonstrated the ability to elevate tryptophan metabolism among kynurenine pathway, activate IDO1/KYN pathway and inhibit PI3K/AKT/NF-κB signaling pathway in liver of AIH mice.</div></div><div><h3>Conclusion</h3><div>Pretreatment with HCDEAE (90 mg/kg·d<sup>−1</sup>, i.g.) for 9 days could effectively alleviate the liver inflammation and injure, protect intestinal barriers, attenuate spleen impairment, maintain Treg-Th17 cell equilibrium in Con A-induced AIH mice, via re-profiling gut microbiota, modulation of tryptophan metabolism in the gastrointestinal tract and in liver, to activate IDO1/KYN pathway and inhibit the abnormal activation of PI3K/AKT/NF-κB signaling pathway in liver. The present study highlighted the potential of HCDEAE as a drug candidate for AIH.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119578"},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624790","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}
Yumeng Zhang , Haizhu Jin , Wenyue Jia , Yuqi Liu , Yuru Wang , Shuyan Xue , Yang Liu , Huiqin Hao
{"title":"Ermiao San attenuating rheumatoid arthritis via PI3K/AKT/mTOR signaling activate HIF-1α induced glycolysis","authors":"Yumeng Zhang , Haizhu Jin , Wenyue Jia , Yuqi Liu , Yuru Wang , Shuyan Xue , Yang Liu , Huiqin Hao","doi":"10.1016/j.jep.2025.119615","DOIUrl":"10.1016/j.jep.2025.119615","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>As a classic formula, Ermiao San (EMS) characterized by its less medicinal flavor and strong potency had been proven to be effective and safe in the treatment of rheumatoid arthritis (RA) during clinical experience and our previous research.</div></div><div><h3>Aim of the study</h3><div>The therapeutic characteristics of multi-component and multi-target of traditional Chinese medicine prompted us to further investigated the effective compounds of EMS, and evaluated its potential mechanisms in treating RA.</div></div><div><h3>Materials and methods</h3><div>Ultra-high-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS) was used to analyze the primary absorption components of EMS in rat serum, with secondary mass spectrometry used to assist in identifying the structures of the compounds. Open field experiments, H&E staining, safranin-O-turquoise staining, ELISA, and other methods were applied to verify the alleviating effects of EMS on exercise capacity, inflammation, and cartilage damage in CIA rats. The RA-FLS model was established using TNF-<em>α</em>, and observed the effects of EMS on cell migration and invasion were observed through wound healing and transwell assays. In addition, immunohistochemistry and western blotting were employed to investigate the PI3K/AKT/mTOR/HIF-1<em>α</em> pathway both <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Seventeen compounds were identified in rat serum, which were considered as active ingredients involved in the improvement of RA by EMS. Furthermore, EMS demonstrated the outstanding anti-RA ability, as evidenced by the improvement in foot swelling and arthritis scores, alleviation of pathological changes in joint tissue, inhibition of inflammatory factors, and restoration of exercise ability. <em>In vivo</em> data showed that EMS reduced joint injury through the PI3K/AKT/mTOR/HIF-1<em>α</em> signaling pathway. <em>In vitro</em> studies indicated that TNF-<em>α</em> induced the expression of Glut1 and HK2 proteins, accelerated the glycolysis rate, and promoted migration and invasion of RA-FLS cells, leading to adverse outcomes. However, EMS regulated the expression of glycolysis-related molecules, HK2 and Glut1 through the PI3K/AKT/mTOR/HIF-1<em>α</em> pathway, thereby inhibiting inflammation, migration, and invasion of RA-FLS cells.</div></div><div><h3>Conclusion</h3><div>The beneficial effects of EMS in CIA rats can be attributed to the inhibition of glycolysis in synovial fibroblasts via the PI3K/AKT/mTOR/HIF-1<em>α</em> pathway. This finding further enriches our understanding of the mechanisms by which EMS contributes to the treatment of RA.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119615"},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624789","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}
Xiaolong Li , Qingmiao Zhu , Zi Yang , Mengyu Zhu , ZhiJun Xie , Yongsheng Fan , Ting Zhao
{"title":"The Jieduquyuziyin prescription alleviates systemic lupus erythematosus by modulating B cell metabolic reprogramming via the AMPK/PKM2 signaling pathway","authors":"Xiaolong Li , Qingmiao Zhu , Zi Yang , Mengyu Zhu , ZhiJun Xie , Yongsheng Fan , Ting Zhao","doi":"10.1016/j.jep.2025.119626","DOIUrl":"10.1016/j.jep.2025.119626","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Jieduquyuziyin prescription (JP) is an enhanced formula derived from the “Sheng Ma Bie Jia Tang” in the Golden Chamber. JP is an empirical formula approved for use in the treatment of systemic lupus erythematosus (SLE) in hospitals across China, demonstrating notable therapeutic effects. It has been shown to suppress B cell activation and alleviate symptoms; however, its underlying mechanism remains unclear.</div></div><div><h3>Aim of the study</h3><div>The aim of this study is to investigate the effect of JP on B cell metabolic reprogramming in the treatment of SLE and to elucidate the underlying regulatory mechanisms.</div></div><div><h3>Materials and methods</h3><div>Core targets and pathways regulating B cell activation were identified through sequencing of activated and resting B cells from SLE patients and network pharmacology of JP. Targeted metabolomics was employed to assess JP's effect on B cell metabolism. In vivo experiments evaluated the effects of JP, JP combined with a PKM2 inhibitor, or an AMPK inhibitor on SLE activity, B cell activation and glycolysis.</div></div><div><h3>Results</h3><div>Bioinformatics analyses identified PKM as a core target in B cell activation, which was significantly upregulated and linked to the inhibition of AMPK signaling. JP reduced B cell glycolysis and activation, leading to significant improvements in disease pathology. The combination of JP with an AMPK inhibitor diminished the therapeutic effect. Further studies suggested that JP inhibits glycolysis-dependent B cell activation via the AMPK/PKM2 pathway, reducing germinal center responses and effector B cells.</div></div><div><h3>Conclusion</h3><div>This study reveals that the AMPK/PKM2 pathway is a promising therapeutic target for regulating immune metabolic imbalance in SLE B cells. Additionally, it provides evidence that JP may improve SLE by activating the AMPK/PKM2 pathway to inhibit glycolysis-dependent B cell activation, laying the foundation for further investigation of its therapeutic mechanisms.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119626"},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624791","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":"Amygdalin's neuroprotective effects on acute ischemic stroke in rats","authors":"Kentaro Kimura , Yu-Huei Liu , Ching-Liang Hsieh","doi":"10.1016/j.jep.2025.119621","DOIUrl":"10.1016/j.jep.2025.119621","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Amygdalin, a key component of Peach kernel (<em>semen persicae</em>), also known as Taoren, is a traditional Chinese herb known for promoting blood circulation and alleviating blood stasis, especially in stroke treatment. This study aimed to explore the effects of amygdalin on neurological function in a rat model of acute ischemic stroke.</div></div><div><h3>Methods</h3><div>We induced acute ischemic stroke in Sprague-Dawley rats by occluding the right middle cerebral artery (MCAO) for 30 min, followed by reperfusion. Amygdalin was administered intraperitoneally at doses of 5 mg, 10 mg, and 20 mg per kilogram starting 24 h post-reperfusion for three consecutive days. We assessed cerebral infarct volume and neurological function, and analyzed the brain tissue using western blotting.</div></div><div><h3>Results</h3><div>Amygdalin significantly reduced cerebral infarct volume resulting from MCAO in the 5-mg group (amygdalin 5 mg/kg; 18.02 ± 7.51 %), 10-mg group (amygdalin 10 mg/kg; 16.25 % ± 6.35 %) and 20-mg group (amygdalin 20 mg/kg; 12.26 ± 6.69 %) compared to the sham group (phosphate buffer saline; 28.99 ± 6.36 %) (all <em>p</em> < 0.001). The 10-mg and 20-mg groups showed significantly lower modified neurological severity scores (mNSS) than the sham group 5 days post-reperfusion (<em>p</em> < 0.05, <em>p</em> < 0.0001, respectively). Performance on the rotarod test also improved significantly in the 10-mg group (<em>p</em> < 0.05) and 20-mg group (<em>p</em> < 0.0001) compared to the sham group, and the distance traveled in the open-field test increased significantly in the 5-mg group (<em>p</em> < 0.001), 10-mg group (<em>p</em> < 0.0001) and 20-mg group (<em>p</em> < 0.0001) compared to the sham group. Western blotting revealed that the expression of uncleaved caspase-3 in the cerebral cortex was greater in the sham group compared to the control (without MCAO and treatment) and the 20-mg groups (both <em>p</em> < 0.05), while the expression of caspase-9 was greater in the control and 20-mg groups than in the sham group (both <em>p</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>Intraperitoneal administration of amygdalin for three days reduced cerebral infarct volume and improved neurological function in a rat model of acute ischemic stroke. Additionally, amygdalin decreased uncleaved caspase-3 expression and increased caspase-9 expression. The findings suggest that amygdalin plays a neuroprotective role through modulation of apoptosis process via the intrinsic pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119621"},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620516","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}
Siqi Tang , Kaixin Wei , Yi Xu , Rongying Xu , Wenwen Wan , You Sun , Hao Huang , Xiaojun Li
{"title":"Network pharmacology combines cellular experiments to investigate the anti-inflammatory phytochemicals of vine of Pueraria montana var. lobata and their mechanism","authors":"Siqi Tang , Kaixin Wei , Yi Xu , Rongying Xu , Wenwen Wan , You Sun , Hao Huang , Xiaojun Li","doi":"10.1016/j.jep.2025.119592","DOIUrl":"10.1016/j.jep.2025.119592","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Pueraria montana</em> var. <em>lobata</em> (PM) has the effects of relieving muscle stiffness and fever, generating body fluids and quenching thirst, resolving rashes, raising yang and stopping diarrhea, unblocking meridians, and detoxifying alcohol. It is commonly used for the management of conditions including stiff neck and back pain, thirst, diabetes, unresolved measles, external fever with headache, dysentery, diarrhea, dizziness and headache, stroke with hemiplegia, chest and heart pain, and alcohol poisoning. However, research on the material basis and mechanism of action of its anti-inflammatory efficacy is still quite lacking<em>.</em></div></div><div><h3>Aim of the study</h3><div>The objective is to look into the inflammation-dampening characteristics of PM through <em>in vitro</em> studies and to accurately identify the phytochemicals within the therapeutic herb that correlate with its customary applications.</div></div><div><h3>Materials and methods</h3><div>A comprehensive phytochemical investigation was carried out using chromatographic and spectral techniques to explore the constituents of PM. Potential targets of the active chemical that might reduce inflammation were predicted using network pharmacology. The inhibition of inflammatory mediators in RAW264.7 cells stimulated by lipopolysaccharide (LPS) was used to measure the anti-inflammatory effects <em>in vitro</em>.</div></div><div><h3>Results</h3><div>The research revealed that the PM chloroform extract exhibited significant anti-inflammatory action by efficiently preventing NO release in LPS-activated RAW264.7 cells. Further phytochemical analysis led to the identification and characterization of 29 natural products, including 4 new compounds (<strong>1</strong>–<strong>4</strong>). Among these, compounds <strong>1</strong>, <strong>4</strong>, <strong>7</strong>, <strong>9</strong>–<strong>18</strong>, and <strong>20</strong>–<strong>25</strong> exhibited significant anti-inflammatory activity, with compound <strong>1</strong> showing the most potent effect. Subsequent network pharmacology, along with molecular docking and molecular dynamics simulations, suggested that <strong>1</strong> targets several key anti-inflammatory pathways, including HSP90AA1, MAPK, mTOR, and NF-κB. <em>In vitro</em> validation confirmed that the mechanism of anti-inflammation of <strong>1</strong> involves modulation of the HSP90AA1/MAPK/mTOR/NF-κB signaling pathways.</div></div><div><h3>Conclusions</h3><div>This study not only more or less supports the traditional use of PM for its anti-inflammatory properties but also introduces novel pterocarpan-type isoflavone as promising agent for inflammation management.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119592"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610654","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}
Lei Wu , Yan Sun , Lingang Zhao , Shan Xing , Ruiyi Liu , Nga Lee Wong , Yuesong Lin , Chenghao Song , Chao Lu , Hailou Zhang
{"title":"Lancao decoction alleviates Alzheimer’s disease: Depending on activating CaMKII to protect neuronal refunction by reducing β-amyloid in the hippocampus","authors":"Lei Wu , Yan Sun , Lingang Zhao , Shan Xing , Ruiyi Liu , Nga Lee Wong , Yuesong Lin , Chenghao Song , Chao Lu , Hailou Zhang","doi":"10.1016/j.jep.2025.119619","DOIUrl":"10.1016/j.jep.2025.119619","url":null,"abstract":"<div><h3>Ethnopharmacological relevancy</h3><div>Lancao decoction (LC) is a traditional Chinese medicine (TCM) formulation mentioned in the \"Huangdineijing”, known for its ability to dispel turbidity and eliminate heat. TCM believes that the etiology of Alzheimer’s disease (AD) is phlegm turbidity, and the fiery internal obstruction of the gods, which suggests that LC has the possibility of treating.</div></div><div><h3>Aim of the study</h3><div>This investigation will examine the possibilities of LC to improve AD and uncover the underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>Gas chromatography (GC) and HPLC-MS were used to identify the content of the primary elements in LC and test the stability of its extraction. The function of LC in ameliorating AD was characterized by utilizing behavioral assessments such as the Morris water maze (MWM) and the Y-maze in AD modeling mice. Levels of molecular signaling and neurogenesis within the hippocampus was assessed using Western blot and immunostaining. Pharmacological interventions were used to explore the association of specific targets with neurogenesis and synaptic proteins and their contributions in LC improvement of AD.</div></div><div><h3>Results</h3><div>The main components of LC include p-Cymene, 3-Methoxy-p-cymene, neryl acetate, gallic acid, protocatechuic acid and euparin. APP/PS1 mice displayed behavioral characteristics indicative of memory and learning deficits, such as a notably longer time taken to reach the platform and reduced time spent in the area without the platform in the Morris Water Maze (MWM), as well as a longer delay in exploring the new arm and less time spent in the new arm in the Y-maze, when compared to C57BL6/J mice. However, these impairments were alleviated by chronic treatment with either LC or donepezil (DON) over a period of 14 days. Additionally, the phosphorylated levels of CaMKII and the amounts of synaptic proteins (synapsin1 and PSD95) were greatly diminished within the hippocampal region of APP/PS1 mice, which were also reversed by LC or DON. In addition, Aβ area was obviously increased in the hippocampus of the APP/PS1 murine model, which was also reversed by LC or DON. Inhibition of CaMKII activities not only blunted LC’s therapeutic actions of AD, but also blocked the enhancements of LC on synaptic proteins in the hippocampus, the quantity of cells that are co-stained with BrdU and DCX, and Ki67-positive cells located in the dentate gyrus (DG) of the hippocampus.</div></div><div><h3>Conclusion</h3><div>The results indicated that LC activated CaMKII to relieve Aβ formation, thereby enhancing neuronal functions in the hippocampus, and thus alleviated AD, which provided a theoretical basis for a deeper understanding of the mechanism, clinical application, and subsequent research of LC in alleviating AD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119619"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614971","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}
Xiaohang Zhang , Yawen Cai , Meng Chen , Li Chen , Yaqing Mao , Runtian He , Peishan Yang , Min Xu , Hui Yan , Qiulong Zhao
{"title":"Danshen-Chuanxiong-Honghua ameliorates neurological function and inflammation in traumatic brain injury in rats via modulating Ghrelin/GHSR","authors":"Xiaohang Zhang , Yawen Cai , Meng Chen , Li Chen , Yaqing Mao , Runtian He , Peishan Yang , Min Xu , Hui Yan , Qiulong Zhao","doi":"10.1016/j.jep.2025.119625","DOIUrl":"10.1016/j.jep.2025.119625","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Guanxin II, proposed by Chen Keji (National master of traditional Chinese medicine), possesses neuroprotective effect. Interestingly, its simplified prescription Danshen-Chuanxiong-Honghua (DCH) can also clinically ameliorate cerebral impairment and improve spatial cognitive deficits, similar to the function of original formula.</div></div><div><h3>Aim of the study</h3><div>We aimed to elucidate the rationality of DCH's natural existence, qualitatively identify DCH-derived phytochemicals, thereby to validate cerebral protective effect, and expose the potential mechanism of DCH and its main absorbed compound ferulic acid (FA).</div></div><div><h3>Materials and methods</h3><div>The natural rationality of DCH's existence for treating TBI was verified using data mining. The qualitative analysis of DCH extract-derived phytochemicals was conducted through liquid chromatography with mass spectrometry (LC-MS). Controlled cortical impact (CCI) was chosen to establish TBI model. Neurological behavior tests, blood-brain barrier (BBB) permeability test, brain water content measurement, and proinflammatory factors consisting of IL-6, IL-1β, and TNF-α of plasma, and HPA axis-related hormone levels of DA, NA, 5-HT, ghrelin, and BDNF in hippocampus were analyzed by enzyme-linked immunosorbent assay. Network pharmacology was employed to predict potential targets and pathways of DCH intervening TBI. Growth hormone secretagogue receptor (GHSR) antagonist [D-Lys3]-GHRP-6 (D-Lys3) was injected intraperitoneally in TBI rats after waking up. Molecular docking and pharmacological experiment with D-Lys3 were used to verify the pathway.</div></div><div><h3>Results</h3><div>Twenty-six phytochemicals were identified based on LC-MS. FA, as the primary contributor of DCH, alleviated disruption of BBB and reduced brain edema, suppressed the secretion of proinflammatory factors, such as IL-6, IL-1β, TNF-α, as well as HPA axis-related hormones such as DA, NA, and 5-HT, and ghrelin, and BDNF by regulating the Ghrelin/GHSR pathway. These results were validated by GHSR receptor antagonist, as well as molecule docking.</div></div><div><h3>Conclusions</h3><div>Taken together, DCH, when prescribed for the treatment of TBI, has a certain degree of reasonableness. FA, as the main absorbed component, demonstrated a similar function to DCH in improving the blood-brain barrier, promoting neural recovery, and anti-inflammatory effects in TBI rats, primarily via modulating Ghrelin/GHSR.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119625"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615755","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}
Ye Liu , Zicheng Zhang , Yimeng Zhao, Ruoyu Jiang, Zhihua Geng, Yujie Tao, Jiarui Zhang, Weiwei Tao
{"title":"Zhizichi decoction alleviates depressive-like behaviors through modulating mitochondria-associated membrane via the IP3R3-GRP75-VDAC1 complex","authors":"Ye Liu , Zicheng Zhang , Yimeng Zhao, Ruoyu Jiang, Zhihua Geng, Yujie Tao, Jiarui Zhang, Weiwei Tao","doi":"10.1016/j.jep.2025.119628","DOIUrl":"10.1016/j.jep.2025.119628","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Zhizichi Decoction (ZZCD), a traditional Chinese medicine (TCM), is derived from the combination of <em>Gardenia jasminoides</em> J. Ellis [Rubiaceae] and <em>Semen Sojae Praeparatum</em>, a fermented derivative of Glycine max (L.) Merr. [Leguminosae]. ZZCD has demonstrated anti-inflammatory properties and the potential to promote neural plasticity. Neuroinflammation is believed to contribute to the development of depressive symptoms.</div></div><div><h3>Aim of the study</h3><div>This study investigates the potential antidepressant effects of ZZCD, focusing on its role in regulating neuroinflammatory responses and mitochondria-associated membrane (MAM) structure.</div></div><div><h3>Materials and methods</h3><div>Using high-performance liquid chromatography (HPLC), we identified five active ingredients in ZZCD. We then evaluated its effect in a chronic social defeat stress (CSDS) mouse model. A combination of Network pharmacology analysis, Western-blot, immunostaining, enzyme-linked immunosorbent assay (ELISA), co-immunoprecipitation (CO-IP), mitochondrial transmembrane potential (ΔΨm), and transmission electron microscopy (TEM) was adopted to elucidate the mechanisms by which ZZCD improves MAM structure, inhibits neuroinflammation, and exerts antidepressant effects. Finally, according to the molecular docking results, a GRP75 overexpression viral vector was constructed to manipulate the MAM-related protein GRP75, further validating the mechanism of ZZCD's antidepressant effect.</div></div><div><h3>Results</h3><div>ZZCD treatment significantly ameliorated depressive-like behaviors induced by CSDS in mice and reversed adverse changes in endoplasmic reticulum (ER) stress, MAM structure, and mitochondria injury. In addition, ZZCD effectively reduced microglial inflammatory activation and suppressed the increased expression of pro-inflammatory cytokines. Finally, the antidepressant effects of ZZCD were primarily mediated through the IP3R3-GRP75-VDAC1 complex, as demonstrated by the overexpression of the GRP75 protein.</div></div><div><h3>Conclusion</h3><div>In summary, ZZCD exerts antidepressant effects in the CSDS model by improving the MAM structure, alleviating neuroinflammation, and enhancing mitochondrial function.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119628"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614996","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}