Xiaopei Yang , Yanmei He , Zhuorui Li, Xiaoyan Zhou, Lixian Mu, Jing Wu, Hailong Yang
{"title":"Sarcandra glabra (Thunb.) Nakai relieves pain behavior by inhibiting NaV1.7 channels","authors":"Xiaopei Yang , Yanmei He , Zhuorui Li, Xiaoyan Zhou, Lixian Mu, Jing Wu, Hailong Yang","doi":"10.1016/j.jep.2025.120002","DOIUrl":"10.1016/j.jep.2025.120002","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Sarcandra glabra</em> (Thunb.) Nakai has been traditionally utilized to alleviate pain, treat chronic bronchitis, and enhance immune function. Despite its wide-ranging applications in traditional medicine, detailed studies on its analgesic mechanisms remain limited.</div></div><div><h3>Aim of the study</h3><div>The objective was to evaluate the pain-relieving properties of raw extracts from <em>S. glabra</em> and understand the molecular mechanisms responsible for its pain relief benefits.</div></div><div><h3>Materials and methods</h3><div>By collecting <em>S. glabra</em> plant materials from Yunnan Province and using ethanol extraction methods, the ethanol extract of <em>S. glabra</em> (ZJF) was prepared and evaluated for its anti-nociceptive activity using hot plate-induced and acetic acid-induced pain tests. Simultaneously, using HEK293T cells expressing the voltage-gated sodium channel subtype Na<sub>V</sub>1.7, patch-clamp recordings were employed to study the inhibitory effects of ZJF on the Na<sub>V</sub>1.7 channel and to screen for the key bioactive compound isofraxidin. Additionally, studies were conducted on the inhibitory characteristics of isofraxidin against the Na<sub>V</sub>1.7 channel, and its <em>in vivo</em> anti-nociceptive activity was assessed in a mouse model.</div></div><div><h3>Results</h3><div>The crude extracts of <em>S. glabra</em> plant effectively mitigated pain sensation, showing robust analgesic activity in mice pain models induced by heat and acetic acid. Electrophysiological screening revealed that isofraxidin is the bioactive compound in <em>S. glabra</em> responsible for its analgesic properties. The current-voltage and conductance-voltage relationships of isofraxidin's inhibition of the Na<sub>V</sub>1.7 channel suggest that isofraxidin directly binds to the pore region of the Na<sub>V</sub>1.7 channel.</div></div><div><h3>Conclusion</h3><div>In preclinical evaluations, <em>S. glabra</em> and isofraxidin have demonstrated potential as effective anti-nociceptive agents. Their ability to alleviate pain is likely due to their inhibition of the Na<sub>V</sub>1.7 channel, which is crucial for pain initiation, transmission, and regulation. These findings shed light on the molecular mechanisms behind the analgesic properties of <em>S. glabra</em>. Additionally, isofraxidin shows great potential in the creation of new pain-relief medications that target the Na<sub>V</sub>1.7 channel.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120002"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142623","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}
Jang Hoon Kim , Denis Nchang Che , Ji Hyeon Park , Jae Young Shin , Seon Il Jang , Byoung Ok Cho
{"title":"Anti-inflammatory effects of Elsholtzia ciliata extract on Poly I:C-treated RAW264.7 cells","authors":"Jang Hoon Kim , Denis Nchang Che , Ji Hyeon Park , Jae Young Shin , Seon Il Jang , Byoung Ok Cho","doi":"10.1016/j.jep.2025.120026","DOIUrl":"10.1016/j.jep.2025.120026","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Inflammation is a vital biological response to noxious stimuli, including physical injury and pathogenic infection, and involves immune cells and various inflammatory mediators, limiting cell damage and eliminating pathogens. Although essential for healing, inflammation can cause symptoms, such as fever, swelling, pain, and itching, potentially reducing quality of life. <em>Elsholtzia ciliata</em> used in traditional medicine has numerous medicinal characteristics such as antiviral, antibacterial, antipyretic, diaphoretic, carminative, astringent, and diuretic effects.</div></div><div><h3>Aim of the study</h3><div>This study aimed to evaluate the anti-inflammatory properties of <em>E. ciliata</em> extract (ECE) in RAW264.7 cells treated with polyinosinic polycytidylic acid (Poly I:C).</div></div><div><h3>Materials and methods</h3><div>PGE<sub>2</sub>, IL-1β, TNF-α, IFN-β, and IL-6 levels were quantified by ELISA and/or real-time PCR. COX-2 and iNOS expression was analyzed using western blotting and real-time PCR. Phosphorylation and expression levels of signaling proteins, including AKT, IRF3, TBK1, STAT1, MAPKs, IκB, and IκK were analyzed using western blotting. The active substance of ECE was determined using high-performance liquid chromatography-mass spectrometry (HPLC-MS).</div></div><div><h3>Results</h3><div>Our detections revealed that ECE inhibited the levels of nitric oxide and central inflammatory mediators, such as iNOS and COX-2. Furthermore, ECE downregulated the expression of pro-inflammatory cytokines, including PGE<sub>2</sub>, IL-1β, TNF-α, IFN-β, and IL-6. Additionally, ECE inhibited the phosphorylation of several cell signaling pathways, including AKT, TBK1/IRF3, MAPK, and NF-κB, in Poly I:C-treated RAW264.7 cells.</div></div><div><h3>Conclusions</h3><div>These results highlight <em>E. ciliata</em> as a candidate for mitigating virus-induced inflammation, providing valuable insights into its use in the development of new anti-inflammatory therapeutics.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120026"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138082","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}
Mengqi Xia , Zhiqiang Li , Cuiping Yang , Yilei Wang , Jianjian Zhang , Guoyue Zhong , Hui Ouyang , Yulin Feng
{"title":"Rubia cordifolia L. extract ameliorates vitiligo by inhibiting the CXCL10/CXCL9/STAT1 signaling pathway","authors":"Mengqi Xia , Zhiqiang Li , Cuiping Yang , Yilei Wang , Jianjian Zhang , Guoyue Zhong , Hui Ouyang , Yulin Feng","doi":"10.1016/j.jep.2025.120027","DOIUrl":"10.1016/j.jep.2025.120027","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Rubia cordifolia</em> L. (RCL<strong>)</strong> is a traditional herbal medicine with a long history of use. It has been employed to treat conditions such as abnormal uterine bleeding, primary dysmenorrhea, allergic purpura, eczema, and psoriasis. In Uyghur traditional medicine, it is also utilized to manage vitiligo, tinea, skin scars, and inflammatory wounds. However, the precise mechanism through which RCL improves vitiligo is still not fully understood.</div></div><div><h3>Aim of the study</h3><div>This research sought to examine the therapeutic impacts of RCL on vitiligo, determine whether its effects on the progression of vitiligo are facilitated via the CXCL10/CXCL9/STAT1 pathway, and perform an analysis of the chemical composition along with the identification of RCL.</div></div><div><h3>Materials and methods</h3><div>Chemical composition identification of RCL extract was performed using UHPLC-QTOF-MS/MS. A mouse model of vitiligo was created to assess the therapeutic effectiveness of RCL by analyzing the expression of CD8<sup>+</sup> T cells, performing HE staining, conducting melanin staining, evaluating TYR activity, and measuring the levels of inflammatory cytokines. Transcriptomic and metabolomic analyses were conducted to explore the mechanisms underlying RCL-mediated improvement of vitiligo.</div></div><div><h3>Results</h3><div>A total of 156 compounds were identified in RCL, predominantly including anthraquinones, naphthoquinones, and terpenoids. RCL treatment significantly reduced CD8<sup>+</sup> T cell expression, downregulated expression of cytokines that promote inflammation, and upregulated TYR activity and melanin production. Transcriptomic and metabolomic analyses identified the CXCL10/CXCL9/STAT1 signaling pathway and the metabolism of lysophosphatidylcholine and leukotriene B4 as key mechanisms underlying RCL's therapeutic effects on vitiligo, indicating that RCL ameliorates vitiligo by modulating autoimmunity and attenuating inflammatory responses. Western blotting and qPCR further validated that RCL inhibits the production of proteins linked to the CXCL10/CXCL9/STAT1 axis, including CXCL10, CXCL9, STAT1, and CXCR3. Additionally, RCL reduced the expression of inflammatory markers such as IL-1RAP, IL-6, IL-17A, KNG1, and PLA2G4E, further supporting its anti-inflammatory and immunoregulatory properties.</div></div><div><h3>Conclusions</h3><div>Our study demonstrates that RCL ameliorates the progression of vitiligo by modulating autoimmunity and attenuating inflammatory responses. The underlying mechanisms may involve mediating the CXCL10/CXCL9/STAT1 axis and regulating lysophosphatidylcholine and leukotriene B4 metabolism.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120027"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138119","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}
Huiling Jiang , Huantao Yang , Hui Li , Yujuan Wang , Lidu Shen , Xiaobi Adu , Junxiong Zhang , Hang Zhou , Likai Pu , Shiying Zhang , Jiacheng Guo , Aiping Tong , Hengxiu Yan
{"title":"Anti-herpes simplex virus type 1 activity of the Rohdea chinensis (Baker) N. Tanaka aqueous extracts","authors":"Huiling Jiang , Huantao Yang , Hui Li , Yujuan Wang , Lidu Shen , Xiaobi Adu , Junxiong Zhang , Hang Zhou , Likai Pu , Shiying Zhang , Jiacheng Guo , Aiping Tong , Hengxiu Yan","doi":"10.1016/j.jep.2025.120024","DOIUrl":"10.1016/j.jep.2025.120024","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Herpes simplex virus type 1 (HSV-1) is a prevalent neurotropic pathogen that establishes lifelong latency in the peripheral nervous system, posing substantial clinical challenges due to its recurrent infections and emerging drug resistance. <em>Rohdea chinensis</em> (Baker) N. Tanaka, a traditional Chinese herbal medicine, has been historically used for heat-clearing, detoxifying, wind-dampness dispelling, blood-stasis removing, and pain-relieving properties. Despite its common folk use in Leshan, Sichuan Province, for treating herpes simplex infections, the chemical composition and antiviral activity of <em>Rohdea chinensis</em> remain largely uninvestigated.</div></div><div><h3>Aim of the study</h3><div>The aim of this study was to clarify the chemical composition and antiviral activity of the <em>Rohdea chinensis</em> aqueous extract (RCAE), and preliminarily speculate the possible mechanism of its antiviral effect.</div></div><div><h3>Materials and methods</h3><div>The chemical profile of RCAE was characterized using UPLC-Q-TOF-MS/MS, identifying 9 major compounds. The antiviral effects of RCAE were assessed through in <em>vitro</em> and in <em>vivo</em> models, including direct virucidal assays, HSV-1 adhesion inhibition, and a mouse model of flank scratch HSV-1 infection. Immunomodulatory effects were evaluated by analyzing dendritic cell (DC) maturation, CD8<sup>+</sup> T cell differentiation, and cytokine expression. Additionally, HSV-1 latent reactivation models were established to assess RCAE's impact on viral persistence in the dorsal root ganglion (DRG). Molecular docking studies were conducted to determine potential interactions between RCAE bioactive compounds and HSV-1 glycoprotein D (gD).</div></div><div><h3>Results</h3><div>The overall anti-HSV-1 effect of RCAE on Vero cells was determined and the EC<sub>50</sub> value was 7.994 μg/mL. RCAE directly killed HSV-1 and inhibited HSV-1 adhesion in <em>vitro</em> (<em>P</em> < 0.001, 30 μg/mL RCAE treated groups vs HSV-1 group), and alleviated viral infection and inflammation of the skin involving the NF-κB pathway (<em>P</em> < 0.001, different doses of RCAE treated groups vs HSV-1 group), as well as anti-viral infection of the brain and DRG in HSV-1-induced mice (<em>P</em> < 0.05, 0.6 g/mL RCAE treated groups vs HSV-1 group). Interestingly, RCAE played an antiviral role by increasing the maturation of DC in mice, enhancing the antigen presentation ability of DC, promoting the differentiation of CD8<sup>+</sup>T cells and the secretion of CXCL1 and IFN-γ, and inhibiting the immune escape of HSV-1 virus (<em>P</em> < 0.05, 0.6 g/mL RCAE treated groups vs HSV-1 group). Besides, RCAE prevented the reactivation of HSV-1 in <em>vitro</em> (<em>P</em> < 0.001, 0.6 g/mL RCAE treated groups vs HSV-1 group). HSV gD is a critical viral glycoprotein that plays a central role in viral attachment to host cells, intercellular spread,","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120024"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142264","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}
Weiyi Zhang , Shulipan Mulatia , Miaomiao Zhang , Lei Huang , Ju Chen , Yarong Peng , Jun Li , Ajiaikebaier Aisa
{"title":"Esculetin inhibited fever, pain, and inflammatory responses via binding to HSC70","authors":"Weiyi Zhang , Shulipan Mulatia , Miaomiao Zhang , Lei Huang , Ju Chen , Yarong Peng , Jun Li , Ajiaikebaier Aisa","doi":"10.1016/j.jep.2025.120022","DOIUrl":"10.1016/j.jep.2025.120022","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Viola tianshanica Maxim</em>, a member of the Violaceae plant family, has been traditionally used in Uighur medicine to treat pneumonia, headaches, and other ailments. A preliminary study demonstrated its antipyretic activity; however, the active components responsible for this effect have not yet been elucidated.</div></div><div><h3>Aim of the study</h3><div>In light of the traditional use of Viola <em>tianshanica</em> Maxim as an anti-inflammatory and analgesic agent in Uighur medicine, this study aims to investigate the effects of esculetin, an ethanol-extracted active compound from Viola tianshanica, on inflammation induced by lipopolysaccharide (LPS) and to explore its underlying mechanisms of action. The study seeks to elucidate the molecular pathways through which esculetin exerts its therapeutic effects and to provide scientific evidence supporting its traditional medicinal applications.</div></div><div><h3>Materials and methods</h3><div>The antipyretic effect was evaluated using a yeast-induced hyperthermia model. The antinociceptive effect was assessed using the acetic acid-induced writhing test and the egg white-induced paw edema method. The chemical biology method was used to design and synthesize the alkynyl-esculetin molecular probe, and the potential target protein was identified through network pharmacology analysis, magnetic trapping technology, Western blotting (WB) analysis, cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR).</div></div><div><h3>Results</h3><div>We observed that esculetin could inhibit fever, pain, and inflammatory responses, suppress LPS-induced cyclooxygenase-2 (COX-2) and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) expression, and reduce the levels of related pro-inflammatory factors, such as interleukin (IL-1β), IL-12, and tumor necrosis factor-alpha. Network pharmacology analysis indicated that the MAPK pathway may play a key role. Meanwhile, gene ontology analysis revealed that heat shock protein binding is involved in this process. Target fishing, CETSA, SPR, and WB assays demonstrated that esculetin targeted heat shock cognate 70 (HSC70) and reduced its protein stability. Additionally, esculetin downregulated the phosphorylation of extracellular signal-regulated kinase, protein kinase B (Akt), p38 mitogen-activated protein kinase (p38/MAPK), and AMP-activated protein kinase (AMPK). Molecular docking indicated that hydrophobic interactions and hydrogen bonding are the primary binding forces. Subsequently, HSC70 knockdown abolished the anti-inflammatory effects of esculetin.</div></div><div><h3>Conclusion</h3><div>The present study indicates that esculetin exhibited antipyretic, analgesic, and anti-inflammatory effects through binding with HSC70 and downregulated the p38/MAPK pathway. This study provides a new perspective for developing antipyretic, analgesic, and anti-inflammatory drugs.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120022"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131293","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":"BaZiBuShen inhibition of oocyte ferroptosis in primordial follicles through activation of NF2-YAP pathway for the treatment of chemotherapy-induced premature ovarian insufficiency.","authors":"Xiaoni Zhu, Xiling Zhao, Jing Zhang, Yi Zhang, Xianhui Dong, Yunlong Hou, Zhenhua Jia, Ying Zhang, Weijuan Gao","doi":"10.1016/j.jep.2025.119945","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119945","url":null,"abstract":"<p><strong>Ethnopathological relevance: </strong>BaZiBuShen (BZBS) is an innovative, patented traditional Chinese medicine known for its kidney-tonifying and anti-aging effects. It contains active ingredients such as flavonoids and amino acid analogues, which have anti-inflammatory and antioxidant properties, and is used to alleviate symptoms of \"kidney essence\" deficiency.</p><p><strong>Aim of the study: </strong>This study evaluated the efficacy of BZBS on cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) and explored its possible mechanism of action.</p><p><strong>Methods: </strong>POI models in rats were established using CTX to assess the therapeutic effects of BZBS. HPLC-MS was used to analyze the components, while ELISA was adopted to determine the serum hormone levels. Ovarian morphology and number of follicles were evaluated by H&E staining. The ultrastructure of mitochondria was examined by TEM. The expression levels of proteins related to ferroptosis and the NF2-YAP signalling pathway were analyzed using immunohistochemistry, immunofluorescence, and Western blotting.</p><p><strong>Results: </strong>In CTX-induced POI rats, BZBS treatment effectively restored ovarian weight, while simultaneously decreasing serum FSH and LH levels and increasing E<sub>2</sub> levels. Histological analysis of the ovaries revealed that BZBS significantly increased the number of primordial, growing, and mature follicles, as well as reducing the number of atretic follicles. Furthermore, BZBS treatment mitigated ferroptosis by decreasing key markers Fe<sup>2+</sup>, TFR, ACSL4, and restoring the levels of GSH and GPX4. Additionally, BZBS modulated the expression of critical proteins involved in ferroptosis and cell signalling pathways. Specifically, it down-regulated p-RB1, while up-regulating SLC7A11 and RB1. Moreover, BZBS upregulates NF2 while downregulating YAP expression and its nuclear translocation, thereby regulating the NF2-YAP signaling pathway involved in ferroptosis.</p><p><strong>Conclusions: </strong>In a CTX-induced POI rat model, BZBS effectively restores hormonal levels, mitigates ovarian damage, and curbs excessive primordial follicle activation. It also modulates ferroptosis-related protein expression, activates the NF2-YAP pathway, and could provide a potential therapeutic approach for POI.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119945"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142267","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":"LC-MS/MS profiling and toxicological evaluation of Argania spinosa extract: Acute and subacute studies in Swiss Albino mice with in vivo and in silico approaches","authors":"Fatima Zahra Lafdil , Ghizlane Nouioura , Mohamed EL Fadili , Hicham Lafdil , Hassane Mekhfi , Raffaele Conte , Hatem A. Abuelizz , Fahd Kandsi","doi":"10.1016/j.jep.2025.120009","DOIUrl":"10.1016/j.jep.2025.120009","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Argania spinosa</em> (L.) Skeels, <em>argan</em> tree, scientifically known as (Arganier, أرݣان, ارڨان) and formerly referred to as <em>Sideroxylon spinosum</em>, is a tree endemic to southwestern Morocco. It is widely recognized for its numerous ethnobotanical and pharmacological properties, making it a valuable resource both ecologically and economically.</div></div><div><h3>Aim of the study</h3><div>The objective of the current study was to evaluate the acute and subacute toxicity profiles of <em>Argania spinosa</em> leaves extracts in mice, as well as the composition determined by LC–MS/MS, was employed to analyze and identify the compounds present in the extract. The primary compound in the studied extract, was selected for molecular docking analysis to explore its inhibitory mechanism against toxicity proteins.</div></div><div><h3>Materials and methods</h3><div>In the acute study, the extract was given to adult Swiss Albino mice via oral and intraperitoneal routes at doses ranging from 0 to 7 g/kg. In the subacute dose study, the extract was administered orally to adult mice at daily doses of 100, 250, and 500 mg/kg for 28 days. Body weight, along with selected biochemical and hematological parameters, was monitored. At the end of the treatment period, histological evaluations of the liver, kidney, and spleen were performed to identify any potential organ damage.</div></div><div><h3>Results</h3><div>Seventeen compounds were detected in the extract using LC–MS/MS analysis, with luteolin-7-O-glucoside, isorhamnetin-7-O-pentose, and quercetin-3-O-glucoside being the most prevalent. The predicted pharmacokinetic properties, indicate that the isolated compounds are well-absorbed, with a high human intestinal absorption. The acute toxicity evaluation revealed LD<sub>50</sub> values of 6 g/kg for oral administration and 4 g/kg for intraperitoneal administration of the extract. During the subacute toxicity assessment, no notable alterations in body weight or organ weights were observed. Similarly, no changes in hematological or biochemical parameters were noted. Microscopic examination of vital organs such as the liver, kidneys, and spleen revealed no significant lesions.</div></div><div><h3>Conclusion</h3><div>In conclusion, the leaves of <em>Argania spinosa</em>, revealing an interesting phytochemical composition. Furthermore, they exhibited no toxicity, making them a potential source of beneficial compounds for various applications, such as pharmaceuticals, and food products.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120009"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142456","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}
Ao Xue , Deping Zhao , Hongdan Xu , Xia Lei , Dalong Li , Yifan Ren , Qian Zhou , Qi Qiu , Liangyu Cai , Yafeng Zhang , Ning Zhang
{"title":"Erzhi pill promotes norepinephrine synthesis in locus coeruleus through ERβ-TFAP2A-TH plays a neuroprotective role","authors":"Ao Xue , Deping Zhao , Hongdan Xu , Xia Lei , Dalong Li , Yifan Ren , Qian Zhou , Qi Qiu , Liangyu Cai , Yafeng Zhang , Ning Zhang","doi":"10.1016/j.jep.2025.120015","DOIUrl":"10.1016/j.jep.2025.120015","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Erzhi Pill (EZP), a classical Chinese herbal formula for yin-nourishing and kidney-tonifying, has been traditionally prescribed for insomnia and amnesia, and shows therapeutic potential for Alzheimer's disease (AD). However, its active components and precise mechanisms of action against AD remain elusive.</div></div><div><h3>Aim of the study</h3><div>This study aimed to identify the key active components and molecular targets of EZP responsible for improving cognitive dysfunction and to elucidate its underlying mechanisms.</div></div><div><h3>Matreials and methods</h3><div>Behavioral and histomorphological analyses will be used to validate the efficacy of EZP in ameliorating cognitive impairment in lipopolysaccharide (LPS)-induced models. Untargeted metabolomics characterized metabolic profile alterations in the locus coeruleus (LC), while targeted metabolomics focused on specific metabolic pathways. Microdialysis coupled with high-resolution mass spectrometry (HR-MS) analyzed EZP's chemical components in LC dialysates. Network pharmacology and molecular docking predicted potential targets, with binding affinities validated by surface plasmon resonance (SPR). Molecular biology techniques were employed to investigate relevant signaling pathways.</div></div><div><h3>Results</h3><div>EZP significantly improved learning and memory capabilities in LPS-induced models, accompanied by enhanced neuronal activity. Metabolomic profiling revealed that EZP exerted its effects primarily through modulation of alanine, aspartate, and glutamate metabolism pathways, as well as phenylalanine and tyrosine metabolic networks. Specifically, EZP treatment resulted in decreased tyrosine (Tyr) levels and increased norepinephrine (NE) concentrations in the LC. Western blot analysis further demonstrated upregulated expression of tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DβH) proteins in LC tissues. Phytochemical analysis identified 45 prototype components and 14 metabolites in EZP, among which apigenin and wedelolactone were characterized as potential bioactive ingredients. Network pharmacology combined with molecular docking revealed estrogen receptor β (ERβ) as a critical target mediating EZP's anti-AD effects. SPR validated stronger binding affinity of apigenin and wedelolactone to ERβ compared with G-protein-coupled receptor 30 (GPR30). Mechanistic studies showed that these compounds activated ERβ signaling, restored TFAP2A/TH transcriptional activity, and promoted NE biosynthesis, thereby ameliorating cognitive deficits in AD models.</div></div><div><h3>Conclusion</h3><div>This study not only elucidates that EZP ameliorates cognitive dysfunction in AD)via the ERβ-TFAP2A/TH signaling pathway but also proposes NE augmentation as a novel therapeutic strategy for AD management.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"350 ","pages":"Article 120015"},"PeriodicalIF":4.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127834","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}