{"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}
Congjie Yan , Zexi Tian , Weiquan Ruan , Mengfen Wu , Weidong Wang , Zenggen Liu
{"title":"Erianin isolated from Dendrobium huoshanense alleviated neuroinflammation in MPTP-induced Parkinson's disease model via NF-κB/NLRP3 pathway","authors":"Congjie Yan , Zexi Tian , Weiquan Ruan , Mengfen Wu , Weidong Wang , Zenggen Liu","doi":"10.1016/j.jep.2025.119620","DOIUrl":"10.1016/j.jep.2025.119620","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Parkinson's disease (PD) is one of the most common neurodegenerative disorders, yet effective therapeutic options remain limited. <em>Dendrobium huoshanense</em> (DH), a medicinal and edible herb mainly distributed in Ta-pieh Mountains of Central China, has been used to treat disorders of consciousness and chronic nervous diseases in the local hospital for thousands of years. Erianin, a bioactive bibenzyl compound isolated from DH, has emerged as a potential neuroprotective agent due to its anti-inflammatory and antioxidant properties.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the neuroprotective effects of Erianin in the treatment of PD and the underlying mechanisms, particularly focusing on inflammation and oxidative stress, through both <em>in vivo</em> and <em>in vitro</em> models.</div></div><div><h3>Materials and methods</h3><div>A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model was employed. The protective effects of Erianin were evaluated through neurobehavioral tests, immunohistochemistry, immunofluorescence, Nissl staining, serum biochemical tests, and Western blotting. The role of Erianin in modulating the NF-κB/NLRP3 pathway was investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.</div></div><div><h3>Results</h3><div>Erianin significantly alleviated MPTP-induced motor deficits, reduced neuroinflammation, and reversed abnormal secretion of inflammatory and oxidative stress factors in the serum. Additionally, Erianin suppressed the gene expression of NOD-like receptor protein 3 (NLRP3) and tyrosine hydroxylase (TH) in the striatum of PD mice. And, Erianin inhibited the activation of the NF-κB/NLRP3 pathway, decreased the production of oxidative stress factors, and reversed the secretion of inflammatory mediators in LPS-stimulated BV-2 microglia cells.</div></div><div><h3>Conclusion</h3><div>Erianin exerts neuroprotective effects in Parkinson's disease primarily by inhibiting the NF-κB/NLRP3 signaling pathway. These findings suggest that Erianin holds promise as a potential therapeutic candidate for the treatment of PD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119620"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615756","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}
Xiao-Lan Zhao , Li-Yue Xu , Ke-Di Li , Fei Tang , Dong Liu , Jing-Nan Zhang , Zhang-Jing Cao , Cheng Peng , Hui Ao
{"title":"Exploring dried ginger essential oil as a therapeutic strategy for 5-FU-induced mucositis: Gut microbiota and tryptophan metabolite IAA-AHR/IL-22/STAT3 signaling axis","authors":"Xiao-Lan Zhao , Li-Yue Xu , Ke-Di Li , Fei Tang , Dong Liu , Jing-Nan Zhang , Zhang-Jing Cao , Cheng Peng , Hui Ao","doi":"10.1016/j.jep.2025.119616","DOIUrl":"10.1016/j.jep.2025.119616","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>5-Fluorouracil (5-FU) commonly induces severe mucositis, causing pain, inflammation, and gastrointestinal dysfunction, which significantly increases patient morbidity and reduces quality of life. In Ayurveda, Traditional Chinese Medicine, and other ethnopharmacological practices, dried ginger has been widely used to alleviate symptoms such as nausea, vomiting, diarrhea, and inflammation, highlighting its important role in traditional medicine. Aim of the study: This study explored the potential of dried ginger essential oil (DGEO) in mitigating intestinal epithelial barrier damage in mice with mucositis induced by 5-FU.</div></div><div><h3>Methods</h3><div>The therapeutic effects of DGEO were evaluated by measurements of weight changes, diarrhea scores, ELISA, and H&E. Further investigations included 16S rRNA sequencing, untargeted metabolomics, molecular docking, and HPLC-MS/MS to explore its underlying mechanisms, with validation performed using western blotting and ELISA.</div></div><div><h3>Results</h3><div>The results demonstrated that DGEO was effective in alleviating mucositis symptoms. It also improved the gut microbiota, enhanced the biotransformation of tryptophan to indole-3-acetic acid (IAA), and elevated the protein expressions of the AHR, CYP1A1, and p-STAT3, as well as level of IL-22. Moreover, DGEO improved the expressions of tight junction (TJ) proteins and anti-apoptotic proteins, enhancing intestinal barrier integrity.</div></div><div><h3>Conclusion</h3><div>These findings indicated that DGEO ameliorated 5-FU-induced mucositis by modulating gut microbiota and the tryptophan metabolite IAA-AHR/IL-22/STAT3 signaling axis, providing new insights into its therapeutic applications, particularly its ability to regulate gut microbiota and related signaling pathways.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119616"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614967","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}
Hong-Xiang Jiang , Jun-Hong Chai , Lan Zhou , Xue Gao , Xue-Qing Liu , Wen-Fei Wang , Jun Liang , Hai-Xue Kuang , Yong-Gang Xia
{"title":"Exploration of scientific connotation of “Yin-Jing” medical properties of Cyathula officinalis via potentiating therapeutic effect, guidance and targetability","authors":"Hong-Xiang Jiang , Jun-Hong Chai , Lan Zhou , Xue Gao , Xue-Qing Liu , Wen-Fei Wang , Jun Liang , Hai-Xue Kuang , Yong-Gang Xia","doi":"10.1016/j.jep.2025.119629","DOIUrl":"10.1016/j.jep.2025.119629","url":null,"abstract":"<div><h3>Ethnic pharmacological relevance</h3><div>“<em>Cyathula officinalis</em> Kuan (COK)” has the effect of “guiding the drug downward” and can enhance the efficacy of formula, e.g., Shentong Zhuyu Decoction (STZYD). However, there is currently no scientific basis on COK to guide drugs to target organs in STZYD.</div></div><div><h3>Aim of the study</h3><div>The main objective of this study was to unclose the scientific connotations of the Yin-Jing medicinal properties of COK using molecular biology and modern chemical methods.</div></div><div><h3>Materials and methods</h3><div>A rat model of adjuvant arthritis was established. The optimal dose of STZYD was determined by observing a series of indicators, and the therapeutic effects of STZYD and [STZYD - COK] were compared. The water decoction of COK was divided into five fragments (i.e., Fr. A-E) by macroporous adsorption resin and alcohol deposition methods. The Fr. A-E were further characterized by a combination of multiple chromatographic and spectral techniques. The potentiating therapeutic effects, guidance and targetability tests were used to evaluate “Yin-Jing” function by compatible combination of other drugs using pharmacological indicators, pharmacokinetics, high-performance liquid chromatography (HPLC) and small animal live imaging (SALI) techniques.</div></div><div><h3>Results</h3><div>The optimal dose of STZYD was confirmed to be 1 × dose and COK increased the efficacy of [STZYD - COK]. The results of chemical characterization showed that the main components of Fr. A-E were polysaccharide, fructooligosaccharide and small M<sub>w</sub> fructan, saponins and flavonoid glycosides, steroidal ketones, organic acids esters, respectively. Pharmacological experiments showed that Fr. A, Fr. B and Fr. E were attributed to potentiate therapeutic effects. Guidance assays showed that Fr. B enhanced drug distribution and uptake in the kidneys, joints and cells. Targetability assays further confirmed that Fr. B had apparent targetability toward the joints and kidneys rather than other organs and tissues.</div></div><div><h3>Conclusions</h3><div>This study for the first time combined potentiating therapeutic effects, guidance and targeting evaluation system, and identified Fr. B as the pharmacodynamic material basis of COK's Yin-Jing medicinal properties.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"346 ","pages":"Article 119629"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614951","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}
Jinfeng Shang , Guijinfeng Huang , Bohong Wang , Jingyi Wang , Wanting Wei , Yiran Cui , Xin Liu
{"title":"Shuxuetong injection inhibits pyroptosis in acute ischemic stroke via CD44/NLRP3/GSDMD signal","authors":"Jinfeng Shang , Guijinfeng Huang , Bohong Wang , Jingyi Wang , Wanting Wei , Yiran Cui , Xin Liu","doi":"10.1016/j.jep.2025.119618","DOIUrl":"10.1016/j.jep.2025.119618","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Acute ischemic stroke (AIS) is an important cause of death and disability in the world. Based on the blood stasis syndrome of stroke, Shuxuetong Injection (SXT) is a representative prescription for the treatment of AIS, which extracted by modern technology from <em>Whitmania pigra</em> Whitman (Shuizhi) and <em>Pheretima aspergillum</em> E.Perrier (Dilong).</div></div><div><h3>Aim of the study</h3><div>This study is in order to examine whether SXT regulates pyroptosis in AIS via Cluster of Differentiation 44 (CD44)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/gasdermin D (GSDMD) signal.</div></div><div><h3>Materials and methods</h3><div>The rats were randomly divided into sham group, model (transient middle cerebral artery occlusion, 24 h) group, SXT low-dose group (0.27 mL/kg), SXT medium-dose group (0.54 mL/kg), SXT high-dose group (1.08 mL/kg) and positive drug group (edaravone injection, 1.35 mL/kg). Transient middle cerebral artery occlusion (tMCAO, 24 h) model of rats was set up. Neurological deficit score, tetrazolium red staining, hematoxylin-eosin staining, and Nissl staining were used to observe and screen out the optimal dosage for improving AIS. Mechanism research indicators included transmission electron microscopy and Western blot. Adeno-associated virus (AAV)-CD44 and small interfering RNA (siRNA) of CD44 were used for knocking down the CD44 expression level to verify whether SXT could resist pyroptosis through CD44. The oxygen and glucose deprivation/re-oxygenation (OGD/R, 24 h) model of PC12 cells was used for in vitro pharmacological validation. Molecular docking, cellular thermal shift assay and drug affinity responsive target stability were employed to assess the binding affinity of critical components for the CD44 protein.</div></div><div><h3>Results</h3><div>SXT conspicuously mitigated the neurological function scores and cerebral infarct volume in tMCAO rats, thereby safeguarding nerve cells. In vitro, SXT not only enhanced the viability of PC12 cells subjected to OGD/R but also mitigated cellular swelling and inflammatory infiltration. The optimal dose was 1.08 mL/kg (rats) or 72.56 mg/mL (PC12 cells). SXT reduced pyroptosis and inflammation in tMCAO rats and OGD/R cells by decreasing the expression levels of GSDMD-N, NLRP3 and CD44. In addition, after knocking down the expression level of CD44 by using AAV-CD44 and siRNA-CD44, it was found that the pyroptosis of AIS intervened by SXT was closely related to the CD44/NLRP3/GSDMD signal. The pivotal constituent of SXT, xanthine, exhibited pronounced binding affinity towards the CD44 protein, thereby demonstrating the capacity to stabilize this molecular target.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that Shuxuetong Injection inhibits pyroptosis in acute ischemic stroke via CD44/NLRP3/GSDMD signal.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119618"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614989","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":"Exploring the mechanisms of cow placental peptides in delaying liver aging based on mitochondrial energy metabolism","authors":"Zeru Zhang , Yuxin Luo , Hanwen Zhang , Zhi Zeng, Weijian Zheng, Yuquan Zhao, Yixin Huang, Liuhong Shen","doi":"10.1016/j.jep.2025.119593","DOIUrl":"10.1016/j.jep.2025.119593","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Placenta is a kind of traditional Chinese medicine, known as “Ziheche”. The role of cow placental peptides (CPP) in delaying liver aging has been reported, and in-depth exploration of the specific regulatory mechanisms is of great significance for the recycling and utilization of CPP and the development of natural anti-aging drugs.</div></div><div><h3>Aim of the study</h3><div>To investigate the protective effects and mechanisms of CPP on liver aging induced by D-galactose (D-gal) in mice from the perspective of mitochondrial energy metabolism.</div></div><div><h3>Methods</h3><div>An aging model was induced in mice using D-gal. The body weight and liver index of mice were measured, followed by staining and electron microscopy to observe liver morphology and aging markers. Reactive oxygen species (ROS) levels and antioxidant-related indicators were assessed, and mitochondrial function was evaluated. Finally, changes and mechanisms in liver transcriptomics and targeted mitochondrial energy metabolomics were analyzed and integrated to elucidate the regulatory pathways through which CPP delays liver aging.</div></div><div><h3>Results</h3><div>CPP improved liver structural damage, oxidative stress, and mitochondrial dysfunction induced by D-galactose in aging mice. It increased the final body weight and liver index, alleviated hepatocyte swelling and degeneration, enhanced liver antioxidant capacity, and restored normal mitochondrial morphology and function. The combined analysis of targeted mitochondrial energy metabolomics and liver transcriptomics revealed that CPP directly or indirectly regulated mitochondrial energy metabolism and delayed aging by influencing the cAMP signaling pathway, PI3K-Akt signaling pathway, oxidative phosphorylation, and other pathways, thereby modulating related genes and metabolites.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119593"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597135","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}