Lina Yin , Tingting Niu , Ling Li , Wei Yu , Bo Han , Asma Rehman , Kewu Zeng
{"title":"Research advancements in molecular glues derived from natural product scaffolds: Chemistry, targets, and molecular mechanisms","authors":"Lina Yin , Tingting Niu , Ling Li , Wei Yu , Bo Han , Asma Rehman , Kewu Zeng","doi":"10.1016/j.chmed.2025.01.001","DOIUrl":"10.1016/j.chmed.2025.01.001","url":null,"abstract":"<div><div>The mechanism of action of traditional Chinese medicine (TCM) remains unclear. Historically, research on TCM has mainly focused on exploring the mechanisms of active components acting on single targets. However, it is insufficient to explain the complex mechanisms by which these active components in TCM treat diseases. In recent years, the emergence of molecular glues (MGs) theory has provided new strategies to address this issue. MGs are small molecules that can promote interactions between proteins at their interface. The characteristic of MGs is to establish connections between diverse protein structures, thereby enabling a chemically-mediated proximity effect that triggers a wide spectrum of biological functions. Natural products are the result of billions of years of evolutionary processes in the natural environment. Thus, the extensive structural diversity of natural products renders them a rich source of MGs, including polyketides, terpenoids, steroids, lignans, organic acids, alkaloids and other classes. Currently, several well-known natural MGs, including the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK506), as well as the anticancer agent taxol, have been incorporated into clinical practice. Meanwhile, the advancement of new technologies is propelling the discovery of novel MGs from natural products. Thus, we primarily summarize a growing variety of MGs from natural origins reported in recent years and categorize them based on the chemical structural types. Moreover, the main sources of TCM are natural products. The discovery of natural MGs promises to provide a new perspective for the elucidation of the molecular mechanism behind the efficiency of TCM. In summary, this review aims to provide insights from the perspective of natural products that could potentially influence TCM and modern drug development.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 2","pages":"Pages 235-245"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuanyuan Zhang , Fazhi Su , Enlin Zhu , Yanping Sun , Haixue Kuang , Qiuhong Wang
{"title":"A systematical review on traditional Chinese medicine treating chronic diseases via regulating ferroptosis from the perspective of experimental evidence and clinical application","authors":"Yuanyuan Zhang , Fazhi Su , Enlin Zhu , Yanping Sun , Haixue Kuang , Qiuhong Wang","doi":"10.1016/j.chmed.2025.01.003","DOIUrl":"10.1016/j.chmed.2025.01.003","url":null,"abstract":"<div><div>Ferroptosis is a unique regulated form of cell death that is distinct from apoptosis, necrosis, and other well-characterized regulated cell death types, and plays an important role in the occurrence and development of chronic metabolic diseases, including diabetes, hypertension, hyperlipidemia, and non-alcoholic steatohepatitis. Recently, increasing evidence has supported traditional Chinese medicine (TCM) as a new hot spot for the treatment of chronic metabolic diseases by mediating ferroptosis. Unfortunately, few systematic reviews have described the importance of TCM in treating chronic metabolic diseases through the ferroptosis pathway. In the current review, the mechanism of ferroptosis and the roles of ferroptosis in chronic metabolic diseases are summarized. Additionally, this review illustrates that the regulation of ferroptosis by TCM could be an effective approach for treating chronic metabolic diseases based on experimental evidence and clinical application. In summary, this work will improve the understanding of ferroptosis and the ability of TCM to regulate ferroptosis in chronic metabolic diseases, thereby promoting the development and application of natural TCM.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 2","pages":"Pages 246-260"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MYB polymorphism molecular marker: A novel molecular marker for authenticity and geographical origin identification of Citri Reticulatae Pericarpium","authors":"Qiqing Cheng , Ziyu Tang , Yue Ouyang , Chunsong Cheng , Chichou Lao , Hao Cui , Hua Zhou , Yongshu Liang","doi":"10.1016/j.chmed.2025.02.006","DOIUrl":"10.1016/j.chmed.2025.02.006","url":null,"abstract":"<div><h3>Objective</h3><div><em>Citri Reticulatae Pericarpium</em> (Chenpi, CRP) is one of the most used traditional Chinese medicines with great medicinal, dietary and collection values, among which the <em>Citrus reticulata</em> cv. ‘Chachi’ (<em>Citrus reticulata</em> cv. Chachiensis) from Guangdong Xinhui is the geoherb of CRP. Xinhui CRP in the market was often counterfeited with other varieties or origins, molecular identification method can effectively distinguish different CRP varieties, but it’s still a difficult problem to identify the same CRP variety from different origin. It is necessary to discover a new molecular marker to ensure the safe and effective application of Xinhui CRP.</div></div><div><h3>Methods</h3><div>We selected one of the most studied transcription factor families in <em>Citrus</em> genus, MYB, to design the specific candidate primers on the conserved region. The primers with good band repeatability and high polymorphism were screened for PCR amplification of the test materials, and the genetic similarity coefficient among different families, genera, species, and origins were calculated. The cluster analysis was performed by unweighted pair group method using arithmetic average (UPGMA).</div></div><div><h3>Results</h3><div>A total of ten MYB primers were screened out to identify Xinhui CRP from plants from different family (<em>Panax ginseng</em> and <em>Morus alba</em>), genus (<em>Clausena lansium</em> and <em>Zanthoxylum schinifolium</em>), and species (<em>Citrus reticulata</em>, <em>C. sinensis</em> and <em>C. maxima</em>). Furthermore, two from the ten primers, M1 and M10, were found to distinguish Xinhui CRP from other origins. There were 169, 113, 133 and 134 polymorphic bands in the identification of different families, genera, species, and origins respectively, and the accordingly polymorphism ration were 79.88%, 76.87%, 79.20% and 82.84%. Moreover, M1 was discovered to be the best primer to identify Xinhui CRP from other seven origins, the cluster analysis results based on the genetic similarity coefficients were consistent with the geographical distribution.</div></div><div><h3>Conclusion</h3><div>This study established a novel molecular identification method according to MYB transcription factor, which can analyze the potential parental relationship of CRP germplasm, as well as identify the quality and origins of Xinhui CPR.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 2","pages":"Pages 296-306"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuyu Chen , Yun Yang , Yangyang Liu , Chun Sui , Jianhe Wei
{"title":"Analysis of fungal composition in different layers of Bantou agarwood-forming trunk of Aquilaria sinensis revealing presence of Aspergillus-inhibiting substances in agarwood sites","authors":"Xuyu Chen , Yun Yang , Yangyang Liu , Chun Sui , Jianhe Wei","doi":"10.1016/j.chmed.2025.02.001","DOIUrl":"10.1016/j.chmed.2025.02.001","url":null,"abstract":"<div><h3>Objective</h3><div>The objective of this study was to analyse fungal composition and exploit application potential in the Bantou (BT) agarwood-forming trunk of <em>Aquilaria sinensis.</em></div></div><div><h3>Methods</h3><div>BT agarwood is a naturally formed agarwood that was collected after cutting. Total genomic DNA of the fungi in BT agarwood was extracted by the hexadecyltrimethy ammonium bromide (CTAB) method, followed by PCR amplification and library construction. The effective tags were obtained by the HiSeq2500 platform, and the data were subjected to bioinformatics and statistical analyses.</div></div><div><h3>Results</h3><div>A total of 7 850 040 effective tags were obtained, Ascomycota was the most abundant fungus at the phylum level, with a relative abundance of 56.36%–61.44%, followed by Basidiomycota, with a relative abundance of 10.49%–20.39%. Dothideomycetes, Agaricomycetes and Sordariomycetes were dominant at the class level, accounting for 26.21%–33.88%, 8.40%–17.66%, and 18.41%–24.11%, respectively. <em>Lignosphaeria</em>, <em>Phaeoacremonium</em> and <em>Hermatomyces</em> were dominant at the genus level, with relative abundances of 6.25%–7.64%, 1.95%–9.05% and 1.5%–5.4%, respectively. Diversity and richness analysis showed that the fungal composition in the agarwood formation sites (agarwood layer, upper agarwood layer and lower agarwood layer) were significantly lower than those in the decomposing layer and the healthy layer. That is, the fungal diversity and richness were significantly reduced during agarwood formation by the action of open wounds. The fungal community structure in the decomposing layer and agarwood formation sites obviously differed from that in the healthy layer. The number of <em>Aspergillus</em> taxa in agarwood formation sites decreased significantly (healthy layer is 0.5%, decomposing layer is 0.022%, upper agarwood layer is 0.012%, agarwood layer is 0.01%, and lower agarwood layer is 0.013%), indicating that agarwood may contain potential substances to inhibit the growth of <em>Aspergillus</em>.</div></div><div><h3>Conclusion</h3><div>Agarwood from agarwood formation sites contains potential substances that inhibit <em>Aspergillus</em>, which provides valuable information for the control of the genus of <em>Aspergillus</em>.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 2","pages":"Pages 315-321"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenze Wu , Yan Mi , Qingqi Meng , Ning Li , Wei Li , Pu Wang , Yue Hou
{"title":"Natural polyphenols as novel interventions for aging and age-related diseases: Exploring efficacy, mechanisms of action and implications for future research","authors":"Wenze Wu , Yan Mi , Qingqi Meng , Ning Li , Wei Li , Pu Wang , Yue Hou","doi":"10.1016/j.chmed.2024.09.001","DOIUrl":"10.1016/j.chmed.2024.09.001","url":null,"abstract":"<div><div>Natural polyphenols are a group of components widely found in traditional Chinese medicines and have been demonstrated to delay or prevent the development of aging and age-related diseases in recent years. As far as we know, the studies of natural polyphenols in aging and aging-related diseases have never been extensively reviewed. In the present paper, we reviewed recent advances of natural polyphenols in aging and common age-related diseases and the current technological methods to improve the bioavailability of natural polyphenols. The results showed that natural polyphenols have the potential to prevent or treat aging and common age-related diseases through multiple mechanisms. Nanotechnology, structural modifications, and matrix processing could provide strong technical support for the development of natural polyphenols to prevent or treat aging and age-related diseases. In conclusion, natural polyphenols have important potential in the prevention and treatment of aging and age-related diseases.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 2","pages":"Pages 279-291"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancement of apoptosis in HCT116 and HepG2 cells by Coix lacryma-jobi var. lacryma-jobi seed extract in combination with sorafenib","authors":"Supawadee Parhira , Guoyuan Zhu , Apirath Wangteeraprasert , Suphunwadee Sawong , Pennapha Suknoppakit , Julintorn Somran , Naphat Kaewpaeng , Khemmachat Pansooksan , Dumrongsak Pekthong , Piyarat Srisawang","doi":"10.1016/j.chmed.2025.02.005","DOIUrl":"10.1016/j.chmed.2025.02.005","url":null,"abstract":"<div><h3>Objective</h3><div><em>Coix lacryma-jobi</em>, a highly regarded Asian herb widely used in traditional Chinese medicine, is recognized for its dual benefits in promoting overall health and treating various diseases. While it exhibits moderate anticancer efficacy when used alone, this study investigated the enhanced anticancer potential of raw and cooked <em>Coix lacryma-jobi</em> var. <em>lacryma-jobi</em> (CL) seed extracts in combination with sorafenib against HCT116 and HepG2 cancer cell lines. The combination of sorafenib with other anticancer agents, including natural extracts, has garnered significant attention as a promising strategy for developing more effective cancer therapies.</div></div><div><h3>Methods</h3><div>Dry powders of raw (R) and cooked (C) CL seeds, obtained from a local commercial source in Thailand, were extracted and fractionated using ethanol (E), dichloromethane (D), ethyl acetate (A), and water (W) to produce eight fractions: CLRE, CLCE, CLRD, CLCD, CLRA, CLCA, CLRW, and CLCW. The coixol content in raw and cooked seed extracts was quantified and expressed as μg of coixol per gram of extract. The cytotoxic effects of these fractions were evaluated against HCT116 and HepG2 cells using the MTT assay. Fractions demonstrating the most significant cytotoxic responses were combined with sorafenib to evaluate their synergistic effects. Apoptosis induction and mitochondrial membrane potential (MMP) were assessed, and the underlying mechanism of apoptosis was explored by analyzing reactive oxygen species (ROS) generation and antioxidant protein expression levels. Additionally, the combination treatment’s effect on the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway was investigated.</div></div><div><h3>Results</h3><div>One gram of CLCE and CLCD extracts contained higher coixol levels (7.02 μg and 9.69 μg, respectively) compared to CLRE and CLRD (2.66 μg and 5.96 μg, respectively). Coixol content in CLRA, CLRW, and CLCW fractions was undetectable under the study conditions. All extract fractions exhibited IC<sub>50</sub> values exceeding 1 mg/mL after 24- and 48-hour incubations with HCT116 and HepG2 cells, indicating limited cytotoxicity when used independently. CLRD and CLCD fractions were selected for combination studies at a concentration of 1 mg/mL, combined with sub-IC<sub>50</sub> concentrations of sorafenib to minimize its side effects. This combination significantly increased cytotoxicity, inducing apoptosis in HCT116 and HepG2 cells by elevating ROS levels and reducing the expression of superoxide dismutase 2 and catalase. Furthermore, the combination treatment downregulated the PI3K/AKT/mTOR pathway, indicating a targeted anticancer mechanism.</div></div><div><h3>Conclusion</h3><div>The combination of CLCD with sorafenib demonstrates significant potential as a strategy for future anticancer therapies. This CL seed extract, cultivated and commercially a","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 2","pages":"Pages 322-339"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lixue He , Shixing Edi , Jun Ma , Zilin Kong , Chunguang Dai , Linfang Huang , Rui Zeng , Kaijun Gou
{"title":"Prevention and treatment of radiation injury by traditional Chinese medicine: A review","authors":"Lixue He , Shixing Edi , Jun Ma , Zilin Kong , Chunguang Dai , Linfang Huang , Rui Zeng , Kaijun Gou","doi":"10.1016/j.chmed.2024.09.005","DOIUrl":"10.1016/j.chmed.2024.09.005","url":null,"abstract":"<div><div>Nuclear radiation exposure events and tumor radiotherapy are highly susceptible to a range of psychological, physiological and other health problems, which can seriously affect patients’ quality of life. It has been shown that 87.5 % of tumor patients are exposed to varying degrees of radiation injury during radiotherapy. The treatment of radiation injury (RI) in modern medicine is limited to drug therapy, cell therapy, etc. Among them, the most chemical drugs cause many adverse reactions including fatigue, nausea, vomiting, etc., and there are very few drugs dedicated to the treatment of RI. Traditional Chinese medicine (TCM) is a rich natural medicinal resource, which has a wide range of pharmacological activities, multiple targets of action and minimal toxic side effects. Many studies have demonstrated that TCM and its compound preparations have enormous potential in the treatment of radiation induced comprehensive diseases. However, TCM is limited in clinical application due to its slow onset of action, complex active ingredients, and low bioavailability. Therefore, the article reviews the application, molecular mechanisms, and new dosage forms of TCM in the prevention and treatment of RI. On this basis, we will focus on discussing the development advantages and application prospects of the combination of traditional Chinese and Western medicine to achieve highly efficient treatment of RI. This review aims to provide scientific and effective drug delivery strategies and basic theoretical support for the clinical effective treatment of RI with TCM, and further promote the innovative development of TCM.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 2","pages":"Pages 220-234"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Yao , Meng Zhang , Shaolei Zhao , Hongjian Yu , Jingze Zhang , Dailin Liu
{"title":"Research and utilization status of Lophatherum gracile: A medicinal and food homologous plant","authors":"Bin Yao , Meng Zhang , Shaolei Zhao , Hongjian Yu , Jingze Zhang , Dailin Liu","doi":"10.1016/j.chmed.2024.07.006","DOIUrl":"10.1016/j.chmed.2024.07.006","url":null,"abstract":"<div><div><em>Lophatheri Herba</em> (Danzhuye in Chinese) is derived from the dried stems and leaves of <em>Lophatherum gracile</em> and has a long history of use as a medicinal and food source. Flavonoids and phenolic acids are the main active ingredients in <em>Lophatheri Herba</em>, which produce diuretic, anti-inflammatory, and antipyretic effects. Flavonoid glycosides and hydroxybenzoic acids are respectively the main structure in 44 flavonoids and 16 phenolic acids obtained from <em>Lophatheri Herba.</em> Modern pharmacological studies have found that the main chemical constituents of <em>Lophatheri Herba</em> play important roles in anti-inflammatory, cardioprotective, hepatoprotective and hypoglycaemic effects. Studies have demonstrated that flavonoid monomers, for example, luteolin, isoorientin, luteolin-7-<em>O</em>-<em>β</em>-<em>D</em>-glucoside and apigenin are more effective in exerting the above pharmacological effects. In addition, <em>Lophatheri Herba</em> is used in different food products as the main ingredient or as an accessory. This review describes <em>Lophatheri Herba</em> in terms of its chemical composition, pharmacological effects and efficacy, food development and applications, and clinical utility, and discusses the problems facing its use. This study provides valuable ideas and a scientific basis for the future development and use of <em>L. gracile</em>.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 2","pages":"Pages 261-278"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epigenetics and traditional Chinese medicine: A noteworthy research area","authors":"Chunfu Wu","doi":"10.1016/j.chmed.2025.02.004","DOIUrl":"10.1016/j.chmed.2025.02.004","url":null,"abstract":"","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 2","pages":"Pages 201-202"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Wu , Yan Xu , Hao Cai , Zhengying Hua , Meimei Luo , Letao Hu , Nong Zhou , Xinghong Wang , Weidong Li
{"title":"Overexpression of SULT1E1 alleviates salt-processed Psoraleae Fructus-induced cholestatic liver damage","authors":"Yu Wu , Yan Xu , Hao Cai , Zhengying Hua , Meimei Luo , Letao Hu , Nong Zhou , Xinghong Wang , Weidong Li","doi":"10.1016/j.chmed.2024.11.002","DOIUrl":"10.1016/j.chmed.2024.11.002","url":null,"abstract":"<div><h3>Objective</h3><div>Salt-processed <em>Psoraleae Fructus</em> (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined.</div></div><div><h3>Methods</h3><div>By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity <em>in vivo</em>. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments.</div></div><div><h3>Results</h3><div>A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the “estrogen signaling pathway” identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder <em>in vivo</em>. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups.</div></div><div><h3>Conclusion</h3><div>The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 2","pages":"Pages 392-403"},"PeriodicalIF":4.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}