ETHNOPHARMACOLOGICAL RELEVANCEGentiana rigescens Franch. (G. rigescens), known as "Dian Long Dan" in Southern Yunnan Herbal, has a long history in traditional Chinese medicine for treating hepatitis, allergies, postherpetic neuralgia, cholecystitis and rheumatism.AIM OF THE STUDYThis study aims to comprehensively analyze the phenolic composition of G. rigescens, evaluate its potential anti-inflammatory effects, elucidate underlying mechanisms, and identify its in vivo bioactive phenolic constituents.MATERIALS AND METHODSThe extraction of G. rigescens phenolic compounds (GRP) was optimized using the Box-Behnken response surface method, with four phenolic compounds (mangiferin, esculetin, ferulic acid and kaempferol) used as quality index markers. GRP's phytochemical composition was subsequently profiled via UPLC-Q-TOF-MS/MS analysis. Anti-inflammatory activity and mechanisms were assessed in LPS-stimulated RAW264.7 cells and murine models, utilizing NO production assays, ELISA, qRT-PCR, Western blotting and histopathological analysis. Bioactive phenolic compounds in blood were identified post-oral administration for in vivo activity prediction.RESULTSThe optimal extraction conditions for GRP were determined as follows: Soxhlet extraction using acetone with hydrochloric acid 0.06 mol/L, at a liquid-to-solid ratio of 132: l. for 6.6 h. Seventy-one of phenolic compounds were identified in GRP using UPLC-Q-TOF-MS/MS. GRP significantly inhibited LPS-induced NO production in RAW 264.7 macrophages and reduced pro-inflammatory cytokines IL-6, IL-1β, and TNF-α while increasing anti-inflammatory IL-10. In the carrageenan-induced inflammatory model, GRP exhibited a 69.81% inhibition rate of toe swelling at high doses (1 g/kg), along with protective effects against joint injury, as observed in histological assessments. Mechanistically, GRP downregulated mRNA levels of inflammatory cytokines and reduced the expression of inflammatory proteins iNOS, COX-2, p65, p-p65 and P-IκB as shown by Western blotting. Twenty-five of phenolic compounds, including mangiferin, swertianolin, acacetin, umbelliferone and caffeic acid, were identified in vivo in the blood, indicating potential bioactive roles.CONCLUSIONSThis study provides the first comprehensive profile of the phenolic composition of G. rigescen, alongside a detailed investigation of its anti-inflammatory activity, mechanisms, and in vivo bioactive components. These findings highlight the therapeutic potential of Dian Long Dan's phenolic constituents and support further research on G. rigescens.

2025-02-01·Biomedical Chromatography

Identification of the Pharmacological Components and Its Targets of Sanghuang by Integration of Nontarget Metabolomics and Network Pharmacology Analysis

Article

作者: Wang, Yongzhong ; Lu, Hengqian ; Zhang, Jintao

ABSTRACTThe objective of this study is to comprehensively to identify the core pharmacological components and their respective targets of three medicinal fungi Sanghuangs including Sanghuangporus vaninii (SV), Sanghuangporus lonicericola (SL), and Inonotus hispidus (IH). Metabolomics analysis indicated that a total of 495 and 660 differential metabolites were obtained in mycelium and fermentation broth samples among three Sanghuangs, respectively. The network pharmacology analysis showed that 6‐[1]‐ladderane hexanol, R‐nostrenol, candidone, ellagic acid, and quercetin were the overlapping active ingredients of three Sanghuang species for diabetes mellitus, immune system disease, and neoplasm. Certonardosterol A, dalamid, and ethylene brassylate are unique active ingredients in SV, and certonardosterol K, kaempferide, and esculetin are unique active ingredients in SL. Asbestinine, neoandrographolide, isosakuranetin, and daucosterin are unique active ingredients in IH. Accordingly, the common core targets of active ingredients of the three Sanghuangs were ESR1, PIK3CA, and LYN. PRKCA, EGFR, and STAT3 were the unique targets of SV, SL, and IH, respectively. The primary active components and their respective targets, in addition to the component–target interaction of Sanghuangs that have been identified in the present study, provide a foundation for future research on the prevention and treatment of disease using Sanghuangs.

2025-01-10·Science Advances

Blocking the isoflavone chemoreceptor in Phytophthora sojae to prevent disease

Article

作者: Xu, Xia ; Yin, Zhiyuan ; Qiao, Zijin ; Ji, Peiyun ; Pei, Yong ; Bao, Yazhou ; Ou, Kangmiao ; Zhong, Zengtao ; Zhou, Hao ; Shen, Danyu ; Song, Wen ; Dou, Daolong ; Huang, Tao ; Si, Jierui

Inhibiting pathogen chemotaxis is a promising strategy for reducing disease pressure. However, this strategy is currently in the proof-of-concept stage. Here, Phytophthora sojae was used as a model, as its biflagellated zoospores could sense genistein, a soybean root exudate, to navigate host and initiate infection. We identify P. sojae IRK1 (isoflavone-insensitive receptor kinase 1) as a receptor for genistein, with PsIRK2 functioning as a coreceptor that enhances the binding affinity of PsIRK1 to genistein and regulates chemotaxis by phosphorylating G protein α subunit. Last, we identify an antagonist, esculetin, which disrupts the PsIRK1-genistein interaction, thereby preventing P. sojae infection by repelling zoospores. Our findings reveal the mechanism by which P. sojae senses host genistein and demonstrate a strategy for disease prevention by targeting the chemoreceptor.

100 项与 Esculetin 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
动脉粥样硬化	临床前	-	CSIR-Indian Institute of Chemical Biology	2024-05-17
动脉粥样硬化	临床前	-	Academy of Scientific & Innovative Research	2024-05-17