{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:17:02Z","timestamp":1787894222951,"version":"build-2784847793"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"crossref","award":["2024A1515012809"],"award-info":[{"award-number":["2024A1515012809"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Major Science and Technology Project on Traditional Chinese Medicine in Guangzhou","award":["2025QN003"],"award-info":[{"award-number":["2025QN003"]}]},{"name":"Scientific Research Project of Traditional Chinese Medicine Bureau of Guangdong Province","award":["20251034"],"award-info":[{"award-number":["20251034"]}]},{"award":["20251034"],"award-info":[{"award-number":["20251034"]}],"id":[{"id":"https:\/\/ror.org\/05vkkzf98","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University-Hospital Joint Fund Project of Guangzhou University of Chinese Medicine","award":["GZYSE2024G07"],"award-info":[{"award-number":["GZYSE2024G07"]}]},{"award":["GZYSE2024G07"],"award-info":[{"award-number":["GZYSE2024G07"]}],"id":[{"id":"https:\/\/ror.org\/03qb7bg95","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangdong Medical Science and Technology Research Fund Project","award":["B2026103"],"award-info":[{"award-number":["B2026103"]}]},{"name":"Guangdong Provincial Administration of Traditional Chinese Medicine Scientific Research Project","award":["20262004"],"award-info":[{"award-number":["20262004"]}]},{"name":"Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine","award":["KFKT25064"],"award-info":[{"award-number":["KFKT25064"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objective: Traditionally derived from the dried leaves of Microcos paniculata L., Microctis folium (M. folium) has been employed to manage various inflammatory and metabolic conditions. Despite its reported hypolipidemic potential, the active constituents contributing to this effect and their molecular mechanisms of action remain to be determined. Therefore, this study aimed to systematically identify the active hypolipidemic constituents of M. folium and elucidate their mechanisms of action through an integrated strategy combining chemical profiling, pharmacokinetic screening, network pharmacology, and experimental validation. Methods: UPLC fingerprint and UPLC-QQQ-MS\/MS were employed to characterize and quantify the chemical constituents of M. folium. Pharmacokinetic analysis was conducted to identify systemically absorbed compounds. Network pharmacology was applied to predict potential targets and signaling pathways. The lipid-lowering effects were subsequently validated in vitro using an oleic acid\/palmitic acid (OA\/PA)-induced lipid accumulation model in HepG2 cells and in vivo in a Triton WR-1339-induced hyperlipidemia mouse model. Results: UPLC fingerprint analysis identified 15 common peaks among 21 batches of M. folium, with similarity values ranging from 0.885 to 0.990, indicating good chemical consistency. Eighteen representative compounds were quantified, among which flavone C-glycosides and phenolic acids were predominant. Pharmacokinetic results demonstrated that multiple M. folium\u2019s constituents were absorbed into systemic circulation. Network pharmacology analysis identified 73 potential targets related to hyperlipidemia and highlighted the PI3K-Akt signaling pathway as a key regulatory pathway. In vitro experiments showed that M. folium\u2019s compounds significantly reduced intracellular lipid accumulation and oxidative stress in OA\/PA-induced HepG2 cells. Furthermore, in vivo studies demonstrated that vitexin, ferulic acid, isoferulic acid, and N-trans-feruloyltyramine significantly reduced serum and hepatic lipid levels, including TC, TG, and LDL-c, alleviated hepatic steatosis, and improved liver injury and oxidative stress markers in Triton WR-1339-induced hyperlipidemic mice. Conclusions:\u00a0M. folium exerts significant lipid-lowering effects through multi-component and multi-target mechanisms involving regulation of lipid metabolism and oxidative stress, partly mediated by activation of the PI3K-Akt signaling pathway. These findings provide a scientific basis for the development of M. folium\u2019s natural agents for the treatment of hyperlipidemia.<\/jats:p>","DOI":"10.3390\/ph19091349","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:59:23Z","timestamp":1787741963000},"page":"1349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Hypolipidemic Constituents from Microctis folium Using an Integrated Strategy of Chemical Profiling, Pharmacokinetics, Network Pharmacology and Experimental Validation"],"prefix":"10.3390","volume":"19","author":[{"given":"Zhihao","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine Analysis, Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou 510095, China"},{"name":"Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou 510095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchang","family":"Liu","sequence":"additional","affiliation":[{"name":"The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Analysis, Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou 510095, China"},{"name":"Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou 510095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhui","family":"Ouyang","sequence":"additional","affiliation":[{"name":"The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingnian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Analysis, Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou 510095, China"},{"name":"Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou 510095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weitao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Analysis, Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou 510095, China"},{"name":"Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou 510095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5912-8434","authenticated-orcid":false,"given":"Guanlin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Analysis, Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou 510095, China"},{"name":"Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou 510095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108775","DOI":"10.1016\/j.steroids.2020.108775","article-title":"Potential role of mycosterols in hyperlipidemia\u2014A review","volume":"166","author":"Das","year":"2021","journal-title":"Steroids"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2165\/00002018-200730030-00003","article-title":"Psychiatric adverse reactions with statins, fibrates and ezetimibe: Implications for the use of lipid-lowering agents","volume":"30","author":"Tatley","year":"2007","journal-title":"Drug Saf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.2147\/DDDT.S514498","article-title":"The Active Components of Traditional Chinese Medicines Regulate the Multi-Target Signaling Pathways of Metabolic Dysfunction-Associated Fatty Liver Disease","volume":"19","author":"Song","year":"2025","journal-title":"Drug Des. 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