{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:28:14Z","timestamp":1785432494248,"version":"3.56.0"},"reference-count":163,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370299"],"award-info":[{"award-number":["81370299"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["81370299"],"award-info":[{"award-number":["81370299"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National College Student Innovation and Entrepreneurship Training Program","award":["2019A078"],"award-info":[{"award-number":["2019A078"]}]},{"name":"National College Student Innovation and Entrepreneurship Training Program","award":["2021A082"],"award-info":[{"award-number":["2021A082"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Human diseases remain a major global health challenge, requiring effective therapeutic strategies. Traditional Chinese medicine (TCM) has been widely used in clinical settings. Many natural compounds, such as flavonoids from TCM, exhibit diverse pharmacological activities. Alpinetin and pinocembrin are structurally related flavonoids. Alpinetin is derived from Zingiberaceae plants, and pinocembrin is extracted from wild marjoram (origanum vulgare) or other natural sources. They possess a wide range of pharmacological activities or biological effects, including anti-inflammatory, anti-tumor, liver and kidney protection, cardiovascular protection, and antibacterial activities. Methods: The present comparative review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using four major databases (PubMed, EMBASE, Web of Science, and Cochrane Library), as well as CNKI without language restrictions. Results: Pharmacokinetic studies reveal distinct absorption, metabolism, and excretion profiles. Alpinetin and pinocembrin undergo glucuronidation and interact with cytochrome P450 enzymes and transporters. However, alpinetin has demonstrated approximately 1.5-fold higher plasma exposure and slower clearance compared to pinocembrin. Mechanistically, alpinetin exerted therapeutic effects through modulation of the NF-\u03baB\/MAPK, PI3K\/Akt, and PPAR-\u03b3 signaling pathways, resulting in a 2- to 3-fold reduction in pro-inflammatory cytokines. In contrast, pinocembrin exerted protective activity through the inhibition of HMGB1\/TLR4 signaling, regulation of endoplasmic reticulum stress, and activation of Nrf2\/HO-1, leading to a 1.8-fold increase in antioxidant enzyme activity. The minimum inhibitory concentrations were reduced by 2- to 4-fold against Gram-positive bacteria compared to alpinetin. Conclusions: These findings highlight the pharmacological potential of alpinetin and pinocembrin as promising candidates for the development of novel anti-tumor, anti-inflammatory, liver and kidney protection, cardiovascular protection, and antibacterial agents. However, research on the pharmacological actions of alpinetin and pinocembrin is still in the preclinical stage. Further research is required to validate their efficacy in clinical settings, especially for translation to clinical studies. This is critical to translating these natural flavonoids into effective therapeutic agents while addressing the regulatory challenges and pathways associated with botanical drugs in human diseases.<\/jats:p>","DOI":"10.3390\/ph19050734","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T14:05:46Z","timestamp":1778162746000},"page":"734","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Pharmacological Actions of Alpinetin and Pinocembrin\u2014A Comparative Review"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2914-2860","authenticated-orcid":false,"given":"Xinxiang","family":"Chen","sequence":"first","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0454-2048","authenticated-orcid":false,"given":"Siu Kan","family":"Law","sequence":"additional","affiliation":[{"name":"Independent Researcher, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huajian","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Panyu Central Hospital of Guangzhou Medical University, Guangzhou 511400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenying","family":"Yu","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiao","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert Wing Nang","family":"Leung","sequence":"additional","affiliation":[{"name":"School of Graduate Studies, Lingnan University, Tuen Mun, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5107-8105","authenticated-orcid":false,"given":"Chuanshan","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Feng","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref_1","first-page":"809","article-title":"Qu\u2019est-ce qu\u2019une maladie? 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