Xinxiang Chen

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-κB/MAPK, PI3K/Akt, and PPAR-γ 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.

Alpinetin, a distinctive plant-derived dihydroflavonoid from cardamom seeds, represents an under-explored chemical scaffold compared to common flavonoids like quercetin or kaempferol. While many flavonoids have shown general cardioprotective potential, the structural specificity of alpinetin may confer unique pharmacological advantages. Inspired by its historical use in traditional Chinese medicine for cardiac discomfort, this study systematically investigated its efficacy against acute myocardial infarction (AMI). In a rat AMI model, alpinetin demonstrated superior infarct size reduction and functional recovery relative to other tested flavonoids. It significantly attenuated key AMI pathologies—including inflammatory infiltration, CD68+ macrophage activation, IL-6/TNF-α release, collagen deposition, and cardiomyocyte apoptosis—more effectively than common flavonoid benchmarks. Mechanistically, alpinetin selectively targeted the TLR4/MyD88/NF-κB signaling axis with notable potency, a pathway not robustly modulated by other flavonoids in the screening. These findings not only validate the traditional wisdom of cardamom but also establish alpinetin as a structurally and mechanistically distinct flavonoid with high translational promise, offering a new candidate for the targeted treatment of ischemic heart disease.