Pharmacological Potential and Molecular Targets of Tetrahydrofurofuranoid Lignans From Magnoliae Flos

Xiaohan Yi, Zixuan Xiao, Jiaxue Chen, Guoren Chen, Ping Ma School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of ChinaCorrespondence: Ping Ma, School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, No.1166, Liutai Avenue, Wenjiang District, Chengdu, 611137, People’s Republic of China, Email [email protected]: Tetrahydrofurofuranoid lignans (TFLs) are lignans extracted from the dried flower buds of Magnoliae Flos (MF). The chemical structures of the seven major constituents, magnolin, fargesin, aschantin, lirirresinol B dimethyl ether, epimognolin, eudesmin, and kobusin, are strikingly similar. Despite their potential therapeutic effects against various pathological conditions, their underlying mechanisms have not been systematically analyzed. The primary objective of this review was to examine the mechanisms by which TFLs exert therapeutic effects on inflammation, allergies, cancer, cardiovascular diseases, metabolic disorders and osteoarticular diseases. Data were retrieved from scientific databases, including PubMed, Web of Science, and Google Scholar, up to November 2024. The search terms employed included “Magnoliae Flos” or “Magnolia” and “Lignans” “Tetrahydrofurofuranoid” “Magnolin” “Fargesin” “Aschantin” “Lirirresinol B dimethyl ether” “Epimagnolin” “Eudesmin” and “Kobusin.” TFLs have been demonstrated to treat various inflammatory diseases through inhibition of signaling pathways, including NF-κB and MAPK. Additionally, allergic reactions are suppressed via inhibition of mast cell degranulation-related receptors. Furthermore, anticancer activity is achieved by triggering signaling pathways such as PI3K/AKT/mTOR, ERK/MEK, and P53. Besides enhancing glucose metabolism, TFLs suppress adipogenesis through downregulation of pathways involving PI3K/Akt, Akt/AMPK, and P-selectin expression. Fargesin, a notable compound derived from MF, exerts cardioprotective effects by inhibiting the cAMP/PKA pathway and counteracts atherosclerosis through the downregulation of the TLR4/NF-κB signaling pathway. Notably, TFLs also demonstrate the ability to reduce melanin synthesis by suppressing tyrosinase, associated proteins, MITF, and enzymes involved in melanogenesis. Growing research highlights diverse pharmacological attributes of TFLs, providing critical insights for future studies aimed at developing novel therapeutics exhibiting enhanced efficacy and minimal toxicity for inflammation, cancer, cardiovascular disorders, diabetes, skin ultraviolet damage and osteoporosis.Keywords: Xin-yi, Magnolia, Lignans, pharmacology, mechanisms, toxicity