[Research progress on intervention of active components of Bupleuri Radix in metabolic dysfunction-associated fatty liver disease based on multiple parallel strike theory].

Metabolic dysfunction-associated fatty liver disease(MAFLD) is a prevalent chronic liver disease worldwide. Due to its complex pathogenesis, there is currently no specific drug capable of intervening throughout the entire pathological process, nor a unified and definitive treatment protocol in clinical practice. In traditional Chinese medicine, MAFLD falls under the category of diseases such as "hypochondriac pain" and "liver disease", with the core pathogenesis being "stagnation of the liver meridian and obstruction of Qi movement". The pharmacological characteristics of Bupleuri Radix(BR), which "soothes the liver, relieves stagnation, and promotes Qi movement", are highly consistent with this pathogenesis. Furthermore, data mining studies have shown that BR is among the most frequently used herbs in TCM clinical protocols for treating MAFLD, and its herb pairs and classic formulas have demonstrated favorable therapeutic effects in clinical application. Modern pharmacological studies have also confirmed that BR is rich in active ingredients, including saponins(e.g., saikosaponin A/D/B2), volatile oils(e.g., D-limonene, hexanoic acid), flavonoids(e.g., quercetin, rutin, kaempferol), and polysaccharides. These active ingredients can target multiple pathological aspects of the "multiple parallel hits" in MAFLD, such as improving insulin resistance(IR), alleviating endoplasmic reticulum stress(ERS), repairing mitochondrial function, regulating oxidative stress(OS) response, modulating intestinal microbiota imbalance, and inhibiting inflammasome activation, thereby slowing the progress of MAFLD. Its mechanism of action is closely related to the regulation of PI3K/Akt, PPAR, Nrf2, AMPK, MAPK, PINK1/Parkin, NLRP3 inflammasome and the "gut-liver axis", reflecting the integrative regulatory advantages of TCM's multi-component, multi-target and multi-mechanism approach. Future in-depth studies should focus on precise component profiling of BR, validation of key targets, and the synergistic mechanisms within "formula-component" interactions to better leverage the value of BR in the prevention and treatment of MAFLD.