Morutamins A-L from Morus alba L. Root Bark with Inhibitory Effects on Epidermal Growth Factor Receptor and Toll-Like Receptor-Mediated NF-κB/AP-1 Activation

Abstract

Morus alba L. root bark (MAR, “Sang-Bai-Pi” in traditional Chinese medicine) has been traditionally used for the treatment of inflammatory disorders. Phytochemical investigation of MAR yielded 11 new flavanones and one new chalcone (1–12, morutamins A–L), along with 27 known compounds (13–39). Their structures and absolute configurations were elucidated by combining HRESIMS and NMR analyses with DP4 and DP4+ probability calculations and ECD data. Among these, morutamin L (12) exhibited potent anti-inflammatory and immunomodulatory activities by inhibiting epidermal growth factor receptor and toll-like receptor agonist-induced NF-κB/AP-1 activation, which were explored through network pharmacology, molecular docking, and experimental verification. SwissADME analysis further indicated that morutamin L possesses favorable oral bioavailability and drug-likeness profiles. These findings highlight M. alba root bark as a promising source of lead compounds for the development of functional food ingredients or nutraceuticals targeting inflammation-related disorders.