Morutamins A-L from Morus alba L. Root Bark with Inhibitory Effects on Epidermal Growth Factor Receptor and Toll-Like...

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.