Thonningianin A

Thonningianins A (1) and B (2), have been isolated from the African medicinal herb Thonningia sanguinea and their structures elucidated by interpretation of spectroscopic data. Both 1 and 2 showed strong free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) as shown by ESR analysis ¹⁾.

Results indicate that the antioxidant properties of Th A involve radical scavenging, anti-superoxide formation and metal chelation ²⁾.

Four ellagitannin flavonoids, including pinocembrin-7-O-[4″,6″-hexahydroxydiphenoyl]-glucoside (PHG), pinocembrin-7-O-[3″-O-galloyl-4″,6″-hexahydroxydiphenoyl]-glucoside (PGHG), thonningianin A (TA), and thonningianin B (TB), were identified to be autophagy enhancers in PCP.

Among these, TA exhibited the strongest autophagy induction effect, and the mechanistic study demonstrated that TA activated autophagy via the AMPK/ULK1 and Raf/MEK/ERK signaling pathways. In addition, TA effectively promoted the autophagic degradation of NLRP3 inflammasome in Aβ(1-42)-induced microglial cells and ameliorated neuronal damage via autophagy induction. In vivo, TA activated autophagy and improved behavioral symptoms in C. elegans. Furthermore, TA might penetrate the blood-brain barrier and could improve cognitive function and ameliorate the Aβ pathology and the NLRP3 inflammasome-mediated neuroinflammation via the AMPK/ULK1 and Raf/MEK/ERK signaling pathways in APP/PS1 mice.

Zhou et al. identified thonningianin A as a potent microglial autophagy enhancer in enthorum chinense Pursh (PCP) that promotes the autophagic degradation of the NLRP3 inflammasome to alleviate the pathology of Alzheimer's disease via the AMPK/ULK1 and Raf/MEK/ERK signaling pathways, which provides novel insights for TA in Alzheimer's disease treatment ³⁾.