Isolation of Lessertiosides A and B and Other Metabolites from Lessertia frutescens and Their Neuroprotection Activity

Lessertia frutescens (synonym Sutherlandia frutescens) is an important South African medicinal plant used traditionally to treat different human pathologies and is considered an adaptogenic plant. This study sought to isolate compounds from the plant and determine their protective potentials using SH-SY5Y cells and MPP⁺ (1-methyl-4-phenylpyridinium) to mimic Parkinson's disease. The phytochemical analysis of a 70% aqueous methanolic extract of L. frutescens leaves resulted in the isolation and identification of 11 pure compounds (1-11), among which compounds 1 and 2 were identified as new metabolites. The new compounds were characterised using IR, UV, NMR, and HRESIMS and were given the trivial names lessertiosides A (1) and B (2). Additionally, the flavonoids 8-methoxyvestitol (7) and mucronulatol (8) were isolated for the first time from the plant. The biological actions show that the isolated compounds had negligible toxicity on SH-SY5Y cells and improved cell viability in the cells exposed to MPP⁺. Furthermore, as a mechanism of action, the compounds could sustain cellular ATP generation and prevent MPP⁺-induced apoptotic cell death. Our findings provide evidence for the neuroprotective properties of compounds isolated from L. frutescens in MPP⁺-induced neuronal damage for the first time and create an avenue for these compounds to be further investigated to elucidate their molecular targets.