Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. However, its poor systemic bioavailability fails to explain the potent pharmacological effects and hinders its clinical application. Using experimental and theoretical approaches, we compared curcumin and its degradation products for its biological activities against Alzheimer’s disease (AD), including the superoxide anion radical (O2.–)-scavenging activity, Aβ fibrils (fAβ) formation-inhibiting activity, and enzymatic inhibition activity. We showed that compared to the parent compound curcumin, the degradation products mixture possessed higher O2.–-scavenging activity and stronger inhibition against fAβ formation. The docking simulations revealed that the bioactive degradation products should make important contribution to the experimentally observed enzymatic inhibition activities of curcumin. Given that curcumin is readily degraded under physiological condition, our findings strongly suggested that the degradation products should make important contribution to the diverse biological activities of curcumin. Our novel findings not only provide novel insights into the complex pharmacology of curcumin due to its poor bioavailability, but also open new avenues for developing therapeutic applications of this natural product.

The food additive curcumin shows many benefits for human health but has low solubility and stability, which leads to its low bioavailability. After oral administration, curcumin undergoes biotransformation by gut microbiota in digestive tracts, and thus it is interesting to characterize the biotransformation products of curcumin and assess their bioactivities to help us understand the pharmacology. Herein a bacterial strain of Bacillus megaterium DCMB-002 isolated from mice feces, showed the capability of transforming curcumin to its various derivatives. The tracing high performance liquid chromatogram coupled with quadrupole time-of-flight tandem mass spectra (HPLC-Q-TOF MS n ) led to the identification of seven hydrogenation transformation metabolites through reduction, hydroxylation, demethylation and demethoxylation etc, six of which were reported for the first time. The metabolites exhibited moderate antioxidant activity. The findings provided insights into the microbial biotransformation of curcumin and roles of gut microbiota in its pharmacological effects. ARTICLE HISTORY