In vivo metabolism combined network pharmacology to identify anti-constipation constituents in Aloe barbadensis Mill

Aloe barbadensis Mill. (Aloe vera), is a homology of medicine and food plant, widely applied in functional food, cosmetics, and medicine. Aloe vera whole leaf extract, one of the most popular traditional Chinese medicines (TCMs), is mainly used in China to treat functional constipation.To elucidate the active constituents of Aloe vera for treating functional constipation.Prototype constituents and metabolites in rat plasma and excreta after oral administration of Aloe vera whole leaf extract were identified by UPLC-Q-TOF/MS, and the pharmacokinetics (PK) properties of its key anti-constipation constituents speculated by network pharmacology were investigated via the established UFLC-MS/MS method.A total of 13 prototype constituents and 56 metabolites were identified in rat plasma, urine, and feces after oral administration of Aloe vera. Among them, aloesin, aloenin, aloin B, aloin A, and aloe-emodin were intimately connected to the core targets of constipation in network pharmacology analysis, and recognized as major anti-constipation constituents in Aloe vera. The validated quantitative method of the six active constituents in rat plasma exhibited good linearity, and lower limits of quantification (0.64-1.95 ng/mL). Aloin A, aloin B, aloeresin D and aloe-emodin exhibited better absorption and slower elimination rate, whereas the others, including aloesin and aloenin showed fast absorption and elimination in rat plasma after oral administration of Aloe vera. Aloin A and its isomer aloin B present similar Tmax and t1/2 but different AUC and Cmax values, indicating different relative bioavailability. The results suggested that aloin A, aloin B and aloe-emodin may be key constituents of Aloe vera for the treatment of constipation, and the other constituents including aloeresin D also contribute to its anti-constipation.This study will benefit understanding the contributions of those constituents for the anti-constipation effect of Aloe vera and also provide valuable information for its application in functional food development and clinics.