Acute oral toxicity and angiotensin-converting enzyme (ACE) inhibitory activity of the aqueous fractions of the methanol leaf extract of Psychotria luzoniensis

This study investigated the acute oral toxicity, in vitro angiotensin-converting enzyme (ACE) inhibitory activity, and metabolite profile of the aqueous fraction of the methanol leaf extract of Psychotria luzoniensis (PLAF), a plant endemic to the Philippines. ACE inhibition was evaluated in the crude extract, fractions, and sub-fractions through IC50 determination. The most bioactive fraction was further subjected to acute oral toxicity testing in mice at the limit dose of 2000 mg/kg body weight, while metabolite profiling was performed using UHPLC-QTOF-MS/MS. PLAF exhibited the strongest ACE inhibition (IC50 34.38 {+/-} 1.86 {micro}g/ml), prompting subsequent fractionation. Among the sub-fractions (PLAF-1A - 1E), PLAF-1D demonstrated the most potent activity (IC50 9.70 {+/-} 0.10 {micro}g/ml). Acute toxicity evaluation of PLAF revealed no mortality, behavioral abnormalities, or significant alterations in body weight, organ weights, serum biochemical parameters (SGPT, SGOT, BUN, creatinine, LDH), or histopathological changes in the liver, kidney, and heart. These findings indicate an LD50 greater than 2000 mg/kg. Metabolite profiling showed candidate flavonoids previously associated with ACE inhibition, including quercetin, kaempferol, rutin, and hyperin. Other putative compounds detected include 4-(3,4-dihydroxyphenyl)-7-hydroxy-2-oxo-2H-chromen-5-yl-{beta}-D-glucopyranoside, juncein, and butin which are rarely reported in other Psychotria species. In this study, the ACE inhibitory activity and favorable toxicity profile of P. luzoniensis highlight its pharmacological potential to support further isolation of bioactive compounds and in vivo blood pressure studies.