Polyphenol‑Enriched Fraction and the Compounds Isolated from Garcinia indica Fruits Ameliorate Obesity through Suppression of Digestive Enzymes and Oxidative Stress

Objective: To explore the anti-obesity effect of polyphenol‑enriched fraction and the compounds isolated from G. indica fruits through the inhibition of key metabolizing enzymes and oxidative stress. Materials and Methods: Fruits of G. indica were extracted with methanol that was subjected to liquid–liquid extraction to yield ethyl acetate fraction (FGIEF), chloroform, butanol, and aqueous fractions. The extract and the fractions were screened for the total polyphenols content (TPC), total flavonoids content (TFC), pancreatic lipase (PL) and α‑amylase inhibition, and antioxidant activity. The effect of FGIEF on the viability of 3T3‑L1 preadipocytes using 3‑(4,5‑dimethylthiazol‑2‑yl) 2,5‑diphenyltetrazolium bromide assay was assessed. FGIEF was subjected to normal‑phase medium‑pressure liquid chromatography (MPLC) to isolate compounds 1–3. Docking studies of representative polyphenols and the isolated compounds 1–3 with PL were undertaken to derive supporting evidence. Results: Among all the fractions, FGIEF was found to have the highest TPC (375.6 ± 4.5 gallic acid equivalent mg/g) and TFC (237.2 ± 6.2 quercetin equivalent mg/g). The extract and fractions showed concentration‑dependent digestive enzyme inhibition and antioxidant effect. FGIEF inhibited PL and α‑amylase (IC50 values 257.3 ± 3.7 and 349.7 ± 5.8 µg/mL, respectively). FGIEF did not induce any cell death up to 800 µg/mL. MPLC of FGIEF led to the isolation of luteolin (1), napthyldioxolol (2), and oleantrienoic acid glucoside (3). Preferential inhibition by polyphenols compared to other compounds was notable in the docking studies. Conclusion: The study suggests that the fruits of G. indica exhibit anti-obesity effect through the inhibition of digestive enzymes that can be mainly attributed to the presence of polyphenols.