Methanolic Extract of Cissus quadrangularis Attenuates Diet-Induced Obesity Through Hypophagia and Adiponectin Secretagogue Activity, Independent of Digestive Enzyme Inhibition

Abstract

Cissus quadrangularis (Vitaceae), locally known as Hadjod, is a constituent of numerous commercial anti-obesity formulations, yet the pharmacological basis of its weight-reducing action has remained inadequately resolved, with most supportive evidence originating from industry-sponsored trials that did not interrogate mechanism at the bench level. The present study standardised a methanolic extract of C. quadrangularis stem (CQME, β-ecdysone content 0.87 ± 0.04% w/w by validated HPTLC) and evaluated its digestive-enzyme-inhibitory, toxicological and anti-obesity profile in a high-fat-diet (HFD)-fed Wistar rat model, benchmarked against orlistat and a comparator ethanolic extract of Momordica charantia (MCEE).

CQME showed only weak, non-specific inhibition of pancreatic lipase, α-amylase and α-glucosidase; the apparent lipase-inhibitory activity observed in the initial assay (IC₅₀ 214.6 µg/mL) collapsed almost completely on repetition in the presence of 1% w/v bovine serum albumin (18.9% versus 56.3% inhibition at 250 µg/mL, p<0.0001), confirming that CQME does not act as a genuine digestive-enzyme inhibitor. Acute and 28-day repeated-dose toxicity studies established a no-observed-adverse-effect level of 1000 mg/kg/day. In the 8-week HFD efficacy study, the high dose of CQME (500 mg/kg) lowered terminal body weight by 11.1% relative to HFD-control (p<0.05), a reduction attributable principally to a 14.2% fall in food intake (p<0.05) rather than to any change in feed efficiency ratio (5.52 ± 0.40% versus 5.87 ± 0.42% in HFD-control, not significant), indicating a centrally mediated, hypophagic mode of action. CQME lowered total cholesterol and triglycerides by 18.3% and 28.1% respectively and reduced HOMA-IR by 34.2% (all p<0.05--0.01), but its most distinctive effect was a 54.8% elevation of serum adiponectin (from 3.65 ± 0.42 to 5.65 ± 0.58 µg/mL; p<0.001 versus HFD-control) --- significantly greater than that produced by MCEE (+18.5%, p=0.082), orlistat (+22.7%, p<0.05), or the aqueous extract (+9.0%, not significant). This adiponectin elevation correlated with selective resolution of hepatic inflammation and a shift toward smaller adipocytes, consistent with adiponectin-mediated adipose tissue remodelling. Hepatic histology showed a selective reduction in lobular inflammation with only partial improvement in steatosis, consistent with an adiponectin-mediated anti-inflammatory action rather than simple caloric restriction.

These findings identify CQME as a botanical adiponectin secretagogue and hypophagic agent that is mechanistically distinct from lipase-inhibitor-type anti-obesity agents such as orlistat, and provide the first specificity-controlled evidence that its traditional reputation for weight management is not attributable to luminal enzyme inhibition.