Plumbagin exerts antiobesity effects through inhibition of pancreatic lipase and adipocyte differentiation

Abstract

Plumbagin is a naphthoquinone found in the roots of Plumbago zeylanica. Here, we report an investigation to evaluate its antiobesity activity. The preliminary binding affinity of plumbagin to human pancreatic lipase (PL) was determined using molecular docking simulation. The in vitro PL inhibitory potential and the kinetics of inhibition were studied to validate and confirm the results obtained from molecular docking. The IC for PL was found to be 82.08 ± 9.47 μM, and the kinetics of inhibition was found to be of the mixed type. Further, the in vivo evaluation revealed that rats treated with plumbagin 1 mg/kg showed significant decrease in serum triglycerides (TG) and area under the curve of serum TG when compared with vehicle-treated rats. It was also seen that plumbagin possessed significant antiadipogenic effect as demonstrated by reduced oil red O staining and decreased TG contents. Thus, we conclude that plumbagin is a promising molecule to combat obesity and further optimization of plumbagin to yield plumbagin analogues will result in its improved activity profile.

Chrysin mitigated obesity by regulating energy intake and expenditure in rats

“…The serum TG levels were estimated using a commercial kit (Erba Mannheim®, GmbH) and the area under the curve (AUC) of serum TG was determined. 12 …”

A mechanistic review of plumbagin effects againts diabetes and obesity

“…In contrast, plumbagin was shown to inhibit lipolysis. Study by Pai et al (2018) showed that plumbagin inhibited porcine pancreatic lipase (IC50 82.08±9.47 μM), an enzyme that involves in the catalytic degradation of triglycerides. Inhibition kinetics study showed that plumbagin inhibited lipase in a mixed type mode.…”

“…Docking study of the ligand-protein binding showed that plumbagin interacted with pancreatic lipase by noncovalent binding through Ser153 and the carbonyl moiety of the plumbagin. At cellular level, anti-obesity activity of plumbagin may also be accounted due to its ability to inhibit differentiation of adipocyte cells 46 .…”

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“…Lipase activity was assayed by the colorimetric method 23 , by measuring the amount of 4-nitrophenol released from 4-nitrophenyl palmitate (p-NPP) substrate. A stock solution of p-nitrophenyl palmitate was prepared in isopropanol and sonicated until complete dissolution of p-NPP.…”