Siamese neem flower extract suppresses cholesterol absorption by interfering NPC1L1 and micellar property in vitro and in intestinal Caco-2 cells

Abstract

Siamese neem (Azadirachta indica A. Juss var. siamensis Valeton ) ( A. indica ) leaf extract, a traditional ayurvedic medicine, has been reported to exhibit antipyretic, antibacterial, antidyslipidemic, and antihyperglycemia effects. This study investigated the mechanism of hypocholesterolemic effect of methanolic extract of Siamese neem flowers in in vitro studies and in Caco-2 cells. Pancreatic cholesterol esterase and 3-hydroxy 3-methylglutaryl-CoA (HMG-CoA) reductase activities were assessed. Cholesterol micelle formation was prepared for in vitro cholesterol physicochemical property analyses, micelle size and solubility, and transport of cholesterol into the Caco-2 cells. The expression of niemann-pick C1 like 1 (NPC1L1), and its major regulator, peroxisome proliferator-activated receptor δ (PPARδ), were determined by western blot and real time polymerase chain reaction, respectively. A. indica flower extract inhibited pancreatic cholesterol esterase activity and increased cholesterol micelles size. Uptake of cholesterol into Caco-2 cells was inhibited by A. indica flower extract in a dose-dependent manner. In addition, A. indica extract inhibited HMG-CoA reductase activity, resulting in low level of intracellular cholesterol accumulation, together with increased cytosolic NPC1L1 protein expression and decreased PPARδ gene expression. In conclusion, A. indica flower extract has cholesterol-lowering effects by inhibiting intestinal cholesterol absorption, interfering micellar cholesterol formation, and attenuating cholesterol synthesis. As such, A. indica flower extract has potential for developing into nutraceutical product for prevention of hypocholesterolemia.

Salvia officinalis flowers extract ameliorates liver and kidney injuries induced by simultaneous intoxication with ethanol/castor oil

“…However, the protective potential of SF‐AE is in line with Duangjai et al. (2019) who showed that Azadirachta indica extract exerted, in vitro, a powerful lipid profile parameters regulatory activity.…”

Effect of Neem Leaf Extract on Reproductive Potential of Male Rats Fed High-Fat Diet

“…The content of compounds in neem can interfere with cholesterol absorption and inhibit de novo cholesterol synthesis (Duangjai et al, 2019). The content of alkaloids is able to inhibit the performance of lipase enzymes in the gastrointestinal tract so that fat absorption in the body is reduced (Budiarto et al, 2016).…”