Nimbolide attenuate the lipid accumulation, oxidative stress and antioxidant in primary hepatocytes

Abstract

Nimbolide is a bioactive compound found in Azadirachta indica. This work was devised to investigate the potential effects of nimbolide on intracellular lipid deposition and its associated redox modulation in primary hepatocytes (Heps). Lipid accumulation was induced in Heps by supplementing 1 mM oleic acid for 24 h which was marked by significant accumulation of lipids. The results demonstrated that nimbolide can decrease intracellular cholesterol, free fatty acids and triglycerides. Nimbolide may also improve hepatocytes function through its antioxidant effects by inhibiting oxidative DNA damage and lipid peroxidation by curtailing the reactive oxygen species levels. Further it also restore the mitochondrial potential, improving the endogenous antioxidant levels such as GSH and antioxidant enzyme activities. Nimbolide increased (P < 0.05) liver X receptor-α (LXRα), peroxisome proliferator-activated receptor-γ (PPARγ) and sterol regulatory element-binding protein-1c (SREBP1c) gene expression in Heps. The biological significance of nimbolide may involve hypolipidemic effect, lipid peroxidation inhibition, DNA damage inhibition, ROS inhibition, restoring mitochondrial function, increases in GSH and SOD & CAT activities, and direct regulation of LXRα, PPARγ and SREBP1c gene expression. Nimbolide may be used as effective lipid lowering compound and lipid deposition-induced Heps changes.

Protective role of germinated mung bean against progression of non-alcoholic steatohepatitis in rats: A dietary therapy to improve fatty liver health

“…The excised liver tissues were processed as mentioned in Alshammari, Balakrishnan, and Chinnasamy (). The pathophysiological changes in NAFLD, treated animals, and healthy control liver sections were observed as explained by Xin et al ().…”

“…Newly prepared cDNA was used as a template for quantitative real‐time polymerase chain reaction (qRT‐PCR). The cDNA were quantified as explained Alshammari et al (). Table shows the primer sequence used to amplify the gene of interest.…”

Nimbolide, a Neem Limonoid, Is a Promising Candidate for the Anticancer Drug Arsenal

“…Nimbolide was reported to significantly lower the levels of cholesterol, free fatty acids and triglycerides, as well as lipid deposition-induced changes in primary hepatocytes. Additionally, nimbolide also improved hepatocyte function by multiple mechanisms including inhibition of reactive oxygen species (ROS)-induced oxidative DNA damage and lipid peroxidation, enhancement of antioxidant defenses, and by regulating the expression of liver X receptor-α (LXRα), peroxisome proliferator-activated receptor-γ (PPAR-γ), and sterol regulatory element-binding protein-1c (SREBP1c) …”

“…Additionally, nimbolide also improved hepatocyte function by multiple mechanisms including inhibition of reactive oxygen species (ROS)-induced oxidative DNA damage and lipid peroxidation, enhancement of antioxidant defenses, and by regulating the expression of liver X receptor-α (LXRα), peroxisome proliferator-activated receptor-γ (PPARγ), and sterol regulatory element-binding protein-1c (SREBP1c). 25 3.4. Detoxifying, Antioxidant, and Antigenotoxic Effects.…”

Harnessing the Anti-Cancer Natural Product Nimbolide for Targeted Protein Degradation

“…In the context of cancer, nimbolide has been shown to inhibit tumorigenesis and metastasis without causing any toxicity or unwanted side effects across a wide range of cancers 10,11,[13][14][15][16][17] . While previous studies suggest that nimbolide impairs cancer pathogenicity through modulating signaling pathways and transcription factors linked to survival, growth, invasion, angiogenesis, inflammation, and oxidative stress the direct targets of nimbolide still remain poorly characterized 10,15,[18][19][20][21][22] .…”