Effects of betulinic acid on inflammation and apoptosis intrinsic pathway in a chronic neuroinflammation model induced by lipopolysaccharide in rats

Aim: This thesis aimed to evaluate the effects of betulinic acid on inflammation and the intrinsic apoptotic pathway in a lipopolysaccharide (LPS)-induced experimental neuroinflammation model using molecular, biochemical, and histopathological analyses. Material and Method: Rats were divided into four groups: Control, LPS, BA, and BA+LPS. LPS (1 mg/kg, i.p.) and betulinic acid (10 mg/kg, i.p.) were administered intermittently for 28 days. Brain tissue and serum samples were analyzed for systemic biochemical parameters and CASP3, CASP9, BAX, BCL-2, NF-κB, and Cyt c levels using ELISA, RT-qPCR, and histopathological methods. Results: In the LPS group, serum BUN, total protein, direct bilirubin, sodium, and chloride levels increased, whereas calcium levels decreased (P < 0.05). BA administration showed regulatory effects on several biochemical parameters. Oxidative stress analyses demonstrated increased MDA levels in the BA+LPS group, while GSH and SOD levels were elevated in the LPS group (P < 0.05). Tissue ELISA analyses revealed increased CASP3 levels in the BA group and increased Cyt c levels in the BA+LPS group (P < 0.05). Serum ELISA findings showed elevated Cyt c and decreased BCL-2 levels in the BA+LPS group (P < 0.05). NF-κB gene expression increased in the LPS group but decreased in BA and BA+LPS groups. Cyt c expression increased in LPS and BA+LPS groups, whereas BCL2 gene expression decreased in BA and BA+LPS groups (P < 0.05). Histopathological examination revealed infiltration, edema, hyperemia, and hemorrhage in the LPS group, while these alterations were reduced in BA-treated groups. Conclusion: Betulinic acid may exert regulatory and neuroprotective effects on inflammatory, oxidative, and mitochondrial apoptotic processes in LPS-induced neuroinflammation. Keywords: Betulinic Acid, LPS, Neuroinflammation, Apoptosis, Inflammation