Multifaceted neuroprotective role of Buchanania lanzan seeds in diabetic neuropathy: In vivo and in silico studies.
📄 Abstract
Buchanania lanzan Spreng. (Anacardiaceae) seeds (BLHA) are the cheaper alternative to almonds used in the confectionery industry. The flour powder of seeds is used as a thickening agent to prepare sauces and flavourings for a batter. The socioeconomic importance of this species lies in its medicinal properties for curing diabetes. The study explored the multifaceted neuroprotective role of BLHA (500 mg/kg) in hyperlipidic high-fat diet streptozotocin (HFD/STZ)-induced type2 diabetic neuropathy (T2DN) rats via glucose metabolism, insulin resistance, and inflammation to mitigate nerve damage. Molecular docking analysis was performed to identify specific molecular targets of bioactive compounds in T2DN pathogenesis. Serum diabetic parameters, such as serum glucose (SG), insulin (SI), total protein (TP), triglycerides (TG), blood urea nitrogen (BUN), creatinine (Cr), HDL-C, and LDL-C, were studied. A strong correlation between HbA1C and insulin resistance assessed by HOMA-IR. Oxidative stress triggers the production of free radicals, so the antioxidant indicators in serum, tissues, and proinflammatory cytokines in the liver, brain, and pancreas were measured in T2DN rats. Effects on neurochemicals, BACE1, Aβ BLHA at 500 mg/kg significantly improved hyperglycemic (SG, SI, HOMA-IR, HbA1C), hepatic (AST, ALT, ALP, TP, TB), dyslipidemic (TC, TG, HDL-C, LDL-C), and kidney function markers (creatinine, BUN) in T2DN rats. BLHA restored oxidative (CAT, GSH, SOD, MDA) and cytokine markers (TNF-α, IL6) in the liver, pancreas, and brain cortex. Oxidative stress-impaired neurotransmitters were alleviated by enhancing cholinesterase (AChE, BChE) and BACE1 activities, and by ameliorating Aβ The multifaceted actions of dietary polyphenols, antioxidants, and antidiabetic compounds (Catechol, 2-Hydroxy-5-methylbenzaldehyde, 8-Octadecenoic acid methyl ester, n-Hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl ester, β-Sitosterol, Hexadecenoic acid methyl ester) in BLHA modulated glucose metabolism, restored HOMA-IR, and reduced inflammation by protecting against oxidative stress, as a result, it improved neurotransmission and reduced neuropeptide aggregation in T2DN rats. The dock score of β-sitosterol (AChE: -12.7; BChE: -14.8; IL6: -9.8; and Atp1a3: -13.3 kcal/mol) correlated with the experimental evidence.