Abstract
Diabetic encephalopathy is one of the serious emerging complication of diabetes. Securidaca inappendiculata is an important medicinal plant with excellent antioxidant and anti-inflammatory properties. This study investigated the neuroprotective effects of S. inappendiculata polyphenol rich extract (SiPE) against diabetic encephalopathy in rats and elucidated the potential mechanisms of action. Type 2 diabetes mellitus (T2DM) was induced using high fructose solution/intraperitoneal injection of streptozotocin and the diabetic rats were treated with SiPE (50, 100 and 200 mg/kg) for 8 weeks. Learning and memory functions were assessed using the Morris water and Y maze tests, depressive behaviour was evaluated using forced swimming and open field tests, while neuropathic pain assessment was assessed using hot plate, tail immersion and formalin tests. After the experiments, acetylcholinesterase (AChE), oxidative stress biomarkers and proinflammatory cytokines, caspase-3 and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) were determined by ELISA kits. In addition, the expression levels of p38, phospho-p38 (p-p38), nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by western blot analyses. The results indicated that SiPE administration significantly lowered blood glucose level, attenuated body weight loss, thermal/chemical hyperalgesia, improved behavioural deficit in the Morris water maze, Y maze test and reduced depressive-like behaviours. Furthermore, SiPE reduced AChE, caspase-3, NF-κB, malonaldehyde malondialdehyde levels and simultaneously increased antioxidant enzymes activity in the brain tissues of diabetic rats. SiPE administration also significantly suppressed p38 MAPK pathway and upregulated the Nrf2 pathway. The findings suggested that SiPE exerted antidiabetic encephalopathy effects via modulation of oxidative stress and inflammation.
Highlights
Type 2 diabetes mellitus (T2DM) is a lifelong complex metabolic disease that affects several millions of individuals globally
Significant and dose dependent decrease was observed in the final FBG levels of rats that received S. inappendiculata polyphenol rich extract (SiPE) (50, 100 and 200 mg/kg) after 8 weeks of supplementation when compared to the untreated DECA group (Figure 2A)
The diabetic rats treated with SiPE showed increased brain weight when compared to DECA control group (Figure 2C)
Summary
Type 2 diabetes mellitus (T2DM) is a lifelong complex metabolic disease that affects several millions of individuals globally. T2DM is characterized by unrelenting rise in blood glucose levels (hyperglycemia) resulting from several factors including insulin resistance, unhealthy lifestyle and obesity (BagliettoVargas et al, 2016; Zeliha and Canan, 2018; Gao et al, 2021). T2DM has been linked to multiple devastating complications such as neuropathy, cardiovascular disease, nephropathy, retinopathy and encephalopathy (Olatunji et al, 2018). Diabetic encephalopathy (DE) is a microvascular complication that affects the central nervous system (CNS), the brain. The clinical features associated with DE includes progressive cognitive dysfunction, electrophysiological, structural and neurochemical abnormalities, leading to degeneration of the CNS and dementia (Cai et al, 2011; Soares et al, 2012; Biessels and Despa, 2018; Chen et al, 2018). It has been demonstrated that prolonged chronic hyperglycemia and hyperlipidemia contributes to the pathogenesis of DE (Chen et al, 2021)
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