Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways

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.

Thioredoxin-1 Is a Target to Attenuate Alzheimer-Like Pathology in Diabetic Encephalopathy by Alleviating Endoplasmic Reticulum Stress and Oxidative Stress

Varying degrees of central nervous system neuropathy induced by diabetes mellitus (DM) contribute to a cognitive disorder known as diabetic encephalopathy (DE), which is also one of the independent risk factors for Alzheimer’s disease (AD). Endoplasmic reticulum stress (ERS) plays a critical role in the occurrence and development of DE and AD. However, its molecular mechanism remains largely unknown. This study aims to investigate whether thioredoxin-1 (Trx-1) could alleviate DE and AD through ERS, oxidative stress (OS) and apoptosis signaling pathways. Mice were randomly divided into a wild-type group (WT-NC), a streptozotocin (STZ)-treated DM group (WT-DM), a Trx-1-TG group (TG-NC) and a Trx-1-TG DM group (TG-DM). Diabetic animals showed an increase in the time spent in the target quadrant and the number of platform crossings as well as AD-like behavior in the water maze experiment. The immunocontent of the AD-related protein Tau and the levels of cell apoptosis, β-amyloid (Aβ) plaque formation and neuronal degeneration in the hippocampus of the diabetic group were increased. Some key factors associated with ERS, such as protein disulfide isomerase (PDI), glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1α (IRE1α), tumor necrosis factor receptor-associated factor 2 (TRAF2), apoptosis signal-regulating kinase-1 (ASK1), c-Jun N-terminal kinase (JNK), protein kinase RNA (PKR)-like ER kinase (PERK), and C/EBP homologous protein (CHOP), were upregulated, and other factors related to anti-oxidant stress, such as nuclear factor erythroid 2-related factor (Nrf2), were downregulated in the DM group. Moreover, DM caused an increase in the immunocontents of caspase-3 and caspase-12. However, these changes were reversed in the Trx-1-tg DM group. Therefore, we conclude that Trx-1 might be a key factor in alleviating DE and AD by regulating ERS and oxidative stress response, thus preventing apoptosis.

Experience in using Mexidol-Vet® for the treatment and prevention of diabetic encephalopathy in cats older than 7 years

Diabetics is difficult endocrine disease of animals and human. Prediction in early diagnosis in cats is fairly favorable, but there is a number of consequences, that diabetics may entails. Diabetic encephalopathy is one of those consequences. Using antioxidants is one of really perspective methods of treatment pathologies of the nervous system. One of those antioxidants is Mexidol-Vet. In This article we describe antioxidant influence in course of the underlying diseas

Curcumin and its analog alleviate diabetes-induced damages by regulating inflammation and oxidative stress in brain of diabetic rats

Background Diabetic encephalopathy is a severe diabetes complication with cognitive dysfunction and neuropsychiatric disability. The mechanisms underlying diabetic encephalopathy is believed to be relevant with oxidative stress, vascular amylin deposition, immune receptors, inflammation, etc. This study wanted to evaluate the ability of curcumin and its analog A13 to alleviate oxidative stress and inflammation in diabetes-induced damages in brain. Methods Sixty adult male Sprague–Dawley rats were divided into 5 groups: normal control (NC) group, diabetes mellitus (DM) group, curcumin-treated diabetes mellitus (CUR) group, high dose of A13-treated diabetes mellitus (HA) group, low dose of A13-treated diabetes mellitus (LA) group. Activation of the nuclear factor kappa-B (NF-κB p65) pathway was detected by RT-qPCR, immunohistochemical (IHC) staining and Western blot; oxidative stress was detected by biochemical detection kit; brain tissue sections were stained with hematoxylin–eosin (HE) staining and Myelin staining. Results RT-qPCR, IHC staining and Western blot showed that curcumin and A13 treatment could inhibit the NF-κB p65 pathway. Curcumin and A13 increased the activity of superoxide dismutase and decreased the malondialdehyde level in the brain of diabetic rats. Furthermore, HE staining and Myelin staining demonstrated that the histological lesions of the brain in diabetic rats could be significantly ameliorated by curcumin and A13. Conclusion Curcumin analog A13 could alleviate the damages in the brain of diabetes rats by regulating the pathways of inflammation and oxidative stress. A13 may be a new potential therapeutic agent for diabetic encephalopathy.

Curcumin and its analog alleviate diabetes-induced damages by regulating inflammation and oxidative stress in brain of diabetic rats​

Background: Diabetic encephalopathy is a severe diabetes complication with cognitive dysfunction and neuropsychiatric disability. The mechanisms underlying diabetic encephalopathy is believed to be relevant with oxidative stress, vascular amylin deposition, immune receptors, inflammation, etc. This study wanted to evaluate the ability of curcumin and its analog A13 to alleviate oxidative stress and inflammation in diabetes-induced damages in brain. Methods: Sixty adult male Sprague-Dawley rats were divided into 5 groups: normal control (NC) group, diabetes mellitus (DM) group, curcumin-treated diabetes mellitus (CUR) group, high dose of A13-treated diabetes mellitus (HA) group, low dose of A13-treated diabetes mellitus (LA) group. Activation of the nuclear factor kappa-B (NF-κB p65) pathway was detected by RT-qPCR, immunohistochemical (IHC) staining and Western blot; oxidative stress was detected by biochemical detection kit; brain tissue sections were stained with hematoxylin–eosin (HE) staining and Myelin staining. Results: RT-qPCR, IHC staining and Western blot showed that curcumin and A13 treatment could inhibit the NF-κB p65 pathway. Curcumin and A13 increased the activity of superoxide dismutase and decreased the malondialdehyde level in the brain of diabetic rats. Furthermore, HE staining and Myelin staining demonstrated that the histological lesions of the brain in diabetic rats could be significantly ameliorated by curcumin and A13.Conclusion: Curcumin analog A13 could alleviate the damages in the brain of diabetes rats by regulating the pathways of inflammation and oxidative stress. A13 may be a new potential therapeutic agent for diabetic encephalopathy.