Neuropathic pain is a common disorder characterized by negative and positive subjective signs and symptoms ranging from numbness to crippling pain. Type 2 diabetes mellitus (T2DM) is the primary cause of neuropathy and neuropathic pain. Diabetic neuropathic pain (DPN) is one of the most common diabetes mellitus complications. The study was aimed to analyze the efficacy and safety of Pregabalin, Duloxetine, and their combination with Epalrestat in T2DM neuropathic patients. The study was conducted on 200 subjects. The patients were divided into 4 groups each comprising of 50 patients. Group I(P) was subjected to Pregabalin (150 mg O.D), Group II (D) to Duloxetine (60 mg O.D), Group III (P + E) to Pregabalin + Epalrestat (150 mg + 100 mg (O.D), and Group IV (D + E) to Duloxetine +Epalrestat (60 mg + 100 mg (O.D) and) for a period of 6 months. Various clinical parameters like vibration perception threshold, gycated haemoglobin level, visual analog scale, DPNdiabetic diagnostic questionnaire, advance glycated end products, thiobarbituric acid reactive substances, C-reactive proteins, SF12 score, and cost-effectiveness were assessed at baseline and 3 and 6 months. Results demonstrated that Pregabalin and Epalrestat therapy has a better effect on neuropathic pain reduction than Duloxetine and Epalrestat with strict glycemic control and favorably contributes to the health effective benefits by inhibiting disease progression and fulfills the alternate goals of management of DPN. It has been suggested that Pregabalin and Epalrestat therapy is more efficacious and armamentarium for patients with DPN. It has been suggested that Group III therapy is more efficacious, cost-effective, and armamentarium for patients with DPN.

Physical activity and stress are environmental modifiers for various neurodegerative disorders. The consistent psychological restraint stress has impacts the neurobiological changes like brain shrinkage or inhibiting the neurogenesis, mainly affecting the hippocampal CA3 region and exacerbating various neuropathologies. Therefore, stress directly modulates the pathology and neurobiology of human beings. The current research was designed to evaluate the anti-stress ability of trigonelline in behavioral and biochemical changes caused by restraint stress in mice. Various stressful stimuli have affected numerous physiological-based physical processes. There is no particular pharmacotherapy available to date which can count as stress reduction therapy. In the present study, female mice were subjected to restraint stress in flat bottomed restrainers with dimensions of 1.5″ dia × 4″, for 3.5 hours. The behavioral alterations by inducing restraint test were analyzed by using a battery of tests like social interaction, hole board, open field test, and elevated plus maze. The investigation of inducing restraint stress was processed which further resulted in exploratory behavior of grouped mice. Social behavior was measured by exploring the number of head dips and frequency of rearing in the hole board test. Apart from this, biochemical parameters, such as thiobarbituric acid reacting substance (TBARS), catalase (CAT), reduced glutathione (GSH) levels, myeloperoxidase, and superoxide dismutase (SOD), were analyzed. Mice treated with trigonelline (25 and 50 mg/kg, i.p.) significantly (p < 0.05) and dose-dependently attenuate stress-induced behavior and oxidative alterations, when compared to the stress control group. The current study confirmed the ameliorating effect of the trigonelline in restraint stress effect by attenuating the increased levels of MPO (Myeloperoxidase) and TBARS as stress parameters and enhancing the levels of protective enzymes such as GSH, SOD, and CAT. Hence, the study proposed a protective mechanism of trigonelline ameliorating stress by modulating the nuclear factor erythroid 2-related factor 2 pathways and oxidative stress.

The present study investigated the role of syringic acid (SA) in the renal protection mediated through the nitric oxide synthase (NOS) pathway in rodents treated with cisplatin (CP) with a single nephrotoxic dose of 5 mg/kg (i.p.) on the day the study commenced. The nephrotoxicity caused by a single dose of CP was assessed by measuring renal functional test (in serum and urine), oxidative stress parameters, and histopathological evaluation with hematoxylin and eosin stain in renal tissue on day 5, i.e., the last day of the study. The Administration of SA provides significant (p < 0.05) dose-mediated (50 and 100 mg/kg, p.o.) nephroprotection in CP-treated male Wistar rats. Pretreatment with NOS inhibitor, L-nitroarginine methyl ester (20 mg/kg, i.p.) in rats abolished the nephroprotective prospective of SA. SA-mediated activation of the NOS pathway has been hypothesized to contribute to renoprotection.