Glucose regulation by newly synthesized boronic acid functionalized molecules as dipeptidyl peptidase IV inhibitor: a potential compound for therapeutic intervention in hyperglycaemia.

Management of type 2 diabetes mellitus (T2DM) using dipeptidyl peptidase IV (DPP IV) inhibitors is gaining precedence as this enzyme plays an indispensable role in cleaving and inactivating peptides, such as glucagon-like peptide-1 (GLP-1), incretin hormones, and glucose-dependent insulinotropic polypeptide (GIP). There are several DPP IV inhibitors used to treat T2DM, but limited by side effects such as disturbed GIT, flu-like symptoms, etc. Thus, there is an urgent need for the development of novel and better DPP IV inhibitors for the management of the same. In the present study, we investigated the effect of new boronic acid-based thiazole compounds as DPP IV inhibitors. We used substituted anilines that were progressively modified through a multi-step synthesis and then chemically characterised. These molecules have good binding affinity and molecular interactions at the active site of the DPP IV enzyme. Two boronic acid-based molecules, i.e. PC06R58 and PC06R108, were used for the assessment of their in-vitro enzymatic activities. Both molecules (PC06108 and PC06R58) exhibited potent uncompetitive DPP IV enzyme inhibition at two different concentrations of 90.9 and 15.6 nM, respectively, compared to sitagliptin having an IC50 of 17.3 nM. Furthermore, the oral glucose tolerance test suggested significantly reduced blood glucose levels at 20 mg/kg of the body weight upon administration of PC06R58 and PC06R108 molecules in rats after glucose ingestion (2 g/kg of the body weight). The compounds showed satisfactory DPP IV inhibition. Furthermore, DPP IV inhibitory activity and acceptable pre-ADME/Tox profile indicate it is a lead compound in this novel class of DPP IV inhibitors.Communicated by Ramaswamy H. Sarma.

Emerging role of nanomedicine in the treatment of neuropathic pain.

Neuropathic pain (NeP) is a complex chronic pain condition associated with nerve injury. Approximately, 7-10% of the general population across the globe is suffering from this traumatic condition, but the existing treatment strategies are inadequate to deliver pain relief and are associated with severe adverse effects. To overcome these limitations, lot of research is focussed on developing new molecules with high potency and fewer side effects, novel cell and gene-based therapies and modification of the previously approved drugs by different formulation aspects. Nanomedicine has attracted a lot of attention in the treatment of many diverse pathological conditions because of their unique physiochemical and biological properties. In this manuscript, we highlighted the emerging role of nanomedicine in different therapies (drug, cell and gene), also we emphasised on the challenges associated with nanomedicine such as development of well-characterised nanoformulation, scaling of batches with reproducible results and toxicity along with this we discussed about the future of nanomedicine in the treatment of neuropathic pain.

Astaxanthin ameliorates behavioral and biochemical alterations in in-vitro and in-vivo model of neuropathic pain.

Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains limited. Astaxanthin, a marine natural drug, having potent anti-oxidant and anti-inflammatory activities is known to possess neuroprotective effects. However, effects of astaxanthin against nerve injury induce chronic pain remains unknown. Overactivity of glutamatergic NMDARs results in excitotoxicity which may participate in astrocytic and microglial activation during pathology which further contribute to the development of neuropathic pain. In this study, we investigate the effects of astaxanthin on oxido-inflammatory and NMDA receptor down-regulation pathway by using in-silico, in-vitro and in-vivo models of neuropathic pain. In-silico molecular docking study ascertained the binding affinity of astaxanthin to NMDA receptors and showed antagonistic effects. Data from in-vitro studies suggest that astaxanthin significantly reduces the oxidative stress induced by the lipopolysaccharides in C6 glial cells. In male Sprague dawley rats, a significant attenuation of neuropathic pain behavior was observed in Hargreaves test and von Frey hair test after astaxanthin treatment. Findings from the current study suggest that astaxanthin can be used as potential alternative in the treatment of chronic neuropathic pain. However, more detailed investigations are required to further probe the in-depth mechanism of action of astaxanthin.