Antidiabetic potency and molecular insights of natural products bearing indole moiety: A systematic bioinformatics investigation targeting AKT1.

Diabetic mellitus (DM) is a chronic disorder, and type 2 DM (T2DM) is the most prevalent among all categories (nearly 90%) across the globe every year. With the availability of potential drugs, the prevalence rate has remained uncontrollable, while natural resources showed a promising potency, and exploring such potential candidates at the preclinical stage is essential. An extensive literature search selected 89 marine and plant-derived indole derivatives with anti-inflammatory, antioxidant, lipid-lowering, etc., activities. However, as we know, drugs have not been able to convert from 'lead' to 'mainstream' due to inadequate drug-ability profiles, as our systematic investigation proved and selected herdmanine_A (HERD_A) and penerpene_D (PENE_D) as the most potential antidiabetic candidates from the library of indole derivatives. Based on our previous network pharmacology study, we selected three new target enzymes: Acetyl-CoA carboxylase 2 (ACACB; PDB ID: 3JRX), cyclin-dependent kinase 4 (CDK4; PDB ID: 3G33), and alpha serine/threonine-protein kinase 1 (AKT1; PDB ID: 3O96) to assess the antidiabetic potency of selected indole derivatives through binding energy or docking score. To conduct molecular docking studies with these enzymes, we used the PyRx-AutoDock platform. Furthermore, molecular dynamic simulation at 100 ns, physicochemical analysis, pharmacokinetics, toxicity assessment, and drug-likeness evaluation suggested that HERD_A and penerpene PENE_D were the most potent inhibitors against AKT1 compared to koenimbine (most potential based on the recorded IC50 value) and murrayakonine_A (most potential based on the docking score). In summary, HERD_A and/or PENE_D have the potential to be used as alternative therapeutic agent for the treatment of diabetes after some pharmacological investigation.

Translation and Validation of ID-Migraine Questionnaire to North-Indian Vernacular Languages.

Background: ID-Migraine is an established screening tool for migraine. Translation and validation in more languages can increase its reach and scope. Aim: To translate and validate ID-Migraine for screening migraine patients in two North-Indian vernacular languages, that is, Hindi and Punjabi. Methods: ID Migraine was translated into Hindi and Punjabi. Subjects with headaches in outpatient clinics were administered the questionnaire according to their preferred language of choice and referenced clinical evaluations, performed by an experienced neurologist, based on current the ICHD-3 diagnostic criteria. Results: One hundred subjects with complaints of headaches and 60 healthy controls were recruited after informed consent. Of the 100 subjects with headaches, 73 (73%) screened positive with a translated version of ID-Migraine, and 60 (60%) were eventually diagnosed with migraine without aura. The sensitivity of the Hindi version of ID-Migraine was 94% (95% confidence intervals, 79% to 99%); specificity, 56% (95% CI, 31% to 78%); positive predictive value, 79% (95% CI, 69% to 86%) and negative predictive value, 83% (95% CI, 55% to 95%). The Punjabi version demonstrated a sensitivity of 86% (95% CI, 68% to 96%); specificity, 43% (95% CI, 23% to 66%); PPV, 68% (95% CI, 58% to 76%); and NPV, 69% (95% CI, 44% to 86%). Conclusion: The translated versions of ID-Migraine demonstrated high sensitivity and fair specificity for screening migraine in Indian subjects who speak and understand Hindi and Punjabi.

Role of Omics in Migraine Research and Management: A Narrative Review.

Migraine is a neurological disorder defined by episodic attacks of chronic pain associated with nausea, photophobia, and phonophobia. It is known to be a complex disease with several environmental and genetic factors contributing to its susceptibility. Risk factors for migraine include head or neck injury (Arnold, Cephalalgia 38(1):1-211, 2018). Stress and high temperature are known to trigger migraine, while sleep disorders and anxiety are considered to be the comorbid conditions with migraine. Studies have reported various biomarkers, including genetic variants, proteins, and metabolites implicated in migraine's pathophysiology. Using the "omics" approach, which deals with genetics, transcriptomics, proteomics, and metabolomics, more specific biomarkers for various migraine can be identified. On account of its multifactorial nature, migraine is an ideal study model focusing on integrated omics approaches, including genomics, transcriptomics, proteomics, and metabolomics. The current review has been compiled with an aim to focus on the genomic alterations especially involved in the regulation of glutamatergic neurotransmission, cortical excitability, ion channels, solute carrier proteins, or receptors; their expression in migraine patients and also specific proteins and metabolites, including some inflammatory biomarkers that might represent the migraine phenotype at the molecular level. The systems biology approach holds the promise to understand the pathophysiology of the disease at length and also to identify the specific therapeutic targets for novel interventions.