Protective role of harmol against β-cell toxicity and glucose dysregulation in type 2 diabetes mellitus.

Hypogonadism in males has been identified as one of the risk factors for type 2 diabetes mellitus (T2DM). Testosterone treatment is beneficial for T2DM in both preclinical and clinical studies. Testosterone enhances insulin secretion and maintains β-cell health by activating androgen receptors (AR).

An in-depth review of PPARγ modulators as anti-diabetes therapeutics.

Drug metabolism and pharmacokinetics (DMPK) plays a crucial role in optimizing peroxisome proliferator-activated receptor gamma (PPARγ) modulators by influencing metabolism, therapeutic efficacy, and safety. Rosiglitazone is primarily metabolized by cytochrome 2C8 (CYP2C8) and CYP2C9, with the CYP2C83 polymorphism increasing clearance, reducing efficacy, and altering fluid retention. Troglitazone metabolism via CYP3A4 and CYP2C8 generates a reactive quinone metabolite, depleting glutathione (GSH), elevating mitochondrial oxidative stress, and inducing hepatotoxicity.

Probing the dark chemical matter against PDE4 for the management of psoriasis using in silico, in vitro and in vivo approach.

The potential downsides for the present treatment for psoriasis are drug resistance, reduced efficacy, risk of mental episodes, and drug interactions. Hence, this study aims to discover a new drug for psoriasis by considering global research efforts and exploring underrepresented chemical space regions. The objective was to identify novel PDE4D inhibitors from the dark chemical matter (DCM) database for treating psoriasis.

Synthesis and evaluation of novel ethyl ferulate derivatives as potent Keap1 inhibitors to activate the Nrf2/ARE pathway in Parkinson's disease.

The Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2 related factor 2/Antioxidant Response Elements (Keap1/Nrf2/ARE) pathway is essential for neuronal resilience against the complex pathogenesis of Parkinson's disease (PD). Activating this pathway by covalently modifying Keap1 cysteine residues is a promising strategy for regulating neuroprotective gene expression. Our study aimed to identify phytochemicals that could irreversibly inhibit Keap1.

Ligandrol Ameliorates High-Fat Diet- and Streptozotocin-Induced Type 2 Diabetes Mellitus and Prevents Pancreatic Islets Degeneration.

Androgen therapy has been shown to alleviate type 2 diabetes mellitus (T2DM) but is also associated with severe side effects such as prostate cancer. The present study aims to identify the best hit selective androgen (AR) modulator by studies and then investigates its antidiabetic effects in high-fat diet- and streptozotocin (STZ)-induced T2DM male rat model. Molecular docking and molecular dynamics (MD) studies were carried out using Maestro 13.

Phytoconstituents of Citrus limon (Lemon) as Potential Inhibitors Against Multi Targets of SARS-CoV-2 by Use of Molecular Modelling and In Vitro Determination Approaches.

In the present work, phytoconstituents from Citrus limon are computationally tested against SARS-CoV-2 target protein such as Mpro - (5R82.pdb), Spike - (6YZ5.pdb) &RdRp - (7BTF.

Molecular insights into the potential effects of selective estrogen receptor β agonists in Alzheimer's and Parkinson's diseases.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders. Pathologically, AD and PD are characterized by the accumulation of misfolded proteins. Hence, they are also called as proteinopathy diseases.

Network-based drug repositioning of linagliptin as a potential agent for uterine fibroids targeting transforming growth factor-beta mediated fibrosis.

Uterine fibroid is the most common non-cancerous tumor with no satisfactory options for long-term pharmacological treatment. Fibroblast activation protein-α (FAP) is one of the critical enzymes that enhances the fibrosis in uterine fibroids. Through STITCH database mining, we found that dipeptidyl peptidase-4 inhibitors (DPP4i) have the potential to inhibit the activity of FAP.

Rational Design of Dual Inhibitors for Alzheimer's Disease: Insights from Computational Screening of BACE1 and GSK-3β.

Background: Alzheimer's disease (AD) is one of the most concerned neurodegenerative disorders across the world characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs), leading to cognitive decline and memory loss. Targeting key pathways involved in AD like Aβ and NFT pathways, are crucial for the development of effective therapeutic strategies. In this study, we aimed to identify and establish promising dual inhibitors targeting BACE1 and GSK-3β, two proteins implicated in Aβ and NFT formation respectively.

The identification of cianidanol as a selective estrogen receptor beta agonist and evaluation of its neuroprotective effects on Parkinson's disease models.

Aim: The present study aims to identify selective estrogen receptor beta (ERβ) agonists and to evaluate the neuroprotective mechanism in Parkinson's disease (PD) models.

Main Methods: In-silico studies were carried out using Maestro and GROMACS. Neuroprotective activity and apoptosis were evaluated using cytotoxicity assay and flow cytometry respectively.

Side effects based network construction and drug repositioning of ropinirole as a potential molecule for Alzheimer's disease: an , , and study.

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Drug repositioning is a process of finding new therapeutic applications for existing drugs. One of the methods in drug repositioning is to use the side-effect profile of a drug to identify a new therapeutic indication.

A preliminary study to identify existing drugs for potential repurposing in breast cancer based on side effect profile.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death in women after lung cancer. The present study aims to identify potential drug candidates using the PROMISCUOUS database for breast cancer based on side effect profile and then proceed with and studies. PROMISCUOUS database was used to construct a group of drugs that share maximum side effects with letrozole.

A Perspective on Therapeutic Applications and Strategies to Mitigate Toxicity of Metallic Nanoparticles.

Metallic nanoparticles (MNPs) have been widely used for diagnostic and therapeutic purposes in clinical practice. A number of MNP formulations are being investigated in clinical trials for various applications. This increase in the use of NPs results in higher exposure to humans, leading to toxicity issues.

Importance of Fibrosis in the Pathogenesis of Uterine Leiomyoma and the Promising Anti-fibrotic Effects of Dipeptidyl Peptidase-4 and Fibroblast Activation Protein Inhibitors in the Treatment of Uterine Leiomyoma.

Uterine fibroid or leiomyoma is the most common benign uterus tumor. The tumor is primarily composed of smooth muscle (fibroid) cells, myofibroblast, and a significant amount of extracellular matrix components. It mainly affects women of reproductive age.

Identification of (2,3)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate as multiple inhibitors of SARS-CoV-2 targets; a systematic molecular modelling approach.

Coronavirus disease of 2019 (COVID-19) is a zoonotic disease caused by a new severe acute respiratory syndrome (SARS-CoV-2) which has quickly resulted in a pandemic. Recent anti-COVID-19 drug discoveries are leaning towards repurposing phytochemicals which have been previously reported for SARS and MERS-CoV outbreaks. However, they have been either virtually screened or tested so far against mono targets and the potent derivatives of virtually sorted lead molecules remain elusive.

The principal molecular mechanisms behind the activation of Keap1/Nrf2/ARE pathway leading to neuroprotective action in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder. PD is associated with the loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain. Present therapies for PD provide only symptomatic relief by restoring the dopamine (DA) level.

G-Lymphatic, Vascular and Immune Pathways for Aβ Clearance Cascade and Therapeutic Targets For Alzheimer's Disease.

Alzheimer's disease is an age-related neurodegenerative disease. The factors causing Alzheimer's disease are numerous. Research on humans and rodent models predicted various causative factors involved in Alzheimer's disease progression.

Syringaresinol as a novel androgen receptor antagonist against wild and mutant androgen receptors for the treatment of castration-resistant prostate cancer: molecular docking, and molecular dynamics study.

Phytoestrogens are dietary estrogens having similar structure as of estrogen. Some of these phytoestrogens are androgen receptor (AR) antagonists and exhibit preventive role in the prostate cancer. However, in androgen-independent prostate cancer (AIPC) the ARs were mutated (T877A, W741L, F876L, etc.

Rational Design, Synthesis, and In Vitro Neuroprotective Evaluation of Novel Glitazones for PGC-1α Activation via PPAR-γ: a New Therapeutic Strategy for Neurodegenerative Disorders.

In the present study, two structurally diverse novel glitazones were designed and synthesized for activation of central PGC-1α signaling through stimulation of PPAR-γ receptor. The functional interaction between PGC-1α and PPAR-γ is a key interaction in the normal physiology of neuroprotective mechanism. Therefore, activation of PPAR-γ-dependent PGC-1α co-activator signaling could be an effective strategy to exhibit neuroprotection in several neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and cerebral ischemia.

Design, Synthesis and Evaluation of Novel Substituted (5-methyl-1H-pyrazol-3-yl)- 1,3,4-oxadiazole as Potent Androgen Receptor Antagonist.

Background: Androgen Receptor (AR) is one of the highly explored targets for the treatment of prostate cancer. The emergence of point mutation in the Ligand Binding Domain (LBD) of AR has resulted in the development of resistance against AR antagonist. The point mutation T877A, W741L and F876L confer resistance to flutamide, bicalutamide and enzalutamide respectively.

Design, Synthesis and Biological Evaluation of Novel 1, 3- thiazolidine-2, 4-diones as Anti-prostate Cancer Agents.

Background: Androgen receptor is an attractive target for the treatment of prostate cancer. The 1,3- thiazolidine-2,4-diones possess a wide diversity of important biochemical effects and interesting pharmacological properties.

Objective: The aim of the study is to find the experimental and computational methods to investigate the interference of 1,3-thiazolidine-2,4-diones with androgen receptor against prostate cancer.