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Wnt/β-catenin signaling in hypoxia-induced pulmonary artery smooth muscle cell proliferation - Role of bioactive molecule of Mucuna pruriens

Sun, 01 Jun 2025 00:00:00 GMT

Title: Wnt/β-catenin signaling in hypoxia-induced pulmonary artery smooth muscle cell proliferation - Role of bioactive molecule of Mucuna pruriens Authors: Supriya, Bhosale Abstract: Introduction: Pulmonary hypertension (PH) is a progressive, life-threatening disease characterized by vascular remodeling, constriction, and thrombosis, primarily driven by excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs). Hypoxia is a key trigger in PH pathogenesis. The Wnt/β-catenin signaling pathway, critical for cell fate, migration, and organogenesis, plays a pivotal role in PH, with β- catenin mediating transcriptional activation of target genes upon Wnt ligand stimulation. Targeting Wnt/β-catenin signaling represents a promising therapeutic strategy for PH. This study examines its role in hypoxia-exposed PASMCs and evaluates the therapeutic potential of gallic acid and β-sitosterol through in-silico and in-vitro approaches. Objective: To study the role of isolated biomolecules from Mucuna pruriens gallic acid and β-sitosterol on Wnt/ β-catenin mRNA expression in the human pulmonary artery smooth muscle cells exposed to hypoxia. Method: The current study used a computational method based on the ligand-protein interaction technique to determine the therapeutic potential of gallic acid and β- sitosterol with the Wnt/ β catenin pathway. The same compounds are used to investigate. The Invitro study explored the role of gallic acid and β-sitosterol in hypoxia-exposed PASMC lines. Result and Discussion: The current study identified different pharmacological properties of gallic acid and β-sitosterol bioactive molecules to analyze the in silicoADME/T properties. All were within Lipinski’s rule acceptable range, and molecular docking analysis showed that β-sitosterol has more interaction sites with Wnt5a. The Invitro study revealed that when HPASMC is exposed to hypoxia, there is downregulation of the Wnt5a gene and upregulation of the β-catenin gene. β-sitosterol and gallic acid can be attributed to inhibiting the β-catenin pathway via the downregulation of β-catenin gene expression. Conclusion: The present study focused on in-silico phytochemical analysis and in vitro investigations to evaluate the potential therapeutic role of isolated biomolecules from Mucuna pruriens seed extract β-sitosterol and gallic acid in hypoxia-exposed pulmonary artery smooth muscle cells (HPASMCs). These findings suggest that Mucuna pruriens, or its bioactive molecule gallic acid and β-sitosterol, may exert protective effects against hypoxia-induced vascular remodeling by targeting the Wnt/β-catenin signaling pathway.

Modulation of NFKB ligand RANKL Signaling Lipopolysaccharide Induced Rheumatoid Arthritis Cell Line by Pithecellobium dulce.

Sun, 01 Jun 2025 00:00:00 GMT

Title: Modulation of NFKB ligand RANKL Signaling Lipopolysaccharide Induced Rheumatoid Arthritis Cell Line by Pithecellobium dulce. Authors: Soumya T, Tungal Abstract: ntroduction: In the world, 1% of people suffer from chronic inflammatory autoimmune diseases like rheumatoid arthritis (RA). The individual with rheumatoid arthritis suffers from synovial inflammation, cartilage degradation, joint destruction, leading to reduced quality of life. The disease pathogenesis involves the activation of pro- inflammatory cytokines and NF-κB ligand RANKL signaling pathway. The research on plant-based drug design and discovery is to target pathways to find promising phytochemical alternatives for relieving symptoms of RA and other chronic diseases. This study aimed to investigate the role of bioactive compounds Pithecellobium dulce gallic acid and quercetin, in modulating the NF-κB ligand RANKL signaling pathway by targeting MMP-1 expression through in silico and in vitro approaches. Objective: To evaluate the effect of isolated bioactive compounds from Pithecellobium dulce fruit gallic acid, and quercetin on mRNA expression of MMP-1 in NF-kB ligand RANKL signaling. Method: The study involved In Silico and experimental in vitro methods. Ligand– protein interaction studies were conducted to assess gallic acids and quercetin’s therapeutic potential in targeting the NF-κB ligand RANKL signaling pathway. Additionally, green-synthesized Pd-Cu nanoparticles (Pd-CuNPs) were characterized and evaluated. Pharmacokinetic properties, drug-likeness, gastrointestinal absorption, blood-brain barrier permeability, and solubility were predicted using ADME/T tools. Molecular interaction and molecular dynamics simulation were performed to identify potential interactions. The gene expression of MMP-1 was evaluated through RT-PCR in treated rheumatoid arthritis cells. Results: In silico analysis confirmed gallic acid and quercetin have favourable pharmacokinetic and safety profiles. Docking and simulation studies identified strong binding affinities with target proteins. Experimental In vitro results revealed a significant downregulation of MMP-1 mRNA expression in treated RA cells, gallic acid (0.299 ± 0.25, p < 0.05), Pd-CuNPs (0.432 ± 0.22), quercetin (0.519 ± 0.01), and crude extract (0.633 ± 0.03), compared to control. Conclusion: The study demonstrated that gallic acid, quercetin, and Pd-CuNPs exhibit promising modulatory effects on the NF-κB ligand RANKL signaling pathway. These findings support their potential as plant-based alternative agents for managing inflammatory disease like rheumatoid arthritis

Effect of bioactive molecules from phytochemical data base as possible therapeutic agents on aortic tissue proteins (ACE2 and MMP-7) in hypertensive rat model using in silico and in vivo methods

Thu, 01 Aug 2024 00:00:00 GMT

Title: Effect of bioactive molecules from phytochemical data base as possible therapeutic agents on aortic tissue proteins (ACE2 and MMP-7) in hypertensive rat model using in silico and in vivo methods Authors: Sanakousar, Patel Abstract: In conclusion, β-sitosterol supplementation demonstrates promising therapeutic possibilities in modifying cardiovascular complications associated with L NAME-induced hypertension in rats. Its beneficial effects encompass regulating body weight, heart rate, blood pressure, autonomic functions, oxidative stress, and MMP-7 gene expression in cardiovascular remodelling. This study provides valuable insights into the various mechanisms underlying the cardioprotective effects of β-sitosterol. It highlights its significance as a potential adjunctive therapy for hypertension and associated cardiovascular disorders. Further research is needed to elucidate its precise mechanisms of action and therapeutic efficacy in clinical settings.

Genetic and Molecular Profiling of Neuroligin3, Neuroligin4X and Neuroligin4Y Genes in Autism Spectrum Disorder among the Population of North Karnataka

Sun, 01 Jan 2023 00:00:00 GMT

Title: Genetic and Molecular Profiling of Neuroligin3, Neuroligin4X and Neuroligin4Y Genes in Autism Spectrum Disorder among the Population of North Karnataka Authors: Hegde, Rajat Veerabhadra Abstract: Autism Spectrum Disorder (ASD) or Autism (MIM 209850) is a complex heterogeneous neurodevelopmental disorder. It manifests before the age of three (1). Although autism can be diagnosed at any age, it is described as a “developmental disorder” because symptoms generally appear in the first two years of life. Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is a diagnostic guide created by the American Psychiatric Association that healthcare providers use to diagnose different mental disorders/illnesses. People with ASD often have featured early onset dysfunctions in verbal and non-verbal communication, impairments in social interaction and repetitive and stereotyped behaviours and interests (2). Autism is known as a “spectrum” disorder because there is wide variation in the type and severity of symptoms that individuals experience. Individuals of all genders, races, ethnicities, and economic backgrounds can be diagnosed with ASD. Although ASD can be a lifelong disorder, treatments and services can improve a person’s symptoms and daily functioning. The previous version of the DSM, i.e. the DSM-4, included autism under the umbrella of pervasive developmental disorder and divided autism into five distinct categories ranging from Asperger's syndrome (often used to describe mild or high-functioning autism) to autistic disorder, which indicated severe autism. The 5 diagnostic ranges include autistic disorder, Asperger’s disorder, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS), Rett’s disorder and Childhood Disintegrative Disorder (CDD). But the recent version of the DSM, i.e. DSM-V combines all of these into a spectrum of single diagnosis called autism spectrum disorder with different levels of severity (Fig.1) (3).