Current Chemical Biology - Volume 19, Issue 1, 2025

Guanine Protein-coupled Receptor 17 (GPR17) plays pivotal roles in various physiological processes and diseases. However, the discovery of ligands binding to GPR17 remains an active area of research.

In this study, we utilized our recently published GPCR-specific deep learning approach, molecular docking, and molecular dynamics simulations. Specifically, the DeepGPCR model, employing graph convolutional networks, was used to screen the extensive ZINC database for potential ligands.

This computational pipeline identified three highly promising lead compounds, ZINC000044404209, ZINC000229938097, and ZINC000005158963. Molecular dynamics simulations confirmed the stability of the protein-ligand complexes while binding free energy calculations highlighted the crucial molecular forces stabilizing these interactions. Notably, ZINC000229938097 exhibited particularly favorable binding energy values among the compounds assessed.

Our study underscores the efficacy of computational methodologies in identifying potential drug candidates targeting GPR17. Understanding the molecular mechanisms underlying GPR17 activation holds significant promise for developing tailored therapies for Glioblastoma Multiforme.

Arterial thrombosis represents the most commonly feared consequence of cardiovascular disease and a leading cause of death globally. Cardiovascular disease, liver, and kidney are closely linked conditions, and disease in one organ can lead to dysfunction in the other.

The current research aims to examine the therapeutic impact of Ech-A on arterial thrombosis induced by FeCl3 complications on liver and kidney function.

Twenty-four rats were assigned into four groups (n= 6), sham and thrombotic model groups were orally administered 2% DMSO, while the other groups were treated with two dosages of Ech-A (1 and 10 mg/kg, body weight). After seven days of administration, the left common carotid arteries of all groups were exposed to 50% ferric chloride for 10 min, except those of the sham group rats exposed to normal saline.

The oral administration of Ech-A caused a significant increase in partial thromboplastin time, prothrombin time, glutathione, catalase, nitric oxide, and glutathione S-transferase. While aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase activities as well as creatinine, uric acid, urea, and malondialdehyde concentrations were significantly decreased (p< 0.05). The histological examination revealed a definite improvement in the liver and kidney tissues in the Ech-A groups.

The current investigation revealed that arterial thrombosis induced by FeCl3 in rats causes complications in the kidneys and liver. Additionally, it demonstrates the beneficial impact of Ech-A on coagulation parameters and liver and kidney function. Despite this, the current study has few limitations. Firstly, the molecular mechanism regarding the protective effect of Ech-A on liver and kidney complications caused by arterial thrombosis has not been investigated. Secondly, no reference drug has been utilised to compare with Ech-A.

Hyperlipidaemia, characterized by elevated triglyceride and cholesterol levels in the blood, is linked to premature aging and degenerative diseases, often driven by free radicals. Antioxidants can help address these issues by neutralizing free radicals. Luffa acutangula leaves are known for their antioxidant properties due to their content of flavonoids and phenolic compounds.

This study aimed to extract, fractionate, and analyze the phytochemical composition of Luffa acutangula leaves and to evaluate their antioxidant and antihyperlipidemic activities across different fractions: ethyl acetate, chloroform, hexane, and methanol.

The extraction was performed using 96% methanol and liquid-liquid fractionation with solvents n-hexane, ethyl acetate, chloroform, and methanol. Phytochemical screening and antioxidant activity assessments were conducted on the methanolic extract, with LC-MS/MS analysis revealing various phytoconstituents. Antioxidant activity was measured using standard methods, along with enzyme inhibition assays.

Methanol extraction yielded 19.73% of the extract, with the methanol fraction providing the highest dried extract (41.64%), followed by the ethyl acetate fraction at 14.09%. The methanolic extract contained flavonoids, phenolic compounds, and other phytoconstituents. The ethyl acetate fraction showed the lowest IC50 value (22.04, 115.2, and 69.74) for DPPH, ABTS, and FRAP, respectively, demonstrating the strongest antioxidant potential. The ethyl acetate fraction displayed maximum antihyperlipidemic potential (IC50-17.85 for HMG-CoA reductase). Each fraction exhibited varying yields and secondary metabolites, with the ethyl acetate fraction showing the most significant antioxidant and antihyperlipidemic effects.

This study provided comprehensive information regarding the extraction, fractionation, and phytochemical composition of Luffa acutangula leaves, noting that the ethyl acetate fraction possesses significant antioxidant and antihyperlipidemic potential.