A network pharmacology approach to assess Reno-protective and -curative effects of methanolic extract of Malva neglecta Wallr in gentamicin induced renal toxicity rat model

Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.

In Silico Study of Protein-Protein Interactions in Mapks and pp2cs of Medicago sativa Discloses its Docking Sites Variations

Abstract A wide variety of cellular mechanisms such as cell division and metabolic processes are maintained by protein-protein interactions (PPIs). The identification of PPI through laboratory techniques is costly, time-consuming, difficult, and challenging. However, computational techniques were generated for PPIs prediction. In alfalfa (Madicago sativa), PPI was predicted among 12 MsMAPKs and 4 MsPP2Cs using a docking approach. For homology modelling, the Swiss model was employed while PROCHECK, ERRAT, and Verify3D were used to validate 3D models. The Ramachandran plots were obtained from PROCHECK which showed value more than 90% (nPP2C1, PP2C1, PP2C, and MSK-3 revealed 92.9%, 94.2%, 92.4%, and 91.1% respectively) for high-quality structures. The HawkDock server and the BIPSPI server were used to analyse protein docking and predict interaction sites, respectively. Our findings demonstrated that MsPP2C docking sites play an important role in the identification and docking of MsMAPKs. The binding free energy ranged from -0.16Kcal/mol to -49.15Kcal/mol for all MsMAPKs and MsPP2Cs, indicating that they interact. Docking site analysis showed that there were 48 pairs of PPIs which indicated that MsPP2Cs can perform a vital role in other signaling pathways. This study found that all MsPP2Cs have docking sites for MsMAPKs, indicating that this method can accurately determine protein-protein interactions.

Chemical characterization, docking studies, anti-arthritic activity and acute oral toxicity of Convolvulus arvensis L. leaves

Objective: To evaluate acute oral toxicity and anti-arthritic activity of the methanolic extract of Convolvulus arvensis L. leaves. Methods: Safety was assessed by acute oral toxicity (OECD 425) study. Anti-arthritic activity was explored by in vitro (inhibition of protein denaturation) and in vivo (Complete Freund's adjuvant-induced arthritis and carrageenan-induced inflammation) methods. Antioxidant potential was determined by assessing ferric reducing power, DPPH inhibition, and H2O2 scavenging assays. Furthermore, molecular docking was done to check interactions between the plant constituents and cyclooxygenases (COX-1 and COX-2). Quercetin, gallic acid, caffeic acid, syringic acid, sinapic acid, and vanillic acid were quantified by HPLC and eight compounds were identified by GC-MS analysis. Results: No mortality and abnormality in biochemical parameters were observed in the toxicity study. Histological analysis of vital organs also supported these biochemical results. The in vitro and in vivo studies showed that the methanolic extract of leaves of Convolvulus arvensis exhibited dose-dependent anti-arthritic and anti-oxidant potential. Molecular docking showed better interactions of plant compounds with cyclooxygenases as compared to standard ibuprofen. Conclusions: Convolvulus arvensis exhibits strong anti-arthritic activity, justifying the traditional use of the herbal drug.