Beneficial Effects of PIN1 Inhibition on Diabetes Mellitus: A Concise Review Meeramol C. Chellappan, Soumya Vasu, Shriraam Mahadevan, Muthu Kumaradoss Kathiravan, Saravanan Jayaraman, Soniya Naik Endocrine Metabolic Immune Disorders Drug Targets, 2025 Type 2 diabetes mellitus is a long-term medical illness in which the body either becomes resistant to insulin or fails to produce it sufficiently. Mostly, combinatorial therapy is required to control blood glucose levels. However, combinatorial therapy has detrimental side effects. The prevalence of the cases and subsequent increases in medical costs of the same intimidate human health globally. While there have been a lot of studies focused on developing diabetic regimens that work to lower blood glucose levels, their effectiveness is short-lived because of unfavorable side effects, such as weight gain and hypoglycemia. In recent years, the PIN1 (protein interacting with NIMA) enzyme has attracted the attention of researchers. Previous studies suggested that PIN1 may act on the various substrates that are involved in the progression of T2DM and also help in the management of diabetes-related disorders. Thus, the focus of the current review is to examine the correlation between PIN1, T2DM and its related disorders and explore the possibility of developing novel therapeutic targets through PIN1 inhibition.
Exploring phytoconstituents for Parkinson’s disease: Insights from network pharmacology, molecular modeling and in vivo investigations Shiva Priya, Divakar Selvaraj, Rashi Jain, Kavyashree G. S., Soumya V., Venkatesh Gunasekaran, Ramu G., Saravanan Jayaram Thai Journal of Pharmaceutical Sciences, 2025 Background: The network pharmacology approach is used to identify novel therapeutic agents that target multiple disease targets through analysis of complex disease networks by integrating systems biology and computational approaches. Objectives: The present study aims to identify the principal targets implicated in the pathogenesis of Parkinson’s disease (PD) and major phytoconstituents that could potentially modulate the major targets to achieve therapeutic benefits in PD through a network pharmacology-based approach. Materials and Methods: The DisGeNET database was used to select the major targets involved in the pathogenesis of PD. The most important targets among the selected proteins were identified through analysis of topological parameters, such as degree, betweenness centrality, and closeness centrality using Cytoscape software. The phytoconstituents present in the selected botanicals were identified from databases and were subjected to the prediction of pharmacokinetic parameters. The binding affinity, free energy, and binding stability of the selected phytochemicals with the target proteins were evaluated using molecular docking, MM-GBSA, and molecular dynamics (MD), respectively, using Schrodinger software. The effect of berberine on catalepsy, motor coordination, locomotion, and memory was evaluated using rotenone-induced PD in rats. Results: Based on topological parameters and pharmacokinetic profile, 4 proteins (A2A, CNR1, REN, and STAT3) and 6 phytoconstituents (berberine, bisacumol, capsaicin, ferulic acid, cinnamic acid, and geranyl acetate) were selected, respectively, for further studies. Among the chosen ligands, berberine exhibited maximum binding affinity with A2A (−9.90 kcal/mol), REN (−7.89 kcal/mol), STAT3 (−3.93 kcal/mol), and second highest with CNR1 (−9.07 kcal/mol). Berberine also showed better free energy scores in MM-GBSA with three targets, A2A (−86.44 kcal/mol), REN (−108.93 kcal/mol), and CNR1 (75.18 kcal/mol). The root mean square deviation of berberine with all four targets in MD indicated good ligand-target stability. A significant improvement in the catalepsy test, motor coordination, locomotion, and memory in animals treated with 25 and 50 mg/kg of berberine compared with the control group. Conclusion: The current network pharmacology-based study reveals that berberine could act as a beneficial agent in PD through the alteration of multiple receptors.
UNVEILING THE THERAPEUTIC POTENTIAL OF GINKGO BILOBA: A NETWORK PHARMACOLOGY APPROACH FOR PARKINSON'S DISEASE Shiva PRİYA, Mehak TYAGI, Devadharshini DHANDAYUTHAPANI, Jayaram SARAVANAN Ankara Universitesi Eczacilik Fakultesi Dergisi, 2024 Objective: The aim of the current study is to identify the major phytoconstituents in Ginkgo biloba that could modulate the role of major therapeutic targets involved in the pathogenesis of Parkinson’s disease using approaches in network pharmacology. Material and Method: The phytoconstituents in Ginkgo biloba and their therapeutic targets and the targets of Parkinson’s disease were identified using various online databases and software. The identified phytoconstituents were subjected to evaluation of several pharmacokinetic properties and druglikeness study. The phytoconstituents with favourable pharmacokinetic and druglikeness properties and targets with better topological parameters were subjected to molecular docking study and MMGBSA analysis. Result and Discussion: This study identified the presence of 125 major phytoconstituents in Ginkgo biloba and out of 125 phytoconstituents, 30 phytoconstituents passed the pharmacokinetics and druglikeness property. The therapeutic targets for these selected phytoconstituents were found to be 468 and the disease targets in PD were found to be 2033. The common targets between phyto-targets and disease targets were found to be 44 targets. Out of 44 common targets, 5 top proteins CNR1, HPGDS, AR, RXRA and HDAC1 were identified on the basis of the topological parameters such as degree centrality and betweenness centrality in the Cytoscape 3.9.1 software. The docking studies and MMGBSA analysis revealed that beta-eudesmol has better interaction with the top 5 therapeutic targets.
Side effects based network construction and drug repositioning of ropinirole as a potential molecule for Alzheimer’s disease: an in-silico, in-vitro, and in-vivo study Amritha Chakkittukandiyil, Saurav Chakraborty, Ram Kothandan, Emdormi Rymbai, Santhosh Kumar Muthu, Soumya Vasu, Deepak Vasudevan Sajini, Deepa Sugumar, Zubair Baba Mohammad, Saravanan Jayaram, Kalirajan Rajagopal, Vadivelan Ramachandran, Divakar Selvaraj Journal of Biomolecular Structure and Dynamics, 2024 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. The drugs with similar side-effects may act on similar biological targets and could affect the same biochemical process. In this study, we explored the Food and Drug Administration-approved drugs using PROMISCUOUS database to find those that have adverse effects profile comparable with the ligands being studied or used to treat AD. Here, we found that the ropinirole, a dopamine receptor agonist, shared a maximum number of side-effects with the drugs proven beneficial for treating AD. Furthermore, molecular modelling demonstrated that ropinirole exhibited strong binding affinity (-9.313 kcal/mol) and best ligand efficiency (0.49) with sigma-1 receptor. Here, we observed that the quaternary amino group of ropinirole is essential for binding with sigma-1 receptor. Molecular dynamic simulation indicated that the movement of the carboxy-terminal helices (α4/α5) could play a major role in the receptor's physiological functions. The neurotoxicity induced by Aβ25-35 in SH-SY5Y cells was reduced by ropinirole at concentrations 10, 30, and 50 µM. The effect on spatial learning and memory was examined in mice with Aβ25-35 induced memory deficit using the radial arm maze. Ropinirole (10 and 20 mg/kg) significantly improved the short and long-term memories in the radial arm maze test. Our results suggest that ropinirole has the potential to be repositioned for AD treatment.Communicated by Ramaswamy H. Sarma.
GC-MS analysis and in silico docking of constituents of Cinnamomum malabatrum against CYP450 17α and CYP450 19 (Aromatase)- Key targets for hyperandrogenism V. Soumya, S. Deepa, Knolin.K. Thachil, J. Saravanan, R. Hariprasad Drug Research, 2023 Poly cystic ovary syndrome (PCOS) is considered as one of the common hormonal disorders affecting 6–20% of women in their reproductive age with characteristic features include anovulatory infertility, hyperandrogenism, cystic follicles and insulin resistance. The gene CYP play an important role in pathophysiology of hyperandrogenism associated with PCOS. An elevated androgens are reported in PCOS condition due to overexpression of the enzyme CYP450 17 α. As well as diminished levels of aromatase (CYP450 19) were observed in several hyperandrogenic PCOS patients. The powdered leafy material of Cinnamomum malabatrum was subjected to Soxhlet extraction. The plant extract was subjected to Gas chromatography-MS analysis (GC-MS), and the chromatogram obtained revealed the presence of active chemical constituents like 1(10),9(11)-B-Homolanistadiene for the first time and other potential compounds. Hypothesis has raised to interpret the efficiency of phytoconstituents of Cinnamomum malabatrum on these enzyme targets and which may be a novel drug candidate for the treatment and maintenance of hyperandrogenism associated with PCOS. Thus, the results obtained from the in-silico study of Cinnamomum malabatrum leaf extract using computational approaches indicate that the phytoconstituents have good affinities for the selected two key targets. ADME and PASS studies has been performed for active phytoconstituents homolanistadiene, β-sitosterol, cycloartenol and a pyrazole derivative, and results revealed the Lipinski drug-likeness and pharmacological potential. In conclusion, this work throws a new insight into the possibility of the active phytoconstituents on binding the two active CYP45017 α and CYP45019 aromatase enzymes which facilitates development of novel compounds for hyperandrogenism associated with PCOS.
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