KLE University's College Of Pharmacy (KLESCOPH) is private institute for higher education in pharmacy in Hubli, Karnataka, India. It was established in 1985 by the KLE Society.
DPP-4 inhibitors have been shown to reverse amyloid deposition in Alzheimer's disease (AD) patients with cognitive impairment. Ocimum sanctum L. leaves reported the presence of important phytoconstituents which are reported to have DPP-4 inhibitory activity. To investigate the effects of petroleum ether extract of Ocimum sanctum L. (PEOS) in Intracerebroventricular streptozotocin (ICV-STZ) induced AD rats. ICV-STZ (3 mg/kg) was injected bilaterally into male Wistar rats, while sham animals received the artificial CSF. The ICV-STZ-induced rats were administered with three doses of PEOS (100, 200, and 400 mg/kg, p.o.) for thirty days. All experimental rats were subjected to behaviour parameters (radial arm maze task and novel object recognition test), neurochemical parameters such as GLP-1, Aβ42, and TNF-α levels, and histopathological examination (Congo red staining) of the left brain hemisphere. PEOS significantly reversed the spatial learning and memory deficit exhibited by ICV-STZ-induced rats. Furthermore, PEOS also shows promising results in retreating Aβ deposition, TNF α, and increasing GLP-1 levels. The histopathological study also showed a significant dose-dependent reduction in amyloid plaque formation and dense granule in PEOS -treated rats as compared to the ICV-STZ induced rats (Negative control). The results show that extract of Ocimum sanctum L. attenuated ICV-STZ-induced learning and memory deficits in rats and has the potential to be employed in the therapy of AD.
The synthesis of thiazole linked pyrimidine and chalcone derivatives 20a-j was achieved by the Claisen-condensation reaction between thiazole-aldehyde and different types of aryl ketones in the presence of piperidine in ethanol at reflux for 12 h time. These derivatives were tested for their cytotoxicity values against MCF-7, A2780, A549 and Colo-205 cell lines with Etoposide as standard drug by utilizing MTT reduction assay protocol. Among the synthesized derivatives, the derivative 20a with 3,4,5-trimethoxyaryl ring showed superior anticancer effect on all cell lines, with IC50 values from MCF-7 = 0.05 ± 0.007 µM; A549 = 0.11 ± 0.047 µM; Colo-205 = 0.66 ± 0.062 µM and A2780 = 0.96. ± 0.075 µM. Molecular docking studies targeting human Topoisomerase IIβ revealed that several synthesized compounds, 20a, 20b, 20f, 20 g, and 20j exhibited notable binding affinities (− 5.9 to − 5.5 kcal/mol) in comparison to the standard drug Etoposide (− 6.5 kcal/mol). These candidates showed favourable interactions with critical active site residues such as GLN778, ASP479, ARG503, and MET782, which are crucial for stabilizing the topoisomerase–DNA complex. The interaction patterns suggest a potential mechanism for modulation at the protein-DNA interface. Among these, compound 20a exhibited a favourable binding and interaction profile, positioning it as a promising hit for the development of novel anticancer therapeutics.
Activation modulated stimuli-responsive systems (AMS), commonly known as raft-forming systems (RFS), are an innovative platform within gastroretentive drug delivery technologies. These pH-triggered systems transform orally administered liquids from sol to a low-density, viscous floating gel or "raft" by ionotropic gelation upon contact with gastric-ions. Typically, composed of smart hydrophilic polymers, effervescent, and cross-linking agents, AMS stay buoyant in stomach and release drugs instantly in response to physiological stimuli to meet urgent clinical needs. These systems are especially valuable for drugs targeting local gastric action, reducing systemic exposure. AMS can be custom-designed to release therapeutic agents that exhibit high solubility or good stability in response to acidic conditions in stomach to maximize bioavailability. Owing to the strategic location, proximal to absorption window and ability to control release in stomach, AMS has the proven potential to improve the absorption of several therapeutics. AMS can be tailored to modulate microenvironment pH and thereby enhance delivery of drugs that exhibit solubility or stability challenges in an acidic milieu. This review is an attempt to offer an entirely new dimension to the composition, formulation strategies, evaluation techniques, and applications of AMS. Recent advances include development of systems comprising smart polymers that respond to specific physiological stimuli, multi-responsive systems, nanotechnology-integrated, and 3D printed systems. Despite challenges in formulation stability, scale-up, and reproducibility, these systems have generated considerable regulatory and commercial interest globally. Thus, AMS have emerged as a unique and innovative platform with high translational potential to leverage immense clinical benefits of diverse therapeutic agents.
Ailanthus excelsa Roxb. (Tree of Heaven), native to Central and Southern India, is traditionally recognized for diverse medicinal properties. However, its molecular mechanisms in metabolic disorder management remain largely unexplored. In the present study the hydroalcoholic bark extract of A. excelsa was analyzed by GC-MS/MS to identify bioactive phytoconstituents. Identified metabolites were subjected to network pharmacology, molecular docking, 100 ns MD simulations, FEL mapping, PCA, and DFT calculations. In vitro enzyme inhibition assays were performed against pancreatic lipase and HMG-CoA reductase to validate computational findings.The GC-MS/MS profiling revealed bioactive metabolites mapped to obesity-associated signaling pathways, including MAPK, PI3K-Akt, and Ras. Protein-protein interaction and target prediction highlighted key molecular nodes such as CCND1, INSR, PIK3CA, PIK3CG, RXRA, MTOR, and AKT1. Among the metabolites, AE4 exhibited better binding affinity towards the pancreatic lipase and HMG-CoA, with binding affinity superior to orlistat and simvastatin. MD simulations, FEL, and PCA confirmed stable enzyme-ligand complexes with persistent hydrogen bonding, hydrophobic, and water-bridge interactions. DCCM analysis indicated ligand-induced stabilization of intra-domain interactions. DFT results demonstrated that AE4 had the lowest HOMO-LUMO energy gap (0.144 eV) and highest softness, signifying enhanced chemical reactivity and stability.This integrated chemico-pharmacological investigation identifies AE4 as a promising lead metabolite from A. excelsa with potential therapeutic application in obesity and related metabolic disorders.
Inflammation is a complex biological response driven by excessive activation of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), which play pivotal roles in chronic inflammatory diseases. Given the safety and wide clinical use of atorvastatin, this study aimed to explore its potential repurposing as an anti-inflammatory agent through the inhibition of these cytokines. Molecular docking was performed to predict the binding affinity and interaction profile of atorvastatin with TNF-α, IL-1β, and IL-6, followed by 200 ns molecular dynamics (MD) simulations, principal component analysis (PCA), and energy calculations to evaluate the stability and energetics of the complexes. Furthermore, the anti-inflammatory effects of atorvastatin (5–20 µM) were evaluated in LPS-stimulated RAW 264.7 macrophages using MTT cytotoxicity, cytokine assays (TNF-α, IL-6, IL-1β), and nitric oxide quantification. Docking study revealed strong binding affinity toward TNF-α (− 7.9 kcal/mol) through hydrogen bonding, supported by stable MD trajectories. The MM-GBSA binding energy (− 72.90 ± 4.38 kcal/mol) confirmed a favorable and stable interaction predominantly driven by hydrophobic and van der Waals forces. In -vitro study revealed, that atorvastatin showed no cytotoxicity and produced a strong dose-dependent inhibition of TNF-α, IL-6, IL-1β, and nitric oxide levels, with maximal anti-inflammatory activity observed at 20 µM. These findings suggest that atorvastatin may directly inhibit TNF-α and related cytokines, thereby modulating NF-κB–mediated inflammatory signaling. This study provides molecular-level insight supporting the repurposing of atorvastatin as a promising multi-target anti-inflammatory therapeutic.
