Damodar Nayak Ammunje

Breast cancer is a prevalent and aggressive tumor affecting women, known for its molecular diversity and treatment resistance. This study investigates the anticancer potential of Icariin (ICA), a flavonol glycoside derived from Herba epimedii, against breast cancer using network pharmacology and molecular simulation. Using the SwissTargetPrediction database and GeneCards, the researchers identified 98 common targets shared by ICA and breast cancer. Gene ontology (GO) and KEGG enrichment analyses highlighted the targets' roles in the regulation of apoptosis, inflammatory signaling, receptor tyrosine kinase activity, chemokine signaling, sphingolipid metabolism, and VEGF pathways. Molecular docking revealed ICA's strong binding affinity for key oncogenic proteins, with binding energies ranging from −12 to −7.5 kcal/mol, particularly to SER783, THR862, ASP863, LYS753, and ARG849. Molecular dynamics (MD) simulations demonstrated the structural stability of the ICA‐HER2 complex, which maintained strong hydrogen bonds and exhibited minimal conformational changes over a 1000 ns trajectory, with average RMSD values of 1.7 Å for the protein and 1.0 Å for the protein‐ligand complex. Furthermore, ICA exhibited favorable pharmacokinetic properties, including moderate solubility and negligible inhibition of cytochrome P450. These findings support the hypothesis that ICA may serve as a valuable natural compound for treating HER2‐driven breast cancer; it requires further experimental validation.

The study aimed to identify the potential acetylcholinesterase (AChE) inhibitors for effective Alzheimer’s treatment from existing FDA-approved drugs through a drug repurposing technique via computational tools. Further, to evaluate the anti-Alzheimer’s potency of the identified drug with the help of a suitable drug delivery system through in vivo pharmacological studies. The molecular docking and dynamics simulation studies indicated that letrozole has a significant binding affinity of -9.6 kcal/mol and a better interaction with AChE. The physicochemical properties of letrozole-encapsulated solid lipid nanoparticles (L-SLNs) were characterized and confirmed. Initially, acute toxicity tests of L-SLNs were performed according to OECD 423 guidelines. Biochemical studies revealed that L-SLNs significantly decreased brain Acetylcholine esterase activity induced by scopolamine, but L-SLNs significantly increased AChE activity compared to the Shaam control group. Histopathological evaluation of brain regions revealed significant insights into the neuroprotective potential of L-SLNs in an Alzheimer’s disease (AD) rat model. Treatment with L-SLNs demonstrated dose-dependent neuroprotection across all studied brain regions. At a low dose of L-SLNs (2.5 mg/kg), neuronal and glial cells in the cortical and hippocampal regions showed improved regularity, although some disorganization persisted. At a mid-dose of L-SLNs (5 mg/kg), the histopathological architecture further normalized, with neurons and glial cells exhibiting regular arrangement and morphology akin to normal cells. The high dose of L-SLNs (10 mg/kg) provided the most significant protection, with neuronal and glial cells displaying near-normal arrangement and morphology in the cortical, hippocampal, and Substantia Nigra regions. This study highlights the importance of SLNs-based drug delivery systems in improving the efficacy of existing therapeutic agents in neurodegenerative conditions.

Alzheimer's disease (AD) is a gradual degenerative ailment of the nervous system that is marked by the buildup of amyloid-β plaques and neurofibrillary tangles. This accumulation causes problems with the connections between nerve cells and the loss of these cells. This review paper explores the complex pathophysiology of AD, analyzing the neuronal loss reported in key brain regions like the entorhinal cortex, amygdala, hippocampus, and cortical association areas. The text also examines subcortical nuclei participation, such as the noradrenergic locus coeruleus, serotonergic dorsal raphe, and cholinergic basal nucleus. Also, this review discusses the importance of tau protein hyperphosphorylation, oxidative stress, and metal ion dysregulation in the evolution of AD. Moreover, it explores the cholinergic theory and the influence of the APOE (apolipoprotein E) genotype on the effectiveness of therapy. This article thoroughly summarizes the current knowledge on AD, including its clinical symptoms and possible treatment approaches, by combining several theories and new targets. The study highlights the connection between the degree of tangle development and the severity of dementia, underlining the need for creative methods to tackle the complex difficulties of discovering drugs for AD.

Parkinson’s disease (PD) is an advanced neurodegenerative condition distinguished by the rapid decline of dopamine neurons in the midbrain, leading to an imbalance in dopamine and acetylcholine levels, precipitating associated symptoms. The main objective of this work was to fabricate solid lipid nanoparticles (SLNs) loaded with S-carboxymethyl-L-cystine (SC) for enhanced delivery to the brain. This study examines the impact of these SLNs on rotenone (RT) caused Parkinson’s disease (PD) in both rat and zebrafish models. The process of loading SC into SLNs was achieved through the solvent evaporation-emulsification method. The SC-encapsulated solid lipid nanoparticles (SCSLNs) were subjected to physicochemical evaluation, and their properties were verified. For 28 days, the rats received subcutaneous injections of RT at a dosage of 2 mg × kg⁻¹ body weight. Additionally, the rats in the experimental group received SCSLNs from the 14th to the 28th days of the trial. Interestingly, the locomotor activity, grip strength, and exploratory behaviour of the rats with SCSLNs significantly improved. Furthermore, it was observed that the quantities of acetylcholinesterase (AchE) inside the brain tissue had increased, and oxidative biomarkers had decreased. In addition, there was a discernible decrease in Lewy body development and cellular damage compared to the positive control group. Zebrafish were dosed with SCSLNs simultaneously as they were subjected to a 5 µg × L⁻¹ RT concentration for 28 days during the experiment. AchE levels in the fish brain increased, resulting in improved locomotor activity in the SCSLN group of zebrafish. The findings of this investigation imply that using SCSLNs may reduce Parkinson’s disease symptoms via enhanced delivery of SC into the brain.

Biologics targeting matrix‐degrading proteases, cartilage repair, and inflammation are emerging as promising approaches for osteoarthritis (OA) treatment. Recent research highlights biologic‐human placental tissue (HPT) as a potential OA therapy due to its biocompatibility, abundant protein biofactors, and ability to reduce cartilage degradation by suppressing protease expression. Microneedles (MNs) are receiving growing attention for enhancing transdermal delivery of biologics as an alternative to conventional subcutaneous injections. The lyophilized human placental extract (LHP) loaded polymeric MNs are fabricated using a micromolding technique for transdermal delivery. Ex vivo release studies reveal that MNs exhibit a gradual and consistent release of LHP, indicating a sustained delivery profile. LHP‐MNs are nontoxic and anti‐inflammatory in nature against human skin cells and interleukin (IL‐1β) induced synovial cells. Furthermore, the in vivo study shows that LHP‐MNs substantially improve behavioral parameters in OA rat models and lower serum concentrations of tumor necrosis factor‐ α (TNF‐α) and cartilage oligomeric matrix protein (COMP) biomarkers, thereby alleviating knee and ankle joint injuries. Histopathological analysis indicates that LHP‐MNs significantly preserve cartilage integrity. The study results suggest that employing polymeric MNs for transdermal delivery of LHP can be a promising treatment approach for OA, with the added benefit of excellent patient compliance.

Eukaryotic organisms contain an enzyme family called poly (ADP-ribose) polymerases (PARPs), which is responsible for the poly (ADP-ribosylation) of DNA-binding proteins. PARPs are members of the cell signaling enzyme class. PARP-1, the most common isoform of the PARP family, is responsible for more than 90% of the tasks carried out by the PARP family as a whole. A superfamily consisting of 18 PARPs has been found. In order to synthesize polymers of ADP-ribose (PAR) and nicotinamide, the DNA damage nick monitor PARP-1 requires NAD+ as a substrate. The capability of PARP-1 activation to boost the transcription of proinflammatory genes, its ability to deplete cellular energy pools, which leads to cell malfunction and necrosis, and its involvement as a component in the process of DNA repair are the three consequences of PARP-1 activation that are of particular significance in the process of developing new drugs. As a result, the pharmacological reduction of PARP-1 may result in an increase in the cytotoxicity toward cancer cells.

Artificial intelligence (AI) speeds up the drug development process and reduces its time, as well as the cost which is of enormous importance in outbreaks such as COVID-19. It uses a set of machine learning algorithms that collects the available data from resources, categorises, processes and develops novel learning methodologies. Virtual screening is a successful application of AI, which is used in screening huge drug-like databases and filtering to a small number of compounds. The brain’s thinking of AI is its neural networking which uses techniques such as Convoluted Neural Network (CNN), Recursive Neural Network (RNN) or Generative Adversial Neural Network (GANN). The application ranges from small molecule drug discovery to the development of vaccines. In the present review article, we discussed various techniques of drug design, structure and ligand-based, pharmacokinetics and toxicity prediction using AI. The rapid phase of discovery is the need of the hour and AI is a targeted approach to achieve this.

Introduction: Parkinson's disease (PD) is a chronic, devastating neurodegenerative disorder marked by the death of dopaminergic neurons in the midbrain's substantia nigra pars compacta (Snpc). In alpha-synuclein (α-Syn) self-aggregation, the existence of intracytoplasmic inclusion bodies called Lewy bodies (LBs) and Lewy neurites (LNs) causes PD, which is a cause of neuronal death. Methods: The present study is aimed at finding potential bioactive compounds from Cynodon dectylon that can degrade α-Syn aggregation in the brain, through in silico molecular docking investigations. Graph theoretical network analysis was used to identify the bioactive compounds that target α-Syn and decipher their network as a graph. From the data repository, twenty-nine bioactive chemicals from C. dactylon were chosen and their structures were retrieved from Pubchem. On the basis of their docking scores and binding energies, significant compounds were chosen for future investigation. The in silico prediction of chosen compounds, and their pharmacokinetic and physicochemical parameters were utilized to confirm their drug-likeness profile. Results: During molecular docking investigation the bioactive compounds vitexin (-7.3 kcal.mol-1) and homoorientin (-7.1 kcal.mol-1) showed significant binding energy against the α-Syn target protein. A computer investigation of molecular dynamics simulation study verifies the stability of the α-Syn-ligand complex. The intermolecular interactions assessed by the dynamic conditions indicate that the bioactive compound vitexin has the potency to prevent α-Syn aggregation. Conclusion: Interestingly, the observed results indicate that vitexin is a potential lead compound against α-Syn aggregation, and in vitro and in vivo studies are warranted to confirm the promising therapeutic capability.