Current Indian Science - Volume 3, Issue 1, 2025

The worldwide increase of antimicrobial resistance in ESKAPE pathogens, which includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp., constitutes a substantial public health hazard, constraining treatment alternatives and elevating morbidity and mortality rates. As traditional antibiotics diminish in efficacy, phytochemicals are capturing interest due to their varied antibacterial characteristics and decreased susceptibility to developing antibiotic resistance. Phytochemicals, such as alkaloids, terpenes, phenolics, flavonoids, and organosulfur compounds, have multi-target processes that might provide innovative strategies for addressing infections caused by ESKAPE pathogens.

The investigation sought to evaluate the effectiveness and mechanisms via which different phytochemicals could hinder and destroy the resistance pathways of ESKAPE bacteria, emphasizing their potential to serve as therapeutic agents in combating antimicrobial resistance.

Investigation demonstrates that some phytochemicals may disrupt many bacterial functions, such as cell wall production, membrane integrity, quorum sensing, and biofilm development in ESKAPE pathogens. For example, carvacrol from essential oils has shown efficacy against S. aureus by reducing staphyloxanthin synthesis and altering regulatory proteins, including SarA. Furthermore, conessine has altered resistance in A. baumannii by inhibiting the AdeIJK efflux pump. Flavonoids like resveratrol and curcumin have shown synergistic benefits with conventional antibiotics by improving their effectiveness while minimizing toxicity. These chemicals address several resistance pathways, impairing the ability of infections to build resistance.

Phytochemicals provide an opportunity to facilitate the development of novel therapies targeting antimicrobial resistance in ESKAPE bacteria. Extensive efficacy and distinctive multi-target mechanisms of phytochemicals provide them promising candidates for combination therapy, possibly reinstating antibiotic effectiveness and decelerating the development of resistance. Additional investigation into the increase of bioavailability and clinical usage is essential to fully exploring the medicinal potential of phytochemicals.

Biofilms are complex microbial communities, exhibiting antibiotic resistance that makes their inhibition difficult. Iron availability is known to affect biofilm formation. Biofilm inhibition can be achieved by altering iron concentrations. One aspect of this study involved the evaluation of the effects of iron salts such as ferric ammonium citrate (FAC), ferrous sulfate (FeSO4), and chelating agents like ethylenediaminetetraacetic acid (EDTA) on biofilm formation. In addition, the study explored the effect of bioactive compounds from natural sources, including plant extracts and food waste derivatives, for biofilm inhibition and control.

This study investigated the effect of iron salts on biofilm formation in Staphylococcus aureus and Escherichia coli. Additionally, methanolic extracts of food wastes of onion, potato, sweet lime, and banana peels were screened for their antimicrobial and anti-biofilm activity. Biofilm quantification was performed using crystal violet (CV) staining assays.

50 μM of Ferrous sulphate and EDTA was used, which significantly inhibited biofilm formation in both S. aureus ATCC 25923 and E. coli. DH5α FAC increased E. coli DH5α biofilm formation by 27%, while decreasing S. aureus ATCC 25923 biofilms by 48%. In contrast, the addition of Ferrous Sulphate led to a 61.12% reduction in E. coli DH5α biofilm. EDTA, an iron chelator, significantly reduced biofilm formation in both S. aureus ATCC 25923 and E. coli DH5α by 64% and 63%, respectively. Food waste extracts exhibited varying degrees of biofilm inhibition: hot onion extract showed a 63% reduction in E. coli DH5α biofilm, while its cold counterpart reduced E. coli DH5α and S. aureus ATCC 25923 biofilms by 36% and 27%, respectively. Cold banana extracts inhibited E. coli DH5α biofilm by 72%, and potato extracts (hot and cold) reduced E. coli DH5α biofilm by 76.30% and 77.70%, and S. aureus ATCC 25923 by 59% and 32.04%, respectively. Sweet lime hot extract reduced S. aureus ATCC 25923 biofilms by 42.30%, whereas its cold extract led to enhanced biofilm formation.

The findings demonstrate that both iron modulation and natural bioactive compounds derived from food wastes affect the dynamics of biofilms differently in Gram-positive and Gram-negative bacteria. Iron limitation and chelation effectively disrupted biofilm establishment, while metabolites from food wastes exerted additional inhibitory effects, highlighting an eco-friendly approach to biofilm control. The variations in the effects of different extracts suggest that the stability of bioactive compounds and temperature play crucial roles in biofilm inhibition.

In this study, it was observed that iron modulation and the use of bioactive compounds derived from food waste can effectively inhibit biofilm formation. These findings suggest sustainable strategies for biofilm control and could aid in developing alternative antimicrobial approaches.

Glioblastoma (GBM) is a highly aggressive brain cancer with limited therapeutic options. The epidermal growth factor receptor (EGFR) plays a critical role in tumor progression, making it a promising target for novel treatments. This study aimed to identify plant-derived phytochemicals as potential EGFR inhibitors to enhance the management of GBM.

Computational approaches were utilized, including virtual screening of phytochemicals from the NPACT database against the EGFR crystal structure (PDB ID: 5XWD). Molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling, and 50 ns molecular dynamics (MD) simulations were performed to evaluate binding affinity, pharmacokinetic properties, and complex stability using metrics, such as root mean square deviation (RMSD), radius of gyration (Rg), and solvent-accessible surface area (SASA). Cytotoxicity was assessed against the SF-295 GBM cell line.

Three phytochemicals, 2,3-dihydrowithaferin A, strophanthidin, and 6,8-diprenyleriodictyol, demonstrated strong EGFR binding affinities (-8.5 to -7.9 kcal/mol), favorable drug-like properties, and optimal ADMET profiles. MD simulations confirmed stable binding for 2,3-dihydrowithaferin A and 6,8-diprenyleriodictyol, with low RMSD (<2.5 Å), compact Rg (<2.2 nm), and reduced SASA. Only 6,8-diprenyleriodictyol exhibited cytotoxicity against SF-295 GBM cells (Pa = 0.383).

The findings position 6,8-diprenyleriodictyol as a promising EGFR inhibitor due to its balanced binding affinity, pharmacokinetic profile, and selective cytotoxicity, potentially addressing limitations of current EGFR inhibitors like erlotinib in GBM. The stable binding and favorable ADMET properties suggest potential for CNS penetration; however, the P-glycoprotein substrate status warrants further investigation. However, there is a need for in vitro and in vivo validation to confirm its efficacy and selectivity.

6,8-Diprenyleriodictyol emerges as a lead candidate for EGFR-targeted GBM therapy, supported by its strong binding, favorable pharmacokinetics, and cytotoxicity against GBM cells. Further experimental studies are needed to validate its therapeutic potential and overcome challenges, such as BBB penetration.

To overcome the drugs’ low bioavailability and/ or solubility, the development of novel oral delivery approaches using lipid-based formulations has been of growing interest. Curcumin being a Class IV drug, has poor solubility and poor permeability. One of the biggest obstacles to its use in therapeutic treatment is this.

In order to increase drug bioavailability, this research aimed to create Solid Dispersion Lipid Particles (SDSLs), in which Solid Dispersion (SD) was enclosed in solid lipid particles as the drug's core packaging.

For this, Curcumin (CUR) was selected as a model drug, PEG 6000 was used as a polymer, Stearic acid was used as the lipid phase, and Poloxomer 188 was used as a surfactant. Different batches of SD were formulated by solvent evaporation method. SDSLs were prepared by the melt-emulsification ultrasonication method and characterized for their % yield, % drug loading, % drug encapsulation efficiency, zeta potential, FTIR spectroscopy, XRD studies, in vitro drug release, and ex vivo permeation.

The optimized formulation showed the highest % EE and sustained in vitro drug release. The release mechanism was Super Case II, and the Higuchi equation was the best fit for the data.

SDSLs have sustained release effects and demonstrated enhanced ex vivo permeability which could lead to improved bioavailability. These studies demonstrate that SDSL could be a promising oral formulation for enhanced bioavailability.

The escalation of metabolic imbalance in obesity not only diminishes lifespan but also accelerates the cellular and biomolecular mechanisms of aging. This study aimed to explore the effect of intermittent fasting on FOXO3 expression, proteasome activity, and oxidative stress in obesity as parameters that play a role in the aging molecular process.

A randomized clinical trial was conducted in Jakarta. The study enrolled 50 obese males, divided into a control group of 25 individuals and an intervention group of 25 individuals. Over the course of 8 weeks, the intervention group adhered to a 5:2 intermittent fasting regimen, fasting for two days each week, specifically on Mondays and Thursdays. The food intake was monitored through food records and analyzed using the NutriSurvey 2007 program. Prior to and following the intervention, whole blood samples were collected for the analysis of FOXO3 expression, proteasome activity, and oxidative stress, assessed by measuring carbonyl, reduced glutathione/GSH, and total antioxidant capacity.

The fasting group exhibited a lower consumption of complex carbohydrates, fats, and proteins compared to the control. Notably, there was a significant increase in FOXO3 expression and proteasome activity observed in the intermittent fasting group compared to the control. Furthermore, oxidative stress was mitigated in the intermittent fasting group, as evidenced by a decrease in carbonyl and an increase in GSH levels and total antioxidant capacity.

The 5:2 intermittent fasting over an 8-week period promotes increased FOXO3 expression and proteasome activity while reducing oxidative stress, thereby potentially delaying the aging process in obesity.

This study has been registered online at www.clinicaltrial.gov (ID: NCT04319133).

Among fertile women, Polycystic Ovarian Syndrome (PCOS) is a prevalent metabolic and endocrine condition. This disorder is characterised by hyperandrogenism (high levels of male hormones), recurrent anovulation (ovulation failure), and polycystic ovaries. Infertility, hirsutism, and irregular menstruation are typical symptoms. The primary objective of this review is to provide a current and comprehensive approach to treating PCOS.

The databases PubMed, Frontiers, ScienceDirect, Springer, Wiley, and MDPI were utilised for the literature search. We used keywords, such as PCOS, hirsutism, medicinal plants, obesity, anovulation, and related variations to identify relevant articles and materials.

The findings indicated that several herbal remedies, such as Saraca asoca, Moringa oleifera, Asparagus racemosus, Glycyrrhiza glabra, Panax ginseng, and Cimicifuga racemosa, as well as various natural compounds, including glycosides, anthraquinones, chlorogenic acid, apigenin, epigenin, and flavonoids, show preliminary evidence supporting their potential in the management of PCOS.

Herbal treatments are appealing because they are natural and may have fewer side effects. Several herbs have shown promise in managing PCOS symptoms. While traditional treatments for PCOS remain important, the growing interest in complementary and alternative therapies highlights the need for further research into the efficacy and safety of medicinal plants. Alternative approaches may include lifestyle modifications, nutritional supplements, and the use of herbal remedies.

This review primarily focuses on evaluating the efficacy of herbal medicines in the management of PCOS. The drawbacks of traditional therapy are driving an increase in interest in alternative treatments for PCOS management. New scientific findings and their application in conventional therapy suggest that they may play a crucial role in the overall treatment of this complex illness.

Urinary Tract Infections (UTIs) represent one of the most common microbial diseases affecting individuals across age groups. This study aimed to investigate the microbiological profile and antibiotic utilization patterns among UTI patients at a tertiary care hospital.

A prospective observational study was conducted at the Maharishi Markandeshwar Institute of Medical Science and Research (MMIMSR), Mullana, Ambala. The study duration was from January 1, 2021, to April 30, 2021. A total of 323 patients aged 12 years and above with culture-confirmed UTIs receiving antimicrobial treatment were included. Data collected included demographics, urine culture results, and antimicrobial susceptibility patterns.

Out of 323 urine samples analyzed, 165 (51.08%) showed significant microbial growth. The majority of positive cases were from females (54.7%) and patients aged 50–70 years. Escherichia coli (44%) was the most prevalent organism, followed by Enterococcus spp. (11.14%), Klebsiella pneumoniae (8.9%), Pseudomonas aeruginosa (8.04%), and Staphylococcus aureus (6.19%). Gram-negative isolates exhibited high resistance to ampicillin (70%) and nalidixic acid (10.5%), but were more sensitive to nitrofurantoin (10.8%), imipenem (8.6%), and meropenem (7.4%). Gram-positive organisms showed sensitivity to tigecycline (6.5%), linezolid (7.1%), and sulfamethoxazole (7.7%).

The study demonstrates a significant prevalence of multidrug-resistant pathogens in UTIs. Escherichia coli remains the most frequent uropathogen. The findings underscore the importance of regular microbiological surveillance and sensitivity profiling to inform empirical treatment decisions. The inclusion of patients aged 12 and above ensures broader representation across age demographics.

UTIs in tertiary care settings are predominantly caused by Escherichia coli, with varying levels of antibiotic resistance. Local sensitivity patterns should guide empirical treatment. The implementation of antimicrobial stewardship programs is essential to combat the rising trend of antimicrobial resistance.

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia and associated complications, including cardiovascular disease, neuropathy, and renal impairment. While conventional therapies such as insulin and oral hypoglycemics manage glycemia, they often fail to address the underlying metabolic disturbances or prevent long-term complications. This has prompted interest in complementary approaches, including traditional herbal formulations.

A comprehensive literature review was conducted across PubMed, Scopus, Google Scholar, and the AYUSH Research Portal for the period 1951–2024. Search terms included ‘Nishamalaki Churna,’ ‘Amla,’ ‘Haridra,’ ‘diabetes,’ ‘oxidative stress,’ and ‘insulin resistance.’ Classical Ayurvedic texts were reviewed alongside experimental and clinical studies. The inclusion criteria encompassed peer-reviewed research on Nishamalaki Churna (NAC) or its components (Emblica officinalis and Curcuma longa) in the context of diabetes.

Amla improves insulin sensitivity and reduces oxidative stress due to its high antioxidant and vitamin C content. Haridra, rich in curcumin, exhibits anti-inflammatory and insulin-sensitizing effects. In combination, NAC demonstrates synergistic action, improving glucose metabolism and metabolic regulation. Preclinical studies report decreased blood glucose and HbA1c, enhanced antioxidant enzyme activity, and inhibition of carbohydrate-digesting enzymes. Clinical trials have revealed improvements in fasting/postprandial glucose levels, lipid profiles, and symptomatic relief, with minimal side effects.

NAC offers a multifaceted therapeutic effect through antioxidant, anti-inflammatory, and metabolic regulatory mechanisms. Its polyherbal composition provides a synergistic approach distinct from single-agent pharmaceuticals. However, challenges in formulation standardization and the need for large-scale clinical validation persist.

NAC holds promise as a safe, complementary intervention in type 2 diabetes management, warranting further clinical investigation.

This study aims to identify and evaluate novel KRAS G12C inhibitors using in-silico methods, focusing on molecular docking and ADMET profiling to optimize binding affinity, pharmacokinetics, and safety profiles.

The KRAS G12C mutation is a key driver of oncogenesis in aggressive cancers, including non-small cell lung cancer. Although inhibitors such as sotorasib have been developed, challenges like hepatotoxicity and resistance limit their clinical use.

This study seeks to design and assess potential KRAS G12C inhibitors with superior binding interactions and pharmacokinetic properties compared to existing drugs.

Molecular docking simulations were conducted to evaluate the binding affinities of inhibitors, followed by ADMET profiling to assess pharmacokinetics, drug-likeness, and toxicity.

Novel compounds, such as CID_137278727, demonstrated higher binding affinities (-10.8 kcal/mol) and favourable ADMET profiles compared to sotorasib (-8.1 kcal/mol). Key interactions with residues GLU62, TYR96, and CYS12 were identified, though hepatotoxicity remains a concern.

In-silico approaches have identified promising KRAS G12C inhibitors with enhanced efficacy and pharmacokinetics, highlighting the potential of computational methods in advancing targeted therapies for KRAS-driven cancers.

The presence of synthetic dyes like Congo Red in wastewater poses serious and persistent environmental health hazards as a result of their toxicity and stability. Therefore, developing an efficient and reusable adsorbents for the elimination of dye is quite important in order to address water pollution challenges.

The study aims to classify the efficacy of sodium borohydride-reduced Bent/Fe NPs and crude bentonite in removing Congo Red dye from aqueous solutions.

Sodium Borohydride was utilized in order to synthesize Bent/Fe NPs, dragging its reducing capacities in order to enhance its adsorption properties. Batch adsorption experiments were performed in order to estimate the removal efficacy under multiple conditions consisting of initial dye concentration, pH and contact time. Adsorption isotherms and kinetics were analyzed using Freundlich and pseudo-second-order models.

Bent/Fe NPs exhibited significant removal efficiency, reaching up to 91.97% removal of Congo Red dye with an initial concentration of 40 mg/L in alkaline conditions. Adsorption data was found to align well with the Freundlich isotherm model, signifying heterogeneous adsorption sites. It also fitted well with pseudo-second-order kinetic model indicating that chemisorption is the dominant mechanism taking place. Also, the adsorbent displayed excellent reusability, preserving substantial efficiency up to three cycles.

Sodium borohydride reduced Bent/Fe NPs offer an assuring, efficient and reusable solution for Congo Red dye removal from aqueous solution. The high adsorption capacity and, its affinity with alkaline conditions and its excellent reusability make them a feasible choice for wastewater treatment applications.