Saurabh Gupta

Introduction: Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and associated complications, often linked to oxidative stress and impaired insulin signaling. This study investigates the antidiabetic and antioxidant effects of the ethanolic extract of Sapindus trifoliatus leaves (STLE) in alloxan-induced diabetic rats, with a focus on modulation of the PI3K/AKT signaling pathway. Methods: Phytochemical analysis revealed the presence of flavonoids and saponins in STLE. Acute toxicity testing confirmed its safety. Alloxan-induced diabetic rats were treated with STLE, and evaluated using oral glucose tolerance tests (OGTT), fasting blood glucose levels, lipid profile analysis, and antioxidant enzyme assays (GSH, SOD, CAT, and MDA). Liver tissues were examined histologically to assess morphological changes. Results: STLE significantly reduced fasting blood glucose levels and improved glucose tolerance. Treated rats exhibited improved lipid profiles, with reductions in total cholesterol, triglycerides, and LDL, and an increase in HDL levels. Antioxidant enzyme levels (GSH, SOD, CAT) were elevated, while MDA levels decreased, indicating reduced oxidative stress. Histological studies revealed improved liver architecture in treated groups. Discussion: The antidiabetic and antioxidant effects of STLE suggest its action may be mediated via activation of the PI3K/AKT pathway, supporting its traditional use in diabetes treatment. Conclusion: STLE demonstrates promising antidiabetic and antioxidant potential in vivo, indicating its therapeutic relevance in managing diabetes and associated complications. Further studies are needed to explore its molecular mechanisms and clinical applicability in detail.

Antimicrobial resistance (AMR) is a worldwide health crisis challenging existing antibiotics, leading to increased mortality. Since their discovery in the early twentieth century, antibiotics have transformed medicine and saved countless lives. But today, the worrying increase in antibiotic resistance casts a shadow over the discovery of antibiotics. The abuse and overuse of antibiotics has led to the unrelenting adaptability of microbes, which is the cause of this global issue. With particular attention on ciprofloxacin (CIP), 2nd generation fluoroquinolones work by preventing DNA gyrase and topoisomerase IV from performing their vital functions, which include transcription, recombination, replication, and condensed DNA remodeling. Numerous researchers have developed CIP derivatives that are promising treatments, but factors such as overuse, multiple drug therapy, and misuse contribute to widespread resistance along with different side effects. So, to overcome such problems, diverse strategies to enhance CIP efficacy are examined, including synthetic approaches such as hybridization, Mannich reaction, and oxidation, aiming to modify the structure of CIP and create novel compounds with potentially enhanced biological activities, improved efficacy, or reduced side effects, which happens as a result of chemical and physical changes, typically involving one or more reactions. Along with this, nanotechnology for drug delivery and synergistic combinations with aminoglycosides, tobramycin, or azithromycin, antimicrobial peptides (AMPs) and monoclonal antibodies (mAbs) offer potential to combat multidrug-resistant strains. This review provides insights into potential breakthroughs necessary to overcome AMR challenges and advance effective emerging synthetic and delivery approaches for antibacterial treatments. Overall, we have compiled different emerging strategies to develop CIP derivatives with the aim of discovering new and more effective ways to combat drug-resistant infections.

Background: This research explored the antimicrobial, antifungal, and in vivo anticandidal activities of two herbal extracts: Ocimum basilicum (HEOB) and Ocimum sanctum (HEOS). Additionally, the study analyzed the phytochemical components of these extracts. Aim: To examine the efficacy of HEOB and HEOS extracts in terms of their antimicrobial, antifungal, and anti-candidal activities and analyze their phytochemical composition, antioxidant potential, and immunomodulatory properties in vivo. Methods: Dried flowers and leaves from Ocimum basilicum and Ocimum sanctum were extracted using a cold maceration process with a 1:1 ethanol-water solution. Phytochemical analysis followed established protocols, and the total phenolic and flavonoid contents were measured using colourimetric methods. HPLC was used to determine the concentrations of specific compounds, including rosmarinic acid, rutin, eugenol, and quercetin. Antioxidant activity, specifically nitric oxide (NO) scavenging and antimicrobial properties, was assessed in vitro using the cup plate method. In vivo studies were conducted on immunocompromised mice with systemic candidiasis, treated with plant extracts at 200 and 400 mg/kg or with ketoconazole as a control. Survival rates, tissue histology, and leukocyte counts were evaluated, and statistical analysis was performed using ANOVA. Results: HEOB and HEOS extracts possess strong antimicrobial and antioxidant activities, largely due to flavonoids such as rutin, quercetin, rosmarinic acid and eugenol. In vivo experiments revealed that both extracts effectively reduced fungal load, increased survival rates, and alleviated immunosuppression in mice with systemic candidiasis. The extracts also exhibited significant immunomodulatory properties by boosting cellmediated immune responses. At higher concentrations, the antifungal performance of HEOB and HEOS was similar to that of ketoconazole. Conclusion: HEOB and HEOS exhibited strong antibacterial, antifungal, and anticandidal properties, showing significant effectiveness in treating systemic candidiasis. Their immunomodulatory effects and ability to boost cell-mediated immunity make these extracts promising options for addressing systemic candidiasis, particularly in individuals with weakened immune systems. This research offers valuable insights and sets the stage for future investigations into the treatment of oral and vaginal candidiasis.

Neurodegenerative diseases (NDs), including Alzheimer’s, Amyotrophic lateral sclerosis, Huntington’s, and Parkinson’s, present an increasingly widespread health burden globally with limited curative or treatment modalities, mostly having symptomatic attenuation. Berberine (BBR) is an isoquinoline alkaloid that occurs naturally and has been proposed as a potential neuroprotectant, since it has been found to exert multiple effects to modulate most of the pathological hallmarks of NDs, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and protein aggregation. Although it shows promise, the practical utilization of BBR is marred by low oral bioavailability, high rate of oxidation, and low blood-brain barrier permeability. To combat these issues, recent developments in nanotechnology, especially in the use and creation of lipidic, inorganic, and polymeric nano-particles, have dramatically altered the pharmacokinetics and pharmacodynamics of BBR. This article summarizes recent advances in BBR-based nanoformulations and emphasizes the translational potential of BBR-based nanopreparations to improve treatment response in NDs. It also describes the molecular foundation of the neuroprotective effects of BBR and its possible place in clinical practice. Future nanocarrier development and investigation of BBR mechanisms will be essential to the development of the next generations of therapeutics in NDs. Graphical abstract

Introduction: Laurus nobilis (bay laurel) is a widely used plant known for its culinary, cosmetic, therapeutic, and pharmacological properties. Its leaves are particularly valued due to their rich content of bioactive compounds, such as essential oils, phenolic substances, flavonoids, and alkaloids. This review aimed to provide a comprehensive overview of the botanical characteristics, chemical composition, and therapeutic and industrial applications of these compounds. Methods: An extensive literature review was conducted using scientific databases to collect and analyze published studies on the botanical traits, chemical constituents, traditional uses, pharmacological activities, and industrial applications of L. nobilis leaves. Results: The analysis revealed that bay leaves contain a variety of bioactive components, notably essential oils, phenolics, flavonoids, and alkaloids. These compounds exhibit significant pharmacological properties, including anti-inflammatory, antimicrobial, antioxidant, and anticancer activities, as supported by various in vitro and in vivo studies. Discussion: The findings underscore the therapeutic relevance of L. nobilis leaves, aligning with traditional medicinal practices and modern pharmacological research. However, limitations exist in terms of standardized extraction methods and clinical trials, which must be addressed to validate and optimize their therapeutic use. Conclusion: Laurus nobilis leaves are a promising natural source of pharmacologically active compounds. Their diverse applications across traditional medicine, modern pharmacology, and industrial sectors highlight their continuing relevance and potential for broader utilization.

The development of multiple sclerosis (MS) heavily depends on cellular senescence, which results in permanent cell cycle arrest that subsequently leads to tissue damage alongside chronic inflammation. Senescent cells inside the central nervous system (CNS) use pro-inflammatory substances to damage CNS cells while also causing cellular breakdown, which becomes two main elements in MS development. The development and severity of illness within experimental autoimmune encephalomyelitis (EAE) animal models can be attributed to senescence. Physical tests conducted on MS patients have revealed the presence of senescence markers, which might serve as indicators for monitoring disease activity. A potential method to combat illness progression consists of employing senolytics alongside other modulators, but scientists must find solutions regarding specificity and safety concerns and determine optimal times for intervention. The assessment of unintentional tissue damage from treatments requires thorough investigation since these treatments could potentially affect normal tissues. Long-term studies must develop reliable biomarkers that detect cellular aging in individuals so they can get personalized medical care which enables better management of MS with targeted treatment plans. Eventually, senescence-targeted therapies will develop into new therapeutic approaches for delaying multiple sclerosis disease progression while improving treatment results.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder in the elderly, characterized by extracellular amyloid β‑ (Aβ) plaque deposition and intracellular neurofibrillary tangles (NFTs). Impaired autophagy, the cellular pathway for degrading damaged organelles and misfolded proteins, and cellular senescence, permanent cell cycle arrest with proinflammatory secretions, have emerged as key contributors to AD pathogenesis.Methods: We performed a narrative review of recent mechanistic and preclinical studies investigating (1) autophagic flux and its role in Aβ and tau clearance; (2) the accumulation and secretory phenotype of senescent cells in the aging brain; (3) interactions between autophagy impairment and senescence; and (4) the efficacy of autophagy enhancers (e.g., rapamycin and metformin) and senolytic agents in rodent models of AD.Results: Defective autophagosome–lysosome fusion in AD causes autophagic vacuole buildup with amyloid precursor protein and β‑secretase, boosting Aβ generation and hindering tau clearance, promoting neurofibrillary tangles. In AD models, senescent neurons and microglia release pro‑inflammatory cytokines (SASP), fueling neuroinflammation and synaptic dysfunction. Decline in autophagy induces senescence and blocks clearance in a vicious cycle. Rapamycin and metformin restore autophagic flux, reduce Aβ and tau pathologies, and improve memory. Senolytics clear senescent cells, reduce inflammation, and rescue cognition.Conclusion: Dysregulated autophagy and cellular senescence interact to drive the progression of AD. Targeting these pathways with autophagy‐boosting drugs and senolytic agents holds promise for disease‐modifying therapies aimed at halting or reversing neurodegeneration in Alzheimer's disease.