Department of Pharmacy

Permanent URI for this collectionhttp://localhost:4000/handle/123456789/1931

Browse

Subject: search.filters.subject.Pharmacy Department

Search Results

Now showing 1 - 10 of 29
  • No Thumbnail Available
    Item
    Management and prevention of neurodegenerative disorders: can antioxidant-rich dietary interventions help?
    (MDPI, 2025-09) Pandey, Murali Monohar
    Neurodegenerative diseases are associated with the senescence of functional neurons, which hampers brain functions. These diseases are caused by the accumulation of reactive oxygen species, reactive nitrogen species, cholinesterase malfunction, neuronal inflammation, and mitochondrial dysfunction. The incidence of neurodegenerative disease has been on the rise. Current therapeutic interventions are expensive, exhibit poor efficacy, and have numerous side effects. Several studies have explored the potential of crucial dietary substances rich in antioxidants and micronutrients in alleviating the clinical manifestations of such deadly diseases. Consumption of sufficient antioxidants, fatty acids, and polyphenols in regular diets delays the onset of neurodegenerative diseases. Several medicinal plants, such as Withania somnifera, Curcuma longa, Panax ginseng, Ginkgo biloba, aloe vera, Punica granatum, and various phytoextracts, contain such micronutrients in reasonable amounts. Specific dietary interventions, supplements, and patterns such as the Mediterranean-DASH intervention for neurodegenerative delay, ketogenic, paleolithic, and Wahls elimination diets have been beneficial in neurodegenerative conditions. These diet interventions and other functional foods can be an attractive, non-invasive, and inexpensive approach in the management and prevention of neurodegenerative conditions. This review discusses potential pharmacological bases involved in neurodegeneration, covering mitochondrial damage, impaired mitophagy, neuroinflammation, ferroptosis, glymphatic clearance dysfunction, brain–body interactions, and disruption of vagus nerve stimulation. The review further highlights clinical diet interventions and assorted functional foods, including fruits, vegetables, vitamins, specific supplements, and special diets, for neurodegenerative conditions. The discussion extends insights into clinical research and trials of these functional foods under neurodegenerative conditions. Overall, dietary interventions show promise in the prevention and management of neurodegenerative conditions.
  • No Thumbnail Available
    Item
    Recent advancements in parallel and tandem reaction-based fluorogenic probes for tracing enzymatic activities
    (Elsevier, 2025-11) Sidhu, Jagpreet Singh
    Optical imaging is a non-invasive and indispensable technique for tracing enzymatic activities at a molecular level. However, unintended activation or off-target accumulation of imaging probes often leads to false-positive signals. Moreover, the use of multiple fluorophores to detect distinct biomarkers is limited by variability in cellular uptake and subcellular localization within complex biological environments. To address these deficiencies, multi-locked fluorogenic probes have been developed to target multiple biomarkers simultaneously. These probes typically employ parallel or tandem-locked configuration, wherein enzyme-specific substrates quench the fluorescence of reporter motifs until activation occurs. Recent advancements in multi-locked probes have revealed many opportunities for advancing non-invasive diagnostic chemical tools. This review systematically compiles recent progress in the development of enzyme-responsive dually locked probes for bio-imaging applications. It provides a comprehensive analysis of their underlying mechanisms and design strategies. The review concludes with a summary of current achievements and future perspectives in this rapidly evolving field.
  • No Thumbnail Available
    Item
    Esculetin and phloretin combination mitigates acute kidney injury-diabetes comorbidity via regulating mitophagy and inflammation: a dual-pronged approach
    (Wiley, 2025-03) Jadhav, Hemant R.; Gaikwad, Anil Bhanudas
    Induction of PINK1/Parkin-mediated mitophagy and reducing inflammation via targeting the TLR4/NF-κB axis simultaneously could be a promising therapy for the complex pathophysiology of AKI-diabetes comorbidity. Earlier, esculetin by mitophagy activation and phloretin by inhibiting inflammation have shown promising renoprotection. Therefore, we aimed to evaluate the synergistic renoprotective ability of esculetin and phloretin combination against AKI-diabetes comorbidity. AKI-diabetes comorbidity was mimicked in vivo by bilateral ischemia/reperfusion injury (IRI) in diabetic rats and in vitro by sodium azide-induced hypoxia/reperfusion injury (HRI) under hyperglycemic conditions. The cells were pretreated with esculetin (50 μM) and phloretin (50 μM) for 24 h. Similarly, the diabetic AKI rats received esculetin (50 mg/kg/day, p.o.) and phloretin (50 mg/kg/day, p.o.) pretreatment for 4 days and 1 h before surgery. Further, the obtained samples were utilized for different experiments. Esculetin and phloretin in diabetic AKI rats preserved kidney function and prevented kidney injury, indicated by reduced plasma creatinine, blood urea nitrogen, and kidney injury molecule 1. Esculetin improved mitophagy, indicated by increased mitophagosome formation, increased PINK1, Parkin, LC3B, and decreased p62 expression. Similarly, phloretin suppressed the diabetic AKI-related increased expression of inflammatory mediators including NF-κB, TLR4, TNF-α, and MCP-1. Moreover, combination therapy showed a more pronounced effect via synergistically improving mitophagy, maintaining ΔΨm, preventing mitochondrial dysfunction, reducing inflammation, and apoptosis. Esculetin and phloretin combination ameliorated AKI-diabetes comorbidity more effectively than their monotherapies. Esculetin upregulated the PINK1/Parkin-mediated mitophagy, and phloretin reduced inflammation by inhibiting the TLR4/NF-κB axis, thereby synergistically preventing kidney dysfunction.
  • No Thumbnail Available
    Item
    Corrigendum to: Design and development of chromene-3-carboxylate derivatives as antidiabetic agents: Exploring the antidiabetic potential via dual inhibition of angiotensin II type 1 receptor and neprilysin enzyme
    (Elsevier, 2025-10) Gaikwad, Anil Bhanudas; Jadhav, Hemant R.
    Diabetes mellitus, particularly type II diabetes mellitus, is a metabolic condition that has a substantial impact on the health of individuals. The implication of diabetes with increased risk of cardiovascular diseases (CVD) and, consequently, myocardial infarction is well established. However, developing new antidiabetic drugs with an established efficacy on cardiovascular health is an underdeveloped area of research. To address this, in the present study, a new series of chromene-3-carboxylate derivatives (1B1–1B22) as dual inhibitors of Angiotensin II Type 1 Receptor (AT1R) and Neprilysin (NEP), which are recognized targets in diabetes with CVD, is reported. The compounds were rationally designed and synthesized, considering the pharmacophoric features of these two targets. The evaluation was performed via glucose uptake, α-amylase, AT1R, and NEP inhibition assay. The derivatives were found to increase glucose uptake and inhibit all three targets, of which compound 1B15 was the most active. The most active compound, 1B15, reduced the oxidative stress and restored the mitochondrial membrane potential. The biological findings were further corroborated by in silico studies, which included molecular modelling and dynamics. It was deduced that 1B15 remains unionized in acidic to weak basic pH and may be passively absorbed. Further, the molecule was found to undergo hydroxylation as a means of Phase I metabolism and glucuronic conjugation in Phase II. The wet lab experiments on 1B15 further validated the insilico absorption and metabolism prediction. The compounds, particularly 1B15, could be explored further as a lead for its utility as an antidiabetic with profound implications on cardiovascular health.
  • No Thumbnail Available
    Item
    A novel combination of exogenous klotho combined with telmisartan ameliorated diabetic cardiomyopathy via an antifibrotic mechanism
    (Wiley, 2025-09) Jadhav, Hemant R.; Gaikwad, Anil Bhanudas
    Diabetic cardiomyopathy (DCM) is a progressive heart disorder associated with diabetes mellitus, leading to structural and functional cardiac abnormalities. The mechanisms responsible include renin-angiotensin-aldosterone (RAAS) activation, inflammation, apoptosis, and metabolic disturbances. Despite well-established epidemiological links, treatments for DCM are elusive. This study evaluated the efficacy of a novel combination of recombinant Klotho (KL) and the angiotensin receptor blocker telmisartan (TEL) in treating DCM, as well as investigating potential mechanisms involved. DCM was induced with a single dose of streptozotocin (55 mg/kg, i.p.), followed by a 4-week induction period. For treatment, rats were assigned to five groups: Normal control (NC), Diabetic control (DC), DC + KL (0.01 mg/kg, S.C.), DC + TEL (10 mg/kg, p.o.), and KL + TEL combination. Plasma biochemistry assessed cardiac damage (LDH, CK-MB) and stress markers (ANP, BNP). Electrocardiogram (ECG) measured heart parameters, including heart rate (HR), QTc, JT interval, RR interval, and Tpeak–Tend intervals. Histological analysis (H&E, Masson's trichrome, and Picrosirius red) was performed to assess myocardial structure and fibrosis. Lastly, immunohistochemistry analysis was performed to check the expression of transforming growth factor-β1 (TGF-β1), pSMAD 2/3, matrix metalloproteinase 9 (MMP9), and PRKN. KL and TEL combination treatment significantly reduced cardiac damage markers, reduced ECG abnormalities, including QTc, improved HR while suppressing pro-fibrotic signaling, enhancing mitophagy, and decreasing fibroblast proliferation. The involvement of pathways involving TGF-β1, pSMAD-2/3, MMP9, and pFOXO3a conferred protection to the heart in experimental in-vivo settings. These findings suggest that the combination of KL and TEL effectively mitigates key pathological features of DCM, highlighting its potential as a targeted treatment strategy.
  • No Thumbnail Available
    Item
    Emerging in diabetic cardiomyopathy: molecular pathways and targets for therapeutic intervention
    (Wiley, 2025) Jadhav, Hemant R.
    Amongst various complications presented by diabetes, diabetic cardiomyopathy (DCM) is one of the most prominent and vexing complications. Due to the absence of consensus on prevention and treatment strategies, along with limitations in current therapies, a fresh perspective is essential and a requirement of the time. The succeeding review explores research that provides insights into novel molecular targets that could possibly evolve as breakthroughs in restraining the pathological hallmarks of DCM, such as inhibition of cardiomyocyte fibrosis or modulation of various inflammatory pathways, apoptotic pathways such as PANoptosis, cuproptosis, and ferroptosis, and mitochondrial dysfunction. This review shall also explore various RNA-targeting therapeutic areas that can combat the consecution of DCM. Therapeutic intervention targeting Phosphodiesterase 4D (PDE4D), LGR6 (G-protein-coupled receptor containing leucine-rich repeats 6), Interferon gamma inducible protein 16 (IFI16), Growth differentiation factor 11(GDF11), Transcription factor EB(TFEB), Secreted frizzled-related protein 1 (SFRP1), Fibroblast growth factor -21 (FGF21), Takeda G protein-coupled receptor-5 (TGR5), Nuclear receptor of the subfamily 4 (NR4A3), Enhancer of zeste homolog 2 (EZH2), and RNA-based therapeutics such as piR112710 and TUG1 are reviewed. Moreover, how these molecular targets intersect with DCM pathology, and how they can be further explored in a drug discovery paradigm for DCM management, is discussed.
  • No Thumbnail Available
    Item
    Can breakthroughs in dermal and transdermal macromolecule delivery surmount existing barriers and revolutionize future therapeutics?
    (Springer, 2025-05) Mittal, Anupama; Chitkara, Deepak
    The delivery of macromolecules through dermal and transdermal routes presents both significant challenges and transformative opportunities in therapeutic applications. This review highlights the most recent advancements and innovative strategies aimed at overcoming the barriers associated with macromolecular delivery. Cutting-edge approaches such as the use of adjuvants (e.g., hyaluronic acid-based and chemical penetration enhancers), bioactive peptides with diverse functionalities, and mechanical force techniques—including iontophoresis, microneedles, and electroporation—are thoroughly explored. While various strategies have been implemented to enhance skin delivery, they often present significant challenges, particularly for macromolecules. Addressing these challenges requires integrating novel technologies and understanding the interplay between biological barriers and delivery mechanisms. Furthermore, the role of nanotechnology, through systems like nanoemulsions, polymeric nanoparticles, and transferosomes, is examined for its ability to protect macromolecules and regulate their release. Notably, this review provides unique perspectives on the interplay between these strategies and their potential to revolutionise future therapeutics. By highlighting key trends and advancements in macromolecule delivery, this review underscores the importance of innovative approaches in overcoming existing barriers and enabling efficient drug administration.
  • No Thumbnail Available
    Item
    Autophagy as a potential therapeutic target in regulating improper cellular proliferation
    (Frontiers Media, 2025-05) Chitkara, Deepak
    Autophagy is a degradative process that makes rapid turnover of old and impaired proteins and organelles possible. It is highly instigated by stress signals, like starvation, and contributes to the cell’s homeostasis. Autophagy performs a crucial function in keeping cell genomic integrity stable. Impaired autophagic flux is implicated in neurodegenerative diseases, abnormal ageing, and cancerous diseases. In diseases like cancer, autophagy performs a dualistic function; it can have both a tumor-suppressive and supportive role. Autophagy in the initial phases of tumorigenesis maintains the integrity of the genome and, if it fails, leads to cell death, thus having a tumor-suppressive role. Meanwhile, autophagy also imparts the function of the pro-survival mechanism in the latter stages of tumorigenesis and supports the cancerous cells in surviving conditions like hypoxia and increased oxidative stress. Autophagy also helps cancerous cells develop drug resistance in some cases. Thus, modulation of the autophagic mechanism is a possible therapeutic strategy in cancer therapy as its inhibition can sensitise cancer cells to anti-cancerous drugs. The promotion of autophagy, in some cases, can also safeguard cells from toxic protein aggregation and enhanced oxidative stress. Excessive autophagy can result in autophagic cell death. Autophagy also regulates several cellular processes and cell death pathways, like apoptosis. Therefore, an in-depth knowledge of the autophagy process and its regulating molecules is critically important. Pharmaceutical small molecules or cellular target modulation can help modulate the cellular autophagy process in the context of specific disease conditions.
  • No Thumbnail Available
    Item
    Simultaneous estimation of rapamycin, temozolomide and its metabolites using UPLC-ESI-MS/MS and its application to pharmacokinetics in C6-glioma bearing animals
    (Elsevier, 2025-09) Mittal, Anupama; Chitkara, Deepak
    Therapeutic drug monitoring (TDM) plays a crucial role in the optimization of drug dosage profiles and establishing an optimal balance between toxicity and its effectiveness. Developing TDM methods for simultaneous estimation of multiple molecules with diverse physiochemical properties is quite complicated and difficult to achieve. Thus, hindering the quantitative estimation for TDM and in-depth analysis from bench to clinical settings. Therefore, the current study reports a bioanalytical method for the simultaneous determination of anticancer and immunosuppressant molecules (namely rapamycin, temozolomide, and its metabolites) in a single injection using whole blood as a biological matrix.
  • No Thumbnail Available
    Item
    cRGD-functionalized nanohybrid conjugates codelivering temozolomide and rapamycin for treating Glioblastoma multiforme: in vitro and in vivo evaluation
    (ACS, 2025-10) Mittal, Anupama; Chitkara, Deepak
    The conventional treatment of glioblastoma multiforme primarily uses Temozolomide as a chemoadjuvant alongside debulking surgery and radiotherapy; however, resistance, as well as tumor recurrence, remains a common outcome. Employing combination therapy to target multiple pathways while improving delivery with advanced systems has always been sought after. Herein, we report cRGD-functionalized hybrid polymeric nanoconjugates that could deliver Temozolomide (TMZ) and rapamycin (RAP) (cRGD-Hybrid TMZ/R NCs) as a dual payload. The cRGD-Hybrid TMZ/R NCs were thoroughly characterized, exhibiting a particle size and surface zeta potential of 141.83 nm (PDI 0.233) and −0.168 mV, respectively. The nanoconjugates carrying TMZ and RAP as dual payloads were initially screened for synergism by determining their combination index in C6 and U87MG glioma cells. Further, in vitro cell-based assays showed improved cellular uptake, cytotoxicity, and apoptotic potential of hybrid nanoconjugates. Thereafter, the cRGD-Hybrid TMZ/R NCs were evaluated in a C6-cell-induced syngeneic orthotropic glioma model in Sprague–Dawley rats, exhibiting an improved therapeutic outcome including, reduced hemispherical width (RH/LH) ratios, tumor burden, and improved survival rates compared to the free drug(s) counterpart. The histopathological evaluation indicated no major sign of toxicity in vital organs such as heart, lungs, liver, kidney, and spleen, affirming the biocompatibility of the developed cRGD-Hybrid TMZ/R nanoconjugates. In conclusion, amalgamating the cRGD cell-penetrating peptide with polymer hybrid nanoconjugates presents a better approach for delivering multiple payloads in the treatment of GBM.