Department of Pharmacy
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Item Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management(University of Murcia, 2024) Shrivastava, RichaSarcopenia is a progressive and generalized loss of skeletal muscle and functions associated with ageing with currently no definitive treatment. Alterations in gut microbial composition have emerged as a significant contributor to the pathophysiology of multiple diseases. Recently, its association with muscle health has pointed to its potential role in mediating sarcopenia. The current review focuses on the association of gut microbiota and mediators of muscle health, connecting the dots between the influence of gut microbiota and their metabolites on biomarkers of sarcopenia. It further delineates the mechanism by which the gut microbiota affects muscle health with progressing age, aiding the formulation of a multi-modal treatment plan involving nutritional supplements and pharmacological interventions along with lifestyle changes compiled in the review. Nutritional supplements containing proteins, vitamin D, omega-3 fatty acids, creatine, curcumin, kefir, and ursolic acid positively impact the gut microbiome. Dietary fibres foster a conducive environment for the growth of beneficial microbes such as Bifidobacterium, Faecalibacterium, Ruminococcus, and Lactobacillus. Probiotics and prebiotics act by protecting against reactive oxygen species (ROS) and inflammatory cytokines. They also increase the production of gut microbiota metabolites like short-chain fatty acids (SCFAs), which aid in improving muscle health. Foods rich in polyphenols are anti-inflammatory and have an antioxidant effect, contributing to a healthier gut. Pharmacological interventions like faecal microbiota transplantation (FMT), non-steroidal anti-inflammatory drugs (NSAIDs), ghrelin mimetics, angiotensin-converting enzyme inhibitors (ACEIs), and butyrate precursors lead to the production of anti-inflammatory fatty acids and regulate appetite, gut motility, and microbial impact on gut health. Further research is warranted to deepen our understanding of the interaction between gut microbiota and muscle health for developing therapeutic strategies for ameliorating sarcopenic muscle loss.Item Arsenic exposure alters liver metabolism and accelerates skeletal muscle atrophy in female BALB/c Mice(Springer, 2025-10) Shrivastava, RichaThe liver and skeletal muscle are metabolically interconnected organs vital for maintaining systemic homeostasis. Arsenic toxicity is known to adversely affect both organs individually, yet the mechanistic link between arsenic-induced liver dysfunction and skeletal muscle deterioration remains unclear. This study aimed to investigate whether arsenic-induced alterations in hepatic metabolism are associated with changes in skeletal muscle health. BALB/c mice were divided into four groups: Control, 0.2 ppm arsenic, 2 ppm arsenic, and 20 ppm arsenic. For 30 days, sodium arsenite was administered in the drinking water ad libitum. Arsenic exposure led to elevated serum ALT and AST levels, increased hepatic lipid accumulation, and dysregulated the expression of oxidative stress defense components (Nrf2/Keap1), lipid metabolism regulators (PPAR-γ and PPAR-α), β-oxidation and lipogenic enzymes (CPT-1, and SREBP-1), as well as hepatic energy sensors (p-mTOR and p-AMPK). These hepatic changes were accompanied by oxidative stress and elevated proinflammatory cytokines (TNF-α, IL-6) in the liver and serum. Concurrently, skeletal muscle exhibited functional decline, as evidenced by decreased grip strength and elevated serum creatine kinase levels. Histological and Succinate dehydrogenase (SDH) analysis further revealed atrophy, characterized by reduced fiber cross-sectional area and a fiber-type shift from fast-twitch (Type II) to slow-twitch (Type I) fibers respectively. At the molecular level, arsenic exposure upregulated the muscle-specific ubiquitin ligases MuRF1 and atrogin-1, accompanied by NF-κB activation, indicating increased proteolysis and inflammation. Additionally, decreased irisin expression in both liver and muscle and reduced serum insulin levels indicated systemic metabolic dysregulation. Correlation analysis of inflammatory markers with indices of liver and muscle injury, together with evidence of crosstalk between these tissues, revealed significant associations. Collectively, these findings suggest that arsenic-induced hepatic disturbances may indirectly contribute to skeletal muscle wasting via systemic inflammation, supporting the possible involvement of a liver–muscle axis in arsenic toxicity.Item Therapeutic strategies to modulate gut microbial health: approaches for sarcopenia management(2024) Shrivastava, RichaSarcopenia is a progressive and generalized loss of skeletal muscle and functions associated with ageing with currently no definitive treatment. Alterations in gut microbial composition have emerged as a significant contributor to the pathophysiology of multiple diseases. Recently, its association with muscle health has pointed to its potential role in mediating sarcopenia. The current review focuses on the association of gut microbiota and mediators of muscle health, connecting the dots between the influence of gut microbiota and their metabolites on biomarkers of sarcopenia. It further delineates the mechanism by which the gut microbiota affects muscle health with progressing age, aiding the formulation of a multi-modal treatment plan involving nutritional supplements and pharmacological interventions along with lifestyle changes compiled in the review. Nutritional supplements containing proteins, vitamin D, omega-3 fatty acids, creatine, curcumin, kefir, and ursolic acid positively impact the gut microbiome. Dietary fibres foster a conducive environment for the growth of beneficial microbes such as Bifidobacterium, Faecalibacterium, Ruminococcus, and Lactobacillus. Probiotics and prebiotics act by protecting against reactive oxygen species (ROS) and inflammatory cytokines. They also increase the production of gut microbiota metabolites like short-chain fatty acids (SCFAs), which aid in improving muscle health. Foods rich in polyphenols are anti-inflammatory and have an antioxidant effect, contributing to a healthier gut. Pharmacological interventions like faecal microbiota transplantation (FMT), non-steroidal anti-inflammatory drugs (NSAIDs), ghrelin mimetics, angiotensin-converting enzyme inhibitors (ACEIs), and butyrate precursors lead to the production of anti-inflammatory fatty acids and regulate appetite, gut motility, and microbial impact on gut health. Further research is warranted to deepen our understanding of the interaction between gut microbiota and muscle health for developing therapeutic strategies for ameliorating sarcopenic muscle loss.Item Fighting against the pandemic or threatening the environment? Unforeseen challenges during COVID-19 pandemic(Oxford, 2021-09) Shrivastava, RichaIn the current scenario of COVID-19 outbreak whereby the virus spreads through fomites and aerosols, there has been a huge increase in the use of soaps, sanitizers and personal protective equipment’s (PPEs) which in turn is causing huge amount of liquid and solid waste generation. We briefly describe here as how this pandemic is causing an impact on global environment. We also provide a rationale of using a modelled treatment framework using a reverse logistic network as temporary waste management measure during this pandemic.Item Role of Pharmacists during and Post COVID-19 Pandemic-An Indian Perspective(IJOPP, 2022-04) Shrivastava, RichaThe multiple outbreaks of COVID-19 have led to a public health crisis, affecting millions across the globe. The healthcare fraternity is shouldering a huge responsibility and is working tirelessly to curb the spread of the disease. These unprecedented times demand that the usual roles of pharmacists be modified. Pharmacists have to rise up to the challenges and strategize accordingly. Many nations are trying to tackle the repercussions of the second wave of COVID-19 and the latest third wave by OMICRON variant, which has punctured the healthcare system and led to question the resource management and governance failures that have affected thousands of lives. It is difficult to bring the situation under control in several places, predominantly middle and lowincome countries. Thus, to succeed in providing all the healthcare services, changes pertaining to operations, supply management, safety precautions, spreading awareness, vaccination drives, etc., must be incorporated by healthcare workers, especially the pharmacists, to create a maximum positive change. This article highlights the roles and responsibilities of the pharmacists that they can fulfil during and post this pandemic. It also reviews the nature of their functioning, the roles that they can adapt, and identifies places wherein their roles can be expanded or modified in accordance with the countryspecific guidelines.Item Importance of Dietary Supplements to the Health(Bentham Science, 2021) Shrivastava, RichaThe term “dietary supplement” defines a comprehensive and diverse category of products that are essential to our health but are absent or insufficient in the diet and may be needed to take separately; requirement of dietary supplements varies at different stages of life, such as infant, child-adult, pregnancy, lactation, and geriatrics. Dietary supplements are not medicines, nor should they be considered a substitute for food. The USFDA defines dietary supplements in part as a product taken by mouth that contains “dietary ingredients.” Nutritional ingredients comprise vitamins, minerals, amino acids, and herbs or botanicals, in addition to other substances that can be considered to supplement the diet. The market is flooded with various dosage forms of dietary supplements, such as capsules, tablets, powders, energy bars, liquids, etc. These include vitamins, minerals, herbal products containing extracts from herbs as well as algae and fungi, concentrate, metabolite, constituent, or extract, enzyme supplements, essential amino, and fatty acids. This article describes the importance of the dietary supplement, its source, diseases that arise from deficiency, and the recommended doses for different groups.Item Design and development of PEGylated liposomal formulation of HER2 blocker Lapatinib for enhanced anticancer activity and diminished cardiotoxicity(Elsevier, 2018-09) Shrivastava, RichaBreast cancer is most frequently diagnosed cancer and fifth leading cause of death in women. About 20–30% of all breast cancers overexpress HER2/neu receptors. Lapatinib is a dual tyrosin kinase inhibitor of EGFR and HER2. It exhibits its anticancer effect via blocking intracellular domain of HER2 receptor in breast cancer. Lapatinib belongs to class II of BSC classification due to its poor solubility restricting its clinical application. Due to presence of HER2 receptor on cardiomyocytes, it is associated with generation of cardiotoxicity. The present study was aimed to design a PEGylated liposomal formulation of Lapatinib and evaluate its anticancer potential. Lapatinib liposomes were prepared using lipid layer hydration method and its characterization was done by determining its particle size, zeta potential, entrapment efficiency and in vitro release profiling. The anti-tumor activity of PEGylated liposomal formulation was evaluated in xenografted tumor induced by MDA-MB-453 breast cancer cells in chick embryos. The anti-tumor effect of lapatinib was enhanced by its PEGylated liposomal preparation as it led to the reduction in tumor size to a greater extent compared to the embryos treated with free lapatinib. Flowcytometric analysis and immunoflurescence study using cleaved PARP antibody demonstrated the enhanced apoptotic potential of PEGylated liposomes of lapatinib. SGOT levels, marker for cardiotoxicity and hepatotoxicity, significantly decreased in serum of embryos treated with PEGylated liposomes of lapatinib compared to free drug treated embryos. Hence, the PEGylated liposomal formulation of lapatinib can be used as a therapeutic strategy against HER2 positive breast cancer either alone or in combination with conventional anticancer agents and hormonal therapies.Item AzaGly-Appended Peptidomimetics Structurally Related to PTR6154 as Potential PKB/Akt Inhibitors(Wiley, 2017-04) Shrivastava, RichaSynthesis of AzaGly-appended peptidomimetics with improved biological and biochemical properties. Robust synthesis of azapeptide on solid support is demonstrated without noticeable hydantoin formation. The azapeptide derived from the GSK-3β substrate exhibited improved properties in terms of Akt kinase inhibitory activity and basal degradation, proteolytic degradation, conformation and binding affinities.Item Pharmacological activation of aldehyde dehydrogenase 2 promotes osteoblast differentiation via bone morphogenetic protein-2 and induces bone anabolic effect(Elsevier, 2017-02) Shrivastava, RichaAldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2). Silencing ALDH2 in osteoblasts abolished the alda-1 effects. Further, alda-1 attenuated the acetaldehyde-induced lipid-peroxidation and oxidative stress. BMP-2 is essential for bone regeneration and alda-1 increased its expression in osteoblasts. We then showed that alda-1 (40 mg/kg dose) augmented bone regeneration at the fracture site with concomitant increase in BMP-2 protein compared with control. The osteogenic dose (40 mg/kg) of alda-1 attained a bone marrow concentration that was stimulatory for osteoblast differentiation, suggesting that the tissue concentration of alda-1 matched its pharmacologic effect. In addition, alda-1 promoted modeling-directed bone growth and peak bone mass achievement, and increased bone mass in adult rats which reiterated its osteogenic effect. In osteopenic ovariectomized (OVX) rats, alda-1 reversed trabecular osteopenia with attendant increase in serum osteogenic marker (procollagen type I N-terminal peptide) and decrease in oxidative stress. Alda-1 has no effect on liver and kidney function. We conclude that activating ALDH2 by alda-1 had an osteoanabolic effect involving increased osteoblastic BMP-2 production and decreased OVX-induced oxidative stress.Item Cyclooxygenase-2 Inhibition Attenuates Hypoxic Cancer Cells Induced M2-Polarization of Macrophages(CMB Association, 2014-12) Shrivastava, RichaTumor associated macrophages (TAMs), represent a major subpopulation of tumor infiltrating immune cells. These alternatively activated M2-polarized macrophages are well known for their pro-tumor functions. Owing to their established role in potentiating tumor-neovasculogenesis and metastasis, TAMs have emerged as promising target for anti-cancer immunotherapy. One of the key TAMs related phenomenon that is amenable to therapeutic intervention is their phenotype switching into alternatively activated M2-polarized macrophages. Hindering macrophage polarization towards a pro-tumor M2 phenotype, or better still reprogramming the M2 like TAMs towards M1 subtype is being considered a beneficial anti-cancer strategy. Hypoxic tumor milieu has been proposed as one of the most plausible factor governing M2-polarization of macrophages. We recently demonstrated that hypoxic tumor cells imparted a pro-angiogenic M2 skewed phenotype to macrophages. Furthermore, sizeable body of data indicates for participation of cyclooxygenase-2 (COX-2) in macrophage polarization. Concordantly, inhibition of COX-2 is associated with impaired macrophage polarization. Prompted by this in the current study we decided to explore if inhibition of COX-2 activity via chemical inhibitors may prevent hypoxic cancer cell induced M2-polarization of macrophages. We observed that treatment with Flunixin meglumine, an established preferential inhibitor of COX-2 activity markedly inhibited hypoxic cancer cell induced of M2-polarization of macrophages thereby indicating for usage of COX-2 inhibition as possible anti-cancer treatment modality.