BITS Faculty Publications

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    Network pharmacology combined with molecular docking and dynamics to assess the synergism of esculetin and phloretin against acute kidney injury-diabetes comorbidity
    (Springer, 2024-04) Jadhav, Hemant R.; Gaikwad, Anil Bhanudas
    Acute kidney injury (AKI) is a global health concern with high incidence and mortality, where diabetes further worsens the condition. The available treatment options are not uniformly effective against the complex pathogenesis of AKI–diabetes comorbidity. Hence, combination therapies based on the multicomponent, multitarget approach can tackle more than one pathomechanism and can aid in AKI–diabetes comorbidity management. This study aimed to investigate the therapeutic potential of esculetin and phloretin combination against AKI–diabetes comorbidity by network pharmacology followed by validation by molecular docking and dynamics. The curative targets for diabetes, AKI, esculetin, and phloretin were obtained from DisGeNET, GeneCards, SwissTargetPrediction database. Further, the protein–protein interaction of the potential targets of esculetin and phloretin against AKI–diabetes comorbidity was investigated using the STRING database. Gene ontology and pathway enrichment analysis were performed with the help of the DAVID and KEGG databases, followed by network construction and analysis via Cytoscape. Molecular docking and dynamic simulations were performed to validate the targets of esculetin and phloretin against AKI–diabetes comorbidity. We obtained 6341 targets for AKI–diabetes comorbidity. Further, a total of 54 and 44 targets of esculetin and phloretin against AKI–diabetes comorbidity were retrieved. The top 10 targets for esculetin selected based on the degree value were AKR1B1, DAO, ESR1, PLK1, CA3, CA2, CCNE1, PRKN, HDAC2, and MAOA. Similarly, phloretin’s 10 key targets were ACHE, CDK1, MAPK14, APP, CDK5R1, CCNE1, MAOA, MAOB, HDAC6, and PRKN. These targets were enriched in 58 pathways involved in the pathophysiology of AKI–diabetes comorbidity. Further, esculetin and phloretin showed an excellent binding affinity for these critical targets. The findings of this study suggest that esculetin and phloretin combination as a multicomponent multitarget therapy has the potential to prevent AKI–diabetes comorbidity.
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    Epigenetic restoration of endogenous Klotho expression alleviates acute kidney injury-diabetes comorbidity
    (Elsevier, 2022-01) Gaikwad, Anil Bhanudas
    The present study aimed at exploring the mechanisms behind Klotho regulation in hyperglycemia augmented AKI. In addition, epigenetic ways to restore the Klotho expression in AKI-diabetes comorbidity have been evaluated.
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    Depression Associated Disorders: Comorbidity, eurobiological and eurobehavioural Link
    (Pharmacologyonline, 2010) Mahesh, R.
    Comorbidity commonly refers to the co-occurrence (or dual diagnosis) of two disorders or syndromes in the same patient, regardless of whether the disorders are coincidentally or causally linked. Indeed, illnesses have been classified in discrete diagnostic categories although no sharp discontinuities in symptom distributions are observed across most mental disorders. Depression is a relatively common psychiatric comorbididy of most neurological disorders, with prevalence rates ranging between 20 and 50% among patients with stroke, multiple sclerosis, epilepsy, Parkinson’s disease and dementia. Furthermore, depression is an independent predictor of poor quality of life in these patients and has a negative impact on the response to treatment, course and recovery of neurological deficits. Comorbid depressive disorders in neurologic patients can be indistinguishable to the primary mood disorders and may mimic major depression, dysthymic, minor depressive, and bipolar disorders described in the DSM-IV classification of mood disorders. In addition, the great overlap of medical and psychiatric symptoms in depression and neurologic disorders may lead to both false-positive and false-negative diagnoses of depression. Patient with comorbid condition have lower response rate and /or a longer time to response, greater reports of side effect early in treatment and greater likely hood of dropping out. In this review, we focus on comorbid disorder associated with depression.
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    Evaluation of Anti-depressant and Analgesic- Like Activity of Ondansetron in Rodents Model of Co-morbid Pain and Depression
    (IJPER, 2015-02) Mahesh, R.; Yadav, Sushil
    Although a clinical connection between pain and depression has long been recognized, how these two conditions interact remains unclear. Here we report the comorbidity of pain and depression-like behavior. The antidepressant and analgesic like activity of Ondansetron (OND, 0.25-2mg/kg) were investigated in animal models of acute depression (forced swim test ) and pain ( tail flick test) , existence of co-morbidity of pain and depression was simulated in surgical models in rats like olfactory bulbectomy (OBX) model of chronic depression and chronic constrictive injury (CCI) of chronic pain conditions. Acute administration of OND (0.5-2mg/kg i.p) significantly reduced the duration of immobility in mice in FST and increased the time latency in tail flick test. Behavioural anomalies shown by OBX rats in open field test was significantly reversed by OND (1-2 mg/kg p.o) but OBX rats failed to show the any kind of nociception. Further OND successfully reversed pain in CCI rats. In addition to reversal of pain, OND (1-2mg/kg p.o) significantly reduced the hyperactivity exhibited by CCI rats in open field test suggesting the effect of OND in co-morbid pain and depression. OND exhibited significant antidepressant and analgesic like effect as indicated by its ability to reduce swim stress induced immobility and reduction in writhing. The present study showed that OND has equal efficacy in comorbid pain and depression-like behavioural mediated through serotonergic system.
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    Evaluation of Anti-depressant and Analgesic- Like Activity of Ondansetron in Rodents Model of Co-morbid Pain and Depression
    (IJPER, 2015-02) Mahesh, R.; Yadav, Sushil
    Although a clinical connection between pain and depression has long been recognized, how these two conditions interact remains unclear. Here we report the comorbidity of pain and depression-like behavior. The antidepressant and analgesic like activity of Ondansetron (OND, 0.25-2mg/kg) were investigated in animal models of acute depression (forced swim test ) and pain ( tail flick test) , existence of co-morbidity of pain and depression was simulated in surgical models in rats like olfactory bulbectomy (OBX) model of chronic depression and chronic constrictive injury (CCI) of chronic pain conditions. Acute administration of OND (0.5-2mg/kg i.p) significantly reduced the duration of immobility in mice in FST and increased the time latency in tail flick test. Behavioural anomalies shown by OBX rats in open field test was significantly reversed by OND (1-2 mg/kg p.o) but OBX rats failed to show the any kind of nociception. Further OND successfully reversed pain in CCI rats. In addition to reversal of pain, OND (1-2mg/kg p.o) significantly reduced the hyperactivity exhibited by CCI rats in open field test suggesting the effect of OND in co-morbid pain and depression. OND exhibited significant antidepressant and analgesic like effect as indicated by its ability to reduce swim stress induced immobility and reduction in writhing. The present study showed that OND has equal efficacy in comorbid pain and depression-like behavioural mediated through serotonergic system.