Department Of Pharmacology
Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/108
Browse
10 results
Search Results
Item Exploring the ameliorative potential of Bacopa monnieri in acetic acid induced ulcerative colitis in mice(Taylor and Francis Ltd., 2023-07-10T00:00:00) Devi, Karam; Bali, Anjana; Bhatia, Pankaj; Singh, Nirmal; Jaggi, Amteshwar SinghThe aim of the present study was to evaluate the role of Bacopa monnieri in acetic-acid-induced ulcerative colitis in mice. Acetic acid (3%v/v, in 0.9% saline) was infused intrarectally to induce ulceration in mice. Administration of acetic acid resulted in severe inflammation of the colon along with an increase in the myeloperoxidase (MPO) activity assessed on 7th day. Treatment with Bacopa monnieri extract (20 mg/kg and 40 mg/kg, p.o) and saponin-rich fraction (5 mg/kg and 10 mg/kg; p.o) for 7 days i.e. 2 days before and 5 days after acetic acid infusion, significantly attenuated the colonic inflammation in a dose-dependent manner. Furthermore, it also reduced the MPO levels and the disease activity score as compared to the control group. It may be concluded that Bacopa monnieri has the potential for ameliorating acetic-acid-induced colitis and its saponin-rich fraction may be responsible for this effect. � 2023 Informa UK Limited, trading as Taylor & Francis Group.Item Insights into receptor tyrosine kinases signaling in neurodegenerative disorders: opportunities and translational perspectives(Elsevier, 2023-07-06T00:00:00) Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh; Bali, AnjanaReceptor tyrosine kinases (RTKs) are a group of membrane-bound receptors comprising of extracellular ligand-binding domain, a transmembrane domain, and an intracellular catalytic domain. RTKs play a crucial role in various cellular processes including cellular growth, motility, cell differentiation, and cell metabolism. The dysregulation of RTK activity is a contributing factor in the progression of many neurodegenerative disorders. Studies revealed the alterations rearranged during transfection, epidermal growth factor receptor 1, vascular endothelial growth factor-B TAM receptors, and tropomyosin receptor kinase in neurodegenerative disorders. Further, PI3K/Akt/GSK-3? and Wnt/catenin signaling pathways are found to be major pathways for neuronal survival and neurite outgrowth induced by RTKs. This chapter summarizes the most important aspects of RTK subfamilies and their intraneuronal signaling mechanisms in different neurodegenerative disorders. The understanding of the fundamental mechanisms of RTKs in neurodegenerative disorders has important implications for the selection of a suitable neuroprotective agent. � 2023 Elsevier Inc. All rights reserved.Item Ephrin B/EphB in neuropathic pain: Role and molecular mechanisms(John Wiley and Sons Inc, 2023-07-04T00:00:00) Kaur, Sahibpreet; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar SinghEphrins are protein ligands that act through the tyrosine kinase receptor family, Eph receptors. The role of ephrin/Eph in the critical processes involved in the development of the nervous system, including axon guidance and cell migration, has been well documented. Moreover, studies have shown an upregulation of ephrin B1/EphB1 and ephrin B2/EphB2 in neuropathic pain of different etiology. The activation of the ephrin B/EphB system in the dorsal root ganglion and dorsal horn of the spinal cord may be essential in initiating and maintaining neuropathic pain. Accordingly, it can be proposed that the pharmacological inhibitors of EphB receptors may be potentially employed to manage the manifestations of pain. One of the primary mechanisms involved in ephrin B/EphB-mediated synaptic plasticity includes phosphorylation and activation of NMDA receptors, which may be secondary to activation of different kinases, including MAP kinases (MAPK), protein kinase C (PKC), and Src family kinases (SFK). The other molecular mechanisms may include activation of inflammatory cytokines in the spinal cord, caspase-3, calpain-1, phosphoinositide 3-kinase (PI3K), protein kinase A (PKA), and cAMP Response Element-Binding Protein (CREB). The present review discusses the role and molecular mechanisms involved in ephrin B/EphB-mediated neuropathic pain of different etiology. � 2023 Soci�t� Fran�aise de Pharmacologie et de Th�rapeutique. Published by John Wiley & Sons Ltd.Item A focus on Rho/ROCK signaling pathway: An emerging therapeutic target in depression(Elsevier B.V., 2023-03-08T00:00:00) Hanifa, Mohd; Singh, Mohini; Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh; Bali, AnjanaDepression is the most common mental health disorder worldwide; however, the exact cellular and molecular mechanisms of this major depressive disorder are unclear so far. Experimental studies have demonstrated that depression is associated with significant cognitive impairment, dendrite spine loss, and reduction in connectivity among neurons that contribute to symptoms associated with mood disorders. Rho/Rho-associated coiled-coil containing protein kinase (ROCK) receptors are exclusively expressed in the brain and Rho/ROCK signaling has gained considerable attention as it plays a crucial role in the development of neuronal architecture and structural plasticity. Chronic stress-induced activation of the Rho/ROCK signaling pathway promotes neuronal apoptosis and loss of neural processes and synapses. Interestingly, accumulated evidence has identified Rho/ROCK signaling pathways as a putative target for treating neurological disorders. Furthermore, inhibition of the Rho/ROCK signaling pathway has proven to be effective in different models of depression, which signify the potential benefits of clinical Rho/ROCK inhibition. The ROCK inhibitors extensively modulate antidepressant-related pathways which significantly control the synthesis of proteins, and neuron survival and ultimately led to the enhancement of synaptogenesis, connectivity, and improvement in behavior. Therefore, the present review refines the prevailing contribution of this signaling pathway in depression and highlighted preclinical shreds of evidence for employing ROCK inhibitors as disease-modifying targets along with possible underlying mechanisms in stress-associated depression. � 2023 Elsevier B.V.Item Investigations on Rho/ROCK signaling in post-traumatic stress disorder-like behavior in mice(Elsevier B.V., 2023-02-14T00:00:00) Sree, Aluri Bhavya; Hanifa, Mohd; Bali, AnjanaPost-Traumatic Stress Disorder (PTSD) is a chronic condition that occurs in response to a traumatic event, and consequently, enhances the threat sensitivity. Rho/ROCK signaling has been implicated in the consolidation of fear memory, stress, depression, anxiety, and traumatic brain injury. However, its role in post-traumatic stress disorder remains elusive. Therefore, the present study was designed to explore the role of fasudil, a Rho/ROCK inhibitor, a mouse model of PTSD. Mice were subjected to underwater trauma stress followed by three situational reminders. Underwater trauma (UWT) significantly increased the freezing behavior, a marker of the formation of aversive memory, in response to situational reminders on the 3rd, 7th, and 14th days, suggesting the significant development of PTSD. Trauma and situational reminders were also associated with significant changes in behavioral parameters in open field, social interaction and actophotometer tests, along with a reduction in serum corticosterone levels. Fasudil (10 and 15 mg/kg) and sertraline (15 mg/kg), a standard drug for PTSD, significantly decreased the freezing behaviour in response to situational reminders, suggesting the inhibition of the formation of aversive fear memory. However, fasudil and sertraline did not modulate normal memory functions, as assessed on elevated plus maze test, before subjecting mice to traumatic stress. Treatment with fasudil and sertraline significantly restored the behavioral changes and normalized the corticosterone levels. Fasudil-mediated blockade of the Rho/ROCK pathway may be responsible for blocking the formation of aversive memory during the traumatic event, which may be manifested in form of decreased contextual fear response during situational reminders. � 2023 Elsevier B.V.Item Exogenous fetuin-A protects against sepsis-induced myocardial injury by inhibiting oxidative stress and inflammation in mice(John Wiley and Sons Inc, 2023-01-17T00:00:00) Sidheeque Hassan, V.; Hanifa, Mohd; Navik, Umashanker; Bali, AnjanaSepsis-induced myocardial injury is a consequence of septicemia and is one of the major causes of death in intensive care units. A serum glycoprotein called fetuin-A is secreted largely by the liver, tongue, placenta, and adipose tissue. Fetuin-A has a variety of biological and pharmacological properties. The anti-inflammatory and antioxidant glycoprotein fetuin-A has shown its efficacy in a number of inflammatory disorders including sepsis. However, its protective role against sepsis-induced myocardial injury remains elusive. The purpose of this work is to explore the role of fetuin-A in mouse models of myocardial injury brought on by cecal ligation and puncture (CLP). CLP significantly induced the myocardial injury assessed in terms of elevated myocardial markers (serum CK-MB, cTnI levels), inflammatory markers (IL-6, TNF-?) in the serum, and oxidative stress markers (increased MDA levels and decreased reduced glutathione) in heart tissue homogenate following 24 h of ligation and puncture. Further, hematoxylin and eosin (H&E) staining showed considerable histological alterations in the myocardial tissue of sepsis-developed mice. Interestingly, fetuin-A pretreatment (50 and 100 mg/kg) for 4 days before the CLP procedure significantly improved the myocardial injury and was evaluated in perspective of a reduction in the CK-MB, cTnI levels, IL-6, and TNF-? in sepsis-developed animals. Fetuin-A pretreatment significantly attenuated the oxidative stress and improved the myocardial morphology in a dose-dependent manner. The present study provides preliminary evidence that fetuin-A exerts protection against sepsis-induced cardiac dysfunction in vivo via suppression of inflammation and oxidative damage. � 2023 Soci�t� Fran�aise de Pharmacologie et de Th�rapeutique.Item Demystifying the dual role of the angiotensin system in neuropathic pain(Churchill Livingstone, 2022-05-26T00:00:00) Kaur, Sahibpreet; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar SinghNeuropathic Pain is caused by damage to a nerve or disease of the somatosensory nervous system. Apart from the blood pressure regulating actions of angiotensin ligands, studies have shown that it also modulates neuropathic pain. In the animal models including surgical, chemotherapeutic, and retroviral-induced neuropathic pain, an increase in the levels of angiotensin II has been identified and it has been proposed that an increase in angiotensin II may participate in the induction of neuropathic pain. The pain-inducing actions of the angiotensin system are primarily due to the activation of AT1 and AT2 receptors, which trigger the diverse molecular mechanisms including the induction of neuroinflammation to initiate and maintain the state of neuropathic pain. On the other hand, the pain attenuating action of the angiotensin system has been attributed to decreasing in the levels of Ang(1�7), and Ang IV and an increase in the levels of bradykinin. Ang(1�7) may attenuate neuropathic pain via activation of the spinal Mas receptor. However, the detailed molecular mechanism involved in Ang(1�7) and Ang IV-mediated pain attenuating actions needs to be explored. The present review discusses the dual role of angiotensin ligands in neuropathic pain along with the possible mechanisms involved in inducing or attenuating the state of neuropathic pain. � 2022 Elsevier LtdItem Exploring the role of cAMP in gabapentin-mediated pain attenuating effects in chroniconstriction injury model in rats(Faculdade de Ciencias Farmaceuticas (Biblioteca), 2022-06-07T00:00:00) Sharma, Deepankshi; Jaggi, Amteshwar Singh; Arora, Kiran; Bali, AnjanaIt has been shown that an increase in cAMP leads to pain sensitization and gabapentin is shown to decrease cAMP levels. However, the impact of drugs modulating cAMP levels on analgesic actions of gabapentin is not studied. The present study investigates the effect of milrinone on pain attenuating effects of gabapentin in chronic constriction injury (CCI). Neuropathic pain was induced by putting four loose ligatures around the sciatic nerve. The pain assessment was done by noting the paw withdrawal threshold in the pinprick test, paw withdrawal latency in hot plate test and paw withdrawal duration in acetone drop test before surgery and on 14th-day post-surgery. There was a significant development of cold allodynia, mechanical and heat hyperalgesia on 14th day in CCI rats. Gabapentin (100 mg/kg) treatment for 14 days significantly attenuated pain, while milrinone (50 mg/kg) treatment for 14 days significantly exacerbated neuropathic pain in CCI-subjected rats. Milrinone (30 and 50 mg/kg) also attenuated analgesic actions of gabapentin in CCI-subjected rats, suggests that gabapentin may abolish neuropathic pain by increasing the intracellular levels of cAMP in CCI-subjected rats. � 2022, Faculdade de Ciencias Farmaceuticas (Biblioteca). All rights reserved.Item Molecular Mechanism of Beneficial Effects of Probiotics in Alcohol-Induced Liver Disorder(Springer Nature, 2022-05-04T00:00:00) Bali, Anjana; Jaggi, Amteshwar Singh; Chawla, Viney; Pottoo, Faheem Hyder; Chawla, Pooja A.Regular consumption of alcohol remains a predominant cause of a variety of hepatic disorders. There exist many alcohol-induced liver diseases including steatosis, steatohepatitis, and cirrhosis. Microflora of the gut has been considered as important in the pathophysiology of different disorders and long-term alcohol consumption significantly disrupts the intestinal flora composition and gut microbiota in liver disorders. Recent research studies have shown that probiotics significantly modulate the gut microbiota as well as ameliorate alcohol consumption-induced intestinal barrier dysfunction. Thus, targeting the gut�liver axis may be beneficial in the above-mentioned disorders. Interestingly, the investigations on the use of probiotics in alcohol-induced liver diseases are gaining more clinical importance. It has been shown that probiotics bring about an improvement in the responses of the immune system and significantly bring down the generation of free radicals induced by alcohol. Further, they reduce the inflammatory cytokines in the liver and intestine. Besides, studies have shown that the use of probiotics significantly increases fatty acid ?-oxidation and decreases lipogenesis which is beneficial in the management of hepatic steatosis induced by alcohol. The current book chapter will focus on the use of probiotic species in preventing and treating alcohol-induced liver disorders along with the underlying potential mechanism of action. � Springer Nature Singapore Pte Ltd. 2022.Item Exploring the Potential Role of Nf-Kb Signaling Cascade in Stress Adaptation(Walsh Medical Media, LLC, 2021-12-22T00:00:00) Bali, Anjana; Jaggi, Amteshwar Singh; Bhavya, Aluri SreeThe present study aimed to investigate the role of NF-kB signaling in stress adaptation during exposure of repeated immobilization stress of varying duration in mice. Animals were subjected to two paradigms of immobilization stress i.e., short duration (30 minutes) or long duration (120 minutes). Mice were subjected to homotypic stressor for 5 days to induce stress adaptation. Actophotometer, open field, social interaction and hole board tests were performed to assess stress-associated alteration in behavior; while serum corticosterone levels were measured as a biochemical parameter of stress induction. The levels of p-NF-kB were assessed in stress sensitive prefrontal cortex region. A single episode of short as well as long immobilization stress resulted in changes in behavior, increased plasma corticosterone levels and p-NF-kB levels in prefrontal cortex. In contrast, continuous exposure to short as well as long stress restored behavior, corticosterone and p-NF-kB levels. Treatment with diethyldithiocarbamic acid (DDTC), a selective NF-kB inhibitor, attenuated acute stress associated changes in behavior and corticosterone levels. Moreover, DDTC restored the NF-kB levels in stress subjected mice. It suggests that acute stress may increase the levels of p-NF-kB in the prefrontal cortex may be responsible for the induction of behavioral and biochemical changes. Therefore, NF-kB may serve as an important target in inducing stress adaptation in immobilization stress. Copyright: �2021 Bali A, et al..