Alok Shiomurti Tripathi

Background: Obesity contributes to multiple chronic diseases and remains a critical global health challenge. Objectives: This study evaluated the therapeutic effects of lyoniresinol on high-fat diet-induced obesity and its underlying molecular mechanisms. Methods: Network pharmacology was used to identify potential targets of lyoniresinol in obesity treatment, followed by validation using molecular docking. High-fat diet-induced obese rats received lyoniresinol (30 mg/kg/day) for six weeks. The primary efficacy endpoints were insulin sensitivity, assessed by the oral glucose tolerance test (OGTT), insulin tolerance test (ITT), fasting glucose, and fasting insulin, and adiposity measures, including body weight and regional fat mass. The key secondary endpoint was uncoupling protein 1 (UCP1) expression in adipose tissue, evaluated by Western blotting and immunohistochemistry. Mechanistic validation comprised analysis of the phosphorylation status of c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K), and mammalian target of rapamycin (mTOR) by Western blotting. Exploratory assessments included serum lipid profiles, inflammatory cytokines, oxidative stress biomarkers, and histopathological examination. Results: Network pharmacology identified 50 shared targets between lyoniresinol and obesity. Molecular docking indicated favorable binding to JNK, PI3K, and mTOR. For the primary endpoints, lyoniresinol treatment was associated with reduced body weight gain, restored normoglycaemia, enhanced insulin sensitivity, and decreased regional adipose tissue mass. For the key secondary endpoint, UCP1 expression was upregulated, suggesting the browning of white adipose tissue. For the exploratory endpoints, lyoniresinol was associated with improved dyslipidaemia, reduced oxidative stress, suppressed pro-inflammatory cytokines and C-reactive protein (CRP), and attenuated adipocyte hypertrophy. For mechanistic validation, lyoniresinol treatment was associated with suppressed JNK phosphorylation and activation of PI3K/mTOR signaling in adipose tissue, suggesting potential involvement of the JNK/PI3K/mTOR pathway in these effects. Conclusions: Based on the primary efficacy endpoints, lyoniresinol was associated with improved insulin sensitivity and reduced adiposity in obese rats. The key secondary endpoint (UCP1 upregulation) and mechanistic validation (altered JNK/PI3K/mTOR phosphorylation) further support its association with the browning of white adipose tissue. These findings suggest that lyoniresinol may represent a multi-target candidate for further investigation in obesity-related metabolic disorders; however, the precise molecular mechanisms require additional validation.

This study investigates the potential protective effects of eugenol on cecal ligation puncture (CLP) induced sepsis rat model. CLP was used to induce sepsis in rats and then treated with eugenol at doses of 25 and 50 mg/kg, i.p. for a duration of 7 days. Effects of eugenol was observed on survival rates, markers of oxidative stress, inflammatory cells, and markers in rats. Further network pharmacology study was performed to assess the possible targets for eugenol in the management of sepsis. An interaction study of selected proteins, that is, ADORA2A and HDAC8, with eugenol was observed with a docking study. The eugenol‐treated group showed an improvement in the survival rate in the sepsis group of rats. Treatment with eugenol ameliorates oxidative stress, inflammatory mediators, and cells in sepsis rats. Histopathological changes (spleen and lung tissue) were observed to be ameliorates in group of rats treated with eugenol versus the sepsis group. Network pharmacology suggest the 14 common target of interaction between eugenol and sepsis, which was further observed for immunomodulation molecular pathway of sepsis with STRING pathway and gene ontology study. Docking study shows binding strength of ADORA2A‐eugenol and HDAC8‐eugenol complex was observed to be −6.5 and −5.6 kcal/mol, respectively. Data of investigation concludes that eugenol enhances survival rate in sepsis in rats by reducing inflammation and oxidative stress, as it promotes the immune cell function and neutrophil trapping to xenobiotics and is digested by enhancing oxidative stress in immune cells.

Epilepsy is one of the most prevalent chronic medical conditions that really can affect individuals at any age. A broader study of the pathogenesis of the epileptic condition will probably serve as the cornerstone for the development of new antiepileptic remedies that aim to treat epilepsy symptomatically as well as prevent the epileptogenesis process or regulate its progression. Cellular changes in the brain include oxidative stress, neuroinflammation, inflammatory cell invasion, angiogenesis, and extracellular matrix associated changes. The extensive molecular profiling of epileptogenic tissue has revealed details on the molecular pathways that might start and sustain cellular changes. In healthy brains, epilepsy develops because of vascular disruptions, such as blood–brain barrier permeability and pathologic angiogenesis. Key inflammatory mediators are elevated during epileptic seizures, increasing the risk of recurrent seizures and resulting in secondary brain injury. Prostaglandins and cytokines are well-known inflammatory mediators in the brain and, after seizures, their production is increased. These inflammatory mediators may serve as therapeutic targets in the clinical research of novel antiepileptic medications. The functions of inflammatory mediators in epileptogenesis are covered in this review. Oxidative stress also plays a significant role in the pathogenesis of various neurological disorders, specifically epilepsy. Antioxidant therapy seems to be crucial for treating epileptic patients, as it prevents neuronal death by scavenging excess free radicals formed during the epileptic condition. The significance of antioxidants in mitochondrial dysfunction prevention and the relationship between oxidative stress and inflammation in epileptic patients are the major sections covered in this review.

Obesity is a metabolic disorder that could be the reason for the development of several disorders, and its management is necessary. The investigation evaluated the beneficial effect of rhynchophylline on high-fat diet (HFD)-induced obese rats. Obesity was induced with the HFD for 4 weeks, and rhynchophylline at 50 and 100 mg/kg was administered intraperitoneally (i.p.) for the next 4 weeks in the respective groups. Blood glucose and lipid profiles were estimated in rhynchophylline-treated HFD-induced obese rats. Levels of cytokines, reactive oxygen species (ROS), and oxidative stress parameters were estimated in the liver tissue and blood of all the groups of rats. The weight of adipose tissue and other organs, such as the liver and pancreas, was measured in the rats. The binding affinity of rhynchophylline with 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, in silico) was estimated through a docking study. Treatment with rhynchophylline ameliorated the altered levels of glucose and lipid profiles in the serum of the obese rats. The weight of adipose tissue isolated from different regions of the body was reduced in the rhynchophylline-treated group compared to that in the obese group. There was a significant reduction of oxidative stress in the rhynchophylline-treated group compared with the obese group of rats. The in silico study showed that rhynchophylline binds with HMG-CoA reductase with a binding energy of −8.37 kcal/mol. In conclusion, data from the report reveal that rhynchophylline reduces obesity by promoting the conversion of white adipose tissue (WAT) to brown adipose tissue (BAT), as it interacts with HMG-CoA reductase in HFD-induced obese rats.

Purpose: To investigate the potential protective effects of ononin on cecal ligation puncture (CLP) induced sepsis rat model. Methods: CLP was used to induce sepsis in rats and then treated with ononin at doses of 25 and 50 mg/kg intraperitoneally for seven days. The daily assessment included measurements of food and water intake, as well as body weight in the different rat groups. The study also examined the effects of ononin on survival rates, level of tumor necrosis factor (TNF)-α, interleukin (IL)-16, IL-6, C-reactive protein in the serum, and markers of oxidative stress in tissue homogenates of rats. The weight of spleen and lung tissue were also estimated in ononin-treated sepsis group. Additionally, histopathological examinations of lung and liver tissues were conducted in sepsis rats using hematoxylin and eosin staining. Results: The ononin-treated group showed significant improvements in food and water intake, as well as body weight, compared to the sepsis group of rats. Survival rate was also improved in the ononin-treated group. Ononin ameliorates oxidative stress and inflammatory mediators in sepsis rats. Histopathological changes (liver and lung tissue) were observed to be ameliorated in the group of rats treated with ononin versus the sepsis group. Conclusion: Ononin enhances survival rate in sepsis in rats by reducing inflammation and oxidative stress.

Diabetic neuropathy (DN) is a chronic diabetic complication, which is difficult to manage. The current investigation evaluates the effect of Nerium oleander(NO) in the management of diabetic neuropathy (DN). Diabetic neuropathy was induced by streptozotocin (STZ) [60 mg/kg, i.p.] and treated with NO 150 mg/kg and 300 mg/kg, per oral (p.o.) for two week. Blood glucose level, analgesic response, muscle coordination, and intestinal transit were estimated in DN rats. Oxidative stress and inflammation were estimated in DN rats. Loss of muscle coordination, swim Endurance and analgesic response were attenuated by NO treatment in DN rats. Mediators of inflammation and oxidative stress parameters were ameliorated in NO treated DN rats. The given study concluded that NO has beneficial for the management of DN by regulating oxidative stress and inflammatory mediators.

Aging is a process of time‐associated depletion in the physiological functions, essential for the survival and reproducibility of living beings. Some age‐related disorders can be successfully controlled with some biomedical techniques or pharmaceutical approaches. There are some precise remedies that demonstrate conspicuous promise in the preclinical and clinical setup of extending lifespan or enhancing health by altering natural senescence. The sirtuin family of proteins is one of the most favorable targets for antiaging strategies. Sirtuins were initially identified as transcription repressors in yeast, but today they are known to exist in bacteria and eukaryotes, as well as humans. The SIRT (1–7) family of proteins in humans is made up of seven members, each of which has either mono‐ADP ribosyl transferase or deacetylase activity. Researchers suggest that sirtuins are essential for cell metabolism and play a major role in how cells react to various stimuli, such as oxidative or genotoxic stress. A healthy lifestyle, which includes exercise and a balanced diet, has been demonstrated to impact health span by adjusting the levels of sirtuins, suggesting the involvement of sirtuins in extending human longevity. The hunt for sirtuin activators is among the most extensive and comprehensive research subjects in the present scenario. Some optimism has been generated to investigate antiaging therapies by natural compounds, such as curcumin and others. This review article highlights the role of sirtuins in native senescence and their primordial roles in the progression of several life‐threatening diseases. Further, it also provides recent information on the sirtuin activators and inhibitors and their therapeutic benefits.

The pancreas is a heterocrine gland that has both exocrine and endocrine parts. Most pancreatic cancer begins in the cells that line the ducts of the pancreas and is called pancreatic ductal adenocarcinoma (PDAC). PDAC is the most encountered pancreatic cancer type. One of the most important characteristic features of PDAC is neuropathy which is primarily due to perineural invasion (PNI). PNI develops tumor microenvironment which includes overexpression of fibroblasts cells, macrophages, as well as angiogenesis which can be responsible for neuropathy pain. In tumor microenvironment inactive fibroblasts are converted into an active form that is cancer‐associated fibroblasts (CAFs). Neurotrophins they also increase the level of Substance P, calcitonin gene‐related peptide which is also involved in pain. Matrix metalloproteases are the zinc‐associated proteases enzymes which activates proinflammatory interleukin‐1β into its activated form and are responsible for release and activation of Substance P which is responsible for neuropathic pain by transmitting pain signal via dorsal root ganglion. All the molecules and their role in being responsible for neuropathic pain are described below.