Ernest Adeghate

β‐Caryophyllene (BCP), a selective agonist of cannabinoid receptor type 2 (CB2), has garnered attention as a promising nutraceutical agent for modulating organ damage. The current study aimed at evaluating the pharmacological role of BCP in Thioacetamide (TAA)‐induced liver fibrosis, with particular attention to the involvement of CB2‐mediated signaling. Following the induction of fibrosis by TAA, rats were treated with BCP for 6 weeks. In a separate group, AM630, a selective CB2 receptor antagonist, was co‐administered with BCP in order to validate CB2‐dependent actions. TAA administration triggered significant hepatocellular injury. In addition, TAA activated necroptotic cellular death, shown in the upregulated RIPK1/RIPK3/p‐MLKL expression. Growth factors' signaling was disrupted and liver regeneration was impaired. On the contrary, BCP treatment ameliorated oxidative stress, mitigated inflammation, and decreased hepatic stellate cells' activation. This was accompanied by reduced collagen deposition and attenuated fibrosis. BCP markedly abrogated necroptosis and decreased the stimulation of fibrogenic and angiogenic signaling. Additionally, BCP potentiated hepatocytes' survival and restored hepatic regenerative capacity. AM630 co‐treatment abolished BCP's protective effects, confirming the CB2 receptors‐dependent effects. Given findings highlight BCP as a potential therapeutic agent for liver fibrosis and delineate endocannabinoid system's role in modulating organ fibrosis.

This study explored how different physical training settings affect hormonal and metabolic responses in male Wistar rats ( n = 28). Rats were randomly assigned to a control (no‐exercise), ET4 (4‐week training), ET8 (8‐week training), DT4 (4 week training and then 4‐week detraining), and PCA (4‐week training and then 4‐week detraining + PCA). Serum hormones, muscle secretions, glycogen, pyruvate, HK, and PFK were analyzed. The groups were compared using one‐way ANOVA, with Cohen’s d and Pearson’s correlation for associations. Machine learning models predicted body weight and glucose levels from training settings. Eight‐week training significantly elevated IL‐6 ( p = 0.021, d = 2.04), IGF‐1 ( p = 0.012, d = 1.96), cortisol ( p = 0.0277, d = 1.677) and testosterone‐to‐cortisol ( p = 0.009, d = 2.465), and leptin ( p = 0.001, d = 3.098) vs. control. Furthermore, 4–8 weeks of training resulted in a significant increase in the number of skeletal muscle satellite cells compared with the respective control groups. Myostatin was reduced with 4‐week training ( p = 0.002, d = 2.273) and further after 8 week ( p = 0.014, d = 1.613). PCA supplementation increased pyruvate levels ( p = 0.005, d = 1.31). Key correlations were found between IL‐6 and ghrelin ( r = −0.52, p = 0.005), FGF‐21 and T/A ( r = 0.47, p = 0.012), and IGF‐1 with aldosterone ( r = 0.47, p = 0.012) and cortisol ( r = −0.50, p = 0.006). Machine learning revealed total training weeks as the strongest predictor of body weight (XGBoost), while recent training (last 2 weeks) best predicted glucose levels (LightGBM). Metabolic adaptations emerged within 2 weeks, including improvement in IL‐6, IGF‐1, ghrelin, cortisol, aldosterone, and blood glucose, with effects amplified by 8 weeks of training. PCA supplementation regulated energy metabolism during detraining.

Background: Diabetes mellitus (DM), a metabolic disorder that leads to chronic hyperglycemia, is one of the topmost global public health concerns according to the International Diabetes Federation. Adropin is a peptide hormone that is primarily involved in energy homeostasis, but its involvement in other biological activities such as lowering hyperlipidemia, and diminishing insulin resistance has also been reported. In this study, we aimed to explore additional effects of adropin on oxidative stress, inflammation, and cell proliferation in an animal model of type 1 DM. Methods: To achieve our aim, normal and diabetic Wistar rats were treated with adropin (2.1 μg/kg/day) for a period of 10 days. Pancreatic tissue samples were collected for histomorphological analysis and inflammation assay, while blood was collected for oxidative stress assay. Results: Our results showed that diabetes induction stimulated cell proliferation in both exocrine and endocrine pancreas, and adropin dramatically attenuated this effect in pancreatic exocrine tissue, but not in the islet of Langerhans. In addition, adropin significantly increased glutathione reductase expression in pancreatic tissue, and augmented serum total glutathione in the diabetic rats compared to diabetic untreated rats. Conclusion: Our study indicates the potential role of adropin in alleviating oxidative stress in DM.

Liver fibrosis is associated with increased rates of morbidity and mortality. At present, there are no specific treatments that can directly reverse hepatic fibrosis. The endocannabinoid system has been found to play a significant role in regulating the development and progression of liver diseases, in addition to having protective effects. In this study, we investigate the protective potential of β-Caryophyllene (BCP) against Thioacetamide (TAA)-induced liver fibrosis. Wistar rats were injected with TAA (200 mg/kg) three times per week for 8 weeks to induce liver fibrosis. They also received oral BCP before the TAA injections. AM630 (1 mg/kg) was administered to confirm the CB2 receptor-dependent effect of BCP. The BCP treatment (50 mg/kg) protected against cell injury and potentiated antioxidant defense by replenishing hepatic GSH, improving catalase activity, and inhibiting the formation of MDA. The co-administration of BCP mitigated the TAA-induced inflammatory response by decreasing the release of proinflammatory cytokines. Histological examination showed preserved cellular integrity, decreased collagen deposits with other extracellular matrix proteins, and low levels of myofibroblast activation. In addition, the BCP-treated rats demonstrated upregulated sirtuin 1 (SIRT1) expression, which had a direct inhibitory effect on hypoxia inducible factor (HIF-1α). AM630 pre-treatment inhibited all the aforementioned protective mechanisms of BCP. Based on our findings, BCP exerts protective effects in liver fibrosis, which can be attributed to its agonist action on CB2 receptors. This study provides preclinical evidence of the potential preventative benefits of BCP in liver fibrosis.

Inflammatory bowel diseases (IBDs), such as ulcerative colitis, and Crohn’s disease are chronic idiopathic inflammatory diseases of the gastrointestinal system involving interaction between genetic and environmental factors mediating the occurrence of oxidative stress and inflammation. There is no permanent cure for IBD except long-term treatment or surgery (resection of the intestine), and the available agents in the long term appear unsatisfactory and elicit numerous adverse effects. To keep the disease in remission, prevent relapses and minimize adverse effects of currently used medicines, novel dietary compounds of natural origin convincingly appear to be one of the important therapeutic strategies for the pharmacological targeting of oxidative stress and inflammation. Therefore, it is imperative to investigate plant-derived dietary agents to overcome the debilitating conditions of IBD. In the present study, the effect of α-Bisabolol (BSB), a dietary bioactive monoterpene commonly found in many edible plants as well as important components of traditional medicines, was investigated in acetic acid (AA)-induced colitis model in rats. BSB was orally administered to Wistar male rats at a dose of 50 mg/kg/day either for 3 days before or 30 min after induction of IBD for 7 days through intrarectal administration of AA. The changes in body weight, macroscopic and microscopic analysis of the colon and calprotectin levels in the colon of rats from different experimental groups were observed on day 0, 2, 4, and 7. The levels of myeloperoxidase (MPO), a marker of neutrophil activation, reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid peroxidation, and the levels of pro-inflammatory cytokines were measured. AA caused a significant reduction in body weight and induced macroscopic and microscopic ulcers, along with a significant decline of endogenous antioxidants (superoxide dismutase (SOD), catalase, and GSH), with a concomitant increase in MDA level and MPO activity. BSB significantly improved the AA-induced reduction in body weight, colonic mucosal histology, inhibited MDA formation, and restored antioxidant levels along with a reduction in MPO activity. AA also induced the release of pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-23 (IL-23) and tumor necrosis factor-α (TNF-α). Furthermore, AA also increased levels of calprotectin, a protein released by neutrophils under inflammatory conditions of the gastrointestinal tract. BSB treatment significantly reduced the release of calprotectin and pro-inflammatory cytokines. The findings of the present study demonstrate that BSB has the potential to improve disease activity and rescue colonic tissues from damage by inhibiting oxidative stress, lipid peroxidation and inflammation. The findings are suggestive of the benefits of BSB in IBD treatment and substantiate its usefulness in colitis management, along with its gastroprotective effects in gastric ulcer.

Type 2 diabetes mellitus (T2DM) is known to increase the risk of fragility fractures; however, the underlying mechanism is still elusive. Reduced miR-155 and elevated RHOA are known to drive bone resorption, but their role in T2DM remains unclear. This study investigates bone remodeling imbalances in T2DM through miR-155 and RHOA expression profiling. Three-month-old female Wistar rats were fed a high-calorie diet for 3 weeks, followed by intraperitoneal injections of two lower doses of streptozotocin at weekly intervals to induce T2DM. Bone analysis from diabetic rats tested using qRT-PCR showed significantly reduced miR-155 levels and elevated RHOA. Histological analysis showed a 12.65% increase in Tb.Sp, 10.07% decrease in Tb.Th, and significant increase (p < 0.05) in apoptotic osteocytes. The bone turnover marker CTx-1 level was increased by 20.84%, and RANKL levels were significantly increased in T2DM. IL-1β and TNF-α were increased in T2DM. Bone resorption is more likely to occur in T2DM as both IL-1β and TNF-α work synergistically to promote osteoclastogenesis. MiR-155 could be an important modulator of bone remodeling in T2DM and a potential therapeutic target for diabetic osteopathy.

There is an exponential increase in the global prevalence of non-alcoholic fatty liver disease (NAFLD) in all populations. The objective of this review is to examine how different cultures and molecular entities influence the progression of NAFLD. Research databases, including PubMed, Scopus, the American Diabetes Association, the American Liver Foundation, and Diabetes UK, were used to retrieve information. Our data analysis showed that cultural norms shape the perceptions of health, illness, and mortality, thus influencing how individuals view themselves and express their experiences and may also affect decisions related to treatment and healthcare. Cultural competence, the ability to understand and navigate cultural differences, is essential for eliciting patient and practitioner perspectives and integrating this understanding into diagnostic and treatment plans. By acknowledging and respecting a patient’s cultural background, healthcare providers can foster trust, improve care quality, enhance acceptance of diagnoses, and boost treatment adherence. Although cultural factors play a crucial role in the progression of NAFLD, the disease is also shaped by genetic predispositions, molecular mechanisms, and comorbidities. Molecular pathways involved in the development and progression of NAFLD include alterations in lipid metabolism, insulin signaling, insulin resistance, oxidative stress, defective gut microbiome, and inflammation. This study concludes that a combination of cultural preferences and molecular factors has contributed to the worldwide exponential rise in the prevalence of NAFLD, which in turn has led to an increase in the prevalence of comorbidities such as cardiovascular diseases, diabetes mellitus, and metabolic syndrome.

Diabetes mellitus affects 537 million adults around the world. Adropin is expressed in different cell types. Our aim was to investigate the cellular localization in the endocrine pancreas and its effect on modulating pancreatic endocrine hormone release in streptozotocin (STZ)-induced diabetic rats. Adropin expression in the pancreas was investigated in normal and diabetic rats using immunohistochemistry and immunoelectron microscopy. Serum levels of insulin, glucagon pancreatic polypeptide (PP), and somatostatin were measured using a Luminex^® χMAP (Magpix^®) analyzer. Pancreatic endocrine hormone levels in INS-1 832/3 rat insulinoma cells, as well as pancreatic tissue fragments of normal and diabetic rats treated with different concentrations of adropin (10⁻⁶, 10⁻⁹, and 10⁻¹² M), were measured using ELISA. Adropin was colocalized with cells producing either insulin, glucagon, or PP. Adropin treatment reduced the number of glucagon-secreting alpha cells and suppressed glucagon release from the pancreas. The serum levels of GLP-1 and amylin were significantly increased after treatment with adropin. Our study indicates a potential role of adropin in modulating glucagon secretion in animal models of diabetes mellitus.

Diabetes mellitus (DM) is a condition of abnormal carbohydrate metabolism, leading to persistent hyperglycemia. It is defined as a fasting blood glucose over 7.0 mmol/L, a 2-hour plasma post-meal of 11.1 mmol/L, or HbA1C values over 6.5% (48 mmol/L). DM affects almost 600 million people globally with an annual cost of around three trillion US dollars. These data indicate that DM is a global health burden that warrants attention. Complications of DM include nephropathy, retinopathy, neuropathy, and cardiomyopathy. DM-induced hyperglycemia causes oxidative stress, inflammation, endothelial and mitochondrial abnormality, and subsequently, cardiomyopathy. Hyperglycemia stimulates many signaling pathways including polyol, and hexokinase, resulting in the formation of vascular endothelial lesions, free radicals and carbonyl anions, transforming growth factor-β1, fibronectin, and nuclear factor kappa-B, which increase fibrosis and inflammation in the myocardium. All of these pathological processes lead to defective vascular permeability and hypoxia in cardiac tissue, ischemia, and eventually heart failure, and sudden cardiac death. The onset of diabetic cardiomyopathy could be delayed with a healthy lifestyle (balanced diet, physical activity, sleep, low stress, non-smoking). GLP-1 receptor agonists with or without SGLT2i are beneficial additions for the treatment of diabetic cardiomyopathy.