Mohamad Nasser

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Background: Stroke remains a leading cause of mortality worldwide. Ischemic stroke, caused by arterial occlusion, induces sensorimotor deficits and memory impairments. Excessive activity of the brain angiotensin II type 1 receptor (AT1R) is associated with hypertension and cerebral ischemia. Candesartan (CN), an AT1R blocker, improves cerebrovascular blood flow. Pomegranate ( Punica granatum ) is rich in polyphenolic antioxidants that reduce oxidative stress and inflammation, suggesting potential neuroprotective effects in cerebral ischemia. Aim: This study compared the neuroprotective effects of CN administered alone or in combination with pomegranate (POM) in a rat model of cerebral ischemia induced by chronic unilateral carotid artery ligation. Methods: Cerebral ischemia was induced by ligation of the right common carotid artery (RCCA) in adult rats. Animals were randomly assigned to four groups: sham control, untreated ischemic, ischemic treated with CN, and ischemic treated with CN + POM. Sensorimotor and cognitive functions were assessed 1–15 days post-surgery using beam balance (BB), beam walking (BW), modified sticky-tape (MST), novel object recognition (NOR), and the Morris water maze (MWM) tests. Results: RCCA ligation induced marked sensorimotor deficits and memory impairments. Both CN monotherapy and CN + POM treatment equally restored sensorimotor function to sham-control levels, as demonstrated by BB, BW, and MST tests. In contrast, CN + POM treatment showed greater efficacy than CN alone in improving short-term recognition and spatial memory, as demonstrated by NOR and MWM performance. Conclusion: CN effectively reverses ischemia-induced sensorimotor deficits, whereas the addition of POM confers specific and enhanced protection against cognitive impairment, indicating distinct mechanisms underlying sensorimotor and memory recovery after cerebral ischemia.

Excessive lipolysis in white adipose tissue (WAT) leads to insulin resistance (IR) and ectopic fat accumulation in insulin-sensitive tissues. However, the impact of G _i -coupled receptors in restraining adipocyte lipolysis through inhibition of cAMP production remained poorly elucidated. Given that the G _i -coupled P2Y ₁₃ receptor (P2Y ₁₃ -R) is a purinergic receptor expressed in WAT, we investigated its role in adipocyte lipolysis and its effect on IR and metabolic dysfunction-associated steatotic liver disease (MASLD). In humans, mRNA expression of P2Y ₁₃ -R in WAT was negatively correlated to adipocyte lipolysis. In mice, adipocytes lacking P2Y ₁₃ -R displayed higher intracellular cAMP levels, indicating impaired G _i signaling. Consistently, the absence of P2Y ₁₃ -R was linked to increased lipolysis in adipocytes and WAT explants via hormone-sensitive lipase activation. Metabolic studies indicated that mice lacking P2Y ₁₃ -R showed a greater susceptibility to diet-induced IR, systemic inflammation, and MASLD compared with their wild-type counterparts. Assays conducted on precision-cut liver slices exposed to WAT conditioned medium and on liver-specific P2Y ₁₃ -R–knockdown mice suggested that P2Y ₁₃ -R activity in WAT protects from hepatic steatosis, independently of liver P2Y ₁₃ -R expression. In conclusion, our findings support the idea that targeting adipose P2Y ₁₃ -R activity may represent a pharmacological strategy to prevent obesity-associated disorders, including type 2 diabetes and MASLD.

Background: Lung cancer is the second most common cancer worldwide. Eucalyptus plant extract has been shown to have anti-neoplastic effects. We investigated the antitumor effect of ethanolic and aqueous extracts of Eucalyptus camaldulensis collected at different altitudes on A549. In addition, we evaluated the additive effect of its combination with low-dose cisplatin (CDDP). Methods: Qualitative and quantitative analyses of secondary metabolites present in the plants were carried out. The antioxidant and cytotoxic activities of the different extracts on A549 were evaluated using the 2.2-diphenyl-1-picrylhydrazyl radical scavenging activity and neutral red assay, respectively. The cytotoxic effect of the combination of certain extract concentrations with low-dose CDDP on A549 cells was studied. Results: In the Ethanoic extract, a higher number of active substances and antioxidant activities were observed. The four E. camaldulensis extracts showed cytotoxic activity on A549 cells, with a higher cytotoxicity for the Ethanoic extract and the sea-level altitude species. Moreover, the dual exposure of cells to both E. camaldulensis extracts and a low dose of Cisplatin showed an additional cytotoxic effect on A549 cells in certain concentrations. Conclusions: This study opens novel therapeutic options in combinational therapies of Eucalyptus camaldulensis with low-dose CDDP for the treatment of adenocarcinoma cells of human lungs.

Chronic cerebral ischemia with a notable long-term cessation of blood supply to the brain tissues leads to sensorimotor defects and short- and long-term memory problems. Neuroprotective agents are used in an attempt to save ischemic neurons from necrosis and apoptosis, such as the antioxidant agent Eucalyptus. Numerous studies have demonstrated the involvement of the renin-angiotensin system in the initiation and progression of cardiovascular and neurodegenerative diseases. Candesartan is a drug that acts as an angiotensin II receptor 1 blocker. We established a rat model exhibiting sensorimotor and cognitive impairments due to chronic cerebral ischemia induced by the ligation of the right common carotid artery. Wistar male rats were randomly divided into five groups: Sham group, Untreated Ligated group, Ischemic group treated with Eucalyptus (500 mg/kg), Ischemic group treated with Candesartan (0.5 mg/kg), and Ischemic group treated with a combination of Eucalyptus and Candesartan. To evaluate the sensorimotor disorders, we performed the beam balance test, the beam walking test, and the modified sticky test. Moreover, the object recognition test and the Morris water maze test were performed to assess the memory disorders of the rats. The infarct rat brain regions were subsequently stained using the triphenyltetrazolium chloride staining technique. The rats in the Sham group had normal sensorimotor and cognitive functions without the appearance of microscopic ischemic brain lesions. In parallel, the untreated Ischemic group showed severe impaired neurological functions with the presence of considerable brain infarctions. The treatment of the Ischemic group with a combination of both Eucalyptus and Candesartan was more efficient in improving the sensorimotor and cognitive deficits (p < 0.001) than the treatment with Eucalyptus or Candesartan alone (p < 0.05), by the comparison to the non-treated Ischemic group. Our study shows that the combination of Eucalyptus and Candesartan could decrease ischemic brain injury and improve neurological outcomes.

Background: Lung and breast cancers are common in the world and represent major public health problems. Systemic chemotherapy is an effective way to prolong survival but it is associated with side effects. Plants are used as traditional treatments for many types of cancers, mostly in combination with chemotherapy. We investigated the antitumor effect of ethanolic (EE) and aqueous (AE) extracts of Eucalyptus camaldulensis on human alveolar adenocarcinoma basal epithelial cells (A549) and breast adenocarcinoma cell line (MCF-7) and checked the synergistic effect of the combination with low-dose cisplatin (CDDP). Methods: AE and EE were characterized for their secondary metabolites including content of phenol and antioxidant activity of both extracts. Cell viability was tested by the neutral red assay and MTT. Combinations of extract with low-dose CDDP on A549, MCF-7 cells, and normal cells peripheral blood mononuclear cells was used to study cell viability. Results: AE contains higher level of active constituents than EE. Higher antioxidant activity was observed in AE. Both extracts showed cytotoxic activity on A549 and MCF-7 cells. Moreover, combining E. camaldulensis with low-dose CDDP increases significantly the cell death of treated cells in comparison to those treated with CDDP alone. Conclusions: Our results highlight a new therapeutic concept that combines Eucalyptus camaldulensis with low-dose CDDP to treat lung and breast adenocarcinoma.

(1) Plants, due to their phytochemicals, have long been known for their pharmacological potential and medicinal value. Verjuice, the acidic juice of unripe green grape, is still poorly characterized in terms of its chemical composition and biological activities. (2) In this study, we characterized the chemical composition, antioxidant and antitumor potential of verjuice extract. Folin–Ciocalteu and aluminum chloride reagents were used to identify the total phenol and total flavonoid composition. Various conventional methods were used to quantify the alkaloids and tannins. DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay and Neutral Red assay were used to assess the antioxidant and antitumor activities, respectively. (3) We showed that the verjuice extract contains alkaloids, tannins, and a high quantity of total flavonoids and total phenols. Besides its antioxidant activity, verjuice significantly repressed human pulmonary adenocarcinoma (A549) cells’ viability in both dose- and time-dependent manners. Moreover, verjuice extract significantly enhanced the anticancer potential of cisplatin. (4) Altogether, these observations suggest a potential use of verjuice as a natural antitumor remedy.