Objective: To investigate the effects of Δ⁹-tetrahydrocannabinol, the principal psychoactive compound of Cannabis sativa, and cannabinol, a Δ⁹-tetrahydrocannabinol degradative product, on human non-small cell lung cancer cells. Methods: Δ⁹-Tetrahydrocannabinol and cannabinol were tested for anticancer activity in human non-small cell lung cancer (A549) cells. The effects on cell proliferation, apoptosis, and phosphorylation profiles were examined. The effects of Δ⁹-tetrahydrocannabinol and cannabinol on tumor growth were also investigated using a xenograft nude mouse model. Apoptosis and targeted phosphorylation were verified by immunohistochemistry. Results: Δ⁹-Tetrahydrocannabinol and cannabinol significantly inhibited cell proliferation and increased the number of apoptotic cells in a concentration-dependent manner. The Δ⁹-tetrahydrocannabinol- and cannabinol-treated cells had lower levels of phosphorylated protein kinase B [AKT (S473)], glycogen synthase kinase 3 alpha/beta, and endothelial nitric oxide synthase compared to the controls. The study of xenograft mice revealed that tumors treated with 15 mg/kg Δ⁹-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly smaller than those of the control mice. The tumor progression rates in mice treated with 15 mg/kg Δ⁹-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly slower than in the control group. Conclusions: These findings indicate that Δ⁹-tetrahydrocannabinol and cannabinol inhibit lung cancer cell growth by inhibiting AKT and its signaling pathways, which include glycogen synthase kinase 3 alpha/beta and endothelial nitric oxide synthase.

Objective: To explore the protective effects of anthrahydroquinone- 2,6-disulfonate (AH₂QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH₂QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH₂QDS group was given AH₂QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL- 6, TNF-α, apelin-APJ (the apelin-angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH₂QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH₂QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH₂QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH₂QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH₂QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH₂QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH₂QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH₂QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH₂QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH₂QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.

Objective: To evaluate the potential effect of human Wharton’s jelly mesenchymal stem cells (hWJMSCs) on acute respiratory distress syndrome in lipopolysaccharide (LPS)-induced rats. Methods: The hWJMSCs (5×10⁴/mL, 5×10⁵/mL, 5×10⁶/mL) were administered to rats on day 1 and day 8 after being induced by LPS (5 mg/kg body weight). TNF-α levels in the lung and IL- 18 and IL-1β levels in the serum were measured using ELISA. In addition, caspase-1 expression in lung tissues was quantified using qRT-PCR, and NF-κB and IL-6 expressions were assessed using immunohistochemistry. Results: The hWJMSCs decreased TNF-α levels in the lung and plasma IL-18 and IL-1β levels. Moreover, the hWJMSCs downregulated the expressions of caspase-1, IL-6, and NF-κB in lung tissues. Conclusions: The hWJMSCs can decrease inflammatory markers of acute respiratory distress syndrome in a rat model and may be further investigated for the treatment of acute respiratory distress syndrome.

Objective: To investigate the role of Mirabilis jalapa root extracts in restoration of glucose homeostasis in alloxan-induced hyperglycemic Wistar albino rats. Methods: Experimental hyperglycemic rats were treated daily with 200 and 400 mg/kg of Mirabilis jalapa extracts after initial fasting for 6 h. Two-hour postprandial glucose and changes in body weight were monitored during treatment. After 14 d, the rats were sacrificed and blood was collected for biochemical assessment of serum glucose and insulin levels, lipid profile, and oxidative stress markers. Histopathological examinations of harvested pancreas were also carried out. Results: Mirabilis jalapa root extracts at 200 and 400 mg/kg increased the body weight of hyperglycemic rats. Postprandial glucose levels of the extract-treated hyperglycemic groups progressively declined during treatment compared with the untreated hyperglycemic control group (P<0.05). The lipid profile indices of the untreated negative control group were significantly elevated (P<0.05), which were reversed by treatment with Mirabilis jalapa extracts. The remarkable increases in antioxidant enzyme activities and a significant decrease in malondialdehyde levels were observed in the hyperglycemic group treated with Mirabilis jalapa extracts. Mirabilis jalapa extracts also significantly increased serum insulin levels (P<0.05). In addition, histopathological examinations of the pancreas revealed a significant cell population within the islet nests of the extract-treated hyperglycemic groups. Conclusions: Mirabilis jalapa extract can restore glucose homeostasis and show hypoglycemic and hypolipidemic effects in hyperglycemic rats. Further studies are needed to verify the active components of the plant and the underlying mechanism of action in the future.

Objective: To investigate the prophylactic efficacy of date palm fruit extract against doxorubicin-induced hepatotoxicity in Wistar albino rats. Methods: The rats were equally and randomly assigned to 6 groups: group 1 (untreated control), group 2 and 3 given daily oral administration of prophylactic aqueous extract of date palm fruit at 0.75 and 1.5 mg/kg body weight, respectively, and group 4, 5 and 6 intraperitoneally injected with doxorubicin at 15 mg/kg on day 30. Rats in group 5 and 6 received daily oral administration of aqueous extract of date palm fruit at 0.75 and 1.5 mg/kg body weight, respectively, for 30 d. The phytochemicals identified by GC-MS analysis were analyzed using in silico study. Antioxidant enzymes, liver enzymatic, biochemical parameters and histopathological analysis were determined to evaluate hepatoprotective activity of date extract. Results: Aqueous extract of date palm fruit significantly mitigated doxorubicin-induced changes in activities of liver enzymes, reduced reactive oxygen species levels, and suppressed lipid peroxidation and DNA damage. Moreover, aqueous extract of date palm fruit reduced doxorubicin-induced hepatic lesions. Molecular docking studies showed that most compounds of aqueous extract of date palm fruit identified via GC-MS had good interaction with proteins of human pregnane X receptor, oxygenase-1, and CYP2C9. Conclusions: The aqueous extract of date palm fruit mitigates doxorubicin-mediated DNA damage and hepatotoxicity, and restores normal liver function and may be a promising agent against the deleterious effects of doxorubicin.