Asian Pacific Journal of Tropical Biomedicine

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Natural products include several diverse compounds that have been found to be effective against cancer. Discovering anticancer compounds in nature is a multistep and complex process that requires pre-clinical and clinical studies. Only a few of the available natural products are used to treat cancer since most of them have very high complexity and low bioavailability. Therefore, the process of anticancer drug discovery requires a straightforward and effective method to assess anticancer activity using in vitro assays. This review summarizes various cell-based assays and techniques used to measure cell viability, migration, and apoptosis, focusing in particular on the principles, mechanisms, advantages, and disadvantages of each assay to provide a preliminary platform for cancer drug discovery.

Objective: To investigate the effect of Moringa oleifera leaf extract on angiogenesis and inflammatory process in a rat model of streptozotocin-induced diabetic nephropathy. Methods: Four weeks after a single injection of 50 mg/kg streptozotocin, rats were treated with 100 or 200 mg/kg/day Moringa oleifera leaf extract, 1 mg/kg/day dapagliflozin, or a combination of Moringa oleifera leaf extract and dapagliflozin for further eight weeks. Renal function, kidney histology, and gene expression were evaluated at the end of the experiment. Results: Renal function of diabetic rats was significantly impaired as evidenced by increased blood urea nitrogen, albuminuria, 24-h proteinuria, and high creatinine clearance which indicated glomerular hyperfiltration. In addition, diabetic rats showed an increase in gene expressions of vascular endothelial growth factor-A (VEGF-A), angiopoietin-2 (Ang2), the Ang2/Ang1 ratio, tumor necrosis factor-α, interleukin-1β and monocyte chemoattractant protein-1. Immunohistochemical staining demonstrated a significant increase in the density of glycoprotein CD34. Moringa oleifera leaf extract markedly improved all renal dysfunction markers and modulated the upregulated expression of angiogenic factors and inflammatory genes. Conclusions: Moringa oleifera leaf extract could suppress abnormal angiogenesis and inflammatory processes possibly by downregulating gene expression of angiogenesis factors and proinflammatory cytokines.

Objective: To evaluate the effect of Senna petersiana leaf extracts on key digestive enzymes and FeSO₄-induced oxidative injury. Methods: Dried Senna petersiana leaf powder (60 g) was defatted in n-hexane and then extracted sequentially at room temperature with dichloromethane, methanol, and distilled water. The total phytochemical content of the extracts was estimated using established methods. The in vitro antioxidant, anti-lipase, and antidiabetic activities and the effect of the extracts on intestinal glucose absorption and FeSO₄-induced pancreatic oxidative injury were determined using different protocols. Moreover, GC-MS analysis was performed to identify the main compounds of the plant extract. Molecular docking analysis was also carried out to evaluate the binding energy of compounds with digestive enzymes. Results: Senna petersiana leaf extracts showed significant antioxidant activities in FRAP, DPPH, and hydroxyl radical scavenging assays. They also inhibited pancreatic lipase and lowered intestinal glucose absorption by suppressing activities of α-amylase and α-glucosidase. Treatment with the extracts also lowered lipid peroxidation (malondialdehyde), nitric oxide level, acetylcholinesterase, and ATPase activities with simultaneous improvement of antioxidant (catalase, superoxide dismutase, glutathione) capacity in the type 2 diabetes model of oxidative pancreatic injury. GC-MS characterization of the extracts revealed the presence of stilbenoids, alkaloids, and other compounds. Molecular docking screening assay indicated the extract phytochemicals showed strong interaction with the active site amino acids of the targeted digestive enzymes. Among the Senna petersiana compounds, veratramine had the highest affinity for α-amylase and lipase, whereas dihydrostilbestrol was most attracted to α-glucosidase. Conclusions: Senna petersiana inhibits carbohydrate digestive enzymes, reduces intestinal glucose absorption, and exerts ameliorative effects on FeSO₄-induced oxidative pancreatic injury with significant antioxidant capabilities. Detailed in vivo studies are underway to understand the plant’s therapeutic potential in diabetes management.

Objective: To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice. Methods: Swiss strain of albino female mice were divided into 6 groups of 5 animals in each: Group I (control group), group II (doxorubicin, 10 mg/kg, i.v.), group III, IV, and V (Nigella sativa oil; 1.5, 3, and 6 mL/kg, respectively), group Ή (Nigella sativa oil per se; 6 mL/kg, p.o.). The duration of treatment was 15 d (10 days’ pre-treatment and 5 days’ post-treatment) and doxorubicin was administered on day 11th of the treatment schedule. Following Nigella sativa oil treatment, neurobehavioral tests, cardiac hypertrophy tests, and biochemical tests in serum and tissues were performed. Neurological tests included assessment of anxiety-like behavior in the elevated plus maze, spontaneous alternation behavior in the cross maze, and depression-like behavior in modified forced swim tests. Biochemical tests included serum lactate dehydrogenase and creatinine kinase-MB, malondialdehyde and reduced glutathione in tissues. Lastly, molecular docking was used to estimate the affinity of the phytoconstituents of Nigella sativa oil with histone deacetylases. Results: Nigella sativa oil treatment significantly (P<0.001) restored doxorubicin-induced neurobehavioral changes, decreased lactate dehydrogenase and creatinine kinase-MB in the plasma, malondialdehyde contents in tissues, and increased reduced glutathione level. Besides, no significant alteration was observed in Nigella sativa oil per se group as compared to the control. Molecular docking showed that Nigella sativa oil components had appreciable binding affinitiy with the protein cavities of HDAC1 and HDAC6. Conclusions: The result shows that Nigella sativa oil exerts anxiolytic, antidepressant, and memory-enhancing effects in addition to cardioprotective effect against doxorubicin-induced cardiomyopathy in mice. The modulatory effect of Nigella sativa oil on oxidative stress could contribute to the cardioprotective effect and associated neurobehavioral changes in mice.

Online since 13^th December 2017