Evaluation of the cytotoxic, anticancer, and genotoxic activities of Acacia nilotica flowers and their effects on N-methyl-N-nitrosourea-induced genotoxicity in mice.

PURPOSE: In this study, two main research objectives were examined: (1) the cytotoxic and anticancer activities of the aqueous methanol extract from Acacia nilotica flowers on three human cancer cells, namely lung A549, breast MCF-7, and leukemia THP-1 cells, and (2) the genotoxic effects of A. nilotica extract and its influence on DNA damage induced by N-methyl-N-nitrosourea (MNU) in mice. METHODS: Mice were orally treated with A. nilotica extract (200, 500, and 800 mg/kg for 4 days) with or without MNU (80 mg/kg intraperitoneally for 24 h). RESULTS: In vitro experiments showed that A549 cells were the most sensitive to A. nilotica extract among the tested cell lines. A. nilotica extract inhibited A549 cell proliferation by blocking the cell cycle at the G2/M phase and accumulating apoptotic cells in the sub-G0/G1 phase in A549 cells. In vivo experiments showed that MNU induced positive and negative genotoxicity in bone marrow cells and spermatocytes, respectively. Negative genotoxicity was observed in A. nilotica extract-treated groups only. However, A. nilotica extract (800 mg/kg) remarkably increased comet tail formation in bone marrow cells. Unexpectedly, the absence of antigenotoxicity was observed in three cotreated groups with A. nilotica extract and MNU compared with the MNU-treated group. Astonishingly, cotreatment with MNU and A. nilotica extract at a dose above 200 mg/kg remarkably increased micronucleus and comet tail formation in bone marrow cells compared with the MNU-treated group. CONCLUSIONS: A. nilotica extract possessed anticancer activity with relative genotoxic effects at high doses.

Costus speciosus extract protects against the oxidative damage of zearalenone via modulation of inflammatory cytokines, Nrf2 and iNOS gene expression in rats.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin that induces severe health disturbances in humans and animals. This study aimed to determine the bioactive compounds in Costus speciosus extract (CSE) using GC-MS and evaluate its protective capability against ZEN-induced oxidative damage, genotoxicity, and cytotoxicity in rats. Six groups of male Sprague Dawley rats were treated orally for 15 days including the control group, CSE-treated groups at low (200 mg/kg b. w) or high (400 mg/kg b. w) dose, ZEN-treated group (40 µg/kg b. w), and the groups treated with ZEN plus the low or the high dose of CSE. Blood and tissue samples were collected for different assays and pathological analyses. The results of GC-MS indicated the identification of 6 compounds and Azulene was the major. Animals that received ZEN showed severe disturbances in serum biochemical, cytokines, oxidative stress indicators, mRNA expression of iNOS, Nrf2, and inflammatory-related genes. ZEN also increased micronucleated polychromatic erythrocytes (MNPCEs) and comet tail formation in bone marrow cells along with the disturbances in the histological architecture of the liver and kidney. Co-administration of CSE plus ZEN could normalize the majority of the tested parameters and the histological picture at a dose as low as 200 mg/kg b. w. Therefore, CSE protects against ZEN toxicity via its antioxidant activity, modulation of iNOS, inflammatory-related genes, and the Nrf2 pathway and it could be used in the endemic regions.

Polyphenol Content, Antioxidant, Cytotoxic, and Genotoxic Activities of Bombax ceiba Flowers in Liver Cancer Cells Huh7.

OBJECTIVE: Bombax ceiba (red Silk cotton tree) has great ethnopharmacological significance due to its widespread use to treat various diseases such as dysentery, inflammation, and tuberculosis. Despite decades of research, the studies on the in vitro anticancer/genotoxic activity of B. ceiba flower remains restricted. Thus, the present research explored the effect of ethanol extract from B. ceiba flowers on three human cancer cells, including lung A549 and liver HepG2 and Huh7 cell lines. METHODS: Cytotoxic and genotoxic activity of B. ceiba extract was examined by MTT and comet assay, respectively. Further, B. ceiba extract was analysed to determine total polyphenol content and DPPH antiradical scavenging activity. RESULTS: ethanol extract from B. ceiba flowers had a high polyphenols content with very potent antioxidant activity. Further, B. ceiba extract displayed moderate cytotoxicity against Huh7 cells and no cytotoxicity against HepG2 and A549 cells. The comet assay findings showed that Huh7 cells treated with four concentrations of B. ceiba extract (» IC50, ½ IC50, IC50, and double IC50) increased the comet tail formation within 48 h in a concentration-dependent manner. CONCLUSION: ethanol extract from B. ceiba flowers exhibited its cytotoxicity through induction of DNA fragmentation in Huh7 cells.

Nanoencapsulation of thyme essential oil: a new avenue to enhance its protective role against oxidative stress and cytotoxicity of zinc oxide nanoparticles in rats.

Although the green synthesis of nanometals is eco-friendly, the toxicity or safety of these biosynthesized nanoparticles in living organisms is not fully studied. This study aimed to evaluate the potential protective role of encapsulated thyme oil (ETO) against zinc oxide nanoparticles (ZnO-NPs). ETO was prepared using a mixture of whey protein isolate, maltodextrin, and gum Arabic, and ZnO-NPs were synthesized using parsley extract. Six groups of male Sprague-Dawley rats were treated orally for 21 days which included the control group, ZnO-NP-treated group (25 mg/kg body weight (b.w.)), ETO-treated groups at low or high dose (50, 100 mg/kg b.w.), and the groups that received ZnO-NPs plus ETO at the two tested doses. Blood and tissue samples were collected for different assays. The results showed that carvacrol and thymol were the major components in ETO among 13 compounds isolated by GC-MS. ZnO-NPs were nearly spherical and ETOs were round in shape with an average size of 38 and 311.8 nm, respectively. Administration of ZnO-NPs induced oxidative stress, DNA damage, biochemical, ctyogentical, and histological changes in rats. ETO at the tested doses alleviated these disturbances and showed protective effects against the hazards of ZnO-NPs. It could be concluded that encapsulation of thyme oil using whey protein isolate, maltodextrin, and gum Arabic improved the antioxidant properties of ETO, probably possess synergistic effects, and can be used as a promising tool in pharmaceutical and food applications.

Inhibitory activity of black mulberry (Morus nigra) extract against testicular, liver and kidney toxicity induced by paracetamol in mice.

Black mulberry (Morus nigra) leaves is broadly used in traditional medicine worldwide. However, there are no scientific reports regarding testicular protection, hepato-and nephroprotective activities of M. nigra leaves. The present investigation was assessed the protective mechanism by which methanol extract from M. nigra leaves suppressed the damaging effects induced by paracetamol (APAP) in different mouse tissues. Male mice were orally given APAP (500 mg/kg) with or without M. nigra extract (150, 300, and 500 mg/kg) for four consecutive days. The results showed that crude extract possessed potent antioxidant activity (EC50 = 42.97 µg extract/mL) due to the presence of a high amount of polyphenol and flavonoid compounds. Gallic acid, chlorogenic acid, catechin, and rutin were isolated from the n-butanol fraction of M. nigra extract. Unexpectedly, oral administration of APAP did not induce chromosomal aberrations in mouse bone marrow; however, it produced damaging effects on testis, liver, and kidney tissues. Interestingly, M. nigra extract suppressed APAP-induced genotoxicity by lowering meiotic chromosomal aberrations in spermatocytes, morphological sperm abnormalities, and % DNA damage in comet tail in the liver and kidney tissues. The altered levels of glutathione S transferase activity, lipid peroxidation, liver, and kidney functions were significantly reversed when M. nigra was given to APAP group. The restoring of the histo-architectural distortions and decreasing over-expression of p53 protein as determined by immunohistochemistry in the liver, kidney, and testis sections were strengthened the protective activity of M. nigra extract. Conclusion, the bioactive components in the leaves of black mulberry appear to be a good candidate for genetic protection, treatment of oxidative stress-induced organotoxicity.

In Vitro Antioxidant and Antiproliferative Activities of Novel Orange Peel Extract and It's Fractions on Leukemia HL-60 Cells.

In the present work, novel orange peel was extracted with 100%EtOH (ethanol) and fractionated into four fractions namely F1, F2, F3, F4 which were eluted from paper chromatographs using 100%EtOH, 80%EtOH, 50%EtOH and pure water respectively. The crude extract and its four fractions were evaluated for their total polyphenol content (TPC), total flavonoid content (TFC) and radical scavenging activity using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Their cytotoxic activity using WST assay and DNA damage by agarose gel electrophoresis were also evaluated in a human leukemia HL-60 cell line. The findings revealed that F4 had the highest TPC followed by crude extract, F2, F3 and F1. However, the crude extract had the highest TFC followed by F4, F3, F2, and F1. Depending on the values of EC50 and trolox equivalent antioxidant capacity, F4 possessed the strongest antioxidant activity while F1 and F2 displayed weak antioxidant activity. Further, incubation HL-60 cells with extract/fractions for 24h caused an inhibition of cell viability in a concentration- dependent manner. F3 and F4 exhibited a high antiproliferative activity with a narrow range of IC50 values (45.9 - 48.9 µg/ml). Crude extract exhibited the weakest antiproliferative activity with an IC50 value of 314.89 µg/ml. Analysis of DNA fragmentation displayed DNA degradation in the form of a smear-type pattern upon agarose gel after incubation of HL-60 cells with F3 and F4 for 6 h. Overall, F3 and F4 appear to be good sources of phytochemicals with antioxidant and potential anticancer activities.

In Vitro Anticancer Activities of Anogeissus latifolia, Terminalia bellerica, Acacia catechu and Moringa oleiferna Indian Plants.

The present study was designed to evaluate in vitro anti-proliferative potential of extracts from four Indian medicinal plants, namely Anogeissus latifolia, Terminalia bellerica, Acacia catechu and Moringa oleiferna. Their cytotoxicity was tested in nine human cancer cell lines, including cancers of lung (A549), prostate (PC-3), breast (T47D and MCF-7), colon (HCT-16 and Colo-205) and leukemia (THP-1, HL-60 and K562) by using SRB and MTT assays. The findings showed that the selected plant extracts inhibited the cell proliferation of nine human cancer cell lines in a concentration dependent manner. The extracts inhibited cell viability of leukemia HL-60 and K562 cells by blocking G0/G1 phase of the cell cycle. Interestingly, A. catechu extract at 100 µg/mL induced G2/M arrest in K562 cells. DNA fragmentation analysis displayed the appearance of a smear pattern of cell necrosis upon agarose gel electrophoresis after incubation of HL-60 cells with these extracts for 24 h.