Middle Eastern Plants with Potent Cytotoxic Effect Against Lung Cancer Cells.

Cancer is one of the leading causes of increasing global mortality with uprising health concerns and threats. Unfortunately, conventional chemotherapy has substantial side effects, limiting its relevance and prompting a quest for safe and efficient alternatives. For thousands of years, plants have provided a rich reservoir for curing a variety of ailments, including cancer. According to the World Health Organization, medicinal plants would be the best source of medications. However, only 25% of drugs in the present pharmacopoeia are derived from plants. Hence, further research into different plants is required to better understand their efficacy. Twenty extracts of widely distributed Middle Eastern plants were screened for the cytotoxic effect against lung cancer cell lines (A549). Eleven plants showed IC50 below 25 µg/mL, consequently, the bioactive extracts were further fractionated by graded precipitation using absolute ethanol. All fraction A (FA; crude polysaccharides precipitate) showed potent IC50, 0.2-5.5 µg/mL except the FA of Brassica juncea, Silybum marianum, and Phaseolus vulgaris, whereas FB fractions (filtrate) of Anastatica hierochuntica, Plantago ovate, Tussilago farfara, and Cucurbita moschata had lower efficacy than other fractions with IC50 values in the range of 0.1-7.7 µg/mL. The fractions of FA Taraxacum officinale and FB Ziziphus spina possess the most potent cytotoxic activity with IC50, 0.2 and 0.1 µg/mL, respectively. Moreover, cell cycle analysis of both fractions revealed an arrest at G1/S-phase and activation of apoptosis rather than necrosis as the mode of cell death. Therefore, T. officinale and Z. spina fractions may pave the way to manage lung carcinoma as an alternative and complementary food regimen.

Melatonin and zinc supplements with physical and mental activities subside neurodegeneration and hepatorenal injury induced by aluminum chloride in rats: Inclusion of GSK-3ß-Wnt/ß-catenin signaling pathway.

Alzheimer's disease (AD) is an irreversible, progressive cognitive dysfunction. Inflammaging is the greatest common factor between AD and hepatorenal malfunction. This study aimed to use melatonin (MEL) and zinc sulfate (Zn) in addition to physical and mental activities (PMA) to ameliorate AlCl3-induced AD as well as investigate their impact on the associated hepatorenal impairment. METHODS: Seven groups of rats each received: saline (control group), AlCl3 (70 mg/kg, i.p.), PMA, either alone or with a combination of Mel (10 mg/kg, p.o) and/or Zn (16 mg/kg, p.o). Neurological deterioration was assessed after 5 weeks using behavioral tests, histopathological examination, and measurements of acetylcholinesterase (ACHE), brain monoamines, oxidative stress, and inflammatory markers, Amyloid precursor protein (APP), amyloid-ß (Aß), tau levels, and brain derived neurotrophic factor (BDNF). Moreover, the GSK-3ß-Wnt/ß-catenin signaling pathway was assessed. Additionally, oxidative stress and inflammatory markers were determined in liver and kidney tissues with concurrent evaluation of hepatic and renal functions. RESULTS: The histopathological examination revealed a cerebral cortex and hippocampus deterioration in the AD group with a decline in spatial learning and memory, besides a significant increase in AD markers in the brain and disturbance in GSK-3ß-Wnt/ß-catenin signaling. The AD group showed hepatorenal injuries supported by elevated oxidative stress and inflammatory markers. However, adding Mel and Zn to PMA significantly attenuated the neurodegeneration and enhanced hepatic and renal functions by ameliorating oxidant and inflammatory markers. CONCLUSIONS: Combining Mel and Zn supplements with PMA defends against AlCl3-induced AD by modulating GSK-3ß-Wnt/ß-catenin signaling and palliates the associated hepatorenal dysfunction.

Correlation of Chillies Capsaicinoids Contents with their Cytotoxic Effects against Hepatocarcinoma Cells.

BACKGROUND AND OBJECTIVE: Chillies are delicious spices that are used extensively. Capsaicinoids, the major constituents of chillies with reported anti-cancer effects, have been determined with non-specific colorimetric methods. A rapid and reproducible method for extraction and quantification of the major chillies capsaicinoids; capsaicin, dihydrocapsaicin (DHC) and nordihydrocapsaicin (n-DHC), was reported, moreover study of their cytotoxic activity. MATERIALS AND METHODS: This study has covered the extraction of capsaicinoids from red and green-colored chillies followed by their quantification using HPLC-UV method after validation. Furthermore, the correlation of capsaicinoids contents with their in vitro hepatocarcinoma cytotoxicity was represented by Pearson's correlation coefficient. RESULTS: Capsaicinoids contents are ranged from 1219.88-15098.67 ng mg-1 of Dried Extract (DE). Capsaicin exhibits the lowest IC50 when compared to doxorubicin (9.201±0.91 and 16.1±0.82 µg mL-1, respectively). The exhibited activities of methanol extracts of red and green-colored chillies (IC50 = 20.21±1.72 and 16.02±0.69 µg mL-1, respectively) may attribute to their excessive contents of capsaicinoids (6975.42 and 15098.67 ng mg-1 DE, respectively). Capsaicin and n-DHC contents have a negative correlation with cytotoxic activity. CONCLUSION: Green-colored chillies were found to be more cytotoxic in comparison with red-colored chillies that may be relative to their high content of capsaicinoids. The present investigation suggests that capsaicinoids contents correlate with cytotoxic activity.

Aldose reductase inhibitor form Cassia glauca: A comparative study of cytotoxic activity with Ag nanoparticles (NPs) and molecular docking evaluation.

UPLC-MS/MS profiling of Cassia glauca leaves extract revealed the identification of 10 flavonoids. Kaempferol 3-O-ß-D-rutinoside was isolated and studied for its cytotoxic activity. It showed high cytotoxic effects against MCF-7 (IC50 of 4.6±0.038 µg/ml) and HepG-2 (IC50 of 8.2±0.024 µg/ml) cancer cell lines, compared to the leaves extracts, their Ag nanoparticles, and doxorubicin. Moreover, Kaempferol 3-O-ß-D-rutinoside exerted a synergistic cytotoxic effect with doxorubicin on MCF-7 cell lines. It was discovered as kinases and aldose reductase inhibitor while rationalizing its cytotoxic activity through molecular docking study. Thus, it is expected that the cardiotoxic effects of doxorubicin can be also decreased by using Kaempferol 3-O-ß-D-rutinoside due to its aldose reductase inhibitory effect. These findings suggested that Kaempferol 3-O-ß-D-rutinoside could be used in combination with chemotherapeutic drugs to increase the sensitivity to their cytotoxic activity and protect against their side effects.

Geraniol activates Nrf-2/HO-1 signaling pathway mediating protection against oxidative stress-induced apoptosis in hepatic ischemia-reperfusion injury.

Geraniol (GOH) is a natural essential oil that possesses antioxidant, anti-inflammatory, and antiapoptotic properties by various signaling pathways. Liver ischemia-reperfusion injury (IRI) is a serious event that triggers liver dysfunction or even failure. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcriptional factor, maintains cellular defense mechanism through antioxidant and anti-inflammatory properties. To detect GOH effect against liver IRI through the activation of the Nrf2/HO-1 antioxidant pathway, five groups of rats were randomized to normal, sham, IR, GOH, and GOH/IR. Blood samples and liver tissues were collected to measure various biochemical parameters related to liver function, and oxidative stress as well as inflammatory and apoptotic indicators besides liver tissue histopathology was evaluated by light microscopy. GOH induces activation of Nrf2 along with the upregulation of HO-1 expression. Also, the antioxidant activity of GOH was shown by the elevation of total antioxidant capacity and GSH levels, together with normalizing malondialdehyde. Regarding the anti-inflammatory effect of GOH, it suppresses the levels of TNF-α, iNOS, and COX-2. Additionally, the antiapoptotic effect of GOH, Bax, and caspase-3, 9 were reduced in liver tissue. GOH is a promising hepatoprotective agent in liver IRI through the activation of Nrf2/HO-1 antioxidant pathway.