Apoptosis-inducing anti-proliferative and quantitative phytochemical profiling with in silico study of antioxidant-rich Leea aequata L. leaves.

Natural products have been important parts of traditional medicine since ancient times, with various promising health effects. Leea aequata (L. aequata), a natural product, has been widely used for treating several diseases due to its promising pharmacological activities. Therefore, the present study aimed to explore the phytochemical profiling and molecular docking of the antioxidant-rich part of L. aequata leaves and its antiproliferative activity. L. aequata leaves were extracted with methanol, followed by fractionation with the respective solvents to obtain the petroleum ether, chloroform, ethyl acetate, and aqueous fractions. The antioxidant activity was evaluated by spectrophotometric methods. The cytotoxic and antiproliferative activities were detected using MTT colorimetric and confocal microscopy methods, respectively. Phytochemical compositions were analyzed using gas chromatography‒mass spectrometry analysis. Computer aided (molecular docking SwissADME, AdmetSAR and pass prediction) analyses were undertaken to sort out the best-fit phytochemicals present in the plant responsible for antioxidant and anticancer effects. Among the fractions, the ethyl acetate fraction was the most abundant polyphenol-rich fraction and showed the highest antioxidant, reducing power, and free radical scavenging activities. Compared to untreated MCF-7 cells, ethyl acetate fraction-treated MCF-7 cells showed an increase in apoptotic characteristics, such as membrane blebbing, chromatin condensation, and nuclear fragmentation, causing apoptosis and decreased proliferation of HeLa and MCF-7 cells. Furthermore, gas chromatography mass spectrometry data revealed that the ethyl acetate fraction contained 16 compounds, including methyl esters of long-chain fatty acids, which are the major chemical constituents. Moreover, hexadecanoic acid, methyl ester; 9-octadecenoic acid (Z)-, methyl ester; 9,12-octadecadienoic acid, methyl ester (Z, Z) and phenol, 2,4-bis(1,1-dimethylethyl) are known to have antioxidant and cytotoxic activity, as confirmed by computer-aided models. A strong correlation was observed between the antioxidant and polyphenolic contents and the anticancer activity. In conclusion, we explored the possibility that L. aequata could be a promising source of antioxidants and anticancer agents with a high phytochemical profile.

TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells.

Unsatisfied kinetochore-microtubule attachment activates the spindle assembly checkpoint to inhibit the metaphase-anaphase transition. However, some cells eventually override mitotic arrest by mitotic slippage. Here, we show that inactivation of TORC1 kinase elicits mitotic slippage in budding yeast and human cells. Yeast mitotic slippage was accompanied with aberrant aspects, such as degradation of the nucleolar protein Net1, release of phosphatase Cdc14, and anaphase-promoting complex/cyclosome (APC/C)-Cdh1-dependent degradation of securin and cyclin B in metaphase. This mitotic slippage caused chromosome instability. In human cells, mammalian TORC1 (mTORC1) inactivation also invoked mitotic slippage, indicating that TORC1 inactivation-induced mitotic slippage is conserved from yeast to mammalian cells. However, the invoked mitotic slippage in human cells was not dependent on APC/C-Cdh1. This study revealed an unexpected involvement of TORC1 in mitosis and provides information on undesirable side effects of the use of TORC1 inhibitors as immunosuppressants and anti-tumor drugs.

Traditional uses and pharmacological activities of the genus leea and its phytochemicals: A review.

OBJECTIVES: Plants have been used as traditional medicine (TM) since ancient times and TM remains an effective treatment option in the primary health care system in developing countries, including Bangladesh. There are several reasons to use plants as TM, which are cheaply and easily available and have a cultural heritage of their uses across generations. Leea, a genus of the Vitaceae family, possesses a large number of medicinal plants. In this review, the literature data on the traditional uses and pharmacological activities of Leea species and their phytochemicals are compiled. All the information was collected from the scientific databases. RESULTS: Leea species are endemic that have opened a promising research field to identify new leads against different diseases. Leea contains approximately 70 species, which are widely distributed throughout the Northern and Eastern Australia, South and Southeast Asia and parts of Africa. The Leea plants are used traditionally in different ailments such as fever, diarrhea, dysentery, joint pain, rheumatism, diabetes, bone fracture, body ache, wound, sexual disorders, and so on. The majority of the Leea species are the medicinal plants, which have anticancer, cytotoxic, antimicrobial, antidiabetic, hepatoprotective, cardiovascular, and CNS activity. Moreover, phytochemicals such as flavonoids, glycosides, phenols, terpenoids, steroids, volatile oils, alkaloids, proteins, quinine derivatives, tannins, saponins, and many other organic compounds have been reported in the Leea species (Leea indica, Leea macrophylla, Leea asiatica, Leea aequata, Leea rubra and Leea guineensis). The presence of phytochemicals and the in vitro and in vivo biological activities reported of these plants support their use as TM. Though original research articles related to the Leea genus are available, supportive reviews on phytochemicals and pharmacological activities remain scarce. CONCLUSION: Leea species are used as TM in different ailments and have a real interest in their diverse pharmacological properties. Also, Leea species contain a remarkable number of bioactive compounds. This review has provided a comprehensive report on the plants of Leea genus to identify its therapeutic potential and future prospects for betterment research. However, chemical and biological investigations of several species of Leea genus remain unexplored. Therefore, further studies on these species are necessary, especially regarding pharmacological properties, isolation of the compounds and mechanism of action for the development of new drugs.

The anticancer activity of two glycosides from the leaves of Leea aequata L.

Two compounds (7-O-methylmearnsitrin (7-OM) and roseoside A (RA) were identified and characterized from the leaves of Leea aequata (L. aequata) L. The cytotoxicity of 7-OM and RA on HeLa cells was performed using MTT. The 7-OM and RA showed significant inhibition of HeLa cell proliferation with an IC50 of 22 and 20 µg/mL, respectively when compared with the standard vincristin sulphate (VS) (IC50 of 15 µg/mL). Moreover, the 7-OM and RA significantly inhibit other cancer cells (HEK-293, H228, and H3122) when compared with the VS and the cytotoxic activity of the compounds might show through the induction of apoptosis. Strikingly, annexin-V and PI signals could barely be detected in control cells, while strong fluorescence densities were observed in response to treatment indicating that these compounds have capacity to induce HeLa cell apoptosis. Our results suggest that the anticancer activity of 7-OM and RA was due to the induction of apoptosis.

Mediating role of arsenic in the relationship between diet and pregnancy outcomes: prospective birth cohort in Bangladesh.

BACKGROUND: Epidemiological evidence suggests that arsenic (As) exposure during pregnancy may reduce infant birth weight. One significant source of As exposure is diet; thus, As may indirectly affect infant growth by mediating the effect of maternal diet on birth weight (BW). This study evaluated the potential mediating effect of As in the relationship between maternal diet and BW, gestational age (GA), and gestational weight gain (GWG). METHOD: The study used a prospective birth cohort in Bangladesh that captured the dietary habits of 1057 pregnant women through validated semi-quantitative food frequency questionnaires. We applied a causal mediation model with counterfactual approach and performed analyses with and without adjustment for total energy intake. Other potential confounders captured by self-report questionnaire were exposure to secondhand tobacco smoke, betel nut chewing, maternal age, education level, household income level, physical activity level during pregnancy, and daily hours spent cooking over open fire. RESULT: No association was found between maternal toenail As and BW. Higher absolute and energy-adjusted protein, fat and fiber intakes were associated with higher toenail As and lower GA and GWG, while higher absolute and energy-adjusted carbohydrate intake was associated with lower toenail As and greater GA and GWG. Mediation analysis showed significant natural indirect effects by toenail As in the relationships between absolute fat, carbohydrate and fiber intake with GA. Specifically, 3% (95% CI: 1-6%) of the association between carbohydrate intake and GA was mediated by change in toenail As, 6% (95% CI: 1-9%) for absolute fat intake and 10% (95% CI: 4-13%) for absolute fiber intake. After adjusting for total energy, no significant mediating effect was observed, suggesting the mediating effect might be due to measurement error or that absolute amount of As exposure rather than the amount in relationship to total energy intake was a more important factor to consider when understanding the negative implication of As on fetal growth. CONCLUSION: The mediating effect of As in the relationship between maternal diet and birth outcome was small and might be due to measurement error.