The study under investigation focuses on in vitro antiproliferative efficacy of the flavonoid morin and the mechanisms by which it inhibits the growth of colon cancer using SW480 colon cancer cells with emphasis on Warburg effect. It was found that the cell proliferation was significantly inhibited by morin in a dose and time dependent manner. Morin induced apoptosis that was correlated with increased levels of reactive oxygen species formation and loss of mitochondrial membrane potential of the cells. In addition, an increase in cleaved PARP, cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and Bax as well as a decrease in Bcl 2 was observed, indicating morin is inducing both intrinsic as well as extrinsic pathway of apoptosis. This was further confirmed by using downstream caspase 3 inhibitor which indicated that caspase 3 inhibition reduces morin induced cell death. Moreover, the impact of morin on over all energy status when determined in terms of total cellular ATP level showed a decline with low level of glucose uptake and Glut1 expression. The results indicate that morin exerts antiproliferative activity by inducing apoptosis and by reducing Warburg effect in the evaluated cell lines and provide preliminary evidence for its anticancer activity.

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Enhanced oxidative stress contributes to pathological changes in diabetes and its complications. Thus, strategies to reduce oxidative stress may alleviate these pathogenic processes. Herein, we have investigated Naringin mediated regulation of glutathione (GSH) & intracellular free radical levels and modulation of glucose uptake under oxidative stress in L6 cell lines. The results from the study demonstrated a marked decrease in glutathione with a subsequent increase in free radical levels, which was reversed by the pretreatment of Naringin. We also observed that the increased malondialdehyde level, the marker of lipid peroxidation on induction of oxidative stress was retrieved on Naringin pretreatment. Addition of Naringin (100 μM) showed approximately 40% reduction in protein glycation in vitro. Furthermore, we observed a twofold increase in uptake of fluorescent labeled glucose namely 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2 - NBDG) on Naringin treatment in differentiated L6 myoblast. The increased uptake of 2-NBDG by L6 myotubes may be attributed due to the enhanced translocation of GLUT4. Our results demonstrate that Naringin activate GSH synthesis through a novel antioxidant defense mechanism against excessive Reactive Oxygen Species (ROS) production, contributing to the prevention of oxidative damage in addition to its effect on glycemic control.

The study quantified the major phenolics in different fractions of seeds and evaluated their cardioprotective efficacy. Gallic acid, ellagic acid, cinnamic acid, quercetin, syringic acid and ferulic acid were the major polyphenols present in different fractions of seeds. The cardioprotective effect of seed fractions in modulating angiotensin converting enzyme (ACE), HMG-CoA reductase, LDL oxidation and tertiary butyl hydrogen peroxide (TBHP) induced oxidative stress in H9c2 cardiac cell lines were investigated. effectively attenuated the cellular oxidative stress in H9c2 cardiomyoblasts. These fractions possessed inhibitory potential against ACE, HMG-CoA reductase and LDL oxidation. Molecular docking studies of the predominant polyphenols with ACE and HMG-CoA proteins revealed the binding interactions of these compounds, thus confirming their modulation of activity. The present study demonstrated the cardioprotective efficacy of seed fractions which can be attributed to the presence of phenolic acids and flavonoids.

The present study evaluated antidiabetic potential of fractions of Syzygium cumini seeds and identified major polyphenolic compounds in them. Potential α‐glucosidase and α‐amylase inhibition (IC50 1.7 and 7.62 μg/ml, respectively) was demonstrated by 70% methanol fraction while significant dipeptidyl peptidase‐IV inhibition (88.1%) was demonstrated by methanol fraction. A fourfold increase in glucose uptake in L6 cells following the pretreatment of 70% methanol fraction (26.9%) further confirmed the antidiabetic potential of S. cumini seeds. The total phenolic (906 mg GAE/g dry weight) and flavonoid content (233 mg QE/g dry weight) were highest in 70% methanol fraction. Phenolic profiling of fractions through HPLC showed the presence of quercetin, cinnamic acid, syringic acid, ferulic acid, ellagic acid, and gallic acid, which was further confirmed through LC–Q‐ToF (MS/MS). Major phenolics identified were docked with studied enzymes and analyzed. All the results suggest that S. cumini seed fractions have significant potential in the management of diabetes. Practical applications Syzygium cumini is well known for its antidiabetic property. However, the seeds are underutilized and not well explored scientifically. The results from present study explain the antidiabetic potential of S. cumini seeds. The study also provides an insight about the compounds present in the seeds and the mechanism by which the antidiabetic property is imparted. The results thus provide a scientific validation for the antidiabetic property of under‐utilized S. cumini seeds. Further scientific validations in in vivo can pave way for the exploration of S. cumini seeds in the management of diabetes against the adverse effects of the commonly used synthetic antidiabetic drugs.