Esculentoside A Inhibits Proliferation, Colony Formation, Migration, and Invasion of Human Colorectal Cancer Cells.

Esculentosides include a group of plant-derived compounds with tremendous pharmacological potential. The antiproliferative effects of esculentoside A against different colorectal cancer cells were evaluated. We found that the proliferation of all the colorectal cancer cells was halted by esculentoside A. The IC50 of esculentoside A ranged from 16 to 24 µM against different colorectal cancer cells. Investigation of the underlying molecular mechanism revealed that esculentoside A caused an increase in the colorectal cancer cells at the G1 phase of the cell cycle, indicative of G0/G1 cell cycle arrest. The percentage of G1 cells increased from 22.68% in control to 54.23% at 16 µM esculentoside A. We also found that the colony formation of HT-29 cells was inhibited by 59% at 24 µM esculentoside A. Finally, effects of esculentoside A on the motility of HT-29 colorectal cancer cells were investigated, and it was found that esculentoside A caused a significant decline in HT-29 colorectal cancer cell migration and invasion. The migration and invasion of esculentoside A-treated HT-29 cells were 45% and 51% higher, respectively, than those of untreated cells. Summing up, these results suggest that esculentoside A exhibits antiproliferative effects against human colorectal cancer cells.

Cirsilineol Inhibits the Proliferation of Human Prostate Cancer Cells by Inducing Reactive Oxygen Species (ROS)-Mediated Apoptosis.

Cirsilineol has been reported to exhibit anticancer effects against several human cancer cell lines. The present study was designed to evaluate the anticancer effects of cirsilineol against the human DU-145 prostate cancer cells. The results showed that cirsilineol suppressed the proliferation of DU-145 cancer cells in a dose-dependent manner with minimal cytotoxic effects against the normal cells. The IC50 of cirsilineol was found to be 7 µM and 110 µM against prostate cancer DU-145 and normal HPrEC prostate cells, respectively. Acridine orange and ethidium bromide (AO/EB) staining showed that cirsilineol induced apoptosis in DU-145 prostate cancer cells. The Annexin V/PI staining further confirmed the induction of apoptosis in DU-145 cells. The western blot analysis showed that cirsilineol suppressed the expression of Bax and upregulated the expression of Bcl-2 in prostate cancer DU-145 cells. Moreover, cirsilineol caused a dose-dependent increase in reactive oxygen species (ROS) levels in prostate cancer. Wound healing and Transwell assays showed that cirsilineol inhibits migration and invasion of DU-145 prostate cancer cells. Summing up, the results suggest that cirsilineol suppresses the proliferation of prostate cancer cells and may prove to be a beneficial lead molecule for the development of chemotherapy for prostate cancer.

Assessment of Antioxidative and Alpha-Amylase Potential of Polyherbal Extract.

The present study aims to prepare a polyherbal formulation (PHF) of Azadirachta indica (Neem), Aloe barbadensis (Aloe vera), Allium sativum (garlic), Acacia arabica (Babul), and Aegle marmelos (Bel) and evaluation of antidiabetic and antioxidant activity utilizing the in vitro model. Air-dried powder of 5 medicinal plants, which are divided into equal portions, and PHF, is prepared by the soxhlet technique using polar and nonpolar solvents. The PHF is screened for the phytochemical screening, and then the antidiabetic activity is determined by alpha-amylase inhibition. The extracts thus obtained are also subjected to the inhibition assay by the use of (DNS) dinitro salicylic acid. The antioxidant activity was determined by the DPPH radical scavenging assay, H2O2 scavenging assay, and TBARS assay. In in vitro study, the result revealed polyherbal formulation in which hot water extract has the topmost inhibitory effect on alpha-amylase activity, ranging from 20.4% to 79.5% with an IC50 value of 48.98 ± 0.31 µg/ml. This extract clearly showed the effective lowering of postprandial hypertriglyceridemia (PPHG). In the antioxidant activity carried out by using the (DPPH) radical scavenging assay, the highest result was obtained by the concentration of 250 µg/ml, which was around 77.2 ± 0.05 with statistical significance compared with control (a: p < 0.01; b: p < 0.001), while in the GTA method, the highest result was obtained by the concentration of 250 µg/ml, which was around 78.2 ± 0.05, and in the case of the TBARS assay, the concentration of 250 µg/ml gave around 76.2 ± 0.03 anti-oxidant value. In conclusion, the study shows that polyherbal formulation has superior antidiabetic activity and antioxidant properties.

COVID-19 Infection in Pregnancy: A Review.

Coronavirus disease 2019 (COVID-19), which is a highly contagious viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a catastrophic effect on the world's demographics, resulting in more than 3.8 million deaths worldwide and establishing itself as the most serious global health crisis since the 1918 influenza pandemic. Several questions remain unanswered regarding the effects of COVID-19 disease during pregnancy. Although most infections are mild in high-risk populations, the severe disease frequently leads to intubation, intensive care unit admission, and, in some cases, death. Hormonal and physiological changes in the immune and respiratory systems, cardiovascular function, and coagulation may affect the progression of COVID-19 disease in pregnancy. However, the consequences of coronavirus infection on implantation, fetal growth and development, labor, and newborn health have yet to be determined, and, consequently, a coordinated global effort is needed in this respect. Principles of management concerning COVID-19 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and co-infection, fetal and uterine contraction monitoring, prevention, and / or treatment of thromboembolism early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. This review focuses on COVID-19 during pregnancy, its management, and the area where further investigations are needed to reduce the risk to mothers and their newborns.

Phytochemicals from Leucas zeylanica Targeting Main Protease of SARS-CoV-2: Chemical Profiles, Molecular Docking, and Molecular Dynamics Simulations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a contemporary coronavirus, has impacted global economic activity and has a high transmission rate. As a result of the virus's severe medical effects, developing effective vaccinations is vital. Plant-derived metabolites have been discovered as potential SARS-CoV-2 inhibitors. The SARS-CoV-2 main protease (Mpro) is a target for therapeutic research because of its highly conserved protein sequence. Gas chromatography-mass spectrometry (GC-MS) and molecular docking were used to screen 34 compounds identified from Leucas zeylanica for potential inhibitory activity against the SARS-CoV-2 Mpro. In addition, prime molecular mechanics-generalized Born surface area (MM-GBSA) was used to screen the compound dataset using a molecular dynamics simulation. From molecular docking analysis, 26 compounds were capable of interaction with the SARS-CoV-2 Mpro, while three compounds, namely 11-oxa-dispiro[4.0.4.1]undecan-1-ol (-5.755 kcal/mol), azetidin-2-one 3,3-dimethyl-4-(1-aminoethyl) (-5.39 kcal/mol), and lorazepam, 2TMS derivative (-5.246 kcal/mol), exhibited the highest docking scores. These three ligands were assessed by MM-GBSA, which revealed that they bind with the necessary Mpro amino acids in the catalytic groove to cause protein inhibition, including Ser144, Cys145, and His41. The molecular dynamics simulation confirmed the complex rigidity and stability of the docked ligand-Mpro complexes based on the analysis of mean radical variations, root-mean-square fluctuations, solvent-accessible surface area, radius of gyration, and hydrogen bond formation. The study of the postmolecular dynamics confirmation also confirmed that lorazepam, 11-oxa-dispiro[4.0.4.1]undecan-1-ol, and azetidin-2-one-3, 3-dimethyl-4-(1-aminoethyl) interact with similar Mpro binding pockets. The results of our computerized drug design approach may assist in the fight against SARS-CoV-2.