Apoptotic Potential of Iloneoside from Gongronema latifolium Benth against Prostate Cancer Cells Using In Vitro and In Silico Approach.

Prostate cancer is a major cause of cancer-related mortality in men worldwide. The anti-proliferative activity of Gongronema latifolium leaf extracts on some cancer cells has been reported. Herein, we investigated the growth inhibitory effect of the Gongronema latilolium leaf methanol extract and isolated pregnane (iloneoside) against prostate cancer cell lines using the MTT cell proliferation assay, apoptosis quantification, cell cycle analysis using flow cytometry and computational analysis molecular docking, molecular dynamics simulation (MDs), binding free energy computation and cluster analysis.

Cholinergic Inhibition and Antioxidant Potential of Gongronema latifolium Benth Leaf in Neurodegeneration: Experimental and In Silico Study.

The use of Gongronema latifolium for the management of various forms of neurological disorders has generated a lot of interest in the need to further investigate its neurotherapeutic constituents. This work, therefore, focused on assessing the inhibitory potential of selected bioactive components derived from G. latifolium against key neurotherapeutic targets and oxidant species associated with neurodegeneration using in vitro analysis and biomolecular modelling.

Mechanisms of stretch-induced electro-anatomical remodeling and atrial arrhythmogenesis.

Atrial fibrillation (AF) is the most common cardiac rhythm disorder, often occurring in the setting of atrial distension and elevated myocardialstretch. While various mechano-electrochemical signal transduction pathways have been linked to AF development and progression, the underlying molecular mechanisms remain poorly understood, hampering AF therapies. In this review, we describe different aspects of stretch-induced electro-anatomical remodeling as seen in animal models and in patients with AF.

Comparative Therapeutic Effect of Single/Combined Administration of Saxagliptin, Metformin and Intranasal Insulin on Dexamethasone Induced Insulin Resistance in Albino Wistar Rat Model.

Glucocorticoids have therapeutic benefits in the management of several inflammatory and immunological disorders. Despite these medicinal effects, they have the drawback of causing metabolic disorders such as hyperglycemia, insulin resistance etc., which is known to be a key indicator of metabolic syndrome.

Oxidized dietary lipids induce vascular inflammation and atherogenesis in post-menopausal rats: estradiol and selected antihyperlipidemic drugs restore vascular health in vivo.

Background: Thermoxidation of edible oil through deep fat frying results in the generation of several oxidized products that promote lipid peroxidation and ROS production when eaten. Consumption of thermoxidized oil in post-menopausal conditions where the estrogen level is low contributes to cardiovascular disease. This study evaluates the role of estradiol and antihyperlipidemic agents (AHD) in restoring the vascular health of ovariectomized (OVX) rats fed with thermoxidized palm oil (TPO) and thermoxidized soya oil (TSO) diets.

Identification of potential inhibitors of cholinergic and β-secretase enzymes from phytochemicals derived from Gongronema latifolium Benth leaf: an integrated computational analysis.

Neurodegenerative disorders (NDDs) are associated with increased activities of the brain acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-secretase enzyme (BACE1). Inhibition of these enzymes affords therapeutic option for managing NDDs such as Alzheimer's disease (AD) and Parkinson's disease (PD). Although, Gongronema latifolium Benth (GL) has been widely documented in ethnopharmacological and scientific reports for the management of NDDs, there is paucity of information on its underlying mechanism and neurotherapeutic constituents.

Inhibition mechanism of alpha-amylase, a diabetes target, by a steroidal pregnane and pregnane glycosides derived from Benth.

Alpha-amylase is widely exploited as a drug target for preventing postprandial hyperglycemia in diabetes and other metabolic diseases. Inhibition of this enzyme by plant-derived pregnanes is not fully understood. Herein, we used , , and studies to provide further insights into the alpha-amylase inhibitory potential of selected pregnane-rich chromatographic fractions and four steroidal pregnane phytochemicals (SPPs), viz: marsectohexol (P1), 3--[6-deoxy-3--methyl-β-D-allopyranosyl-(1→14)-β-D-oleandropyranosyl]-11,12-di--tigloyl-17β-marsdenin (P2), 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl]-17β-marsdenin (P3), and 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-canaropyranosyl]-17β-marsdenin (P4) derived from Benth.

Antimalarial phytochemicals as potential inhibitors of SARS-CoV-2 guanine N7-methyltransferase (nsp 14): an integrated computational approach.

The inhibition of capping enzymes such as guanine-N7-methyltransferase (GMT) is an attractive target for regulating viral replication, transcription, virulence, and pathogenesis. Thus, compounds that target the Severe Acute Respiratory Syndrome Corona Virus 2 GMT (S2GMT) will enhance drug development against COVID-19. In this study, an in-house library of 249 phytochemicals from African medicinal plants was screened using computational approaches including homology modeling, molecular docking, molecular dynamic simulations, binding free energy calculations based on molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) and Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) analysis for inhibitors of S2GMT.

African derived phytocompounds may interfere with SARS-CoV-2 RNA capping machinery via inhibition of 2'-O-ribose methyltransferase: An perspective.

Despite the ongoing vaccination against the life-threatening COVID-19, there is need for viable therapeutic interventions. The S-adenosyl-l-Methionine (SAM) dependent 2-O'-ribose methyltransferase (2'-O-MTase) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a therapeutic target against COVID-19 infection. In a bid to profile bioactive principles from natural sources, a custom-made library of 226 phytochemicals from African medicinal plants with especially anti-malarial activity was screened for direct interactions with SARS-CoV-2 2'-O-MTase (S2RMT) using molecular docking and molecular dynamics (MD) simulations as well as binding free energies methods.

Combined Intranasal Insulin/Saxagliptin/Metformin Therapies Ameliorate the Effect of Combined Oral Contraceptive- (COC-) Induced Metabolic Syndrome (MetS) with a Major Target on Glucose Metabolism in Adult Female Wistar Rats.

Objective: To evaluate the effect of the chronic use of combined oral contraceptives (COCs: ethinyl estradiol and levonorgestrel) on the indices of metabolic syndrome in adult female Wistar rats and possible therapeutic management.

Materials And Methods: 64 female Wistar rats received either distilled water, norethindrone (NOR), COC, intranasal insulin (INI), metformin (MET), saxagliptin (SAX), INI+MET, and INI+SAX. After 8 weeks of exposure to COC, the animals were sorted into the therapeutic groups.

SARS-CoV-2 host cell entry: an in silico investigation of potential inhibitory roles of terpenoids.

Background: Targeting viral cell entry proteins is an emerging therapeutic strategy for inhibiting the first stage of SARS-CoV-2 infection. In this study, 106 bioactive terpenoids from African medicinal plants were screened through molecular docking analysis against human angiotensin-converting enzyme 2 (hACE2), human transmembrane protease serine 2 (TMPRSS2), and the spike (S) proteins of SARS-CoV-2, SARS-CoV, and MERS-CoV. In silico absorption-distribution-metabolism-excretion-toxicity (ADMET) and drug-likeness prediction, molecular dynamics (MD) simulation, binding free energy calculations, and clustering analysis of MD simulation trajectories were performed on the top docked terpenoids to respective protein targets.

Antidiabetic and antihyperlipidemic effects of aqueous extract of in streptozotocin-nicotinamide induced type 2 diabetic rats.

Background: is among the evergreen plants native to West Africa. It is used in the management of various ailments including anemia, fever, asthma and diabetes. This study evaluated the antidiabetic and antihyperlipidemic effect of in streptozotocin-nicotinamide-induced type 2 diabetic rats.

Dual targeting of cytokine storm and viral replication in COVID-19 by plant-derived steroidal pregnanes: An in silico perspective.

The high morbidity and mortality rate of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection arises majorly from the Acute Respiratory Distress Syndrome and "cytokine storm" syndrome, which is sustained by an aberrant systemic inflammatory response and elevated pro-inflammatory cytokines. Thus, phytocompounds with broad-spectrum anti-inflammatory activity that target multiple SARS-CoV-2 proteins will enhance the development of effective drugs against the disease. In this study, an in-house library of 117 steroidal plant-derived pregnanes (PDPs) was docked in the active regions of human glucocorticoid receptors (hGRs) in a comparative molecular docking analysis.

Alkaloids and flavonoids from African phytochemicals as potential inhibitors of SARS-Cov-2 RNA-dependent RNA polymerase: an perspective.

Corona Virus Disease 2019 (COVID-19) is a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Exploiting the potentials of phytocompounds is an integral component of the international response to this pandemic. In this study, a virtual screening through molecular docking analysis was used to screen a total of 226 bioactive compounds from African herbs and medicinal plants for direct interactions with SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).

Prevention of SARS-CoV-2 cell entry: insight from interaction of drug-like alkaloids with spike glycoprotein, human ACE2, and TMPRSS2.

COVID-19 is a respiratory disease caused by SARS-CoV-2, an enveloped positive sense RNA virus. The SARS-CoV-2 spike glycoprotein, angiotensin-converting enzyme 2 (ACE2) and human transmembrane protease serine 2 (TMPRSS2) are essential for the host cell-mediated viral entry. Targeting these proteins represent viable options to stop the first stage of infection and transmission.

Potential inhibitors of coronavirus 3-chymotrypsin-like protease (3CL): an screening of alkaloids and terpenoids from African medicinal plants.

The novel coronavirus disease 2019 (COVID-19) caused by SARS-COV-2 has raised myriad of global concerns. There is currently no FDA approved antiviral strategy to alleviate the disease burden. The conserved 3-chymotrypsin-like protease (3CL), which controls coronavirus replication is a promising drug target for combating the coronavirus infection.

Subchronic exposure to ; its neurotoxic potentials in young adult female Wistar rats.

Background: (camphor) {CHO} is a chemical substance used mostly amongst the Yoruba ethnic group in Western Nigeria to treat infantile colic during early childhood. This study assess the neurotoxic potentials of following sub-chronic exposure in female albino Wistar rats.

Methods: Twenty-eight female rats (mean weight of 130 g) were randomly selected and assigned into four (4) groups.

Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from and Studies.

Plant-based therapies are being explored to prevent or treat several cancer types. The antioxidant properties of plant are well established. In our previous work, we demonstrated the presence of cytotoxic compounds in the methanol extract of (MEP) with potent activity against human leukemia cells.

Safety effect of fractions from methanolic leaf extract of on reproduction in male wistar rats.

This study evaluates the reproductive toxicity of ethyl acetate and butanolic fractions from crude methanolic leaf extract of in male Wistar rats. Acute toxicity was assessed to determine the safety dose, Sub-chronic reproductive toxicity studies were carried out by administering daily 25, 100 and 400 mg/kg body weight doses of the fractions to respective group of animals and 1 ml of normal saline daily for the control group for 28 days. Blood, epididymis and testes were harvested for reproductive hormones, sperm parameters, and histopathologic analysis respectively.

Fisetin targets YB-1/RSK axis independent of its effect on ERK signaling: insights from in vitro and in vivo melanoma models.

The anti-proliferative activity of dietary flavonoid fisetin has been validated in various cancer models. Establishing its precise mechanism of action has proved somewhat challenging given the multiplicity of its targets. We demonstrated that YB-1 promotes epithelial-to-mesenchymal transition and its inhibition suppressed tumor cell proliferation and invasion.

Iloneoside: a cytotoxic ditigloylated pregnane glycoside from the leaves of Gongronema latifolium Benth.

Gongronema latifolium Benth (Asclepiadaceae) is an edible-green-leafy vegetable with known medicinal value. A chemical investigation of the 80% methanolic extract of the leaves led to the isolation of a new pregnane glycoside: iloneoside (3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→14)-β-D-oleandropyranosyl]-11,12-di-O-tigloyl-17β-marsdenin), together with four known constituents. Their chemical structures were determined by spectroscopic analysis.

Comparative Antileukemic Activity of a Tetranorditerpene Isolated from Polyalthia longifolia Leaves and the Derivative against Human Leukemia HL-60 Cells.

The discovery of potent cytotoxic isolates from botanicals provides an opportunity to explore this viable tool for cancer chemoprevention. The antileukemic potential of clerodane diterpene from Polyalthia longifolia leaves has already been established. However, in this present study, utilizing chromatographic techniques we report for the first time, the isolation of a rare tetranorditerpene (compound 1) from P.

A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats.

Background: The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study.