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Purpose: To investigate the effect of derivatives of cinnamic acid on the proliferation of CHO-1 and HeLa cell lines. Methods: Three Acrylohydrazones (7–9) derived from cinnamic acid hydrazides (6) as well as five cinnamic acid derivatives were studied in the current study (1–5). All the synthesized compounds were characterized by physical and spectral data. Two of the synthesized acrylohydrazones compounds (8 and 9) were novel. The antiproliferative activity of these compounds on cervical adenocarcinoma (HeLa) and Chinese Hamster Ovarian (CHO-1) cells, with abnormal p53tumour suppressor gene, was investigated. The compounds were also studied through molecular docking and molecular dynamics (MD) simulation for possible interaction with important therapeutic targets (PDB: 3PP0 and 3EQM for HeLa and 2OCJ and 3ZME for CHO). Results: Compound 7exhibits the highest inhibitory effect on the CHO-1 cancer cell line with an IC50 = 4.2 ± 0.6 µg/mL as compared with the standard doxorubicin (IC50 = 0.8 ± 0.01 µg/mL) and demonstrates a weak inhibitory effect on the HeLa cell line. Compounds 1–5 had no inhibitory activity on the CHO-1 cell line, while compounds 7and 9were moderately toxic to the two cell lines. The acrylohydrazones (7–9) demonstrated the highest binding tendencies to the target proteins. Also, the lead compounds (compounds 7–9) complexed with the protein targets were stable in a 100 ns MD simulation. Conclusion: Therefore, the acrylohydrazones (compounds 7–9)would be of interest in the treatment/management of ovarian and cervical cancer among women.

AbstractThe emergence of varying levels of resistance to currently available antimalarial drugs significantly threatens global health. This factor heightens the urgency to explore bioactive compounds from natural products with a view to discovering and developing newer antimalarial drugs with novel mode of actions. Therefore, we evaluated the inhibitory effects of sixteen phytocompounds from Cymbopogon citratusleaf extract against Plasmodium falciparumdrug targets such as P. falciparumcircumsporozoite protein (PfCSP), P. falciparummerozoite surface protein 1 (PfMSP1) and P. falciparumerythrocyte membrane protein 1 (PfEMP1). In silicoapproaches including molecular docking, pharmacophore modeling and 3D-QSAR were adopted to analyze the inhibitory activity of the compounds under consideration. The molecular docking results indicated that a compound swertiajaponin from C. citratusexhibited a higher binding affinity (−7.8 kcal/mol) to PfMSP1 as against the standard artesunate-amodiaquine (−6.6 kcal/mol). Swertiajaponin also formed strong hydrogen bond interactions with LYS29, CYS30, TYR34, ASN52, GLY55 and CYS28 amino acid residues. In addition, quercetin another compound from C. citratusexhibited significant binding energies −6.8 and −8.3 kcal/mol with PfCSP and PfEMP1, respectively but slightly lower than the standard artemether-lumefantrine with binding energies of −7.4 kcal/mol against PfCSP and −8.7 kcal/mol against PfEMP1. Overall, the present study provides evidence that swertiajaponin and other phytomolecules from C. citratushave modulatory properties toward P. falciparumdrug targets and thus may warrant further exploration in early drug discovery efforts against malaria. Furthermore, these findings lend credence to the folkloric use of C. citratusfor malaria treatment.Communicated by Ramaswamy H. Sarma

Air pollution is the second largest risk to health in Africa, and children with asthma are particularly susceptible to its effects. Yet, there is a scarcity of air pollution exposure data from cities in sub-Saharan Africa. We aimed to identify potential exposure reduction strategies for school children with asthma living in urban areas in sub-Saharan Africa.

Male infertility has become a problem worldwide, and recent research has emphasized the development of more effective therapy options. Among natural compounds, rutin has been widely studied for its potential to treat dysfunction related to male infertility, including a reduction in sperm quality, spermatogenesis disruption and structural disruption in the testis. A thorough review of scientific literature published in several databases, including Google Scholar, PubMed/MEDLINE and Scopus, was used to synthesize the present state of research on the role of rutin in male reproductive health. Rutin has been shown to possess antiapoptotic, antioxidant and anti-inflammatory activities, among others, which are crucial in the management of male infertility. Numerous investigations have shown that rutin protects against male infertility and have explored the underlying mechanisms involved. The present review, therefore, assesses the therapeutic mechanisms involved in male infertility treatment using rutin. Rutin was able to mitigate the induced oxidative stress, apoptosis, inflammation, and related physiological processes that can cause testicular dysfunction.

The mitophagy process, a type of macroautophagy, is the targeted removal of mitochondria. It is a type of autophagy exclusive to mitochondria, as the process removes defective mitochondria one by one. Mitophagy serves as an additional level of quality control by using autophagy to remove superfluous mitochondria or mitochondria that are irreparably damaged. During spermatogenesis, mitophagy can influence cell homeostasis and participates in a variety of membrane trafficking activities. Crucially, it has been demonstrated that defective mitophagy can impede spermatogenesis. Despite an increasing amount of evidence suggesting that mitophagy and mitochondrial dynamics preserve the fundamental level of cellular homeostasis, little is known about their role in developmentally controlled metabolic transitions and differentiation. It has been observed that male infertility is a result of mitophagy's impact on sperm motility. Furthermore, certain proteins related to autophagy have been shown to be present in mammalian spermatozoa. The mitochondria are the only organelle in sperm that can produce reactive oxygen species and finally provide energy for sperm movement. Furthermore, studies have shown that inhibited autophagy-infected spermatozoa had reduced motility and increased amounts of phosphorylated PINK1, TOM20, caspase 3/7, and AMPK. Therefore, in terms of reproductive physiology, mitophagy is the removal of mitochondria derived from sperm and the following preservation of mitochondria that are exclusively maternal.

AbstractThe worldwide expanding increment in cancer pervasiveness is disturbing and this disease ranks among the main causes of mortality in both developing and developed countries. Unfortunately, available treatment options come with serious side effects and do not guarantee complete success. Although numerous models have been proposed for the development of better therapeutic agent, however the exact mechanism are still poorly understood. This then calls for continued research aimed at developing new drugs as an alternative or adjuvant anticancer agents. Here we have identified five vital proteins (CDK-2, Bcl-2, CDK-6, VEGFR, and IGF-1R) that aid tumor growth and we inhibited the activity of these proteins with Puerarin. Puerarin is an isoflavonoid C-glycosides used as a therapeutic agent against various human ailments. Our findings revealed that Puerarin fulfilled Veber’s rule. Added to this, CDK-6 and Bcl-2 had better glide scores for puerarin than the control (doxorubicin) and molecular simulation showed the stability of the complexes. These findings suggest that inhibiting CDK-6 and Bcl-2 with Puerarin could prove more effective in the management of cancer than doxorubicin. Overall, this study provides a new direction that could facilitate rational drug design for cancer.Communicated by Ramaswamy H. Sarma

Alcoholism has been linked to problems with male reproductive function. The combined effects of alcohol, cannabis, and tobacco were compared in this study. A total of 35 rats were assigned randomly into seven groups A-G: animals in A were administered distilled water. Animals in B-G were either administered alcohol orally (30 ml 40% alcohol) or exposed to smoke from ignited tobacco (exposure to smoke from 0.7 g tobacco for 5 min) or cannabis (exposure to smoke from 0.7 g tobacco and cannabis for 5 min): B (orally administered alcohol), C (exposed to the smoke from tobacco), D (exposed to smoke from cannabis), E (treated with alcohol and exposed to smoke from tobacco), F (treated with alcohol and exposed to smoke from cannabis), G (treated with alcohol and exposed to smokes from tobacco and cannabis). Assays were carried on the testicular homogenate after a 14-day treatment. There was a significant increase in activity of alkaline phosphatase (P≤ 0.05), concentrations of cholesterol, glutathione reductase, and malondialdehyde in treated rats by the co-administration of alcohol with cannabis and tobacco compared with the control group. The combined treatment also caused degeneration and morphological distortions of testicular cells. The biochemical and histoarchitectural change was due to oxidative damage attributable to the synergistic effects. The high binding energy of tetrahydrocannabinol ligand to prostate acid phosphatase may be a prediction that the ligand can have an inhibitory effect on the function of enzymes in the prostate.

Blighia sapida (BS) has been shown to be rich sources of antioxidant, thus, we evaluated effects of B. sapida Koenig stem bark ethanol extract (BSE) on lipid metabolism and hematological indices in diabetes rats.

Ethanolic extract of Trichilia prieureana leaves have been reported to exhibitanti-hyperglycemic activities without detailed information on the anti-diabetic activities. This study investigated the anti-diabetic activity of aqueous extract of T. prieureana leaves (AETPL) in type 2 diabetic (T2DM) male rats.

Diabetes is a group of medical conditions characterized by the body's inability to effectively control blood glucose levels, due to either insufficient insulin synthesis in type 1 diabetes or inadequate insulin sensitivity in type 2 diabetes. According to this research, the PI3K/AKT pathway of Ocimum gratissimum leaf flavonoid-rich extracts in streptozotocin-induced diabetic rats was studied. We purchased and used a total of forty (40) male Wistar rats for the study. We divided the animals into five (5) different groups: normal control (Group A), diabetic control (Group B), low dose (150 mg/kg body weight) of Ocimum gratissimum flavonoid-rich leaf extract (LDOGFL) (Group C), high dose (300 mg/kg body weight) of Ocimum gratissimum flavonoid-rich leaf extract (HDOGFL) (Group D), and 200 mg/kg of metformin (MET) (Group E). Streptozotocin induced all groups except Group A, which serves as the normal control group. The experiment lasted for 21 days, following which we sacrificed the animals and harvested their brains for biochemical analysis on the 22nd day. We carried out an analysis that included reduced glutathione (GSH), glutathione transferases (GST), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), along with GLUT4, MDA, pro-inflammatory cytokines, NO, neurotransmitters, cholinergic enzyme activities, cardiolipin, and the gene expression of PI3K/AKT. The obtained result indicates that the flavonoid-rich extracts of O. gratissimum significantly enhanced the levels of GSH, GST, CAT, GPx, and SOD, as well as GLUT4 and cardiolipin. The levels of GSH, GST, CAT, GPx, and SOD, as well as GLUT4 and cardiolipin, were significantly increased by gratissimum. Moreover, the extracts decrease the levels of MDA, pro-inflammatory cytokines, NO, neurotransmitters, and cholinergic enzyme activities. Additionally, the flavonoid-rich extracts of O. gratissimum significantly improved the AKT and PI3K gene expressions in diabetic rats. gratissimum had their AKT and PI3K gene expressions significantly (p<0.05) improved. The findings indicate that O. gratissimum leaf flavonoids have the potential to treat diabetes mellitus. gratissimum leaf flavonoids possess therapeutic potential in themselves and can be applied in the management of diabetes mellitus. Although further analysis can be carried out in terms of isolating, profiling, or purifying the active compounds present in the plant’s extract.

Background: In recent years, there has been an exponential increase in the global burden of cancer which has been associated with several factors including environmental influence, aging, diet, infectious agents, hormonal imbalance and chronic inflammation, among others. Cancerous cells utilize more glucose for its proliferation and survival than normal cells. Thus, the regulation of glucose consumption of cancerous cells through the inhibition of glucose transporter-4-protein (GLUT4) encoded by solute carrier family-2-member-4-gene (Slc2a4) by selected phytochemicals from Solanum xanthocarpum may serve as a new therapeutic candidate for the treatment of cancer. Methods: The seven identified potential inhibitors of GLUT4 from Solanum xanthocarpum were retrieved from PubChem database. Examination of their drug-likeness, toxicity prediction and molecular docking studies of these compounds with GLUT4 were carried out using online tools such as Molinspiration, PreADMET V.2.0 and Patchdock server. Results: The findings revealed that, five out of the seven compounds fulfil oral drugability of Lipinski’s rule of five (RO5) while two slightly meet the criteria of RO5. Conversely, five of the compounds are predicted to be mutagen while the remaining two are predicted to be safe for the body. Additionally, stigmasterol glucoside has higher binding-affinity (7590) with GLUT4 when compared to doxorubicin (6600) the control. Conclusion: These findings suggest that stigmasterol glucoside from Solanum xanthocarpum could be a promising therapeutic agent with better therapeutic efficacy than doxorubicin in the treatment of cancer via the inhibition of GLUT4.

This study investigated the ameliorative potential of Zingiber officinaleRoscoe extract against lead-induced brain damage in rats.

In Africa, the fruit, leaf, seed and roots of Carica papayaLinn. are generally used to treat a variety of diseases such as malaria, cancer, and cardiovascular diseases. In this study, we evaluated the protective potentials of aqueous extract of C. papayaroots on arsenic-induced biochemical and genotoxic effects in Wistar rats. Rats were induced intraperitoneal with sodium arsenate (dissolved in distilled water at 3 mg/kg body weight) for 21 days and the animals were administered simultaneously with 200 mg/kg body weight vitamin C, 100 and 150 mg/kg body weight of the C. papayaLinn. root aqueous extract once daily for three weeks. Results obtained reveals that activities of plasma 8-OHdG, serum lipids concentration, atherogenic index (AI), coronary artery index (CRI), aspartate transaminase, alanine transaminase, alkaline phosphatase, total bilirubin levels were elevated significantly (p < 0.05) and catalase, glutathione peroxidase, superoxide dismutase, plasma hematological profile were progressively reduced (p < 0.05) in arsenic-alone exposed rats. Significant increase in the quantity of chromosomal aberrations (CA), micronuclei (MN) frequency, oxidative damages in the bone marrow cells from arsenic alone rats was observed. Though, mitotic index scores in these cells were progressively reduced (p < 0.05). In animals administered with aqueous extract of C. papayaroots and vitamin C, the altered parameters were significantly recovered towards the levels observed in normal control rats. These results suggest that aqueous C. papayaroots preparations might have therapeutic potential as a supplement that can be applied in arsenic poisoning.

Objectives:Inflammation plays a crucial role in many of the metabolic abnormalities. The prototypic marker of inflammation is C-reactive protein (CRP), Nitric Oxide (NO), inducible nitric oxide synthase (iNOS) and their inhibition is considered a promising strategy to combat inflammation. Here, we report the anti-inflammatory mechanism of Carica papayaroot aqueous extract in sodium arsenic-induced renal dysfunction.

To investigate the in vitroantioxidant activity of ethanolic extract of Artocarpus heterophyllus(A. heterophyllus) stem bark and its inhibitory effect on α-amylase and α-glucosidase.

A high increase witnessed in type II diabetes mellitus (T2DM) globally has increasingly posed a serious threat to global increases in liver cancer with the association between diabetes mellitus type II and the survival rate in liver cancer patients showing unstable findings. An increase in the development and progression of chronic liver disease from diabetes mellitus patients may be connected to cancer of the liver with several links such as Hepatitis B and C virus and heavy consumption of alcohol. The link between T2DM patients and liver cancer is centered on non-alcoholic fatty liver disease (NAFLD) which could be a serious threat globally if not clinically addressed. Several reports identified metformin treatment as linked to a lower risk of liver cancer prognosis while insulin treatment or sulphonylureas posed a serious threat. Mechanistically, the biological linkage between diabetes type II mellitus and liver cancer are still complex to understand with only the existence of a relationship between NAFLD and high level of energy intake and diabetes mellitus induces hepatic damage, increased liver weight thereby causes multiple pro-inflammatory cytokines that lead to the development of liver cancer. Therefore, this review gives an account of the pathophysiological importance of liver cancer position with T2DM, with the role of NAFLD as an important factor that bridges them.

Cadmium has been considered a risk factor for humans as it accumulates in body tissues, such as the liver, lungs, kidneys, bones, and reproductive organs. The aim of the present study was to evaluate the effect of Irvingia gabonensis (IG) against cadmium (Cd)- induced nephrotoxicity. The study was performed on twenty (20) male rats divided into four groups: control group, cadmium group (4 mg/kg/day, intraperitoneally), cadmium + extract (200 mg/kg body weight by oral gavage) and cadmium + extract (400 mg/kg body weight by oral gavage). Changes in the kidney biochemical markers, namely glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), aminotransferase (ALT), aspartate aminotransferase (AST) activities and levels of malondialdehyde (MDA), urea, and creatinine were determined in serum. Histological examinations were monitored. Exposure to Cd lowered the activities of kidney antioxidants, while it increased LPO levels. Levels of all disrupted parameters were alleviated by co-administration of IG extract. The malondialdehyde concentration of the rats treated with 200 and 400 mg/kg body weight of the extract significantly decreased (p<0.05) compared with the untreated cadmium rats. Yet the creatinine concentration decreased significantly (p<0.05) when the cadmium animals treated with 200 and 400 mg/kg body weight of the extract were compared with the cadmium control. Furthermore, histological alterations in the kidney were observed in cadmium untreated rats and these were ameliorated in cadmium treated rats by co-administration of IG extract. IG showed apparent protective and curative effect on Cd-induced nephrotoxicity

Conventional drugs, as means of alternative medicine, have been in use in the Asian andAfrican nations and some developed countries for the treatment of ailments and cure of diseases.Objective: Puerarin, a naturally occurring isoflavone in numerous plants, is one of the conventionalmedication that possess anti-inflammatory and immunoregulatory properties for the treatment ofcardiac illnesses, osteonecrosis, Parkinsons disease, Alzheimers disease, and other circulatoryconditions. Puerarin is extensively distributed in numerous organs including the kidney, mammarygland, femur, tibia, stomach, liver, pancreas, brain, and lungs, but at a low rate because of its pooravailability. However, when co-administered with compounds like gastrodin that can convey it intothe cell, it shows a wide range of pharmacological properties, including antioxidant, antidiabetic,antimicrobial, antiviral, anti-inflammatory, anticancer, anti-Alzheimers, hepatoprotective, and neuroprotectiveactivity. The biotransformation process of puerarin showed that it is well metabolizedwith daidzein, being the main hydrolyzed product. Puerarin is well tolerated in the body with adosage of up to 250 mg/kg per day, does not initiate any toxic side effects but rather shows a widerange of beneficial and pharmacological properties.

Acetylcholinesterase (AChE) has been an effective target for insecticide development which is a very important aspect of the global fight against insect-borne diseases. The drastic reduction in the sensitivity of insects to AChE-targeting insecticides like organophosphates and carbamates have increased the need for insecticides of natural origin. In this study, we used Drosophila melanogasteras a model to investigate the insecticidal and AChE inhibitory potentials of Cymbopogon citratusand its bioactive compounds. Flies were exposed to 100 and 200 mg/mL C. citratusleaf extract for a 3-h survival assay followed by 45 min exposure for negative geotaxis and biochemical assays. Molecular docking analysis of 45 bioactive compounds of the plant was conducted against Drosophila melanogasterAChE (DmAChE). Exposure to C. citratussignificantly reduced the survival rate of flies throughout the exposure period and this was accompanied by a significant decrease in percentage negative geotaxis, AChE activity, catalase activity, total thiol level and a significant increase in glutathione-S-transferase (GST) activity. The bioactive compounds of C. citratusshowed varying levels of binding affinities for the enzyme. (+)-Cymbodiacetal scored highest (−9.407 kcal/mol) followed by proximadiol (−8.253 kcal/mol), geranylacetone (−8.177 kcal/mol), and rutin (−8.148 kcal/mol). The four compounds occupied the same binding pocket and interacted with important active site amino acid residues as the co-crystallized ligand (1qon). These compounds could be responsible for the insecticidal and AChE inhibitory potentials of C. citratusand they could be further explored in the development of AChE-targeting insecticides.

Artocarpus heterophyllusLam (Moraceae) stem bark has been used locally in managing diabetes mellitus with sparse scientific information. This study investigates the in vitro antioxidant potential of polyphenolic-rich extract of A heterophyllusstem bark as well as its antidiabetic activity in streptozotocin-induced diabetic rats. Fifty male Wistar rats were used with the induction of diabetes by a single intraperitoneal injection of streptozotocin (45 mg/kg body weight) and were orally administered 400 mg/kg free and bound phenols of A heterophyllusstem bark. The animals were sacrificed on the 28th day of the experiment using the cervical dislocation method; antihyperglycemia and anti-inflammatory parameters were subsequently assessed. The polyphenolic extracts demonstrated antioxidant potentials (such as hydrogen peroxide and diphenyl-1-picrylhydrazyl), as well as strong inhibitory activity against amylase and glucosidase. There was a significant (P< .05) increase in glycogen, insulin concentration, pancreatic β-cell scores (HOMA-β), antioxidant enzymes and hexokinase activities, as well as glucose transporter concentration in diabetic animals administered the extracts and metformin. Also, a significant (P< .05) reduction in fasting blood glucose, lipid peroxidation, glucose-6-phosphatase, and all anti-inflammatory parameters were observed in diabetic rats administered the extracts and metformin. The extracts demonstrated antidiabetic potential, which may be useful in the management of diabetes mellitus

In this study, anti-hyperglycemic and anti-inflammatory activities of polyphenolic-rich extract of Syzygium cuminileaves in alloxan-induced diabetic rats were determined. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg body weight) in female Wistar rats. The rats were orally administered with 400 mg/kg free phenol, 400 mg/kg bound phenol, and 5 mg/kg metformin, respectively. On the 14th day of oral administration, the animals were sacrificed, anti-hyperglycemic and anti-inflammatory were assessed. Fasting blood glucose and glycated hemoglobin levels; homeostasis model assessment–insulin resistance scores, lipid peroxidation concentration, glucose-6-phosphatase activity, and all concentrations of anti-inflammatory studied in alloxan-induced diabetic rats were significantly (P< .05) reduced with the administration of polyphenolic-rich extract of Syzygium cuminileaves. Also there was significant (P< .05) increase in glycogen and insulin concentrations, pancreatic β-cell scores, antioxidant enzymes and hexokinase activities, as well as glucose transporter levels in diabetic animals administered with polyphenolic-rich extract of S cuminileaves. The results indicate that S cuminileaves possess anti-hyperglycemic and anti-inflammatory activities.