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Background: For decades, the resident of Zuru emirate have used herbal medicine to treat liver-related diseases including jaundice. Therefore, the present study was designed to investigate and document the herbal medicine used for treating jaundice in Zuru emirate. Method: Oral interviews and questionnaire were used to document information on medicinal plants, medicinal practices, and demographic profiles of respondents. The medicinal plants that were mentioned were collected, identified, and assigned voucher numbers. The names were further authenticated using www.theplantlist.org and theworldfloraonline.org. Thereafter, the methanol stem bark extracts of three of the most frequently mentioned plants were subjected to in vitro bilirubin degradation assay. Result: A total of 46 TMPs Traditional medicine practitioners responded and cited 28 medicinal plants and medicinal practices used to treat jaundice. The most frequently mentioned plants were Erythrina senegalensis (19.6%) followed by Cochlospermum planchonii (13%), and Anogeissus leiocarpus (13%). The herbal remedies were prepared using different parts of the plants as boiled juice or powder and mostly taken as juice with pap or fresh raw cow milk. The in vitro bilirubin degradation assay revealed a time-dependent and dose-dependent bilirubin degradation by Anogeissus leiocarpus (63.05 %), Erythrina senegalensis (46.33%), and Cochlospermum planchonii (27.45%). Conclusion: The present findings revealed the medicinal plants that are used to treat jaundice and the potential jaundice ameliorative effect of these plants may involve bilirubin degradation. Future in vitro and in vivo mechanistic studies should investigate the jaundice ameliorative potency of these plants.

Current research on triple-negative breast cancer (TNBC) has resulted in delineation into the quadruple-negative breast cancer (QNBC) subgroup. Epigenetic modifications such as DNA methylation, histone posttranslational modifications and associated changes in chromatin architecture have been implicated in breast cancer pathogenesis. Herein, the authors highlight genes with observed epigenetic modifications that are associated with more aggressive TNBC/QNBC pathogenesis and possible interventions. Advanced literature searches were done on PubMed/MEDLINE, Scopus and Google Scholar. The results suggest that nine epigenetically altered genes/differentially expressed proteins in addition to the downregulated androgen receptor are associated with TNBC aggressiveness and could be implicated in the TNBC to QNBC transition. Thus, restoring the normal expression of these genes via epigenetic reprogramming could be therapeutically beneficial to TNBC and QNBC patients.When the androgen hormone receptor becomes inactive in triple-negative breast cancer (TNBC) patients, it results in another subtype of breast cancer called quadruple-negative breast cancer (QNBC). This is because these patients already lack the biological activities of three other important hormone receptors. The functions of these receptors are targeted by some drugs used in the management of breast cancers, so the lack of these receptors in TNBC and QNBC patients is thought to be linked with poor response to treatment. Some epigenetic modifications are involved in a more severe disease that is very difficult to control in TNBC patients and could facilitate its transition to the more aggressive QNBC subtype. Treatment response could be improved by restoring the normal function of the altered genes by reversing the observed epigenetic alterations.

Hepatocellular carcinoma (HCC) is currently the third most common cancer-related death worldwide. HCC is associated with a high mortality rate due to early recurrence and its distant metastasis to the nearby organs. Current treatment options include surgical removal and transplantation as well as chemotherapy, which remains a major challenge to patient treatment. Flavokawain B (FKB) is a natural bioactive molecule capable of providing effective therapy against this life-threatening disease. This study investigates the effects of Flavokawain B (FKB) on the growth and development of metastatic hepatocellular carcinoma. HepG2 cells were used in this study and a neutral red assay was performed to determine the anti-proliferation effects of FKB at varying concentrations. Cell scratch and exclusion zone assays were performed to assess the inhibitory effects of FKB on cell migration and invasion and relative mRNA levels were quantified using the RT-qPCR. FKB inhibited the proliferation of HepG2 cells at an IC50 value of 28 µM, which conforms to its apoptosis-inducing effects. Cell migration and invasion were significantly inhibited at 7, 14, and 28 µM of FBK. UCK2 expression was significantly downregulated after FKB treatments. Inhibition of STAT3 expression subsequently induced the downregulation of VEGF and HIF-1α expressions. Our data suggest that FKB inhibits HepG2 proliferation and suppresses its metastasis abilities, thus providing a potential alternative and viable strategy against HCC.

This study investigates the effects of Flavokawain B (FKB) on the growth and development of metastatic hepatocellular carcinoma. HepG2 cells were used in this study and a neutral red assay was performed to determine the anti-proliferation effects of FKB at varying concentrations. Cell scratch and exclusion zone assays were performed to assess the inhibitory effects of FKB on the cell migration and invasion and relative mRNA levels were quantified using the RT-qPCR. FKB inhibited the proliferation of HepG2 cells at an IC50 value of 28 µM, which conforms to its apoptosis-inducing effects. Cell migration and invasion were significantly inhibited at 7, 14 and 28 µM of FBK. UCK2 expression was significantly downregulated after FKB treatments. Inhibition of STAT3 expression subsequently induced the downregulation of VEGF and HIF-1α expressions. Our data suggest that FKB inhibits HepG2 proliferation and suppresses its metastasis abilities, thus providing a potential alternative and viable strategy against HCC.

Aldose reductase, a key enzyme of the polyol pathway catalyses NADPH-dependent reduction of glucose to sorbitol. Increased activity of this enzyme is considered a major factor contributing to the development of diabetic complications hence could be an important target in the treatment of these complications. In this work, a database of sesquiterpenes was prepared and screened for their drug-like properties based on the Lipinski’s rule of 5. The co-crystallised structure of aldose reductase was obtained from the Protein Databank and prepared for docking. In silico docking experiments was performed on Autodock tools using 198 sesquiterpene lactones that passed screening, and compounds with the lowest binding energy and favourable binding interactions were selected for molecular docking simulation. Six of the best ranking compounds selected had binding energies ranging from–11.96 Kcal/mol to -9.45 Kcal/mol and were comparable to the energy of the standard inhibitor Idd594 used in the study. They also show good complementarity in their binding to the residues of the binding pocket. The results suggest that dehydrooopodin (1), 11(S),13-dihydrolactucopicrin (2), and Chrysanin (3) offered potential inhibitory activities toward aldose reductase and may serve as lead compounds for in vivo validation as aldose reductase inhibitors. Keywords: Sesquiterpene lactones, Aldose reductase, Binding energy, Molecular docking, Autodock

Natron consumption has been implicated in the pathogenesis of peripartum cardiomyopathy. This work evaluates the effect of natron on the antioxidant status and lipid profile of postpartum rats administered graded doses of natron for four consecutive weeks. After treatment, the rats were assessed for antioxidant status, malondialdehyde level, and lipid profile. The results revealed that natron caused a significant decrease (P ˂ 0.05) in the activity of catalase in rats administered with 300 mg/kg of natron compared to control. The activities of superoxide dismutase and glutathione peroxidase decreased in a dose-dependent manner; however, the difference was not statistically significant when compared with control. Serum levels of antioxidant minerals were also significantly decreased (P ˂ 0.05) at higher doses of natron in comparison to control. There was a significant increase (P < 0.05) in the malondialdehyde level in rats administered with 200 and 300 mg/kg of natron when compared with control. Natron at higher doses caused a significant increase (P ˂ 0.05) in the level of the lipid profile parameters except for high-density lipoprotein-cholesterol that decrease significantly (P ˂ 0.05). This study demonstrated that the administration of natron at high doses induced dyslipidemia and oxidative stress in postpartum rats. PRACTICAL APPLICATION: This research reports the implication of a high intake of natron to health and to establish the relationship between natron intake and peripartum cardiomyopathy (PPCM) using an animal model. Natron has health benefits; however, its consumption at high doses should be discouraged as it can lead to oxidative stress (OS) and dyslipidemia. The results suggest that OS due to natron may contribute to the pathogenesis of PPCM. A high concentration of natron can be used to induce an animal model of PPCM, which would be of practical application in studying the molecular basis and possible discovery of therapeutics for the disease.

Cancer is a rapidly growing non-communicable disease worldwide that is responsible for high mortality rates, which account for 9.6 million death in 2018. Dihydroartemisinin (DHA) is an active metabolite of artemisinin, an active principle present in the Chinese medicinal plant

Kebbi state is endowed with medicinal plants that have been used by different tribes especially the Hausa-Fulani, Dakarkari and Gungawa to treat different ailments such as cancer for decades. Therefore, this study is aimed at documenting the medicinal plants used for treating cancer in Kebbi state. Demographic data, personal information of willing informants and information on plants used and mode of treatment was collected via administration of a structured questionnaire. Data was collected and analysed, whereas, cited plants were collected, identified and assigned voucher numbers. The study revealed a total of 48 medicinal plants across 25 different families. Prosopis africana (Guill. & Perr.) Taub ranked first with a citation frequency of 44.9%. The Hausa-Fulani tribes were predominantly the traditional medicine practitioners (53.6%). Plants parts used include leaf, bark, root and whole plant. Generally, the herbal medicine is prepared as a powder and mixed with local beverages (kunu or fura) and administered orally 2–3 times daily. Whereas, residues of the powder are topically applied. Future studies should investigate the antiproliferative potency, determine the mechanisms mediating the cytotoxic potency and isolate the cytotoxic compounds from the active frequently mentioned, scarcely investigated and uninvestigated plants.

A mutation in p53 is frequently reported in nearly 50% of all of human cancers arising from DNA-binding core domain of p53. DNA-contact mutant R273H rendered p53 at dysfunctional state due to the substitution of single residue Arg273 for His273. Here, natural bioactive compounds curcumin, alpinetin and flavokawain B were investigated for possible stabilisation of wild-type p53 expression in vitro using HT-29 cells harbouring R273H rendered p53. Accordingly, all the bioactive compounds were able to induce the expression of wild-type p53 both at the levels of gene and protein expression. A dose-dependent induction of p53 was evident at 12.5, 25 and 50 μM concentration. The present study has shown that the bioactive compounds may have restored the wild-type p53 functional activity in tumour cells expressing R273H mutant p53. Keywords: Curcumin, Alpinetin, Flavokawain B, p53, R273H

The global burden of colorectal cancer (CRC) is increasing annually. CRC could develop from genetic and phenotypic factors involving changes in gene expression. Incredibly, the human genome transcribes into non-coding RNAs, among which long non-coding RNAs (lncRNAs) signify the most crucial part of the transcriptome in multicellular organisms. lncRNAs affect gene expression at multiple levels, from transcription to protein localization and stability. Recent studies have implicated lncRNA small nucleolar RNA host gene 15 (SNHG15) in cancers occurrence and progression. Previously, an indication suggests SNHG15 overexpression triggers proliferation, metastasis, and impedes apoptosis in CRC. Further, through its activity of binding micro-RNAs, lncRNA SNHG15 modulates genes associated with CRC progression and promotes CRC resistance to chemotherapeutic drugs. Here, we reviewed recent findings on the various mechanisms and roles of lncRNA SNHG15 implicated in CRC tumorigenesis. We further highlight how SNHG15 plays a vital role in regulating critical pathways linked to the development and progression of CRC. Finally, we highlight how SNHG15 can be modulated for CRC treatments and the various therapeutic strategies to be implored when targeting SNHG15 in the context of CRC treatments. Findings from these studies present SNHG15 as a potential therapeutic target for preventing and treating CRC.

Mitracarpus hirtus (L.) DC. is a weed plant commonly used for the treatment of eczema. The potential of the plant to treat cancer has not been emphasized, hence the need to explore its anticancer potential. M. hirtus was extracted and subjected to petition with solvents of increasing polarity. Its cytotoxic potential was evaluated against MCF-7, HepG2, and HeLa cells using the Neutral red assay and further verified through morphological assessment and DNA fragmentation assay. Crude chloroform fraction (CCF) displayed a cytotoxic effect on all the cell lines with low IC50 concentrations ranging from 11–17.87 µg/mL. Morphological assessment of MCF-7 exposed to CCF indicates apoptotic cell death and is further confirmed by its DNA fragmentation. Our data suggest that M. hirtus is a potential source for mining anticancer agents.

Cytokine storm is a phrase used to refer to an abrupt upsurge in the circulating levels of various pro-inflammatory cytokines, causing increased stimulation and activity of immune cells during disease conditions. The binding of pattern recognition receptors to pathogen-associated molecular patterns during COVID-19 infection recruits response machinery involving the activation of transcription factors and proteins required for a robust immune response by host cells. These immune responses could be influenced by epigenetic modifications as evidenced by significant variations in COVID-19 pathophysiology and response to therapy observed among patients across the globe. Considering that circulating levels of interleukin 1, tumor necrosis factor-α, and interleukin 6 are significantly elevated during cytokine storm in COVID-19 patients, genetic and epigenetic variations in the expression and function of these proteins could enhance our understanding of the disease pathogenesis. Treatment options that repress the transcription of specific cytokine genes during COVID-19 infection could serve as possible targets to counteract cytokine storm in COVID-19. Therefore, the present article reviews the roles of cytokines and associated genes in the COVID-19 cytokine storm, identifies epigenetic modifications associated with the disease progression, and possible ameliorative effects of some vitamins and minerals obtained as epigenetic modifiers for the control of cytokine storm and disease severity in COVID-19 patients. PRACTICAL APPLICATIONS: COVID-19 causes mortality and morbidity that adversely affect global economies. Despite a global vaccination campaign, side effects associated with vaccination, misconceptions, and a number of other factors have affected the expected successes. Cytokine storm in COVID-19 patients contributes to the disease pathogenesis and response to therapy. Epigenetic variations in the expression of various cytokines could be implicated in the different outcomes observed in COVID-19 patients. Certain vitamins and minerals have been shown to interfere with the expression and activity of cytokines implicated in cytokine storm, thereby counteracting observed pathologies. This review examines cytokines implicated in cytokine storm in COVID-19, epigenetic modifications that contribute to increased expression of identified cytokines, specific foods rich in the identified vitamins and minerals, and suggests their possible ameliorative benefits. The article will be beneficial to both scientists and the general public who are interested in the role of vitamins and minerals in ameliorating COVID-19.

Epidemiologically, metabolic disorders have garnered much attention, perhaps due to the predominance of obesity. The early postnatal life represents a critical period for programming multifactorial metabolic disorders of adult life. Though altricial rodents are prime subjects for investigating neonatal programming, there is still no sufficiently generalised literature on their usage and methodology. This review focuses on establishing five approach-based models of neonatal rodents adopted for studying metabolic phenotypes. Here, some modelled interventions that currently exist to avoid or prevent metabolic disorders are also highlighted. We also bring forth recommendations, guidelines and considerations to aid research on neonatal programming. It is hoped that this provides a background to researchers focused on the aetiology, mechanisms, prevention and treatment of metabolic disorders.

Introduction: For decades, viral diseases have been treated using medicinal plants and herbal practices in the northern part of Nigeria. Though scarcely investigated, these medicinal plants could serve as potential sources for novel antiviral drugs against emerging and remerging viral diseases. Therefore, this study is aimed at investigating the medicinal practices and plants used to treat emerging and re-emerging viral diseases including hepatitis, poliomyelitis, monkeypox, smallpox, yellow fever, Lassa fever, meningitis, and COVID-19 in some northern states; Katsina, Kebbi, Kwara and Sokoto states. Method: Administered questionnaires and oral interviews were used to collect information on medicinal plants, method of preparation of herbal formulations, diagnosis, and treatment of viral diseases. Medicinal plants were collected, botanically identified, and assigned voucher numbers. The plant names were verified using www.theplantlist.org , www.worldfloraonline.org and the international plant names index. Result: A total of 280 participating herbal medicine practitioners (HMPs) mentioned 131 plants belonging to 65 families. Plant parts such as roots, bark, leaf, seed, and fruit were prepared as a decoction, concoction, infusion, or ointment for oral and topical treatment of viral diseases. Moringa oleifera (75.3%), Elaeis guineensis Jacq. (80%), and Acacia nilotica (70%) were the most frequently mentioned plants in Kebbi, Kwara and Sokoto states, respectively. Conclusion: The study revealed scarcely investigated and uninvestigated medicinal plants used to treat hepatitis, poliomyelitis, monkeypox, smallpox, yellow fever, Lassa fever, meningitis, and COVID-19. Future studies should be conducted to determine the antiviral potency and isolate novel bioactive agents from these plants against viral diseases.

It is now glaring that sickle cell anaemia is still one of the highest leading inbred hemoglobinopathy amongst Africans. This study examined the antisickling effects of quercetin via modulation of deoxy-haemoglobin, redox homeostasis and alteration of functional chemistry in human sickle erythrocyte using in silico and in vitro models while espousing preventive and curative approaches. Quercetin was docked against deoxy-haemoglobin and 2, 3-bisphosphoglycerate mutase, with binding energies (−30.427 and −21.106 kcal/mol) and Ki of 0.988μM and 0.992μM at their catalytic sites via strong hydrophobic and hydrogen bond interactions. Induction of sickling was done using 2% metabisulphite at 3h. Treatment with quercetin prevented sickling outstandingly at 5.0μg/mL and reversed same at 7.5μg/mL, 83.6% and 75.9%, respectively. Quercetin also significantly (P

Clausenidin is a pyranocoumarin majorly found in medicinal herbs of the Rutaceae family used to treat cancer patients locally in Asia. The compound is presumed to have anti-cancer cell effect but its exact mechanism of action is still unknown. The study aimed to evaluate the effect of pure clausenidin on p53-mediated apoptosis as well as other cell death pathways in colon cancer (HT-29) cell lines. The anti-proliferative effect of clausenidin by cell cycle and annexin V assay using flow cytometry was evaluated. Morphological analysis of the treated cells was performed using scanning and transmission electron microscopy. Furthermore, the effect of p53 mRNA on cell cycle and apoptosis-related genes and proteins in clausenidin-treated HT-29 cells was investigated using qPCR and Western blot assays, respectively. Clausenidin induced a p53 dependent G0/G1 cell cycle arrest in HT-29 cells. It was also observed that the anti-cancer cell effect of clausenidin occurred via p53 mediated activation of p21, bax and transrepression of survivin and bcl 2 that culminated in the apoptosis of colon cancer cells. The transmission electron microscopy (TEM) micrographs confirmed the occurrence of apoptosis in clausenidin-treated HT-29 cells. Clausenidin is a potent anti-HT-29 cell agent that can be used to treat colon tumors. Key words: Clausenidin, p53, p21, apoptosis, cell cycle.

Parental dietary choices and/or nutritional interventions in the offspring are critical to early life development, especially during the periods of active developmental plasticity in the offspring. Exposure to a high-fructose, high-fat diet during the fetal or neonatal period predisposes the affected individuals to the development of one or more features of metabolic syndrome, such as dyslipidemia, insulin resistance, diabetes, and associated cardiovascular diseases, later in their life. Owing to the increasing global prevalence of metabolic syndrome and multiple side effects that accompany conventional medicines, much attention is directed towards medicinal plants and phytochemicals as alternative interventions. Several studies have investigated the potential of natural agents to prevent programmed metabolic syndrome. This present review, therefore, highlights an inextricable relationship between the administration of medicinal plants or phytochemicals during the intrauterine or neonatal period, and the prevention of metabolic dysfunction in adulthood, while exploring the mechanisms by which they exert such an effect. The review also identifies plant products as a novel approach to the prevention and management of metabolic syndrome.

Cancer metastasis research has emerged in recent years as one of the most important topics of debate in the discovery and development of novel anticancer therapies. Colorectal cancer (CRC), the third most common cancer worldwide, has a high mortality rate due to recurrence and distant metastasis to the liver. Several non-coding RNAs (ncRNAs) have been linked to metastatic CRC (mCRC), including the long non-coding RNA (lncRNA) Metastasis-Associated Lung-Adenocarcinoma Transcript 1 (MALAT1). MALAT1 is an RNA that has been linked to tumor cell proliferation, progression, epithelial-mesenchymal transition (EMT), cell migration and invasion, metastasis, and survival in mammalian species. Previously, there was no convincing evidence linking MALAT1 to mCRC. Studies have shown that MALAT1 functions as a competitive endogenous RNA (ceRNA) with microRNAs (miRNAs) and interacts directly with oncogenes and proteins. This RNA also activates several signaling pathways, including Wnt/β-catenin, PI3K/Akt/mTOR, and EMT. Meanwhile, standard chemotherapy and immunotherapy are the current treatment options for mCRC patients. However, evidence-based studies have recently demonstrated that inhibiting the MALAT1 RNA transcript can be considered as a treatment option for mCRC, highlighting the need to investigate its roles as a therapeutic target in mCRC. Thus, in this review, we looked at studies that linked MALAT1 to multiple signaling pathways implicated in mCRC, as well as its potential as a therapeutic target for the treatment of mCRC.

More than half a century ago, zinc was established as an essential micronutrient for normal human physiology. In silico data suggest that about 10% of the human proteome potentially binds zinc. Many proteins with zinc-binding domains (ZBDs) are involved in epigenetic modifications such as DNA methylation and histone modifications, which regulate transcription in physiological and pathological conditions. Zinc metalloproteins in epigenetics are mainly zinc metalloenzymes and zinc finger proteins (ZFPs), which are classified into writers, erasers, readers, editors, and feeders. Altogether, these classes of proteins engage in crosstalk that fundamentally maintains the epigenome’s modus operandi. Changes in the expression or function of these proteins induced by zinc deficiency or loss of function mutations in their ZBDs may lead to aberrant epigenetic reprogramming, which may worsen the risk of non-communicable chronic diseases. This review attempts to address zinc’s role and its proteins in natural epigenetic programming and artificial reprogramming and briefly discusses how the ZBDs in these proteins interact with the chromatin.

Breast cancer is one of the leading causes of death among women. We employed in silico model to predict the mechanism of actions of selected novel compounds reported against breast cancer using ADMET profiling, drug likeness and molecular docking analyses. The selected compounds were andrographolide (AGP), dipalmitoylphosphatidic acid (DPA), 3-(4-Bromo phenylazo)-2,4-pentanedione (BPP), atorvastatin (ATS), benzylserine (BZS) and 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (TCD). These compounds largely conform to ADMETlab and Lipinki’s rule of drug likeness criteria in addition to their lesser hepatotoxic and mutagenic effects. Docking studies revealed a strong affinity of AGP versus NF-kB (− 6.8 kcal/mol), DPA versus Cutlike-homeobox (− 5.1 kcal/mol), BPP versus Hypoxia inducing factor 1 (− 7.7 kcal/mol), ATS versus Sterol Regulatory Element Binding Protein 2 (− 7.2 kcal/mol), BZS versus Ephrin type-A receptor 2 (− 4.4 kcal/mol) and TCD versus Ying Yang 1 (− 9.4 kcal/mol). Likewise, interaction between the said compounds and respective gene products were evidently observed with strong affinities; AGP versus COX-2 (− 9.6 kcal/mol), DPA versus Fibroblast growth factor receptor (− 5.9 kcal/mol), BPP versus Vascular endothelial growth factor (− 5.8 kcal/mol), ATS versus HMG-COA reductase (− 9.1 kcal/mol), BZS versus L-type amino acid transporter 1 (− 5.3 kcal/mol) and TCD versus Histone deacytylase (− 7.7 kcal/mol), respectively. The compounds might potentially target transcription through inhibition of promoter-transcription factor binding and/or inactivation of final gene product. Thus, findings from this study provide a possible mechanism of action of these xenobiotics to guide in vitro and in vivo studies in breast cancer. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40203-020-00057-8) contains supplementary material, which is available to authorized users.

Background Zinc deficiency is associated with adverse effects on maternal health and pregnancy outcomes. These consequences have been reported over the years from zinc supplementation trials and observational studies whereby outcomes of maternal, foetal and infant health were measured. Owing to the importance of zinc in the functions of epigenetic enzymes, pre-clinical studies have shown that its deficiency could disrupt biological activities that involve epigenetic mechanisms in offspring. Thus, this review assessed the link between epigenetics and the effects of maternal zinc deficiency on the offspring’s health in animal studies. Methods Research articles were retrieved without date restriction from PubMed, Web of Science, ScienceDirect, and Google Scholar databases, as well as reference lists of relevant articles. The search terms used were “zinc deficiency”, “maternal zinc deficiency”, “epigenetics”, and “offspring.” Six studies met the eligibility criteria and were reviewed. Results All the eligible studies reported maternal zinc deficiency and observed changes in epigenetic markers on the progeny during prenatal and postnatal stages of development. The main epigenetic markers reported were global and gene specific methylation and/ or acetylation. The epigenetic changes led to mortality, disruption in development, and risk of later life diseases. Conclusion Maternal zinc deficiency is associated with epigenetic modifications in offspring, which induce pathologies and increase the risk of later life diseases. More research and insight into the epigenetic mechanisms could spring up new approaches to combat the associated disease conditions.

The aim of this study was to evaluate the potentials of rutin on 2,5-hexanedione-induced toxicities. Two successive phases were involved using in silico and in vivo approaches. The in silico was adopted for potential oral toxicity and docking. The in vivo was carried-out in two stages for two weeks; the ameliorative (stage 1, first week), preventive, and curative studies (stage 2, extended to second week). In stage 1, rats were divided into four groups of seven each (distilled water, 3% (v/v) 2,5-hexanedione, 10 mg/kg rutin, and co-administration). In stage 2, the experimental groups were given either rutin or 2,5-hexanedione and treated in reverse order. Lipid peroxidation, protein carbonyl, and DNA fragmentation in tissues and bone marrow cells micronucleus were determined. The predicted Median lethal dose (LD50) of >5000 mg/kg and toxicity class of five (5) indicates the safety of rutin when orally administered. 2,5-Hexanedione comfortably docked in to the active sites of SOD (-22.857Kcal/mol; KI = 0.9621 µM), GPx (-11.2032Kcal/mol; KI = 0.9813 µM), and CAT (-16.446Kcal/mol; KI = 0.9726 µM) with strong hydrogen bond and hydrophobic interactions. However, only strong hydrophobic interaction was observed in the case of DNA (-3.3296Kcal/mol; KI = 0.9944). In vivo findings revealed deleterious effects of 2,5-hexanedione through induction of oxidative and chromosomal/DNA damage characterized by higher level of malondialdehyde, micronuclei formations, and DNA fragmentation. These have invariably, validates the findings from in silico experiments. Furthermore, rutin was able to ameliorate, protect, and reverse these effects, and was relatively non-toxic corroborating toxicity predictions. Rutin exhibited counteractive effects on 2,5-hexanedione-induced oxidative, chromosomal, and DNA damage.

Imaobong Christopher Etti,1,2 Abdullah Rasedee,3 Najihah Mohd Hashim,4 Ahmad Bustamam Abdul,5 Arifah Kadir,6 Swee Keong Yeap,7 Peter Waziri,5 Ibrahim Malami,5 Kian Lam Lim,8 Christopher J Etti9 1Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia; 2Department of Pharmacology and Toxicology, University of Uyo, Uyo, Nigeria; 3Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia; 4Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 5MAKNA-Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia; 6Department of Veterinary Preclinical Science, Universiti Putra Malaysia, Serdang, Malaysia; 7Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia; 8Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras, Selangor, Malaysia; 9Department of Agricultural and Food Engineering, University of Uyo, Uyo, Nigeria Abstract: Artonin E is a prenylated flavonoid compound isolated from the stem bark of Artocarpus elasticus. This phytochemical has been previously reported to be drug-like with full compliance to Lipinski’s rule of five and good physicochemical properties when compared with 95% of orally available drugs. It has also been shown to possess unique medicinal properties that can be utilized in view of alleviating most human disease conditions. In this study, we investigated the cytotoxic mechanism of Artonin E in MCF-7 breast cancer cells, which has so far not been reported. In this context, Artonin E significantly suppressed the breast cancer cell’s viability while inducing apoptosis in a dose-dependent manner. This apoptosis induction was caspase dependent, and it is mediated mainly through the intrinsic pathway with the elevation of total reactive oxygen species. Gene and protein expression studies revealed significant upregulation of cytochrome c, Bax, caspases 7 and 9, and p21 in Artonin E-treated MCF-7 cells, while MAPK and cyclin D were downregulated. Livin, a member of the inhibitors of apoptosis, whose upregulation has been noted to precede chemotherapeutic resistance and apoptosis evasion was remarkably repressed. In all, Artonin E stood high as a potential agent in the treatment of breast cancer. Keywords: Artonin E, breast cancer, apoptosis, cell cycle, livin

Background: Breast cancer has been reported to be among the frequently diagnosed cancer in women worldwide despite advances in early detection and treatment. Several drugs are currently used for chemoprevention as a result of a number of drawbacks associated with breast cancer therapy. Aim: This review focuses on the metabolism and toxicological implications of these drugs against breast cancer/ carcinogenesis. Methodology: Relevant articles on the commonly used anti-breast cancer drugs (raloxifene, tamoxifen, anastrozole, letrozole and exemestane) used in chemoprevention were searched using the major scientific databases including Scopus, Embase, PubMed/ Medline, Sciencedirect and Google Scholar. Results: The mechanism of action of estrogen receptor modulators are basically mediated via binding to estrogen receptors leading agonistic and antagonistic effects, whereas that of aromatase inhibitors involved the suppression of estrogen concentration in plasma via inhibition or inactivation of aromatase. Both estrogen receptor and aromatase modulators are good candidates for breast cancer chemoprevention, with latter being the most appropriate. However, it has been observed that pharmacodynamics nature of these xenobiotics, often yields some undesirable outcomes after administration which may be linked to resistance and other biological side effects, following phase I/II reactions, bioactivation within and around breast tissue microenvironment vis-a-vis distant tissues. Various findings indicated the manifestation of genotoxicity, organ toxicity and oxidative/nitrosative stress at low, moderate and high doses, thereby complicating the already existing precarious condition. Moreover, interindividual variations were also observed amongst patients, suggesting a critical role of genetic polymorphism. Also, variable side effects including osteoporosis, musculoskeletal events, such as arthralgia and myalgia were found to be predominant. Conclusion: The aromatase inhibitors seem to be most appropriate when it comes to application by virtue of their metabolic functions and fates. The reason is that raloxifene and tamoxifen are not the ideal drugs to reduce the incidence of primary invasive breast cancer because their safety and efficacy don’t reach the desired optimal agent level. However, adequate care should be taken while prescribing, as well as during and after treatment with constant close monitoring of patients for any possible biochemical and clinical manifestations vis-a-vis the issue of pharmacogenetics.

This study was designed to investigate the alteration of redox status by commonly used antimalarials in Nigeria. Drugs used were artemisinin, artesunate, chloroquine, coartem and quinine at the final concentrations of 0.5–8.0 mg/mL. Blood samples were collected from malarial patients and apparently healthy humans for comparison. Reduced glutathione, catalase, superoxide dismutase (SOD) activities, protein content and lipid peroxidation were determined. All drugs significantly ( p < 0.05) increases the protein level relative to control in normal blood, whereas in the infected, a significant ( p < 0.05) reduction was observed. In normal blood, the antimalarials dose dependently decreased ( p < 0.05) SOD and catalase activities with significant ( p < 0.05) increase in the infected. The level of glutathione in normal blood significantly ( p < 0.05) increases as compared with control, whereas in the infected, similar observation was made except that the levels were less, relative to control sample. Malondialdehyde level significantly ( p < 0.05) increases with increase in drugs concentration even though less than the level in the control with few exceptions. These effects were dose dependent and more pronounced in non-malarial conditions. Commonly used antimalarials might alter the redox status in both healthy and non-healthy subjects thereby inducing oxidative stress.

Background: Antimalarial drugs are medicines that are used to prevent or treat malaria effectively at different stages in the life cycle of the malarial parasites. In spite of this, a good number of these drugs have the potential to cause harm when they are misused or abused. Objective: This study was undertaken to evaluate the effects of commonly-used antimalarial drugs in the North Western region of Nigeria on haemolysis and DNA fragmentation in the blood of normal and malarial infected humans ex vivo. Method: The drugs used were artemisinine, artesunate, chloroquine, coartem and quinine (0.5-8.0 mg/ml). Haemolysis, haemoglobin status and DNA fragmentations were assayed for using standard procedures. Results: It was observed that all the drugs induced a remarkable dose-dependent haemolysis with more pronounced effects on apparently healthy humans. There was a significant (P < 0.05) decrease in the level of haemoglobin in normal blood samples when compared with control samples. Contrariwise, in the malaria-infected blood, the haemoglobin level significantly (P < 0.05) increased as compared with control. The drugs caused an exceptional significant (P < 0.05) induction of DNA fragmentation when compared with control. Conclusion: Commonly-used antimalarial drugs induced haemolysis and altered haemoglobin status which may spontaneously increases the cellular iron levels; a substrate for Fenton and Haber Weiss reactions, and eventually induces DNA fragmentation. Hence, adequate care should be taken during prescription with total avoidance for self medications and/or drugs abuse as a result of their adverse effects within the red blood cells and its immediate microenvironment.

Recent advances in functional foods-based research have increasingly become an area of major interest because it affects human health and activities. Functional foods are classes of foods with health promoting and disease preventing properties in addition to multiple nutritional values and of such type is honey. Acacia honey is a type of honey produced by bees (Apis mellifera) fed on Acacia flowers, hence the name. This review focuses on the potential biological activities of Acacia honey which includes quality, antioxidant, immuno-modulatory, antiproliferative and neurological properties at in vitro and in vivo levels. Based on our review, Acacia honey used from various researches is of high purity, contains some bioactive compounds ranging from vitamins, phenolics, flavonoids and fatty acids. It's highly nutritional with strong antioxidant and immuno-modulatory potentials which may therefore be considered a potential candidate for both cancer prevention and treatment. Neurologically, it may be considered as a viable therapeutic agent in the management of Alzheimer's disease.

Recent advances in functional foods-based research have increasingly become an area of major interest because it affects human health and activities. Functional foods are classes of foods with health promoting and disease preventing properties in addition to multiple nutritional values and of such type is honey. Acacia honey is a type of honey produced by bees (Apis mellifera) fed on Acacia flowers, hence the name. This review focuses on the potential biological activities of Acacia honey which includes quality, antioxidant, immuno-modulatory, antiproliferative and neurological properties at in vitro and in vivo levels. Based on our review, Acacia honey used from various researches is of high purity, contains some bioactive compounds ranging from vitamins, phenolics, flavonoids and fatty acids. It's highly nutritional with strong antioxidant and immuno-modulatory potentials which may therefore be considered a potential candidate for both cancer prevention and treatment. Neurologically, it may be considered as a viable therapeutic agent in the management of Alzheimer's disease.