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The 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 citratus leaf extract against Plasmodium falciparum drug targets such as P. falciparum circumsporozoite protein (PfCSP), P. falciparum merozoite surface protein 1 (PfMSP1) and P. falciparum erythrocyte membrane protein 1 (PfEMP1). In silico approaches 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. citratus exhibited 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. citratus exhibited 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. citratus have modulatory properties toward P. falciparum drug 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. citratus for malaria treatment. Communicated by Ramaswamy H. Sarma

Reactive species, such as those of oxygen, nitrogen, and sulfur, are considered part of normal cellular metabolism and play significant roles that can impact several signaling processes in ways that lead to either cellular sustenance, protection, or damage. Cellular redox processes involve a balance in the production of reactive species (RS) and their removal because redox imbalance may facilitate oxidative damage. Physiologically, redox homeostasis is essential for the maintenance of many cellular processes. RS may serve as signaling molecules or cause oxidative cellular damage depending on the delicate equilibrium between RS production and their efficient removal through the use of enzymatic or nonenzymatic cellular mechanisms. Moreover, accumulating evidence suggests that redox imbalance plays a significant role in the progression of several neurodegenerative diseases. For example, studies have shown that redox imbalance in the brain mediates neurodegeneration and alters normal cytoprotective responses to stress. Therefore, this review describes redox homeostasis in neurodegenerative diseases with a focus on Alzheimer’s and Parkinson’s disease. A clearer understanding of the redox-regulated processes in neurodegenerative disorders may afford opportunities for newer therapeutic strategies.

Hypoxia-inducible factors (HIFs) are transcription factors that initiate the expression of cellular processes to cope with hypoxic conditions. HIFs are principal regulators of hypoxic adaptation, regulating gene expression involved in glycolysis, erythropoiesis, angiogenesis, proliferation, and stem cell function under low O2. HIFs may play a pivotal role in tumor survival and metastasis in cancer formation and growth. Likewise, HIFs play a key role in microbial pathogenesis, particularly in host-pathogen interaction. Because of the role that HIF-1alpha plays in the biology of cancer and infections, it is a potential therapeutic target not only for malignant growth but also for parasitic infection. Several reports have demonstrated the up-regulation of host cellular HIFs due to infection-induced hypoxia. Hypoxia-inducible pathways have attracted great interest in the down-regulation of prolyl hydroxylase for treating inflammatory diseases and infections by viruses, protozoa, or bacteria, among other pathogens. Interestingly, increasing evidence suggests that HIFs play an important regulatory role in inflammation. For example, in macrophages, HIFs regulate glycolytic energy generation and optimize innate immunity, control pro-inflammatory gene expression, mediate the killing of pathogens and influence cell migration. Therefore, a good understanding of the biochemical mechanism of hypoxia signaling pathways will shed more light on how it could help identify and develop new treatment strategies for cancer and parasitic diseases, including viral, bacterial, fungal and protozoa infections.

This study evaluates the probable effects of induced reproductive toxicity by cadmium and its amelioration by gallic acid (GA). Adult female rats were daily administered with cadmium (CdCl2) (5 mg/kg) singly or combined with GA (20 mg/kg) for 14 days to evaluate the effect on antioxidant status and ovary function using biochemical and histological analysis. Cadmium-treated rats alone revealed a considerable increment in total body weight and ovaries’ weight due to muscle wasting. However, GA + cadmium reversed considerably the tread and offered protection against cadmium-induced muscle wasting. Cadmium treatment alone decreased reduced glutathione (GSH) level, activities of superoxide dismutase (SOD), and catalase (CAT) and also increased malondialdehyde (MDA) level. Besides, the administration of GA alone or in combination mitigated the cadmium-mediated decrease in GSH, SOD, and CAT, respectively. Serum concentrations of estrogen (E), testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were reduced significantly in cadmium-treated rats. Histopathology of the ovaries showed a considerable reduction in follicle number. GA treatment alone and CdCl2 + GA-treatment group decreased cell death of follicular cells in the ovaries of rats and increased serum reproductive hormones. Taken together, gallic acid prevented the deleterious impacts of CdCl2 on the biomarkers of oxidative stress, antioxidant enzymes, and ovarian histopathological structure.

Aims: This study was designed to examine the pattern of psychoactive drugs use among long-distance truck drivers in Ado-Ekiti, Ekiti state, Nigeria. Study Design: This was a descriptive cross sectional study. Place and Duration: The study was conducted at the converging motor park for truck drivers in Ado-Ekiti, south-west Nigeria between September and December 2019. Methods: The pattern of psychoactive drugs use among 306 adult male truck drivers was determined using a semi-structured questionnaire in addition to a sociodemographic questionnaire. Data was analyzed and logistic regression was used to identify significant predictors of illicit drug use. Results: Among the 306 study participants, 43.7% consumed alcohol. The major non-prescription drugs used by the truck drivers were cough syrups (67.0%); analgesics (49.3%); cannabis (39.9%); amphetamine/methamphetamine (33.0%) and tranquilizers (32.0%). Opioid analgesics like tramadol (35.1%) and morphine (22.3%) were the commonly used analgesics. The predictor of psychoactive drugs use among the long-distance truck drivers is the co-use of alcohol and tobacco (AOR (1.71) 95% CI (1.24–2.36%). Conclusion: There is a high rate of psychoactive drugs use among truck drivers. There is an urgent need to educate the truck drivers on the adverse implications of illicit drug use and the need to abstain for better health promotion.

Abstract: The use of herbal remedies for medicinal purposes is becoming more popular around the world. As a result, plants have become viable treatment options for a variety of diseases. Garcinia kola (bitter kola) is a perennially grown plant in the Guttiferae family that has been evaluated and reported to have numerous health-promoting properties. Kolaviron is a biflavanoid and major phytochemical found in Garcinia kola that includes Garcinia Biflavanoid-1 (GB-1), kolaflavanone, and Garcinia Biflavanoid-2 (GB-2). It is obtained as a fraction extracted from Garcinia kola. Kolaviron's pharmacological properties include anti-inflammatory, anti-spasmodic, ameliorative, anti-asthmatic, anti-cancer, anti-malarial, hepatoprotective, antioxidant, anti-atherogenic, neuroprotective, anti-diabetic, and anti-amnesic properties. Kolaviron is recommended for use in clinical settings because it has been shown to have a high therapeutic efficacy in clinical trials. The purpose of this review is to assess the therapeutic efficacy of kolaviron.

Background Our previous reports demonstrated the prospects of a new series of imidazoles as a source of alternative anti-parasite treatments, thus warranting further studies that include toxicity profiling. Objective In this study, we evaluated three imidazoles: bis-imidazole (compound 1), phenyl-substituted 1H-imidazole (compound 2), and thiopene-imidazole (compound 3) for cellular toxicity and possible mechanisms. Methods The three (3) compounds were assessed for in vitro cytotoxic action. Additionally, we probed likely mechanistic actions of these imidazoles. Findings showed dose-dependent cellular toxicity by these imidazoles. Results In the presence of antioxidant (Trolox), cytotoxicity was improved for compounds 2 and 3 but not for compound 1. Meantime, compound 7 promoted reactive oxygen species (ROS) production, which was abated in the presence of a standard antioxidant (Trolox). Additionally, the three (3) imidazoles impaired mitochondrial membrane potential (MMP). While MMP was not restored after treatment removal, the addition of antioxidant (Trolox) improved MMP for compounds 2 and 3 treatment. Additionally, compound 1 elevated expression of hypoxia-inducing factor 1-alpha (HIF-1α). This may not be unconnected with the capacity of compound 1 to cause oxidative stress. Conclusion We show evidence that supports the cytotoxic action of imidazoles involves likely impairment to redox balance and mitochondrial membrane potential. The findings help our understanding of the mechanistic action of these imidazoles in living cells, and altogether may boost their prospects as new and alternative anti-protozoans.

Breast cancer (BC) is one of the most common and recurring diseases and the second leading cause of death in women. Despite prevention, diagnostics, and therapeutic options such as radiation therapy and chemotherapy, the number of occurrences increases every year. Therefore, novel therapeutic drugs targeting specifically different checkpoints should be developed against breast cancer. Among drugs that can be developed to treat breast cancer, natural products, such as plant-derived compounds, showed significant anti-breast cancer properties. These substances belong to different chemical classes such as flavonoids, terpenoids, phenolic acids, and alkaloids. They exert their in vitro and in vivo cytotoxic activities against breast cancer cell lines via different mechanisms, including the inhibition of extrinsic and intrinsic apoptotic pathways, the arrest of the cell cycle, and the activation of autophagy. Moreover, they also exhibit anti-angiogenesis and antimetastatic action. Moreover, chemoprevention effects of these bioactive compounds were signaled only for certain drugs. Therefore, the aim of this review is to highlight the pharmacological actions of medicinal plants and their bioactive compounds on breast cancer. Moreover, the role of these substances in breast cancer chemoprevention was also discussed.

The study investigated the effects of Zingiber officinale root and Vernonia amygdalina leaf on the brain redox status of Wistar rats. Twenty-four (24) rats weighing 160 ± 20 g were randomly assigned into four (4) groups, each with six (6) rats. Animals in Group 1 (control) were orally administered distilled water (1 mL), while the test groups were orally administered 5 mg/mL of either Z. officinale, V. amygdalina infusion, or a combination of both, respectively, for 7 days. The rats were sacrificed at the end of treatments and blood and tissue were harvested and prepared for biochemical assays. Results showed that administration of V. amygdalina and Z. officinale, as well as their coadministration, reduced the levels of malondialdehyde (MDA), nitric oxide (NO), acetylcholinesterase (AChE), and myeloperoxidase (MPO) in rat brain tissue compared with the control group. Conversely, coadministration of V. amygdalina and Z. officinale increased the levels of reduced glutathione (GSH) in rat brain tissue compared with the control group. However, the administration of the infusions singly, as well as the combination of both infusions, did not have any effect on the rat brain levels of glutathione peroxidase (GPx) and catalase (CAT) antioxidant enzymes compared to the control. Taken together, the findings indicate that the V. amygdalina and Z. officinale tea infusions have favorable antioxidant properties in the rat brain. The findings are confirmatory and contribute to deepening our understanding of the health-promoting effects of V. amygdalina and Z. officinale tea infusions.

The world is going green; hence, environmentally friendly practices that would conserve natural resources for the future generation are encouraged. As a consequence, the world is less concerned about the numerous applications of nanotechnology, especially in the health sector; rather, it is more concerned about the sustainability of functionalized nanomaterials. Thus, the future of nanotechnology depends on its ability to ‘go green'. Green nanotechnology attempts to synthesize improved, nontoxic, and biocompatible nanomaterials with sustainable benefits using eco-friendly materials. Although green nanotechnology is considered a sustainable, viable, and biocompatible approach to the production of eco-friendly nanomaterials, there are shortcomings especially in microbial handling and process optimization. In this chapter, the authors aim to appraise not only the use of biocompatible approaches for the synthesis of nanoparticles and/or nanomaterials but also their shortcomings.

Botanicals with remarkable pharmacological properties include Zingiber officinale Roscoe [Zingiberaceae] (ginger) and Gymnanthemum amygdalinum (Delie) Sch. Bip [Asteraceae] (bitterleaf). The plants are frequently used as teas and decoctions, and have been studied in the treatment of various illnesses. Thus, this study investigated the in vitro antioxidant activities and chemical fingerprints of ginger and bitter leaf infusions separately and as a combination. In addition, we assessed the effects of the tea infusions on rat liver and kidney indices. The findings from this study showed that the bitterleaf infusion had the highest phenolic content (21.77 ± 3.140 µg gallic acid equivalent/mg) in comparison with that of ginger (15.17 ± 1.50 µg gallic acid equivalent/mg) and their combination (8.81 ± 0.48 µg gallic acid equivalent/mg). The ginger infusion had the highest flavonoid content (547.15 ± 1.17 µg quercetin equivalent/mg), which was preceded by bitterleaf (473.02 ± 10.48 µg quercetin equivalent/mg) and the ginger and bitterleaf infusion (415.08 ± 4.15 µg quercetin equivalent/mg). Furthermore, our results showed that the tea infusions had no significant effect on the liver function indices (ALT and AST) compared to the control. In contrast, the rat plasma urea significantly increased in the groups given bitterleaf and a combination of ginger and bitterleaf infusions, while creatinine significantly decreased in the group that received the combined form of the infusion. The GC-MS analysis of ginger and bitterleaf infusions revealed that n-hexadecanoic acid, oleic acid, and ergosterol were most abundant in the bitterleaf infusion. At the same time, gingerol, 2-butanone, and 4-(4-hydroxy-3-methoxyphenyl) were the most abundant in the ginger infusion. Together, the findings are not only evidence in support of the medicinal value of these plants but also reinforce their prospects as nutriceuticals.

Type-2 diabetes mellitus (T2DM), is considered being a multifaceted disorder that presents a major therapeutic problem. Despite the widespread efforts in managing T2DM, drug discovery therapies remain insufficient. There are several new and vital antidiabetic drug agents under examination of many research clusters. Computational tools have influenced drug discovery at several levels. Hence, this study aimed to explain the molecular interactions via an in silico simulation approach between Aframomum melegueta seed-derived compounds as antidiabetic agents against carbohydrate metabolism regulatory target proteins (DPP-4, GSK-3, and GLP-1) involved in T2DM. Pharmacophore modeling, Auto-QSAR, induced-fit docking (IFD) simulation, free energy of binding affinity through the MM-GBSA method, and molecular docking were used to sort out the compounds as well as determining their drug ability. The results revealed the pharmacophore models created from the structures of DPP-4, GSK-3, and GLP-1 could determine the lead candidates with a restorative ability rate found near 100% of the actives in the comprehensive decoy database ranking. We predicted the pIC50 values of the compounds via a learning-based machine that was created by auto-QSAR. We authenticated the created model to confirm its analytical procedure. The greatest models attained for DPP-4, GSK-3, and GLP-1 were kpls_desc_35 (R2 = 0.73 and Q2 = 0.73), kpls_desc_4 (R2 = 0.72 and Q2 = 0.66), and kpls_radical_14 (R2 = 0.88 and Q2 = 0.64) and these confirmed models were used to predict the bioactivities of the hit candidates. While several isolated bioactive compounds from Aframomum melegueta revealed a better binding affinity score, binding free energy along with observance of RO5, only three compounds (ethinyl estradiol, 8-gingerol, and zingerone) revealed a more satisfactory pIC50. Thus, these compounds can be novel candidates for drug discovery in diabetes treatment.

Background Therapeutic options for toxoplasmosis are limited. This fact underscores ongoing research efforts to identify and develop better therapy. Previously, we reported the anti-parasitic potential of a new series of derivatives of imidazole. Objective In the current investigation, we attempted the investigation of the possible action mechanism of few promising anti-parasite imidazole derivatives namely C1 (bis-imidazole), C2 (phenyl-substituted 1H-imidazole) and C3 (thiophene-imidazole) Methods We evaluated if oxidative stress, hypoxia as well as metabolic reprogramming of host l -tryptophan pathway form part of the parasite growth inhibition by imidazoles. Anti-parasite assay was performed for imidazoles at concentrations ranging from 0 to 10 μM, while pyrimethamine was used as reference drug to validate assay. Results Imidazole compounds restricted parasite growth dose-dependently. However, in the presence of an antioxidant (Trolox), l -tryptophan and/or CoCl2 (chemical inducer of hypoxia), the growth inhibitory efficacy of imidazoles was appreciably abolished. Further, imidazole treatment led to elevated level of reactive oxygen species, while reducing parasite mitochondrial membrane potential compared with control. In contrast, imidazole had no effect on host HIF-1α level suggesting its exclusion in the anti-parasite action. Conclusion Taken together, imidazole-based compounds might restrict parasite growth by causing oxidative stress. The findings provide new insight on the likely biochemical mechanisms of imidazoles as prospective anti-parasite therapy. Data gives new perspective that not only underscores the anti-parasite prospects of imidazoles, but implicates the host l -tryptophan pathway as a feasible treatment option for T. gondii infections.

Background. TheMoringa oleiferaplant has been implicated for several therapeutic potentials.Objective. To evaluate whether addition ofM. oleiferato diet has protective effect against nickel-induced nephrotoxicity in rats.Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4) in normal saline and sustained on either normal diet or diets supplemented withMoringa oleiferaat different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively.Results. NiSO4exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4exposure. However, addition ofM. oleiferato diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4exposure. In contrast, the damages were ameliorated by theM. oleiferasupplemented diets.Conclusion. The addition ofM. oleiferato diet afforded significant protection against nickel-induced nephrotoxicity.