Mitophagy and spermatogenesis: Role and mechanisms.

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.

Goethite and Hematite Nanoparticles Show Promising Anti-Toxoplasma Properties.

Toxoplasma gondii is an intracellular parasitic protozoan with a high infection rate in mammals, including humans, and birds. There is no effective vaccine, and treatment relies on antiparasitic drugs. However, existing antiprotozoal drugs have strong side effects and other problems; therefore, new treatment approaches are needed. Metal nanoparticles have attracted increased interest in the biomedical community in recent years because of their extremely high surface area to volume ratio and their unique reactivity that could be exploited for medicinal purposes. Previously, we confirmed the anti-Toxoplasma effects of gold, silver, and platinum nanoparticles, in a growth inhibition test. Here, we asked whether the anti-Toxoplasma effect could be confirmed with less expensive metal nanoparticles, specifically iron oxide nanoparticles (goethite and hematite). To improve the selective action of the nanoparticles, we modified the surface with l-tryptophan as our previous findings showed that the bio-modification of nanoparticles enhances their selectivity against T. gondii. Fourier-Transform Infrared Spectroscopy (FTIR) analysis confirmed the successful coating of the iron oxide nanoparticles with l-tryptophan. Subsequently, cytotoxicity and growth inhibition assays were performed. L-tryptophan-modified nanoparticles showed superior anti-Toxoplasma action compared to their naked nanoparticle counterparts. L-tryptophan enhanced the selective toxicity of the iron oxide nanoparticles toward T. gondii. The bio-modified nanoparticles did not exhibit detectable host cell toxicity in the effective anti-Toxoplasma doses. To elucidate whether reactive oxygen species contribute to the anti-Toxoplasma action of the bio-modified nanoparticles, we added Trolox antioxidant to the assay medium and found that Trolox appreciably reduced the nanoparticle-induced growth inhibition.

In silico modeling revealed phytomolecules derived from Cymbopogon citratus (DC.) leaf extract as promising candidates for malaria therapy.

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.

Anti-malarial and haematological evaluation of the ethanolic, ethyl acetate and aqueous fractions of Chromolaena odorata.

Malaria is a global health challenge with endemicity in sub-Saharan Africa, where there are multiple drug-resistant strains and limited access to modern health care facilities, especially in rural areas. Studies indicate that African traditional medicine could make a substantial contribution to the reduction of malaria-related deaths and achievement of universal health coverage (UHC), particularly in these regions. Thus, this study evaluated the curative antimalarial effects of Chromolaena odorata leaf extract using mouse model. Forty-five (45) albino mice weighing between 18 and 22 g were grouped into nine groups of 5 animals each. Animals in groups 2-9 were infected with the chloroquine-resistant strain of Plasmodium berghei, while animals in groups 3-9 were subsequently treated with 10 mg/kg chloroquine, a combination of 1.4 mg/kg artemether and 8.75 mg/kg lumefantrine (Coartem), and varying concentrations of the fraction from the aqueous leaf extract of C. odorata at day 3 post-infection. The findings from this study indicate that treatment with 400 mg/kg of the ethanolic fraction of the crude extract resulted in a significant decrease in parasite load (97.6%), which was comparable to the activities of the conventional drugs chloroquine (98.6%) and Coartem (98.8%). The ethyl acetate and ethanolic fractions at 400 mg/kg also ameliorated the significant alterations in the red blood cells, white blood cells, and platelets of the infected animals. The high antimalarial activity displayed by the ethanolic fraction could be due to the presence of quercetin and kaempferol, as detected by high performance liquid chromatography (HPLC) analysis. The findings suggest that the fractions from C. odorata could serve as an alternative source of malaria therapy, particularly in sub-Saharan Africa.

In Vivo Efficacy of Curcumin and Curcumin Nanoparticle in Trypanosoma congolense, Broden 1904 (Kinetoplastea: Trypanosomatidae)-Infected Mice.

Curcumin (CUR) is known for its wide folkloric effects on various infections; however, its solubility status has remained a hindrance to its bioavailability in the host. This study evaluated the comparative effects of CUR and CUR-nanoparticle in vitro on T. congolense, T. b. brucei, and T. evansi. Additionally, CUR and CUR-nanoparticle anti-Trypanosoma efficacy were assessed in vivo against T. congolense. All the CUR-nanoparticles were two folds more effective on the T. congolense as compared to CUR in vitro, with recorded efficacy of 3.67 ± 0.31; 7.61 ± 1.22; and 6.40 ± 3.07 µM, while the CUR-nanoparticles efficacy was 1.56 ± 0.50; 28.16 ± 9.43 and 13.12 ± 0.13 µM on T. congolense, T. b. brucei, and T. evansi, respectively. Both CUR and CUR-nanoparticles displayed moderate efficacy orally. The efficacy of CUR and CUR-nanoparticles in vivo was influenced by solubility, presence of food, and treatment period. CUR-treated mice were not cured of the infection; however, the survival rate of the orally treated mice was significantly prolonged as compared with intraperitoneal-treated mice. CUR-nanoparticles resulted in significant suppression of parasitemia even though relapsed was observed. In conclusion, CUR and CUR-nanoparticles possess moderate efficacy orally on the trypanosomes as compared to the intraperitoneal treatment.

Exploring redox imbalance and inflammation for asthma therapy.

BACKGROUND: Asthma is a prolonged inflammatory disorder of the airways, that affects an estimated 300 million people worldwide. Asthma is triggered by numerous endogenous and exogenous stimuli with symptoms like wheezing, cough, short of breath, chest tightening, airway obstruction, and hyperreactivity observed in patients. OBJECTIVE: The review seeks to identify targets of redox imbalance and inflammation that could be explored to create effective treatments for asthma. METHODS: The methodology involved a search and review of literature relating to asthma pathogenesis, redox homeostasis, and inflammation. RESULTS:  Eosinophils and neutrophils are involved in asthma pathogenesis. These inflammatory cells generate high levels of endogenous oxidants such as hydrogen peroxide and superoxide, which could result in redox imbalance in the airways of asthmatics. Redox imbalance occurs when the antioxidant systems becomes overwhelmed resulting in oxidative stress. Oxidative stress and inflammation have been linked with asthma inflammation and severity. Reactive oxygen species (ROS)/reactive nitrogen species (RNS) cause lung inflammation by activating nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), activator protein-1, as well as additional transcription factors. These factors stimulate cytokine production which ultimately activates inflammatory cells in the bronchi, causing lung cellular injury and destruction. ROS/RNS is also produced by these inflammatory cells to eradicate invading bacteria. Antioxidant treatments for asthma have not yet been fully explored. CONCLUSION: Redox and inflammatory processes are viable targets that could be explored to create better therapy for asthma.

Natural antioxidants from some fruits, seeds, foods, natural products, and associated health benefits: An update.

Antioxidants are compounds that inhibit the oxidation of other molecules and protect the body from the effects of free radicals, produced either by normal cell metabolism or as an effect of pollution and exposure to other external factors and are responsible for premature aging and play a role in cardiovascular disease. degenerative diseases such as cataracts, Alzheimer's disease, and cancer. While many antioxidants are found in nature, others are obtained in synthetic form and reduce oxidative stress in organisms. This review highlights the pharmacological relevance of antioxidants in fruits, plants, and other natural sources and their beneficial effect on human health through the analysis and in-depth discussion of studies that included phytochemistry and their pharmacological effects. The information obtained for this review was collected from several scientific databases (ScienceDirect, TRIP database, PubMed/Medline, Scopus, Web of Science), professional websites, and traditional medicine books. Current pharmacological studies and evidence have shown that the various natural antioxidants present in some fruits, seeds, foods, and natural products have different health-promoting effects. Adopting functional foods with high antioxidant potential will improve the effective and affordable management of free radical diseases while avoiding the toxicities and unwanted side effects caused by conventional medication.

The In Vitro Anti-Parasitic Activities of Emodin toward Toxoplasma gondii.

Currently, toxoplasmosis affects nearly one-third of the world's population, but the available treatments have several limitations. This factor underscores the search for better therapy for toxoplasmosis. Therefore, in the current investigation, we investigated the potential of emodin as a new anti-Toxoplasma gondii while exploring its anti-parasitic mechanism of action. We explored the mechanisms of action of emodin in the presence and absence of an in vitro model of experimental toxoplasmosis. Emodin showed strong anti-T. gondii action with an EC50 value of 0.03 µg/mL; at this same effective anti-parasite concentration, emodin showed no appreciable host cytotoxicity. Likewise, emodin showed a promising anti-T. gondii specificity with a selectivity index (SI) of 276. Pyrimethamine, a standard drug for toxoplasmosis, had an SI of 2.3. The results collectively imply that parasite damage was selective rather than as a result of a broad cytotoxic effect. Furthermore, our data confirm that emodin-induced parasite growth suppression stems from parasite targets and not host targets, and indicate that the anti-parasite action of emodin precludes oxidative stress and ROS production. Emodin likely mediates parasite growth suppression through means other than oxidative stress, ROS production, or mitochondrial toxicity. Collectively, our findings support the potential of emodin as a promising and novel anti-parasitic agent that warrants further investigation.

L-tryptophan-titanium oxide nanoparticles showed selective anti-Toxoplasma gondii activity and improved host biocompatibility.

Toxoplasma gondii, the etiological agent of toxoplasmosis, currently affects nearly one-third of the human population. Treatment options for toxoplasmosis are limited, which underscores the need for new drugs. In the present study, we screened nanoparticles (NPs) of titanium dioxide (TiO2) and molybdenum (Mo) for their potential to inhibit the growth of T. gondii in vitro. NPs of TiO2 and Mo showed non-dose-dependent anti-T. gondii activity with EC50 values of 157.6 and 253 µg/mL, respectively. Previously, we showed that amino acid modification of NPs enhances their selective anti-parasite toxicity. Therefore, to enhance the selective anti-parasitic action of TiO2, we modified the NP surface using alanine, aspartate, arginine, cysteine, glutamate, tryptophan, tyrosine, and bovine serum albumin. The bio-modified TiO2 showed anti-parasite activity with EC50 values ranging from 45.7 to 286.4 µg/mL. At effective anti-parasite concentrations, modified-TiO2 showed no appreciable host cytotoxicity. Of the eight bio-modified TiO2, tryptophan-TiO2 showed the most promising anti-T. gondii specificity and improved host biocompatibility with a selectivity index (SI) of 49.1 versus 7.5 for TiO2 (note, pyrimethamine, a standard drug for toxoplasmosis, has an SI of 2.3). Furthermore, our data indicate that redox modulation may be part of the anti-parasite action of these NPs. Indeed, augmentation with trolox and l-tryptophan reversed the growth restriction caused by the tryptophan-TiO2 NPs. Collectively, these findings suggest that the parasite toxicity was selective and not a result of general cytotoxic action. Furthermore, surface modification with amino acids such as l-tryptophan not only enhanced the anti-parasitic action of TiO2 but also improved the host biocompatibility. Overall, our findings indicate that the nutritional requirements of T. gondii represent a viable target for the development of new and effective anti-T. gondii agents.

Plantain-based diet decreases oxidative stress and inflammatory markers in the testes of rats exposed to atrazine.

Exposure to the herbicide atrazine (ATZ) has deleterious effects on male fertility. This fact underscores the need for measures to protect against the detrimental impact of atrazine exposure on male fertility. The study assessed the protective effects of plantain-based diet (PBD) on rat testes exposed to ATZ by exploring oxid-inflammatory homeostasis. The study evaluated the preventive and therapeutic effects of PBD in a two-phased experiment. Male rats were randomized into seven groups for therapeutic model (Control, ATZ only, ATZ recovery, ATZ + 50% PBD, ATZ + 25% PBD, ATZ + 12.5% PBD and ATZ + quercetin-QUE) while the preventive model had ten groups (Control, ATZ, 50% PBD + ATZ, 25% PBD + ATZ, 12.5% PBD + ATZ and QUE + ATZ). The oxidative stress parameters (DNA fragmentation and MDA level), purinergic activity (ATPase), acetylcholine esterase, and inflammatory markers (NO level, MPO activity, and TNF-α) were increased while the Nrf2 levels were decreased by the ATZ treatment. However, the PBD was able to restore the oxido-inflammatory parameters in the rat testes. The chemical fingerprint of the diet revealed that the diets contained 16 bioactive compounds with quercetin being the most prominent compound. Overall, treatment with PBD was able to protect and prevent the toxicity caused by ATZ by modulating the redox and inflammatory status as well as purinergic activity in the rat testes.

Elucidation of the anti-plasmodial activity of novel imidazole and oxazole compounds through computational and in vivo experimental approaches.

The development of resistance to conventional antimalarial therapies, along with the unfavorable impact of the COVID-19 pandemic on the global malaria fight, necessitates a greater focus on the search for more effective antimalarial drugs. Targeting a specific enzyme of the malaria parasite to alter its metabolic pathways is a reliable technique for finding antimalarial drug candidates. In this study, we used an in silico technique to test four novel imidazoles and an oxazole derivative for inhibitory potential against Plasmodium lactate dehydrogenase (pLDH), a unique glycolytic enzyme necessary for parasite survival and energy production. The promising imidazole compounds and the oxazole derivative were then tested for anti-plasmodial efficacy in Plasmodium berghei-infected mice. With a binding energy of -6.593 kcal/mol, IM-3 had the best docking score against pLDH, which is close to that of NADH (-6.758 kcal/mol) and greater than that of chloroquine (-3.917 kcal/mol). The test compounds occupied the enzyme's NADH binding site, with IM-3 forming four hydrogen bonds with Thr-101, Pro-246, His-195 and Asn-140. Infected mice treatment with IM-3, IM-4 and OX-1 exhibited significantly reduced parasitemia over a four-day treatment period when compared to the infected untreated animals. At 5, 10 and 20 mg/kg, IM-3 demonstrated the highest anti-plasmodial activity, suppressing parasitemia by 86.13, 97.71 and 94.11%, respectively. PCV levels were restored by IM-3 and IM-4, and the three selected compounds reduced the lipid peroxidation induced by P. berghei infection in mice. Thus, these compounds may be considered for further development as antimalarial medicines.Communicated by Ramaswamy H. Sarma.

Molecular docking, pharmacophore modelling, MD simulation and in silico ADMET study reveals bitter cola constituents as potential inhibitors of SARS-CoV-2 main protease and RNA dependent-RNA polymerase.

A mini survey was employed in the search of herbs and spices which people believe could prevent them from contracting COVID-19. Phytochemicals which have been earlier implicated for the bioactivity of the afore-mentioned herbs and spices were identified through literature search. The phytochemicals were then subjected to pharmacore modelling, molecular docking and molecular dynamics simulation in order to identify phytochemicals that could serve as inhibitors of 3-Chymotryprin-like protease and RNA dependent-RNA polymerase of SARS-CoV-2. The drug-likeness and toxicity profile of the phytochemicals were afterwards predicted via ADMET studies. The mini survey showed ginger, garlic, bitter cola, as the lead-herbs which could find application in anti- COVID-19 therapy. Literature search revealed 27 phytochemicals were implicated for bioactivity of these herbs. Of these 27 phytoconstituents that were docked with 3-chymotrypsin-like protease and RNA dependent-RNA polymerase, the constituents of bitter cola had lower docking scores than other phytochemicals. MD simulation results showed that Garcinia biflavonoid I displayed less comformational changes and the better binding free energy. Also, the garcinia biflavonoids had relatively safe ADMET predictions. Hence, Garcinia biflavonoids and some other constituents of bitter cola could be further modified so as to obtain safe pharmaceutical intervention for the COVID-19 challenge.Communicated by Ramaswamy H. Sarma.

Impact of COVID-19 lockdown and health risk modeling of polycyclic aromatic hydrocarbons in Onne, Nigeria.

The people living in Onne are highly vulnerable to PAH exposure due to constant exposure to black soot through oral, dermal, and inhalation routes. This work aims to determine the PAHs profile of selected soils in Onne, to determine the health risks associated with PAHs exposure through the soil, and to determine the impact of reduced industrial and other activities on the PAHs profile and associated public health risks. This study evaluated 16 priority polycyclic aromatic hydrocarbon (PAHs) pollutants in soil samples from the four (4) major clans in Onne using a gas chromatography flame ionization detector (GC-FID) during and after the COVID-19 lockdown. The results showed a differential presence of PAHs during and after the lockdown. Of the 16 priority PAHs, 10 and 8 PAHs were respectively detected during and after the COVID-19 lockdown. High molecular weight PAHs such as benzo(k)fluoranthene and benzo(a)anthracene were major contributors during the lockdown, while low molecular weight PAHs such as naphthalene, acenaphthylene, and fluorene were present at higher levels after the lockdown. An assessment of health risk by incremental lifetime cancer risks revealed that the entire population of Onne might be at risk of cancer development across periods, though a higher risk was presented during the lockdown. In addition, children under the age of 18 may be at greater risk. To the best of our knowledge, there is no previous report on the impact of the COVID-19 lockdown on soil PAH profile and health risks, with particular attention to the Onne industrial host community. Earlier work considered the ecological risks of heavy metals on dumpsites in Onne. Taken together, the PAH-contaminated soil in Onne poses an immediate health concern. Therefore, reduced anthropological activities, as evident during the COVID-19 lockdown, may play a role in exposure and cancer risk reduction. While there may not be another lockdown due to the challenging impacts associated with a physical lockdown, firmly controlled economic activity can be a solution if embraced by stakeholders. The COVID-19-lockdown was encumbered with restricted movements and security checks, which limited the number of samples collected. However, the Local Government Council (Department of the Environment) granted permission for the researchers to work with a minimal threat to their lives.

Chemical fingerprinting, comparative in vitro antioxidant properties, and biochemical effects of ginger and bitterleaf infusion.

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.

Common NLRP3 inflammasome inhibitors and Covid-19: Divide and conquer.

Severe SARS-CoV-2 infection causes systemic inflammation, cytokine storm, and hypercytokinemia due to activation of the release of pro-inflammatory cytokines that have been associated with case-fatality rate. The immune overreaction and cytokine storm in the infection caused by SARS-CoV-2 may be linked to NLRP3 inflammasome activation which has supreme importance in human innate immune response mainly against viral infections. In SARS-CoV-2 infection, NLRP3 inflammasome activation results in the stimulation and synthesis of natural killer cells (NKs), NFκB, and interferon-gamma (INF-γ), while inhibiting IL-33 expression. Various efforts have identified selective inhibitors of NLRP3 inflammasome. To achieve this, studies are exploring the screening of natural compounds and/or repurposing of clinical drugs to identify potential NLRP3 inhibitors. NLRP3 inflammasome inhibitors are expected to suppress exaggerated immune reaction and cytokine storm-induced-organ damage in SARS-CoV-2 infection. Therefore, NLRP3 inflammasome inhibitors could mitigate the immune-overreaction and hypercytokinemia in Covid-19 infection.

Zingiber officinale and Vernonia amygdalina Infusions Improve Redox Status in Rat Brain.

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.

Antidiabetic Activity of Elephant Grass (Cenchrus Purpureus (Schumach.) Morrone) via Activation of PI3K/AkT Signaling Pathway, Oxidative Stress Inhibition, and Apoptosis in Wistar Rats.

Ethnopharmacological Relevance: The management of diabetes over the years has involved the use of herbal plants, which are now attracting interest. We assessed the antidiabetic properties of aqueous extract of C. purpureus shoots (AECPS) and the mechanism of action on pancreatic ß-cell dysfunction. Methods: This study was conducted using Thirty-six 36) male Wistar rats. The animals were divided into six equal groups (n = 6) and treatment was performed over 14 days. To induce diabetes in the rats, a single dose of 65 mg/kg body weight of alloxan was administered intraperitoneal along with 5% glucose. HPLC analysis was carried out to identified potential compounds in the extract. In vitro tests α-amylase, and α-glucosidase were analyzed. Body weight and fasting blood glucose (FBG) were measured. Biochemical parameters, such as serum insulin, liver glycogen, hexokinase, glucose-6-phosphate (G6P), fructose-1,6-bisphosphatase (F-1,6-BP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-ĸB), were analyzed. Additionally, mRNA expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), B-cell lymphoma 2 (Bcl-2), and proliferating cell nuclear antigen (PCNA) were each evaluated. Results: This in vitro study showed inhibitory potency of Cenchrus purpureus extract (AECPS) as compared with the positive controls. AECPS showed a gradual decrease in alloxan-induced increases in FBG, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-c), G6P, F-1,6-BP, malondialdehyde (MDA), IL-6, TNF-α, and NF-ĸB and increased alloxan-induced decreases in liver glycogen, hexokinase, and high density lipoprotein (HDL-c). The diabetic control group exhibited pancreatic dysfunction as evidenced by the reduction in serum insulin, homeostasis model assessment of ß-cell function (HOMA-ß), expressions of PI3K/AKT, Bcl-2, and PCNA combined with an elevation in homeostatic model assessment of insulin resistance (HOMA-IR). High performance liquid chromatography (HPLC) revealed 3-O-rutinoside, ellagic acid, catechin, rutin, and kaempferol in AECPS. Conclusion: AECPS showed efficient ameliorative actions against alloxan-induced pancreatic dysfunction, oxidative stress suppression as well as, inflammation, and apoptosis via the activation of PI3K/AKT signaling pathways.

WITHDRAWN: Common NLRP3 inflammasome inhibitors and Covid-19: Divide and Conquer.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Hypoxia and the Kynurenine Pathway: Implications and Therapeutic Prospects in Alzheimer's Disease.

Neurodegenerative diseases (NDs) like Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease predominantly pose a significant socioeconomic burden. Characterized by progressive neural dysfunction coupled with motor or intellectual impairment, the pathogenesis of ND may result from contributions of certain environmental and molecular factors. One such condition is hypoxia, characterized by reduced organ/tissue exposure to oxygen. Reduced oxygen supply often occurs during the pathogenesis of ND and the aging process. Despite the well-established relationship between these two conditions (i.e., hypoxia and ND), the underlying molecular events or mechanisms connecting hypoxia to ND remain ill-defined. However, the relatedness may stem from the protective or deleterious effects of the transcription factor, hypoxia-inducible factor 1-alpha (HIF-1α). The upregulation of HIF-1α occurs in the pathogenesis of most NDs. The dual function of HIF-1α in acting as a "killer factor" or a "protective factor" depends on the prevailing local cellular condition. The kynurenine pathway is a metabolic pathway involved in the oxidative breakdown of tryptophan. It is essential in neurotransmission and immune function and, like hypoxia, associated with ND. Thus, a good understanding of factors, including hypoxia (i.e., the biochemical implication of HIF-1α) and kynurenine pathway activation in NDs, focusing on Alzheimer's disease could prove beneficial to new therapeutic approaches for this disease, thus the aim of this review.

The anti-parasite action of imidazole derivatives likely involves oxidative stress but not HIF-1α signaling.

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.