Antioxidant and inflammatory-modulating properties of ginger and bitterleaf teas.

The present study evaluated the effects of ginger and bitterleaf tea infusions on redox and inflammatory balance in rats. Twenty-four Wistar rats with weights of between 160 and 180 g were assigned into four (4) groups (n = 6). The control group received distilled water, while the remaining groups were administered tea infusions of ginger, bitterleaf, or a combination of both at 5 mg/mL, respectively. Bitterleaf and ginger teas elevated the levels of superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione in rat plasma and liver, while malondialdehyde levels decreased. Furthermore, ginger tea caused an increase in the expression of nuclear factor erythroid-2-related factor 2 (Nrf-2) and reduced tumor necrosis factor alpha (TNF-α). The GC-MS analysis of the teas identified 77 chemical compounds, among which gingerol and precocene I were predominant. Collectively, the findings indicate, in particular, that ginger tea may boost antioxidant and anti-inflammatory capacity by increasing Nrf-2 levels.

Comparison of the risk of hospital admission, need for ventilation, sepsis, pneumonitis and death among the recent monkeypox outbreak and historical outbreaks.

BACKGROUND: The course of monkeypox can be severe. Our aim was to retrospectively compare the risk of hospital admission, the need for ventilation, sepsis, pneumonitis and death between the recent outbreak and historical outbreaks. MATERIALS AND METHODS: Cases of monkeypox were retrieved from the TriNetX database and assigned to either cohort I (recent outbreak between May 1st and September 16th, 2022) and cohort II (historical outbreaks before May 1st, 2022). After matching for age distribution, statistical analysis was performed. RESULTS: Of 640 patients with monkeypox 81 subjects per cohort remained after matching (mean age±standard deviation = 36.1±18.3 years). Within 56 days after diagnosis 10 patients per cohort were hospitalized (12.4%) and/or developed sepsis (12.4%). The risk of ventilation and pneumonitis were significantly lower among cohort I compared with cohort II (0 vs. 10 cases; risk difference = 12.4%; p = 0.001; Log-Rank test). No cases of death were recorded. CONCLUSION: Even though monkeypox provides a risk of severe courses, the infection is self-limiting in most cases. Unlike past outbreaks, the risk of ventilation and pneumonitis may be relatively low among recent outbreaks.

Dietary supplementation of Allium cepa skin alters intramuscular fat, muscle cholesterol, and fatty acids in rabbits.

BACKGROUND: The high polyunsaturated fatty acids content of rabbit meat predisposes it to oxidative deterioration, which often results in reduced product quality and shelf life. This fact highlights the need to improve the antioxidant status of rabbit meat. This study investigated the effects of dietary supplementation of Allium cepa skin (ACS) on growth, carcass, intramuscular fat, muscle fatty acids, cholesterol content, meat quality, antioxidant status, and sensory attributes of hind leg muscle of rabbits. Sixty-three, 28-day-old, male New Zealand rabbits (654 ± 25 g) were randomly allocated into 21 pens of three rabbits. The pens were randomly assigned to one of three dietary treatments - ACS-0: basal diet (BD) only; ACS-25: BD + 25 g kg-1 ACS; and ACS-50: BD + 50 g kg-1 ACS - for 56 days and then euthanized. RESULTS: Dietary ACS did not affect growth performance and retail cuts of rabbits. Muscle cholesterol was lower (P < 0.05) in ACS-supplemented rabbits than in controls. Dietary ACS lowered (P < 0.05) dissectible fat, intramuscular fat content, C14:0, C16:0, C18:0, C18:2n-6, and C20:4n-6 levels and enhanced (P < 0.05) C18:3n-3, C20:5n-3, C22:6n-3, and C22:5n-3 concentration. Dietary ACS increased muscle catalase activity in rabbits. Sensory qualities, malondialdehyde and carbonyl contents, and physicochemical attributes of hind leg muscle of rabbits after chill storage were not influenced by dietary ACS supplementation. CONCLUSION: Supplementation with 50 g kg-1 ACS reduced intramuscular fat and cholesterol content and improved muscle n-3 fatty acids without impairing the physicochemical and sensory properties of rabbit meat. © 2021 Society of Chemical Industry.

L-leucine stimulation of glucose uptake and utilization involves modulation of glucose - lipid metabolic switch and improved bioenergetic homeostasis in isolated rat psoas muscle ex vivo.

The antidiabetic effect of l-leucine has been attributed to its modulatory effect on glucose uptake and lipid metabolism in muscles. However, there is a dearth on its effect on glucose metabolism in muscles. Thus, the present study investigated the effect of l-leucine - stimulated glucose uptake on glucose metabolism, dysregulated lipid metabolic pathways, redox and bioenergetic homeostasis, and proteolysis in isolated psoas muscle from Sprague Dawley male rats. Isolated psoas muscles were incubated with l-leucine (30-240 µg/mL) in the presence of 11.1 mMol glucose at 37 ˚C for 2 h. Muscles incubated in only glucose served as the control, while muscles not incubated in l-leucine and/or glucose served as the normal control. Metformin (6.04 mM) was used as the standard antidiabetic drug. Incubation with l-leucine caused a significant increase in muscle glucose uptake, with an elevation of glutathione levels, superoxide dismutase, catalase, E-NTPDase and 5'nucleotidase activities. It also led to the depletion of malondialdehyde and nitric oxide levels, ATPase, chymotrypsin, acetylcholinesterase, glycogen phosphorylase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and lipase activities. There was an alteration in lipid metabolites, with concomitant activation of glycerolipid metabolism, fatty acid metabolism, and fatty acid elongation in mitochondria in the glucose-incubated muscle (negative control). Incubation with l-leucine reversed these alterations, and concomitantly deactivated the pathways. These results indicate that l-leucine-enhanced muscle glucose uptake involves improved redox and bioenergetic homeostasis, with concomitant suppressed proteolytic, glycogenolytic and gluconeogenetic activities, while modulating glucose - lipid metabolic switch.

Oxidative testicular injury: effect of L-leucine on redox, cholinergic and purinergic dysfunctions, and dysregulated metabolic pathways.

The antioxidant and anti-proinflammatory activities of L-leucine were investigated on oxidative testicular injury, ex vivo. In vitro analysis revealed L-leucine to be a potent scavenger of free radicals, while inhibiting acetylcholinesterase activity. Oxidative injury was induced in testicular tissues using FeSO4. Treatment with L-leucine led to depletion of oxidative-induced elevated levels of NO, MDA, and myeloperoxidase activity, with concomitant elevation of reduced glutathione and non-protein thiol levels, SOD and catalase activities. L-leucine caused a significant (p < 0.05) alteration of oxidative-elevated acetylcholinesterase and chymotrypsin activities, while concomitantly elevating the activities of ATPase, ENTPDase and 5'-nucleotidase. L-leucine conferred a protective effect against oxidative induced DNA damage. Molecular docking revealed molecular interactions with COX-2, IL-1 beta and iNOS. Treatment with L-leucine led to restoration of oxidative depleted ascorbic acid-2-sulfate, with concomitant depletion of the oxidative induced metabolites: D-4-Hydroxy-2-oxoglutarate, L-cystine, adenosine triphosphate, maleylacetoacetic acid, cholesteryl ester, and 6-Hydroxy flavin adenine dinucleotide. Treatment with L-leucine reactivated glycolysis while concomitantly deactivating oxidative-induced citrate cycle and increasing the impact-fold of purine metabolism pathway. L-leucine was predicted not to be an inhibitor of CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4, with a predicted LD50 value of 5000 mg/Kg and toxicity class of 5. Additionally, L-leucine showed little or no in vitro cytotoxicity in mammalian cells. These results suggest the therapeutic potentials of L-leucine on oxidative testicular injury, as evident by its ability to attenuate oxidative stress and proinflammation, while stalling cholinergic dysfunction and modulating nucleotide hyrolysis; as well as modulate oxidative dysregulated metabolites and their pathways.

New Series of Imidazoles Showed Promising Growth Inhibitory and Curative Potential Against Trypanosoma Infection.

The Trypanosoma spp. cause animal and human trypanosomiasis characterized with appreciable health and economic burden mostly in developing nations. There is currently no effective therapy for this parasitic disease, due to poor drug efficacy, drug resistance, and unwanted toxicity, etc. Therefore, new anti-Trypanosoma agents are urgently needed. This study explored new series of imidazoles for anti-Trypanosoma properties in vitro and in vivo. The imidazoles showed moderate to strong and specific action against growth of T. congolense. For example, the efficacy of the imidazole compounds to restrict Trypanosoma growth in vitro was ≥ 12-fold specific towards T. congolense relative to the mammalian cells. Additionally, the in vivo study revealed that the imidazoles exhibited promising anti-Trypanosoma efficacy corroborating the in vitro anti-parasite capacity. In particular, three imidazole compounds (C1, C6, and C8) not only cleared the systemic parasite burden but cured infected rats after no death was recorded. On the other hand, the remaining five imidazole compounds (C2, C3, C4, C5, and C7) drastically reduced the systemic parasite load while extending survival time of the infected rats by 14 days as compared with control. Untreated control died 3 days post-infection, while the rats treated with diminazene aceturate were cured comparable to the results obtained for C1, C6, and C8. In conclusion, this is the first study demonstrating the potential of these new series of imidazoles to clear the systemic parasite burden in infected rats. Furthermore, a high selectivity index of imidazoles towards T. congolensein vitro and the oral LD50 in rats support anti-parasite specific action. Together, findings support the anti-parasitic prospects of the new series of imidazole derivatives.

Imidazole derivatives as antiparasitic agents and use of molecular modeling to investigate the structure-activity relationship.

Toxoplasmosis is a common parasitic disease caused by Toxoplasma gondii. Limitations of available treatments motivate the search for better therapies for toxoplasmosis. In this study, we synthesized a series of new imidazole derivatives: bis-imidazoles (compounds 1-8), phenyl-substituted 1H-imidazoles (compounds 9-19), and thiopene-imidazoles (compounds 20-26). All these compounds were assessed for in vitro potential to restrict the growth of T. gondii. To explore the structure-activity relationships, molecular analyses and bioactivity prediction studies were performed using a standard molecular model. The in vitro results, in combination with the predictive model, revealed that the imidazole derivatives have excellent selectivity activity against T. gondii versus the host cells. Of the 26 compounds screened, five imidazole derivatives (compounds 10, 11, 18, 20, and 21) shared a specific structural moiety and exhibited significantly high selectivity (> 1176 to > 27,666) towards the parasite versus the host cells. These imidazole derivatives are potential candidates for further studies. We show evidence that supports the antiparasitic action of the imidazole derivatives. The findings are promising in that they reinforce the prospects of imidazole derivatives as alternative and effective antiparasitic therapy as well as providing evidence for a probable biological mechanism.

In Vitro Screening to Identify Anti-Toxoplasma Compounds and In Silico Modeling for Bioactivities and Toxicity.

Toxoplasmosis, which affects more than a billion people worldwide, is a common parasitic infection caused by the obligate intracellular parasite, Toxoplasmagondii. Current treatment strategies have several limitations, including unwanted side effects and poor efficacy. Therefore, newer therapies are needed for toxoplasmosis. Drug repurposing and screening of a vast array of natural and/or synthetic compounds is a viable option for antiparasitic drug discovery. In this study, we screened 62 compounds comprising natural products (NPs) and FDA-approved (FDA) drugs, to identify the hit compounds that suppress the growth of T. gondii. To determine the parasite inhibitory potential of the compounds, host mammalian cells were infected with a transgenic T. gondii strain, and the viability of the parasite was evaluated by luminescence. Of the 62 compounds, tubericidin, sulfuretin, peruvoside, resveratrol, narasin and diacetoxyscirpenol of the natural product isolates, as well as bortezonib, 10-Hydroxycamtothecin, mebendazole, niflumic acid, clindamycin HCl, mecamylamine, chloroquine, mitomycin C, fenbendazole, daunorubicin, atropine, and cerivastatin of FDA molecules were identified as "hits" with ≥ 40 percent anti-parasite action. Additionally, mitomycin C, radicicol, naringenin, gitoxigenin, menadione, botulin, genistin, homobutein, and gelsemin HCl of the natural product isolates, as well as lomofungin, cyclocytidine, prazosin HCl, cerivastatin, camptothecin, flufenamic acid, atropine, daunorubicin, and fenbendazole of the FDA compounds exhibited cytotoxic activity, reducing the host viability by ≥ 30 percent. Our findings not only support the prospects of drug repurposing, but also indicate that screening a vast array of molecules may provide viable sources of alternative therapies for parasitic infection.

Anti-apoptotic and antioxidant mechanisms may underlie the abrogative potential of Ocimum gratissimum Linn. Leaf extract and fractions against trastuzumab-induced cardiotoxicity in Wistar rats.

Clinical use of trastuzumab (TZM), has been widely associated with increased incidence of cardiotoxicity. Ocimum gratissimum Linn. is a household medicinal plant popularly used for treating inflammatory conditions. In this study, we investigated the abrogative potential of 100 mg/kg/day of the ethanol leaf extract of Ocimum gratissimum Linn. (OG) and its petroleum ether (PEOG), ethyl acetate (EAOG) and ethanol (EOG) fractions in TZM intoxicated Wistar rats for 7 days using anthropometric, biochemical, histopathological and immunohistochemical endpoints. In addition, secondary metabolite constituents in OG and its fractions were determined through Gas Chromatography-Mass Spectrometry (GC-MS). The study results showed that oral pretreatments with OG and OG fractions as well as the fixed dose valsartan-lisinopril (VAL-LSP) combination effectively ameliorated and restore nearly normal levels the TZM-altered plasma cardiac troponin I and antioxidant profile which were corroborated by histopathological and immunohistochemical findings as indicated by the inhibition of TZM-induced activation of caspases-3 and - 9 and profound upregulation of BCL-2 expression. Phytoscan of OG and its fractions showed the presence of thymol and in high amount. Overall, our findings revealed the cardioprotective potentials of OG, OG fractions and fixed dose VAL-LSP combination against TZM-induced cardiotoxicity which probably was mediated via abrogation of cardiomyocyte apoptosis and antioxidant mechanisms.

Isolation, characterization and anti-inflammatory activity of compounds from the Vernonia amygdalina.

The need to explore the abundance of natural products cannot be overemphasized particularly in the management of various disease conditions. In traditional medical practice, Vernonia amygdalina has been widely adopted in the management of various inflammatory disorders. The objective of this investigation was to isolate the bioactive principles from the stem-bark and root of V. amygdalina and assess the anti-inflammatory (in vitro) activity of both the crude extracts and the isolated compounds. Following extraction with the methanol, the extract was subjected to gravity column chromatography and the resultant fractions was further purified to obtained pure compounds. The structural elucidation of the compounds were based on data obtained from 1H to 13C nuclear magnetic resonance (NMR) spectroscopies as well as fourier transform infrared (FT-IR). Using diclofenac as a control drug, the albumin denaturation assay was used to determine the in vitro anti-inflammatory activity of the extracts and isolates. Three distinct compounds characterized are vernoamyoside D, luteolin-7-α-o-glucuronide, and vernotolaside, a new glycoside. When compared to diclofenac, which has an IC50 of 167.8 µg/mL, luteolin-7-α-o-glucuronide, vernoamyoside D, and vernotolaside all showed significant inhibitions with respective IC50 values 549.8, 379.5, and 201.7 µg/mL. Vernotolaside is reported for the first time from the root. The assertion that the plant is used in traditional medicine for the management of inflammatory disorder is somewhat validated by the confirmation of the existence of the compounds with the biochemical actions. Further validation of the isolated compounds would be required in animal studies.

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.

Dietary Plukenetia conophora seed alters muscle cholesterol, antioxidant enzymes, and fatty acids in growing rabbits.

The influence of dietary inclusion of Plukenetia conophora seed (PCS) on growth, carcass, muscle antioxidant enzymes, fatty acids, meat quality, and sensory attributes of Longissimus thoracis et lumburum muscle in rabbits was examined. Seventy-two, 28 d old male New Zealand rabbits (750 ± 20 g) were randomly allotted to diets containing either no PCS (PCS-0), 2.5% PCS (PCS-2.5) or 5% PCS (PCS-5) for eight weeks, and euthanized. PCS-5 rabbits had higher (P < 0.05) body and carcass weights than the PCS-0 rabbits. Dietary PCS improved feed efficiency in rabbits. Muscle antioxidant enzymes activities and total phenols were higher while muscle cholesterol was lower (P < 0.05) in supplemented meat than the PCS-0 meat. The concentration of C22:6n-3, C20:5n-3 and C18:3n-3 was higher (P < 0.05) in the supplemented meat than the PCS-0 meat. Sensory attributes, carbonyl, and TBARS values and physicochemical properties of meat did not differ among diets. Supplementation of PCS-5 enhances muscle n-3 fatty acids without impairing the sensory properties, and oxidative stability of rabbit meat.

Canarimoic acid: new tirucallane triterpene with antisalmonellal activity from the stem bark of Canarium schweinfurthii Engl.

One new tirucallane triterpene named as canarimoic acid (1), and three known analogues: 3ß-hydroxytirucalla-8,24-dien-21-oic acid (2), 3α-acetyltirucalla-8,24-diene-21oic acid (3) and 3-oxotirucalla-8,24-dien-21-oic (4) were isolated from the hydro-ethanolic crude extract of Canarium schweinfurthii. Their structures were established by extensive analysis of 1 D and 2 D NMR data in conjunction with mass spectrometry and by comparison with those reported in the literature. The evaluation of their antisalmonellal activity using broth microdilution method showed that compound 3 was the most active (MIC =16 µg/mL) against Salmonella Typhi and Salmonella Typhimurium followed by compound 1 (MIC= 32 µg/mL) against Salmonella Typhi and Salmonella Enteritidis.

Targeting the initiation and termination codons of SARS-CoV-2 spike protein as possible therapy against COVID-19: the role of novel harpagide 5-O-ß-D-glucopyranoside from Clerodendrum volubile P Beauv. (Labiatae).

The global spread of the coronavirus infections disease - 2019 (COVID-19) and the search for new drugs from natural products particularly from plants are receiving much attention recently. In this study, the therapeutic potential of a new iridoid glycoside isolated from the leaves of Clerodendrum volubile against COVID-19 was investigated. Harpagide 5-O-ß-D-glucopyranoside (HG) was isolated, characterised and investigated for its druglikeness, optimized geometry, and pharmacokinetics properties. Its immunomodulatory was determined by chemiluminescence assay using polymorphonuclear neutrophils (PMNs) in addition to T-cell proliferation assay. In silico analysis was used in determining its molecular interaction with severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). HG displayed potent druglikeness properties, with no inhibitory effect on cytochrome P450 (1A2, 2C19, 2C9, 2D6 and 3A4) and a predicted LD50 of 2000 mg/kg. Its 1H-NMR chemical shifts showed a little deviation of 0.01 and 0.11 ppm for H-4 and H-9, respectively. HG significantly suppressed oxidative bursts in PMNs, while concomitantly inhibiting T-cell proliferation. It also displayed a very strong binding affinity with the translation initiation and termination sequence sites of spike (S) protein mRNA of SARS-COV-2, its gene product, and host ACE2 receptor. These results suggest the immunomodulatory properties and anti-SARS-COV-2 potentials of HG which can be explored in the treatment and management of COVID-19.Communicated by Ramaswamy H. Sarma.

Underutilized legumes, Cajanus cajan and Glycine max may bring about antisickling effect in sickle cell disease by modulation of redox homeostasis in sickled erythrocytes and alteration of its functional chemistry.

The antisickling and anti-oxidative effect of the Cajanus cajan, Glycine max, and their blends were investigated in sickled erythrocytes. The powdered samples were analyzed for their nutritional and anti-nutritional constituents. Their aqueous extracts were analyzed for in vitro antioxidant activities. The extracts were incubated with sickled erythrocytes at 37°C for 6 hours and the antisickling effect examined via microscopic analysis. The blend was the most active and its incubated cells were subjected to anti-oxidative analysis which covers for GSH, SOD, catalase, and lipid peroxidation (LPO). Chemical functional group of the treated cells was analyzed with FTIR spectroscopy. The in silico binding of the predominant amino acid to hemoglobin was also investigated. An increased concentration of leucine was observed in the blend compared to that of C. cajan and G. max, respectively. Vitamins C, B6, and B9 were the only vitamins observed in the blend. Phytate and oxalate were present in all samples. All extracts displayed significant (p < .05) scavenging activities. Treatment with the blend exacerbated SOD and catalase activities as well as the GSH level, while suppressing LPO. FTIR analysis of the treated cells showed the presence of hydrophobic functional groups. Leucine was the predominant amino acid, and it showed a potent molecular interaction with HIS-87 residue of the alpha chain of 1HCO. C. cajan and G. max blend inhibited sickling activities of sickle erythrocytes, while concomitantly exacerbating their endogenous antioxidant enzymes activity and modification of the functional chemistry. PRACTICAL APPLICATIONS: Cajanus cajan and Glycine max are among the common underutilized legumes in Nigeria. Aside their nutritional properties, these legumes have been used from time immemorial for the treatment and management of various ailments. Sickle cell anemia is a class of hemoglobinopathy common in Sub-Saharan Africa. There have been concerns about its treatment owing to the increasing scourge of the disease coupled to the financial burden of its management. This study reports the ability of the potentials of the legumes to prevent sickling activities of sickled erythrocytes and the possible biochemical mechanism involved.

Nanoparticles as antimicrobial and antiviral agents: A literature-based perspective study.

The scientific explorations of nanoparticles for their inherent therapeutic potencies as antimicrobial and antiviral agents due to increasing incidences of antibiotic resistance have gained more attention in recent time. This factor amongst others necessitates the search for newer and more effective antimicrobial agents. Several investigations have demonstrated the prospects of nanoparticles in the treatment of various microbial infections. The therapeutic applications of nanoparticles as either delivery agent or broad spectrum inhibition agents in viral and microbial investigations can no longer be overlooked. Their large surface area to volume ratio made them an indispensable substance as delivery agents in many respect. Various materials have been used for the synthesis of nanoparticles with unique properties channelised to meet specific therapeutic requirement. This review focuses on the antibacterial, antifungal, and antiviral potential of nanoparticles with their probable mechanism of action.

In pursuit of new anti-malarial candidates: novel synthesized and characterized pyrano-benzodioxepin analogues attenuated Plasmodium berghei replication in malaria-infected mice.

Malaria, a parasitic disease, is one of the major causes of morbidity and mortality, particularly in the tropics. Following the increased resistance of the primary causative parasite, Plasmodium sp, to the mainstream drug, artemisinin combination therapies (ACTs), combating malaria incidences, morbidity and mortality have remained elusive. Novel pyrano-benzodioxepin derivatives (DHA-PABA and DHA-LEVO) were synthesized and characterized using Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopies. The compounds were subjected to standard in vivo antimalarial screening (using chloroquine-sensitive strain) in mice, and the toxicity was also determined using a standard assay. The observed elevation in serum alkaline phosphatase and acid phosphatase activity in the untreated and the group administered lower doses of DHA-LEVO is an indication of the hepatic stage of the parasite in the experimental animal, which is accompanied by significant perturbation in the membrane of the hepatocyte leading to leakage of this enzyme out of the liver cells. The semisynthetic pyrano-benzodioxepin derivatives act rapidly by clearing the parasite load from the blood. The novel pyrano-benzodioxepin candidates containing endoperoxide functionality hold promise in the pursuit of new monotherapy drug candidates against the virulent strain of the plasmodium.

Translational suppression of SARS-COV-2 ORF8 protein mRNA as a Viable therapeutic target against COVID-19: Computational studies on potential roles of isolated compounds from Clerodendrum volubile leaves.

The open reading frame 8 (ORF8) protein of SARS-CoV-2 has been implicated in the onset of cytokine storms, which are responsible for the pathophysiology of COVID-19 infection. The present study investigated the potential of isolated compounds from Clerodendrum volubile leaves to stall oxidative bursts in vitro and interact with ORF8 mRNA segments of the SARS-CoV-2 whole genome using computational tools. Five compounds, namely, harpagide, 1-(3-methyl-2-butenoxy)-4-(1-propenyl)benzene, ajugoside, iridoid glycoside and erucic acid, were isolated from C. volubile leaves, and their structures were elucidated using conventional spectroscopy tools. Iridoid glycoside is being reported for the first time and is thus regarded as a new compound. The ORF8 mRNA sequences of the translation initiation sites (TIS) and translation termination sites (TTSs) encoding ORF8 amino acids were retrieved from the full genome of SARS-CoV-2. Molecular docking studies revealed strong molecular interactions of the isolated compounds with the TIS and TTS of ORF8 mRNA. Harpagide showed the strongest binding affinity for TIS, while erucic acid was the strongest for TTS. The immunomodulatory potentials of the isolated compounds were investigated on neutrophil phagocytic respiratory bursts using luminol-amplified chemiluminescence technique. The compounds significantly inhibited oxidative burst, with 1-(3-methyl-2-butenoxy)-4-(1-propenyl)benzene having the best activity. Ajugoside and erucic acid showed significant inhibitory activity on T-cell proliferation. These results indicate the potential of C. volubile compounds as immunomodulators and can be utilized to curb cytokine storms implicated in COVID-19 infection. These potentials are further corroborated by the strong interactions of the compounds with the TIS and TTS of ORF8 mRNA from the SARS-CoV-2 whole genome.

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.

Quercetin and/or Ascorbic Acid Modulatory Effect on Phenobarbital-Induced Sleeping Mice Possibly through GABAA and GABAB Receptor Interaction Pathway.

Depressive disorder is a recurrent illness that affects large numbers of the general population worldwide. In recent years, the goal of depression treatment has moved from symptomatic response to that of full remission. However, treatment-resistant depression is a major challenge in the treatment of depression or depression-related disorders. Consensus opinion, therefore, suggests that effective combined aggressive initial treatment is the most appropriate strategy. This study aimed to evaluate the effects of quercetin (QUR) and/or ascorbic acid (AA) on Phenobarbital-induced sleeping mice. QUR (50 mg/kg) and/or AA (25 mg/kg) with or without intraperitoneally pre-treated with GABA receptor agonist (diazepam: 2 mg/kg, i.p.) or antagonist (Flumazenil: 2.5 mg/kg, i.p.) to underscore the effects, as well as the possible involvement of the GABA receptor in the modulatory action of QUR and AA in sleeping mice. Additionally, an in silico study was undertaken to predict the involvement of GABA receptors in the sleep mechanism. Findings suggest that the pretreatment of QUR and AA modulated the onset and duration of action of the standard drugs in experimental animals. The acute administration of QUR and/or AA significantly (p < 0.05) reversed the DZP-mediated onset of action and slightly reversed the duration of sleep time in comparison to the vehicle (control) group. A further combination of QUR or AA with the FLU resulted in an enhancement of the onset of action while reducing the duration of action, suggesting a FLU-like effect on the test animals. In in silico studies, AA and QUR showed good to moderate binding affinities with GABAA and GABAB receptors. Both QUR and AA produced a stimulatory-like effect on mice, possibly through the GABAA and GABAB receptor interaction pathways. Further studies are necessary to verify this activity and clarify the exact mechanism of action(s) involved.