Genetic and epigenetic modulations in toxicity: The two-sided roles of heavy metals and polycyclic aromatic hydrocarbons from the environment.

This study emphasizes the importance of considering the metabolic and toxicity mechanisms of environmental concern chemicals in real-life exposure scenarios. Furthermore, environmental chemicals may require metabolic activation to become toxic, and competition for binding sites on receptors can affect the severity of toxicity. The multicomplex process of chemical toxicity is reflected in the activation of multiple pathways during toxicity of which AhR activation is major. Real-life exposure to a mixture of concern chemicals is common, and the composition of these chemicals determines the severity of toxicity. Nutritional essential elements can mitigate the toxicity of toxic heavy metals, while the types and ratio of composition of PAH can either increase or decrease toxicity. The epigenetic mechanisms of heavy metals and PAH toxicity involves either down-regulation or up-regulation of some non-coding RNAs (ncRNAs) whereas specific small RNAs (sRNAs) may have dual role depending on the tissue and circumstance of expression. Similarly, decrease DNA methylation and histone modification are major players in heavy metals and PAH mediated toxicity and FLT1 hypermethylation is a major process in PAH induced carcinogenesis. Overall, this review provides the understanding of the metabolism of environmental concern chemicals, emphasizing the importance of considering mixed compositions and real-life exposure scenarios in assessing their potential effects on human health and diseases development as well as the dual mechanism of toxicity via genetic or epigenetic axis.

Low Dose of Nickel and Benzo [a] Anthracene in Rat-Diet, Induce Apoptosis, Fibrosis, and Initiate Carcinogenesis in Liver via NF-Æ˜ß Pathway.

Environmental contaminants such as polycyclic aromatic hydrocarbon (PAH) and heavy metals are major contaminants of food such as fish thus serving as source of exposure to human. This study was designed to evaluate the carcinogenic risk and other risks associated with long-term consumption of environmentally relevant dose of nickel and benzo [a] anthracene in rats. Thirty-six (36) male rats weighing between 80 and 100 g were assigned into 6 groups of 6 animals each; normal, nickel-, and benzo [a] anthracene-exposed groups for 12 and 24 weeks, respectively. Micronucleus and comet analyses were done in the blood, liver, and bone marrow. Liver function, redox, and inflammatory markers (AST, ALT, GGT, SOD, GSH, MDA, protein carbonyl, protein thiol, total protein, IL-10, 1L-1ß, TNF-α, TGF-ß NF-Ƙß, and 8-oxodeoxyguansine) were analysed by standard methods. Immuno-histochemical quantification of Bax, Bcl2, and Erk 1/2 as well as mRNA expression of cyclin D1 was done in liver. From the results, weight gain was observed in varying degrees throughout the exposure period. The polychromatic erythrocytes/normochromatic erythrocytes ratio > 0.2 indicates no cytotoxic effects on the bone marrow. Percentage-MnPCE in blood significantly (p < 0.05) increased throughout exposure duration. Percentage tail DNA in blood was significantly (< 0.05) increased at weeks 20 and 24 in the exposed groups and in liver at weeks 12 (16.22 ± 0.47) and 24 (17.00 ± 0.36) of nickel-exposed rats. The aspartate amino transferase (AST):alanine amino transferase (ALT) ratio indicated fatty liver disease in the benzo [a] anthracene (0.90) and acute liver injury in the nickel (> 10 times greater than the upper limits of the reference group) exposed groups during the first 12 weeks. Observation from the histological and cytological data of the liver revealed the presence of inflammation, fibrosis, and high nuclear/cytoplasmic ratio, respectively, in the nickel and benzo [a] anthracene groups. Only benzo [a] anthracene induced liver oxidative stress with significant (p < 0.05) decrease in SOD (0.64 ± 0.02) activity and increase in protein carbonyl (7.60 ± 0.80 × 10-5) and MDA (57.10 ± 6.64) concentration after 24 weeks. Benzo [a] anthracene up-regulated the cyclin D1 expression and significantly (p < 0.05) increased the levels of the cytokines. Nickel and benzo [a] anthracene significantly (p < 0.05) increased the Bax (183.45 ± 6.50 and 199.76 ± 10.04) and Erk 1/2 (108.25 ± 6.41 and 136.74 ± 4.22) levels when compared with the control (37.43 ± 22.22 and 60.37 ± 17.86), respectively. Overall result showed that the toxic effects of nickel and benzo [a] anthracene might involve fibrosis, cirrhosis, apoptosis, and inflammation of the liver. As clearly demonstrated in this study, benzo [a] anthracene after the 24 weeks of exposure stimulates carcinogenic process by suppressing the liver antioxidant capacity, altering apoptotic, cell proliferation, and differentiation pathways.

Evaluation of long-term effects of nickel and benzo [a] anthracene contaminated diets in rats' kidney; mimicking human exposure from food.

OBJECTIVES: Accumulative effects of heavy metals and polycyclic aromatic hydrocarbon could result in various toxicities. This study evaluated the effects of long-term exposure to low doses of nickel and benzo [a] anthracene on the kidney of rats, simulating human exposure through food. METHODS: Thirty-six (36) Male rats weighing between 80-100 g were assigned into six groups of 6 animals each; Group A (normal), Group B1 and B2 (fed nickel contaminated feed for 12 and 24 weeks), Group C1 and C2 (fed benzo [a] anthracene contaminated feed for 12 and 24 weeks). Blood and kidney of the rats were harvested after animal sacrifice. Serum creatinine and urea concentration and renal Superoxide Dismutase (SOD) activity, GSH, MDA, protein carbonyl, and total protein concentration by spectrophotometric methods. While the concentration of 8-oxodeoxyguanosine in kidney was determined by ELISA method and protein carbonyl by colorimetric method. Renal histological analysis was done with H and E staining. Statistical analysis was performed with Statistical Package for Social Sciences (SPSS) and statistical significance was accepted 95 percent confidence level. RESULT: From the results, urea concentration increased significantly (P<0.05) in the nickel exposed group after 24 weeks exposure whereas creatinine concentration increased significantly (P<0.05) after 12 weeks of exposure when compared with the control. Comparison of the serum urea and creatinine level of the benzo [a] anthracene exposed group with the control showed no significant (P>0.05) difference. Histological observations indicate glomerular atrophy and widened capsular space haemorrhagic areas, visceral and parietal layer of the Bowman's capsule, the proximal convoluted tubule in the nickel exposed group while the kidney of benzo (a) anthracene exposed rats showed deviation in the histo-architecture of the renal parenchyma as evidenced by glomerular atrophy and widened Bowman's capsular space and focal haemorrhagic areas. Protein thiol level and Superoxide dismutase activity was significantly (P<0.05) depleted in the benzo [a] anthracene exposed groups. The levels of total protein, protein carbonyl, and 8-oxodeoxyguanosine were significantly (P<0.05) elevated in the nickel and benzo [a] anthracene exposed groups. CONCLUSION: This study demonstrated the oxidative stress causing effects of benzo [a] anthracene and nickel in the kidney. It also shows that consistent exposure to low doses of the contaminants for a lifetime might result in renal oxidative stress with consequential loss of renal function.

Ginger mitigated the health risks associated with arsenic-contamination of rats feed via inflammatory and apoptosis regulation.

Millions of people around the world are inadvertently exposed to arsenic through drinking water and food. However, food spices possess antioxidants and anti-inflammatory potentials. Therefore, this study evaluated the protective potentials of Zingiber officinale (ginger) against the toxic effects of arsenic in male Wistar rats. Thirty-six Wistar rats were assigned into 6 groups (n = 6); group A1 and A2 (control), group B1 and B2 were fed with arsenic-contaminated feed (3.45x10-3 mg/kg), group C1 and C2 were feed with arsenic-contaminated feed (3.45x10-3 mg) supplemented with ginger respectively for 12 and 24 weeks. The blood, bone marrow, and liver of rats were harvested and prepared for various analyses. Micronucleus and Comet analysis were performed for the genotoxicity assessment every 4 weeks. Activities of AST, ALT, GGT, and SOD, and the concentration of GSH, MDA, protein carbonyl, protein thiol, and total protein, were measured by spectrophotometric methods. Quantification of IL-10, 1 L-1ß, TNF-α, TGF-ß NF-Ƙß, and 8-oxodeoxyguanosine was done by ELISA method while Bax, Bcl2, and Erk 1/2 were quantified by immuno-histochemical staining. mRNA expression of cyclin D1 was quantified using qRT-PCR. Statistical analysis was performed with SPSS and statistical significance was accepted when p<0.05. Result showed significant (p<0.05) decrease in the haemoglobin concentration, red blood cell, lymphocyte counts, tail DNA and MnPCE of rats fed arsenic-contaminated feed compared with control. The supplementation with ginger significantly reduced serum activities of AST and GGT (p<0.05). Ginger supplementation also lowered the arsenic indued increases in liver MDA, protein carbonyl and 8-OXdG levels. Ginger restores to near normal the histological changes due to arsenic exposure. In the arsenic-exposed group, liver IL-10, IL-1ß and TNF-α decreased significantly (p<0.05) at week 24 whereas, NF-Æ˜ß and TGF-ß increased significantly (p 0.05) at weeks 12 and 24 and TNF-α, Bcl2 at week 24. mRNA expression of cyclin D1 was significantly (p<0.05) downregulated in the arsenic and ginger-supplemented groups. This study showed that long-term consumption of arsenic resulted in immunosuppression, anaemia and activated anti-apoptotic process that was mitigated due to ginger supplementation.

Heavy metal concentrations in four fish species from the Lagos lagoon and their human health implications.

Background: Lagos lagoon is constantly being polluted from industrial and human activities. Fishes from Lagos lagoon contribute significant percentages of fish consumption in the Lagos metropolises. Therefore, this study evaluated heavy metal concentrations in tissues of four fish species (Sarotherodon melanotheron, Chrysichthys nigrodigitatus, C. gariepinus, and Ethmalosa fimbriata) from Lagos lagoons and their human health implication. Concentrations of heavy metals and potential health hazard to consumers were evaluated with reference to Estimated Daily Intake (EDI), Target Hazard Quotient (THQ) and Cancer Risk (CR). Results: Concentration of the heavy metals in the fish tissues was below the maximum permissible limit in fish. Similarly, the. EDI of the heavy metals in all the tissues was below the recommended allowance whereas, the. THQ estimated for the heavy metals in the tissues of the fish were less than 1. Consumption of arsenic, nickel, and cadmium in the fish might however pose carcinogenic risk. Conclusions: Although, the measured heavy metal concentration were within permissible limits for human consumption, the calculated health risk values indicated that Arsenic, cadmium and nickel might pose significant health risks to consumers. Therefore, biomonitoring of heavy metal accumulation in tissues of fishes must be put into consideration by regulatory authority.

Polycyclic aromatic hydrocarbons distribution in fish tissues and human health risk assessment on consumption of four fish species collected from Lagos Lagoon, Nigeria.

Lagos Lagoon is a very popular lagoon in Lagos state that receives effluents from neighboring industries. These effluents tend to increase the level of contaminants in the lagoon, thereby creating more stressors for aquatic animals. Determination of polycyclic aromatic hydrocarbons (PAHs) in four commonly consumed fish species from the lagoon and the prediction of possible health risks associated with their consumption were performed in this study. Various levels of PAH were detected in the fish tissues with the highest total concentration of PAH in Sarothoredon melanotheron. High concentrations of benzo(a)pyrene were noticed in Sarothoredon melanotheron and Ethmalosa fimbriata, and their values were above the guideline value of 0.002 µg/g. The dietary daily intake (DDI) value in S. melanotheron 82.00 ×10-5 µg/g/day was highest. Carcinogenic toxic equivalents (TEQ) showed that consumption of S. melanotheron had higher potential to pose carcinogenic risks, while the excess cancer risk (ECR) index for the PAHs in all the assessed fish species was beyond threshold values indicating potential carcinogenic risk from their consumption. No significant association was found between the concentration of PAHs and the size of the fish. Target hazard quotient (THQ) results suggested absence of potential non-carcinogenic risk if individual PAH in the fish are consumed frequently. The study however established possible carcinogenic human health risk from consumption of the fish obtained from Lagos Lagoon. The study recommends monitoring of contamination and consumption of fish from harvest sites within the study region.

Potential inhibitory properties of structurally modified quercetin/isohamnetin glucosides against SARS-CoV-2 Mpro; molecular docking and dynamics simulation strategies.

Concerned organizations and individuals are fully engaged in seeking appropriate measures towards managing Severe Acute Respiratory Syndrome Coronavirus 2 (SAR-CoV-2) infection because of the unprecedented economic and health impact. SAR-CoV-2 Main protease (SARS-CoV-2 Mpro) is unique to the survival and viability of the virus. Therefore, inhibition of Mpro can block the viral propagation. Thirty (30) derivatives were built by changing the glucosides in the Meta and para position of quercetin and isohamnetin. Molecular docking analysis was used for the screening of the compounds. Dynamics simulation was performed to assess the stability of the best pose docked complex. Molecular mechanics binding free energy calculation was done by Molecular Mechanics/Poisson-Boltzmann Surface Area (MMPBSA). Overall analysis showed that the compounds are allosteric inhibitors of SARS-CoV-2 Mpro. Dynamic simulation analysis established the stability of Mpro-ISM-1, Mpro-ISD-3, Mpro-IST-2, Mpro-QM-2, and Mpro-QD-6 complexes with a maximum of 7 hydrogen bonds involved in their interaction. The MMPBSA binding free energies for ISM-1, ISD-3, IST-2, QM-2, and QD-6 were -92.47 ± 9.06, -222.27 ± 32.5, 180.72 ± 47.92, 156.46 ± 49.88 and -93.52 ± 48.75 kcal/mol respectively. All the compounds showed good pharmacokinetic properties, while only ISM-1 inhibits hERG and might be cardio-toxic. Observations in this study established that the glucoside position indeed influenced the affinity for SARS-CoV-2 Mpro. The study also suggested the potentials of ISD-3, QM-2 and QD-6 as potent inhibitors of the main protease, further experimental and clinical studies are however necessary to validate and establish the need for further drug development processes. Therefore, future studies will be on the chemical synthesis of the compounds and investigation of the in-vitro inhibition of SARS-CoV-2.

Angiotensin converting enzyme inhibitors from medicinal plants: a molecular docking and dynamic simulation approach.

Angiotensin converting enzyme (ACE) is a key enzyme and mediator in the aetiology of high blood pressure (HBP) and hypertension. As one of the leading cause of untimely death worldwide, there is a lot of research and studies on the management and treatment of hypertension. The usage of medicinal plants in the management of hypertension as alternative to synthetic allopathic drugs is a common practice in folkloric and traditional medicine. Therefore, this study was aimed to investigate the ACE inhibitory activity of some medicinal plants which are commonly used in the treatment of HBP in southwestern part of Nigeria using extensive in-silico approach. Compounds identified in the plants through GC-MS technique, together with Lisinopril were docked against ACE protein. It was observed that only 40 of the compounds had binding affinity ≥ - 6.8 kcal/mol which was demonstrated by the standard drug (lisinopril). Interaction between the compounds and ACE was via conventional hydrogen, carbon hydrogen, alkyl, pi-alkyl, pi-carbon, and Van Der Wall bonds among others. Most of these compounds exhibited drug like properties, without violating majority of the physicochemical descriptors and Lipinski rule of 5. The ADMET evaluation revealed that only 2 compounds (cyclopentadecanone and oxacycloheptadecan-2-one) which were identified in Bacopa florinbunda plant were predicted non-toxic and thus were subjected to molecular dynamics and simulation with ACE. From the molecular dynamics and mechanics analysis, both cyclopentadecanone and oxacycloheptadecan-2-one showed high stability and inhibitory potentials when bound to ACE. Oxacycloheptadecan-2-one was more stable than lisinopril and cyclopentadecanone in the ligand-ACE complex; we therefore suggested its experimental and clinical validation as drug candidates for the treatment of hypertension. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-022-00135-z.

Checkpoints and immunity in cancers: Role of GNG12.

Cancer progression is enhanced through cell proliferation, with the crucial role of the transducer and transmembrane -signal regulator (GNG12) bringing it to the fore. Dysregulation of cancer cell metabolism, evasion of the immune system, cell cycle, apoptosis, and chemoresistance result from inconsistent initiation of the NF-kB signaling pathway. We excerpt from previous studies that overactivation of the canonic NF-kB cascade occurs in varieties of tumor cells, which results in the growth of lymphovascular invasion, as well as neural invasion. Recently, research has adduced that a particular G protein- coupled receptor (GNG12) is silently involved in the activation of the NF-kB signal, which supports the evasion of cancer immunity and in turn activates cancer proliferation, angiogenesis, and immunotherapeutic resistance. While the likely impact of GNG12 in relation to the progression of tumors is being established, there is insufficient knowledge regarding the functions and mechanisms of GNG12 in cancer immunity. Furthermore, the cancer-associated role as well as the clinical correlation of GNG12 have long been unknown; thus, their identification is more likely to pave the path for a novel regime of tumor suppression. In this study, we established the silent role of GNG12 in activating NF-kB genes and the synergism between NF-kB and PD-L1 expression. Captivatingly, we reported that silencing GNG12 gene downregulates the transcription of PD-L1 gene. We therefore suggested that GNG12 is a risk factor for several cancers, and a possible target for immunotherapy.

Overcoming immunotherapeutic resistance in PDAC: SIRPα-CD47 blockade.

A daily increase in the number of new cases of pancreatic ductal adenocarcinoma remains an issue of contention in cancer research. The data revealed that a global cumulated case of about 500, 000 have been reported. This has made PDAC the fourteenth most occurring tumor case in cancer research. Furthermore, PDAC is responsible for about 466,003 deaths annually, representing the seventh prevalent type of cancer mortality. PDAC has no salient symptoms in its early stages. This has exasperated several attempts to produce a perfect therapeutic agent against PDAC. Recently, immunotherapeutic research has shifted focus to the blockade of checkpoint proteins in the management and of some cancers. Investigations have centrally focused on developing therapeutic agents that could at least to a significant extent block the SIRPα-CD47 signaling cascade (a cascade which prevent phagocytosis of tumors by dendritic cells, via the deactivation of innate immunity and subsequently resulting in tumor regression) with minimal side effects. The concept on the blockade of this interaction as a possible mechanism for inhibiting the progression of PDAC is currently being debated. This review examined the structure--function activity of SIRPα-CD47 interaction while discussing in detail the mechanism of tumor resistance in PDAC. Further, this review details how the blockade of SIRPα-CD47 interaction serve as a therapeutic option in the management of PDAC.

Phyllanthus amarus attenuated derangement in renal-cardiac function, redox status, lipid profile and reduced TNF-α, interleukins-2, 6 and 8 in high salt diet fed rats.

High salt diet (HSD) has been implicated in the etiopathogenesis of immune derangement, cardiovascular disorders and, metabolic syndromes. This study investigated the protective effect of ethanol extract of Phyllanthus amarus (EEPA) against high salt diet (HSD) induced biochemical and metabolic derangement in male Wistar rats. The rats were divided into 5 groups of 6 animals each as follows; control group fed with normal rat chow, negative control group, fed HSD only, animals on HSD treated orally with 75 mg/kg, 100 mg/kg, and, 150 mg/kg EEPA once daily. At the end of 8 weeks treatment, lipid profile (TG, TC, LDL, and VLDL), oxidative stress (catalase, reduced glutathione, and malondialdehyde), inflammatory (TNF-a, interleukins 2, 6, and 8), cardiac (lactate dehydrogenase, creatine kinase) and kidney function markers (urea, uric acid, creatinine) were assessed. Serum TG, TC, LDL, and VLDL content were significantly (p < 0.05) elevated in HSD-only fed rats, while HDL was significantly elevated in a concentration-dependent manner in EEPA treated animals. The extract produced a significant (p < 0.05) and dose-dependent increase in the antioxidant enzymes activities and a significant reduction in the malondialdehyde level. A significant (p < 0.05) dose-dependent reduction in serum TNF-alpha, IL-2, 6, and 8 of EEPA treated rats compared with HSD-fed rats was observed. More so, reduction in serum LDH, creatine kinase, creatinine, urea, and uric acid activity of extract-treated animals were noted. EEPA attenuated high salt diet-induced oxidative stress, inflammation, and dyslipidemia in rats.

In silico studies of Potency and safety assessment of selected trial drugs for the treatment of COVID-19.

SARS-CoV-2 has caused millions of infections and hundreds of thousands of deaths globally. Presently, no cure for SARS-CoV-2 infection is available; thus, all hands are on deck for new drug discovery. Although, several studies have reported the potentials of some already approved drugs for the treatment of COVID-19. This study attempted to compare the potency and safety of some these trial drugs via in silico methods. The binding affinity and interactions of the trial drugs with proteins involved in viral polyprotein processing (Papain like protease (PLpro) and Chymotrypsin like-protease (3-CLpro), viral replication (RNA dependent RNA polymerase (RdRp)) and host protease were studied in this work. The pharmacokinetic properties and toxicity potentials of the trial drugs were also predicted using vNN Web Server for ADMET Predictions. From the results, Merimepodib and Dexamethaxone demonstrated the most significant inhibitory potential against the PLpro. The binding affinity (∆G°) for merimepodib was - 7.2 kcal/mol while the inhibition constant was 6.3 µM. The binding affinity of the inhibitors for CLpro ranged from - 5.6 to - 9.5 kcal/mol. whereas Lopinavir (- 7.7 kcal/mol) exhibited the strongest affinity for RdRp. Overall, our results showed that all the ligands have a higher affinity for the 3-Chymotrypsin like protease than the other proteins (PLpro, RdRp, and Host protease). Among these compounds lopinavir, merimepodib and dexamethasone could be inhibitors with potentials for the treatment of SARS-CoV-2. However, the only dexamethasone has attractive pharmacokinetic and toxicity properties probable for drug development; therefore, our study provides a basis for developing effective drugs targeting a specific protein in the SARS-CoV-2 life cycle. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00105-x.

Computational prediction of nimbanal as potential antagonist of respiratory syndrome coronavirus.

The high pathogenic nature of the Middle East Respiratory coronavirus (MER) and the associated high fatality rate demands an urgent attention from researchers. Because there is currently no approved drug for the management of the disease, research efforts have been intensified towards the discovery of a potent drug for the treatment of the disease. Papain Like protease (PLpro) is one of the key proteins involved in the viral replication. We therefore docked forty-six compounds already characterized from Azadirachta indica, Xylopia aethipica and Allium cepa against MERS-CoV-PLpro. The molecular docking analysis was performed with AutoDock 1.5.6 and compounds which exhibit more negative free energy of binding, and low inhibition constant (Ki) with the protein (MERS-CoV-PLpro) were considered potent. The physicochemical and pharmacokinetic properties of the compounds were predicted using the Swissadme web server. Twenty-two of the compounds showed inhibition potential similar to dexamethasone and remdesvir, which had binding affinity of -6.8 and -6.3 kcal/mol respectively. The binding affinity of the compounds ranged between -3.4 kcal/mol and -7.7 kcal/mol whereas; hydroxychloroquine had a binding affinity of -4.5 kcal/mol. Among all the compounds, nimbanal and verbenone showed drug likeliness, they did not violate the Lipinski rule neither were they inhibitors of drug-metabolizing enzymes. Both nimbanal and verbenone were further post-scored with MM/GBSA and the binding free energy of nimbanal (-25.51 kcal/mol) was comparable to that of dexamethasone (-25.46 kcal/mol). The RMSD, RMSF, torsional angle, and other analysis following simulation further substantiate the efficacy of nimbanal as an effective drug candidate. In conclusion, our study showed that nimbanal is a more promising therapeutic agent and could be a lead for the discovery of a new drug that may be useful in the management of severe respiratory coronavirus syndrome.

The Role of Poly-Herbal Extract in Sodium Chloride-Induced Oxidative Stress and Hyperlipidemia in Male Wistar Rats.

Consistent consumption of high salt diet (HSD) has been associated with increased cellular generation of free radicals, which has been implicated in the derangement of some vital organs and etiology of cardiovascular disorders. This study was designed to investigate the combined effect of some commonly employed medicinal plants on serum lipid profile and antioxidant status of aorta, kidney, and liver of high salt diet-fed animals. Out of the total fifty male Wistar rats obtained, fifteen were used for acute toxicity study, while the remaining thirty-five were divided into 5 groups of 7 animals each. Group 1 and 2 animals were fed normal rat chow (NRC) and 16% high salt diet (HSD) only, respectively. Animals in groups 3, 4 and 5 were fed 16% HSD with 800, 400, and 200 mg/kg bw poly-herbal extract (PHE), respectively, once for 28 consecutive days. Serum low-density lipoprotein (LDL), triacylglycerol (TG), total cholesterol (TC) and high-density lipoprotein (HDL), malondialdehyde, nitric oxide, catalase, superoxide dismutase, glutathione peroxidase, glutathione concentration, and activities were assessed in the aorta, kidney, and liver. Poly-herbal extract (p < 0.05) significantly reduced malondialdehyde and nitric oxide concentrations and also increased antioxidant enzymes and glutathione activity. Elevated serum TG, TC, LDL, and TC content in HSD-fed animals were significantly (p < 0.05) reduced to normal in PHE-treated rats while HDL was significantly elevated (p < 0.05) in a concentration-dependent manner in PHE treated animals. Feeding with PHE attenuated high-salt diet imposed derangement in serum lipid profile and antioxidant status in the organs of the experimental rats.

Molecular docking and ADMET studies of Allium cepa, Azadirachta indica and Xylopia aethiopica isolates as potential anti-viral drugs for Covid-19.

Plants are repository of important constituents with proven efficacy against many human diseases including viral diseases. The antiviral activity of many plants including Azadirachta indica, Xylopia aethiopica and Allium cepa has been reported. The novel coronavirus disease is no exception among viral diseases in which plant compounds could serve as potent antagonist. Therefore, our study investigated the inhibitory potentials of Azadirachta indica and Xylopia aethiopica isolates against SARS-CoV-2 viral accessory proteins and the host serine protease. The protein data (SARS-CoV-2 Papain like protease (PLpro) (PDB: 6wx4), Chymotrypsin-like main protease (3CLpro) (PDB:6YB7), SARS-CoV nsp 12 (PDB: 6nus), Host cell protease (TMPRSS1) (PDB:5ce1) were obtained from the protein data bank (PDB), while the SDS format of each Ligands were obtained from Pubchem database. Molecular docking analysis was performed with Auto Dock Vina 1.5.6 and visualization of the interaction between the ligands and protein was done with discovery studio 2019. The ADMET prediction of pharmacokinetics and toxicity properties of the ligands was obtained using vNN Web Server. Our result showed that all the plant isolates demonstrated negative Gibb's free energy, indicating good binding affinity for both the viral and host protein. Overall, twenty-three of the forty-seven isolates showed good binding affinity comparable with dexamethasone that was used as reference drug. Although many of the compounds have good binding affinity for the viral and host proteins, based on the ADMET prediction, only Azadironic acid, Nimbionone, Nimbionol and Nimocinol all from A. indica could serve as potential drug candidate with good pharmacokinetics and toxicity profile. This study provides an insight into potential inhibitors and novel drug candidates for SARS-CoV-2. Further studies will look forward into the wet laboratory validation of Azadironic acid, Nimbionone, Nimbionol and Nimocinol against corona virus disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00682-7.