In silico pharmacokinetic and therapeutic evaluation of Musa acuminata peels against aluminium chloride-induced hepatotoxicity in adult BALB/c mice.

East Africa (Musa spp.), notably Musa acuminata, "Matooke" a staple and economically important food in the region. Here, 12 selected M. acuminata peels extract (MAPE) bioactive compounds were studied for hepatoprotective potentials in aluminium chloride-induced hepatoxicity in adult BALB/c mice. GC-MS analysis was used to identify active components of MAPE. In silico estimation of the pharmacokinetic, the GCMS-identified compounds' toxicity profile and molecular docking were compared with the standard (Simvastatin) drug. Hepatotoxicity was induced using aluminium-chloride treated with MAPE, followed by biochemical and histopathological examination. Twelve bioactive compounds 2,2-Dichloroacetophenone (72870), Cyclooctasiloxane 18993663), 7-Hydroxy-6,9a-dimethyl-3-methylene-decahydro-azuleno[4,5-b]furan-2,9-dione (534579), all-trans-alpha-Carotene (4369188), Cyclononasiloxane (53438479), 3-Chloro-5-(4-methoxyphenyl)-6,7a-dimethyl-5,6,7,7a-tetrahydro-4H-furo[2,3-c]pyridin-2-one (536708), Pivalic acid (6417), 10,13-Octadecadienoic acid (54284936), Ethyl Linoleate (5282184), Oleic acid (5363269), Tirucallol (101257), Obtusifoliol (65252) were identified by GC-MS. Of these, seven were successfully docked with the target proteins. The compounds possess drug likeness potentials that do not inhibits CYP450 isoforms biotransformation. All the docked compounds were chemoprotective to AMES toxicity, hERGI, hERGII and hepatotoxicity. The animal model reveals MAPE protective effect on liver marker's function while the histological studies show regeneration of the disoriented layers of bile ducts and ameliorate the cellular/histoarchitecture of the hepatic cells induced by AlCl3. The findings indicate that MAPE improved liver functions and ameliorated the hepatic cells' cellular or histoarchitecture induced by AlCl3. Further studies are necessary to elucidate the mechanism action and toxicological evaluation of MAPE's chronic or intermittent use to ascertain its safety in whole organism systems.

Methanol Crude Peel Extract of P. granatum Prevents Oxidative Damage in Kidneys of Rats Exposed to Highly Active Antiretroviral Therapy.

Background: Highly Active Antiretroviral Therapy (HAART) has been linked to oxidative damage to kidney cells leading to renal disease in people living with HIV/AIDS on HAART treatment. The toxic effects of HAART affect the patients' quality of life leading to poor adherence to their regimen. Therefore, the purpose of this study was to investigate the nephron-protective activity of methanol crude peel extract of Punica granatum (MPEPG) in HAART-administered Wistar rats. Methods: Thirty male albino Wistar rats weighing between 180-200g were randomly divided into six groups of five rats each. Group one served as normal control and was given distilled water only. Group two serves as a negative control and was given HAART at a dosage of 64 mg/kg. Groups 3 and 4 were given 100 and 400 mg/kg of MPEPG, respectively, while groups 5 and 6 were given MPEPG dosages of 100 and 400 mg/kg along with HAART, respectively, for 40 days. The rats were sacrificed under halothane anaesthesia, and the kidneys were removed for histological evaluation, while blood samples were analyzed for biochemical parameters. Results: In the HAART (TLD) treated group, there was a significantly high amount of MDA and a lower level of the antioxidant enzymes SOD and CAT. Biochemical analysis revealed that animals treated with HAART (TLD) had significantly higher levels of urea and creatinine, which are biomarkers of kidney damage than the normal control animals. In contrast, all the kidney function markers were returned to normal levels in the HAART-treated group after administration of methanol crude peel extract of P. granatum. The kidney tissues of animals given HAART had considerable structural damage as revealed by histopathological studies. When HAART-exposed rats were treated with MPEPG, both the biochemical and histological results significantly improved. Conclusion: Methanol crude peel extract of P. granatum provided effective protection against kidney oxidative injury brought on by HAART because of its anti-oxidant and free radical scavenging properties.

Naringenin: its chemistry and roles in neuroprotection.

According to epidemiological research, as the population ages, neurological illnesses are becoming a bigger issue. Despite improvements in the treatment of these diseases, there are still widespread worries about how to find a long-lasting remedy. Several neurological diseases can be successfully treated with natural substances. As a result, current research has been concentrated on finding effective neuroprotective drugs with improved efficacy and fewer side effects. Naringenin is one potential treatment for neurodegenerative diseases. Many citrus fruits, tomatoes, bergamots, and other fruits are rich in naringenin, a flavonoid. This phytochemical is linked to a variety of biological functions. Naringenin has attracted a lot of interest for its ability to exhibit neuroprotection through several mechanisms. In the current article, we present evidence from the literature that naringenin reduces neurotoxicity and oxidative stress in brain tissues. Also, the literatures that are currently accessible shows that naringenin reduces neuroinflammation and other neurological anomalies. Additionally, we found several studies that touted naringenin as a promising anti-amyloidogenic, antidepressant, and neurotrophic treatment option. This review's major goal is to reflect on advancements in knowledge of the molecular processes that underlie naringenin's possible neuroprotective effects. Furthermore, this article also provides highlights of Naringenin with respect to its chemistry and pharmacokinetics.

Cucumeropsis mannii seed oil protects against Bisphenol A-induced testicular mitochondrial damages.

There has been increasing search for the ameliorative properties of seed oils against toxicants. bisphenol A acts as an estrogenic endocrine-disrupting chemical capable of causing male infertility. This study aimed to explore Cucumeropsis mannii seed oil effects against mitochondrial damage in rats using bisphenol A. Forty-eight rats were randomly assigned to six groups (n = 6) of eight rats each and fed the same food and water for 6 weeks. The group A rats were given 1 mL olive oil, while the ones in group B were given bisphenol A at 100 mL/kg body weight via oral route. Group C received C. mannii seed oil 7.5 mL/kg body weight C. mannii seed oil, while group D, group E, and group F were pre-administered bisphenol A at 100 mL/kg body weight, followed by treatment with C. mannii seed oil at 7.5, 5, and 2.5 mL/kg body weight, respectively. Antioxidant enzymes, glutathione, reactive oxygen species, testicular volume, malondialdehyde, body weight, and testicular studies were done using standard methods. The results of the bisphenol A-administered group showed a significant decrease in the antioxidant enzymes, glutathione, body weight, and testicular volume with elevation in the levels of reactive oxygen species, malondialdehyde, and testicular indices. BPA + CMSO-treated group showed a significant increase in GPx activity compared with BPA-exposed rats. CMSO treatment significantly increased catalase activity in comparison with that of rats exposed to BPA. Remarkably, C. mannii seed oil and bisphenol A co-administration significantly reversed the abnormalities observed in the dysregulated biochemical biomarkers. Our findings suggest that C. mannii seed oil has considerable antioxidant potential which can be explored in therapeutic development against systemic toxicity induced by exposure to bisphenol A. Cucumeropsis mannii seed oil protects against bisphenol A-induced testicular mitochondria damages.

High-pressure acidified steaming with varied citric acid dosing can successfully detoxify mycotoxins.

Mycotoxins are toxic fungal metabolites that exert various toxicities, including leading to death in lethal doses. This study developed a novel high-pressure acidified steaming (HPAS) for detoxification of mycotoxins in foods and feed. The raw materials, maize and peanut/groundnut, were used for the study. The samples were separated into raw and processed categories. Processed samples were treated using HPAS at different citric acid concentrations (CCC) adjusted to pH 4.0, 4.5, and 5.0. The enzyme-linked immunosorbent assay (ELISA) kit method for mycotoxins analysis was used to determine the levels of mycotoxins in the grains, with specific focus on total aflatoxins (AT), aflatoxins B1 (AFB1), aflatoxin G1 (AFG1), ochratoxin A (OTA), and citrinin. The mean values of the AT, AFB1, AFG1, OTA, and citrinin in the raw samples were 10.06 ± 0.02, 8.21 ± 0.01, 6.79 ± 0.00, 8.11 ± 0.02, and 7.39 ± 0.01 µg/kg for maize, respectively (p ≤ .05); and for groundnut (peanut), they were 8.11 ± 0.01, 4.88 ± 0.01, 7.04 ± 0.02, 6.75 ± 0.01, and 4.71 ± 0.00 µg/kg, respectively. At CCC adjusted to pH 5.0, the AT, AFB1, AFG1, OTA, and citrinin in the samples significantly reduced by 30%-51% and 17%-38% for maize and groundnut, respectively, and were reduced to 28%-100% when CCC was adjusted to pH 4.5 and 4.0 (p ≤ .05). The HPAS process either completely detoxified the mycotoxins or at least reduced them to levels below the maximum limits of 4.00-6.00, 2.00, 2.00, 5.00, and 100 µg/kg for AT, AFB1, AFG1, OTA, and citrinin, respectively, set by the European Union, WHO/FAO, and USDA. The study clearly demonstrates that mycotoxins can be completely detoxified using HPAS at CCC adjusted to pH 4.0 or below. This can be widely applied or integrated into many agricultural and production processes in the food, pharmaceutical, medical, chemical, and nutraceutical industries where pressurized steaming can be applied for the successful detoxification of mycotoxins.

UCP-LF and other assay methods for schistosome circulating anodic antigen between 1978 and 2022.

Detection of circulating anodic antigen (CAA) is known for its high sensitivity in diagnosing schistosomiasis infection, even in low-prevalence settings. The Up-Converting Phosphor-Lateral Flow (UCP-LF) assay developed in 2008 presented greater sensitivity than other assay methods in use for CAA detection. Our study aims to comprehensively review all studies conducted in this area and thus generate informed conclusions on the potential for adopting the UCP-LF assay for diagnosing this important yet neglected tropical disease. Using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, we generated search criteria to capture all studies in English journals available in the Scopus and PubMed databases on 20 December 2022. A total of 219 articles were identified, and 84 that met the inclusion criteria were retrieved and eventually included in the study. Twelve different assay methods were identified with a noteworthy transition from enzyme-linked immunosorbent assay (ELISA) to the UCP-LF assay, a laboratory-based assay that may be applicable as a point-of-care (POC) diagnostic test for schistosomiasis. Reducing the time, cost, and dependence on specialized laboratory skills and equipment, especially relating to the trichloroacetic acid extraction step and centrifugation in the UCP-LF CAA assay may go a long way to aid its potential as a POC tool. We also propose the development of a CAA-specific aptamer (short protein/antigen-binding oligonucleotide) as a possible alternative to monoclonal antibodies in the assay. UCP-LF has great potential for POC application.

In-vivo and in-silico studies revealed the molecular mechanisms of Colocasia esculenta phenolics as novel chemotherapy against benign prostatic hyperplasia via inhibition of 5α-reductase and α1-adrenoceptor.

Benign Prostatic Hyperplasia (BPH) is a major cause of lower urinary tract infections and erectile dysfunction thus a major contributor to lowering the quality of life among older men. In this study, we investigated the molecular mechanism of Colocasia esculenta (CE) as a novel agent for BPH chemotherapy. In vivo, we assigned 45 male Wistar albino rats about 6 weeks old into 9 experimental groups (n = 5). BPH was induced in groups 2-9 with 3 mg/kg of Testosterone Propionate (TP) subcutaneously. Group 2 (BPH) was not treated. Group 3 was treated with 5 mg/kg Finasteride (standard drug). Group 4-9 were treated each with 200 mg/kg body weight (b.w) of CE crude tuber extracts/fractions (ethanol, hexane, dichloromethane, ethyl acetate, butanol, aqueous). At the end of treatment, we sampled the rats' serum to check the level of PSA. In silico, we conducted a molecular docking of the crude extract of CE phenolics (CyP) previously reported, targeting 5α-Reductase and α1-Adrenoceptor linked to the BPH progressions. We adopted the standard inhibitors/antagonists (5α-reductase: finasteride; α1-adrenoceptor: tamsulosin) of the target proteins as controls. Furthermore, the pharmacological properties of the lead molecules were studied in terms of ADMET using swissadme and pKCSM resources, respectively. Results showed that administration of TP in male Wistar albino rats significantly (p < 0.05) elevated serum PSA levels whereas CE crude extracts/fractions significantly (p < 0.05) lowered the serum PSA level. Also, fourteen of the CyPs bind to at least one or two of the target proteins with their binding affinity of between - 9.3 to - 5.6 kcal/mol and - 6.9 to - 4.2 kcal/mol, respectively. The CyPs possess better pharmacological properties compared to the standard drugs. Therefore, they have the potentials to be enlisted for clinical trials towards the management of BPH.

Combating Lassa Fever in West African Sub-Region: Progress, Challenges, and Future Perspectives.

Lassa fever (LF) is a rodent-borne disease that threatens human health in the sub-region of West Africa where the zoonotic host of Lassa virus (LASV) is predominant. Currently, treatment options for LF are limited and since no preventive vaccine is approved for its infectivity, there is a high mortality rate in endemic areas. This narrative review explores the transmission, pathogenicity of LASV, advances, and challenges of different treatment options. Our findings indicate that genetic diversity among the different strains of LASV and their ability to circumvent the immune system poses a critical challenge to the development of LASV vaccines/therapeutics. Thus, understanding the biochemistry, physiology and genetic polymorphism of LASV, mechanism of evading host immunity are essential for development of effective LASV vaccines/therapeutics to combat this lethal viral disease. The LASV nucleoprotein (NP) is a novel target for therapeutics as it functions significantly in several aspects of the viral life cycle. Consequently, LASV NP inhibitors could be employed as effective therapeutics as they will potentially inhibit LASV replication. Effective preventive control measures, vaccine development, target validation, and repurposing of existing drugs, such as ribavirin, using activity or in silico-based and computational bioinformatics, would aid in the development of novel drugs for LF management.

Elucidation of chemical profiles and molecular targets of Mondia whitei leave fractions bioactive as novel therapeutics: an in vitro and in silico assay.

BACKGROUND: Mondia whitei root is often used in Africa as a local therapeutic agent for libido enhancement. The fractions of the M. whitei leaves (MWL) lack chemical characterization of their bioactive components and possible molecular targets. We characterized and investigated its molecular target as therapeutic agents in an in vitro and in silico assay. Mineral compositions, antioxidant, and GC-MS characterization were studied. The cytotoxicity effect was measured on HeLa and HT-29 cells by MTT assay. In silico potential inhibitors of Cathepsin B (CathB) as a cancer biomarker were determined. RESULTS: The flame photometry produced marked Na+ and K+. GC-MS revealed eighteen bioactive components. The fractions (chloroformic 47.00, ethanolic 45.52, and aqueous 40.13) of MWL caused a higher inhibition ratio compared to standards. The MWL showed a significant cytotoxic effect on the treated cell lines at concentrations of 150 and 200 µg/ml and 100, 150, and 200 µg/ml for HT-29 and HeLa cells, respectively. Ten bioactives (MWL 4, 5, 6, 8, 9, 10, 14, 15, 17, and 18) showed potential inhibition of CathB with binding affinities of -4.40 to -8.3 Kcal/Mol. However, MWL 4, 9, 14, and 17 which have higher binding affinities (-6.7, -7.1, -8.2, and -8.3, respectively) than the standard inhibitor (-6.5) were the lead molecules. CONCLUSION: These chemical profiles and potential molecular targets unraveled in this study propose that MWL has a promising anticancer activity.

Current Advances in the Management of Diabetes Mellitus.

Diabetes mellitus (DM) underscores a rising epidemic orchestrating critical socio-economic burden on countries globally. Different treatment options for the management of DM are evolving rapidly because the usual methods of treatment have not completely tackled the primary causes of the disease and are laden with critical adverse effects. Thus, this narrative review explores different treatment regimens in DM management and the associated challenges. A literature search for published articles on recent advances in DM management was completed with search engines including Web of Science, Pubmed/Medline, Scopus, using keywords such as DM, management of DM, and gene therapy. Our findings indicate that substantial progress has been made in DM management with promising results using different treatment regimens, including nanotechnology, gene therapy, stem cell, medical nutrition therapy, and lifestyle modification. However, a lot of challenges have been encountered using these techniques, including their optimization to ensure optimal glycemic, lipid, and blood pressure modulation to minimize complications, improvement of patients' compliance to lifestyle and pharmacologic interventions, safety, ethical issues, as well as an effective delivery system among others. In conclusion, lifestyle management alongside pharmacological approaches and the optimization of these techniques is critical for an effective and safe clinical treatment plan.

Effect of ethanol and aqueous extracts of seed pod of Copaifera salikounda (Heckel) on complete Freund's adjuvant-induced rheumatoid arthritis in rats.

The antirheumatoid arthritis potential of ethanol and aqueous extracts of seed pod of Copaifera salikounda (SPCS) was evaluated using the chicken collagen/complete Freund's adjuvant-induced arthritic rats model. Adjuvat-induced rats were treated with varied doses of the extracts (400, 600, and 800 mg/kg body weight) and with reference drug, indomethacin for 21 days. Antiarthritic evaluation was done through measurement of body weight, paw size, inflammatory makers, hematological parameters, cytokines, antioxidant enzymes, reduced glutathione, lipid peroxidation as well as histopathological examinations. Treatment with the ethanol and aqueous extracts of SPCS markedly inhibited the paw size and caused weight gain. The extracts considerably modulated the hematological as well as the antioxidant parameters. Likewise, the extract restored the altered lipid peroxidation, pro-inflammatory mediators, and inflammatory factors which further accentuate the implication in adjuvant-induced arthritis. Thus, the ethanol and aqueous extracts of SPCS showed a significant antiarthritic activity that was statistically analogous to that of indomethacin. Practical applications Copaifera salikounda (Heckel) has been used in treatment of different ailments including rheumatoid arthritis in folklore medicine. This is the first reported proof of the antiarthritic potential of the seed pod. Oxidative stress has been implicated in rheumatoid arthritis. Ethanol extract of SPCS has been shown to be predominantly rich in phenols, terpenoids, alkaloids, and flavonoids which are natural antioxidant. The present study has demonstrated that ethanol and aqueous extracts of SPCS can exert antioxidative and antiinflammatory effects, thus strengthening its antiarthritic potentials.