Although Citrus macroptera (Rutaceae), an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract of Citrus macroptera (EECM) against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups) were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg) was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS) compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested that C. macroptera fruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation.
Objectives: In this present study, antioxidant, anti-hemolytic, cytotoxic and anti-bacterial activities derived from methanol extracts of Bruguiera gymnorrhiza and Heritiera littoralis were investigated in order to determine their medicinal activities.Materials and methods: Folin-Ciocalteu reagent method and aluminum chloride methods were used to determine the mangroves' total phenolics and total flavonoid content, respectively. Antioxidant capacity was assessed via the following methods: 1,1-diphenyl-2-picryl hydroxyl (DPPH), 43 mM H 2 O 2 , Fe 2+ quenching assay, and anti-hemolytic activity. Brine shrimp (Artemia salina L.) lethality assay was also carried out to determine the cytotoxic potential of the mangroves along with antibacterial activity test using five Gram-negative and another two Gram-positive bacterial strains.Results: The mangroves yielded 58.917 ± 0.601 and 36.625 ± 0.551 mg Gallic acid equivalent (GAE)/g sample and 76.417 ± 0.19 and 113.637 ± 0.17 mg quercetin equivalent (QE)/g sample in B. gymnorrhiza and H. littoralis, respectively. Methanol extracts of both mangroves exhibited high radical scavenging activity against DPPH, H 2 O 2 and Fe 2+ radicals. The reductive capacity of the extracts increased with increasing concentrations of samples, and the extracts inhibited H 2 O 2 induced hemolysis in human red blood cells (RBCs). Antioxidant properties were found to be moderately weaker than that of the reference standard, L-ascorbic acid (AA), and Gallic acid (GA). Further, brine shrimp (Artemia salina L.) lethality assay revealed significant cytotoxicity (241.4 and 272.6 μg/mL, respectively). Methanol extracts could also inhibit the growth of pathogenic bacterial strains. Conclusion: This study showed that the crude methanol extract of selected mangrove plants possesses free radical scavenging, anti-hemolytic, cytotoxic and anti-bacterial activity. The experimented plant has the potential to be used as a traditional medicine and replace synthetic drugs. Further studies are necessary to isolate active compounds responsible for the overall antioxidant activity of the crude extracts.
SARS-CoV-2 is the foremost culprit of the novel coronavirus disease 2019 (nCoV-19 and/or simply COVID-19) and poses a threat to the continued life of humans on the planet and create pandemic issue globally. The 3-chymotrypsin-like protease (M PRO or 3CL PRO ) is the crucial protease enzyme of SARS-CoV-2, which directly involves the processing and release of translated non-structural proteins (nsps), and therefore involves the development of virus pathogenesis along with outbreak the forecasting of COVID-19 symptoms. Moreover, SARS-CoV-2 infections can be inhibited by plant-derived chemicals like amentoflavone derivatives, which could be used to develop an anti-COVID-19 drug. Our research study is designed to conduct an in silico analysis on derivatives of amentoflavone (isoginkgetin, putraflavone, 4′′′′′′-methylamentoflavone, bilobetin, ginkgetin, sotetsuflavone, sequoiaflavone, heveaflavone, kayaflavone, and sciadopitysin) for targeting the non-structural protein of SARS-CoV-2, and subsequently further validate to confirm their antiviral ability. To conduct all the in silico experiments with the derivatives of amentoflavone against the M PRO protein, both computerized tools and online servers were applied; notably the software used is UCSF Chimera (version 1.14), PyRx, PyMoL, BIOVIA Discovery Studio tool (version 4.5), YASARA (dynamics simulator), and Cytoscape. Besides, as part of the online tools, the SwissDME and pKCSM were employed. The research study was proposed to implement molecular docking investigations utilizing compounds that were found to be effective against the viral primary protease (M PRO ). M PRO protein interacted strongly with 10 amentoflavone derivatives. Every time, amentoflavone compounds outperformed the FDA-approved antiviral medicine that is currently underused in COVID-19 in terms of binding affinity (− 8.9, − 9.4, − 9.7, − 9.1, − 9.3, − 9.0, − 9.7, − 9.3, − 8.8, and − 9.0 kcal/mol, respectively). The best-selected derivatives of amentoflavone also possessed potential results in 100 ns molecular dynamic simulation (MDS) validation. It is conceivable that based on our in silico research these selected amentoflavone derivatives more precisely 4′′′′′′-methylamentoflavone, ginkgetin, and sequoiaflavone have potential for serving as promising lead drugs against SARS-CoV-2 infection. In consequence, it is recommended that additional in vitro as well as in vivo research studies have to be conducted to support the conclusions of this current research study. Graphical abstract
Medicinal plants possess a surplus of novel and biologically active secondary metabolites that are responsible for counteracting diseases. Traditionally, Gomphandra tetrandra (Wall.) Sleumer is used to treat mental disorders. The present research was designed to explore phytochemicals from the ethanol leaf extract of Gomphandra tetrandra (Wall.) Sleumer to identify the potential pharmacophore(s) in the treatment of neurological disorders. The chemical compounds of the experimental plant were identified through GC-MS analysis. In-vitro antioxidant activity was assessed using different methods. Furthermore, in-vivo neurological activity was assessed in Swiss-albino mice. Computer-aided analysis was appraised to determine the best-fit phytoconstituent of a total of fifteen identified compounds in the experimental plant extract against beta-amyloid precursor protein. The experimental extract revealed fifteen compounds in GC-MS analysis and the highest content was 9, 12, 15-octadecatrienoic acid (z,z,z). The extract showed potent antioxidant activity in in-vitro assays. Furthermore, in in-vivo neurological assays, the extract disclosed significant (p < 0.05) neurological activity. The most favorable phytochemicals as neurological agents were selected via ADMET profiling, and molecular docking was studied with beta-amyloid precursor protein. In the computer-aided study, 1, 5-diphenyl-2h-1, 2, 4-triazoline-3-thione (Pub Chem CID: 2802516) was more active than other identified compounds with strong binding affinity to beta-amyloid precursor protein. The present in vivo and in silico studies revealed neuropharmacological features of G. tetrandra leaf extract as a natural agent against neurological disorders, especially Alzheimer’s disease.
Cumulative studies have provided controversial evidence for the prognostic values of bone morphogenetic protein 5 (BMP5) in different types of cancers such as colon, breast, lung, bladder, and ovarian cancer. To address the inconsistent correlation of BMP5 expression with patient survival and molecular function of BMP5 in relation to cancer progression, we performed a systematic study to determine whether BMP5 could be used as a prognostic marker in human cancers. BMP5 expression and prognostic values were assessed using different bioinformatics tools such as ONCOMINE, GENT, TCGA, GEPIA, UALCAN, PrognoScan, PROGgene V2 server, and Kaplan–Meier Plotter. In addition, we used cBioPortal database for the identification and analysis of BMP5 mutations, copy number alterations, altered expression, and protein–protein interaction (PPI). We found that BMP5 is frequently down-regulated in our queried cancer types. Use of prognostic analysis showed negative association of BMP5 down-regulation with four types of cancer except for ovarian cancer. The highest mutation was found in the R321*/Q amino acid of BMP5 corresponding to colorectal and breast cancer whereas the alteration frequency was higher in lung squamous carcinoma datasets (>4%). In PPI analysis, we found 31 protein partners of BMP5, among which 11 showed significant co-expression (p-value < 0.001, log odds ratio > 1). Pathway analysis of differentially co-expressed genes with BMP5 in breast, lung, colon, bladder and ovarian cancers revealed the BMP5-correlated pathways. Collectively, this data-driven study demonstrates the correlation of BMP5 expression with patient survival and identifies the involvement of BMP5 pathways that may serve as targets of a novel biomarker for various types of cancers in human.
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