Abstract:The aim of the present work was to carry out a bioguided isolation of antiviral chemical constituents from an ethanol extract of leaves from Arrabidaea pulchra (Cham.) Sandwith (EEAPL) that had shown in vitro activity in a previous screening using DNA and RNA viruses. The activity of EEPAL was evaluated against the DNA viruses Human herpesvirus 1 (HSV-1) and Vaccinia virus Western Reserve (VACV-WR) as well as against the RNA viruses Murine encephalomyocarditis virus (EMCV), and Dengue virus 2 (DENV-2) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Cytotoxicity was determined in LLCMK 2 and Vero cells and the Selectivity Indexes (SI) were calculated. The most potent effect was observed against DENV-2 (EC 50 46.8 ± 1.6 µg mL were determined, while no inhibition of the cytopathic effect was observed with EMCV. Bioguided fractionation of EEAPL by partition between immiscible solvents followed by chromatography over a Sephadex LH20 column afforded two arylpropanoid glycosides, verbascoside (AP 1) and caffeoylcalleryanin (AP 2), along with a terpenoid, ursolic acid (AP 3). AP 1 and AP 3 exhibited similar anti-DENV-2 profiles, with SI values OPEN ACCESSMolecules 2013, 18 9920 of 3.8 and 3.1, respectively, while AP 2 was the most effective anti-DENV-2 constituent, with a SI of 20.0. Our results show that A. pulchra leaves ethanol extract (EEAPL) affords compounds with antiviral activity, mainly against DENV-2.
Aims: To evaluate the antiviral activity of Bignoniaceae species occurring in the state of Minas Gerais, Brazil. Methods and Results: Ethanol extracts of different anatomical parts of bignoniaceous plant species have been evaluated in vitro against human herpesvirus type 1 (HSV‐1), vaccinia virus (VACV) and murine encephalomyocarditis virus (EMCV) by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. A total of 34 extracts from 18 plant species selected according to ethnopharmacological and taxonomic criteria were screened. Fifteen of the 34 extracts (44·1%) have disclosed antiviral activity against one or more of the viruses assayed with EC50 values in the range of 23·2 ± 2·5–422·7 ± 10·9 μg ml−1. Conclusions: Twelve of the 34 extracts (35·3%) might be considered promising sources of antiviral natural products, as they have shown EC50 ≤ 100 μg ml−1. The present screening discloses the high potential of the Bignoniaceae family as source of antiviral agents. Significance and Impact of the Study: Active extracts were identified and deserve bioguided studies for the isolation of antiviral compounds and studies on mechanism of action.
Sepsis is a complex disease and is the cause of many deaths worldwide. Sepsis pathogenesis involves a dysregulated inflammatory response with consequent production of inflammatory mediators and reactive species. The production and excessive release of these substances into the systemic circulation trigger various cellular and metabolic alterations that are observed during the disease evolution. Thus, more studies have been carried out to investigate the therapeutic potential of plants such as Morus nigra L., popularly known as black mulberry. Studies have shown that plants belonging to the Morus genus are rich in secondary metabolites such as flavonoids which are associated with important biological activities as antioxidant and anti-inflammatory actions. Based on this context, the objective of our study was to evaluate the anti-inflammatory and antioxidant properties of Morus nigra L. in a sepsis model induced by LPS. Male C57BL/6 mice were distributed in four groups: control, sepsis, sepsis treated with leaf extract of mulberry, and sepsis treated with mulberry pulp. The animals were treated with 100 μL of their respective treatments for twenty-one days. Sepsis was induced at the 21st day with lipopolysaccharide (LPS) by intraperitoneal injection. The animals were euthanized 24 hours after receiving the LPS injection. The data obtained were analyzed in GraphPad Prism 6.0 software. Our results showed that treatment with either extract significantly decreased the number of leukocytes in the bronchoalveolar lavage fluid and serum levels of TNF in septic animals. Regarding the redox status, the treatments significantly decreased the antioxidant activity of the enzyme glutathione peroxidase. Regarding metalloproteinase type 2, it was observed that the treatment with black mulberry pulp was able to significantly reduce the activity of this enzyme concerning the sepsis group. Finally, these results together promoted an increase in the animal's survival that received the black mulberry leaf or pulp extract.
Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC) of 0.247 μmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia and alterations in the carbohydrate, lipid, and protein metabolism. DM is associated with increased oxidative stress and pancreatic beta cell damage, which impair the production of insulin and the maintenance of normoglycemia. Inhibiting oxidative damage and controlling hyperglycemia are two important strategies for the prevention of diabetes. The pulp and leaf extracts of mulberry (Morus nigra L.) have abundant total phenolics and flavonoids, and its antioxidant potential may be an important factor for modulating oxidative stress induced by diabetes. In this study, DM was induced by intraperitoneal injection of alloxan monohydrate (135 mg kg(-1)). Female Fischer rats were divided into four groups: control, diabetic, diabetic pulp, and diabetic leaf extract. Animals in the diabetic pulp and diabetic leaf extract groups were treated for 30 days with M. nigra L. pulp or leaf extracts, respectively. At the end of treatment, animals were euthanized and, liver and blood samples were collected for analysis of biochemical and metabolic parameters. Our study demonstrated that treatment of diabetic rats with leaf extracts decreased the superoxide dismutase (SOD)/catalase (CAT) ratio and carbonylated protein levels by reducing oxidative stress. Moreover, the leaf extract of M. nigra L. decreased the matrix metalloproteinase (MMP)-2 activity, increased insulinemia, and alleviated hyperglycemia-induced diabetes. In conclusion, our study found that the leaf extract of M. nigra L. improved oxidative stress and complications in diabetic rats, suggesting the utility of this herbal remedy in the prevention and treatment of DM.
Aims: To investigate the in vitro antiviral activity of Distictella elongata (Vahl) Urb. ethanol extracts from leaves (LEE), fruits (FEE), stems and their main components. Methods and Results: The antiviral activity was evaluated against human herpesvirus type 1 (HSV-1), murine encephalomyocarditis virus (EMCV), vaccinia virus Western Reserve (VACV-WR) and dengue virus 2 (DENV-2) by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. LEE presented anti-HSV-1 [EC 50 142AE8 ± 5AE3 lg ml )1 ; selectivity index (SI) 2AE0] and anti-DENV-2 activity (EC 50 9AE8 ± 1AE3 lg ml )1 ; SI 1AE5). The pectolinarin (1) isolated from LEE was less active against HSV-1 and DENV-2. A mixture of the triterpenoids ursolic, pomolic and oleanolic acids was also obtained. Ursolic and oleanolic acids have shown antiviral activity against HSV-1. A mixture of pectolinarin (1) and acacetin-7-O-rutinoside (2) was isolated from FEE and has presented anti-DENV-2 activity (EC 50 11AE1 ± 1AE6 lg ml )1 ; SI > 45). Besides the antiviral activity, D. elongata has disclosed antioxidant effect. Conclusions: These data shows that D. elongata has antiviral activity mainly against HSV-1 and DENV-2, besides antioxidant activity. These effects might be principally attributed to flavonoids isolated. Significance and Impact of the Study: Distictella elongata might be considered a promising source of anti-dengue fever phytochemicals.Letters in Applied Microbiology ISSN 0266-8254
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