Incorporation of Cordia glabrata (Mart.) A.DC. extract in microemulsions and their potential antioxidant, photoprotective and virucidal activities / Incorporação de extratos de Cordia glabrata (Mart.) A.DC. em microemulsões e suas potenciais atividades antioxidante, fotoprotetora e virucida

Extracts of species from the Cordia genus have been reported with potential biological activities, such as antioxidant, antimicrobial, antiviral, and antiparasitic. The aim of this study was to develop microemulsions containing ethanolic extracts of C. glabrata leaves and to evaluate their stability and biological activities. The five developed microemulsions presented physicochemical stability and presented Newtonian behavior when submitted to rheological analysis. The diameter values of the globules ranged between 225.74 and 273.33 nm and the zeta potential of the formulations remained between -22.40 and -25.08. All phenolic acids of the extract, quantified by HPLC, showed consistency after being microemulsified. The EC50 values for the antioxidant activity by the DPPH scavenging method ranged between 38.13 and 45.54 µgmL-1, and between 34.46 and 39.60 mM for the ABTS+ scavenging method. The virucidal activity presented a CV50 <0.195 µgmL-1 and a selectivity index greater than 20. The photoprotection results ranged between 2.14 to 2.84. The study revealed stable microemulsions and potentiation of the antioxidant effect in the microemulsified extracts.

Extratos de espécies do gênero Cordia têm sido relatados com potencial atividade biológica, como antioxidante, antimicrobiana, antiviral e antiparasitária. O objetivo deste estudo foi desenvolver microemulsões contendo extratos etanólicos de folhas de C. glabrata e avaliar sua estabilidade e atividades biológicas. As cinco microemulsões desenvolvidas apresentaram estabilidade físico-química e apresentaram comportamento newtoniano quando submetidas à análise reológica. Os valores de diâmetro dos glóbulos variaram entre 225,74 e 273,33 nm e o potencial zeta das formulações permaneceu entre -22,40 e -25,08. Todos os ácidos fenólicos do extrato, quantificados por CLAE, apresentaram consistência após serem microemulsionados. Os valores de EC50 para a atividade antioxidante pelo método de eliminação DPPH variaram entre 38,13 e 45,54 µgmL-1, e entre 34,46 e 39,60 mM para o método de eliminação ABTS+. A atividade viricida apresentou CV50 <0,195 µgmL-1 e índice de seletividade maior que 20. Os resultados da fotoproteção variaram entre 2,14 a 2,84. O estudo revelou microemulsões estáveis ​​e potencialização do efeito antioxidante nos extratos microemulsionados.

Topical formulations containing Trichilia catigua extract as therapeutic options for a genital and an acyclovir-resistant strain of herpes recurrent infection.

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infect, respectively, 67% and 13% of the world population, most commonly causing mild symptoms, such as blisters/ulcers. However, severe conditions such as keratitis, encephalitis, and systemic infections may occur, generally associated with the patient's immunological condition. Although Acyclovir® (ACV) and its analogs are the reference drugs for herpetic infections, the number of ACV-resistant HSV infections is growing exponentially. Therefore, new natural products' bioactive compounds have been studied to develop novel effective anti-herpetics. Trichilia catigua is a plant widely used in traditional medicine, including the treatment of skin diseases and sexual infections. In our study, 16 extracts from the bark of T. catigua, obtained with different solvents and their combinations, were evaluated against HSV-1 AR and HSV-2, respectively, ACV resistance and genital strains in vitro. The extracts with the highest selectivity index were used to prepare new topical anti-herpetic formulations and confirmed in vivo. Two new topical formulations were suggested to treat cutaneous and genital herpetic recurrent lesions. The cytotoxicity and antiviral activity were tested using the MTT method. The cytotoxic (CC50) and inhibitory (IC50) concentrations of 50% and the selectivity index (SI: CC50/IC50) were determined. Tc12, Tc13, and Tc16 were added to the formulations. Infected BALB/c mice were treated for 8 days, and the severity of the herpetic lesions was analyzed daily. All CEs showed a CC50 value ranging from 143 to 400 µg/mL, except for Tc3 and Tc10. Tc12, Tc13, and Tc16 showed the best SI in the 0 h, virucidal, and adsorption inhibition assays. In the in vivo test against HSV-1 AR, the infected animals treated with creams were statistically different from the infected non-treated animals and similar to ACV-treated mice. In HSV-2-infected genitalia, similar effects were found for Tc13 and Tc16 gels. The present study demonstrated that extracts from the bark of T. catigua, traditionally used in folk medicine, are a valuable source of active compounds with anti-herpetic activity. The extracts showed a virucidal mechanism of action and prevented the initial stages of viral replication. The cutaneous and genital infections were strongly inhibited by the Tc12, Tc13, and Tc16 extracts. New topical therapeutic alternatives using Trichilia catigua extracts are suggested for patients infected with ACV-resistant strains of HSV.

Contribution of carbohydrate-related metabolism in Herpesvirus infections.

Human herpesviruses are enveloped viruses with double-stranded linear DNA genomes highly prevalent in the human population. These viruses are subdivided into three subfamilies, namely alphaherpesvirinae (herpes simplex virus type 1, HSV-1; herpes simplex virus type 2, HSV-2; and varicella-zoster virus, VZV), betaherpesvirinae (human cytomegalovirus, HCMV; human herpesvirus 6, HHV-6; and human herpesvirus 7, HHV-7) and gammaherpesvirinae (Epstein-Barr virus, EBV; and Kaposi's sarcoma-associated herpesvirus, KSHV). Besides encoding numerous molecular determinants to evade the host antiviral responses, these viruses also modulate cellular metabolic processes to promote their replication. Here, we review and discuss existing studies describing an interplay between carbohydrate metabolism and the replication cycle of herpesviruses, altogether highlighting potentially new molecular targets based on these interactions that could be used to block herpesvirus infections.

Seroprevalence and Vaginal Shedding of Herpes Simplex Virus Type 2 in Pregnant Adolescents and Young Women from Morelos, Mexico.

Adolescents and young people are particularly vulnerable to contracting STIs, including HSV-2; furthermore, vaginal shedding of HSV-2 during pregnancy can cause vertical transmission and neonatal herpes. To evaluate the seroprevalence of HSV-2 and vaginal HSV-2 shedding in adolescent and young pregnant women, a cross-sectional study was carried out in 496 pregnant women-adolescents and young women. Venous blood and vaginal exudate samples were taken. The seroprevalence of HSV-2 was determined by ELISA and Western blot. Vaginal HSV-2 shedding was assessed by qPCR of the HSV-2 UL30 gene. The seroprevalence of HSV-2 in the study population was 8.5% (95% CI 6-11), of which 38.1% had vaginal HSV-2 shedding (95% CI 22-53). Young women presented a higher seroprevalence of HSV-2 (12.1%) than adolescents (4.3%), OR = 3.4, 95% CI 1.59-7.23. Frequent alcohol consumption was significantly associated with HSV-2 seroprevalence, OR = 2.9, 95% CI 1.27-6.99. Vaginal HSV-2 shedding is highest in the third trimester of pregnancy, but this difference is not significant. The seroprevalence of HSV-2 in adolescents and young women is similar to that previously reported in other studies. However, the proportion of women with vaginal shedding of HSV-2 is higher during the third trimester of pregnancy, increasing the risk of vertical transmission.

Phytochemical screening of Cordia glabrata (MART.) A.DC. extracts and its potential antioxidant, photoprotective, antimicrobial and antiviral activities / Triagem fitoquímica de extratos de Cordia glabrata (MART.) A.DC. e sua potencial atividade antioxidante, fotoprotetora, antimicrobiana e antiviral

Species of the genus Cordia have shown biological activities, such as anti-inflammatory, analgesic, antioxidant, antiviral, and antifungal activities. The species Cordia glabrata (MART) A.DC. Has no information concerning its phytochemical profile and possible biological activities. Thus, this study aimed to evaluate this profile in ethanolic extracts of young, adult and senescent leaves, as well as their antioxidant, photoprotective, antimicrobial, and virucidal potentials. Phytochemical analysis was performed by TLC (thin-layer chromatography) and showed the presence of flavonoids, tannins, and terpenes. The evaluation by UPLC-MS/MS (Ultra performance liquid chromatography - tandem mass spectrometer) evidenced the presence of caffeic (3.89 mgL-¹), p-cumaric (6.13 mgL-¹), and ferulic (0.58 mgL-¹) acids, whilst, in GC/MS (Gas chromatography–mass spectrometry) analysis there was a greater amount of palmitic (51.17%), stearic (20.34%), linoleic (9.62%), and miristic (8.16%) fatty acids. The DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ABTS+ (2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radicals were used to verify the potential antioxidant activity, observing a better activity for the leaf extract in the adult phenological stage: 54.63 ± 1.06 µgmL-¹ (DPPH) and 44.21 ± 1.69 mM (ABTS). The potential photoprotective activity of the extracts was determined by spectrophotometry and the in vitro values of SPF (Sun Protection Factor) in young and adult leaves (5.47 and 5.41, respectively) showed values close to the minimum SPF of 6.0 required by ANVISA (Brazilian Health Regulatory Agency). It was not observed an antimicrobial activity for Staphylococcus aureus with a minimum inhibitory concentration of 2000 µgmL-¹, however the anti-herpetic assay against the Herpes simplex virus type 2 (HSV-2) showed a potent virucidal activity at the tested concentrations with CV50 value <0.195 µgmL-¹ and a Selectivity Index (SI = CC50 / CV50) greater than 448. The results [...].(AU)

Espécies do gênero Cordia apresentam atividades biológicas, como anti-inflamatória, analgésica, antioxidante, antiviral e antifúngica. Para a espécie Cordia glabrata (MART) A.DC., ainda não existem informações sobre seu perfil fitoquímico e possíveis atividades biológicas, deste modo, o presente estudo teve como objetivo avaliar este perfil em extratos etanólicos de folhas jovens, adultas e senescentes, bem como o potencial antioxidante, fotoprotetor, antimicrobiano e virucida. A análise fitoquímica foi realizada por CCD (Cromatografia em Camada Delgada), mostrando a presença de flavonóides, taninos e terpenos. Na avaliação por CLAE EM/EM (Cromatografia Líquida de Ultra Eficiência acoplada a Espectrometria de Massas) foi evidenciado a presença dos ácidos caféico (3,89 mgL-¹), p-cumárico (6,13 mgL-¹) e ferúlico (0,58 mgL-¹), paralelamente, na CG/EM (Cromatografia Gasosa acoplada a Espectrometria de Massas) verificou-se maior quantidade dos ácidos graxos palmítico (51,17%), esteárico (20,34%), linoléico (9,62%) e mirístico (8,16%). Os radicais DPPH (2,2-Difenil-1-picrilhidrazil) e ABTS+ (2′-Azino-bis (ácido 3-etilbenzotiazolina-6-sulfônico)) foram utilizados para verificar o potencial antioxidante, observando se uma atividade superior para o extrato da folha em sua fase fenológica adulta: 54,63 ± 1,06 µgmL-¹ (DPPH) e 44,21 ± 1,69 mM (ABTS+). A potencial atividade fotoprotetora dos extratos foi determinada espectrofotometricamente e os valores in vitro de FPS (Fator de Proteção Solar) em folhas jovens e adultas (5,47 e 5,41 respectivamente) apresentaram valores próximos ao FPS mínimo de 6,0 exigido pela ANVISA (Agência Nacional de Vigilância Sanitária). Não foi observada atividade antimicrobiana para Staphylococcus aureus sendo a concentração inibitória mínima de 2000 µgmL-¹, no entanto o ensaio anti-herpético contra o vírus Herpes simplex tipo 2 (HSV-2) mostrou uma potente atividade virucida nas concentrações testadas [...].(AU)

Phytochemical screening of Cordia glabrata (MART.) A.DC. extracts and its potential antioxidant, photoprotective, antimicrobial and antiviral activities

Abstract Species of the genus Cordia have shown biological activities, such as anti-inflammatory, analgesic, antioxidant, antiviral, and antifungal activities. The species Cordia glabrata (MART) A.DC. Has no information concerning its phytochemical profile and possible biological activities. Thus, this study aimed to evaluate this profile in ethanolic extracts of young, adult and senescent leaves, as well as their antioxidant, photoprotective, antimicrobial, and virucidal potentials. Phytochemical analysis was performed by TLC (thin-layer chromatography) and showed the presence of flavonoids, tannins, and terpenes. The evaluation by UPLC-MS/MS (Ultra performance liquid chromatography - tandem mass spectrometer) evidenced the presence of caffeic (3.89 mgL-1), p-cumaric (6.13 mgL-1), and ferulic (0.58 mgL-1) acids, whilst, in GC/MS (Gas chromatographymass spectrometry) analysis there was a greater amount of palmitic (51.17%), stearic (20.34%), linoleic (9.62%), and miristic (8.16%) fatty acids. The DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ABTS+ (2-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radicals were used to verify the potential antioxidant activity, observing a better activity for the leaf extract in the adult phenological stage: 54.63 ± 1.06 µgmL-1 (DPPH) and 44.21 ± 1.69 mM (ABTS). The potential photoprotective activity of the extracts was determined by spectrophotometry and the in vitro values of SPF (Sun Protection Factor) in young and adult leaves (5.47 and 5.41, respectively) showed values close to the minimum SPF of 6.0 required by ANVISA (Brazilian Health Regulatory Agency). It was not observed an antimicrobial activity for Staphylococcus aureus with a minimum inhibitory concentration of 2000 gmL-1, however the anti-herpetic assay against the Herpes simplex virus type 2 (HSV-2) showed a potent virucidal activity at the tested concentrations with CV50 value 0.195 gmL-1 and a Selectivity Index (SI = CC50 / CV50) greater than 448. The results obtained in this study suggest that extracts of leaves of C. glabrata in their adult phenological stage have potential antioxidant, photoprotective and virucidal activity, considering in vitro test results.

Resumo Espécies do gênero Cordia apresentam atividades biológicas, como anti-inflamatória, analgésica, antioxidante, antiviral e antifúngica. Para a espécie Cordia glabrata (MART) A.DC., ainda não existem informações sobre seu perfil fitoquímico e possíveis atividades biológicas, deste modo, o presente estudo teve como objetivo avaliar este perfil em extratos etanólicos de folhas jovens, adultas e senescentes, bem como o potencial antioxidante, fotoprotetor, antimicrobiano e virucida. A análise fitoquímica foi realizada por CCD (Cromatografia em Camada Delgada), mostrando a presença de flavonóides, taninos e terpenos. Na avaliação por CLAE EM/EM (Cromatografia Líquida de Ultra Eficiência acoplada a Espectrometria de Massas) foi evidenciado a presença dos ácidos caféico (3,89 mgL-1), p-cumárico (6,13 mgL-1) e ferúlico (0,58 mgL-1), paralelamente, na CG/EM (Cromatografia Gasosa acoplada a Espectrometria de Massas) verificou-se maior quantidade dos ácidos graxos palmítico (51,17%), esteárico (20,34%), linoléico (9,62%) e mirístico (8,16%). Os radicais DPPH (2,2-Difenil-1-picrilhidrazil) e ABTS+ (2-Azino-bis (ácido 3-etilbenzotiazolina-6-sulfônico)) foram utilizados para verificar o potencial antioxidante, observando-se uma atividade superior para o extrato da folha em sua fase fenológica adulta: 54,63 ± 1,06 µgmL-1 (DPPH) e 44,21 ± 1,69 mM (ABTS+). A potencial atividade fotoprotetora dos extratos foi determinada espectrofotometricamente e os valores in vitro de FPS (Fator de Proteção Solar) em folhas jovens e adultas (5,47 e 5,41 respectivamente) apresentaram valores próximos ao FPS mínimo de 6,0 exigido pela ANVISA (Agência Nacional de Vigilância Sanitária). Não foi observada atividade antimicrobiana para Staphylococcus aureus sendo a concentração inibitória mínima de 2000 gmL-1, no entanto o ensaio anti-herpético contra o vírus Herpes simplex tipo 2 (HSV-2) mostrou uma potente atividade virucida nas concentrações testadas com um valor de CV50 0,195 gmL-1 e um Índice de Seletividade (IS = CC50 / CV50) maior que 448. Os resultados obtidos neste estudo sugerem que extratos de folhas de C. glabrata em seu estágio fenológico adulto apresentam potencial antioxidante, fotoprotetora e virucida, considerando os resultados de testes in vitro.

Phytochemical screening of Cordia glabrata (MART.) A.DC. extracts and its potential antioxidant, photoprotective, antimicrobial and antiviral activities / Triagem fitoquímica de extratos de Cordia glabrata (MART.) A.DC. e sua potencial atividade antioxidante, fotoprotetora, antimicrobiana e antiviral

Abstract Species of the genus Cordia have shown biological activities, such as anti-inflammatory, analgesic, antioxidant, antiviral, and antifungal activities. The species Cordia glabrata (MART) A.DC. Has no information concerning its phytochemical profile and possible biological activities. Thus, this study aimed to evaluate this profile in ethanolic extracts of young, adult and senescent leaves, as well as their antioxidant, photoprotective, antimicrobial, and virucidal potentials. Phytochemical analysis was performed by TLC (thin-layer chromatography) and showed the presence of flavonoids, tannins, and terpenes. The evaluation by UPLC-MS/MS (Ultra performance liquid chromatography - tandem mass spectrometer) evidenced the presence of caffeic (3.89 mgL-1), p-cumaric (6.13 mgL-1), and ferulic (0.58 mgL-1) acids, whilst, in GC/MS (Gas chromatography-mass spectrometry) analysis there was a greater amount of palmitic (51.17%), stearic (20.34%), linoleic (9.62%), and miristic (8.16%) fatty acids. The DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ABTS+ (2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radicals were used to verify the potential antioxidant activity, observing a better activity for the leaf extract in the adult phenological stage: 54.63 ± 1.06 µgmL-1 (DPPH) and 44.21 ± 1.69 mM (ABTS). The potential photoprotective activity of the extracts was determined by spectrophotometry and the in vitro values of SPF (Sun Protection Factor) in young and adult leaves (5.47 and 5.41, respectively) showed values close to the minimum SPF of 6.0 required by ANVISA (Brazilian Health Regulatory Agency). It was not observed an antimicrobial activity for Staphylococcus aureus with a minimum inhibitory concentration of 2000 μgmL-1, however the anti-herpetic assay against the Herpes simplex virus type 2 (HSV-2) showed a potent virucidal activity at the tested concentrations with CV50 value <0.195 μgmL-1 and a Selectivity Index (SI = CC50 / CV50) greater than 448. The results obtained in this study suggest that extracts of leaves of C. glabrata in their adult phenological stage have potential antioxidant, photoprotective and virucidal activity, considering in vitro test results.

Resumo Espécies do gênero Cordia apresentam atividades biológicas, como anti-inflamatória, analgésica, antioxidante, antiviral e antifúngica. Para a espécie Cordia glabrata (MART) A.DC., ainda não existem informações sobre seu perfil fitoquímico e possíveis atividades biológicas, deste modo, o presente estudo teve como objetivo avaliar este perfil em extratos etanólicos de folhas jovens, adultas e senescentes, bem como o potencial antioxidante, fotoprotetor, antimicrobiano e virucida. A análise fitoquímica foi realizada por CCD (Cromatografia em Camada Delgada), mostrando a presença de flavonóides, taninos e terpenos. Na avaliação por CLAE EM/EM (Cromatografia Líquida de Ultra Eficiência acoplada a Espectrometria de Massas) foi evidenciado a presença dos ácidos caféico (3,89 mgL-1), p-cumárico (6,13 mgL-1) e ferúlico (0,58 mgL-1), paralelamente, na CG/EM (Cromatografia Gasosa acoplada a Espectrometria de Massas) verificou-se maior quantidade dos ácidos graxos palmítico (51,17%), esteárico (20,34%), linoléico (9,62%) e mirístico (8,16%). Os radicais DPPH (2,2-Difenil-1-picrilhidrazil) e ABTS+ (2′-Azino-bis (ácido 3-etilbenzotiazolina-6-sulfônico)) foram utilizados para verificar o potencial antioxidante, observando-se uma atividade superior para o extrato da folha em sua fase fenológica adulta: 54,63 ± 1,06 µgmL-1 (DPPH) e 44,21 ± 1,69 mM (ABTS+). A potencial atividade fotoprotetora dos extratos foi determinada espectrofotometricamente e os valores in vitro de FPS (Fator de Proteção Solar) em folhas jovens e adultas (5,47 e 5,41 respectivamente) apresentaram valores próximos ao FPS mínimo de 6,0 exigido pela ANVISA (Agência Nacional de Vigilância Sanitária). Não foi observada atividade antimicrobiana para Staphylococcus aureus sendo a concentração inibitória mínima de 2000 μgmL-1, no entanto o ensaio anti-herpético contra o vírus Herpes simplex tipo 2 (HSV-2) mostrou uma potente atividade virucida nas concentrações testadas com um valor de CV50 <0,195 μgmL-1 e um Índice de Seletividade (IS = CC50 / CV50) maior que 448. Os resultados obtidos neste estudo sugerem que extratos de folhas de C. glabrata em seu estágio fenológico adulto apresentam potencial antioxidante, fotoprotetora e virucida, considerando os resultados de testes in vitro.

Phytochemical screening of Cordia glabrata (MART.) A.DC. extracts and its potential antioxidant, photoprotective, antimicrobial and antiviral activities / Triagem fitoquímica de extratos de Cordia glabrata (MART.) A.DC. e sua potencial atividade antioxidante, fotoprotetora, antimicrobiana e antiviral

Species of the genus Cordia have shown biological activities, such as anti-inflammatory, analgesic, antioxidant, antiviral, and antifungal activities. The species Cordia glabrata (MART) A.DC. Has no information concerning its phytochemical profile and possible biological activities. Thus, this study aimed to evaluate this profile in ethanolic extracts of young, adult and senescent leaves, as well as their antioxidant, photoprotective, antimicrobial, and virucidal potentials. Phytochemical analysis was performed by TLC (thin-layer chromatography) and showed the presence of flavonoids, tannins, and terpenes. The evaluation by UPLC-MS/MS (Ultra performance liquid chromatography - tandem mass spectrometer) evidenced the presence of caffeic (3.89 mgL-¹), p-cumaric (6.13 mgL-¹), and ferulic (0.58 mgL-¹) acids, whilst, in GC/MS (Gas chromatography–mass spectrometry) analysis there was a greater amount of palmitic (51.17%), stearic (20.34%), linoleic (9.62%), and miristic (8.16%) fatty acids. The DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ABTS+ (2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radicals were used to verify the potential antioxidant activity, observing a better activity for the leaf extract in the adult phenological stage: 54.63 ± 1.06 µgmL-¹ (DPPH) and 44.21 ± 1.69 mM (ABTS). The potential photoprotective activity of the extracts was determined by spectrophotometry and the in vitro values of SPF (Sun Protection Factor) in young and adult leaves (5.47 and 5.41, respectively) showed values close to the minimum SPF of 6.0 required by ANVISA (Brazilian Health Regulatory Agency). It was not observed an antimicrobial activity for Staphylococcus aureus with a minimum inhibitory concentration of 2000 µgmL-¹, however the anti-herpetic assay against the Herpes simplex virus type 2 (HSV-2) showed a potent virucidal activity at the tested concentrations with CV50 value <0.195 µgmL-¹ and a Selectivity Index (SI = CC50 / CV50) greater than 448. The results [...].

Espécies do gênero Cordia apresentam atividades biológicas, como anti-inflamatória, analgésica, antioxidante, antiviral e antifúngica. Para a espécie Cordia glabrata (MART) A.DC., ainda não existem informações sobre seu perfil fitoquímico e possíveis atividades biológicas, deste modo, o presente estudo teve como objetivo avaliar este perfil em extratos etanólicos de folhas jovens, adultas e senescentes, bem como o potencial antioxidante, fotoprotetor, antimicrobiano e virucida. A análise fitoquímica foi realizada por CCD (Cromatografia em Camada Delgada), mostrando a presença de flavonóides, taninos e terpenos. Na avaliação por CLAE EM/EM (Cromatografia Líquida de Ultra Eficiência acoplada a Espectrometria de Massas) foi evidenciado a presença dos ácidos caféico (3,89 mgL-¹), p-cumárico (6,13 mgL-¹) e ferúlico (0,58 mgL-¹), paralelamente, na CG/EM (Cromatografia Gasosa acoplada a Espectrometria de Massas) verificou-se maior quantidade dos ácidos graxos palmítico (51,17%), esteárico (20,34%), linoléico (9,62%) e mirístico (8,16%). Os radicais DPPH (2,2-Difenil-1-picrilhidrazil) e ABTS+ (2′-Azino-bis (ácido 3-etilbenzotiazolina-6-sulfônico)) foram utilizados para verificar o potencial antioxidante, observando se uma atividade superior para o extrato da folha em sua fase fenológica adulta: 54,63 ± 1,06 µgmL-¹ (DPPH) e 44,21 ± 1,69 mM (ABTS+). A potencial atividade fotoprotetora dos extratos foi determinada espectrofotometricamente e os valores in vitro de FPS (Fator de Proteção Solar) em folhas jovens e adultas (5,47 e 5,41 respectivamente) apresentaram valores próximos ao FPS mínimo de 6,0 exigido pela ANVISA (Agência Nacional de Vigilância Sanitária). Não foi observada atividade antimicrobiana para Staphylococcus aureus sendo a concentração inibitória mínima de 2000 µgmL-¹, no entanto o ensaio anti-herpético contra o vírus Herpes simplex tipo 2 (HSV-2) mostrou uma potente atividade virucida nas concentrações testadas [...].

Development of a cell-based reporter assay for detection of Human alphaherpesviruses.

Immunosuppressed patients can suffer from Human alphaherpesvirus (HSV) infection with fast evolution, severe atypical symptomatology, and often-fatal outcome. Thus, the development and validation of new methods in vitro and in vivo to promote an early diagnosis and effective treatment of these patients are crucial. Therefore, this work aimed to develop a cell-based reporter assay for the detection of HSV through the transfection of Vero cells with the ICP10 promoter from HSV-2 linked to the pZsGreen1-1 plasmid. The assay was evaluated on Vero cells infected with HSV-1 or HSV-2 and followed by treating them with anti-HSV agents (acyclovir, gallic acid, convallatoxin, and Uncaria sp. extract) or with no anti-HSV activity agents (Passiflora edulis extract and cardenolide derivatives). The GFP expression was increased by both HSV cellular infection, which was detected by flow cytometry and fluorescence microscopy. F2R Zsgreen1-1 cells infection with 200 and 600 PFU/mL of HSV-2 increased the fluorescence intensity, when compared to the controls, by approximately 30% and 60%, respectively. Infection with 100 and 600 PFU/mL of HSV-1 also increased the fluorescence intensity by approximately 20% and 35%, when compared to the controls, respectively. The F2R ZsGreen1-1 system revealed to be an efficient assay, which can be used for clinical diagnosis, antiviral resistance evaluation, HSV cycle studies, and new antiviral drug research.

Herpes simplex virus interference with immunity: Focus on dendritic cells.

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are highly prevalent in the human population. These viruses cause lifelong infections by establishing latency in neurons and undergo sporadic reactivations that promote recurrent disease and new infections. The success of HSVs in persisting in infected individuals is likely due to their multiple molecular determinants involved in escaping the host antiviral and immune responses. Importantly, HSVs infect and negatively modulate the function of dendritic cells (DCs), key immune cells that are involved in establishing effective and balanced immunity against viruses. Here, we review and discuss several molecular and cellular processes modulated by HSVs in DCs, such as autophagy, apoptosis, and the unfolded protein response. Given the central role of DCs in establishing optimal antiviral immunity, particular emphasis should be given to the outcome of the interactions occurring between HSVs and DCs.

Manifestaciones neurológicas del herpes virus simple y varicela zóster / Neurological manifestations of herpes simplex virus and varicella zoster

RESUMEN El espectro de manifestaciones neurológicas secundarias a la infección por la familia de virus Herpesviridae es heterogénea, depende de factores ambientales, de la susceptibilidad inmunológica del huésped (infección de por vida) y la susceptibilidad genética, entre otras variables. Así, el compromiso puede ser fatal en ausencia de un rápido diagnóstico y tratamiento. El objetivo de revisar la neuroinfección por herpesvirus tipo 1 (HSV-1), tipo 2 (HSV-2) y virus de la varicela zóster (VVZ) es profundizar en aquellas manifestaciones clínicas que generan compromiso del sistema nervioso central y periférico, así como contribuir a una detección y confirmación temprana de la infección, establecer un enfoque terapéutico adecuado, que depende del compromiso clínico, y, finalmente, minimizar las complicaciones y secuelas neurológicas a largo plazo.

SUMMARY The spectrum of neurological manifestations secondary to infection by the family of viruses Herpesviridae is heterogeneous depending on environmental factors, susceptibility host immunological (infection for life), genetic susceptibility among other variables. Thus, the compromise can be fatal in the absence of prompt diagnosis and treatment. He objective of reviewing neuroinfection by Herpes virus type 1 (HSV-1), type 2 (HSV-2) and virus varicella zoster (VVZ) is to delve into those clinical manifestations that generate central and peripheral nervous system involvement, seeks to detect and confirm early, and likewise establish an adequate therapeutic approach that depends on the clinical commitment, ultimately minimizing long-term neurological complications and sequelae term.

Pharmacological Inhibition of IRE-1 Alpha Activity in Herpes Simplex Virus Type 1 and Type 2-Infected Dendritic Cells Enhances T Cell Activation.

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are life-long and highly prevalent in the human population. These viruses persist in the host, eliciting either symptomatic or asymptomatic infections that may occur sporadically or in a recurrent manner through viral reactivations. Clinical manifestations due to symptomatic infection may be mild such as orofacial lesions, but may also translate into more severe diseases, such as ocular infections that may lead to blindness and life-threatening encephalitis. A key feature of herpes simplex viruses (HSVs) is that they have evolved molecular determinants that hamper numerous components of the host's antiviral innate and adaptive immune system. Importantly, HSVs infect and negatively modulate the function of dendritic cells (DCs), by inhibiting their T cell-activating capacity and eliciting their apoptosis after infection. Previously, we reported that HSV-2 activates the splicing of the mRNA of XBP1, which is related to the activity of the unfolded protein response (UPR) factor Inositol-Requiring Enzyme 1 alpha (IRE-1α). Here, we sought to evaluate if the activation of the IRE-1α pathway in DCs upon HSV infection may be related to impaired DC function after infection with HSV-1 or HSV-2. Interestingly, the pharmacological inhibition of the endonuclease activity of IRE-1α in HSV-1- and HSV-2-infected DCs significantly reduced apoptosis in these cells and enhanced their capacity to migrate to lymph nodes and activate virus-specific CD4+ and CD8+ T cells. These findings suggest that the activation of the IRE-1α-dependent UPR pathway in HSV-infected DCs may play a significant role in the negative effects that these viruses exert over these cells and that the modulation of this signaling pathway may be relevant for enhancing the function of DCs upon infection with HSVs.

Anti-herpetic Activity of Macrocystis pyrifera and Durvillaea antarctica Algae Extracts Against HSV-1 and HSV-2.

Herpes simplex viruses (HSVs) type 1 (HSV-1) and type 2 (HSV-2) are highly prevalent in the human population, and the infections they produce are lifelong with frequent reactivations throughout life. Both viruses produce uncomfortable and sometimes painful lesions in the orofacial and genital areas, as well as herpetic gingivostomatitis, among other clinical manifestations. At present, the most common treatments against HSVs consist of nucleoside analogs that target the viral polymerases. However, such drugs are poorly effective for treating skin lesions, as they only reduce in 1-2 days the duration of the herpetic lesions. Additionally, viral isolates resistant to these drugs can emerge in immunosuppressed individuals, and second-line drugs for such variants are frequently accompanied by adverse effects requiring medical supervision. Thus, novel or improved therapeutic drugs for treating HSV lesions are needed. Here, we assessed the potential antiviral activity of aqueous extracts obtained from two brown macroalgae, namely Macrocystis pyrifera and Durvillaea antarctica against HSVs. Both extracts showed antiviral activity against acyclovir-sensitive and acyclovir-resistant HSV-1 and HSV-2. Our analyses show that there is a significant antiviral activity associated with proteins in the extract, although other compounds also seem to contribute to inhibiting the replication cycle of these viruses. Evaluation of the algae extracts as topical formulations in an animal model of HSV-1 skin infection significantly reduced the severity of the disease more than acyclovir, as well as the duration of the herpetic lesions, when compared to mock-treated animals, with the D. antarctica extract performing best. Taken together, these findings suggest that these algae extracts may be potential phytotherapeutics against HSVs and may be useful for the treatment and reduction of common herpetic manifestations in humans.

Current Antivirals and Novel Botanical Molecules Interfering With Herpes Simplex Virus Infection.

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are highly prevalent within the human population and are characterized by lifelong infections and sporadic recurrences due to latent neuron infection. Upon reactivations, HSVs may manifest either, symptomatically or asymptomatically and be shed onto others through mucosae body fluids. Although, HSVs can produce severe disease in humans, such as life-threatening encephalitis and blindness, the most common symptoms are skin and mucosal lesions in the oro-facial and the genital areas. Nucleoside analogs with antiviral activity can prevent severe HSV infection, yet they are not very effective for treating skin manifestations produced by these viruses, as they only reduce in a few days at most the duration of lesions. Additionally, HSV variants that are resistant to these antivirals may arise, especially in immunosuppressed individuals. Thus, new antivirals that can reduce the severity and duration of these cutaneous manifestations would certainly be welcome. Here, we review currently available anti-herpetic therapies, novel molecules being assessed in clinical trials and new botanical compounds reported in the last 20 years with antiviral activities against HSVs that might represent future treatments against these viruses.

Prevalence of viral sexually transmitted infections and HPV high-risk genotypes in women in rural communities in the Department of La Paz, Bolivia.

BACKGROUND: Bolivia has the highest prevalence of cervical cancer in South America and the prevalence of viral sexually transmitted infections (STIs) among people in urban cities is increasing. Little is known about the prevalence of viral STIs in rural communities, which generally have limited access to health care. In order to study the prevalence of viral STIs in rural Bolivia, we recruited women from villages and towns in the Department of La Paz in Bolivia. METHODS: Three hundred ninety-four female participants were assessed for IgG-antibodies to herpes simplex virus type 2 (HSV-2), human immunodeficiency virus (HIV) and hepatitis B virus (HBV, anti-HBc), as well as for the presence of HBV surface antigen (HBsAg) in dried blood spots. The prevalence of 12 high-risk types of human papillomavirus (HPV) was assessed by qPCR in dried cervicovaginal cell spots from 376 of these women. χ2 test was used to compare variables between the populations and binary logistic regression was used to identify risk factors associated with the positivity of the tests. RESULTS: The seroprevalence of HSV-2 was 53% and of HBV 10.3%. HBAg was detected in 15.8% of women with anti-HBV antibodies indicating chronic infection. The frequency of high-risk HPV infection was 27%, with the most prevalent high-risk HPV types being HPV 56, 39 and 31 followed by HPV 16 and 18. Finally, none of the 394 women were seropositive for HIV, and about 64% of the studied population was positive for at least one of the viral infections. CONCLUSIONS: Women in Bolivian rural communities in La Paz show a high prevalence of HBV, HPV and, in particular, HSV-2. In contrast, none of the women were HIV positive, suggesting that the HIV prevalence in this population is low. The pattern of high-risk HPV types differed from many other countries with a predominance of HPV-types not included in the Gardasil vaccine which was officially introduced in Bolivia in April 2017.

Herpes simplex virus type 2 meningitis as a manifestation of Good's syndrome.

Good's syndrome is a primary immunodeficiency phenocopy characterized for thymoma and immunodeficiency. The most frequent clinical presentation is recurrent or opportunistic infections, hematological alterations, and chronic diarrhea. We treated a 66-year-old man who consulted for 5 days of headache and diplopia with right sixth cranial nerve palsy at examination. Patient reported chronic diarrhea and prolonged febrile syndrome accompanied by weight loss of 23 kg in the last year. Exhaustive evaluation revealed Herpes simplex virus (HSV) type 2 meningitis, eosinophilic colitis, and type A thymoma. Severe antibody deficiency (hypogammaglobulinemia) associated with thymoma confirmed the diagnosis of Good's syndrome.

Behavioral, Psychological, Gender, and Health Service Correlates to Herpes Simplex Virus Type 2 Infection among Young Adult Mexican-American Women Living in a Disadvantaged Community.

Herpes simplex virus type 2 (HSV-2) is among the most prevalent sexually transmitted infections in the United States. Despite this, there has been limited research on the correlates to HSV-2 among disadvantaged and marginalized women, particularly among Latinas. Data for the present analysis include 125 young adult Mexican-American women enrolled in a longitudinal study in a disadvantaged urban community in San Antonio, Texas. The current rate of tested HSV-2 infection is 56.8%. Our findings suggest strong comorbidity of genital herpes with injecting heroin use, Hepatitis C, sexual violence, incarceration, and mental illness. Contributing to this population's nexus of risk are the low rates of health service utilization among those infected with HSV-2. Integration between behavioral health and primary care, including access to preventative services, are essential for improving the health of Latinas living in disadvantaged neighborhoods.

Histidine-Rich Glycoprotein Inhibits HIV-1 Infection in a pH-Dependent Manner.

Histidine-rich glycoprotein (HRG) is an abundant plasma protein with a multidomain structure, allowing its interaction with many ligands, including phospholipids, plasminogen, fibrinogen, IgG antibodies, and heparan sulfate. HRG has been shown to regulate different biological responses, such as angiogenesis, coagulation, and fibrinolysis. Here, we found that HRG almost completely abrogated the infection of Ghost cells, Jurkat cells, CD4+ T cells, and macrophages by HIV-1 at a low pH (range, 6.5 to 5.5) but not at a neutral pH. HRG was shown to interact with the heparan sulfate expressed by target cells, inhibiting an early postbinding step associated with HIV-1 infection. More importantly, by acting on the viral particle itself, HRG induced a deleterious effect, which reduces viral infectivity. Because cervicovaginal secretions in healthy women show low pH values, even after semen deposition, our observations suggest that HRG might represent a constitutive defense mechanism in the vaginal mucosa. Of note, low pH also enabled HRG to inhibit the infection of HEp-2 cells and Vero cells by respiratory syncytial virus (RSV) and herpes simplex virus 2 (HSV-2), respectively, suggesting that HRG might display broad antiviral activity under acidic conditions.IMPORTANCE Vaginal intercourse represents a high-risk route for HIV-1 transmission. The efficiency of male-to-female HIV-1 transmission has been estimated to be 1 in every 1,000 episodes of sexual intercourse, reflecting the high degree of protection conferred by the genital mucosa. However, the contribution of different host factors to the protection against HIV-1 at mucosal surfaces remains poorly defined. Here, we report for the first time that acidic values of pH enable the plasma protein histidine-rich glycoprotein (HRG) to strongly inhibit HIV-1 infection. Because cervicovaginal secretions usually show low pH values, our observations suggest that HRG might represent a constitutive antiviral mechanism in the vaginal mucosa. Interestingly, infection by other viruses, such as respiratory syncytial virus and herpes simplex virus 2, was also markedly inhibited by HRG at low pH values, suggesting that extracellular acidosis enables HRG to display broad antiviral activity.

Extracts of Equisetum giganteum L and Copaifera reticulate Ducke show strong antiviral activity against the sexually transmitted pathogen herpes simplex virus type 2.

ETHNOPHARMACOLOGICAL RELEVANCE: Equisetum giganteum L and Copaifera reticulate Ducke have been traditionally used by women of the Tacana tribe in the Bolivian Amazonas for genital hygiene and for treatment of genital infection/inflammation. AIM OF THE STUDY: To assess the ability of extracts from Equisetum giganteum L and Copaifera reticulate Ducke to block genital viral infection by herpes simplex virus type 2. MATERIALS AND METHODS: Equisetum giganteum L and Copaifera reticulate Ducke were collected from the Amazon region of La Paz, Bolivia. Extracts were prepared and screened for anti-viral activity against herpes simplex virus type 2 (HSV-2) using both in vitro and in in vivo models of infection. RESULTS: Equisetum giganteum L and Copaifera reticulate Ducke efficiently blocked HSV-2 infection of cell cultures without major cell cytotoxic effects. Extracts of Equisetum giganteum L and Copaifera reticulate Ducke could prevent HSV-2 disease development when administered together with virus in a mouse model of genital HSV-2 infection. In vitro analyses revealed that both plant extracts exerted their anti-HSV-2 effects by interfering with viral cell attachment and entry, but could not block viral replication post entry. CONCLUSIONS: These studies show that extracts of Equisetum giganteum L and Copaifera reticulate Ducke have potent antiviral activities against HSV-2 comparable to those two previously identified plants, Croton lechleri Müll. Arg. and Uncaria tomentosa (Willd. ex Schult.) DC. These studies confirm that plants used by the Tacana tribe could be explored further for the development of novel topical antiviral microbicides.