Phenoxazine Derivatives Suppress the Infections Caused by Herpes Simplex Virus Type-1 and Herpes Simplex Virus Type-2 Intravaginally Inoculated Into Mice

Hayashi, Kyoko; Hayashi, Toshimitsu; Miyazawa, Kenji; Tomoda, Akio

doi:10.1254/jphs.10027fp

Cited by 14 publications

(7 citation statements)

References 22 publications

(30 reference statements)

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“…Genetic or pharmacological inhibition of AKT1 enhanced intracellular killing of Mtb in macrophages by promoting autophagy. The structure of 10-DEBC presents a phenoxazine core, and phenoxazine-derived compounds were shown to exhibit anti-microbial activity, including anti-mycobacterial activity by inhibiting topoisomerase I (Hayashi et al., 2010, Yu et al., 2017). Phenoxazine derivatives were also reported to inhibit mycobacterial efflux pumps involved in resistance to anti-TB drugs (Rodrigues et al., 2011).…”

Section: Discussionmentioning

confidence: 99%

Drug Discovery Platform Targeting M. tuberculosis with Human Embryonic Stem Cell-Derived Macrophages

Seo

Han

et al. 2019

Stem Cell Reports

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A major limitation in anti-tuberculosis drug screening is the lack of reliable and scalable models for homogeneous human primary macrophage cells of non-cancer origin. Here we report a modified protocol for generating homogeneous populations of macrophage-like cells from human embryonic stem cells. The induced macrophages, referred to as iMACs, presented similar transcriptomic profiles and characteristic immunological features of classical macrophages and were permissive to viral and bacterial infection, in particular Mycobacterium tuberculosis (Mtb). More importantly, iMAC production was amenable to scale up. To evaluate iMAC efficiency in high-throughput anti-tuberculosis drug screening, we performed a phenotypic screening against intracellular Mtb, involving a library of 3,716 compounds that included FDA-approved drugs and other bioactive compounds. Our primary screen identified 120 hits, which were validated in a secondary screen by dose-intracellular and-extracellular Mtb assays. Our confirmatory studies identified a novel anti-Mtb compound, 10-DEBC, also showing activity against drug-resistant strains.

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Section: Discussionmentioning

confidence: 99%

Drug Discovery Platform Targeting M. tuberculosis with Human Embryonic Stem Cell-Derived Macrophages

Seo

Han

et al. 2019

Stem Cell Reports

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“…Extravaginal lesions were recorded every day for each animal and scored according to a six‐point scale as follows: 0: no sign of infection; 1: slight genital erythema and edema; 2: moderate genital inflammation; 3: severe exudative genital lesions; 4: hind limb paralysis; and 5: death [Hayashi et al, ]. Then, they were killed on the 11th day by cervical dislocation, and vaginal tissues were removed for ex vivo experiments (histology and biochemical analyses).…”

Section: Methodsmentioning

confidence: 99%

Antiviral Action of Diphenyl Diselenide on Herpes Simplex Virus 2 Infection in Female BALB/c Mice

Sartori

Jardim

Sari

et al. 2015

J of Cellular Biochemistry

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Diphenyl diselenide, (PhSe)2 , is an organoselenium compound with pharmacological actions mostly related to antioxidant and anti-inflammatory properties. The study investigated its antiviral and virucidal actions against herpes simplex virus 2 (HSV-2) infection in vitro and in a vaginal infection model in mice. The plaque reduction assay indicated that (PhSe)2 showed virucidal and antiviral actions reducing infectivity in 70.8% and 47%, respectively. The antiviral action of (PhSe)2 against HSV-2 vaginal infection was performed by infecting mice (10(5) PFU/ml(-1) ) at day 6. The treatment with (PhSe)2 (5 mg/kg/day, intragastric [i.g.]) followed 5 days before and for more 5 days after infection. The extravaginal lesion score was evaluated from days 6 to 10. At day 11, animals were killed, and histological evaluation, determination of viral load, and TNF-α and IFN-γ levels were performed in supernatants of homogenized vaginal tissue. The levels of reactive species (RS), protein carbonyl, non-protein thiols (NPSH), nitrate/nitrite (NOx), and malondialdehyde (MDA), and the activities of myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) were determined. (PhSe)2 reduced the histological damage, extravaginal lesion scores, the viral load of vaginal tissue, and the activity of MPO, but increased the levels of TNF-α, IFN-γ. (PhSe)2 attenuated the increase of RS, MDA, NOx levels and the activity of GR caused by infection. (PhSe)2 also attenuated the reduction of NPSH content and the inhibition of CAT, SOD, and GPx activities. The antiviral action of (PhSe)2 against HSV-2 infection was related to its immunomodulatory, antioxidant, and anti-inflammatory properties. J. Cell. Biochem. 117: 1638-1648, 2016. © 2015 Wiley Periodicals, Inc.

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“…At day 11, extravaginal lesions were recorded for each animal and scored according to a six-point scale as follows: 0-no sign of infection, 1-slight genital erythema and edema, 2-moderate genital inflammation, 3-severe exudative genital lesions, 4-hind limb paralysis and 5-death. 25 Three mice of HSV-2 group died between the fourth and fifth day after HSV-2 infection and have not been included in ex vivo experiments. Afterwards, all mice were anesthetized for blood collection by heart puncture for haematological analysis.…”

Section: Virus Production and Titrationmentioning

confidence: 99%

Protective effect of brown Brazilian propolis against acute vaginal lesions caused by herpes simplex virus type 2 in mice: involvement of antioxidant and anti‐inflammatory mechanisms

Sartori

Pesarico

Pinton

et al. 2011

Cell Biochemistry & Function

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Propolis has been highlighted for its antioxidant, anti-inflammatory and antiviral properties. The purpose of this study was to investigate if brown Brazilian hydroalcoholic propolis extract (HPE) protects against vaginal lesions caused by herpes simplex virus type 2 (HSV-2) in female BALB/c mice. The treatment was divided in 5 days of pre-treatment with HPE [50 mg · kg(-1), once a day, intragastric (i.g.)], HSV-2 infection [10 µl of a solution 1 × 10(2) plaque-forming unit (PFU · ml(-1) HSV-2), intravaginal inoculation at day 6] and post-treatment with HPE (50 mg · kg(-1)) for 5 days more. At day 11, the animals were killed, and the in vivo analysis (score of lesions) and ex vivo analysis [haematological and histological evaluation; superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) activities; reactive species (RS), tyrosine nitration levels, non-protein thiols (NPSH) and ascorbic acid (AA) levels] were carried out. HPE treatment reduced extravaginal lesions and the histological damage caused by HSV-2 infection in vaginal tissues of animals. HPE was able to decrease RS, tyrosine nitration, AA levels and MPO activity. Also, it protected against the inhibition of CAT activity in vaginal tissues of mice. HPE promoted protective effect on HSV-2 infected animals by acting on inflammatory and oxidative processes, and this effect probably is caused by its antioxidant and anti-inflammatory properties.

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Phenoxazine Derivatives Suppress the Infections Caused by Herpes Simplex Virus Type-1 and Herpes Simplex Virus Type-2 Intravaginally Inoculated Into Mice

Cited by 14 publications

References 22 publications

Drug Discovery Platform Targeting M. tuberculosis with Human Embryonic Stem Cell-Derived Macrophages

Drug Discovery Platform Targeting M. tuberculosis with Human Embryonic Stem Cell-Derived Macrophages

Antiviral Action of Diphenyl Diselenide on Herpes Simplex Virus 2 Infection in Female BALB/c Mice

Protective effect of brown Brazilian propolis against acute vaginal lesions caused by herpes simplex virus type 2 in mice: involvement of antioxidant and anti‐inflammatory mechanisms

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