Inhibition of <scp>HSV‐2</scp> infection by pure compounds from <scp><i>Thymus capitatus</i></scp> extract <scp><i>in vitro</i></scp>

Toujani, Marwa Mekni; Rittá, Massimo; Civra, Andrea; Genovese, Salvatore; Epifano, Francesco; Ghram, Abdeljelil; Lembo, David; Donalisio, Manuela

doi:10.1002/ptr.6084

Cited by 36 publications

(29 citation statements)

References 34 publications

(41 reference statements)

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“…It was inactive against rhinoviruses but, reduced the influenza A virus-induced cytopathic effect at non-cytotoxic dilutions (0.03-0.33% v/v) in a dosedependent manner. Thyme extract is also known to inhibit herpes simplex virus infections in vitro [47,48] by inactivating the infectivity of the virus [48].…”

Section: Discussionmentioning

confidence: 99%

Comparative in vitro analysis of inhibition of rhinovirus and influenza virus replication by mucoactive secretolytic agents and plant extracts

Walther

Döring

Schmidtke

2020

BMC Complement Med Ther

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Background Rhinoviruses and influenza viruses cause millions of acute respiratory infections annually. Symptoms of mild acute respiratory infections are commonly treated with over-the-counter products like ambroxol, bromhexine, and N-acetyl cysteine, as well as of thyme and pelargonium extracts today. Because the direct antiviral activity of these over-the-counter products has not been studied in a systematic way, the current study aimed to compare their inhibitory effect against rhinovirus and influenza virus replication in an in vitro setting. Methods The cytotoxicity of ambroxol, bromhexine, and N-acetyl cysteine, as well as of thyme and pelargonium extracts was analyzed in Madin Darby canine kidney (MDCK) and HeLa Ohio cells. The antiviral effect of these over-the-counter products was compared by analyzing the dose-dependent inhibition (i) of rhinovirus A2- and B14-induced cytopathic effect in HeLa Ohio cells and (ii) of influenza virus A/Hong Kong/68 (subtype H3N2)- and A/Jena/8178/09 (subtype H1N1, pandemic)-induced cytopathic effect in MDCK cells at non-cytotoxic concentrations. To get insights into the mechanism of action of pelargonium extract against influenza virus, we performed time-of-addition assays as well as hemagglutination and neuraminidase inhibition assays. Results N-acetyl cysteine, thyme and pelargonium extract showed no or only marginal cytotoxicity in MDCK and HeLa Ohio cells in the tested concentration range. The 50% cytotoxic concentration of ambroxol and bromhexine was 51.85 and 61.24 μM, respectively. No anti-rhinoviral activity was detected at non-cytotoxic concentrations in this in vitro study setting. Ambroxol, bromhexine, and N-acetyl cysteine inhibited the influenza virus-induced cytopathic effect in MDCK cells no or less than 50%. In contrast, a dose-dependent anti-influenza virus activity of thyme and pelargonium extracts was demonstrated. The time-of addition assays revealed an inhibition of early and late steps of influenza virus replication by pelargonium extract whereas zanamivir acted on late steps only. The proven block of viral neuraminidase activity might explain the inhibition of influenza virus replication when added after viral adsorption. Conclusion The study results indicate a distinct inhibition of influenza A virus replication by thyme and pelargonium extract which might contribute to the beneficial effects of these plant extracts on acute respiratory infections symptoms.

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Section: Discussionmentioning

confidence: 99%

Comparative in vitro analysis of inhibition of rhinovirus and influenza virus replication by mucoactive secretolytic agents and plant extracts

Walther

Döring

Schmidtke

2020

BMC Complement Med Ther

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“…Toujani et al [ 71 ] demonstrated T. capitatus activity against HSV-1 and HSV-2 herpes viruses. Ethanol extract (EE) proved to be the most active against both tested viruses.…”

Section: Antiviral Activitymentioning

confidence: 99%

Thymol and Thyme Essential Oil—New Insights into Selected Therapeutic Applications

et al. 2020

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Thymol (2-isopropyl-5-methylphenol) belongs to the phenolic monoterpenes and mostly occurs in thyme species. It is one of the main compounds of thyme essential oil. Both thymol and thyme essential oil have long been used in traditional medicine as expectorant, anti-inflammatory, antiviral, antibacterial, and antiseptic agents, mainly in the treatment of the upper respiratory system. The current search for new directions of biological or therapeutic activities of natural plant substances with known structures includes thyme essential oil and thymol. Novel studies have demonstrated their antibiofilm, antifungal, antileishmanial, antiviral, and anticancer properties. Also, their new therapeutic formulations, such as nanocapsules containing these constituents, can be beneficial in medicinal practice and create opportunities for their extensive use. Extensive application of thymol and thyme essential oil in the healthcare sector is very promising but requires further research and analysis.

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“…The relevant literature have also indicated that carvacrol has an safety and tolerability effect on healthy volunteers through a phaseIclinical trial and possible therapeutic effect on asthmatic patients through a phase II clinical trial in recent years [19,20]. Carvacrol could exert antiviral activity by preventing the death of cells infected with HSV, but the specific mechanism of it against HSV virus has not been reported up to now [21,22]. As a new alternative energy, carvacrol provides a new possibility for the development of HSV treatment and preventive health care drugs with advantages of great source, safety, low toxicity, and nature.…”

Section: Introductionmentioning

confidence: 99%

Antiviral mechanism of carvacrol on HSV-2 infectivity through inhibition of RIP3-mediated programmed cell necrosis pathway and ubiquitin-proteasome system in BSC-1 cells

Wang

et al. 2020

BMC Infect Dis

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Background Carvacrol, as the major components of aromatic plants used for treating human skin diseases including origanum, Satureja, thymus, and coridothymus species, presented a kind of antiviral activity. To explore the mechanisms of carvacrol against herpes simplex virus (HSV) in vitro. Method The BSC-1 cells model of HSV infection was established, and from the two aspects of viral replication level and cell death pathway, the antiviral effects of carvacrol on HSV infected cells were also evaluated by plaque assay under the three modes including prevention, treatment, and direct inactivation. Results In the three ways, the half-maximal effective concentration (EC50) of 2% true carvacrol solution on HSV-2 infected cells were severally 0.43, 0.19 and 0.51 mmol/L, and the corresponding therapeutic index (TI) were 4.02, 9.11 and 3.39, respectively. It’s the opposite of the increased levels caused by HSV-2 infection, that both the expressions at the transcription genes and protein levels of virus own replication key factors (including ICP4, ICP27, VP16, gB, and UL30) and cytokines (including RIP3, TNF-α, and MLKL) of infected cells treated with carvacrol were dose-dependently inhibited. Besides, HSV-2 infection can cause the decrease of intracellular protein ubiquitination level, and carvacrol can reverse the ubiquitination decrease level caused by HSV-2 infection. Conclusion Carvacrol exhibits significant antiviral activity by inhibiting the HSV-2 proliferation process and HSV-2-induced TNF-α increasing levels, decreasing RIP3 and MLKL protein expressions through the intracellular RIP3-mediated programmed cell necrosis pathway. In addition, carvacrol also may exhibit anti-HSV-2 activity by reversing the ubiquitination decrease level caused by HSV-2 infection on the ubiquitin-proteasome system, which provides insights into the molecular mechanism.

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Inhibition of HSV‐2 infection by pure compounds from Thymus capitatus extract in vitro

Cited by 36 publications

References 34 publications

Comparative in vitro analysis of inhibition of rhinovirus and influenza virus replication by mucoactive secretolytic agents and plant extracts

Comparative in vitro analysis of inhibition of rhinovirus and influenza virus replication by mucoactive secretolytic agents and plant extracts

Thymol and Thyme Essential Oil—New Insights into Selected Therapeutic Applications

Antiviral mechanism of carvacrol on HSV-2 infectivity through inhibition of RIP3-mediated programmed cell necrosis pathway and ubiquitin-proteasome system in BSC-1 cells

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