Cytotoxicity and Antiviral Activities of Haplophyllum tuberculatum Essential Oils, Pure Compounds, and Their Combinations against Coxsackievirus B3 and B4

Abstract

Haplophyllum tuberculatum is a plant commonly used in folk medicine to treat several diseases including vomiting, nausea, infections, rheumatism, and gastric pains. In the current study, H. tuberculatum essential oils, hydrosols, the pure compounds R-(+)-limonene, S-(−)-limonene, and 1-octanol, as well as their combinations R-(+)-limonene/1-octanol and S-(−)-limonene/1-octanol, were screened for their cytotoxicity on HEp-2 cells after 24, 48, and 72 h, and then tested for their activity against Coxsackievirus B3 and B4 (CV-B3 and CV-B4) at 3 different moments: addition of the plant compounds before, after, or together with virus inoculation. Results showed that the samples were more cytotoxic after 72 h than after 24 h or 48 h cell contact. However, the combinations R-(+)-limonene/1-octanol and S-(−)-limonene/1-octanol showed less effect on HEp-2 cells than pure R-(+)-limonene and S-(−)-limonene after 24 h, 48 h, and 72 h. 1-octanol exhibited the highest concentration causing 50% cytotoxicity (CC50) on HEp-2 cells after 24 h (CC50 = 93 µg/mL) and 48 h (CC50 = 83 µg/mL). The antiviral assays showed that the tested samples exhibited potent inhibition of CV-B. IC50 values ranged from 0.66 µg/mL to 28.4 µg/mL. In addition, CV-B3 was more sensitive than CV-B4. Both CV-B strains are more inhibited when cells were pretreated with the plant compounds. The hydrosols have no effect, neither on HEp-2 cells nor on the virus. 1-octanol, S-(−), and R-(+)-limonene/1-octanol had important selectivity indexes over time. Although essential oils had potent antiviral activity, they can be considered for application in the pretreatment of cells. However, 1-octanol and the combinations are within the safety limits, and thus, they can be used as an active natural antiviral agent for CV-B3 and CV-B4 inhibition.

Current and Potential Applications of Monoterpenes and Their Derivatives in Oral Health Care

“…Antifungal [24] Disruption of cell wall and cell membrane, which leads to apoptosis [72]; inhibition of adhesion, enzyme se- Antifungal [24] Disruption of cell wall and cell membrane, which leads to apoptosis [72]; inhibition of adhesion, enzyme secretion, and biofilm formation [73] Antiviral [35,74] Interference with virion envelope structures or masking of necessary viral structures [35] Menthol Mentha spp. (mints) [75] Antiviral [76] Attenuation of infection by stimulating TRPM8, which blocks TRPV1-mediated mitochondrial fragmentation Taxus spp.…”

“…Salvia rosmarinus (rosemary) Vitex agnus-castus (chaste tree) [70,71] Antifungal [24] Disruption of cell wall and cell membrane, which leads to apoptosis [72]; inhibition of adhesion, enzyme secretion, and biofilm formation [73] Antiviral [35,74] Interference with virion envelope structures or masking of necessary viral structures [35] Menthol Isoborneol Artemisia annua (sweet wormwood)…”

“…Mentha piperita (peppermint) Mentha spicata (spearmint) Perilla frutescens (beefsteak plant) [83][84][85] Antiviral [82] Inhibition of maturation, fusion, and viral infectivity [82] Mentha spp. (mints) [75] Antiviral [76] Attenuation of infection by stimulating TRPM8, which blocks TRPV1-mediated mitochondrial fragmentation [ Antifungal [24] Disruption of cell wall and cell membrane, which leads to apoptosis [72]; inhibition of adhesion, enzyme secretion, and biofilm formation [73] Antiviral [35,74] Interference with virion envelope structures or masking of necessary viral structures [35] Menthol Mentha spp. (mints) [75] Antiviral [76] Attenuation of infection by stimulating TRPM8, which blocks TRPV1-mediated mitochondrial fragmentation Analgesic and antinociceptive [79] Cytokine inhibition and p38 mitogen-activated protein kinase (p38-MAPK) signal transduction pathway in trigeminal ganglia [79] Perillic acid Perilla frutescens (beefsteak plant) [80,81] Antiviral [82] Inhibition of maturation, fusion, and viral infectivity [82] Perillyl alcohol…”

Promising Role of Emodin as Therapeutics to Against Viral Infections

“…Although the structure, molecular biology and associated pathophysiological mechanisms of CVB have been extensively studied, specific inhibitors have not yet been identified and applied to clinical studies. Therefore, research into natural or synthetic compounds is constantly ongoing in order to find suitable candidates for antiviral effectively ( Hamdi et al, 2021 ). Several in vitro and in vivo studies showed anti-CVB activity of emodin ( Table 4 ).…”

Effects of Essential Oils and Hydrolates on the Infectivity of Murine Norovirus

“…In recent years, EOs have more often been investigated against enveloped viruses [ 13 , 14 , 15 ], while to date, only limited research has looked at the efficacy of EOs against non-enveloped viruses [ 16 , 17 , 18 ]. While the scientific literature on essential oils is relatively abundant, much less is known about hydrosols [ 3 ] and to date, the antiviral effect of hydrosols against human enteric viruses has scarcely been studied [ 19 ]. Enteric viruses have been recognized as an important cause of foodborne disease in developed countries.…”