Effects of thymol and carvacrol on T-helper cell subset cytokines and their main transcription factors in ovalbumin-immunized mice

Abstract

Thymol and carvacrol, two main components of thyme, have several valuable effects on the immune system. This study aims to evaluate the effects of these components on T-helper (TH) cell responses and their subsets in mice immunized with ovalbumin. The effects of these components on: a specific in vivo immune response were evaluated by assessing changes in delayed-type hypersensitivity (DTH); ex vivo splenocyte proliferative responses were evaluated using a BrdU assay gene expression of cytokines and key transcription factors involved in T-cells subset differentiation among the mouse splenocytes were assessed using real-time polymerase chain reaction (PCR); and splenocyte cytokine formation (ex vivo) and levels of the cytokines in mouse sera were measured by ELISA. Mice treated with thymol or carvacrol had reduced DTH responses (26% and 50%, respectively) compared with control mice. Thymol and carvacrol each diminished splenocyte proliferation to nearly 65-72% of control levels (p < 0.01). These agents also led to decreased TH1 [interleukin (IL)-2, interferon (IFN)-γ)], TH2 (IL-4) and TH17 (IL-17A) levels in the splenocyte cultures and in the sera of mice but increased levels of IL-10 and transforming growth factor (TGF)-β. Treated immunized mice showed significantly reduced T-box 21 (T-bet) expression from 3.8 [± 0.3]-fold in untreated ovalbumin-immunized mice to 0.9 [± 0.4]-(thymol) and 0.8 [± 0.2]-fold (carvacrol) (p < 0.01). GATA binding protein 3 (GATA-3) expression declined from 3.4 [± 0.4]- to 0.5 [± 0.3]-fold (thymol) and 0.6 [± 0.4]-fold (carvacrol), whereas RORγc decreased from 13.4 [± 1.6]- to 1.5 [± 0.6]-fold (thymol) and 0.8 [± 0.4]-fold (carvacrol) (p < 0.001). As carvacrol and thymol each suppressed the antigen-specific immune response by reducing TH cell-related cytokines\specific transcription factors, this indicated their potential to modulate destructive immune responses attributed to T-cells over-activation.

Effects of Carvacrol, Thymol and essential oils containing such monoterpenes on wound healing: a systematic review

“…In addition, other studies have shown that carvacrol induces angiogenesis by increasing vascular endothelial growth factor (VEGF) expression . Besides, both monoterpenes also increase TGF‐β in vitro …”

“…[49] Besides, both monoterpenes also increase TGF-b in vitro. [50] The third stage of healing is the most clinically relevant and involves remodelling/maturation. This phase has the fibroblasts as main agents, which produce the collagen and deposit it in a structured way, promoting resistance.…”

Pharmacological Properties and Molecular Mechanisms of Thymol: Prospects for Its Therapeutic Potential and Pharmaceutical Development

“…Thymol (0.7 μg/ml/kg) attenuated ovalbumin induced bronchial allergic asthma by inhibiting oxidative stress in male Wistar albino mice (Al-Khalaf, 2013). In OVA induced mice, thymol (80 mg/kg) suppressed the antigen-specific immune response by inducing reductions T H cells [T H 1, T H 2 and T-helper cell 17 (T H 17)]-related cytokines and key transcription factors, revealed their potential to modulate over-activation of T-cells and the associated destructive immune responses (Gholijani and Amirghofran, 2016). Thymol (50 mg/kg) attenuated oxidative stress mediated bronchial asthma in OVA-Alum induced rat erythrocytes by increasing the status of antioxidants (Mottawie et al, 2011).…”

T helper cells subtypes and their cytokine gene expression affected by carvacrol in sensitized mice administered during sensitization period

“…The proinflammatory effects of TGF-β and its role in airways remodeling in asthma 33 as well as synthesizing of TGF-β during lung inflammation and its increased gene expression in asthmatic patients were reported. 17 Overall, reduction of Th2, Th17 but increased Th1, Th1/Th2 ratio, and Treg cells due to treatment of sensitized animals with carvacrol, may indicate that carvacrol treatment during sensitization period affects Th1/Th2 imbalance. 17 However, the results of current study indicated reduction of IFN-γ, FoxP3 gene expression and IFN-γ/IL-4 ratio but increased IL-4, TGF-β, and IL-17 gene expression in the sensitized group, which was prevented by carvacrol in a concentration-dependent manner in chronic lung inflammation.…”

“…8 The pharmacological effects of carvacrol, such as antioxidative, antimicrobial, antitussive, expectorant, antibacterial, 8 and smooth muscle relaxant effects were shown 9,10 with a possible inhibitory effect on muscarinic 11 and histamine (H 1 ) receptors 12 as well as a stimulatory effect on β-adrenergic receptors. 17 In the current study, the molecular basis of the preventive effects of carvacrol on the level of Th1, Th2, Th17, and Treg specific markers with flow cytometery and main cytokines gene expression by quantitative real-time PCR (qRT-PCR) in chronic sensitized mice, treated during sensitization period, were studied. These studies indicate that carvacrol may affect asthma therapy.…”