Total sesquiterpene lactones isolated from Inula helenium L. attenuates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice.

Abstract

BACKGROUND:

Inula helenium L. is an herb whose anti-inflammatory properties are attributed to its active components, the sesquiterpene lactones (SLs). Our previous study demonstrated that the total sesquiterpene lactones isolated from Inula helenium L. (TSL-IHL), consisting mainly of alantolactone (AL) and isoalantolactone (IAL), may have potential in the prevention and treatment of rheumatoid arthritis (RA). However, the effect of TSL-IHL on atopic dermatitis (AD) has not been studied yet.

AIM OF THE STUDY:

The present study evaluates the potential of TSL-IHL as a treatment for AD.

METHODS/STUDY DESIGNS:

The effects of TSL-IHL on the expression of inflammatory genes and the activation of NF-κB signaling pathway in HaCat cells were examined by quantitative real-time PCR and western blotting, respectively, and compared with those of AL and IAL. The protective effect of TSL-IHL against AD was tested in a mouse model induced by 2,4-dinitrochlorobenzene (DNCB), in which AD-like skin lesions were induced in ICR mice by sensitizing once with 100 µl of 7% DNCB painted on their shaved back skin and then challenging with 20 µl of 0.2% DNCB five times on their right ears at 3 day intervals starting on day 5 post-sensitization.

RESULTS:

TSL-IHL, as well as AL and IAL, could all inhibit TNF-α-induced activation of NF-κB and the expression of TNF-α, IL-1, and IL-4 in HaCat cells in a dose-dependent manner in the range of 0.6-2.4 µg/ml. The topical application of TSL-IHL (1% W/W in emollient cream) attenuated DNCB-induced dermatitis severity and right ear swelling. The serum levels of IgE, TNF-α and IFN-γ in TSL-IHL-treated mice were reduced by 81.39%, 89.69%, and 87.85%, respectively, while the mRNA levels of IL-4, IL-5 and IL-13, in the back-skin lesions of TSL-IHL-treated mice were reduced by 39.21%, 40.62% and 48.12%, respectively, compared with the untreated controls. Histopathological examination showed that TSL-IHL treatment reduced epidermis/dermis thickening and dermal inflammatory infiltration in both ear and back skins.

CONCLUSIONS:

We suggest that TSL-IHL inhibited the development of AD-like skin symptoms by regulating cytokine expression and may be an effective alternative therapy for AD.

• Authors: Qun Wang, Shuang Gao, Guo-Zhen Wu, Niao Yang, Xian-Peng Zu, Wen-Cai Li, Ning Xie, Rong-Rong Zhang, Chen-Wei Li, Zhen-Lin Hu, Wei-Dong Zhang
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 46 Pg. 78-84 (Jul 15 2018) ISSN: 1618-095X [Electronic] Germany
• PMID: 30097125 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier GmbH.

Chemical References

• Cytokines
• Dinitrochlorobenzene
• Lactones
• NF-kappa B
• Plant Extracts
• Sesquiterpenes

Topics

• Animals
• Cell Line
• Cytokines (metabolism)
• Dermatitis, Atopic (chemically induced, drug therapy)
• Dinitrochlorobenzene
• Female
• Humans
• Inula (chemistry)
• Lactones (pharmacology)
• Mice
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• Plant Extracts (pharmacology)
• Sesquiterpenes (pharmacology)
• Skin (drug effects)