Topical treatments of Saussurea costus root and Thuja orientalis L. synergistically alleviate atopic dermatitis-like skin lesions by inhibiting protease-activated receptor-2 and NF-κB signaling in HaCaT cells and Nc/Nga mice.
BACKGROUND
The root of Saussurea costus (Aucklandia lappa Decne, Aucklandiae Radix, SC) and Thuja orientalis L. (TOL) have been traditionally used as anti-inflammatory agents in Korea. However, they have not been studied for the efficacy of atopic dermatitis (AD) treatment, a chronic inflammatory skin disease. We investigated the efficacy of topical applications with 1,3-butyleneglycol extracts of SC and TOL to alleviate the symptoms of AD.


METHODS
HaCaT cells and the dorsal skin of Nc/Nga mice had a local exposure of house mite extracts and 2,4-dinitrochlorobenzene (DNCB), respectively. After lesions developed, we topically applied 1,3-butylen glycol (vehicle; control), SC (30%), TOL (30%), or SC (15%)+TOL (15%) to the skin lesions for 5 weeks. The normal-control was not exposed to DNCB. The skin thickness, mast cell infiltration, serum immunoglobulin E (IgE) and IgG1 and gene expressions of interleukin (IL)-4, IL-13, and IFN-γ in the dorsal skin and HaCaT cells were measured.


RESULTS
Chlorogenic acid (129.6±10.2μg/g) for SC and catechin and apigenin (93.4±13.2 and 16.9±1.3μg/g, respectively) for TOL were used as indicator compounds for the strength of the extracts. SC+TOL decreased the expression of protease-activated receptor-2 and ICAM-1 and the release of TNF-α and IL-6 in HaCaT cells activated by 3μg/mL house mite extracts in comparison to either of SC or TOL alone. In Nc/Nga mice challenged with DNCB, SC+TOL synergistically attenuated clinical symptoms of AD such as erythema, hemorrhage, edema, excoriation and dryness in the dorsal skin better than either SC or TOL alone. Histological analysis of the dorsal skin also showed that SC+TOL treatment significantly and additively decreased the inflammatory cellular infiltrate, including mast cells and eosinophils in comparison to either of SC or TOL. SC+TOL also decreased serum IgE and IgG1 levels and the expression of IFN-γ, IL-4, and IL-13 mRNA in dorsal skin in DNCB-treated Nc/Nga mice.


CONCLUSIONS
SC+TOL relieved the symptoms of AD by reducing pro-inflammatory activity and over-activated immune responses. These data suggest that SC+TOL may be an effective alternative intervention for the management of AD.
Division of Strategic Food Industry Research, Korea Food Research Institute, South Korea; Department of Food Science and Nutrition, Yong In University, South Korea. Electronic address: yhj@kfri.re.kr.
Hye Jeong
HJ
Yang
Division of Nutrition and Metabolism Research, Korea Food Research Institute, South Korea; Department of Food Science and Nutrition, Yong In University, South Korea. Electronic address: kmj@kfri.re.kr.
Min Jung
MJ
Kim
Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea. Electronic address: roypower003@naver.com.
Suna
S
Kang
Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea. Electronic address: a213900@hanmail.net.
Na Rang
NR
Moon
Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea. Electronic address: tpfptm14@daum.net.
Da Sol
DS
Kim
Department of Nanobiomechatronics, Hoseo University, Asan, South Korea. Electronic address: zzzz8238@naver.com.
Na Ra
NR
Lee
Department of Food Science and Nutrition, Yong In University, South Korea. Electronic address: kss@yongin.ac.kr.
Kang Sung
KS
Kim
Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea. Electronic address: smpark@hoseo.edu.
Sunmin
S
Park
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002461:Cell Line, Transformed; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000378:metabolism*; D004357:Drug Synergism; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D030441:Saussurea; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D029783:Thuja
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D010936:Plant Extracts; D044464:Receptor, PAR-2
Atopic dermatitis; Aucklandiae radix; IL-4; Ig E; Mast cells; Saussurea costus root; Thuja orientalis L