Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-κB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1.
OBJECTIVE
The consequences of precipitously rising allergic skin inflammation rates worldwide have accelerated the risk of atopic dermatitis (AD). Natural product-based agents with good efficacy and low risk of side effects offer promising prevention and treatment strategies for inflammation-related diseases. We have already reported that Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) have many pharmacological effects, including anti-inflammatory and anti-allergic effects, but its influence on AD remains unclear. Therefore, we evaluated the inhibitory effect of CKS, mainly platycodin D, on AD-like skin symptoms in mice and the possible mechanisms in cells.


METHODS
Mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB). Four weeks after challenge, mice were treated with oral administration of CKS for 4 weeks. In addition, cells were used to evaluate the effect of CKS, mainly platycodin D, on the TARC expression regulated mechanism.


RESULTS
CKS attenuated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells and mast cells in the ears. Moreover, CKS and platycodin D inhibited TNF-α/IFN-γ-induced TARC expression through the suppression of NF-κB and STAT1 and induction of Nrf2/ARE-mediated hemeoxygenase-1 (HO-1) expression in cells.


CONCLUSIONS
We suggest that CKS and platycodin D inhibited the development of AD-like skin symptoms by regulating cytokine mediators and may be an effective alternative therapy for AD-like skin symptoms.
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Jae Ho
JH
Choi
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Sun Woo
SW
Jin
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Eun Hee
EH
Han
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Bong Hwan
BH
Park
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Hyung Gyun
HG
Kim
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Tilak
T
Khanal
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; Department of Pharmaceutical Engineering, International University of Korea, Jinju, Republic of Korea.
Yong Pil
YP
Hwang
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Minh Truong
MT
Do
Molecular Cancer Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Hyun-Sun
HS
Lee
Department of Food and Medicine, International University of Korea, Jinju, Republic of Korea.
Young Chul
YC
Chung
Department of Food Science and Culinary, International University of Korea, Jinju, Republic of Korea.
Hee Suk
HS
Kim
College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
Tae Cheon
TC
Jeong
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea. Electronic address: hgjeong@cnu.ac.kr.
Hye Gwang
HG
Jeong
D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000188:drug therapy*; D004137:Dinitrochlorobenzene / Q000009:adverse effects; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D031238:Platycodon / Q000737:chemistry*; D050794:STAT1 Transcription Factor / Q000187:drug effects / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D018926:Anti-Allergic Agents; C440574:Changkil; D016207:Cytokines; D004137:Dinitrochlorobenzene; D008565:Membrane Proteins; D016328:NF-kappa B; D010936:Plant Extracts; D050794:STAT1 Transcription Factor; D012503:Saponins; C494080:Stat1 protein, mouse; D014315:Triterpenes; D007073:Immunoglobulin E; C108953:platycodin D; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
Atopic dermatitis; HO-1; NF-κB; Platycodon grandiflorum; STAT1; Saponins