Anti-inflammatory effects of Sanguisorbae Radix water extract on the suppression of mast cell degranulation and STAT-1/Jak-2 activation in BMMCs and HaCaT keratinocytes.
BACKGROUND
Sanguisorbae Radix (SR) is a well-known herbal medicine used to treat inflammatory disease and skin burns in Asia. In addition, it is used to treat many types of allergic skin diseases, including urticaria, eczema, and allergic dermatitis. SR has been reported to exhibit anti-wrinkle, anti-oxidant, and anti-contact dermatitis bioactivities.


METHODS
In this study, we investigated the mechanism underlying the anti-inflammatory effects of SR water extract (WSR) using human keratinocyte (HaCaT) cells and BALB/c mouse bone marrow-derived mast cells (BMMCs). Viability assays were used to evaluate non-cytotoxic concentrations of WSR in both BMMCs and HaCaT cells. To investigate the effect of WSR treatment on the degranulation of IgE/Ag-activated BMMCs, we measured the release of β-hexosaminidase (β-HEX). We determined the production of pro-inflammatory chemokines including thymus and activation regulated chemokine (TARC; CCL17), regulated on activation, normal T-cell expressed and secreted (RANTES; CCL5), macrophage-derived chemokine (MDC; CCL22), and interleukin 8 (IL-8; CXCL8) in stimulated human keratinocytes. The ability of WSR to reduce the expression of pro-inflammatory marker proteins was evaluated by Western blotting in HaCaT cells stimulated with tumor necrosis factor (TNF)-α/interferon (IFN)-γ.


RESULTS
WSR inhibited IgE/Ag-activated mast cell degranulation in BMMCs. Treatment with various concentrations of WSR decreased β-HEX release in a dose-dependent manner with an IC50 of 27.5 μg/mL. In keratinocytes, WSR suppressed TNF-α/IFN-γ-induced chemokine production and pro-inflammatory molecules via a blockade STAT-1, Jak-2, p38, and JNK activation.


CONCLUSIONS
This results demonstrate that WSR inhibits degranulation of IgE/Ag-activated mast cells and inhibits the production of pro-inflammatory chemokines by suppressing the phosphorylation of p38 and JNK in HaCaT cells.
Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea.
Ju-Hye
http://orcid.org/0000-0003-4419-5850
JH
Yang
Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea.
Jae-Myung
JM
Yoo
Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea. wkcho@kiom.re.kr.
Won-Kyung
WK
Cho
Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea. jyma@kiom.re.kr.
Jin Yeul
JY
Ma
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000737:chemistry*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D031993:Sanguisorba / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D010936:Plant Extracts; D050794:STAT1 Transcription Factor; D053614:Janus Kinase 2
Chemokines; Degranulation; Keratinocytes; Mast cells; Sanguisorbae Radix