Protective effects of Ulmus davidiana var. japonica against OVA-induced murine asthma model via upregulation of heme oxygenase-1.
OBJECTIVE
Traditionally, the stem and root bark of Ulmus davidiana var. japonica (Ulmaceae) are Korean herbal medicines used for anti-inflammatory and anticancer therapy. In this study, we investigated the protective effects of Ulmus davidiana var. japonica ethanolic extract (UD) in a murine asthma model. Furthermore, we determined whether heme oxygenase (HO)-1 is required for the protective activity of UD.


METHODS
Airways of ovalbumin (OVA)-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. UD was applied 1h prior to OVA challenge. Mice were administered UD orally at doses of 100 and 200mg/kg once daily on days 18-23. Bronchoalveolar lavage fluid (BALF) was collected 48 h after the final OVA challenge. Levels of interleukin (IL)-4 and IL-5 in BALF were measured using enzyme-linked immunosorbent assays (ELISAs). Lung tissue sections 4 microm in thickness were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration and mucus production with PAS (periodic acid shift reagent) staining, in conjunction with ELISA, immunohistochemistry and Western blot analyses for HO-1 protein expression.


CONCLUSIONS
Orally administered UD significantly inhibited the number of OVA-induced inflammatory cells and IgE production, along with reduced T-helper (Th)2 cytokine levels, such as IL-4 and IL-5, in BALF and lung tissue. In addition, UD induced a marked decrease in OVA-induced reactive oxygen species (ROS), inflammatory cell infiltration and mucus production in lung tissue. These effects were correlated with HO-1 mRNA and protein induction. Our results indicate that UD protects against OVA-induced airway inflammation, at least in part, via HO-1 upregulation.
Lee
Mee-Young
MY
Herbal Medicine EBM Research Center, Korea Institute of Oriental Medicine, Exporo 483, Yusung-gu, Daejeon 305-811, Republic of Korea.
Seo
Chang-Seob
CS
Ha
Heykyung
H
Jung
Dayoung
D
Lee
Hoyoung
H
Lee
Nam-Hun
NH
Lee
Jin-Ah
JA
Kim
Jung-Hoon
JH
Lee
Yeun-Kyung
YK
Son
Jong-Keun
JK
Shin
Hyeun-Kyoo
HK
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D001483:Base Sequence; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D034403:Ulmus / Q000737:chemistry*; D015854:Up-Regulation / Q000187:drug effects*
D017931:DNA Primers; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D010047:Ovalbumin; D006419:Heme Oxygenase (Decyclizing)