Anat Cell Biol.  2017 Jun;50(2):124-134. 10.5115/acb.2017.50.2.124.

Baicalein, wogonin, and Scutellaria baicalensis ethanol extract alleviate ovalbumin-induced allergic airway inflammation and mast cell-mediated anaphylactic shock by regulation of Th1/Th2 imbalance and histamine release

• Bui TT
• Piao CH
• Song CH
• Lee CH
• Shin HS
• Chai OH

• KMID: 2451238
• DOI: http://doi.org/10.5115/acb.2017.50.2.124

Abstract

Asthma is characterized by chronic inflammation, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration into the lungs. In this study, we examined the effects of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on ovalbumin (OVA)-induced asthma by evaluating Th1/Th2 cytokine levels, histopathologic analysis, and compound 48/80-induced systemic anaphylaxis and mast cell activation, focusing on the histamine release from rat peritoneal mast cells. Baicalein, wogonin, and S. baicalensis ethanol extract also decreased the number of inflammatory cells especially eosinophils and downregulated peribronchial and perivascular inflammation in the lungs of mice challenged by OVA. Baicalein, wogonin, and S. baicalensis ethanol extract significantly reduced the levels of tumor necrosis factor α, interleukin (IL)-1β, IL-4, IL-5 and the production of OVA-specific IgE and IgG1, and upregulated the level of interferon-γ and OVA-specific IgG2a. In addition, oral administration of baicalein, wogonin, and S. baicalensis ethanol extract inhibited compound 48/80-induced systemic anaphylaxis and plasma histamine release in mice. Moreover, baicalein, wogonin, and S. baicalensis ethanol extract suppressed compound 48/80-induced mast cell degranulation and histamine release from rat peritoneal mast cells. Conclusively, baicalein and wogonin as major flavonoids of S. baicalensis may have therapeutic potential for allergic asthma through modulation of Th1/Th2 cytokine imbalance and histamine release from mast cells.

Keyword

Baicalein; Wogonin; Scutellaria baicalensis; Th1/Th2 cytokine imbalance; OVA-specific IgE/IgG1/IgG2a

MeSH Terms

Administration, Oral
Anaphylaxis*
Animals
Asthma
Cytokines
Eosinophils
Ethanol*
Flavonoids
Goblet Cells
Histamine Release*
Histamine*
Hyperplasia
Immunoglobulin E
Immunoglobulin G
Inflammation*
Interleukin-4
Interleukin-5
Interleukins
Lung
Mast Cells
Mice
Ovalbumin
Ovum
Plasma
Rats
Scutellaria baicalensis*
Scutellaria*
Tumor Necrosis Factor-alpha
Cytokines
Ethanol
Flavonoids
Histamine
Immunoglobulin E
Immunoglobulin G
Interleukin-4
Interleukin-5
Interleukins
Ovalbumin
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Effect of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on infiltration of inflammatory cells (A–F) and differential cellular components and total cells (G) in bronchoalveolar lavage fluid (BALF) of mice induced by ovalbumin (OVA) sensitization and challenge. (A) Control. (B) Saline. (C) Dexamethasone 1.5 mg/kg. (D) Baicalein 10 mg/kg. (E) Wogonin 10 mg/kg. (F) S. baicalensis ethanol extract 200 mg/kg. Values are presented as the mean±SD (n=6 per group). Data were analyzed using ANOVA followed by Student's t test. ###P<0.001, #P<0.05, significantly different from the value of saline group. ***P<0.001, *P<0.05, significantly different from the value of OVA group. Results are presented as the mean±SD (n=6 per group).

• 

  Fig. 2 Effect of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on ovalbumin (OVA)-induced histopathological changes. Mice were sensitized on days 1 and 14, and challenged on days 27, 28, and 29 by OVA. On days 15 to 26, the treatment groups were also orally treated once daily with saline, dexamethasone 1.5 mg/kg, baicalein 10 mg/kg, wogonin 10 mg/kg, and S. baicalensis ethanol extract 200 mg/kg. Lung tissues from each group were stained with congo red for eosinophils, periodic acid-Schiff (PAS) for goblet cells (white arrows) and mucus (white asterisk) and Masson trichrome for collagen fiber deposits (black arrows). Only a representative picture is shown for each group. Scale bars=100 µm.

• 

  Fig. 3 Effect of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on the serum levels of total IgE (A), ovalbumin (OVA)-specific IgE (B), OVA-specific IgG1 (C), and OVA-specific IgG2 (D). Data were analyzed using ANOVA followed by Student's t test. ###P<0.001, significantly different from the value of saline group. ***P<0.001, **P<0.01, *P<0.05, significantly different from the value of OVA group. Results are presented as the mean±SD (n=6 per group).

• 

  Fig. 4 Effect of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on the levels of Th1/Th2 cytokines in bronchoalveolar lavage fluid. (A) Tumor necrosis factor α (TNF-α). (B) Interleukin (IL)-1β. (C) IL-4. (D) IL-5. (E) IL-12. (F) Interferon γ (IFN-γ). Data were analyzed using ANOVA followed by Student's t test. ###P<0.001, ##P<0.01, #P<0.05, significantly different from the value of saline group. ***P<0.001, **P<0.01, *P<0.05, significantly different from the value of ovalbumin (OVA) group. Results are presented as the mean±SD (n=6 per group).

• 

  Fig. 5 Inhibitory effect of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on compound 48/80-induced systemic anaphylaxis. Five groups of mice (n=7/group) were orally administered saline, baicalein (10 mg/kg body weight [BW]), wogonin (10 mg/kg BW) or S. baicalensis ethanol extract (100, 200, and 400 mg/kg BW), at 24, 12, and 1 hour prior to injection of compound 48/80. The compound 48/80 was intraperitoneally given to mice. (A) Survival rates (%) were monitored for 1 hour after induction of anaphylactic shock. (B) Histamine concentrations in serum were measured by enzyme-linked immunosorbent assay. Each data represents the mean±SD (n=7 per group). Data were analyzed using ANOVA followed by Student's t test. **P<0.01, ***P<0.001, significantly different from the value of saline treated group. Results are presented as the mean±SD. ###P<0.001, significantly different from the value of saline group.

• 

  Fig. 6 Effect of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on rat mast cell degranulation and histamine release from rat peritoneal mast cells (RPMCs). RPMCs were preincubated with dexamethasone, baicalein, wogonin, or S. baicalensis extract at 37℃ for 10 minutes before incubation with compound 48/80. The RPMCs were micrographed within 10 minutes after the addition of saline or compound 48/80 by using inverted phase contrast microscopy. (A) Saline as a control. (B) Compound 48/80 5 µg/ml. (C) Dexamethasone 1.5 mg/ml. (D) Baicalein 10 mg/ml. (E) Wogonin 10 mg/ml. (F) S. baicalensis ethanol extract 200 mg/ml. Scale bars=10 µm (A–F). (G) Quantitation of mast cell degranulation. (H) Histamine release (%). Data were analyzed using ANOVA followed by Student's t test. ###P<0.001, significantly different from the value of saline group. ***P<0.001, **P<0.01, *P<0.05, significantly different from the value of ovalbumin group. Results are presented as the mean±SD (n=6 per group).

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