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S-Petasin, the Main Sesquiterpene of Petasites formosanus, Inhibits Phosphodiesterase Activity and Suppresses Ovalbumin-Induced Airway Hyperresponsiveness.

Shih CH, Huang TJ, Chen CM, Lin YL, Ko WC - Evid Based Complement Alternat Med (2011)

Bottom Line: Both IC(50) and K(i) values for PDE3 were significantly greater than those for PDE4.The PDE4(H) value of S-petasin was >300 μM; therefore, its PDE4(H)/PDE4(L) value was calculated to be >17.In conclusion, the present results for S-petasin at least partially explain why Petasites formosanus is used as a folk medicine to treat asthma in Taiwan.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Taipei Medical University Hospital, Taiwan.

ABSTRACT
S-Petasin is the main sesquiterpene of Petasites formosanus, a traditional folk medicine used to treat hypertension, tumors and asthma in Taiwan. The aim of the present study was to investigate its inhibitory effects on phosphodiesterase (PDE) 1-5, and on ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in a murine model of allergic asthma. S-Petasin concentration-dependently inhibited PDE3 and PDE4 activities with 50% inhibitory concentrations (IC(50)) of 25.5, and 17.5 μM, respectively. According to the Lineweaver-Burk analysis, S-petasin competitively inhibited PDE3 and PDE4 activities with respective dissociation constants for inhibitor binding (K(i)) of 25.3 and 18.1 μM, respectively. Both IC(50) and K(i) values for PDE3 were significantly greater than those for PDE4. S-Petasin (10-30 μmol/kg, administered subcutaneously (s.c.)) dose-dependently and significantly attenuated the enhanced pause (P(enh)) value induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, lymphocytes, neutrophils, eosinophils and levels of cytokines, including interleukin (IL)-2, IL-4 and IL-5, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in bronchoalveolar lavage fluid (BALF) of these mice. In addition, S-petasin (10-30 μmol/kg, s.c.) dose-dependently and significantly attenuated total and OVA-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the IgG(2a) level in serum of these mice. The PDE4(H) value of S-petasin was >300 μM; therefore, its PDE4(H)/PDE4(L) value was calculated to be >17. In conclusion, the present results for S-petasin at least partially explain why Petasites formosanus is used as a folk medicine to treat asthma in Taiwan.

No MeSH data available.


Related in: MedlinePlus

Displacement of [3H]-rolipram by S-petasin (a) and Ro 20-1724 (b) in high-affinity rolipram binding sites of guinea pig whole brain particulates. Each value represents the mean ± SEM (n = 6–9).
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fig4: Displacement of [3H]-rolipram by S-petasin (a) and Ro 20-1724 (b) in high-affinity rolipram binding sites of guinea pig whole brain particulates. Each value represents the mean ± SEM (n = 6–9).

Mentions: S-Petasin (3–300 μM) concentration-dependently displaced the [3H]-rolipram binding on HARBSs of guinea pig brain cell membranes (Figure 4(a)). At the highest concentration (300 μM), however, the percentage displacement by S-petasin was 28.0%±5.7% (n = 7). Owing to the solubility of S-petasin, its concentration cannot exceed 300 μM. In other words, the EC50 value of S-petasin for the displacement was >300 μM. Ro 20-1724 (1–10 000 nM), a selective PDE4 inhibitor, also concentration-dependently displaced [3H]-rolipram binding on HARBSs (Figure 4(b)). In contrast to S-petasin, the percentage of the displacement by Ro 20-1724 at the highest concentration (10 000 nM) was 100%±2.1% (n = 9). The EC50 value of Ro 20-1724 for displacement was 95.8 ± 13.6 nM (n = 9). According to the definition (see Section 2), the PDE4H values of S-petasin and Ro 20-1724 were >300 μM and 95.8 ± 13.6 nM, respectively. Thus, the PDE4H/PDE4L values of S-petasin and Ro 20-1724 were calculated to be >17 and 0.014, respectively.


S-Petasin, the Main Sesquiterpene of Petasites formosanus, Inhibits Phosphodiesterase Activity and Suppresses Ovalbumin-Induced Airway Hyperresponsiveness.

Shih CH, Huang TJ, Chen CM, Lin YL, Ko WC - Evid Based Complement Alternat Med (2011)

Displacement of [3H]-rolipram by S-petasin (a) and Ro 20-1724 (b) in high-affinity rolipram binding sites of guinea pig whole brain particulates. Each value represents the mean ± SEM (n = 6–9).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3094704&req=5

fig4: Displacement of [3H]-rolipram by S-petasin (a) and Ro 20-1724 (b) in high-affinity rolipram binding sites of guinea pig whole brain particulates. Each value represents the mean ± SEM (n = 6–9).
Mentions: S-Petasin (3–300 μM) concentration-dependently displaced the [3H]-rolipram binding on HARBSs of guinea pig brain cell membranes (Figure 4(a)). At the highest concentration (300 μM), however, the percentage displacement by S-petasin was 28.0%±5.7% (n = 7). Owing to the solubility of S-petasin, its concentration cannot exceed 300 μM. In other words, the EC50 value of S-petasin for the displacement was >300 μM. Ro 20-1724 (1–10 000 nM), a selective PDE4 inhibitor, also concentration-dependently displaced [3H]-rolipram binding on HARBSs (Figure 4(b)). In contrast to S-petasin, the percentage of the displacement by Ro 20-1724 at the highest concentration (10 000 nM) was 100%±2.1% (n = 9). The EC50 value of Ro 20-1724 for displacement was 95.8 ± 13.6 nM (n = 9). According to the definition (see Section 2), the PDE4H values of S-petasin and Ro 20-1724 were >300 μM and 95.8 ± 13.6 nM, respectively. Thus, the PDE4H/PDE4L values of S-petasin and Ro 20-1724 were calculated to be >17 and 0.014, respectively.

Bottom Line: Both IC(50) and K(i) values for PDE3 were significantly greater than those for PDE4.The PDE4(H) value of S-petasin was >300 μM; therefore, its PDE4(H)/PDE4(L) value was calculated to be >17.In conclusion, the present results for S-petasin at least partially explain why Petasites formosanus is used as a folk medicine to treat asthma in Taiwan.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Taipei Medical University Hospital, Taiwan.

ABSTRACT
S-Petasin is the main sesquiterpene of Petasites formosanus, a traditional folk medicine used to treat hypertension, tumors and asthma in Taiwan. The aim of the present study was to investigate its inhibitory effects on phosphodiesterase (PDE) 1-5, and on ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in a murine model of allergic asthma. S-Petasin concentration-dependently inhibited PDE3 and PDE4 activities with 50% inhibitory concentrations (IC(50)) of 25.5, and 17.5 μM, respectively. According to the Lineweaver-Burk analysis, S-petasin competitively inhibited PDE3 and PDE4 activities with respective dissociation constants for inhibitor binding (K(i)) of 25.3 and 18.1 μM, respectively. Both IC(50) and K(i) values for PDE3 were significantly greater than those for PDE4. S-Petasin (10-30 μmol/kg, administered subcutaneously (s.c.)) dose-dependently and significantly attenuated the enhanced pause (P(enh)) value induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, lymphocytes, neutrophils, eosinophils and levels of cytokines, including interleukin (IL)-2, IL-4 and IL-5, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in bronchoalveolar lavage fluid (BALF) of these mice. In addition, S-petasin (10-30 μmol/kg, s.c.) dose-dependently and significantly attenuated total and OVA-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the IgG(2a) level in serum of these mice. The PDE4(H) value of S-petasin was >300 μM; therefore, its PDE4(H)/PDE4(L) value was calculated to be >17. In conclusion, the present results for S-petasin at least partially explain why Petasites formosanus is used as a folk medicine to treat asthma in Taiwan.

No MeSH data available.


Related in: MedlinePlus