Institute of Zoonoses, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
PLoS One. 2012;7(4):e34634. doi: 10.1371/journal.pone.0034634. Epub 2012 Apr 26.
Farrerol, isolated from rhododendron, has been shown to have the anti-bacterial activity, but no details on the anti-inflammatory activity. We further evaluated the effects of this compound in two experimental models of lung diseases.
METHODOLOGY/PRINCIPAL FINDINGS: For the asthma model, female BALB/c mice were challenged with ovalbumin (OVA), and then treated daily with farrerol (20 and 40 mg/kg, i.p.) as a therapeutic treatment from day 22 to day 26 post immunization. To induce acute lung injury, female BALB/c mice were injected intranasally with LPS and treated with farrerol (20 and 40 mg/kg, i.p.) 1 h prior to LPS stimulation. Inflammation in the two different models was determined using ELISA, histology, real-time PCR and western blot. Farrerol significantly regulated the phenotype challenged by OVA, like cell number, Th1 and Th2 cytokines levels in the BALF, the OVA-specific IgE level in the serum, goblet cell hyperplasia in the airway, airway hyperresponsiveness to inhaled methacholine and mRNA expression of chemokines and their receptors. Furthermore, farrerol markedly attenuated the activation of phosphorylation of Akt and nuclear factor-κB (NF-κB) subunit p65 both in vivo and in vitro. However, farrerol has no effect on the acute lung injury model.
CONCLUSION/SIGNIFICANCE: Our finding demonstrates that the distinct anti-inflammatory effect of farrerol in the treatment of asthma acts by inhibiting the PI3K and NF-κB pathway.
从杜鹃属植物中分离得到的法呢醇已被证明具有抗菌活性，但关于其抗炎活性尚无详细研究。我们进一步在两种肺部疾病模型中评估了该化合物的作用。
方法/主要发现：在哮喘模型中，雌性 BALB/c 小鼠用卵清蛋白（OVA）进行攻毒，然后从免疫后第 22 天至第 26 天，每天用法呢醇（20 和 40mg/kg，腹腔注射）进行治疗。为了诱导急性肺损伤，雌性 BALB/c 小鼠用 LPS 经鼻腔注射，并在 LPS 刺激前 1 小时用法呢醇（20 和 40mg/kg，腹腔注射）进行治疗。使用 ELISA、组织学、实时 PCR 和 Western blot 来确定两种不同模型中的炎症。法呢醇显著调节了 OVA 所挑战的表型，如 BALF 中的细胞数量、Th1 和 Th2 细胞因子水平、血清中的 OVA 特异性 IgE 水平、气道中的杯状细胞增生、对吸入性乙酰甲胆碱的气道高反应性以及趋化因子及其受体的 mRNA 表达。此外，法呢醇在体内和体外均显著减弱了 Akt 和核因子-κB（NF-κB）亚基 p65 的磷酸化激活。然而，法呢醇对急性肺损伤模型没有影响。
结论/意义：我们的发现表明，法呢醇在治疗哮喘中的独特抗炎作用是通过抑制 PI3K 和 NF-κB 通路发挥作用的。
