Protective effect of the effective part of Andrographis paniculata (Burm.f.) Nees on PM2.5-induced lung injury in rats by modulating the NF-κB pathway

Abstract

Ethnopharmacological relevance: Andrographis paniculata (Burm.f.) Nees, a traditional Chinese herb, has been widely used in various Asian countries as a treatment for upper respiratory tract infections for centuries.

Aim of the study: Continuous inhalation of fine particulate matter (PM_2.5) may induce various respiratory diseases. This study elucidated the protective effect of the effective part of Andrographis paniculata (Burm.f.) Nees (AEP) against PM_2.5-induced lung injury and detailed the underlying mechanism.

Materials and methods: Male Wistar rats were orally administered 0.5% sodium carboxymethylcellulose (CMC-Na), andrographolide (AG) (200 mg/kg) and AEP (100 mg/kg, 200 mg/kg and 400 mg/kg) once a day for 28 days. The rats were intratracheally instilled with PM_2.5 suspension (8 mg/kg) every other day beginning on the 24th day for a total of 3 times. On the 29th day, bronchoalveolar lavage fluid (BALF) was collected to analyze the levels of lactate dehydrogenase (LDH), acid phosphatase (ACP), alkaline phosphatase (AKP), total proteins (TP), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). Hematoxylin & eosin staining was conducted to evaluate the pathological changes in the lung tissues. The protein expression of NF-κB p65 in the lung tissues was analyzed by immunohistochemistry staining. Moreover, the nuclear translocation of NF-κB p65 and the phosphorylation of IκBα were analyzed by western blotting.

Results: PM_2.5 exposure caused lung toxicity, which was characterized by pathological injury and increased levels of LDH, ACP, AKP and TP in BALF. Meanwhile, PM_2.5 exposure induced lung inflammatory response, including infiltration of inflammatory cells and increased levels of inflammatory factors, such as TNF-α and IL-6 in BALF. AEP treatment significantly ameliorated the PM_2.5-induced lung toxicity and the inflammatory response in rats. Moreover, AEP significantly inhibited the PM_2.5-induced upregulation of NF-κB p65 protein expression, phosphorylation of IκBα and nuclear translocation of NF-κB p65 in lung tissue. Compared to AG, AEP exhibited a better ability to alleviate PM_2.5-induced pathological damage and decrease the TP level in the BALF.

Conclusion: AEP could be used to improve PM_2.5-induced lung injury by modulating the NF-κB pathway, and multicomponent therapy with traditional Chinese medicine may be more effective than single-drug therapy.

Keywords: Andrographolide; Lung injury; NF-κB; PM(2.5); The effective part of Andrographis paniculata (Burm.f.) Nees.