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.

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 (PM2.5) may induce various respiratory diseases. This study elucidated the protective effect of the effective part of Andrographis paniculata (Burm.f.) Nees (AEP) against PM2.5-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 PM2.5 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: PM2.5 exposure caused lung toxicity, which was characterized by pathological injury and increased levels of LDH, ACP, AKP and TP in BALF. Meanwhile, PM2.5 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 PM2.5-induced lung toxicity and the inflammatory response in rats. Moreover, AEP significantly inhibited the PM2.5-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 PM2.5-induced pathological damage and decrease the TP level in the BALF. CONCLUSION: AEP could be used to improve PM2.5-induced lung injury by modulating the NF-κB pathway, and multicomponent therapy with traditional Chinese medicine may be more effective than single-drug therapy.

Enhanced anticancer efficacy of cantharidin by mPEG-PLGA micellar encapsulation: An effective strategy for application of a poisonous traditional Chinese medicine.

Cantharidin (CTD), the main active component of a poisonous traditional Chinese medicine (PTCM) Mylabris, exhibits highly effective therapy of hepatocellular carcinoma (HCC); however, the severe toxicity of CTD on the digestive and urinary systems prevents its clinical application. Here, CTD-loaded micelles (mPEG-PLGA-CTD) were prepared for enhancement of the antitumor efficacy and reduction of the toxicity of CTD. mPEG-PLGA-CTD comprised uniform spherical particles with particle size of 25.32 ± 1.25 nm and zeta potential of -5.70 ± 0.76 mV, exhibiting good stability and biocompatibility. mPEG-PLGA-CTD showed high toxicity on HepG2 cells by improving apoptosis and inhibiting protein phosphatases 2A (PP2A) compared to the low toxicity on l-02 hepatocytes. Intravenous injection of mPEG-PLGA-CTD led to a long circulation half-life of drugs, enhanced drug accumulation in the tumor tissues, and reduced drug accumulation in the other organs (e.g., the kidney) due to the enhanced permeability and retention effect compared to injection of free CTD; more importantly, the highly efficient antitumor effect and low systemic toxicity were achieved. A micellar formulation is very useful for enhancement of therapeutic efficacy and reduction of systemic toxicity of PTCMs.