RESUMEN
Background: Azithromycin (AZM) is one of the most common broad-spectrum antibiotics. However, drug resistance is increasing and combination therapy has attracted great attention. AZM is usually combined with traditional Chinese medicine (TCM) preparations with heat-clearing and detoxifying effects, including Kumu injection (KM) made from Picrasma quassioides (D. Don) Benn. Purpose: The present study aimed to investigate synergistic antimicrobial and anti-inflammatory activities of KM plus AZM with the aim of understanding the mechanism of clinical efficacy of combination regimens. Methods: Seven common bacterial clinical isolates and LPS-induced RAW 264.7 cells were used for assay of in vitro potency. The minimum inhibitory concentration (MIC) was determined for each drug, followed by synergy testing through the checkerboard method and fractional inhibitory concentration index (FICI) for quantifying combined antibacterial effects. The rat model of Klebsiella pneumoniae-induced pneumonia was developed and subjected to various drug treatments, namely, AZM, KM, or AZM plus KM, intravenously administered at 75 mg/kg once a day for one week. The combination effects then were evaluated according to pharmacodynamics and pharmacokinetic assessments. Results: KM-AZM combination synergistically inhibits in vitro growth of all the test standard strains except Pseudomonas aeruginosa and also the drug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, Shigella dysenteriae, Klebsiella pneumoniae, and Escherichia coli. Despite an additive effect against NO, KM plus AZM at an equal dose could synergistically suppress overrelease of the inflammatory cytokines TNF-α and IL-6 by LPS-induced RAW 264.7 cells. The combination significantly inhibited the proliferation of K. pneumoniae in the rat lungs, mainly by inactivating MAPKs and NF-κB signaling pathways. KM-AZM combination caused a onefold increase in apparent distribution volume of AZM, along with a significant decrease of AZM level in the livers and heart for pharmacokinetics. Conclusion: KM-AZM combination displayed synergistic antibacterial and anti-inflammatory effects beneficial to the therapeutic potential against bacterial infection.
RESUMEN
While lung cancer poses a serious threat to human health, non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Danggui Buxue Decoction (DBD) is a classical traditional antitumor medicine commonly used in China. However, the potential mechanism of DBD against NSCLC has not yet been expounded. Therefore, this study clarified the potential molecular mechanism and key targets of DBD in NSCLC treatment through several technological advances, such as network pharmacology, molecular docking, and bioinformatics. Firstly, the relative active ingredients and key DBD targets were analyzed, and subsequently, a drug-ingredient-target-disease network diagram was constructed for NSCLC treatment with DBD, resulting in the identification of five main active ingredients and ten core targets according to the enrichment degree. The enrichment analysis revealed that DBD can achieve the purpose of treating NSCLC through the AGE-RAGE signaling pathway in diabetic complications. Secondly, the molecular docking approach predicted that quercetin and hederagenin have the best working mechanisms with PDE3A and PTGS1, while the survival analysis results depicted that high PDE3A gene expression has a relatively poor prognosis for NSCLC patients (p < 0.05). Additionally, PDE3A is mainly distributed in the LU65 cell line that originated from Asian population. In summary, our study results showed that DBD can treat NSCLC through the synergistic correlation between multiple ingredients, multiple targets, and multiple pathways, thus effectively improving NSCLC prognosis. This study not only reflected the medicinal value of DBD but also provided a solid structural basis for future new drug developments and targeted therapies.