PPM1A as a key target of the application of Jiawei­Maxing­Shigan decoction for the attenuation of radiation­induced epithelial­mesenchymal transition in type II alveolar epithelial cells.

Radiation­induced lung tissue injury is an important reason for the limited application of radiotherapy on thoracic malignancies. Previously, we reported that administration of Jiawei­Maxing­Shigan decoction (JMSD) attenuated the radiation­induced epithelial­mesenchymal transition (EMT) in alveolar epithelial cells (AECs) via TGF­ß/Smad signaling. The present study aimed to examine the role of protein phosphatase Mg2+/Mn2+­dependent 1A (PPM1A) in the anti­EMT activity of JMSD on AECs. The components in the aqueous extract of JMSD were identified by high­performance liquid chromatography coupled with electrospray mass spectrometry. Primary rat type II AECs were treated with radiation (60Co γ­ray at 8 Gy) and JMSD­medicated serum. PPM1A was overexpressed and knocked down in the AECs via lentivirus transduction and the effects of JMSD administration on the key proteins related to TGF­ß1/Smad signaling were measured by western blotting. It was found that radiation decreased the PPM1A expression in the AECs and JMSD­medicated serum upregulated the PPM1A expressions in the radiation­induced AECs. PPM1A overexpression increased the E­cadherin level but decreased the phosphorylated (p­)Smad2/3, vimentin and α­smooth muscle actin (α­SMA) levels in the AECs. By contrast, the PPM1A knockdown decreased the E­cadherin level and increased the p­Smad2/3, vimentin and α­SMA levels in the AECs and these effects could be blocked by SB431542 (TGF­ß1/Smad signaling inhibitor). JMSD administration increased the E­cadherin level and decreased the p­Smad2/3, vimentin and α­SMA levels in the AECs; however, these effects could be blocked by siPPM1A­2. In conclusion, PPM1A is a key target of JMSD administration for the attenuation of the radiation­induced EMT in primary type II AECs via the TGF­ß1/Smad pathway.

Jiawei Xianglian Decoction (JWXLD), a Traditional Chinese Medicine (TCM), Alleviates CPT-11-Induced Diarrhea in Mice.

Irinotecan (CPT-11) is used for therapy of various cancers. However, it has several serious adverse reactions such as diarrhea which is caused by SN-38, the active form of CPT-11. This study aimed to evaluate the effectiveness of Jiawei xianglian decoction (JWXLD), which has been widely used for the treatment of diarrhea in China. In this study, a mouse model with delayed diarrhea was generated by CPT-11. Real-time PCR and enzyme-linked immunosorbent assay (ELISA) were performed to explore intestinal microflora and inflammatory cytokine. Hematoxylin and eosin (H&E) staining was used to analyze tissue morphology. We found that 0.12, 0.23, and 0.46 g JWXLD significantly reduced the severity of CPT-11-induced diarrhea. The levels of Lactobacillus (Lacto) and Bifidobacterium (Bifid) were significantly downregulated by CPT-11, and these effects can be reversed by JWXLD treatment. Furthermore, JWXLD was observed to decrease the activity of ß-glucuronidase (ß-GD). Histopathological data showed that CPT-11 induced severe intestinal mucosal injury, which was characterized as grade 6, and JWXLD significantly alleviated the injury. In addition, CPT-11 increased the productions of tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-beta (TNF-ß), interleukin-6 (IL-6), and interleukin-1 (IL-1), but decreased interleukin-15 (IL-15), interleukin-7 (IL-7), and uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). In conclusion, JWXLD can counteract these effects caused by CPT-11 treatment. JWXLD could alleviate CPT-11-induced diarrhea.