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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01332

Liang-Ge-San, a classic traditional Chinese medicine formula, attenuates lipopolysaccharide-induced acute lung injury through up-regulating miR-21

Huayi YANG1,  Zibin LU1, Chuying HUO1, Yuyao CHEN1,  Huihui CAO1, Pei XIE1, Hongling ZHOU1, Dongyi LIU1,  Junshan LIU1, 2 and Linzhong YU1*
  • 1School of Traditional Chinese Medicine, Southern Medical University, China
  • 2Southern Medical University, China

Background: Acute lung injury (ALI) is a life-threatening disease without effective chemotherapy at present. Liang-Ge-San (LGS) is a famous traditional Chinese medicine formula, which is used to treat ALI in China. However, only a few studies have addressed the mechanisms of LGS in ALI.
Purpose: To evaluate the anti-inflammatory effects of LGS on lipopolysaccharide (LPS)-induced ALI, and to explore its underlying molecular mechanism.
Methods: Murine RAW264.7 cells were treated with LGS and LPS (1 μg/ml). The generation of IL-6, TNF-α, IL-1β and IL-4 was detected by ELISA. The protein expressions of STAT3 and P-STAT3 (Tyr705) were determined by Western blotting and fluorescence confocal microscopy. STAT3 transcriptional activity was investigated by luciferase reporter gene assay. qPCR was used to detect the expressions of microRNA-21 (miR-21), STAT3 and IL-6. DSS cross-linking assay was used to assess the change of STAT3 dimer. In vivo anti-inflammatory effects of LGS were evaluated in an ALI mouse model induced by tracheal instillation of LPS (3 mg/kg). The anti-ALI effects were evaluated by ELISA, qPCR, Western blotting, BCA and H&E assays.
Results: LGS suppressed LPS-stimulated IL-6, TNF-α and IL-1β generation, increase the generation of IL-4 in murine macrophages RAW264.7. Moreover, LGS down-regulated protein levels of P-STAT3 (Tyr705) and STAT3, inhibited STAT3 transcriptional activity, and up-regulated miR-21. Furthermore, blockage of miR-21 antagonized the inhibitory effects of LGS on the production of IL-6 and the expressions of P-STAT3 (Tyr705) and STAT3 as well as the formation of STAT3 dimer. Critically, LGS up-regulated the expression of miR-21 and inhibited the protein expressions of STAT3 and P-STAT3 (Tyr705) to reduce the release of IL-6 and inflammatory cell infiltration as well as the degree of edema in LPS-induced ALI mice.
Conclusion: LGS inhibited LPS-induced ALI through up-regulating miR-21 and subsequently inhibiting the STAT3 signaling pathway, thereby decreasing the release of IL-6.

Keywords: Liang-Ge-San, Acute Lung Injury, miR-21, stat3, Inflammation

Received: 29 Jul 2019; Accepted: 18 Oct 2019.

Copyright: © 2019 YANG, LU, HUO, CHEN, CAO, XIE, ZHOU, LIU, LIU and YU. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Linzhong YU, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China, yulzh@smu.edu.cn