Ma xing shi gan decoction eliminates PM2.5-induced lung injury by reducing pulmonary cell apoptosis through Akt/mTOR/p70S6K pathway in rats

Abstract

<jats:title>Abstract</jats:title> <jats:p>The present study was designed to investigate the anti-apoptosis effect of Ma xing shi gan decoction (MXD) on PM2.5-induced lung injury via protein kinase B (Akt)/mTOR/p70S6K pathway. A UPLC-MS/MS system was introduced for component analysis of MXD. Rats were instilled with PM2.5 solution suspension intratracheally to induce acute lung injury. The rats were then orally administered with MXD (16, 8, and 4 g/kg) once a day for 7 consecutive days. The therapeutic effects of MXD were evaluated by Hematoxylin and Eosin (HE) staining. The apoptotic cell death was analyzed by terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay. The alterations in cytochrome c (Cytc) and cleaved-caspase-3 (C-caspase-3) were measured by immunohistochemistry (IHC). The expressions of Bax, B-cell lymphoma 2 (Bcl-2), p-Akt, p-mTOR and p-p70S6K were detected by Western blot. In vitro, PM2.5 exposure model was introduced in A549 cell, followed by incubation with MXD-medicated serum. Hoechst staining was used to determine apoptotic rate. The levels of Bax, Bcl-2, p-Akt, p-mTOR and p-p70S6K were detected by Western blot. Our results in vivo indicated that treatment with MXD decreased histopathological changes score, TUNEL-positive cells rate, expressions of Cytc and C-caspase-3. The in vitro results revealed that incubation with MXD-mediated serum decreased apoptotic rate. Both results in vivo and in vitro demonstrated that MXD inhibited pro-apoptotic protein Bax and promoted anti-apoptotic protein Bcl-2 expression. Likewise, MXD activated Akt/mTOR/p70S6K signal pathway, which was also confirmed by Western immunoblotting. In conclusion, MXD attenuates lung injury and the underlying mechanisms may relate to regulating the apoptosis via Akt/mTOR/p70S6K signaling pathway activation.</jats:p>

Octreotide activates autophagy to alleviate lipopolysaccharide-induced human pulmonary epithelial cell injury by inhibiting the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway

“…AKT/mTOR signaling, a classical autophagy-related pathway, has been implicated in the mechanism investigation about ALI in previous studies [ 30 , 31 ]. To further identify the potential mechanisms of Octreotide mediate cell autophagy in ALI model, the protein levels of related factors in AKT/mTOR signaling were determined using Western blot analysis.…”

The rational dose for MaXingShiGan decoction is crucial for its clinical effectiveness in treating bronchial pneumonia: three randomized, double-blind, dose-parallel controlled clinical studies

“…Originating from the "Shang Han Lun," MaXingShiGan Decoction (MSXG) is a traditional Chinese formula composed mainly of Ephedra sinica Stapf [Ephedraceae; HERBA EPHEDRAE] (MaHaung, MH), Prunus armeniaca L. [Rosaceae; Semen Armeniacae Amarum] (KuXingRen, KXR), Gypsum Fibrosum [Mineral; Gypsum] (ShiGao, SG), and Glycyrrhiza glabra L. [Fabaceae; RADIX GLYCYRRHIZAE] (GanCao, GC). It itself and the derivative formulas such as Lianhua Qingwen Capsules, Han Shi Yi Formula, QingFeiPaiDu Decoction, are commonly employed to treat upper respiratory infections, acute bronchitis, pneumonia, bronchial asthma, and played a pivotal role in the management of the COVID-19 pandemic in China (Zhu and Liu, 2004;Liao et al, 2017;Wang et al, 2020a;Wang et al, 2020b;Tian et al, 2020;Xiao et al, 2020). Additionally, a prior randomized, double-blind, placebo-controlled, multicenter clinical study that we conducted demonstrated the efficacy of MSXG in effectively treating community-acquired childhood pneumonia and significantly improving fever and other clinical symptoms (Zheng et al, 2022).…”