Effects of Nervilia fordii Extract on Pulmonary Fibrosis Through TGF-β/Smad Signaling Pathway

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial pulmonary disease with a poor prognosis. The extract of Nervilia fordii (NFE) has shown remarkable benefit in the treatment of acute lung injury, lung cancer, and severe acute respiratory syndrome (SARS). However, the potential mechanism and efficacy of NFE in the treatment of IPF remain unknown. In this study, a systematic network pharmacology analysis was used to predict the mechanism and efficacy of NFE in the treatment of IPF, based on the major components of NFE elucidated by UPLC-TOF-MS/MS. The potential molecular interactions between the compounds and potential targets were predicted using molecular docking. In vivo, rats with pulmonary fibrosis induced by a single intratracheal injection of bleomycin (BLM) were orally administered NFE for 14 days. Lung index and biochemical levels were determined, and histopathological analysis using hematoxylin and eosin (H&E) and Masson staining was performed. The effects of NFE on fibroblast proliferation in Lipopolysaccharide (LPS) and TGF-β1-induced mouse 3T6 fibroblasts were evaluated in vitro. In total, 20 components were identified in NFE, and 102 potential targets for IPF treatment were predicted. These targets potentially participate in processes regulated by transmembrane receptor protein tyrosine kinase, ERBB2, and et al. Molecular docking results predicted high affinity interactions between three components (rhamnazin, rhamnetin, and rhamnocitrin) and the potential targets, suggesting that TGF-β is the most important potential target of NFE in the treatment of pulmonary fibrosis. NFE significantly decreased the lung index and alleviated BLM-induced pulmonary fibrosis in rats. Histopathological observation of lung tissues showed that NFE alleviated inflammation and collagen deposition in BLM-induced rats. NFE inhibited the migration of LPS- and TGF-β1-induced 3T6 fibroblasts, reduced the contents of hydroxyproline and collagen, and contributed to anti-inflammation and anti-oxidation. With the intervention of NFE, the protein and RNA expression of TGF-β1, a-SMA, Smad3/4, p-Smad3/4, CTGF, and p-ERK1/2 were significantly downregulated, while Smad7 and ERK1/2 were upregulated significantly in vivo and in vitro. These findings indicated that NFE may exert therapeutic effects on pulmonary fibrosis by alleviating inflammation, oxidation, and collagen deposition. The mechanism related to the inhibition of the TGF-β/Smad signaling pathway.

Molecular Mechanisms of Gynostemma pentaphyllum in Prevention and Treatment of Non-Small-Cell Lung Cancer

“…Quercetin has a variety of biological properties, such as antioxidant, anti-inflammatory, and antiapoptosis [22][23][24], which has been widely investigated in human cancers, including lung cancer. It was reported that the antiproliferative [27]. e antitumor effects of rhamnazin were also proved in hepatocellular carcinoma [28].…”

“…The antitumor functions of the other three bioactive compounds are also found in documented reports of lung cancer or other cancers. Yao et al demonstrated that rhamnazin may exert a therapeutic effect on pulmonary fibrosis by alleviating inflammation, oxidation, and collagen deposition via the TGF- β /Smad axis [ 27 ]. The antitumor effects of rhamnazin were also proved in hepatocellular carcinoma [ 28 ].…”

Scorpion Venom Polypeptide Inhibits Pulmonary Epithelial-Mesenchymal Transition in Systemic Sclerosis-Interstitial Lung Disease Model Mice by Intervening TGF-β1/Smad Signaling Pathway

“…The key mechanism of SSc-ILD pathogenesis is persistent lung damage caused by alveoli macrophage activation, which induces the release of a variety of profibrosis cytokines, prompts the conversion of pulmonary epithelial cells to interstitial cells (EMT), and eventually results in the formation of pulmonary fibrosis [ 21 ]. Recently, TCM has been more and more accepted in the treatment of pulmonary fibrosis worldwide [ 22 ]; Yangyin Yiqi Mixture [ 23 ], Nervilia fordii extract [ 24 ], and Inulae Flos [ 25 ] have a good effect on pulmonary fibrosis with few side effects. Although the active role of PESV on SSc-ILD is unclear, a published study has proved that PESV obviously improves fibrosis in rats with doxorubicin-induced acute cardiotoxicity [ 26 ].…”

Cultivable endophytic fungal community associated with the karst endemic plant Nervilia fordii and their antimicrobial activity

“…is a small, terrestrial, and short-lived perennial plant (Orchidaceae) that is endemic to the karst limestone mountains ( Figures 1A–D ) in Guangxi Province, China. The whole plant or the aerial part of N. fordii ( Figure 1E ) are used as premium dishes, herbal tea, and folk medicine ( Qiu et al, 2013 ) because of their excellent pharmacological capacities, such as antimicrobial ( Li et al, 2017 ; Xu et al, 2017 ), anticancer ( Yao et al, 2021 ), antiviral ( Tian et al, 2009 ), and anti-inflammatory ( Yin et al, 2021 ) effects. In particular, this plant was widely used as a main ingredient in traditional Chinese medicine formulations to treat patients with severe acute respiratory syndrome in 2013 ( Qiu et al, 2013 ).…”