2. Academic Validation
  3. n-BuOH extract of Bletilla striata exerts chemopreventive effects on lung against SiO2 nanoparticles through activation of Nrf2 pathway

n-BuOH extract of Bletilla striata exerts chemopreventive effects on lung against SiO2 nanoparticles through activation of Nrf2 pathway

  • Phytomedicine. 2021 Feb:82:153445. doi: 10.1016/j.phymed.2020.153445.
Gang Chen 1,  Wenhui Chang 2,  Xuezheng Li 3,  Longzhe Han 4,  Di Zhou 2,  Yuan Feng 2,  Bingxin Li 2,  Fangying Zhu 5,  Ning Li 6
Affiliations

Affiliations

  • 1 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming China.
  • 2 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 3 Department of PIVAS, Yanbian University Hospital, Yanji, China.
  • 4 Department of Phathology, Yanbian University Hospital, Yanji, China.
  • 5 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming China.
  • 6 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: [email protected].
PMID: 33418138 DOI: 10.1016/j.phymed.2020.153445
Abstract

Background: SiO2 nanoparticles (nm SiO2) are ubiquitous in daily life and are acknowledged to be detrimental to human health. Bletilla striata is a traditional medicine used for generations in China and its polysaccharide has the anti-pulmonary fibrosis effect.

Purpose: To investigate the lung protective effect of the small molecules (n-BuOH extract) of B. striata and clarify the underlying mechanism.

Study design and methods: C57BL/6 mice were subjected to intratracheal instillation with nm SiO2 nanoparticle suspension (7 mg/kg) to construct the in vivo model of nm SiO2-induced lung injury. The chemical profile of the n-BuOH extract of B. striata was investigated by HPLC analysis using authentic samples isolated from B. striata. Gymnoside II with the most potent chemoprotective capacity in the n-BuOH extract was used to clarify the potential bio-active molecular basis of the n-BuOH extract using in vitro experiments. The cytotoxicity, Apoptosis, oxidative stress, and the Nrf2 signaling pathway were examined in SiO2-induced A549 cells. ML385 was adopted to down-regulate the Nrf2 expression.

Results: The n-BuOH extract of B. striata (40 mg/kg) could alleviate the SiO2-induced lung injury by increasing Nrf2 expression and thereby suppressing Bax/Bcl-2 pathway in the nm SiO2-induced mice model. The chemical profile study showed that militarine, gymnoside II, and 4-allyl-2, 6-dimethoxyphenol glucoside were the main constituents of n-BuOH extract. Studies on gymnoside II revealed that it could partially restore the SiO2-induced decline in cell viability while did not affect the growth of normal A549 cells within the concentration range of 1-50 μM, suggesting a protective effect against nm SiO2 in lung A549 cells. The hoechst 33258 staining, flow cytometry, and western blot experiments demonstrated that gymnoside II (25 μM) could partially reverse the SiO2-induced cell Apoptosis and ROS production by enhancing Nrf2, HO-1, and γ-GCSc expressions and Nrf2 silencing by ML385 abrogated the effects of gymnoside II (25 μM) on Apoptosis and ROS production in A549 cells.

Conclusion: The present study suggests that in addition to the polysaccharide, small molecules (n-BuOH extract) of B. striata can also elicit a protective effect on lung injuries through the Nrf2-dependent mechanism and gymnoside II is one of the main bio-active constituents contributing to the n-BuOH extract-elicited lung protective effect against nm SiO2.

Keywords

Chemoprevention; Gymnoside II; Lung injury; Nrf2; nm SiO(2).

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