Protective Effect of Alcohol Extract of Phyllanthi Fructus on Silicosis Mice and Its Correlation with Nrf2/ARE Signaling Pathway

ZHANG Yudie; LI Xin; HE Xiaoyan; WU Lijuan; YU Rong; YANG Peifu; CHEN Dayi

doi:10.13422/j.cnki.syfjx.20230991

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Protective Effect of Alcohol Extract of Phyllanthi Fructus on Silicosis Mice and Its Correlation with Nrf2/ARE Signaling Pathway

更新时间：2023-03-30

- Protective Effect of Alcohol Extract of Phyllanthi Fructus on Silicosis Mice and Its Correlation with Nrf2/ARE Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 9, Pages: 129-136(2023)
- 作者机构：
  
  1.成都中医药大学，成都 611137
  2.凉山州晟森生物科技有限公司，四川西昌 615000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230991
  CLC： R242;R2-0;R2-031;R285;R825.6;R56
- Published：05 May 2023，
  
  Published Online：22 March 2022，
  
  Received：25 October 2021，
- 稿件说明：
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张玉蝶,李欣,何晓艳等.余甘子醇提物对硅肺小鼠的保护作用及与Nrf2/ARE信号通路的相关性[J].中国实验方剂学杂志,2023,29(09):129-136.

ZHANG Yudie,LI Xin,HE Xiaoyan,et al.Protective Effect of Alcohol Extract of Phyllanthi Fructus on Silicosis Mice and Its Correlation with Nrf2/ARE Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(09):129-136.
张玉蝶,李欣,何晓艳等.余甘子醇提物对硅肺小鼠的保护作用及与Nrf2/ARE信号通路的相关性[J].中国实验方剂学杂志,2023,29(09):129-136. DOI： 10.13422/j.cnki.syfjx.20230991.

ZHANG Yudie,LI Xin,HE Xiaoyan,et al.Protective Effect of Alcohol Extract of Phyllanthi Fructus on Silicosis Mice and Its Correlation with Nrf2/ARE Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(09):129-136. DOI： 10.13422/j.cnki.syfjx.20230991.

摘要

目的

探讨余甘子醇提物对二氧化硅（SiO

）诱导的硅肺小鼠的影响及可能的作用机制。

方法

将SPF级雄性昆明小鼠36只随机分为空白组、模型组、余甘子高剂量组（800 mg·kg

-1

）、余甘子中剂量组（400 mg·kg

-1

）、余甘子低剂量组（200 mg·kg

-1

）、汉防己甲素组（0.039 mg·kg

-1

），每组6只。除空白组以外，其余组均采用静式染毒法复制硅肺模型。灌胃28 d后取出肺组织计算脏器系数；采用苏木素-伊红（HE）染色和Masson染色检测小鼠肺组织的组织形态；采用酶联免疫吸附测定法（ELISA）检测血清中的羟脯氨酸（HYP）、超氧化物歧化酶（SOD）、丙二醛（MDA）、过氧化氢酶（CAT）的含量；应用蛋白免疫印迹法（Western blot）和实时荧光定量聚合酶链式反应（Real-time PCR）技术检测核因子E

相关因子2（Nrf2）、血红素氧合酶-1（HO-1）、依赖型辅酶还原酶/醌氧化还原酶1（NQO1）、Kelch样环氧氯丙烷相关蛋白1（Keap1）蛋白和mRNA的表达。

结果

与空白组比较，模型组小鼠肺组织形态结构严重损伤，炎性细胞浸润，纤维组织增生；血清中SOD和CAT的含量均显著减少（

0.01），HYP和MDA的含量均显著增加（

0.01）；肺组织中Nrf2、HO-1、NQO1蛋白与mRNA的表达均显著减少（

0.01），Keap1蛋白与mRNA的表达均明显增加（

0.05，

0.01）。与模型组比较，余甘子高、中剂量组小鼠的肺组织形态结构得到明显恢复，胶原沉积减少；余甘子高、中剂量组血清的SOD和CAT含量均明显增加（

0.05，

0.01），HYP和MDA含量均显著减少（

0.01）；余甘子高、中剂量组肺组织的Nrf2、HO-1、NQO1蛋白与mRNA的表达均明显增加（

0.05，

0.01），Keap1蛋白与mRNA的表达均明显减少（

0.05，

0.01）。

结论

余甘子醇提物可以抑制硅肺小鼠肺纤维化，其机制可能与Nrf2/抗氧化反应元件（ARE）信号通路的调控有关。

Abstract

Objective

To explore the effect and underlying mechanism of alcohol extract of Phyllanthi Fructus on silicosis mice induced by silicon dioxide （SiO

）.

Method

Thirty-six male Kunming mice of SPF grade were randomly divided into a blank group，a model group，high-， medium， and low-dose Phyllanthi Fructus

groups （800， 400， 200 mg·kg

-1

），and a tetrandrine group （0.039 mg·kg

-1

），with six mice in each group. The silicosis model was induced by static SiO

exposure in mice except for those in the blank group. After 28 days of administration by gavage，the lung tissues were collected and the organ coefficient was calculated. Hematoxylin-eosin（HE）staining and Masson staining were used to detect the morphology of lung tissues. The content of hydroxyproline （HYP），superoxide dismutase （SOD），malondialdehyde （MDA）， and catalase （CAT） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and Real-time polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression of nuclear factor E

-related factor 2 （Nrf2），heme oxygenase-1 （HO-1），NAD（P）H：quinone oxidoreductase 1 （NQO1），and Kelch-like ECH-associated protein 1 （Keap1）， respectively.

Result

Compared with the blank group，the model group showed seriously damaged morphological structure of lung tissues with inflammatory cell infiltration and fibrous tissue proliferation， reduced serum content of SOD and CAT（

0.01），increased content of HYP and MDA（

0.01）， down-regulated protein and mRNA expression of Nrf2，HO-1， and NQO1（

0.01），and up-regulated protein and mRNA expression of Keap1 （

0.05，

0.01）. Compared with the model group，the high- and medium-dose Phyllanthi Fructus

groups showed significantly restored morphological structure of lung tissues with reduced collagen deposition， increased serum content of SOD and CAT（

0.05，

0.01），decreased content of HYP and MDA（

0.01）， up-regulated protein and mRNA expression of Nrf2，HO-1， and NQO1 （

0.05，

0.01），and down-regulated protein and mRNA expression of Keap1（

0.05，

0.01）.

Conclusion

The alcohol extract of

Phyllanthi Fructus can inhibit pulmonary fibrosis in silicosis mice，and the underlying mechanism may be related to the regulation of the Nrf2/antioxidant response element （ARE） signaling pathway.

关键词

余甘子硅肺抗纤维化抗氧化核因子E2相关因子2（Nrf2）/抗氧化反应元件（ARE）信号通路

Keywords

Phyllanthi Fructussilicosisanti-fibrosisanti-oxidationnuclear factor E2-related factor 2/antioxidant response element （ARE） signaling pathway

references

郭晓琴.浅析矽肺的临床症状、并发症及治疗［J］.全科口腔医学电子杂志，2018，5（33）：189.

MORRISON C，DAVEY G.Assessment of respiratory function in patients with podoconiosis［J］.Trans R Soc Trop Med Hyg，2009，103（3）：315-317.

李玉洁，贾晓民.矽肺的治疗进展［J］.临床肺科杂志，2017，22（6）：1119-1122.

GROTTO D，SANTA MARIA L D，BOEIRA S，et al.Rapid quantification of malondialdehyde in plasma by high performance liquid chromatography-visible detection［J］.J Pharm Biomed Anal，2007，43（2）：619-624.

ZHANG X，JIA X，MEI L，et al.Global DNA methylation and PTEN hypermethylation alterations in lung tissues from human silicosis［J］.J Thorac Dis，2016，8（8）：2185-2195.

HUANG H，CHEN M，LIU F，et al.N-acetylcysteine tiherapeutically protects against pulmonary fibrosis in a mouse model of silicosis［J］.Biosci Rep，2019，doi：10.1042/BSR20190681http://dx.doi.org/10.1042/BSR20190681.

李少峰，高洁，兰智慧，等.Nrf2/ARE信号通路的调控与肺纤维化［J］.江西医药，2017，52（9）：934-937.

TUNG Y T，HUANG C Z，LIN J H，et al.Effect of Phyllanthus emblica L.fruit on methionine and choline-deficiency diet-induced nonalcoholic steatohepatitis［J］.J Food Drug Anal，2018，26（4）：1245-1252.

HUANG H Z，QIU M，LIN J Z，et al.Potential effect of tropical fruits Phyllanthus emblica L.for the prevention and management of type 2 diabetic complications：A systematic review of recent advances［J］.Eur J Nutr，2021，60（7）：3525-3542.

PINMAI K，CHUNLARATTHANABHORN S，NGAMKITIDECHAKUL C，et al.Synergistic growth inhibitory effects of Phyllanthus emblica and Terminalia bellerica extracts with conventional cytotoxic agents：Doxorubicin and cisplatin against human hepatocellular carcinoma and lung cancer cells［J］.World J Gastroenterol，2008，14（10）：1491-1497.

WANG C C，YUAN J R，WANG C F，et al.Anti-inflammatory effects of Phyllanthus emblica L. on benzopyrene-induced precancerous lung lesion by regulating the IL-1β/miR-101/Lin28B signaling pathway［J］.Integr Cancer Ther，2017，16（4）：505-515.

NICOLIS E，LAMPRONTI I，DECHECCHI M C，et al.Pyrogallol，an active compound from the medicinal plant Emblica officinalis，regulates expression of pro-inflammatory genes in bronchial epithelial cells［J］.Int Immunopharmacol，2008，8（12）：1672-1680.

TAHIR I，KHAN M R，SHAH N A，et al.Evaluation of phytochemicals，antioxidant activity and amelioration of pulmonary fibrosis with Phyllanthus emblica leaves［J］.BMC Complement Altern Med，2016，16（1）：406.

吴丽娟，何晓艳，梁静涛，等.大黄䗪虫丸经p38 MAPK/NF-κB/TGF-β1通路抑制小鼠硅肺纤维化的机制探讨［J］.中国实验方剂学杂志，2021，27（11）：27-34.

国家药典委员会.中华人民共和国药典：一部［M］.北京：中国医药科技出版社，2020：186.

孙晓伟，肖华，宋学术，等.萝卜硫素通过Nrf2/ARE通路缓解矽肺模型大鼠肺组织纤维化及氧化应激的实验研究［J］.临床和实验医学杂志，2020，19（6）：586-589.

WU L J，HE X Y，LIANG J T，et al.Intragastric administration of Dahuang Zhechong pill modulates TGF-β1/smad signaling pathway in murine model of experimental silicosis［J］.J King Saud Univ Sci，2020，32（8）：3223-3229.

PENG H B，WANG R X，DENG H J，et al.Protective effects of oleanolic acid on oxidative stress and the expression of cytokines and collagen by the Akt/NF‑κB pathway in silicotic rats［J］.Mol Med Rep，2017，15（5）：3121-3128.

NARDI J，NASCIMENTO S，GÖETHEL G，et al.Inflammatory and oxidative stress parameters as potential early biomarkers for silicosis［J］.Clin Chim Acta，2018，484：305-313.

PERUZZI C，NASCIMENTO S，GAUER B，et al.Inflammatory and oxidative stress biomarkers at protein and molecular levels in workers occupationally exposed to crystalline silica［J］.Environ Sci Pollut Res Int，2019，26（2）：1394-1405.

CHAPHALKAR R，APTE K G，TALEKAR Y，et al.Antioxidants of Phyllanthus emblica L.Bark extract provide hepatoprotection against ethanol-induced hepatic damage：A comparison with silymarin［J］.Oxid Med Cell Longev，2017，2017：3876040.

TASANARONG A，KONGKHAM S，ITHARAT A.Antioxidant effect of Phyllanthus emblica extract prevents contrast-induced acute kidney injury［J］.BMC Complement Altern Med，2014，14：138.

SHARMA P，JOSHI T，JOSHI T，et al.In silico screening of potential antidiabetic phytochemicals from Phyllanthus emblica against therapeutic targets of type 2 diabetes［J］.J Ethnopharmacol，2020，248：112268.

ZHAO T，SUN Q，MARQUES M，et al.Anticancer properties of Phyllanthus emblica （Indian Gooseberry）［J］.Oxid Med Cell Longev，2015，2015：950890.

FENG F，CHENG P，ZHANG H，et al.The protective role of tanshinone ⅡA in silicosis rat model via TGF-β1/Smad signaling suppression，NOX4 inhibition and Nrf2/ARE signaling activation［J］.Drug Des Devel Ther，2019，13：4275-4290.

PENG L，WEN L，SHI Q，et al.Chelerythrine ameliorates pulmonary fibrosis via activating the Nrf2/ARE signaling pathway［J］.Cell Biochem Biophys，2021，79（2）：337-347.

KIKUCHI N，ISHII Y，MORISHIMA Y，et al.Nrf2 protects against pulmonary fibrosis by regulating the lung oxidant level and Th1/Th2 balance［J］.Respir Res，2010，11（1）：31.

XU Y，TAI W，QU X，et al.Rapamycin protects against paraquat-induced pulmonary fibrosis：Activation of Nrf2 signaling pathway［J］.Biochem Biophys Res Commun，2017，490（2）：535-540.

胡玉伟.Nrf2/ARE信号通路在矽肺发生过程中的机制研究［D］.济南：济南大学，2018.

LI W，ZHANG X，CHEN R，et al.HPLC fingerprint analysis of Phyllanthus emblica ethanol extract and their antioxidant and anti-inflammatory properties［J］.J Ethnopharmacol，2020，254：112740.

TSAI C C，CHOU C H，LIU Y C，et al.Ultrasound-assisted extraction of phenolic compounds from Phyllanthus emblica L.and evaluation of antioxidant activities［J］.Int J Cosmet Sci，2014，36（5）：471-476.

KHAN M T，LAMPRONTI I，MARTELLO D，et al.Identification of pyrogallol as an antiproliferative compound present in extracts from the medicinal plant Emblica officinalis：Effects on in vitro cell growth of human tumor cell lines［J］.Int J Oncol，2002，21（1）：187-192.

THOIDINGJAM S，TIKU A B.Therapeutic efficacy of Phyllanthus emblica-coated iron oxide nanoparticles in A549 lung cancer cell line［J］.Nanomedicine （Lond），2019，14（17）：2355-2371.

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