1.Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Tuberculosis Research Institute, the 8th Medical Center, Chinese PLA General Hospital, Beijing 100091, China
2.Hebei North University, Zhangjiakou 075000, Hebei, China
3.Clinical Laboratory, the 8th Medical Center, Chinese PLA General Hospital, Beijing 100091, China
4.Pathology Department, the 8th Medical Center, Chinese PLA General Hospital, Beijing 100091, China
5.Guangdong Qifang Pharmaceutical Co., Ltd, Guangzhou 510075, China
* zhengy309@126.com;
xueqiongwu@139.com
纸质出版:2022-04
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Comparative study on the anti-tuberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan[J]. 解放军医学杂志(英文版), 2022,9(2):164-183.
Duan et al.: Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan. Mil Med Res, 2021, 8: 34.
Comparative study on the anti-tuberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan[J]. 解放军医学杂志(英文版), 2022,9(2):164-183. DOI: 10.1186/s40779-021-00324-5.
Duan et al.: Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan. Mil Med Res, 2021, 8: 34. DOI: 10.1186/s40779-021-00324-5.
Background:
2
The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis (TB) effects. The anti-TB effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH.
Methods:
2
BALB/c mice aged 6-8 weeks were randomly divided into a normal control group
TB model group
JHW treatment group
and NBXH treatment group. After 3 and 13 weeks of treatment
the therapeutic effect in each group was evaluated by comparing lung histopathology
lung and liver colony counts
the number of spots representing effector T cells secreting IFN-γ in an enzyme-linked immunospot assay (ELISPOT)
and the levels of Th1
Th2
and Th17 cytokines
which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing.
Results:
2
After 13 weeks of treatment
the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (
P
<
0.05). Compared with those in the TB model group
the lung colony counts in the JHW and NBXH groups were significantly decreased (
P
<
0.05)
and the IL-2 and IL-4 levels in the NBXH group were significantly increased (
P
<
0.05). NBXH partly restored significant changes in gene expression caused by
Mycobacterium tuberculosis
(
M. tuberculosis
) infection. According to GO and KEGG analyses
the changes in biological process (BP)
cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent
but they were mainly related to the immune response and inflammatory response in the mouse TB model.
Conclusions:
2
NBXH had therapeutic effects similar to those of JHW in improving lung histopathology
reducing lung colony counts
and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by
M. tuberculosis
infection by regulating immune-related pathways
which clarified the mechanism of action of NBXH.
World Health Organization . Global tuberculosis report . 2020 . https://www.who.int/teams/global-tuberculosis-programme/data https://www.who.int/teams/global-tuberculosis-programme/data . Accessed 22 Jan 2021 .
Zhao GQ , Ren B , Dong XP , Tong TT , Zhang LL , Xiang H . The research progress of chuanbeimu . Pharma Clin Chin Med . 2012 ; 3 ( 6 ): 59 - 64 .
He XR , Wang XX , Fang JC , Zhao ZF , Huang LH , Guo H , et al . Bletilla striata: medicinal uses, phytochemistry and pharmacological activities . J Ethnopharmacol . 2017 ; 195 ( 2017 ): 20 - 38 . https://doi.org/10.1016/j.jep.2016.11.026 https://doi.org/10.1016/j.jep.2016.11.026 .
National Pharmacopoeia Commission . Pharmacopoeia of the people’s republic of China (I) . Beijing Chin Med Sci Tech . 2015 ; 36,72,103,224,277 .
Wang XM . The study on the antibacterial effect of Niubeixiaohe of traditional Chinese medicine in vitro and in vivo experiments . Nanjing Univ Chin Med . 2014 .
Li GM . Study on the mechanism of NiuBeiXiaoHe extract against Mycobacterium tuberculosis . Nanjing Univ TCM . 2017 ; 22 .
Ling YB , Liang Y , Wang XM , Wang L , Zhang JX , Yang YR , et al . The study on the targets of the antituberculosis effect of traditional Chinese medicine Niubeixiaohe extracts . Chin J Antituberc . 2016 ; 38 ( 1 ): 17 - 22 . https://doi.org/10.3969/j.issn.1000-6621.2016.01.006 https://doi.org/10.3969/j.issn.1000-6621.2016.01.006 .
Chen D . The research on the immunology and general pharmacology of the anti-tuberculosis Chinese medicine preparations Niubeixiaohe . Nanjing Univ Chin Med . 2014 ; 38 .
Zhang JG , Wang LP , Sun Y . Jiehewan adjuvant treatment of tuberculosis . Jilin J TCM . 2016 ; 36 ( 8 ): 790 - 2 . https://doi.org/10.13463/j.cnki.jlzyy.2016.08.011 https://doi.org/10.13463/j.cnki.jlzyy.2016.08.011 .
Liu X , Wu XQ . Research progress of traditional Chinese medicine in treatment of multi-drug resistant pulmonary tuberculosis . Chin J Antituberc . 2016 ; 38 ( 1 ): 53 - 6 . https://doi.org/10.3969/j.issn.1000-6621.2016.01.012 https://doi.org/10.3969/j.issn.1000-6621.2016.01.012 .
Yang QS , Yang Y , Wang XP , Chen X . Research progress of Jiehewan in treating tuberculosis . Eval Drug Use Chin . 2017 ; 17 ( 4 ): 571 - 6 . https://doi.org/10.14009/j.issn.1672-2124.2017.04.051 https://doi.org/10.14009/j.issn.1672-2124.2017.04.051 .
Liang Y , Wang XM , Song JY , Wang L , Chen D , Yang YR , et al . Therapeutic effects of traditional Chinese medicine Niubeixiaohe in mouse tuberculosis models . J Ethnopharmacol . 2017 ; 195 ( 2017 ): 318 - 23 . https://doi.org/10.1016/j.jep.2016.11.037 https://doi.org/10.1016/j.jep.2016.11.037 .
Li RX , Liu XZ , Tang ZJ , Xian QY , Wang Y , Zhang J . Establishment of mouse model of acute infection with mycobacterium tuberculosis . J Pub Health and Prev Med . 2007 ; 18 ( 5 ): 12 - 4 . https://doi.org/10.3969/j.issn.1006-2483.2007.05.004 https://doi.org/10.3969/j.issn.1006-2483.2007.05.004 .
Wang YP , Ye PL , Zhang CT , Lu RS , Lu ZF , Liu ZG . Effect of FeiLaoKang on the expression of caspase-3 and IL-2 in mouse model of rifampin-resistant Mycobacterium tuberculosis . Mod TCM . 2015 ; 35 ( 5 ): 146 - 50 . https://doi.org/10.13424/j.cnki.mtcm.2015.05.057 https://doi.org/10.13424/j.cnki.mtcm.2015.05.057 .
Xiang ZG , Lin SZ , Dong N , Yuan W , Xu YF , Qin C . Bacterial load and pathological changes in the spleen and lung of M. tuberculosis hematogenous infected mice . Chin J Comp Med . 2011 ; 21 ( 8 ): 66 - 8 . https://doi.org/10.3969/j.issn.1671-7856.2011.08.017 https://doi.org/10.3969/j.issn.1671-7856.2011.08.017 .
Wu SR , Cai R , Li S , Shen KJ , Jia BZ , Li FR . Effects of Huangkuisu on killing and suppressing mycobacterium tuberculosis . J TCM Univ Hunan . 2011 ; 31 ( 11 ): 19 - 23 . https://doi.org/10.3969/j.issn.1674-070X.2011.11.006.019.05 https://doi.org/10.3969/j.issn.1674-070X.2011.11.006.019.05 .
Lu ZF , Ye PL , Chen XP , Lu RS , Zhang CT , Zhang FH . The effect of Fei-laokang on organ coefficient of rat with isoniazid resistant tuberculosis . Lishizhen Med Res . 2015 ; 26 ( 11 ): 2564 - 5 doi: cnki:sun:szgy.0.2015–11-002. http://doi.org/cnki:sun:szgy.0.2015–11-002.
Kang J , Wang LM , Wang P , Zhao Y , Zhang W , Han WD , et al . Establishment of a mouse model of infection with rifampicin-resistant mycobacterium tuberculosis . Acta Lab Anim Sci Sin . 2011 ; 19 ( 4 ): 320 - 3 . https://doi.org/10.3969/j.issn.1005-4847.2011.04.011 https://doi.org/10.3969/j.issn.1005-4847.2011.04.011 .
Jiang S . The study on the therapeutic effects of DNA vaccines in a murine model of mycobacterium tuberculosis infection . Chongqing Med Univ . 2004 ; 93 .
Jiang JQ , Huang WP , Yan J , Li LW . Observation of anti-tuberculosis effect in Guinea pigs with Jiehewan . Chin J Zoonos . 2009 ; 25 ( 1 ): 89 - 91 . https://doi.org/10.3969/j.issn.1002-2694.2009.01.025 https://doi.org/10.3969/j.issn.1002-2694.2009.01.025 .
Thada S , Ponnana M , Sivangala R , Joshi L , Alasandagutti M , Ansari MS , et al . Polymorphisms of IFN-γ (+874A/T) and IL-12 (+1188A/C) in tuberculosis patients and their household contacts in Hyderabad, India . Hum Immunol . 2016 ; 77 ( 7 ): 559 - 65 . https://doi.org/10.1016/j.humimm.2016.04.016 https://doi.org/10.1016/j.humimm.2016.04.016 .
Yang CY , Hu JC , Liu YW , Ma Y , Yang LY . Effect of vitamin D combined with anti- tuberculosis drugs on the serum levels of IL-1 and interferon gamma of elderly patients with spinal tuberculosis . Mod Biomed . 2017 ; 17 ( 9 ): 1707 - 9 . doi: cnki:sun:swcx.0.2017–09-029. http://doi.org/cnki:sun:swcx.0.2017–09-029.
Xu ZC , Wang XY , Liu Z , Chen GZ , Chen G . The expression of IFN-γ, IL-12 and TNF-α in the serum and lesions of spinal tuberculosis patients and its effects on the disease . Mod Biomed . 2018 ; 18 ( 16 ): 3057 - 61 . https://doi.org/10.13241/j.cnki.pmb.2018.16.012 https://doi.org/10.13241/j.cnki.pmb.2018.16.012 .
Song N , Li GH , Huang Q , Kong C , Wang HH , Xu Y . Construction and immunogenicity of A39 DNA vaccine against latent tuberculosis infection . J Microbe Infect . 2015 ; 10 ( 1 ): 19 - 27 doi: cnki:sun:wswg.0.2015–01-006. http://doi.org/cnki:sun:wswg.0.2015–01-006.
Liu T , Xiang YG , Fan RH , Ma XH , Shi GM , Yu R , et al . Research progress on cytokines in pulmonary tuberculosis patients . Pract Prev Med . 2016 ; 23 ( 7 ): 894 - 6 . https://doi.org/10.3969/j.issn.1006-3110.2016.07.040 https://doi.org/10.3969/j.issn.1006-3110.2016.07.040 .
Su WL , Perng WC , Huang CH , Yang CY , Wu CP , Chen JH . Association of reduced tumor necrosis factor alpha, gamma interferon, and interleukin-1beta (IL-1beta) but increased IL-10 expression with improved chest radiography in patients with pulmonary tuberculosis . Clin Vaccine Immunol . 2010 ; 17 ( 2 ): 223 - 31 . https://doi.org/10.1128/CVI.00381-09 https://doi.org/10.1128/CVI.00381-09 .
Li ZH , Yang YH , Zhang HM , Tian YR , Liu X , Zhang GY , et al . Study on the relationship between the dynamic changes of cytokine levels and drug resistance in patients with pulmonary tuberculosis . Hebei Med . 2008 ; 30 ( 3 ): 332 - 3 . https://doi.org/10.3969/j.issn.1002-7386.2008.03.039 https://doi.org/10.3969/j.issn.1002-7386.2008.03.039 .
Zhang XX , Zhao CF . Determination and clinical significance of serum IL-4, IL-6 and TGF-β in patients with pulmonary tuberculosis . J Pathog Biol . 2012 ; 7 ( 3 ): 195 - 6 .
Liu WS . The dynamic changes of IL-6 and IL-10 in serum of patients with tuberculosis and clinical significance . Nanchang Univ . 2010 ; 16 .
Beamer GL , Flaherty DK , Assogba BD , Stromberg P , Gonzalez-Juarrero M , de Waal MR , et al . Interleukin-10 promotes mycobacterium tuberculosis disease progression in CBA/J mice . J Immunol . 2008 ; 181 ( 8 ): 5545 - 50 . https://doi.org/10.4049/jimmunol.181.8.5545 https://doi.org/10.4049/jimmunol.181.8.5545 .
Hu YL . Research progress of tuberculosis cell immunity and cytokines . Qinghai Med . 2012 ; 42 ( 11 ): 78 - 9 .
Lv Y , Liu WW , Wang C , Zhao H , Wang T , Bai L . The effect of infection with Mycobacterium tuberculosis H37Ra on T cells and the Th1/Th2 reaction in mice . J Pathog Biol . 2019 ; 14 ( 8 ): 905 - 9 .
Van de Veerdonk FL , Teirlinck AC , Kleinnijenhuis J , Kullberg BJ , van Crevel R , van der Meer JW , et al . Mycobacterium tuberculosis induces IL-17A responses through TLR4 and dectin-1 and is critically dependent on endogenous IL-1 . J Leukoc Biol . 2010 ; 88 ( 2 ): 227 - 32 . https://doi.org/10.1189/jlb.0809550 https://doi.org/10.1189/jlb.0809550 .
Lombard R , Doz E , Carreras F , Epardaud M , Le Vern Y , Buzoni-Gatel D , et al . IL-17RA in non-hematopoietic cells controls CXCL-1 and 5 critical to recruit neutrophils to the lung of mycobacteria-infected mice during the adaptive immune response . PLoS One . 2016 ; 11 ( 2 ): e0149455 . https://doi.org/10.1371/journal.pone.0149455 https://doi.org/10.1371/journal.pone.0149455 .
Kozakiewicz L , Chen Y , Xu J , Wang Y , Dunussi-Joannopoulos K , Ou Q , et al . B cells regulate neutrophilia during mycobacterium tuberculosis infection and BCG vaccination by modulating the interleukin-17 response . PLoS Pathog . 2013 ; 9 ( 7 ): e1003472 . https://doi.org/10.1371/journal.ppat.1003472 https://doi.org/10.1371/journal.ppat.1003472 .
Okamoto YY , Umemura M , Yahagi A , O'Brien RL , Ikuta K , Kishihara K , et al . Essential role of IL-17A in the formation of a mycobacterial infectioninduced granuloma in the lung . J Immunol . 2010 ; 184 ( 8 ): 4414 - 22 . https://doi.org/10.4049/jimmunol.0903332 https://doi.org/10.4049/jimmunol.0903332 .
Safar HA , Mustafa AS , Amoudy HA , El-Hashim A . The effect of adjuvants and delivery systems on Th1, Th2, Th17 and treg cytokine responses in mice immunized with mycobacterium tuberculosis-specific proteins . PLoS One . 2020 ; 15 ( 2 ): e0228381 . https://doi.org/10.1371/journal.pone.0228381 https://doi.org/10.1371/journal.pone.0228381 .
Torrado E , Cooper AM . IL-17 and Th17 cells in tuberculosis . Cytokine Growth Factor Rev . 2010 ; 21 ( 6 ): 455 - 62 . https://doi.org/10.1016/j.cytogfr.2010.10.004 https://doi.org/10.1016/j.cytogfr.2010.10.004 .
Sheng YC , Yuan L , Jiang WL , Zhao Q , Xu B . Study on serum Th1 /Th2 cytokines levels and associated factors in pulmonary tuberculosis patients . Shanghai J Prev Med . 2016 ; 28 ( 3 ): 157 - 60 .
Zhang T , Kawakami K , Tang Y . Therapeutic effect of interleukin-12 on murine infection with Mycobacterium tuberculosis through modulating Th1 and Th2 cytokine balance . Chin J Tuberc Respir Dis . 2000 ; 23 ( 6 ): 358 - 60 .
Sun YH , Zhang R , Pei SL . Application of gene expression difference comparison to research of traditional Chinese medicine . Chin Prac Med . 2009 ; 4 ( 30 ): 218 - 20 . https://doi.org/10.3969/j.issn.1673-7555.2009.30.176 https://doi.org/10.3969/j.issn.1673-7555.2009.30.176 .
Karim AF , Chandra P , Chopra A , Siddiqui Z , Bhaskar A , Singh A , et al . Express path analysis identifies a tyrosine kinase Src-centric network regulating divergent host responses to mycobacterium tuberculosis infection . J Biol Chem . 2011 ; 286 ( 46 ): 40307 - 19 . https://doi.org/10.1074/jbc.M111.266239 https://doi.org/10.1074/jbc.M111.266239 .
Mehta M , Rajmani RS , Singh A . Mycobacterium tuberculosis WhiB3 responds to vacuolar pH-induced changes in mycothiol redox potential to modulate phagosomal maturation and virulence . J Biol Chem . 2016 ; 291 ( 6 ): 2888 - 903 . https://doi.org/10.1074/jbc.M115.684597 https://doi.org/10.1074/jbc.M115.684597 .
Liu Y , Zhang YL , Zhang XX , Li CY . Research progress of mycobacterium tuberculosis infection and immune escape mechanism . Chin J Microbiol Immunol . 2015 ; 35 ( 5 ): 398 - 400 . https://doi.org/10.3760/cma.j.issn.0254-5101.2015.05.015 https://doi.org/10.3760/cma.j.issn.0254-5101.2015.05.015 .
Xu JD . Function of rho GTPases in innate immunity of kuruma shrimp and the induction and mechanisms of tyained innate immunity against virus in the shrimp . Shandong Univ . 2018 ; 1 .
Wang XJ , He YL . Research progress of rho kinases in immune cells and autoimmune diseases . Int J Immunol . 2020 ; 43 ( 1 ): 83 - 7 . https://doi.org/10.3760/cma.j.issn.1673-4394.2020.01.016 https://doi.org/10.3760/cma.j.issn.1673-4394.2020.01.016 .
Griffin JN , del Viso F , Duncan AR , Robson A , Hwang W , Kulkarni S , et al . RAPGEF5 regulates nuclear translocation of β-catenin . Dev Cell . 2018 ; 44 ( 2 ): 248 - 60 . https://doi.org/10.1016/j.devcel.2017.12.001 https://doi.org/10.1016/j.devcel.2017.12.001 .
Zhou Y , Wang Q , Mark Evers B , Chung DH . Oxidative stress-induced intestinal epithelial cell apoptosis is mediated by p38 MAPK . Biochem Biophys Res Commun . 2006 ; 350 ( 4 ): 860 - 5 . https://doi.org/10.1016/j.bbrc.2006.09.103 https://doi.org/10.1016/j.bbrc.2006.09.103 .
Duan YQ , Cheng WD , Du J , Zhu LM , Yang XY , Cheng YX , et al . Effect of Sijunzi decoction on SP/CCK and Mapk14 mRNA expression in rats with spleen Qi deficiency . J Chin Med . 2014 ; 37 ( 4 ): 656 - 60 .
Yuan G , Bai Y , Zhang Y , Xu GY , Zhang JF . Data mining mycobacterium tuberculosis pathogenic gene transcription factors and their regulatory network nodes . Int J Genomics . 2018 ; 2018 ( 3 ): 1 - 9 . https://doi.org/10.1155/2018/3079730 https://doi.org/10.1155/2018/3079730 .
Liu XF , Zhai JL , Li WF , Lin ZF . Protective effect of CRISPLD2 protein on acute respiratory disease syndrome induced by lipopolysaecharide in mice . J Navy Med . 2017 ; 38 ( 1 ): 21 - 3 . https://doi.org/10.3969/j.issn.1009-0754.2017.01.008 https://doi.org/10.3969/j.issn.1009-0754.2017.01.008 .
Younis S , Kamel W , Falkeborn T , Wang H , Yu D , Daniels R , et al . Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth . PNAS . 2018 ; 115 ( 16 ): 3808 - 16 .
Yan ZK , Qin ML , Liu YL , Li CR , Liu JJ , Xiao L . Developmental expression of C5aR1 in mouse brain and its effect on the differentiation of NSCs in vitro . Chin Soc Anatomy . 2012 ; 111 .
Zheng J , Dong HJ , Wang CX , Guan WJ , Li YQ . Research progress of targeting and translocation of proteins mediated by signal recognition particle in prokaryote . Acta Microbiol Sin . 2005 ; 45 ( 6 ): 974 - 7 . https://doi.org/10.3321/j.issn:0001-6209.2005.06.033 https://doi.org/10.3321/j.issn:0001-6209.2005.06.033 .
Gao HF , Chen LY , Cheng CS , Chen H , Meng ZQ , Chen Z . SLC5A1 promotes growth and proliferation of pancreatic carcinoma via glucose-dependent AMPK/mTOR signaling . Cancer Manag Res . 2019 ; 11 ( 2019 ): 3171 - 85 . https://doi.org/10.2147/CMAR.S195424 https://doi.org/10.2147/CMAR.S195424 .
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