PDF herunterladen
Planta Med 2023; 89(05): 493-507
DOI: 10.1055/a-1878-5704
Biological and Pharmacological Activity
Original Papers

Scutellaria baicalensis Pith-decayed Root Inhibits Macrophage-related Inflammation Through the NF-κB/NLRP3 Pathway to Alleviate LPS-induced Acute Lung Injury

Fanglei Zhang‡
1   School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, P. R. China
,
Chang Ke‡
1   School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, P. R. China
,
Zhongshi Zhou
1   School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, P. R. China
,
Kang Xu
1   School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, P. R. China
2   Hubei Research Center of Chinese Materia Medica Processing Engineering and Technology, Hubei University of Chinese Medicine, Wuhan, P. R. China
,
Yan Wang
1   School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, P. R. China
,
Yanju Liu
1   School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, P. R. China
2   Hubei Research Center of Chinese Materia Medica Processing Engineering and Technology, Hubei University of Chinese Medicine, Wuhan, P. R. China
,
Jiyuan Tu
1   School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, P. R. China
2   Hubei Research Center of Chinese Materia Medica Processing Engineering and Technology, Hubei University of Chinese Medicine, Wuhan, P. R. China
› InstitutsangabenGefördert durch: Natural Science Foundation of Hubei Province 2021CFB227
Gefördert durch: Special project of guiding local science and technology development by the central government of Hubei Province 2020ZYYD030
› Weitere Informationen
    Lizenzen und Reprints

Abstract

Acute lung injury (ALI) is one of the representative “lung heat syndromes” in traditional Chinese medicine (TCM). Scutellaria baicalensis is an herbal medicine used in TCM for treating lung diseases, due to its remarkable anti-inflammatory and antiviral effects. When used in TCM, S. baicalensis root is divided into two categories: S. baicalensis pith-not-decayed root (SN) and S. baicalensis pith-decayed root (SD). Compared to SN, SD has a better effect on lung diseases. We constructed a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model to study the pharmacodynamic mechanism of SD. The ethanolic extract of Scutellaria baicalensis pith-decayed root (EESD) significantly affected LPS-induced ALI by reducing alveolar interstitial thickening, pulmonary edema, and other pathological symptoms, decreasing the infiltration of inflammatory cells, especially macrophages, and inhibiting IL-1β, TNF-α, and IL-6 transcription and translation. Furthermore, in the THP-1 macrophage model induced by LPS, EESD inhibited the expression of phosphorylated nuclear factor inhibitory protein alpha (p-IκBα), phosphorylated nuclear factor-κB P65 (p-p65), cleaved-caspase-1, cleaved-IL-1β protein, and the release of inflammatory factors in the NF-κB/NLRP3 pathway, inhibiting macrophage function. In vivo experiments yielded similar results. Therefore, the present study clarified the potential of EESD in the treatment of ALI and revealed its potential pharmacodynamic mechanism by inhibiting the NF-κB/NLRP3 inflammasome pathway and suppressing the pro-inflammatory phenotype activation of lung tissue macrophages.

Key words

Scutellaria baicalensis - acute lung injury - macrophages - NF-κB - NLRP3

Supporting Information

    The chromatogram of UPLC analysis and the data of methodological investigation (precision, stability and repeatability) and RT-PCR primer sequences are available as Supporting Information.

  • Ergänzendes Material


Publikationsverlauf

Eingereicht: 13. Januar 2022

Angenommen nach Revision: 18. Juni 2022

Accepted Manuscript online:
18. Juni 2022

Artikel online veröffentlicht:
07. November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Jin XZ, Zheng F. Discussion on pathogenesis and treatment of acute lung injury in Traditional Chinese Medicine. CJTCM 2008; 20: 76-77 DOI: 10.16448/j.cjtcm.2008.01.014.
    CrossrefPubMedGoogle Scholar
  • 2 Parekh D, Dancer RC, Thickett DR. Acute lung injury. Clin Med (Lond) 2011; 11: 615-618 DOI: 10.7861/clinmedicine.11-6-615.
    CrossrefPubMedGoogle Scholar
  • 3 He YQ, Zhou CC, Yu LY, Wang L, Deng JL, Tao YL, Zhang F, Chen WS. Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms. Pharmacol Res 2021; 163: 105224 DOI: 10.1016/j.phrs.2020.105224.
    CrossrefPubMedGoogle Scholar
  • 4 Mowery NT, Terzian WTH, Nelson AC. Acute lung injury. Curr Probl Surg 2020; 57: 100777 DOI: 10.1016/j.cpsurg.2020.100777.
    CrossrefPubMedGoogle Scholar
  • 5 Zhou H, Fan EK, Fan J. Cell-cell interaction mechanisms in acute lung injury. Shock 2021; 55: 167-176 DOI: 10.1097/SHK.0000000000001598.
    CrossrefPubMedGoogle Scholar
  • 6 Wang J, Li R, Peng Z, Hu B, Rao X, Li J. HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NFkappaB signaling pathways. Int J Mol Med 2020; 45: 61-80 DOI: 10.3892/ijmm.2019.4402.
    CrossrefPubMedGoogle Scholar
  • 7 Liu H, He Y, Lu C, Zhang P, Zhou C, Ni Y. Efficacy of pulmonary transplantation of engineered macrophages secreting IL-4 on acute lung injury in C57BL/6J mice. Cell Death Dis 2019; 10: 664 DOI: 10.1038/s41419-019-1900-y.
    CrossrefPubMedGoogle Scholar
  • 8 Huang X, Xiu H, Zhang S, Zhang G. The role of macrophages in the pathogenesis of ALI/ARDS. Mediators Inflamm 2018; 2018: 1664913 DOI: 10.1155/2018/1264913.
    CrossrefPubMedGoogle Scholar
  • 9 Oishi Y, Manabe I. Macrophages in inflammation, repair and regeneration. Int Immunol 2018; 30: 511-528 DOI: 10.1093/intimm/dxy054.
    CrossrefPubMedGoogle Scholar
  • 10 Butt Y, Kurdowska A, Allen TC. Acute lung injury: A Clinical and molecular review. Arch Pathol Lab Med 2016; 140: 245-250 DOI: 10.5858/arpa.2015-0519-RA.
    CrossrefPubMedGoogle Scholar
  • 11 Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol 2020; 15: 123-147 DOI: 10.1146/annurev-pathmechdis-012418-012718.
    CrossrefPubMedGoogle Scholar
  • 12 Chen JJ, Huang CC, Chang HY, Li PY, Liang YC, Deng JS, Huang SS, Huang GJ. Scutellaria baicalensis ameliorates acute lung injury by suppressing inflammation in vitro and in vivo . Am J Chin Med 2017; 45: 137-157 DOI: 10.1142/S0192415X17500100.
    CrossrefPubMedGoogle Scholar
  • 13 Zhi HJ, Zhu HY, Zhang YY, Lu Y, Li H, Chen DF. In vivo effect of quantified flavonoids-enriched extract of Scutellaria baicalensis root on acute lung injury induced by influenza A virus. Phytomedicine 57 2019; 57: 105-116 DOI: 10.1016/j.phymed.2018.12.009.
    CrossrefPubMedGoogle Scholar
  • 14 Zhi H, Jin X, Zhu H, Li H, Zhang Y, Lu Y, Chen D. Exploring the effective materials of flavonoids-enriched extract from Scutellaria baicalensis roots based on the metabolic activation in influenza A virus induced acute lung injury. J Pharm Biomed Anal 2020; 177: 112876 DOI: 10.1016/j.jpba.2019.112876.
    CrossrefPubMedGoogle Scholar
  • 15 Cao X, You G, Li H, Li D, Wang M, Ren X. Comparative investigation for rotten Xylem (Kuqin) and strip types (Tiaoqin) of Scutellaria baicalensis georgi based on fingerprinting and chemical pattern recognition. Molecules 2019; 24: 2431 DOI: 10.3390/molecules24132431.
    CrossrefPubMedGoogle Scholar
  • 16 Chen QY, Wang CQ, Yang ZW, Tang Q, Tan HR, Cai SQ, Wang X. Differences in anti-inflammatory effects between two specifications of Scutellariae Radix in LPS-induced macrophages in vitro . Chin J Nat Med 2017; 15: 515-524 DOI: 10.1016/S1875-5364(17)30077-8.
    CrossrefPubMedGoogle Scholar
  • 17 Zhai JW, Li SQ, Liu YJ, Tu JY, Qu LH, Shi K. Pharmacodynamic difference of Scutellaria baicalensis pith-nodecayed and Scutellaria baicalensis pith-decayed on pneumonia based on antibacterial activity and pathological parameters. Zhong Cao Yao 2018; 49: 4064-4070 DOI: 10.7501/j.issn.0253-2670.2018.17.015.
    CrossrefPubMedGoogle Scholar
  • 18 Hu JH, Liu JY, Zhang FL, Xu J, Lin X, Zhu TX. Comparative study on the protective effects of alcohol extracts of Kuqin and Ziqin on LPS-induced acute lung injury. Zhong Cheng Yao 2020; 42: 2756-2759 DOI: 10.3969/j.issn.1001-1528.2020.10.042.
    CrossrefPubMedGoogle Scholar
  • 19 Ren Y, Liang S, Zheng Y, Deng X, Lei L, Ai J, Li Y, Zhang T, Chen L, Mei Z, Cheng YC, He C. Investigation on the function tropism of Tiaoqin and Kuqin (different specification of Scutellaria baicalensis) by comparing their curative effect on different febrile disease model. J Ethnopharmacol 2021; 268: 113596 DOI: 10.1016/j.jep.2020.113596.
    CrossrefPubMedGoogle Scholar
  • 20 Dagvadorj J, Shimada K, Chen S, Jones HD, Tumurkhuu G, Zhang W, Wawrowsky KA, Crother TR, Arditi M. Lipopolysaccharide induces alveolar macrophage necrosis via CD14 and the P2X7 receptor leading to interleukin-1alpha release. Immunity 2015; 42: 640-653 DOI: 10.1016/j.immuni.2015.03.007.
    CrossrefPubMedGoogle Scholar
  • 21 Karki R, Kanneganti TD. The ‘cytokine storm’: molecular mechanisms and therapeutic prospects. Trends Immunol 2021; 42: 681-705 DOI: 10.1016/j.it.2021.06.001.
    CrossrefPubMedGoogle Scholar
  • 22 Nie Y, Nirujogi TS, Ranjan R, Reader BF, Chung S, Ballinger MN, Englert JA, Christman JW, Karpurapu M. PolyADP-ribosylation of NFATc3 and NF-kappaB transcription factors modulate macrophage inflammatory gene expression in LPS-induced acute lung injury. J Innate Immun 2021; 13: 83-93 DOI: 10.1159/000510269.
    CrossrefPubMedGoogle Scholar
  • 23 Bai C, Li T, Sun Q, Xin Q, Xu T, Yu Wang Y, Wei L. Protective effect of baicalin against severe burninduced remote acute lung injury in rats. Mol Med Rep 2018; 17: 2689-2694 DOI: 10.3892/mmr.2017.8120.
    CrossrefPubMedGoogle Scholar
  • 24 Zhang L, Ren Y, Yang C, Guo Y, Zhang X, Hou G, Guo X, Sun N, Liu Y. Wogonoside ameliorates lipopolysaccharide-induced acute lung injury in mice. Inflammation 2014; 37: 2006-2012 DOI: 10.1007/s10753-014-9932-z.
    CrossrefPubMedGoogle Scholar
  • 25 Tsai CL, Lin YC, Wang HM, Chou TC. Baicalein, an active component of Scutellaria baicalensis, protects against lipopolysaccharide-induced acute lung injury in rats. J Ethnopharmacol 2014; 153: 197-206 DOI: 10.1016/j.jep.2014.02.010.
    CrossrefPubMedGoogle Scholar
  • 26 Yao J, Pan D, Zhao Y, Zhao L, Sun J, Wang Y, You QD, Xi T, Guo QL, Lu N. Wogonin prevents lipopolysaccharide-induced acute lung injury and inflammation in mice via peroxisome proliferator-activated receptor gamma-mediated attenuation of the nuclear factor-kappaB pathway. Immunology 2014; 143: 241-257 DOI: 10.1111/imm.12305.
    CrossrefPubMedGoogle Scholar
  • 27 Tseng TL, Chen MF, Tsai MJ, Hsu YH, Chen CP, Lee TJ. Oroxylin-A rescues LPS-induced acute lung injury via regulation of NF-kappaB signaling pathway in rodents. PLoS One 2012; 7: e47403 DOI: 10.1371/journal.pone.0047403.
    CrossrefPubMedGoogle Scholar
  • 28 Chen H, Bai C, Wang X. The value of the lipopolysaccharide-induced acute lung injury model in respiratory medicine. Expert Rev Respir Med 2010; 4: 773-783 DOI: 10.1586/ers.10.71.
    CrossrefPubMedGoogle Scholar
  • 29 Aripov AN, Kayumov UK, Inoyatova FK, Khidoyatova MR. Role of lungs in the hemostasis system (review of literature). Klin Lab Diagn 2021; 66: 411-416 DOI: 10.51620/0869-2084-2021-66-7-411-416.
    CrossrefPubMedGoogle Scholar
  • 30 Feng T, Zhou L, Gai S, Zhai Y, Gou N, Wang X, Zhang X, Cui M, Wang L, Wang S. Acacia catechu (L.f.) Willd and Scutellaria baicalensis Georgi extracts suppress LPS-induced pro-inflammatory responses through NF-small ka, CyrillicB, MAPK, and PI3K-Akt signaling pathways in alveolar epithelial type II cells. Phytother Res 2019; 33: 3251-3260 DOI: 10.1002/ptr.6499.
    CrossrefPubMedGoogle Scholar
  • 31 Peng LY, Yuan M, Song K, Yu JL, Li JH, Huang JN, Yi PF, Fu BD, Shen HQ. Baicalin alleviated APEC-induced acute lung injury in chicken by inhibiting NF-kappaB pathway activation. Int Immunopharmacol 2019; 72: 467-472 DOI: 10.1016/j.intimp.2019.04.046.
    CrossrefPubMedGoogle Scholar
  • 32 Niu X, Zang L, Li W, Xiao X, Yu J, Yao Q, Zhao J, Ye Z, Hu Z, Li W. Anti-inflammatory effect of Yam Glycoprotein on lipopolysaccharide-induced acute lung injury via the NLRP3 and NF-kappaB/TLR4 signaling pathway. Int Immunopharmacol 2020; 81: 106024 DOI: 10.1016/j.intimp.2019.106024.
    CrossrefPubMedGoogle Scholar
  • 33 Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J, He F, Boassa D, Perkins G, Ali SR, McGeough MD, Ellisman MH, Seki E, Gustafsson AB, Hoffman HM, Diaz-Meco MT, Moscat J, Karin M. NF-kappaB restricts inflammasome activation via elimination of damaged mitochondria. Cell 2016; 164: 896-910 DOI: 10.1016/j.cell.2015.12.057.
    CrossrefPubMedGoogle Scholar
  • 34 Molla MD, Akalu Y, Geto Z, Dagnew B, Ayelign B, Shibabaw T. Role of caspase-1 in the pathogenesis of inflammatory-associated chronic noncommunicable diseases. J Inflamm Res 2020; 13: 749-764 DOI: 10.2147/JIR.S277457.
    CrossrefPubMedGoogle Scholar
  • 35 Chen H, Zhang Y, Zhang W, Liu H, Sun C, Zhang B, Bai B, Wu D, Xiao Z, Lum H, Zhou J, Chen R, Liang G. Inhibition of myeloid differentiation factor 2 by baicalein protects against acute lung injury. Phytomedicine 2019; 63: 152997 DOI: 10.1016/j.phymed.2019.152997.
    CrossrefPubMedGoogle Scholar
  • 36 Pan H, Lin Y, Dou J, Fu Z, Yao Y, Ye S, Zhang S, Wang N, Liu A, Li X, Zhang F, Chen D. Wedelolactone facilitates Ser/Thr phosphorylation of NLRP3 dependent on PKA signalling to block inflammasome activation and pyroptosis. Cell Prolif 2020; 53: e12868 DOI: 10.1111/cpr.12868.
    CrossrefPubMedGoogle Scholar
  • 37 Guarda G, Zenger M, Yazdi AS, Schroder K, Ferrero I, Menu P, Tardivel A, Mattmann C, Tschopp J. Differential expression of NLRP3 among hematopoietic cells. J Immunol 2011; 186: 2529-2534 DOI: 10.4049/jimmunol.1002720.
    CrossrefPubMedGoogle Scholar
  • 38 Zhao JW, Qu LH, Liu YJ, Li SQ, Xu YY, Xiao L. Multi-component content determination combined with UPLC fingerprints and its pattern discrimination evaluation of Scutellaria baicalensis pith-nodecayed and Scutellaria baicalensis pith-decayed. Zhong Yao Cai 2017; 40: 2101-2106 DOI: 10.13863/j.issn1001-4454.2017.09.024.
    CrossrefPubMedGoogle Scholar
  • 39 Kim YS, Hwang JW, Jang JH, Son S, Seo IB, Jeong JH, Kim EH, Moon SH, Jeon BT, Park PJ. Trapa japonica pericarp extract reduces LPS-induced inflammation in macrophages and acute lung injury in mice. Molecules 2016; 21: 392 DOI: 10.3390/molecules21030392.
    CrossrefPubMedGoogle Scholar
  • 40 Zhou T, Sun Y, Wang Y, Chen X, Zhuo L, Bu L, Xu S, Han J, Li X, Shi J. Umbilical cord blood mesenchymal stem cells enhance lipopolysaccharide-induced IL-10 and IL-37 production in THP-1 Cells. Inflammation 2019; 42: 987-993 DOI: 10.1007/s10753-019-00960-z.
    CrossrefPubMedGoogle Scholar
  • 41 Ozleyen A, Yilmaz YB, Tumer TB. Dataset on the differentiation of THP-1 monocytes to LPS inducible adherent macrophages and their capacity for NO/iNOS signaling. Data Brief 2021; 35: 106786 DOI: 10.1016/j.dib.2021.106786.
    CrossrefPubMedGoogle Scholar
  • 42 He XR, Han SY, Li XH, Zheng WX, Pang LN, Jiang ST, Li PP. Chinese medicine Bu-Fei decoction attenuates epithelial-mesenchymal transition of non-small cell lung cancer via inhibition of transforming growth factor beta1 signaling pathway in vitro and in vivo . J Ethnopharmacol 2017; 204: 45-57 DOI: 10.1016/j.jep.2017.04.008.
    CrossrefPubMedGoogle Scholar
  • 43 Yang S, Cui W, Wang M, Xing L, Wang Y, Zhu P, Qu Q, Tang Q. Bufei decoction alleviated bleomycin-induced idiopathic pulmonary fibrosis in mice by anti-inflammation. Evid Based Complement Alternat Med 2020; 2020: 7483278 DOI: 10.1155/2020/7483278.
    CrossrefPubMedGoogle Scholar
  • 44 Xie Y, Zhan X, Tu J, Xu K, Sun X, Liu C, Ke C, Cao G, Zhou Z, Liu Y. Atractylodes oil alleviates diarrhea-predominant irritable bowel syndrome by regulating intestinal inflammation and intestinal barrier via SCF/c-kit and MLCK/MLC2 pathways. J Ethnopharmacol 2021; 272: 113925 DOI: 10.1016/j.jep.2021.113925.
    CrossrefPubMedGoogle Scholar
  • 45 Qu L, Lin X, Liu C, Ke C, Zhou Z, Xu K, Cao G, Liu Y. Atractylodin attenuates dextran sulfate sodium-induced colitis by alleviating gut microbiota dysbiosis and inhibiting inflammatory response through the MAPK pathway. Front Pharmacol 2021; 12: 665376 DOI: 10.3389/fphar.2021.665376.
    CrossrefPubMedGoogle Scholar
  • 46 Linghang Q, Yiyi X, Guosheng C, Kang X, Jiyuan T, Xiong L, Guangzhong W, Shuiqing L, Yanju L. Effects of atractylodes oil on inflammatory response and serum metabolites in adjuvant arthritis rats. Biomed Pharmacother 2020; 127: 110130 DOI: 10.1016/j.biopha.2020.110130.
    CrossrefPubMedGoogle Scholar
  • 47 Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, Mering CV. STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 2019; 47: D607-D613 DOI: 10.1093/nar/gky1131.
    CrossrefPubMedGoogle Scholar
  • 48 Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, Stein TI, Nudel R, Lieder I, Mazor Y, Kaplan S, Dahary D, Warshawsky D, Guan-Golan Y, Kohn A, Rappaport N, Safran M, Lancet D. The GeneCards Suite: From gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics 2016; 54: 1.30.1-1.30.33 DOI: 10.1002/cpbi.5.
    CrossrefPubMedGoogle Scholar
  • 49 Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, Benner C, Chanda SK. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019; 10: 1523 DOI: 10.1038/s41467-019-09234-6.
    CrossrefPubMedGoogle Scholar