Skip to main content
SpringerLink
Log in

Reciprocal effects of Guizhi decoction (桂枝汤) to the Guizhi decoction syndrome by toll-like receptor mRNA expression and cytokines secretion

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To explore the pathological mechanisms of Guizhi Decoction (桂枝汤) syndrome and the therapeutic molecular mechanisms of the Guizhi Decoction, Mahuang Decoction (麻黄汤), Sangju Decoction (桑菊 饮) and Yinqiao Powder (银翘散), as well as the potentially biological basis that Guizhi Decoction is most effective only for the patients with Guizhi Decoction syndrome in clinical practice.

Methods

We first got serum samples from the patients suffering from both upper respiratory tract infection and Guizhi Decoction syndrome identified by the doctors of Chinese medicine (CM) in the clinic. Four formulas with therapeutic actions of pungent warmth or pungent coolness for superficial syndromes were chosen and four kinds of rat serum samples each containing one of the above-mentioned herbal formulas were collected, then the effects of Guizhi Decoction syndromes’ patient serum as well as the effects of sera containing the formulas after being stimulated by the patient serum samples on both the mRNA expression of certain toll-like receptor (TLR) subtypes and the release of some inflammatory cytokines in RAW264.7 cells were tested and analyzed in vitro.

Results

The expression of TLR-3, TLR-4 and TLR-9 mRNA among the 9 tested TLR subforms were up-regulated in the macrophages stimulated by the sera from untreated upper respiratory infection patients with the Guizhi Decoction syndrome (symptomcomplex). The products such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-β from stimulated macrophages through TLR signaling pathways were also increased correspondingly. Interestingly, the changes induced by the Guizhi Decoction syndrome patients’ sera were masked significantly after the macrophages were incubated with the sera from donors treated with Guizhi Decoction. Similarly, the three other exterior-releasing formulas were all effective in reversing the up-regulated changes of certain TLR subforms to different degrees, but both the number of targeted TLRs and efficacy of them seemed to be inferior to that of Guizhi Decoction.

Conclusion

Evidence from these experiments might contribute to the scientific explanation of both the pharmacological mechanisms of Guizhi Decoction and also the CM theory that Guizhi Decoction is specifically prescribed for the treatment of Guizhi Decoction syndrome (The gearing formula to the symptom-complex).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Murray PJ, Wynn TA. Obstacles and opportunities for understanding macrophage polarization. J Leukoc Biol 2011;89:557–563.

    Article  PubMed  CAS  Google Scholar 

  2. Craig A, Mai J, Cai S, Jeyaseelan S. Neutrophil recruitment to the lungs during bacterial pneumonia. Infect Immun 2009;77:568–575.

    Article  PubMed  CAS  Google Scholar 

  3. Parker LC, Prince LR, Sabroe I. Translational mini-review series on Toll-like receptors: networks regulated by Toll-like receptors mediate innate and adaptive immunity. Clin Exp Immunol 2007;147:199–207.

    Article  PubMed  CAS  Google Scholar 

  4. Delbridge LM, O’Riordan MX. Innate recognition of intracellular bacteria. Curr Opin Immunol 2007;19:10–16.

    Article  PubMed  CAS  Google Scholar 

  5. Kim GY, Han MG, Song YS, Shin BC, Shin YI, Lee HJ, et al. Proteoglycan isolated from Phellinus linteus induces Toll-like receptors 2- and 4-mediated maturation of murine dendritic cells via activation of ERK, p38, and NF-kappaB. Biol Pharm Bull 2004;27:1656–1662.

    Article  PubMed  CAS  Google Scholar 

  6. Michelsen KS, Arditi M. Toll-like receptors and innate immunity in gut homeostasis and pathology. Curr Opin Hematol 2007;14:48–54.

    Article  PubMed  CAS  Google Scholar 

  7. Zhao BS, Li LF, Ma YY, Guo SY, Li CH, Huo HR, et al. Effect of Shensuyin on the expression of toll-like receptors and the downstream signaling components on RAW 264.7 cells. China J Chin Mater Med (Chin) 2007;32:327–332.

    Google Scholar 

  8. Wong JP, Christopher ME, Viswanathan S, Dai X, Salazar AM, Sun LQ, et al. Antiviral role of Toll-like receptor-3 agonists against seasonal and avian influenza viruses. Curr Pharm Des 2009;15:1269–1274.

    Article  PubMed  CAS  Google Scholar 

  9. Jiang W, Sun R, Zhou R, Wei HM, Tian ZG. TLR-9 activation aggravates concanavalin A-induced hepatitis via promoting accumulation and activation of liver CD4+ NKT Cells. J Immunol 2009;182:3768–3774.

    Article  PubMed  CAS  Google Scholar 

  10. Romagne F. Current and future drugs targeting one class of innate immunity receptors: the Toll-like receptors. Drug Discov Today 2007;12:80–87.

    Article  PubMed  CAS  Google Scholar 

  11. Lee JY, Kim JY, Lee YG, Byeon SE, Kim BH, Rhee MH, et al. In vitro immunoregulatory effects of Korean mistletoe lectin on functional activation of monocytic and macrophagelike cells. Biol Pharm Bull 2007;30:2043–2051.

    Article  PubMed  CAS  Google Scholar 

  12. Ishihara S, Rumi MA, Ortega-Cava CF, Kazumori H, Kadowaki Y, Ishimura N, et al. Therapeutic targeting of tolllike receptors in gastrointestinal inflammation. Curr Pharm Des 2006;12:4215–4228.

    Article  PubMed  CAS  Google Scholar 

  13. Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, et al. TLR11 Activation of dendritic cells by a protozoan profilin-like protein. Science 2005;308:1626–1629.

    Article  PubMed  CAS  Google Scholar 

  14. Kim BH, Shin HM, Jung SH, Yoon YG, Min KR, Kim Y. Antiinflammatory benzene diamine compound inhibited Tolllike receptor 4-mediated inducible nitric oxide synthase expression and nuclear factor-kappa B activation. Biol Pharm Bull 2005;28:908–911.

    Article  PubMed  CAS  Google Scholar 

  15. Burns K, Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, et al. Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nat Cell Biol 2000;2:346–351.

    Article  PubMed  CAS  Google Scholar 

  16. Zhang D, Zhang GL, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, et al. A Toll-like receptor that prevents infection by uropathogenic bacteria. Science 2004;303:1522–1526.

    Article  PubMed  CAS  Google Scholar 

  17. Ahmad-Nejad P, Hacker H, Rutz M, Bauer S, Vabulas RM, Wagner H. Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur J Immunol 2002;32:1958–1968.

    Article  PubMed  CAS  Google Scholar 

  18. Yoshioka M, Fukuishi N, Kubo Y, Yamanobe H, Ohsaki K, Kawasoe Y, et al. Human cathelicidin CAP18/LL-37 changes mast cell function toward innate immunity. Biol Pharm Bull 2008;31:212–216.

    Article  PubMed  CAS  Google Scholar 

  19. Ikeda Y, Adachi Y, Ishii T, Miura N, Tamura H, Ohno N. Dissociation of Toll-like receptor 2-mediated innate immune response to zymosan by organic solvent-treatment without loss of dectin-1 reactivity. Biol Pharm Bull 2008;31:13–18.

    Article  PubMed  CAS  Google Scholar 

  20. Hazeki K, Nigorikawa K, Hazeki O. Role of phosphoinositide 3-kinase in innate immunity. Biol Pharm Bull 2007;30:1617–1623.

    Article  PubMed  CAS  Google Scholar 

  21. Zhao BS, Huo HR, Ma YY, Liu HB, Li LF, Sui F, et al. Effects of 3-phenyl-propenal on the expression of Toll-like receptors and downstream signaling components on RAW264.7 murine macrophages. Am J Chin Med 2008;36:159–169.

    Article  PubMed  CAS  Google Scholar 

  22. Marta M, Andersson A, Isaksson M, Kampe O, Lobell A. Unexpected regulatory roles of TLR4 and TLR9 in experimental autoimmune encephalomyelitis. Eur J Immunol 2008;38:565–575.

    Article  PubMed  CAS  Google Scholar 

  23. Christensen SR, Shupe J, Nickerson K, Kashgarian M, Flavell RA, Shlomchik MJ. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity 2006;25:417–428.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Tang Center for Herbal Medicine Research, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China

    Xin-liang Du  (杜新亮), Feng Sui  (隋 峰), Hai-ru Huo  (霍海如), Lan-fang Li  (李兰芳), Shu-ying Guo  (郭淑英) & Ting-liang Jiang  (姜廷良)

  2. Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100102, China

    Hong-wei Zhang  (张宏伟) & Kan Luo  (罗 侃)

Authors
  1. Xin-liang Du  (杜新亮)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feng Sui  (隋 峰)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hai-ru Huo  (霍海如)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong-wei Zhang  (张宏伟)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kan Luo  (罗 侃)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lan-fang Li  (李兰芳)
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shu-ying Guo  (郭淑英)
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ting-liang Jiang  (姜廷良)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Feng Sui  (隋 峰).

Additional information

Supported by the National Natural Science Foundation of China (No. 90209006; 81274112) and Beijing Municipal Natural Science Foundation (No. 7112098).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Du, Xl., Sui, F., Huo, Hr. et al. Reciprocal effects of Guizhi decoction (桂枝汤) to the Guizhi decoction syndrome by toll-like receptor mRNA expression and cytokines secretion. Chin. J. Integr. Med. 19, 826–835 (2013). https://doi.org/10.1007/s11655-013-1325-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-013-1325-2

Keywords

Search

Navigation