Skip to main content
SpringerLink
Log in

PF2405, standardized fraction of Scutellaria baicalensis, ameliorates colitis in vitro and in vivo

  • Research Article
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Standardized extraction procedures for herb are as important as their authentication to maintain their quality and ensure their safe use. We had prepared a standardized and purified Scutellaria baicalensis Georgi extract, PF2405, which was enriched with three major components, baicalein, oroxylin A and wogonin. In the present study, we investigated the potential anti-inflammatory effects of PF2405 in vitro and in two different experimental animal models of inflammatory bowel disease. Effect of PF2405 studied in tumor necrosis factor (TNF)-α-induced HT-29 cells in vitro. In vivo experimental colitis models were induced by administration of trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS). PF2405 (50 μg/ml) decreased TNF-α-induced cyclooxygenase (COX)-2 expressions through inhibition of phosphorylation of c-Jun N-terminal kinases and p38 mitogen-activated protein kinase in HT-29 cells. Combination of baicalein (20 μg/ml), oroxylin A (8 μg/ml), and wogonin (2 μg/ml) markedly inhibits TNF-α-induced COX-2 expression when compared with individual components. PF2405 (25 mg/kg b.w.) treatment significantly reduced histopathological severity; suppressed expression of COX-2, TNF-α, and interleukin-1β in TNBS-induced mice. Moreover, PF2405 (25 mg/kg b.w.) has both potent preventive and therapeutic activities in DSS-induced colitis. Collectively, PF2405 shows prominent anti-inflammatory effect that can be used as a new therapeutic approach for intestinal inflammatory disorders.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Alex, P., N.C. Zachos, T. Nguyen, L. Gonzales, T.E. Chen, L.S. Conklin, M. Centola, and X. Li. 2009. Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflammatory Bowel Diseases 15: 341–352.

    Article  PubMed Central  PubMed  Google Scholar 

  • Atreya, R., M. Zimmer, B. Bartsch, M.J. Waldner, I. Atreya, H. Neumann, K. Hildner, A. Hoffman, R. Kiesslich, A.D. Rink, T.T. Rau, S. Rose-John, H. Kessler, J. Schmidt, and M.F. Neurath. 2011. Antibodies against tumor necrosis factor (TNF) induce T-cell apoptosis in patients with inflammatory bowel diseases via TNF receptor 2 and intestinal CD14(+) macrophages. Gastroenterology 141: 2026–2038.

    Article  CAS  PubMed  Google Scholar 

  • Chen, C.C., Y.T. Sun, J.J. Chen, and Y.J. Chang. 2001. Tumor necrosis factor-alpha-induced cyclooxygenase-2 expression via sequential activation of ceramide-dependent mitogen-activated protein kinases, and IkappaB kinase 1/2 in human alveolar epithelial cells. Molecular Pharmacology 59: 493–500.

    CAS  PubMed  Google Scholar 

  • Chen, K., S. Zhang, Y. Ji, J. Li, P. An, H. Ren, R. Liang, J. Yang, and Z. Li. 2013. Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway. PLoS One 8: e72927.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cheng, H., B. Xia, Q. Guo, L. Zhang, F. Wang, L. Jiang, Z. Wang, Y. Zhang, and C. Li. 2007. Sinomenine attenuates 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice. International Immunopharmacology 7: 604–611.

    Article  CAS  PubMed  Google Scholar 

  • Choi, Y.A., O.H. Kang, H.J. Park, J. Tae, D.K. Kim, C.S. Kang, S.C. Choi, K.J. Yun, S.J. Choi, Y.H. Nah, Y.H. Kim, K.H. Bae, and Y.M. Lee. 2005. Effect of processed Scutellaria baicalensis on dextran sulfate sodium-induced colitis in mice. International Journal of Molecular Medicine 16: 667–672.

    PubMed  Google Scholar 

  • Crespo, I., B. San-Miguel, C. Prause, N. Marroni, M.J. Cuevas, J. Gonzalez-Gallego, and M.J. Tunon. 2012. Glutamine treatment attenuates endoplasmic reticulum stress and apoptosis in TNBS-induced colitis. PLoS One 7: e50407.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cury, D.B., S.J. Mizsputen, C. Versolato, L.O. Miiji, E. Pereira, M.A. Delboni, N. Schor, and A.C. Moss. 2013. Serum calprotectin levels correlate with biochemical and histological markers of disease activity in TNBS colitis. Cellular Immunology 282: 66–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • dos Reis, S.B., C.C. de Oliveira, S.C. Acedo, D.D. Miranda, M.L. Ribeiro, J. Pedrazzoli Jr, and A. Gambero. 2009. Attenuation of colitis injury in rats using Garcinia cambogia extract. Phytotherapy research 23: 324–329.

    Article  PubMed  Google Scholar 

  • Dou, W., S. Mukherjee, H. Li, M. Venkatesh, H. Wang, S. Kortagere, A. Peleg, S.S. Chilimuri, Z.T. Wang, Y. Feng, E.R. Fearon, and S. Mani. 2012. Alleviation of gut inflammation by Cdx2/Pxr pathway in a mouse model of chemical colitis. PLoS One 7: e36075.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Finlay, B.B., and S. Falkow. 1997. Common themes in microbial pathogenicity revisited. Microbiology and Molecular Biology Reviews 61: 136–169.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Garg, P., S. Jeppsson, G. Dalmasso, A.M. Ghaleb, B.B. McConnell, V.W. Yang, A.T. Gewirtz, D. Merlin, and S.V. Sitaraman. 2011. Notch1 regulates the effects of matrix metalloproteinase-9 on colitis-associated cancer in mice. Gastroenterology 141: 1381–1392.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Girish, C., and S.C. Pradhan. 2012. Indian herbal medicines in the treatment of liver diseases: Problems and promises. Fundamental & Clinical Pharmacology 26: 180–189.

    Article  CAS  Google Scholar 

  • Harrak, Y., G. Casula, J. Basset, G. Rosell, S. Plescia, D. Raffa, M.G. Cusimano, R. Pouplana, and M.D. Pujol. 2010. Synthesis, anti-inflammatory activity, and in vitro antitumor effect of a novel class of cyclooxygenase inhibitors: 4-(aryloyl)phenyl methyl sulfones. Journal of Medicinal Chemistry 53: 6560–6571.

    Article  CAS  PubMed  Google Scholar 

  • He, J., J. Liang, S. Zhu, J. Li, Y. Zhang, and W. Sun. 2011. Anti-inflammatory effects of Pulvis Fellis Suis extract in mice with ulcerative colitis. Journal of Ethnopharmacology 138: 53–59.

    Article  PubMed  Google Scholar 

  • Hong, T., G.B. Jin, S. Cho, and J.C. Cyong. 2002. Evaluation of the anti-inflammatory effect of baicalein on dextran sulfate sodium-induced colitis in mice. Planta Medica 68: 268–271.

    Article  CAS  PubMed  Google Scholar 

  • Houdeau, E., R. Moriez, M. Leveque, C. Salvador-Cartier, A. Waget, L. Leng, L. Bueno, R. Bucala, and J. Fioramonti. 2007. Sex steroid regulation of macrophage migration inhibitory factor in normal and inflamed colon in the female rat. Gastroenterology 132: 982–993.

    Article  CAS  PubMed  Google Scholar 

  • Jager, S., E.F. Stange, and J. Wehkamp. 2013. Inflammatory bowel disease: An impaired barrier disease. Langenbeck’s Archives of Surgery 398: 1–12.

    Article  PubMed  Google Scholar 

  • Kannan, N., and C. Guruvayoorappan. 2013. Protective effect of Bauhinia tomentosa on acetic acid induced ulcerative colitis by regulating antioxidant and inflammatory mediators. International Immunopharmacology 16: 57–66.

    Article  CAS  PubMed  Google Scholar 

  • Kim, Y.H., D.W. Jeong, Y.C. Kim, D.H. Sohn, E.S. Park, and H.S. Lee. 2007. Pharmacokinetics of baicalein, baicalin and wogonin after oral administration of a standardized extract of Scutellaria baicalensis, PF-2405 in rats. Archives of Pharmacal Research 30: 260–265.

    Article  CAS  PubMed  Google Scholar 

  • Kumagai, T., C.I. Muller, J.C. Desmond, Y. Imai, D. Heber, and H.P. Koeffler. 2007. Scutellaria baicalensis, a herbal medicine: anti-proliferative and apoptotic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines. Leukemia Research 31: 523–530.

    Article  CAS  PubMed  Google Scholar 

  • Lee, S.H., D.H. Sohn, X.Y. Jin, S.W. Kim, S.C. Choi, and G.S. Seo. 2007. 2′,4′,6′-tris(methoxymethoxy) chalcone protects against trinitrobenzene sulfonic acid-induced colitis and blocks tumor necrosis factor-alpha-induced intestinal epithelial inflammation via heme oxygenase 1-dependent and independent pathways. Biochemical Pharmacology 74: 870–880.

    Article  CAS  PubMed  Google Scholar 

  • Lee, S.H., K.S. Song, D.H. Sohn, and G.S. Seo. 2011. Polyozellin blocks tumor necrosis factor alpha-induced interleukin 8 and matrix metalloproteinase 7 production in the human intestinal epithelial cell line HT-29. Archives of Pharmacal Research 34: 91–97.

    Article  CAS  PubMed  Google Scholar 

  • Li, S.P., J. Zhao, and B. Yang. 2011. Strategies for quality control of Chinese medicines. Journal of Pharmaceutical and Biomedical Analysis 55: 802–809.

    Article  CAS  PubMed  Google Scholar 

  • Lim, B.O. 2004. Efficacy of wogonin in the production of immunoglobulins and cytokines by mesenteric lymph node lymphocytes in mouse colitis induced with dextran sulfate sodium. Bioscience, Biotechnology, and Biochemistry 68: 2505–2511.

    Article  CAS  PubMed  Google Scholar 

  • Lim, J.S., M. Yoo, H.J. Kwon, H. Kim, and Y.K. Kwon. 2010. Wogonin induces differentiation and neurite outgrowth of neural precursor cells. Biochemical and Biophysical Research Communications 402: 42–47.

    Article  CAS  PubMed  Google Scholar 

  • Liu, Y.W., Y.W. Su, W.K. Ong, T.H. Cheng, and Y.C. Tsai. 2011. Oral administration of Lactobacillus plantarum K68 ameliorates DSS-induced ulcerative colitis in BALB/c mice via the anti-inflammatory and immunomodulatory activities. International Immunopharmacology 11: 2159–2166.

    Article  CAS  PubMed  Google Scholar 

  • Nan, J.X., E.J. Park, Y.C. Kim, G. Ko, and D.H. Sohn. 2002. Scutellaria baicalensis inhibits liver fibrosis induced by bile duct ligation or carbon tetrachloride in rats. The Journal of Pharmacy and Pharmacology 54: 555–563.

    Article  CAS  PubMed  Google Scholar 

  • Njume, C., and N.I. Goduka. 2012. Treatment of diarrhoea in rural African communities: An overview of measures to maximise the medicinal potentials of indigenous plants. International Journal of Environmental Research and Public Health 9: 3911–3933.

    Article  PubMed Central  PubMed  Google Scholar 

  • Pastorelli, L., C. De Salvo, J.R. Mercado, M. Vecchi, and T.T. Pizarro. 2013. Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: Lessons learned from animal models and human genetics. Frontiers in Immunology 4: 280.

    Article  PubMed Central  PubMed  Google Scholar 

  • Pettersson, J., P.C. Karlsson, U. Goransson, J.J. Rafter, and L. Bohlin. 2008. The flavouring phytochemical 2-pentanone reduces prostaglandin production and COX-2 expression in colon cancer cells. Biological & Pharmaceutical Bulletin 31: 534–537.

    Article  CAS  Google Scholar 

  • Rahimi, Roja. 2010. A review of the efficacy of traditional Iranian medicine for inflammatory bowel disease. World Journal of Gastroenterology 16: 4504–4514.

    Article  PubMed Central  PubMed  Google Scholar 

  • Shrotriya, S., J.K. Kundu, H.K. Na, and Y.J. Surh. 2010. Diallyl trisulfide inhibits phorbol ester-induced tumor promotion, activation of AP-1, and expression of COX-2 in mouse skin by blocking JNK and Akt signaling. Cancer Research 70: 1932–1940.

    Article  CAS  PubMed  Google Scholar 

  • Molodecky, N. A., and G. G. Kaplan. 2010. Environmental risk factors for inflammatory bowel disease. Gastroenterology & hepatology 6: 339–346.

  • Sohn, D. H., Y. C. Kim, E. J. Park, and Y. Z. Zhao. 2006. A purified extract isolated from Scutellaria baicalensis georgi, a method for preparing them and the composition comprising the same having hepato-protecting activity and protecting or treating activity from liver cirrhosis. Korea Patent 1020060048798.

  • Strober, W., and I.J. Fuss. 2011. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology 140: 1756–1767.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sullivan, S., P. Alex, T. Dassopoulos, N.C. Zachos, C. Iacobuzio-Donahue, M. Donowitz, S.R. Brant, C. Cuffari, M.L. Harris, L.W. Datta, L. Conklin, Y. Chen, and X. Li. 2009. Downregulation of sodium transporters and NHERF proteins in IBD patients and mouse colitis models: Potential contributors to IBD-associated diarrhea. Inflammatory Bowel Diseases 15: 261–274.

    Article  PubMed Central  PubMed  Google Scholar 

  • Takenouchi-Ohkubo, N., I. Moro, S. Mukae, Y. Kaneko, and K. Komiyama. 2008. Tumour necrosis factor-alpha-mediated human polymeric immunoglobulin receptor expression is regulated by both mitogen-activated protein kinase and phosphatidylinositol-3-kinase in HT-29 cell line. Immunology 123: 500–507.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wang, D., and R.N. Dubois. 2010. The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 29: 781–788.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yan, F., L. Wang, Y. Shi, H. Cao, L. Liu, M.K. Washington, R. Chaturvedi, D.A. Israel, H. Cao, B. Wang, R.M. Peek Jr, K.T. Wilson, and D.B. Polk. 2012. Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice. American Journal of Physiology. Gastrointestinal and Liver Physiology 302: G504–G514.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yang, X., F. Zhang, Y. Wang, M. Cai, Q. Wang, Q. Guo, Z. Li, and R. Hu. 2013. Oroxylin A inhibits colitis-associated carcinogenesis through modulating the IL-6/STAT3 signaling pathway. Inflammatory Bowel Diseases 19: 1990–2000.

    Article  PubMed  Google Scholar 

  • Yoshida, H., C.E. Yilmaz, and D.N. Granger. 2011. Role of tumor necrosis factor-alpha in the extraintestinal thrombosis associated with colonic inflammation. Inflammatory Bowel Diseases 17: 2217–2223.

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhao, Z., Z. Liang, K. Chan, G. Lu, E.L. Lee, H. Chen, and L. Li. 2010. A unique issue in the standardization of Chinese materia medica: Processing. Planta Medica 76: 1975–1986.

    Article  CAS  PubMed  Google Scholar 

  • Zhou, J., F. Chai, G. Lu, G. Hang, C. Chen, X. Chen, and J. Shi. 2013. TREM-1 inhibition attenuates inflammation and tumor within the colon. International Immunopharmacology 17: 155–161.

    Article  CAS  PubMed  Google Scholar 

  • Zhu, Y., M. Zhu, and P. Lance. 2012. IL1beta-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells. Experimental Cell Research 318: 2520–2530.

    Article  CAS  PubMed  Google Scholar 

  • Zong, J., D.P. Zhang, H. Zhou, Z.Y. Bian, W. Deng, J. Dai, Y. Yuan, H.W. Gan, H.P. Guo, and Q.Z. Tang. 2013. Baicalein protects against cardiac hypertrophy through blocking MEK-ERK1/2 signaling. Journal of Cellular Biochemistry 114: 1058–1065.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Handok Jeseok Foundation (2012).

Author information

Authors and Affiliations

  1. Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea

    Wen-Yi Jiang, Youn-Chul Kim, Dong Hwan Sohn & Sung Hee Lee

  2. Digestive Disease Research Institute, Wonkwang University College of Medicine, Iksan, Jeonbuk, 570-749, Republic of Korea

    Geom Seog Seo

Authors
  1. Wen-Yi Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Geom Seog Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Youn-Chul Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dong Hwan Sohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sung Hee Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sung Hee Lee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, WY., Seo, G.S., Kim, YC. et al. PF2405, standardized fraction of Scutellaria baicalensis, ameliorates colitis in vitro and in vivo. Arch. Pharm. Res. 38, 1127–1137 (2015). https://doi.org/10.1007/s12272-015-0553-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-015-0553-3

Keywords

Search

Navigation