Skip to main content
SpringerLink
Log in

Patchouli Alcohol: a Natural Sesquiterpene Against Both Inflammation and Intestinal Barrier Damage of Ulcerative Colitis

  • Original Article
  • Published:
Inflammation Aims and scope Submit manuscript

A Correction to this article was published on 20 February 2024

This article has been updated

Abstract

Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, characterized by diarrhea, hematochezia, abdominal distension, and abdominal pain. The perpetuation of inflammation and the impairment of the intestinal barrier are part of the main courses of UC, responsible for the deteriorating inflammatory condition. Patchouli alcohol (PA), extracted from Pogostemon cablin Benth., is employed to treat both inflammation and intestinal barrier damage. Its curative effect on UC was testified firstly by TNBS-induced UC, a chemically induced colitis, and further tested by DSS-induced UC, an acute attack stage of UC in which the clinical course of human UC occurs frequently. PA reduced the levels of TNF-α, IFN-γ, IL-1β, IL-6, and IL-17 in serum and decreased the mRNA expression of pro-inflammatory cytokines (e.g., iNOS, COX-2, TNF-α, IL-1β, and IL-6). Concurrently, PA upregulated the expression of tight junction protein (e.g., ZO-1, ZO-2, claudin-1, and occludin) and the mRNA of mucin-1 and mucin-2 in both animal models. Further, PA ameliorated both histological damage and clinical parameters. Thus, PA could credibly reduce the expression of pro-inflammatory cytokines, protect the integrity of intestinal epithelial barrier, and repair the macroscopic colon lesions in both colitis models.

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

Similar content being viewed by others

Change history

Abbreviations

CAC:

Colitis-associated colorectal cancer

CD:

Crohn’s disease

DAI:

Disease activity index

DSS:

Dextran sodium sulfate

IBD:

Inflammatory bowel disease

MPO:

Myeloperoxidase

PA:

Patchouli alcohol

PCR:

Quantitative real-time polymerase chain reaction

TNBS:

Trinitrobenzene sulfonic acid

UC:

Ulcerative colitis

References

  1. Triantafillidis, J.K., E. Merikas, and F. Georgopoulos. 2011. Current and emerging drugs for the treatment of inflammatory bowel disease. Drug Design, Development and Therapy 5: 185–210. https://doi.org/10.2147/DDDT.S11290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kim, D.H., and J.H. Cheon. 2017. Pathogenesis of inflammatory bowel disease and recent advances in biologic therapies. Immune Network 17 (1): 25–40. https://doi.org/10.4110/in.2017.17.1.25.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ng, Siew C., Hai Yun Shi, Nima Hamidi, Fox E. Underwood, Whitney Tang, Eric I. Benchimol, Remo Panaccione, et al. 2017. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies. The Lancet 390 (10114): 2769–2778. https://doi.org/10.1016/s0140-6736(17)32448-0.

    Article  Google Scholar 

  4. Ordás, Ingrid, Lars Eckmann, Mark Talamini, Daniel C. Baumgart, and William J. Sandborn. 2012. Ulcerative colitis. The Lancet 380 (9853): 1606–1619. https://doi.org/10.1016/s0140-6736(12)60150-0.

    Article  Google Scholar 

  5. Cui, G., and A. Yuan. 2018. A systematic review of epidemiology and risk factors associated with Chinese inflammatory bowel disease. Frontiers of Medicine 5: 183. https://doi.org/10.3389/fmed.2018.00183.

    Article  Google Scholar 

  6. Foersch, S., and M.F. Neurath. 2014. Colitis-associated neoplasia: Molecular basis and clinical translation. Cellular and Molecular Life Sciences 71 (18): 3523–3535. https://doi.org/10.1007/s00018-014-1636-x.

    Article  CAS  PubMed  Google Scholar 

  7. Kim, E.R., and D.K. Chang. 2014. Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis. World Journal of Gastroenterology 20 (29): 9872–9881. https://doi.org/10.3748/wjg.v20.i29.9872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. de Souza, H.S., and C. Fiocchi. 2016. Immunopathogenesis of IBD: Current state of the art. Nature Reviews. Gastroenterology & Hepatology 13 (1): 13–27. https://doi.org/10.1038/nrgastro.2015.186.

    Article  CAS  Google Scholar 

  9. Brazil, J.C., N.A. Louis, and C.A. Parkos. 2013. The role of polymorphonuclear leukocyte trafficking in the perpetuation of inflammation during inflammatory bowel disease. Inflammatory Bowel Diseases 19 (7): 1556–1565. https://doi.org/10.1097/MIB.0b013e318281f54e.

    Article  PubMed  Google Scholar 

  10. Turner, J.R. 2009. Intestinal mucosal barrier function in health and disease. Nature Reviews. Immunology 9 (11): 799–809. https://doi.org/10.1038/nri2653.

    Article  CAS  PubMed  Google Scholar 

  11. Danese, S., and C. Fiocchi. 2011. Ulcerative colitis. The New England Journal of Medicine 365 (18): 1713–1725. https://doi.org/10.1056/NEJMra1102942.

    Article  CAS  PubMed  Google Scholar 

  12. D'Ambrosio, A., A. Cossu, A. Amendola, A. Zandri, A. Butera, M. Sanchez, M. Biffoni, A. Pronio, C. Montesani, A. Kohn, R. Pica, and M. Boirivant. 2016. Lamina propria CD4+LAP+ regulatory T cells are increased in active ulcerative colitis but show increased IL-17 expression and reduced suppressor activity. Journal of Crohn’s & Colitis 10 (3): 346–353. https://doi.org/10.1093/ecco-jcc/jjv216.

    Article  Google Scholar 

  13. Wu, D., K. Wu, Q. Zhu, W. Xiao, Q. Shan, Z. Yan, J. Wu, B. Deng, Y. Xue, W. Gong, G. Lu, and Y. Ding. 2018. Formononetin administration ameliorates dextran sulfate sodium-induced acute colitis by inhibiting NLRP3 inflammasome signaling pathway. Mediators of Inflammation 2018: 3048532. https://doi.org/10.1155/2018/3048532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Aggarwal, B.B., H. Ichikawa, P. Garodia, P. Weerasinghe, G. Sethi, I.D. Bhatt, M.K. Pandey, S. Shishodia, and M.G. Nair. 2006. From traditional Ayurvedic medicine to modern medicine: Identification of therapeutic targets for suppression of inflammation and cancer. Expert Opinion on Therapeutic Targets 10 (1): 87–118. https://doi.org/10.1517/14728222.10.1.87.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang, Z., X. Chen, H. Chen, L. Wang, J. Liang, D. Luo, Y. Liu, H. Yang, Y. Li, J. Xie, and Z. Su. 2016. Anti-inflammatory activity of beta-patchoulene isolated from patchouli oil in mice. European Journal of Pharmacology 781: 229–238. https://doi.org/10.1016/j.ejphar.2016.04.028.

    Article  CAS  PubMed  Google Scholar 

  16. Xie, J., Z. Lin, Y. Xian, S. Kong, Z. Lai, S. Ip, H. Chen, H. Guo, Z. Su, X. Yang, Y. Xu, and Z. Su. 2016. (-)-Patchouli alcohol protects against helicobacter pylori urease-induced apoptosis, oxidative stress and inflammatory response in human gastric epithelial cells. International Immunopharmacology 35: 43–52. https://doi.org/10.1016/j.intimp.2016.02.022.

    Article  CAS  PubMed  Google Scholar 

  17. Li, Y.C., S.Z. Peng, H.M. Chen, F.X. Zhang, P.P. Xu, J.H. Xie, J.J. He, J.N. Chen, X.P. Lai, and Z.R. Su. 2012. Oral administration of patchouli alcohol isolated from Pogostemonis Herba augments protection against influenza viral infection in mice. International Immunopharmacology 12 (1): 294–301. https://doi.org/10.1016/j.intimp.2011.12.007.

    Article  CAS  PubMed  Google Scholar 

  18. Jeong, J.B., Y.K. Shin, and S.H. Lee. 2013. Anti-inflammatory activity of patchouli alcohol in RAW264.7 and HT-29 cells. Food and Chemical Toxicology 55: 229–233. https://doi.org/10.1016/j.fct.2012.12.062.

    Article  CAS  PubMed  Google Scholar 

  19. Zheng, Y.F., J.H. Xie, Y.F. Xu, Y.Z. Liang, Z.Z. Mo, W.W. Jiang, X.Y. Chen, Y.H. Liu, X.D. Yu, P. Huang, and Z.R. Su. 2014. Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats. Chemico-Biological Interactions 222: 27–36. https://doi.org/10.1016/j.cbi.2014.08.008.

    Article  CAS  PubMed  Google Scholar 

  20. Sah, S.P., C.S. Mathela, and K. Chopra. 2011. Antidepressant effect of Valeriana wallichii patchouli alcohol chemotype in mice: Behavioural and biochemical evidence. Journal of Ethnopharmacology 135 (1): 197–200. https://doi.org/10.1016/j.jep.2011.02.018.

    Article  PubMed  Google Scholar 

  21. Jeong, J.B., J. Choi, Z. Lou, X. Jiang, and S.H. Lee. 2013. Patchouli alcohol, an essential oil of Pogostemon cablin, exhibits anti-tumorigenic activity in human colorectal cancer cells. International Immunopharmacology 16 (2): 184–190. https://doi.org/10.1016/j.intimp.2013.04.006.

    Article  CAS  PubMed  Google Scholar 

  22. Xian, Y.F., Y.C. Li, S.P. Ip, Z.X. Lin, X.P. Lai, and Z.R. Su. 2011. Anti-inflammatory effect of patchouli alcohol isolated from Pogostemonis Herba in LPS-stimulated RAW264.7 macrophages. Experimental and Therapeutic Medicine 2 (3): 545–550. https://doi.org/10.3892/etm.2011.233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Li, Y.C., Y.F. Xian, S.P. Ip, Z.R. Su, J.Y. Su, J.J. He, Q.F. Xie, X.P. Lai, and Z.X. Lin. 2011. Anti-inflammatory activity of patchouli alcohol isolated from Pogostemonis Herba in animal models. Fitoterapia 82 (8): 1295–1301. https://doi.org/10.1016/j.fitote.2011.09.003.

    Article  CAS  PubMed  Google Scholar 

  24. Yu, X., G. Yang, H. Jiang, S. Lin, Y. Liu, X. Zhang, H. Zeng, Z. Su, S. Huang, L. Shen, and X. Zhang. 2017. Patchouli oil ameliorates acute colitis: A targeted metabolite analysis of 2,4,6-trinitrobenzenesulfonic acid-induced rats. Experimental and Therapeutic Medicine 14 (2): 1184–1192. https://doi.org/10.3892/etm.2017.4577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jang, S.E., J.J. Jeong, S.R. Hyam, M.J. Han, and D.H. Kim. 2014. Ursolic acid isolated from the seed of Cornus officinalis ameliorates colitis in mice by inhibiting the binding of lipopolysaccharide to toll-like receptor 4 on macrophages. Journal of Agricultural and Food Chemistry 62 (40): 9711–9721. https://doi.org/10.1021/jf501487v.

    Article  CAS  PubMed  Google Scholar 

  26. Cho, J.M., S.M. Yun, Y.H. Choi, J. Heo, N.J. Kim, S.H. Kim, and E.H. Kim. 2018. Xanthohumol prevents dextran sulfate sodium-induced colitis via inhibition of IKKbeta/NF-kappaB signaling in mice. Oncotarget 9 (1): 866–880. https://doi.org/10.18632/oncotarget.23183.

    Article  PubMed  Google Scholar 

  27. Qu, C., Z.W. Yuan, X.T. Yu, Y.F. Huang, G.H. Yang, J.N. Chen, X.P. Lai, Z.R. Su, H.F. Zeng, Y. Xie, and X.J. Zhang. 2017. Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism. Pharmacological Research 121: 70–82. https://doi.org/10.1016/j.phrs.2017.04.017.

    Article  CAS  PubMed  Google Scholar 

  28. Lee, S.Y., S.H. Lee, E.J. Yang, E.K. Kim, J.K. Kim, D.Y. Shin, and M.L. Cho. 2015. Metformin ameliorates inflammatory bowel disease by suppression of the STAT3 signaling pathway and regulation of the between Th17/Treg balance. PLoS One 10 (9): e0135858. https://doi.org/10.1371/journal.pone.0135858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ren, T., T. Tian, X. Feng, S. Ye, H. Wang, W. Wu, Y. Qiu, C. Yu, Y. He, J. Zeng, J. Cen, and Y. Zhou. 2015. An adenosine A3 receptor agonist inhibits DSS-induced colitis in mice through modulation of the NF-kappaB signaling pathway. Scientific Reports 5: 9047. https://doi.org/10.1038/srep09047.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang, Y.H., B. Ge, X.L. Yang, J. Zhai, L.N. Yang, X.X. Wang, X. Liu, J.C. Shi, and Y.J. Wu. 2011. Proanthocyanidins from grape seeds modulates the nuclear factor-kappa B signal transduction pathways in rats with TNBS-induced recurrent ulcerative colitis. International Immunopharmacology 11 (10): 1620–1627. https://doi.org/10.1016/j.intimp.2011.05.024.

    Article  CAS  PubMed  Google Scholar 

  31. Galvez, J., G. Coelho, M.E. Crespo, T. Cruz, M.E. Rodriguez-Cabezas, A. Concha, M. Gonzalez, and A. Zarzuelo. 2001. Intestinal anti-inflammatory activity of morin on chronic experimental colitis in the rat. Alimentary Pharmacology & Therapeutics 15 (12): 2027–2039. https://doi.org/10.1046/j.1365-2036.2001.01133.x.

    Article  CAS  Google Scholar 

  32. Mi, H., F.B. Liu, H.W. Li, J.T. Hou, and P.W. Li. 2017. Anti-inflammatory effect of Chang-An-Shuan on TNBS-induced experimental colitis in rats. BMC Complementary and Alternative Medicine 17 (1): 315. https://doi.org/10.1186/s12906-017-1794-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shi, X.Z., J.H. Winston, and S.K. Sarna. 2011. Differential immune and genetic responses in rat models of Crohn’s colitis and ulcerative colitis. American Journal of Physiology. Gastrointestinal and Liver Physiology 300 (1): G41–G51. https://doi.org/10.1152/ajpgi.00358.2010.

    Article  CAS  PubMed  Google Scholar 

  34. Perse, M., and A. Cerar. 2012. Dextran sodium sulphate colitis mouse model: Traps and tricks. Journal of Biomedicine & Biotechnology 2012: 718617. https://doi.org/10.1155/2012/718617.

    Article  CAS  Google Scholar 

  35. da Silva, M.S., S. Sanchez-Fidalgo, E. Talero, A. Cardeno, M.A. da Silva, W. Villegas, A.R. Souza Brito, and C.A. de La Lastra. 2010. Anti-inflammatory intestinal activity of Abarema cochliacarpos (Gomes) Barneby & Grimes in TNBS colitis model. Journal of Ethnopharmacology 128 (2): 467–475. https://doi.org/10.1016/j.jep.2010.01.024.

    Article  PubMed  Google Scholar 

  36. Arrieta, M.C., L. Bistritz, and J.B. Meddings. 2006. Alterations in intestinal permeability. Gut 55 (10): 1512–1520. https://doi.org/10.1136/gut.2005.085373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Han, F., H. Zhang, X. Xia, H. Xiong, D. Song, X. Zong, and Y. Wang. 2015. Porcine beta-defensin 2 attenuates inflammation and mucosal lesions in dextran sodium sulfate-induced colitis. Journal of Immunology 194 (4): 1882–1893. https://doi.org/10.4049/jimmunol.1402300.

    Article  CAS  Google Scholar 

  38. Petersson, J., O. Schreiber, G.C. Hansson, S.J. Gendler, A. Velcich, J.O. Lundberg, S. Roos, L. Holm, and M. Phillipson. 2011. Importance and regulation of the colonic mucus barrier in a mouse model of colitis. American Journal of Physiology. Gastrointestinal and Liver Physiology 300 (2): G327–G333. https://doi.org/10.1152/ajpgi.00422.2010.

    Article  CAS  PubMed  Google Scholar 

  39. Sheng, Y.H., S.Z. Hasnain, T.H. Florin, and M.A. McGuckin. 2012. Mucins in inflammatory bowel diseases and colorectal cancer. Journal of Gastroenterology and Hepatology 27 (1): 28–38. https://doi.org/10.1111/j.1440-1746.2011.06909.x.

    Article  CAS  PubMed  Google Scholar 

  40. McCall, I.C., A. Betanzos, D.A. Weber, P. Nava, G.W. Miller, and C.A. Parkos. 2009. Effects of phenol on barrier function of a human intestinal epithelial cell line correlate with altered tight junction protein localization. Toxicology and Applied Pharmacology 241 (1): 61–70. https://doi.org/10.1016/j.taap.2009.08.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Seo, G.S., W.Y. Jiang, P.H. Park, D.H. Sohn, J.H. Cheon, and S.H. Lee. 2014. Hirsutenone reduces deterioration of tight junction proteins through EGFR/Akt and ERK1/2 pathway both converging to HO-1 induction. Biochemical Pharmacology 90 (2): 115–125. https://doi.org/10.1016/j.bcp.2014.05.006.

    Article  CAS  PubMed  Google Scholar 

  42. Graham, W.V., W. He, A.M. Marchiando, J. Zha, G. Singh, H.S. Li, A. Biswas, M.L.D.M. Ong, Z.H. Jiang, W. Choi, H. Zuccola, Y. Wang, J. Griffith, J. Wu, H.J. Rosenberg, Y. Wang, S.B. Snapper, D. Ostrov, S.C. Meredith, L.W. Miller, and J.R. Turner. 2019. Intracellular MLCK1 diversion reverses barrier loss to restore mucosal homeostasis. Nature Medicine 25 (4): 690–700. https://doi.org/10.1038/s41591-019-0393-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhang, J., Y. Zhao, T. Hou, H. Zeng, D. Kalambhe, B. Wang, X. Shen, and Y. Huang. 2020. Macrophage-based nanotherapeutic strategies in ulcerative colitis. Journal of Controlled Release 320: 363–380. https://doi.org/10.1016/j.jconrel.2020.01.047.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Program of Shanghai Committee of Science and Technology of China [grant no. 17401902300] and the Program of Shanghai Academic/Technology Research Leader of China [grant no. 18XD1403700].

Author information

Author notes

  1. Zhuona Wu and Hairong Zeng contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People’s Republic of China

    Zhuona Wu, Lili Zhang, Tong Zhang & Bing Wang

  2. Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People’s Republic of China

    Zhuona Wu, Yiqiong Pu & Tong Zhang

  3. Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Rd, Shanghai, 200062, People’s Republic of China

    Hairong Zeng & Yi Yuan

  4. School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People’s Republic of China

    Suyun Li

  5. State Key Laboratory of Drug Research & Center for Pharmaceutics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai, 201203, People’s Republic of China

    Bing Wang

Authors
  1. Zhuona Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hairong Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lili Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yiqiong Pu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Suyun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

B.W. and T.Z. contributed to the conception of the paper; Z.N.W. and L.L.Z. contributed significantly to complete manuscript preparation; H.R.Z. performed data analysis; Y.Q.P. and S.Y.L. contributed to the constructive discussions; Y. Y. contributed to refining the ideas. All authors read and approved the review.

Corresponding authors

Correspondence to Yi Yuan, Tong Zhang or Bing Wang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Statement of Informed Consent

All the animal care and experiment studies were approved and conducted in accordance with the guidelines of the Animal Ethical Committee of Shanghai University of Traditional Chinese Medicine (SYXK 2014-0008).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, Z., Zeng, H., Zhang, L. et al. Patchouli Alcohol: a Natural Sesquiterpene Against Both Inflammation and Intestinal Barrier Damage of Ulcerative Colitis. Inflammation 43, 1423–1435 (2020). https://doi.org/10.1007/s10753-020-01219-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-020-01219-8

Key Words

Search

Navigation