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A Novel Biological Role of α-Mangostin via TAK1–NF-κB Pathway against Inflammatory

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Abstract

The oxysterone α-mangostin is isolated from mangosteen husks and is widely used in the treatment of abdominal pain, diarrhea, and dysentery. In this study, we established a lipopolysaccharide (LPS)-induced inflammatory model of rat intestinal epithelial cells (IEC-6 cells), at the same time we used differently concentration α-mangostin to detect its anti-inflammatory activity. We applied doses of α-mangostin (2.5, 5, and 10 μM) and detected apoptosis by flow cytometry, and the Griess reagent and the enzyme-linked immunosorbent assay (ELISA) method detected inflammatory factors such as nitric oxide (NO), prostaglandin (PG) E2, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. We also used quantitative real-time PCR (Q-PCR) to examine inflammatory factors and western blotting to examine the activation of transforming growth factor-activated kinase (TAK)-1-nuclear factor (NF)-κB signaling pathway-related proteins. Finally, we used laser confocal microscopy to detect the effect of the 10 μM α-mangostin on the nuclear import of NF-κB–p65. The results showed that α-mangostin treatment significantly reduced the apoptosis of LPS-stimulated IEC-6 cells, the production of inflammatory factors, the activation of TAK1–NF-κB signaling pathway-related proteins, and the entry of p65 into the nucleus. In conclusion, α-mangostin exerts its anti-inflammatory effects by inhibiting the activation of TAK1–NF-κB and it may be a potential choice for the treatment of inflammation diseases.

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References

  1. Glover, Louise E., J. Scott Lee, and Sean P. Colgan. 2016. Oxygen metabolism and barrier regulation in the intestinal mucosa. Journal of Clinical Investigation 126 (10): 3680–3688.

    Article  PubMed  Google Scholar 

  2. You, B.H., H.S. Chae, J. Song, H.W. Ko, Y.W. Chin, and Y.H. Choi. 2017. α-Mangostin ameliorates dextran sulfate sodium-induced colitis through inhibition of NF-κB and MAPK pathways. International Immunopharmacology 49: 212–221.

    Article  CAS  PubMed  Google Scholar 

  3. Nathan, C. 2002. Points of control in inflammation. Nature 420 (6917): 846–852. https://doi.org/10.1038/nature01320.

    Article  CAS  PubMed  Google Scholar 

  4. Luo, Fen, Rui Zhou, Hui Lei, Yi Mou, ** Zhang, Yi Sun, Tong Chen, Ling He, and Tianhua Yan. 2016. Umbelliferone attenuates lipopolysaccharide-induced acute lung injury linked with regulation of TLRs–MyD88 and RIP140/NF-κB signaling pathways. RSC Advances 6 (100): 97503–97511.

    Article  CAS  Google Scholar 

  5. Qu, Minye, Tao **ang, and Jian Ma. 2017. Yi-Qi-**-Chuan-Fang reduces TSLP elevation caused by LPS + poly (I:C) via inhibiting TLR4/MYD88/NF-κB signaling pathway. Evidence-based Complementary and Alternative Medicine 2017 (3): 3209407.

    PubMed  PubMed Central  Google Scholar 

  6. Pham, Tuan-Anh, Changwoo Han, and Haeil Park. 2017. Synthesis of ochnaflavone analogs and their inhibitory activity on PGE2 and NO production against LPS-treated RAW 264.7 cells. Bulletin of the Korean Chemical Society 38 (6): 681–683.

    Article  CAS  Google Scholar 

  7. So, Y., S.Y. Lee, A.R. Han, J.B. Kim, H.G. Jeong, and C.H. **. 2016. Rosmarinic acid methyl ester inhibits LPS-induced NO production via suppression of MyD88-dependent and -independent pathways and induction of HO-1 in RAW 264.7 cells. Molecules 21 (8): 1083.

    Article  CAS  PubMed Central  Google Scholar 

  8. Mukti, Nur Indah Fajar, Imam Prasetyo, Aswati Mindaryani, and Shofwatunnida’ Septarini. 2018. Preparation of porous carbon as ethylene adsorbent by pyrolysis of extraction waste mangosteen rinds.

  9. Suttirak, W., and S. Manurakchinakorn. 2014. In vitro antioxidant properties of mangosteen peel extract. Journal of Food Science and Technology 51 (12): 3546–3558.

    Article  CAS  PubMed  Google Scholar 

  10. Ming, Guo, **aomeng Wang, **aowang Lu, Hongzheng Wang, and Peter E. Brodelius. 2016. α-mangostin extraction from the native mangosteen (Garcinia mangostana L.) and the binding mechanisms of α-mangostin to HSA or TRF. PLoS One 11 (9): e0161566.

    Article  CAS  Google Scholar 

  11. Rukthong, P., N. Sereesongsang, T. Kulsirirat, B. Nimprayoon, and K. Sathirakul. 2017. Effect of α-mangostin on enhanced transdermal bioavailability of gartanin via efflux transporters. Journal of Bioequivalence and Bioavailability 09 (4).

  12. Nava, Catorce M., G. Acero, J. Pedraza-Chaverri, G. Fragoso, T. Govezensky, and G. Gevorkian. 2016. Alpha-mangostin attenuates brain inflammation induced by peripheral lipopolysaccharide administration in C57BL/6J mice. Journal of Neuroimmunology 297: 20–27.

    Article  CAS  Google Scholar 

  13. Won, Y.S., J.H. Lee, S.J. Kwon, J.Y. Kim, K.H. Park, M.K. Lee, and K.I. Seo. 2014. α-Mangostin-induced apoptosis is mediated by estrogen receptor α in human breast cancer cells. Food & Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 66: 158–165.

    Article  CAS  Google Scholar 

  14. Guzmán-Beltrán, Silvia, Miguel Ángel Rubio-Badillo, Esmeralda Juárez, Fernando Hernández-Sánchez, and Martha Torres. 2015. Nordihydroguaiaretic acid (NDGA) and α-mangostin inhibit the growth of Mycobacterium tuberculosis by inducing autophagy. International Immunopharmacology 31: 149.

    Article  CAS  PubMed  Google Scholar 

  15. Phuong, Nguyen Thi Mai, Ngo Van Quang, Ta Thu Mai, Nguyen Vu Anh, Chutima Kuhakarn, Vichai Reutrakul, and Albert Bolhuis. 2017. Antibiofilm activity of α-mangostin against Staphylococcus aureus. Asian Pacific Journal of Tropical Medicine 10 (12).

  16. Benjakul, R., L. Kongkaneramit, N. Sarisuta, P. Moongkarndi, and C.C. Müller-Goymann. 2015. Cytotoxic effect and mechanism inducing cell death of α-mangostin liposomes in various human carcinoma and normal cells. Anti-Cancer Drugs 26 (8): 824–834.

    Article  CAS  PubMed  Google Scholar 

  17. Widowati, Wahyu, Lusiana Darsono, Jo Suherman, Nurul Fauziah, Maesaroh Maesaroh, and Pande Putu Erawijantari. 2016. Anti-inflammatory effect of mangosteen (Garcinia mangostana L.) peel extract and its compounds in LPS-induced RAW264.7 cells. Natural Product Sciences 22 (3): 147.

    Article  CAS  Google Scholar 

  18. Mowat, A.M., and J.L. Viney. 1997. The anatomical basis of intestinal immunity. Immunological Reviews 156: 145–166.

    Article  CAS  PubMed  Google Scholar 

  19. Rosadini, C.V., and J.C. Kagan. 2017. Early innate immune responses to bacterial LPS. Current Opinion in Immunology 44: 14–19. https://doi.org/10.1016/j.coi.2016.10.005.

    Article  CAS  PubMed  Google Scholar 

  20. Hu, Ling-Na, **an Ying Fang, Hai Liang Liu, Zhe Gao, Xue-Feng Wu, Yang Sun, Xu-Dong Wu, and Qiang Xu. 2013. Protective effects of 18β-glycyrrhetinic acid on LPS-induced injury in intestinal epithelial cells. Chinese Journal of Natural Medicines 11 (1): 24–29.

    Article  CAS  Google Scholar 

  21. Talavera, M.M., S. Nuthakki, H. Cui, Y. **, Y. Liu, and L.D. Nelin. 2017. Immunostimulated arginase II expression in intestinal epithelial cells reduces nitric oxide production and apoptosis. Frontiers in Cell and Developmental Biology 5: 15.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Habashi, Soraya Abbasi, Farzaneh Sabouni, Ali Moghimi, and Saeed Ansari Majd. 2016. Modulation of lipopolysaccharide stimulated nuclear factor kappa B mediated iNOS/NO production by bromelain in rat primary microglial cells. Iranian Biomedical Journal 20 (1): 33–40.

    Google Scholar 

  23. Chen, X., S.A. Tang, E. Lee, Y. Qiu, R. Wang, Duan H. Quan, S. Dan, M. **, and D. Kong. 2015. IVSE, isolated from Inula japonica, suppresses LPS-induced NO production via NF-κB and MAPK inactivation in RAW264.7 cells. Life Sciences 124: 8–15.

    Article  CAS  PubMed  Google Scholar 

  24. Lai, J.L., Y.H. Liu, C. Liu, M.P. Qi, R.N. Liu, X.F. Zhu, Q.G. Zhou, Y.Y. Chen, A.Z. Guo, and C.M. Hu. 2017. Indirubin inhibits LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways. Inflammation 40 (1): 1–12.

    Article  CAS  PubMed  Google Scholar 

  25. Xu, X., P. Yin, C. Wan, X. Chong, M. Liu, P. Cheng, J. Chen, F. Liu, and J. Xu. 2014. Punicalagin inhibits inflammation in LPS-induced RAW264.7 macrophages via the suppression of TLR4-mediated MAPKs and NF-kappaB activation. Inflammation 37 (3): 956–965. https://doi.org/10.1007/s10753-014-9816-2.

    Article  CAS  PubMed  Google Scholar 

  26. Li, Tingting, Jianyan Hu, Shanshan Du, Yongdong Chen, Shuai Wang, and Qiang Wu. 2014. ERK1/2/COX-2/PGE2 signaling pathway mediates GPR91-dependent VEGF release in streptozotocin-induced diabetes. Molecular Vision 20 (7): 1109–1121.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Takeuchi, K., Y. Komatsu, Y. Nakamori, and T. Kotani. 2017. A rat model of ischemic enteritis: pathogenic importance of enterobacteria, iNOS/NO, and COX-2/PGE2. Current Pharmaceutical Design 23 (999): 1–1.

    Google Scholar 

  28. Chae, H.S., Y.M. Kim, J.K. Bae, S. Sorchhann, S. Yim, L. Han, J.H. Paik, Y.H. Choi, and Y.W. Chin. 2016. Mangosteen extract attenuates the metabolic disorders of high-fat-fed mice by activating AMPK. Journal of Medicinal Food 19 (2): 148–154.

    Article  PubMed  Google Scholar 

  29. Kwak, Hyun-Ho, In-Ryoung Kim, Hye-** Kim, Bong-Soo Park, and Su Bin Yu. 2016. α-Mangostin induces apoptosis and cell cycle arrest in oral squamous cell carcinoma cell. Evidence-based Complementary and Alternative Medicine 2016: 5352412.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wang, Yujue, Guang Chen, ** Yang, Yansheng Zhao, and Li Na. 2016. Salvianolic acid B ameliorates cerebral ischemia/reperfusion injury through inhibiting TLR4/MyD88 signaling pathway. Inflammation 39 (4): 1–11.

    Article  CAS  Google Scholar 

  31. Yao, H., C. Hu, L. Yin, X. Tao, L. Xu, Y. Qi, X. Han, Y. Xu, Y. Zhao, and C. Wang. 2016. Dioscin reduces lipopolysaccharide-induced inflammatory liver injury via regulating TLR4/MyD88 signal pathway. International Immunopharmacology 36: 132–141.

    Article  CAS  PubMed  Google Scholar 

  32. Ukil, A., S. Maity, and P.K. Das. 2017. Protection from experimental colitis by theaflavin-3,3′-digallate correlates with inhibition of IKK and NF-kappaB activation. British Journal of Pharmacology 180 (1): 121–131.

    Article  CAS  Google Scholar 

  33. Kim, Sung Hak, Ravesanker Ezhilarasan, Emma Phillips, Daniel Gallegoperez, Amanda Sparks, David Taylor, Katherine Ladner, Takuya Furuta, Hemragul Sabit, and Rishi Chhipa. 2016. Serine/threonine kinase MLK4 determines mesenchymal identity in glioma stem cells in an NF-κB-dependent manner. Cancer Cell 29 (2): 201–213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Li, Hong Bao, **ang Li, Chan Juan Huo, Qing Su, **g Guo, Zu Yi Yuan, Guo Qing Zhu, **ao Lian Shi, ** Jun Liu, and Yu Ming Kang. 2016. TLR4/MyD88/NF-κB signaling and PPAR-γ within the paraventricular nucleus are involved in the effects of telmisartan in hypertension. Toxicology and Applied Pharmacology 305: 93–102.

    Article  CAS  PubMed  Google Scholar 

  35. Nguyen, D.P., J. Li, S.S. Yadav, and A.K. Tewari. 2014. Recent insights into NF-κB signalling pathways and the link between inflammation and prostate cancer. BJU International 114 (2): 168–176.

    Article  CAS  PubMed  Google Scholar 

  36. He, Aiqin, Rui Ji, Jia Shao, Chenyun He, Ming **, and Yunzhao Xu. 2016. TLR4-MyD88-TRAF6-TAK1 complex-mediated NF-κB activation contribute to the anti-inflammatory effect of V8 in LPS-induced human cervical cancer SiHa cells. Inflammation 39 (1): 1–10.

    Article  CAS  Google Scholar 

  37. Weng, Ting, and Cheng Gee Koh. 2017. POPX2 phosphatase regulates apoptosis through the TAK1-IKK-NF-|[kappa]|B pathway. Cell Death & Disease 8 (9): e3051.

    Article  CAS  Google Scholar 

  38. Yang, S., Z. Yu, T. Yuan, L. Wang, X. Wang, H. Yang, L. Sun, Y. Wang, and G. Du. 2016. Therapeutic effect of methyl salicylate 2-O-β-d-lactoside on LPS-induced acute lung injury by inhibiting TAK1/NF-kappaB phosphorylation and NLRP3 expression. International Immunopharmacology 40: 219–228.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by grants from the Bei**g Municipal Science and Technology Project (D171100002117002).

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Authors and Affiliations

  1. College of Animal Science and Technology, Bei**g University of Agriculture (BUA), Bei**g, People’s Republic of China

    Wenshu Zou, Yaran Shi, Na **, Qian Gao, Jiandong Li & Fenghua Liu

  2. Institute of Microbiology Chinese Academy of Sciences, NO.1 Beichen West Road, Bei**g, People’s Republic of China

    Peng Yin

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  1. Wenshu Zou
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Correspondence to Fenghua Liu.

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Zou, W., Yin, P., Shi, Y. et al. A Novel Biological Role of α-Mangostin via TAK1–NF-κB Pathway against Inflammatory. Inflammation 42, 103–112 (2019). https://doi.org/10.1007/s10753-018-0876-6

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