生物活性

• 描述Rhein is a lipophilic anthraquinone extensively found in medicinal herbs. Apoptosis was induced by adjunctive use of rhein with epidermal growth factor receptor (EGFR) inhibitors in pancreatic cancer cells. Suppression of the phosphorylation of STAT3 and EGFR (epidermal growth factor receptor) were also observed as a result of the treatment with a combination of rhein and EGFR inhibitors. Rhein considerably sensitized cells to erlotinib, thus suppressing tumor growth in PANC-1 and BxPC-3 xenograft models^[3]. Rhein possesses pharmacological activity to suppress caspase-1 protease activity and IL-1 βproduction by interfering with the formation of NLRP3 multiprotein complex. Rhein has therapeutic potential for treating NLRP3 inflammasome-mediated diseases such as gouty arthritis^[4]. Rhein exhibits various renoprotective functions, rhein remarkably reversed renal Klotho (a renal-specific antiaging protein) deficiency in adenine-treated mice. The renal protective effects of rhein were largely abolished when Klotho was knocked-down by RNA interferences, suggesting that rhein reversal of Klotho deficiency is essential for its renoprotective actions^[5]. Rhein could effectively block the ATP-induced [Ca2+]c increases in a dose-dependent manner. Besides, rhein also suppressed the production of intracellular reactive oxygen species (ROS) induced by ATP in synoviocytes that was resulted from P2X4-mediated Ca2+ entry. Both rhein and BBG (Brilliant blue G) attenuated these inflammatory gene expressions enhanced by ATP^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02514772	Rheumatoid Arthritis	Phase 3	Completed	-	-
  NCT02778906	Arthralgia Ar... more >>thritis Collapse <<	Phase 3	Unknown	December 2018	Germany ... more >> Klinikum Bad Abbach Recruiting Bad Abbach, Germany Contact: Martin Fleck, Prof. Dr. med.       m.fleck@asklepios.com    Contact: Boris Ehrenstein, Dr. med.       boris.ehrenstein@klinik.uni-r.de    Kerckhoff-Klinik Bad Nauheim Recruiting Bad Nauheim, Germany Contact: Ramona Koenig, Dr. med.       r.koenig@kerckhoff-klinik.de    Contact: Ulf Müller-Ladner, Prof. Dr. med.       u.mueller-ladner@kerckhoff-klinik.de    Charite Berlin Recruiting Berlin, Germany Contact: Eugen Feist, Prof. Dr. med.       eugen.feist@charite.de    Contact: Claudia Kedor, Dr. med.       claudia.kedor@charite.de    Praxis für Rheumatologie und Innere Medizin Recruiting Berlin, Germany Contact: Kirsten Karberg, Dr. med.       kirsten.karberg@arcor.de    Contact: Henning Brandt, Dr. med.       henning.brandt@charite.de    Schlosspark Klinik Recruiting Berlin, Germany Contact: Rieke Alten, Dr. med.       Rieke.Alten@schlosspark-klinik.de    Contact: Christoph Pohl, Dr. med.       christof.pohl@schlosspark-klinik.de    Clinic Burghausen Recruiting Burghausen, Germany Contact: Martin Feuchtenberger, Dr. med.    +49 (0) 86 77 / 880-261    m.feuchtenberger@krk-bgh.de    University Clinic Erlangen Recruiting Erlangen, Germany, 91054 Contact: Axel Hueber, Dr. med. Dr. PhD    +49-913185320193    axel.hueber@uk-erlangen.de    Contact: Juergen Rech, Dr. med.    +49-91318543014    juergen.rech@uk-erlangen.de    Centrum für innovative Diagnostik und Therapie (Ciri) Rheumatologie/Immunologie Recruiting Frankfurt, Germany, 60528 Contact: Frank Behrens, Dr. med.    069/6301-7302    Behrens@ciri-clinical.de    Contact: Harald Burkhardt, Prof. Dr. med.    069/6301-7301    burkhardt@ciri-clinical.de    Universitätsklinik Freiburg Recruiting Freiburg, Germany Contact: Reinhard Voll, Prof. Dr. med.       reinhard.voll@uniklinik-freiburg.de    Contact: Jens Thiel, Dr. med.       jens.thiel@uniklinik-freiburg.de    Sub-Investigator: Nils Venhoff, Dr. med.          Rheumazentrum Ruhrgebiet Recruiting Herne, Germany Contact: Xenofon Baraliakos, Dr. med.       baraliakos@me.com    Contact: Uta Kiltz, Dr. med.       Uta.Kiltz@elisabethgruppe.de    Krankenhaus Porz Am Rhein Recruiting Koeln, Germany Contact: Johannes Strunk, Prof. Dr. med.       j.strunk@khporz.de    Contact: Dennis Schleicht, Dr. med.       D.Scheicht@khporz.de Collapse <<
  NCT02979119	-	-	Recruiting	December 2019	-

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• 参考文献

• [1] Lin S, Fujii M, Hou DX. Rhein induces apoptosis in HL-60 cells via reactive oxygen species-independent mitochondrial death pathway. Arch Biochem Biophys. 2003 Oct 15;418(2):99-107.

  [2] Martel-Pelletier J, Mineau F, et al. In vitro effects of diacerhein and rhein on interleukin 1 and tumor necrosis factor-alpha systems in human osteoarthritic synovium and chondrocytes. J Rheumatol. 1998 Apr;25(4):753-62.

  [3] Yang L, Lin S, Kang Y, et al. Rhein sensitizes human pancreatic cancer cells to EGFR inhibitors by inhibiting STAT3 pathway. J Exp Clin Cancer Res. 2019;38(1):31. Published 2019 Jan 23

  [4] Chang WC, Chu MT, Hsu CY, et al. Rhein, An Anthraquinone Drug, Suppresses the NLRP3 Inflammasome and Macrophage Activation in Urate Crystal-Induced Gouty Inflammation. Am J Chin Med. 2019;47(1):135-151

  [5] Zhang Q, Liu L, Lin W, et al. Rhein reverses Klotho repression via promoter demethylation and protects against kidney and bone injuries in mice with chronic kidney disease. Kidney Int. 2017;91(1):144-156

  [6] Hu F, Zhu D, Pei W, et al. Rhein inhibits ATP-triggered inflammatory responses in rheumatoid rat fibroblast-like synoviocytes. Int Immunopharmacol. 2019;75:105780

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