title: S-Propargyl-Cysteine, a Novel Hydrogen Sulfide Donor, Inhibits Inflammatory Hepcidin and Relieves Anemia of Inflammation by Inhibiting IL-6/STAT3 Pathway.
abstract: Anemia of inflammation (AI) is clinically prevalent and greatly threatens public health. Traditional remedies have raised controversy during clinical practice, calling for alternative therapies. We have recently found that hydrogen sulfide (H2S) inhibits inflammatory hepcidin, the critical mediator of AI. However, due to the chemical property of H2S, there remains an urgent need for a stable H2S donor in AI treatment. Here we reported that S-propargyl-cysteine (SPRC), a novel water-soluble H2S donor, suppressed hepatic hepcidin and corrected hypoferremia induced by lipopolysaccharide. The effects of SPRC were reversed by inhibition of cystathionine γ-lyase, one of the major endogenous H2S synthases. Moreover, SPRC reduced serum hepcidin, improved transferrin saturation, and maintained erythrocyte membrane integrity in a chronic mouse AI model. Consistently, splenomegaly was ameliorated and splenic iron accumulation relieved. Mechanism study indicated that serum IL-6 content and hepatic Il-6 mRNA were decreased by SPRC, in parallel with reduced hepatic JAK2/STAT3 activation. On the whole, our data reveal the inhibition of inflammatory hepcidin by SPRC, and suggest SPRC as a potential remedy against AI.
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China.|Department of Pharmacology, School of Pharmacy, Macau University of Science & Technology, Macau, China.
authors.forename: Minjun
authors.identifier: http://orcid.org/0000-0001-6792-0934
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China.|Department of Pharmacology, School of Pharmacy, Macau University of Science & Technology, Macau, China.
authors.forename: Yi Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D064451:Hepcidins / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D064451:Hepcidins; D015850:Interleukin-6; D008070:Lipopolysaccharides; C556437:S-propargylcysteine; D050796:STAT3 Transcription Factor; D003545:Cysteine; D006862:Hydrogen Sulfide