title: Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation.
abstract: Patients with lupus nephritis show an impaired oxidative status and increased levels of interleukin (IL)-1β and IL-18, which are closely linked to inflammation and correlated with disease activity. Although epigallocatechin-3-gallate (EGCG), the major bioactive polyphenol present in green tea with antioxidant and free radical scavenging activities, has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo, its effectiveness for the treatment of lupus nephritis is still unknown. In the present study, 12-week-old New Zealand black/white (NZB/W) F1 lupus-prone mice were treated daily with EGCG by gavage until sacrificed at 34 weeks old for clinical, pathological, and mechanistic evaluation. We found that the administration (1) prevented proteinuria, renal function impairment, and severe renal lesions; (2) increased renal nuclear factor E2-related factor 2 (Nrf2) and glutathione peroxidase activity; (3) reduced renal oxidative stress, NF-κB activation, and NLRP3 mRNA/protein expression and protein levels of mature caspase-1, IL-1β, and IL-18; and (4) enhanced splenic regulatory T (Treg) cell activity. Our data clearly demonstrate that EGCG has prophylactic effects on lupus nephritis in these mice that are highly associated with its effects of enhancing the Nrf2 antioxidant signaling pathway, decreasing renal NLRP3 inflammasome activation, and increasing systemic Treg cell activity.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Tsai
authors.forename: Shuk-Man
authors.initials: SM
authors.lastname: Ka
authors.forename: Jia-Ming
authors.initials: JM
authors.lastname: Chang
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chen
authors.forename: Hao-Ai
authors.initials: HA
authors.lastname: Shui
authors.forename: Chen-Yun
authors.initials: CY
authors.lastname: Li
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Hua
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Chang
authors.forename: Jiann-Jyh
authors.initials: JJ
authors.lastname: Huang
authors.forename: Sung-Sen
authors.initials: SS
authors.lastname: Yang
authors.forename: Ann
authors.initials: A
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002392:Catechin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000187:drug effects; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008814:Mice, Inbred NZB; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D002392:Catechin; C045651:epigallocatechin gallate