Inhibition of (S)-armepavine from Nelumbo nucifera on autoimmune disease of MRL/MpJ-lpr/lpr mice.
T cell immune responses play important roles in the pathogenesis of systemic lupus erythematosus (SLE). (S)-Armepavine (C19H23O3N; MW313) from Nelumbo nucifera suppresses T cells proliferation. To study its potential benefit on SLE, we examined effects of (S)-armepavine on MRL/MpJ-lpr/lpr mice, which have similar disease features to human SLE. MRL/MpJ-lpr/lpr mice were treated orally with (S)-armepavine for 6 weeks and their SLE characteristics were evaluated. The results revealed that (S)-armepavine prevented lymphadenopathy and elongated life span of MRL/MpJ-lpr/lpr mice. It seemed to be mediated by inhibition of splenocytes proliferation, suppression of interleukin-2 (IL-2), interleukin-4, interleukin-10, and interferon-gamma (IFN-gamma) gene expressions, reduction of glomerular hypercellularity and immune complexes deposition, and decrease of urinary protein and anti-double stranded DNA autoantibody production. Furthermore, the data demonstrated (S)-armepavine impaired IL-2 and IFN-gamma transcripts in human peripheral blood mononuclear cells. We suggest that (S)-armepavine may be an immunomodulator for the management of autoimmune diseases like SLE.
Liu
Chih-Peng
CP
Institute of Pharmacology, National Yang-Ming University, Taiwan, R.O.C.
Tsai
Wei-Jern
WJ
Shen
Chien-Chang
CC
Lin
Yun-Lian
YL
Liao
Jyh-Fei
JF
Chen
Chieh-Fu
CF
Kuo
Yuh-Chi
YC
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D044182:Benzylisoquinolines / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D007376:Interleukin-2 / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008206:Lymphatic Diseases / Q000517:prevention & control; D051379:Mice; D019463:Mice, Inbred MRL lpr; D031653:Nelumbo / Q000737:chemistry*; D010835:Phytohemagglutinins / Q000494:pharmacology; D008517:Phytotherapy; D011507:Proteinuria / Q000517:prevention & control / Q000652:urine; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012639:Seeds / Q000737:chemistry; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015996:Survival Rate
D000470:Alkaloids; D000974:Antibodies, Antinuclear; D044182:Benzylisoquinolines; D016207:Cytokines; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D007371:Interferon-gamma; C064689:armepavine