Dihydrocapsaicin suppresses proinflammatory cytokines expression by enhancing nuclear factor IA in a NF-κB-dependent manner.
Atherosclerosis is a chronic inflammatory disease and represents the leading cause of morbidity and mortality throughout the world. Accumulating evidences have showed that Dihydrocapsaicin (DHC) has been found to exert multiple pharmacological and physiological effects. Nevertheless, the effects and possible mechanism of DHC on proinflammatory response remain largely unexplained.



We found that DHC markedly upregulated NFIA and suppressed NF-κB expression in THP-1 macrophages. Up-regulation of proinflammatory cytokines induced by LPS including TNF-α, IL-1β and IL-6 were markedly suppressed by DHC treatment. We also observed that protein level of NFIA was significantly increased while NF-κB and proinflammatory cytokines were decreased by DHC treatment in apoE(-/-) mice. Lentivirus-mediated overexpression of NFIA suppressed NF-κB and proinflammatory cytokines expression both in THP-1 macrophages and plaque tissues of apoE-/- mice. Moreover, treatment with lentivirus-mediated overexpression of NFIA made the down-regulation of DHC on NF-κB and proinflammatory cytokines expression notably accentuated in THP-1 macrophages and apoE(-/-) mice. In addition, treatment with siRNA targeting NF-κB accentuated the suppression of proinflammatory cytokines by lentivirus-mediated overexpression of NFIA.



These observations demonstrated that DHC can significantly decrease proinflammatory cytokines through enhancing NFIA and inhibiting NF-κB expression and thus DHC may be a promising candidate as an anti-inflammatory drug for atherosclerosis as well as other disorders.
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Jing-Jing
JJ
Zhao
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Yan-Wei
YW
Hu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Chuan
C
Huang
Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Xin
X
Ma
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Chun-Min
CM
Kang
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Yuan
Y
Zhang
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Feng-Xia
FX
Guo
Department of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Jing-Bo
JB
Lu
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Jian-Cheng
JC
Xiu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Yu-Rong
YR
Qiu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Yan-Hua
YH
Sha
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Ji-Juan
JJ
Gao
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Yan-Chao
YC
Wang
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Pan
P
Li
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Bang-Ming
BM
Xu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: nfyyzl@163.com.
Lei
L
Zheng
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: nfyywangqian@163.com.
Qian
Q
Wang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism*; D051839:NFI Transcription Factors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D051839:NFI Transcription Factors; C497592:NFIA protein, human; C497646:Nfia protein, mouse; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D002211:Capsaicin; C012906:dihydrocapsaicin
DHC; Inflammatory cytokines; NF-κB; NFIA