Cortex cinnamomi extract prevents streptozotocin- and cytokine-induced beta-cell damage by inhibiting NF-kappaB.
OBJECTIVE
To clarify the mechanism underlying the anti-diabetic activities of cortex cinnamomi extract (CCE).


METHODS
To induce in vivo diabetes, mice were injected with streptozotocin (STZ) via a tail vein (100 mg STZ/kg body weight). To determine the effects of CCE, mice were administered CCE twice daily for 7 d by oral gavage starting 1 wk before the STZ injection. Blood glucose and plasma insulin concentration were measured as an index of diabetes. Also, to induce cytotoxicity of RINm5F cells, we treated with cytokines (IL-1beta (2.0 ng/mL) and IFN-gamma (100 U/mL)). Cell viability and nitric oxide production were measured colorimetrically. Inducible nitric oxide synthase (iNOS) mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. The activation of NF-kappaB was assayed by using gel mobility shift assays of nuclear extracts.


RESULTS
Treatment of mice with STZ resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by immunohistochemical staining of islets. However, the diabetogenic effects of STZ were completely prevented when mice were pretreated with CCE. The inhibitory effect of CCE on STZ-induced hyperglycemia was mediated through the suppression of iNOS expression. In rat insulinoma RINm5F cells, CCE completely protected against interleukin-1beta and interferon-gamma-mediated cytotoxicity. Moreover, RINm5F cells incubated with CCE showed significant reductions in interleukin-1beta and interferon-gamma-induced nitric oxide production and in iNOS mRNA and protein expression, and these findings correlated well with in vivo observations.


CONCLUSIONS
The molecular mechanism by which CCE inhibits iNOS gene expression appears to involve the inhibition of NF-kappaB activation. These results reveal the possible therapeutic value of CCE for the prevention of diabetes mellitus progression.
Kwon
Kang-Beom
KB
Department of Physiology, School of Oriental Medicine, Wonkwang University, Iksan 570-749, South Korea.
Kim
Eun-Kyung
EK
Jeong
Eun-Sil
ES
Lee
Young-Hoon
YH
Lee
Young-Rae
YR
Park
Jin-Woo
JW
Ryu
Do-Gon
DG
Park
Byung-Hyun
BH
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002460:Cell Line; D002478:Cells, Cultured; D032904:Cinnamomum aromaticum / Q000737:chemistry*; D016207:Cytokines / Q000009:adverse effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013311:Streptozocin
D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D009569:Nitric Oxide; D013311:Streptozocin; D052247:Nitric Oxide Synthase Type II