cyclin-d1 and cinnamaldehyde

Benign prostatic hyperplasia (BPH) is a widespread disorder in elderly men. Cinnamaldehyde, which is a major constituent in the essential oil of cinnamon, has been previously reported to reduce xanthine oxidase activity, in addition to its anti-inflammatory, anti-oxidant, and anti-proliferative activities. Our study was designed to investigate the potential modulatory effects of cinnamaldehyde on testosterone model of BPH in rats through reduction of uric acid level, and suppression of IL-6/JAK1/STAT3 signaling pathway. Cinnamaldehyde (40 and 75 mg/kg) was orally administered to male Wistar rats for 3 weeks, and concurrently with testosterone (3 mg/kg, s.c.) from the second week. Cinnamaldehyde ameliorated the elevation in prostatic weight and index compared to rats treated with testosterone only, that was also confirmed by alleviation of histopathological changes in prostate architecture. The protective mechanisms of cinnamaldehyde were elucidated through inhibition of xanthine oxidase activity and reduced uric acid level. That was accompanied by reduction of the pro-inflammatory cytokines; interleukin-6 (IL-6), IL-1β, tumor necrosis factor-alpha (TNF-α), and the nuclear translocation of the transcription factor NF-κB p65, that could be attributed also to the enhanced anti-oxidant defense by cinnamaldehyde. The protein expression of JAK1, which is IL-6 receptor linked protein, was reduced with subsequently reduced activation of STAT3 protein. That eventually suppressed the formation of the proliferation protein cyclin D1, while elevated Bax/Bcl2 ratio. It can be concluded that reducing uric acid level through xanthine oxidase inhibition and suppression of the inflammatory signaling cascade; IL-6/JAK1/STAT3; by cinnamaldehyde could be a novel and promising therapeutic approach against BPH.

Topics: Acrolein; Animals; Biomarkers; Cell Proliferation; Cyclin D1; Gene Expression Regulation; Immunohistochemistry; Interleukin-6; Janus Kinase 1; Male; Prostate; Prostatic Hyperplasia; Rats; RNA, Messenger; STAT3 Transcription Factor; Uric Acid; Xanthine Oxidase

To observe the effects of Cinnamyl aldehyde (CA) on NIH3T3 cell cycle and explore the possible mechanism further.. Flowcytometry was used for observing cell cycle distribution. Expressions of proliferation cell nuclear antigen (PCNA) and Cyclin D1 protein in NIH3T3 cells were assessed by immunocytochemistry.. After culture with CA for 24 hours, the percentage of populations of S phase was enhanced by 3% (P < 0.05) and cell proliferation index (PrI, S + G2/M) was increased by 3.5% (P < 0.01) , but G2/M phase had no obvious changes. The expressions of Cyclin D1 and PCNA proteins were improved markly by CA compared with controlgroup (P < 0.01).. CA could promote more cells in G0/G1 phase into S phase, which may be related to the regulation of the expressions of PCNA and Cyclin D1.

Topics: Acrolein; Animals; Cell Cycle; Cell Proliferation; Cinnamomum; Cyclin D1; Flow Cytometry; Immunohistochemistry; Mice; NIH 3T3 Cells; Plants, Medicinal; Proliferating Cell Nuclear Antigen; S Phase