Anti-Inflammatory Activity of Sugiol, A Diterpene Isolated fromCalocedrus formosanaBark

Abstract

Sugiol is a diterpene which was isolated and purified from alcohol extracts of the bark of Calocedrus formosana Florin (Cupressaceae). Although sugiol has low inhibitory activity against the DPPH radical, it could effectively reduce intracellular reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-stimulated macrophages. The present study investigated the potential anti-inflammatory activity of sugiol, and the relationship between signal transduction and inflammatory cytokines in vitro. A dose of 30 microM of sugiol was effectively inhibitory for proIL-1beta, IL-1beta and TNF-alpha production, suggesting that sugiol is bioactive against inflammation. Moreover, sugiol reveals a capacity for suppressing the activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) activated by LPS-stimulation in J774A.1 murine macrophages. A low dosage of 10 microM of sugiol completely inhibited ERK1/2 phosphorylation, while 30 microM effectively inhibited JNK1/2 and p38 phosphorylation in LPS-stimulated macrophages. In addition, sugiol significantly inhibited LPS-induced ROS production. Our studies suggest that sugiol's efficacy in inhibiting the inflammatory cytokines of IL-1beta and TNF-alpha could be attributed to a reduction of the ROS that leads to a decrease in the phosphorylation of MAPKs.

Recent developments in anti‐inflammatory natural products

“…88 Sugiol (44), a diterpene from Calocedrus formosana bark was reported to inhibit ROS, pro-IL-1b, IL-1b, and TNF-a production and suppressed the activation of MAPKs, including extracellular signalregulated kinase (ERK), JNK, and p38 in stimulated J774A.1 murine macrophages. 89 Triptolide (45) and tripdiolide (46), diterpene epoxides isolated from Tripterigium wilfordii, down-regulated the COX-2, iNOS, and IL-1b gene expression in LPS-stimulated macrophages. 90 Clinical studies have been performed on the extract of T. wilfordii and substantial work has been reported on triptolide and celastrol (47) (Fig.…”

Diterpenes from Cryptomeria japonica Inhibit Androgen Receptor Transcriptional Activity in Prostate Cancer Cells

“…Most known naturally occurring abietane-type diterpenes have been extracted and identified from species like C. japonica, Taiwania cryptomerioides, Thuja standishii, Juniperus formosana, Cephalotaxus harringtonia, and Vitex rotundifolia [16], [17]. In conclusion, we identified 7 diterpenes from the conifer C. japonica with anti-androgenic effects on PCa 22Rv1-derived 103E cells.…”

“…Despite the high resemblance in chemical conformations of these diterpenes, their dramatic differ- ences in AR inhibition may provide a structure-activity relationship (SAR) for future studies. Compounds 3 and 4 have frequently been reported to have antimicrobial, antiproliferative and cytotoxicity activities [17], [18], [19]. However, compound 2 has only been reported to have antimicrobial activity, and compound 7 has no known biological effects [19].…”

Sugiol inhibits STAT3 activity via regulation of transketolase and ROS-mediated ERK activation in DU145 prostate carcinoma cells

“…Our previous study reported that sugiol exhibits very weak antitumor activity against SW620 (colon), MDA-MB-231 (breast) and NCI-H23 (lung) cells [23]. Many studies investigated the biological activities of sugiol, including its modest anti-tumor [24], anti-inflammatory [25], antimicrobial [26] and aldose reductase inhibitory activities [27], its specific mechanism of action is not known.…”