Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation

Abstract

Ginger, as a food spice, is widely applied due to its extensive effects. Cedrol (CE) found in ginger is a sesquiterpene with anti-inflammatory activity. The objective of this research is to discuss the efficacy of CE on ameliorating rheumatoid arthritis (RA). CE inhibited chronic inflammation and pain in a dose-dependent manner accompanied by rapid onset and long duration. Besides, CE treatment effectively ameliorated the paw edema volume and arthritis score with no significant effect on body weight. Organ index, T-cell and B-cell proliferation, histopathology, and immunohistochemistry demonstrated that CE had immunological enhancement and attenuated RA effects. Remarkably, inhibition of phosphorylated-JAK3 protein, thereby abating the secretion of pro-inflammatory cytokines and inflammation-related mediators, was involved in the potential mechanism of CE efficiency through forming a hydrogen bond with ARG953 and ILE955 in the JAK3 active pocket. At the same time, the pharmacokinetic results showed that the absolute bioavailability of CE at 20, 40, and 80 mg/kg was 30.30, 23.68, and 16.11%, respectively. The current results offered clues for mastering the ameliorated RA of CE and further perfected the effective substance basis on the antiinflammatory effect of ginger, which was beneficial for further applications.

Nutrients and rheumatoid arthritis: From the perspective of neutrophils

“…Cedrol, which can be found in ginger, was also considered able to attenuate inflammation in RA. It was verified by animal models that cedrol could inhibit the phosphorylation of JAK3 protein, thus inhibiting the secretion of pro-inflammatory cytokines, and decreasing the neutrophil count (75).…”

Stereochemical editing logic powered by the epimerization of unactivated tertiary stereocenters

“…We next examined the application of stereoediting as a late-stage diversification strategy. Cedrol is an important fragrance compound, and molecules that contain the cedrane scaffold have shown activity in diverse biological settings ( 30 , 31 ). Studies of structurally related C-7 cedrane epimers have not yet been reported.…”

Innate Immunomodulatory Activity of Cedrol, a Component of Essential Oils Isolated from Juniperus Species

“…Cedrol has been reported to exhibit a number of biological activities, including anticancer [92][93][94] and anti-inflammatory. For example, cedrol was shown to have analgesic and anti-inflammatory effects in complete Freund's adjuvant (CFA)-induced arthritis in rats [95] and in mice with collagen-induced arthritis (CIA) [96]. This sesquiterpene also attenuated neuropathic pain in chronic constriction injury of rats by inhibiting the inflammatory response [97].…”