Oral administration of geraniol ameliorates acute experimental murine colitis by inhibiting pro-inflammatory cytokines and NF-κB signaling

Abstract

Ulcerative colitis is associated with a considerable reduction in the quality of life of patients. The use of phyto-ingredients is becoming an increasingly attractive approach for the management of colitis. Geraniol is a monoterpene with anti-inflammatory and antioxidative properties. In this study, we investigated the therapeutic potential of geraniol as a complementary and alternative medicine against dextran sulphate sodium (DSS)-induced ulcerative colitis in mice. Disease activity indices (DAI) comprising body weight loss, presence of occult blood and stool consistency were assessed for evaluation of colitis symptoms. Intestinal damage was assessed by evaluating colon length and its histology. Pre-treatment with geraniol significantly reduced the DAI score, improved stool consistency (without occult blood) and increased the colon length. The amount of pro-inflammatory cytokines, specifically TNF-α, IL-1β and IL-6 and the activity of myeloperoxidase in colon tissue were significantly decreased in geraniol pre-treated mice. Western blot analyses revealed that geraniol interfered with NF-κB signaling by inhibiting NF-κB (p65)-DNA binding, and IκBα phosphorylation, degradation and subsequent increase in nuclear translocation. Moreover, the expressions of downstream target pro-inflammatory enzymes such as iNOS and COX-2 were significantly reduced by geraniol. Pre-treatment with geraniol also restored the DSS-induced decline in antioxidant parameters such as reduced glutathione and superoxide dismutase activity and attenuated the increase in lipid peroxidation marker, thiobarbituric acid reactive substances and nitrative stress marker, nitrites in colon tissue. Thus, our results suggest that geraniol is a potential therapeutic agent for inflammatory bowel disease.

Medicinal Plants in the Treatment of Colitis: Evidence from Preclinical Studies

“…It also modulated the expression of caspase-3, intercellular adhesion molecule-1, and glycogen synthase kinase-3β as well as the β-catenin, p38 MAPK, NF-κB, and peroxisome proliferator-activated receptor γ signaling pathways in the same way as did sulfasalazine [92]. In addition, treatment with geraniol reversed DSS-induced inflammation and oxidative alterations [93]. However, no study has investigated the effect of citronellal on colitis.…”

Pharmacological Properties of Geraniol – A Review

“…Pretreatment with GE showed an inhibitory effect on the amount of proinflammatory cytokines and the activity of myeloperoxidase in colon tissue. GE downregulated the expression of downstream target proinflammatory enzymes but upregulated antioxidant molecules: GSH and superoxide dismutase activity were suppressed and LPO and nitrites increases were prevented [36].…”

Monoterpenes modulating cytokines - A review

“…The present review also suggested that higher oral doses and enema administration of Ge-OH strongly reduces dysbiosis and systemic inflammation in dextran sulfate sodium-treated mice by significantly decreasing plasma levels of IL-1β, IL-17, IFN-γ, and TNF-α (De Fazio et al, 2016). Also, oral administration of geraniol at doses of 50 and 100 mg/kg body weight ameliorates acute experimental murine colitis by inhibiting the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 and NF-κB signaling (Medicherla et al, 2015).…”