Carnosol Modulates Th17 Cell Differentiation and Microglial Switch in Experimental Autoimmune Encephalomyelitis

Abstract

Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35–55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and reduced demyelination. Further, carnosol inhibited Th17 cell differentiation and signal transducer and activator of transcription 3 phosphorylation, and blocked transcription factor NF-κB nuclear translocation. In the passive-EAE model, carnosol treatment also significantly prevented Th17 cell pathogenicity. Moreover, carnosol exerted its therapeutic effects in the chronic stage of EAE, and, remarkably, switched the phenotypes of infiltrated macrophage/microglia. Taken together, our results show that carnosol has enormous potential for development as a therapeutic agent for autoimmune diseases such as MS.

Carnosol inhibits inflammasome activation by directly targeting HSP90 to treat inflammasome-mediated diseases

“…Previous studies have demonstrated that carnosol targets the NF-κB signaling pathway 40,59,60 , and our data showed that carnosol indeed inhibited NF-κB-mediated pro-IL-1β expression and IL-6 production in BMDMs treated with carnosol before LPS stimulating, indicating it could also prevent the inflammasome priming if added prior to the priming signal. Moreover, carnosol had no effect on expression of pro-IL-1β and IL-6 in BMDMs treated with carnosol after LPS stimulating, suggesting that carnosol can inhibit the priming stage but also plays a role in NLRP3 inflammasome activation step.…”

“…These results revealed that carnosol inhibits NLRC4 inflammasome activation but has no effect on AIM2 inflammasome activation. Previous studies have shown that carnosol disrupts the activation of the NF-κB signaling pathway, which largely controls NLRs and pro-IL-1β expression 40,48 . Our study revealed that when BMDMs were first treated with carnosol for 1 h and then stimulated with LPS for 4 h, carnosol treatment inhibited the expression of pro-IL-1β, TNF-α, and IL-6 in BMDMs (Fig.…”

“…Polyphenols extracted from rosemary exhibit strong antioxidant activity, and carnosol and carnosic acid account for~90% of this antioxidant activity 38,39 . Carnosol has previously been shown to exhibit anti-inflammatory activity and prevent the activation of various inflammatory signaling pathways, such as the NF-κB and mitogen-activated protein kinase (MAPK) 40 pathways. Therefore, carnosol is considered to be promising anti-inflammatory agent.…”

Rosmarinic acid attenuates inflammation in experimentally induced arthritis in Wistar rats, using Freund’s complete adjuvant

“…This confirms that the activity of Punica granatum is due to the presence of active constituents like rosmarinic acid. Rosmarinic acid is also known to produce its activity due to its anti‐oxidative properties . The antioxidant effect of isolated compound was also investigated by analysis of various biochemical parameters, that is GSH, SOD, MDA and TNF‐α.…”

Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota

“…EAE was induced according to our previous study. 19 , 20 EAE mice were randomly divided into two treatment groups, 100 mg/kg PPE or solvent (PBS) were applied daily via oral gavage, at the first day of immunization, onset of disease (10 d), and peak of disease (16 d). After immunization, mice were assessed clinically in a blinded manner using a disease severity scale that is scored according to a 0–5 scale as described previously.…”