Glycyrrhizin, the main active compound in licorice, attenuates pro-inflammatory responses by interfering with membrane-dependent receptor signaling.

Biochem J. 2009 May 14; Schröfelbauer B, Raffetseder J, Hauner M, Wolkerstorfer A, Ernst W, Szolar OHThe triterpene glycoside glycyrrhizin (GL) is the main active compound in licorice. It is used as a herbal medicine owing to its anti-cancer, anti-viral, and anti-inflammatory properties. Its mode of action however remains widely unknown. In this study, we aimed to elucidate the molecular mechanism of GL in attenuating inflammatory responses in macrophages. Using microarray analysis, we found that GL caused a broad block in the induction of pro-inflammatory mediators induced by the toll-like receptor 9 (TLR9) agonist CpG-DNA in RAW 264.7 cells. Furthermore, we found that GL also strongly attenuated inflammatory responses induced by TLR3 and TLR4 ligands. The inhibition was accompanied by reduced activation not only of the NF-kappaB pathway but also of the parallel MAPKs signaling cascade upon stimulation with TLR9 and TLR4 agonists. Further analysis of upstream events revealed that GL treatment reduced cellular attachment and/or uptake of CpG-DNA and strongly impaired TLR4 internalization. Moreover, we found that the anti-inflammatory effects were specific for membrane-dependent receptormediated stimuli, as GL was ineffective in blocking Tnfa induction upon stimulation with phorbol myristate acetate (PMA), a receptor and membrane-independent stimulus. These observations suggest that the broad anti-inflammatory activity of GL is mediated by the interaction with the lipid bilayer thereby attenuating receptor-mediated signaling.

Effects of Bambusae caulis in Liquamen on the development of atopic dermatitis-like skin lesions in hairless mice.

J Ethnopharmacol. 2009 Jun 22; 123(2): 195-200Qi XF, Kim DH, Yoon YS, Li JH, Jin D, Deung YK, Lee KJETHNOPHARMACOLOGICAL RELEVANCE: Bambusae caulis in Liquamen (BCL) is a nutritious liquid extracted from heat-treated fresh bamboo stems. It is an important traditional herbal medicine used to treat coughs and asthma in East Asia. In recent years, it has been studied for its anti-inflammatory, anti-allergenic, and immune-regulating properties. AIM OF THE STUDY: To examine whether BCL suppresses the development of 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in hairless mice. MATERIALS AND METHODS: The effects of BCL were analyzed by measuring transepidermal water loss (TEWL), melanin content, and erythema in the skin, leukocyte numbers and IgE levels in the serum, and mRNA expression of relevant cytokines in the spleen. RESULTS: The transdermal administration of BCL to hairless mice inhibited the development of DNCB-induced AD-like skin lesions by suppressing TEWL, melanin production and erythema of skin, the number of leukocytes and the level of IgE in serum, and the mRNA expression of IL-4, IL-13, and TNF-alpha in the spleen. However, BCL administration increased the expression of IFN-gamma in the spleen. CONCLUSIONS: These findings indicate that BCL suppresses the development of DNCB-induced AD-like skin lesions in hairless mice, suggesting that BCL may be a potential therapeutic agent for AD in a clinical setting.

Chrysanthemum indicum Linné extract inhibits the inflammatory response by suppressing NF-kappaB and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophages.

J Ethnopharmacol. 2009 Apr 21; 122(3): 473-7Cheon MS, Yoon T, Lee do Y, Choi G, Moon BC, Lee AY, Choo BK, Kim HKAIMS OF STUDY: Although the flowers of Chrysanthemum indicum Linné (Asteraceae) have long been used in traditional Korean and Chinese medicine to treat inflammatory diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. We investigated the effects of a 70% ethanolic extract of C. indicum (CIE) on the activities of cellular signaling molecules that mediate inflammatory responses. MATERIALS AND METHODS: Production of NO, PGE(2), TNF-alpha, and IL-1beta by ELISA, mRNA and protein expression of iNOS and COX-2, phosphorylation of MAPKs, and activation of NF-kappaB by RT-PCR and Western blotting were examined in LPS-induced RAW 264.7 macrophages. RESULTS: The CIE strongly inhibited NO, PGE(2), TNF-alpha, and IL-1beta production, and also significantly inhibited mRNA and protein expression of iNOS and COX-2 in LPS-induced RAW 264.7 macrophages, in a dose-dependent manner. Furthermore, the CIE clearly suppressed nuclear translocation of NF-kappaB p65 subunits, which correlated with an inhibitory effect on IkappaBalpha phosphorylation. The CIE also attenuated the activation of ERK1/2 and JNK in a dose-dependent manner. CONCLUSION: Our results suggest that the anti-inflammatory properties of CIE might result from the inhibition of inflammatory mediators, such as NO, PGE(2), TNF-alpha, and IL-1beta, via suppression of MAPKs and NF-kappaB-dependent pathways.

Effects of Kang-Jia-Wan, a Chinese medicinal herb officinal, on apoptosis induction in goiter of rats.

J Ethnopharmacol. 2009 Apr 21; 122(3): 533-40Han Y, Gao L, Sun N, Zhang J, Zhang W, Zhou X, Zhang H, Zhao JETHNOPHARMACOLOGICAL RELEVANCE: Kang-Jia-Wan (KJW), a traditional Chinese herbal medicine, is widely used to treat goiter in the clinics in China. AIM: The mechanisms by which KJW treats goiter are unclear. It is known that insufficient apoptosis of thyrocytes is involved in the formation of goiter. Here, we investigated whether KJW could induce apoptosis in goiter of rats given methimazole (MMI). MATERIALS AND METHODS: Fifty-six Wistar rats were randomly separated into four groups: normal, MMI, MMI+low-dose KJW and MMI+hig h-dose KJW. Except for the normal group (20 rats), all groups (each with 12 rats) were given 0.04% (w/v) MMI in their drinking water. One week later, the rats in MMI+low- and high-dose KJW groups were orally supplemented with KJW at 250 mg/kg d(-1) and 1000 mg/kg d(-1), respectively. RESULTS: After KJW treatment for 12 weeks, the relative thyroid weight (mg/100g body weight) of the MMI+high-dose KJW group decreased significantly. Features of apoptosis were also apparent in thyroid tissues of rats given KJW treatment. Importantly, KJW markedly increased the caspase-3 and Fas protein expression, in a dose-dependent manner, in the thyroid specimens. CONCLUSIONS: These results showed that KJW played a therapeutic role via apoptosis induction in the goitrous glands.