Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line

Abstract

Glycyrrhizin (GL) is known to have various immunomodulating activities and has long been used clinically as an anti-allergic and anti-hepatitis agent. While the potency of GL against lung inflammatory diseases has been expected, the effect of GL on the lung has been poorly understood. Lung fibroblasts are known as a potent producer of inflammatory chemokines, IL-8 and eotaxin 1, by which neutrophils and eosinophils are strongly attracted during inflammation. Therefore, we studied the effects of GL on the production of these chemokines using a human fetal lung fibroblast cell line, HFL-1, stimulated with TNF-alpha and IL-4. Moreover, we examined the structure-activity relationships of GL to explore more beneficial compounds. 18alpha,beta-GL inhibited IL-8 dose-dependently and inhibited eotaxin 1 slightly. 18alpha,beta-Glycyrrhetic acid (GA) did not inhibit IL-8 but inhibited eotaxin 1. The effect of 18alpha,beta-glycyrrhetic acid monoglucuronide (MGA) resembled that of 18alpha,beta-GL but was weaker. Both 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-11-deoxo-olean-12-en-30-oic acid (11-deoxo-GL) and 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-olean-11,13,(18)-dien-30-oic acid (hetero-GL) exhibited inhibitory activity with significant cytotoxicity. 3beta-[(2-O-beta-D-Glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-olean-9,12-dien-30-oic acid (homo-GL) did not have cytotoxicity but its activity was mild like that of 18alpha,beta-GL. 3beta-[(2-O-beta-d-Glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol (hetero-30-OH-GL) and 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-olean-9,12-dien-30-ol (homo-30-OH-GL) showed potent inhibitory effects, at concentrations lower than 18alpha,beta-GL with no significant cytotoxicity. These results suggest that GL-related compounds are effective in reducing chemokine production and that GL-modified compounds including hetero-30-OH-GL and homo-30-OH-GL appear most beneficial in view of their inhibitory capacity with less cytotoxicity.

Juzen-taiho-to, an Herbal Medicine, Activates and Enhances Phagocytosis in Microglia/Macrophages

“…These findings support our previous finding that JTT administration diminished the senile plaque in AD transgenic mouse, which might be due to the enhanced phagocytosis of Aβ by microglia, and the phagocytosis-enhancing effect of JTT might not be accompanied by excessive inflammatoty mediators' production. This is also consistent with the previous reports showing the anti-inflammatory and anti-oxidative activities of the components of JTT Matsui et al 2004). These findings suggest that JTT administration would be a potential therapeutic or preventive approach for AD.…”

“…For example, ginsenoside Rh1 has anti-allergic and anti-inflammatory activities (Park et al 2004); glycyrrhizin extracted from Glycyrrhizae Radix and the extracts of Astragali Radix have anti-inflammatory activities (Shon and Nam 2003;Matsui et al 2004); the extracts from Ginseng Radix, Cinnamomi Cortex, Glycyrrhizae Radix, Radix Paeoniae, and Astragali Radix have anti-oxidative activities (Dhuley 1999;Baltina 2003;Keum et al 2003;Lee et al 2003;Wang et al 2003). Furthermore, recent studies demonstrated that ginsenosides Rg3 and Rh2 inhibited the production of nitric oxide (NO), iNOS and pro-inflammatory cytokines TNF-α , IL-1β in activated microglia (Bae et al 2006).…”

Glycyrrhizic acid nanoparticles inhibit LPS-induced inflammatory mediators in 264.7 mouse macrophages compared with unprocessed glycyrrhizic acid

“…1 Its main components are considered to be the triterpene saponins glycyrrhizin and GA. [18][19][20] Nanomaterials are important materials due to their unique physical and chemical properties. 21 Due to accumulation of nanoparticles in the cell by enhanced permeability and retention effect, nanoparticles achieve new biological properties.…”

Niosomes: a review of their structure, properties, methods of preparation, and medical applications

“…Extracts of G. glabra are purported to be useful in the treatment of dermatitis, eczema, and psoriasis [85,86]. The plant's active compound, ammonium glycyrrhizinate, showed strong anti-inflammatory effects in various models [87,88]. When ammonium glycyrrhizinate was encapsulated in niosomes prepared by using Tween 85, Span 20, and cholesterol in various molar ratios, improved anti-inflammatory activities were observed in chemically induced skin erythema in mice and humans [89].…”