Effects of glycyrrhizic acid and 18β-glycyrrhetinic acid on LPS-induced acute lung injury and their protective roles on Cisplatin-induced nephrotoxicity in BALB/c mice

• Main Authors: An-Zhi Chen, 陳峖覟
• Other Authors: 顏國欽
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/hfk585

碩士 === 國立中興大學 === 食品暨應用生物科技學系所 === 101 === Abstract Licorice (Glycyrrhiza) species are perennial herbaceous Leguminosae plant, as traditional herbal medicine, and widely distributed in Inner Mongolia, Xinjiang and the Northeast of China. The pharmacological activities sush as antimicrobial, antioxidative, antiinflammatory, respiratory protective and renoprotective effects of licorice are mainly represented by main triterpenoid saponins, glycyrrhizic acid (GA) and its metabolite 18β-glycyrrhetinic acid (18βGA). Two kinds of animal model were used to evaluate the protective effects of lipopolysaccharide (LPS)-induced inflammation in lungs and chemical-induced renal toxicity. (A) The effects of GA and 18βGA on LPS-induced acute lung injury in BALB/c mice. (B) The protective roles of GA and 18βGA on cisplatin (CP)-induced nephrotoxicity in BALB/c mice. The protective effects of GA and 18βGA on LPS-induced acute lung injury (ALI) in BALB/c mice were evaluated. The effects of GA and 18βGA on phagocytosis in RAW264.7 cells were also evaluated. Results showed that GA and 18βGA had no effects on tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β levels and neutrophil infiltration in mice airway. GA and 18βGA showed great potentials on upregulating activities of catalase, superoxide dismutase (SOD), glutathione reductase (GRd) and glutathione S-transferase (GST) which were inhibited by LPS treatment in mice lungs (p < 0.05). GA and 18βGA could promote phagocytic activity at 0.2 – 25 μM (p < 0.05) in RAW264.7 cells, but inhibit phagocytic activity above 50 μM. Taking together, neither GA nor 18βGA could inhibit inflammation, but GA and 18βGA would increase the activities of antioxidant enzymes and phagocytosis in order to remove the pathogenic materials and prevent further tissue damage. Based on the properties, GA and 18βGA could improve oxidative damages through enhancement of antioxidant system. Therefore, this study also discussed the protective roles of GA and 18βGA on CP-induced nephrotoxicity. Results showed that pretreatment with GA or 18βGA significantly attenuated the CP-induced parameters such as serum blood urea nitrogen (BUN), creatinine and lactate dehydrogenase (LDH) (p < 0.05). The histopathological examinations also revealed the improvement of renal tubular necrosis, obstructive and degeneration by GA or 18βGA treatment. Moreover, GA and 18βGA prevented oxidative stress through significantly restoring the levels of antioxidant enzyme activities such as catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRd), glutathione S-transferase (GST) and GSH/GSSG ratio, and decreasing lipid peroxidation marker malondialdehyde (MDA) in kidney tissues (p < 0.05). In addition, immunohistochemical examinations revealed that the expressions of pro-inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), TNF-α, IL-1β, IL-6 and high-mobility group box 1 protein (HMGB1) were suppressed by GA or 18βGA treatment. The expressions of renal nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) were up-regulated by GA or 18βGA treatment in CP-induced mice. Taking together, GA and 18βGA might be a potent protective agents through upregulation of protective proteins and antioxidant enzyme activities, which againsts renal oxidative and inflammatory damages caused by cisplatin. In summary, these results confirmed that GA and 18βGA can enhance the immune response and through the activation of antioxidant defense system effectively, leading to avoid biological and chemical tissue damages. The results can be used in the development of funtional food and clinical application. Keyword: glycyrrhizic acid, 18β-glycyrrhetinic acid, lipopolysaccharide, cisplatin, antioxidant