Background and purpose: Glycyrrhizae radix has been widely used as a cytoprotective, plant-derived medicine. We have identified a flavanoid, liquiritigenin, as an active component in extracts of Glycyrrhizae radix. This research investigated the effects of liquiritigenin on the induction of inducible NOS (iNOS) and proinflammatory cytokines by lipopolysaccharide (LPS) in Raw264.7 cells, and on paw oedema in rats. Experimental approach: iNOS expression was determined by western blotting, real-time reverse transcription-PCR and reporter gene analyses. Tumour necrosis factor-a (TNF-a), interleukin (IL)-1b and IL-6 were assayed by ELISA. Gel shift assay and immunoblotting were used to assess NF-kB activation. The effect of liquiritigenin on acute inflammation in vivo was evaluated using carrageenan-induced paw oedema. Key results: Treatment of Raw264.7 cells with liquiritigenin caused inhibition of LPS-induced NF-kB DNA binding activity, due to repression of I-kBa phosphorylation and degradation. Liquiritigenin treatment prevented LPS from increasing the levels of iNOS protein and mRNA in a concentration-dependent manner. Liquiritigenin also suppressed the production of TNF-a, IL-1b and IL-6 from Raw264.7 cells after LPS. In rats, liquiritigenin treatment inhibited formation of paw oedema induced by carrageenan. Conclusion and implications:These results demonstrate that liquiritigenin exerts anti-inflammatory effects, which results from the inhibition of NF-kB activation in macrophages, thereby decreasing production of iNOS and proinflammatory cytokines. Our findings showing inhibition by liquiritigenin of paw oedema as well as inflammatory gene induction will help to understand the pharmacology and mode of action of liquiritigenin, and of the anti-inflammatory use of Glycyrrhizae radix.

Cytoprotective effects of liquiritigenin (LQ) against liver injuries have been reported, but its pharmacokinetics has not been studied in acute hepatitis. Thus, pharmacokinetics of LQ and its two conjugated glucuronide metabolites: 4'-O-glucuronide (M1) and 7-O-glucuronide (M2), in rats with acute hepatitis induced by d-galactosamine/lipopolysaccharide (GalN/LPS) rats or carbon tetrachloride-treated (CCl(4)-treated) rats were evaluated. LQ was administered intravenously (20 mg kg(-1)) and orally (50 mg kg(-1)) to control GalN/LPS and CCl(4)-treated rats. Expression of uridine 5'-diphospho-glucuronosyltransferases 1A (UGT1A) and in vitro metabolism of LQ in hepatic and intestinal microsomes were also measured. After intravenous administration of LQ, area under the plasma concentration-time curve (AUC) of LQ in GalN/LPS rats was significantly smaller than that in controls due to faster non-renal clearance, as a result of its greater free fraction in plasma and faster hepatic blood flow rate than the controls. In CCl(4)-treated rats, the AUC(M1, 0-8 h)/AUC(LQ) and AUC(M2, 0-8 h)/AUC(LQ) ratios were significantly greater than the controls due to decrease in biliary excretion of M1 and M2. However, no significant pharmacokinetic changes were observed in both acute hepatitis rats after oral administration due to comparable intestinal metabolism of LQ. Modification of oral dosage regimen of LQ may not be necessary in patients with acute hepatitis; but human studies are required.

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Bronchial compression as a result of lung herniation after pneumonectomy pulmonary function loss due to pneumonectomy using "'Xe radiospirometry. Chest 1972;62:694-8. Gross examination of the resected lobe showed diffuse honeycombing, especially in the subpleural areas of the lung. There were also two separate masses within the honeycomb area, measuring when fixed 3-0 x 15 x 15cm and 12 x 10 x 0-5 ci. The larger one had a granular cut surface and

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Microspheres are typically used for long-acting injectable formulation, but often the injection site reactions are reported as side effects. This can reduce patient compliance with medication despite the benefit of reducing the number of administrations. Side effects at the injection site are mostly derived from inflammatory reactions. Therefore, it is necessary to minimize inflammatory reactions for the successful development of long-acting diabetes treatments, including GLP-1 receptor agonists. The purpose of this study is to evaluate the injection site reaction in the placebo, semaglutide and tirzepatide microspheres manufactured using the conventional microsphere technology and to investigate the injection site reaction improvement in the placebo, semaglutide and tirzepatide microspheres manufactured using novel technology by adding anti-inflammatory agent, dexamethasone. Skin samples were collected from the injection site of SD rats on days 3 and 8 after the administration of microspheres with or without dexamethasone. The collected skin was stained with H&E to determine infiltration of inflammatory cells, angiogenesis, and fibrosis and was graded. When microspheres manufactured using the conventional method were subcutaneously administered to rats, infiltration of inflammatory cells and fibrous tissue formation occurred on both days 3 and 8. Higher dexamethasone content in the microsphere showed a tendency for the lesser occurrence of inflammation and greater anti-inflammatory effect in the test group. Surprisingly, improvement in the injection site reaction for microspheres containing dexamethasone was observed even at systemic dexamethasone concentrations much lower than the therapeutic level. In conclusion, this novel microsphere containing a small amount of dexamethasone shows potential for the development of a long-acting GLP-1 microsphere injectable for diabetes treatment with reduced injection site reaction. Disclosure Y. Kim: None. E. Seol: None. Funding Ministry of Health & Welfare, Republic of Korea (HI21C1732)