forsythiaside and Pneumonia

The off-label nebulization of Shuang-Huang-Lian (SHL) injection is often utilized to treat respiratory tract infections in China. However, the pulmonary biopharmaceutics of SHL was generally unknown, limiting the rational selection of therapeutic dose and dose frequency.. To characterize the size distribution of nebulized aerosols and to compare the pharmacokinetics and the lung distribution of three chemical makers of SHL, chlorogenic acid (CHA), forsythiaside A (FTA) and baicalin (BC), after intratracheal and intravenous administration of SHL to rats.. The droplet size distribution profiles over nebulization process were dynamically monitored using a laser diffraction method whereas the levels of CHA, FTA and BC in plasma, lung tissues and bronchoalveolar lavage fluids (BALF) were determined by a validated LC-MS/MS assay. The pulmonary anti-inflammatory efficacy was evaluated using a lipopolysaccharide (LPS) induced lung inflammation model as indicated by the level of tumor necrosis factor-α (TNF-α) in BALF.. The nebulization of SHL showed good inhalability and allowed the aerosols to reach the upper or lower respiratory tract dependent on the performance of selected nebulizers. Following intratracheal administration of SHL at different doses, CHA, FTA and BC were absorbed into the bloodstream with the mean absorption time being 67.5, 63.5 and 114 min, respectively, rendering mean absolute bioavailabilities between 42.4% and 61.4% roughly independent of delivered dose. Relative to the intravenous injection, the intrapulmonary delivery increased the lung-to-plasma concentration ratios of CHA, FTA and BC by more than 100 folds and markedly improved the lung availability by 563-676 folds, leading to enhanced and prolonged lung retention. The production of TNF-α in BALF was decreased by ~50% at an intratracheal dose of 125 μL/kg SHL to LPS-treated mice.. The nebulization delivery of SHL is a promising alternative to the intravenous injection for the treatment of respiratory tract infections.

Topics: Administration, Inhalation; Administration, Intravenous; Animals; Anti-Inflammatory Agents; Biological Availability; Bronchoalveolar Lavage Fluid; Chlorogenic Acid; Drugs, Chinese Herbal; Flavonoids; Glycosides; Lipopolysaccharides; Lung; Male; Mice, Inbred BALB C; Nebulizers and Vaporizers; Pneumonia; Rats, Wistar; Tumor Necrosis Factor-alpha

Cigarette smoke has been reported to be the major cause of chronic obstructive pulmonary disease (COPD). It causes persistent inflammation by regulating the redox-sensitive pathways. Forsythiaside, an active constituent isolated from the Chinese medicinal herb Forsythia suspensa, has been reported to have anti-inflammatory and anti-oxidant effects. Thus, in this study, we investigated the protective effects of forsythiaside against cigarette smoke-induced lung inflammation in mice. COPD mice model was established by cigarette smoke. Forsythiaside was given 2h before cigarette smoke exposure for five consecutive days. Bronchoalveolar lavage fluid and lung tissues were collected to assess pathological changes, lipid peroxidation, inflammatory cytokine production, Nrf-2, and NF-κB expression. Our results showed that forsythiaside attenuated the infiltration of inflammatory cells, NO and inflammatory cytokines TNF-α, IL-6 and IL-1β production, and reversed the CS-induced decrease of glutathione/glutathione disulfide (GSH/GSSG) ratio. Western blot analysis showed that forsythiaside inhibited cigarette smoke-induced NF-κB activation. In addition, forsythiaside dose-dependently up-regulated the expression of Nrf2 and HO-1. In conclusion, forsythiaside protected against cigarette smoke-induced lung injury through activating Nrf2 and inhibiting NF-κB signaling pathway.

Topics: Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Cell Count; Cytokines; Glycosides; Heme Oxygenase-1; Lung; Male; Membrane Proteins; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Nicotiana; Nitric Oxide; Pneumonia; Smoke; Spirometry