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This study aimed to explore the protective effects of madecassoside (Mad), a triterpenoid saponin isolated from Centella asiatica herbs, on experimental pulmonary fibrosis (PF) and underlying mechanisms. PF model was established in mice by endotracheal instillation with bleomycin (5 mg/kg). Mice were orally administered with Mad (10, 20, 40 mg/kg) and prednisone (5 mg/kg) for 7 or 21 days. Mad (20, 40 mg/kg) significantly improved lung pathological changes and reduced collagen deposition. In the aspect of collagen synthesis, Mad (20, 40 mg/kg) reduced the expressions of α-smooth muscle actin and transforming growth factor-β1 (TGF-β1), and inhibited the phosphorylations of Smad2 and Smad3 in the lung tissues. However, in vitro, Mad showed little effect on TGF-β1-induced phosphorylation of either Smad2 or Smad3 in primary mouse lung fibroblasts. Moreover, Mad (20, 40 mg/kg) attenuated oxidative damage and inflammation presented at the early stage of PF, evidenced by reduced total leukocytes in the bronchoalveolar lavage fluid, decreased myeloperoxidase activity and malondialdehyde level, and increased super-oxide dismutase activity and glutathione level in lung tissues. On the other hand, Mad (40 mg/kg) elevated the matrix metalloproteinase 1/tissue inhibitor of metalloproteinase 1 ratio in lung tissues of PF mice mainly by downregulating tissue inhibitor of metalloproteinase 1 expression. The present study demonstrated that Mad can ameliorate PF by preventing the deposition of extracellular matrix, which might be achieved mainly through attenuating inflammation and oxidative stress and consequent TGF-β1 overexpression.

Abstract. Inflammation serves an important role in inducing secondary injury following intracerebral hemorrhage (ICH).It has been demonstrated that sparstolonin B (SsnB) is able to attenuate the lipopolysaccharide-induced inflammatory response in sepsis. Mouse ICH models were used to explore the efficacy of SsnB on the ICH-induced inflammatory response. Mice underwent a working memory version of Morris water maze (MWM) test. They underwent 5 successive days of training consisting of 4 trials each day. The ICH model was established on the last training day. Mice were injected intraperitoneally either with vehicle or SsnB once a day for 3 consecutive days following the establishment of the ICH model. The MWM was used to determine the effect of SsnB on short-term memory following ICH. Neurological deficit scores and brain water content were measured following the MWM. Furthermore, the expression of inflammatory factors and signaling molecules downstream of TLR4 were measured. The results demonstrated that 5 mg/kg SsnB significantly improved the MWM path and time latency (P<0.05). Furthermore, neurological deficit scores were decreased in SsnB-treated mice compared with vehicle-treated mice (P<0.01). Brain water content, levels of inflammatory cytokines and the expression of inflammation-associated proteins were also significantly reduced in the SsnB-treated group (P<0.05). These results indicate that SsnB treatment stimulates short-term neurobehavioral recovery and reduces neurological deficits and this may inhibit the inflammatory response. Therefore, SsnB may attenuate the inflammatory response following ICH.

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