Andrographolide Attenuates Inflammation Due to Intra-Abdominal Sepsis by Enhancing Bacterial Clearance in Mice

Purpose: Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or septic shock have a high mortality rate of 30– 50%. Therefore, novel strategies to treat sepsis are urgently needed. Methods: Andrographolide (AD), the main active ingredient of Andrographis paniculata , reportedly exerts beneficial effects on mice with sepsis. However, its exact mechanism of action in attenuating inflammation due to intra-abdominal sepsis remains unclear to date. Hence, this study aimed to examine the therapeutic effects of AD on cecal ligation and puncture (CLP)-induced sepsis and elucidate the underlying mechanisms. Results: Results showed that AD therapy could significantly improve the 7-day survival rate and alleviate pathological organ injury in mice with CLP. In addition, AD treatment decreased the levels of proinflammatory factors, such as tumor necrosis factor-α and interleukin (IL)-6 in the peritoneal cavity fluid and blood and increased the level of anti-inflammatory factor IL-10 in the peritoneal cavity fluid of mice with CLP. Moreover, bacterial counts in the blood and peritoneal lavage fluid were lower in the mice treated with AD than in those untreated. Mechanistically, AD treatment increased the percentage and phagocytic activity of macrophages in the peritoneal cavity. Conclusion: These data showed that AD can improve the survival of mice with intra-abdominal sepsis by enhancing bacterial clearance, as evidenced by the increased percentages and phagocytic activity of macrophages in the peritoneal cavity. This study is the first to demonstrate the protective effects of AD against intra-abdominal sepsis. Plain Language Summary: Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or septic shock have a high mortality rate of 30– 50%. Therefore, novel strategies for treatment of sepsis are urgently needed. Andrographolide (AD), the main active ingredient of Andrographis paniculata , reportedly exerts beneficial effects on mice with sepsis. However, its exact mechanism of action in attenuating inflammation due to intra-abdominal sepsis remains unclear to date. Here, the study aimed to examine the therapeutic effects of AD on cecal ligation and puncture (CLP)-induced sepsis and elucidate the underlying mechanisms. Our findings showed that AD therapy could significantly improve the 7-day survival rate and alleviate pathological organ injury in mice with CLP. In addition, AD treatment decreased the levels of proinflammatory factors, such as tumor necrosis factor-α and interleukin (IL)-6 in the peritoneal cavity fluid and blood and increased the level of anti-inflammatory factor IL-10 in the peritoneal cavity fluid of mice with CLP. Moreover, bacterial counts in the blood and peritoneal lavage fluid were lower in the mice treated with AD than in those untreated. Mechanistically, AD treatment increased the percentage and phagocytic activity of macrophages in the peritoneal cavity. These data showed that AD can improve the survival of mice with intra-abdominal sepsis by enhancing bacterial clearance, as evidenced by the increased percentages and phagocytic activity of macrophages in the peritoneal cavity. This study is the first to demonstrate the protective effects of AD against intra-abdominal sepsis. Keywords: andrographolide, bacterial clearance, inflammatory response, 7-day survival rate, intra-abdominal sepsis