Li Qi Huo Xue Di Wan Attenuates Cardiac and Lung Injury in Mice Exposed to Hypoxia Through Suppression of Apoptosis

Background: Li Qi Huo Xue Di Wan (LQHXDW), a traditional Chinese medicine, is used to treat patients with the symptoms of palpitations, chest tightness, chest pain, and shortness of breath. It is not known, however, whether LQHXDW can reduce high-altitude hypoxia-induced cardiopulmonary injury, what are the specific active ingredients, and what is the exact mechanism behind its cardiopulmonary protection. Objectives: This study intends to investigate the effect of LQHXDW on hypoxia-induced cardiopulmonary injury and the underlying mechanisms. Methods: The components of LQHXDW were identified by UPLC-QTOF-MS. The potential targets of LQHXDW against high-altitude hypoxia were screened via network pharmacology. Mice were subjected to an animal hypoxic chamber for 5 days to establish a high-altitude hypoxia animal model. Rat heart-derived H9c2 cells and human pulmonary artery endothelial cells (HPAECs) were cultured in glucose-free medium under hypoxic conditions (O2 /N2 /CO2, 3/92/5) for 72 h to mimic the high-altitude hypoxia in vivo. Results: The study found that LQHXDW can target apoptosis and inflammation pathways under the condition of high-altitude hypoxia . In mice exposed to hypoxia, LQHXDW reduced cardiac and lung injury, decreased inflammatory responses, and improved cardiac function. In vitro, LQHXDW increased cell viability and reduced apoptosis in cardiomyocytes and pulmonary artery endothelial cells. It also inhibited the activities of caspase-8 and caspase-3, preventing cardiopulmonary apoptosis. Discussion: The study investigates the impact of LQHXDW on hypoxia-induced heart and lung injury using UPLC-QTOF-MS and animal and cell models. Results show that LQHXDW can attenuate injury, prevent apoptosis, and protect the heart and lungs from hypoxia injury. It also demonstrates anti-inflammatory activity, suggesting LQHXDW as a potential candidate for traditional Chinese medicine in high-altitude sickness treatment. Conclusion: LQHXDW can be used as a potential inhibitor of apoptosis for treating high-altitude hypoxia. This study provided a clue for future studies to identify the exact active components of LQHXDW for targeting the pathways of apoptosis.