However, under these same concentrations, viability of A549 and H446 lung cancer cells was inhibited by LLF, but LLF had little effect on the cells after 24?h. astragalin, phloridzin,?and quercetin. The apoptosis-inducing effect of LLF on A549 cells came from these naturally active compounds. Conclusions We have shown in this study that LLF is usually CACNLB3 a bioactive material that can induce apoptosis in A549 cells in vitro, and merits further research and development. Keywords: Human lung cancer A549 cells, Flavonoid, Lotus leaf, C57BL/6J mice, mRNA ROS/p38 MAPK pathway Background Lung cancer is one of the most dangerous malignant tumors in humans. The worlds incidence and death rates are about 1.86?million and 1.6?million per year, respectively. In some countries, death rate of lung cancer is higher than any other type of cancer . Because most lung cancer patients are already in the late stage by the time of diagnosis, the opportunity for surgical treatment has PF-05180999 already been lost, so the main clinical treatments are radiotherapy and chemotherapy . Although most lung cancer patients respond to the initial treatment, the side effects of chemotherapy are severe and drug resistance is usually easily acquired. The effect of second-line chemotherapy is not as good as the first . It is therefore a research priority to find PF-05180999 safe and effective natural bioactive substances for lung cancer prevention and adjuvant treatment. Two main kinds of lotus (Nelumbo nucifera, Gaertn) plants are acknowledged, one is the American lotus in the northeast a part of America; the other is the Chinese lotus, centered in Asia . At present, Chinese lotus is usually widely distributed in Hunan, Hubei, Zhejiang, Jiangsu, and other regions in China . According to traditional Chinese medicine, lotus leaves are mainly used to clear away heat, thirst, and dampness, raise hair, clear Yang, PF-05180999 cool blood, and stop bleeding, diarrhea, and vomiting, and prevent spleen deficiency and other diseases [6C8]. The main active components of lotus leaves are flavonoids and alkaloids. At present, there is extensive research activity on the effects of lotus leaves flavonoids on lowering blood lipids, treatment and prevention of allergy, malignancy, and cardiovascular diseases, as well as its activity as anti-aging, bacteriostatic, and anti-oxidation agent [9C12]. Because of its high bioactivity and low cost, flavonoids from lotus leaves became an important target for research. p38 MAPK and c-Jun N-terminal kinase (JNK) are also known as stress-activated protein kinases (SAPKs) as they are often activated by some environmental stress stimulus and cytokines PF-05180999 that lead to inflammation. Excessive inflammation can cause many diseases, including cancer . The MAPK pathway, especially p38 MAPK, has become an important potential target in inflammation and cancer prevention and treatment . Oxidative stress can induce receptor-dependent apoptosis and damage the mitochondria in normal cells. Mitochondrial dysfunction will further increase ROS accumulation and activate the p38 MAPK pathway . The relationship between ROS/p38 MAPK pathway, inflammation, and tumor growth needs further research, and so do the biological effects of active natural substances on this pathway. There are many studies around the anticancer effect of herb flavonoids. Based on the knowledge derived from previous reports, this study aimed to further elucidate the effects of lotus leaf flavonoids (LLF) on apoptosis of human lung cancer A549 cells, explore the molecular pathways through which LLF exert their inhibitory effects around the growth.