title: Puerarin attenuates glucocorticoid-induced apoptosis of hFOB1.19 cells through the JNK- and Akt-mediated mitochondrial apoptotic pathways.
abstract: Puerarin is an active component of Pueraria lobata, which is a commonly used Chinese herbal medicine for the treatment of osteoporosis. The present study aimed to evaluate the osteoprotective effect of puerarin on glucocorticoid (GC)-induced apoptosis of osteoblasts in vitro. The effects of puerarin on dexamethasone (DEX)-induced cell apoptosis were assessed using enzyme-linked immunosorbent assay and a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and found that the viability of hFOB1.19 cells was significantly increased following exposure to between 10(-6) and 10(-10) M puerarin, with a maximal anti-apoptotic effect at a concentration of 10(-8) M. In addition, compared with the control group, puerarin upregulated the transcription and protein levels of B-cell lymphoma-2 and downregulated B-cell-associated X protein in the hFOB1.19 cells. Puerarin attenuated the DEX-induced release of cytochrome c and cleavage of caspase-3, and treatment with puerarin inhibited the c-Jun N-terminal kinase (JNK) pathway and activated the phosphoinositide 3-kinase (PI3K)/Akt pathway in the hFOB1.19 cells. Furthermore, the Akt inhibitor, LY294002, partly eliminated the protective effect of puerarin on DEX-induced apoptosis, and puerarin combined with the JNK inhibitor, SP600125, suppressed DEX-induced apoptosis to a lesser extent than in the cells treated with SP600125 alone. These results suggested that the JNK and PI3K/Akt signaling pathways mediate the inhibitory effects of puerarin on apoptosis in the hFOB1.19 cells. In conclusion, puerarin prevented DEX-induced apoptosis of hFOB1.19 cells via inhibition of the JNK pathway and activation of the PI3K/Akt signaling pathway in the cells, dependent on the mitochondrial apoptotic pathway. These results support puerarin as a promising target in the treatment of GC-induced osteoporosis.
authors.affiliation: Department of Orthopedic Surgery, The Shengjing Hospital of China Medical University, Liaoning 110004, P.R. China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Orthopedic Surgery, The Shengjing Hospital of China Medical University, Liaoning 110004, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Mu
authors.affiliation: Department of Orthopedic Surgery, The Shengjing Hospital of China Medical University, Liaoning 110004, P.R. China.
authors.forename: Danyang
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Orthopedic Surgery, The Shengjing Hospital of China Medical University, Liaoning 110004, P.R. China.
authors.forename: Guangbin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The Shengjing Hospital of China Medical University, Liaoning 110004, P.R. China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, The Shengjing Hospital of China Medical University, Liaoning 110004, P.R. China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Orthopedic Surgery, The Shengjing Hospital of China Medical University, Liaoning 110004, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D029908:Pueraria / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D005938:Glucocorticoids; D007529:Isoflavones; D003907:Dexamethasone; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; C033607:puerarin