Effects of puerarin on pulmonary vascular remodeling and protein kinase C-α in chronic cigarette smoke exposure smoke-exposed rats

Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Journal of Huazhong University of Science and Technology (Impact Factor: 0.83). 03/2008; 28(1):27-32. DOI: 10.1007/s11596-008-0107-8
Source: PubMed

ABSTRACT In order to investigate the effects of puerarin on pulmonary vascular remodeling and protein kinase C-alpha (PKC-alpha) in chronic exposure smoke rats, 54 male Wistar rats were randomly divided into 7 groups: control group (C group), smoke exposure groups (S4w group, S8w group), puerarin groups (P4w group, P8w group), propylene glycol control groups (PC4w group, PC8w group). Rats were exposed to cigarette smoke or air for 4 to 8 weeks. Rats in puerarin groups also received puerarin. To evaluate vascular remodeling, alpha-smooth muscle actin (alpha-SM-actin) staining was used to count the percentage of completely muscularised vessels to intraacinar pulmonary arteries (CMA/IAPA) which was determined by morphometric analysis of histological sections. Pulmonary artery smooth muscle cell (PASMC) apoptosis was detected by in situ end labeling technique (TUNEL), and proliferation by proliferating cell nuclear antigen (PCNA) staining. Reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence staining and Western blot analysis were done to detect the PKC-alpha mRNA and protein expression in pulmonary arteries. The results showed that in cigarette smoke-exposed rats the percentage of CMA/IAPA and alpha-SM-actin expression were increased greatly, PASMC apoptosis was increased and proliferation was markedly increased; Apoptosis indices (AI) and proliferation indices (PI) were higher than in C group; AI and PI were correlated with vascular remodeling indices; The expression of PKC-alpha mRNA and protein in pulmonary arteries was significantly higher than in C group. In rats treated with puerarin, the percentage of CMA/IAPA and cell proliferation was reduced, whereas PASMC apoptosis was increased; The expression levels of PKC-alpha mRNA and protein were lower than in smoke exposure rats. There was no difference among all these data between S groups and PC groups. These findings suggested that cigarette smoke-induced pulmonary vascular remodeling was most likely an effect of the imbalance of PASMC proliferation and apoptosis. Puerarin appears to be able to reduce cell proliferation and vascular remodeling possibly through PKC signaling transduction pathway.

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    • "/ IAPA ) and alpha - smooth muscle actin expression , increased ar - tery smooth muscle cell ( PASMC ) apoptosis , and atten - uated the mRNA and protein expression of PKC - α . Puerarin ameliorated the cigarette smoke - stimulated pulmonary vascular remodeling probably via activation of the PKC signaling pathway and induction of PASMC apoptosis ( Zhu et al . , 2008b ) . Puerarin impeded the proliferation of four acute myeloid leukemia cell lines , U937 , Kasumi - 1 , HL - 60 , and NB4 cells , interfered with cell cycle process ( Shao et al . , 2010 ) , and elevated the apoptosis rate of acute promyelocytic leukemia cell line NB4 . The mechanism might be associated with the JNK signal pathway ( Tang"
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    ABSTRACT: Puerarin is the major bioactive ingredient isolated from the root of the Pueraria lobata (Willd.) Ohwi, which is well known as Gegen (Chinese name) in traditional Chinese medicine. As the most abundant secondary metabolite, puerarin was isolated from Gegen in the late 1950s. Since then, its pharmacological properties have been extensively investigated. It is available in common foods and is used in alternative medicine. It has been widely used in the treatment of cardiovascular and cerebrovascular diseases, diabetes and diabetic complications, osteonecrosis, Parkinson's disease, Alzheimer's disease, endometriosis, and cancer. The beneficial effects of puerarin on the various medicinal purposes may be due to its wide spectrum of pharmacological properties such as vasodilation, cardioprotection, neuroprotection, antioxidant, anticancer, antiinflammation, alleviating pain, promoting bone formation, inhibiting alcohol intake, and attenuating insulin resistance. However, the direct molecular mechanisms and targets remain unclear. This review provides a comprehensive summary of the pharmacological effects of puerarin. Copyright © 2013 John Wiley & Sons, Ltd.
    Phytotherapy Research 07/2014; 28(7). DOI:10.1002/ptr.5083 · 2.66 Impact Factor
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    • "However, the underlying mechanisms are not fully understood. It is known that overexpression of PKC-α in pulmonary arterioles is involved in the development of pulmonary vascular remodeling in pulmonary hypertension [13] [26] and the K ATP channel opener cromakalim attenuated the pulmonary vasoconstrictory effect of PKC activation [27] . Therefore, in the present study, we used a rat chronic hypoxia exposure model to study whether iptakalim could inhibit the proliferation of PASMCs and pulmonary vascular remodeling by regulating the expression of PKC-α in PASMCs. "
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    ABSTRACT: Iptakalim is a new ATP-sensitive potassium (KATP) channel opener, and it inhibits the proliferation of pulmonary arterial smooth muscle cells (PASMCs) and pulmonary vascular remodeling. However, the underlying mechanism remains unclear. In the present study, we found that iptakalim significantly decreased pulmonary artery pressure, inhibited pulmonary ariery remodeling and PKC-α overexpression in chronic hypoxia in a rat pulmonary hypertension model. Iptakalim reduced hypoxia-induced expression of PKC-α, and abolished the effect of hypoxia on PASMC proliferation significantly in a dose-dependent manner in vitro. Moreover, these effects were abolished by glibenclamide, a selective KATP channel antagonist. These results indicate that iptakalim inhibits PASMC proliferation and pulmonary vascular remodeling induced by hypoxia through downregulating the expression of PKC-α. Iptakalim can serve as a novel promising treatment for hypoxic pulmonary hypertension.
    11/2011; 25(6):392-401. DOI:10.1016/S1674-8301(11)60052-3
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    ABSTRACT: We investigated the antiproliferative effects of baicalein, isolated from Scutellaria baicalensis (Huang-qin), on ET-1-mediated pulmonary artery smooth muscle cells (PASMCs) proliferation and the mechanisms underlying these effects. Intrapulmonary artery smooth muscle cells were isolated and cultured from female Sprague-Dawley rats and used during passages 3-6. The proliferation of PASMCs was quantified by cell counting and XTT assay. The protein expression of TRPC1 and PKCα were determined by western blotting. The cell cycle pattern was assayed by flow cytometry. The intracellular calcium concentrations ([Ca(2+)](i)) were measured using the fluorescent indicator fura-2-AM and flow cytometry. Baicalein (0.3-3 μM) inhibited PASMCs proliferation, promoted cell cycle progression, enhanced [Ca(2+)](i) levels, increased capacitative Ca(2+) entry (CCE), upregulated the canonical transient receptor potential 1 (TRPC1) channel and membrane protein kinase Cα (PKCα) expression induced by ET-1 (0.1 μM). The PKC activator PMA (1 μM) reversed the inhibitory effects of baicalein on ET-1-induced upregulation of TRPC1 expression and S phase accumulation, while the PKC inhibitor chelerythrine (1 μM) potentiated baicalein-mediated G(2)/M phase arrest and TRPC1 channel inhibition. Our findings suggest that baicalein protects against ET-1-induced PASMCs proliferation via modulation of the PKC-mediated TRPC channel.
    Journal of ethnopharmacology 09/2011; 138(2):373-81. DOI:10.1016/j.jep.2011.09.014 · 3.00 Impact Factor
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