tectorigenin and Disease-Models--Animal

The aim of this study was to evaluate the effect of tectorigenin on treating allergic asthma model of guinea pigs and investigate the underlying mechanisms.. Allergic asthma model of guinea pigs was established by sensitizing with ovalbumin (OVA). Then OVA-sensitized guinea pigs were injected with 10 mg/kg tectorigenin, 25 mg/kg tectorigenin or dexamethasone to investigate the effect of tectorigenin.. High dose of tectorigenin effectively decreased the number of coughs, the number of inflammatory cells and the levels of pro-inflammatory factors. Moreover, tectorigenin could inhibit pulmonary fibrosis in guinea pigs sensitized with OVA. In addition, the functions of tectorigenin were realized through downregulating profibrotic factors of transforming growth factor (TGF)-β1, phosphorylated (p)-Smad2/3 and Smad4, upregulating fibrosis-inhibitor of Smad7 and decreasing pro-inflammatory factors of vascular endothelial growth factor A (VEGFA), tumour necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-inhibitor of nuclear factor-kappa B (NF-κB) kinase β (p-IKKβ) and NF-κB.. Tectorigenin could inhibit pulmonary fibrosis and airway inflammation through TGF-β1/Smad signalling pathway and TLR4/NF-κB signalling pathway. Therefore, tectorigenin might be a promising medicine to treat allergic asthma.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Disease Models, Animal; Drug Discovery; Guinea Pigs; Isoflavones; NF-kappa B; Pulmonary Fibrosis; Signal Transduction; Smad Proteins; Toll-Like Receptor 4; Transforming Growth Factor beta1; Up-Regulation

Metabolism of bone is regulated by the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Activation of osteoclasts could lead to osteoporosis. Thus, inhibiting the activity of osteoclasts becomes an available strategy for the treatment of osteoporosis. Tectorigenin is an extract of Belamcanda chinensis In the present study, the anti-osteoclastogenesis effects of tectorigenin were investigated in vitro and in vivo. The results showed preventive and therapeutic effects of tectorigenin at concentrations of 0, 10, 40, and 80 μmol/L in the maturation and activation of osteoclasts. A signalling study also indicated that tectorigenin treatment reduces activation of NF-κB signalling in osteoclastogenesis. Animal experiment demonstrated that tectorigenin treatment (1-10 mg/kg, abdominal injection every 3 days) significantly inhibits bone loss in ovariectomized C57BL/6. Our data suggest that tectorigenin is a potential pharmacological choice for osteoporosis.

Topics: Animals; Bone Resorption; Cell Differentiation; Disease Models, Animal; Humans; Isoflavones; Mice; NF-kappa B; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; RANK Ligand; Signal Transduction; Transcription Factor RelA

Tectorigenin is a plant isoflavonoid originally isolated from the dried flower of Pueraria thomsonii Benth. Although its anti-inflammatory and anti-hyperglycosemia effects have been well documented, the effect of tectorigenin on endothelial dysfunction insulin resistance involved has not yet been reported. Herein, this study aims to investigate the action of tectorigenin on amelioration of insulin resistance in the endothelium. Palmitic acid (PA) was chosen as a stimulant to induce ROS production in endothelial cells and successfully established insulin resistance evidenced by the specific impairment of insulin PI3K signaling. Tectorigenin effectively inhibited the ability of PA to induce the production of reactive oxygen species and collapse of mitochondrial membrane potential. Moreover, tectorigenin presented strong inhibition effect on ROS-associated inflammation, as TNF-α and IL-6 production in endothelial cells was greatly reduced with suppression of IKKβ/NF-κB phosphorylation and JNK activation. Tectorigenin also can inhibit inflammation-stimulated IRS-1 serine phosphorylation and restore the impaired insulin PI3K signaling, leading to a decreased NO production. These results demonstrated its positive regulation of insulin action in the endothelium. Meanwhile, tectorigenin down-regulated endothelin-1 and vascular cell adhesion molecule-1 overexpression, and restored the loss of insulin-mediated vasodilation in rat aorta. These findings suggested that tectorigenin could inhibit ROS-associated inflammation and ameliorated endothelial dysfunction implicated in insulin resistance through regulating IRS-1 function. Tectorigenin might have potential to be applied for the management of cardiovascular diseases involved in diabetes and insulin resistance.

Topics: Animals; Disease Models, Animal; Endothelium, Vascular; Gene Expression Regulation; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Insulin Receptor Substrate Proteins; Insulin Resistance; Isoflavones; Male; Membrane Potential, Mitochondrial; Mitochondria; Palmitic Acid; Rats; Reactive Oxygen Species; Signal Transduction; Tumor Necrosis Factor-alpha

Tectorigenin is one of the main components in rhizomes of Iris tectorum, which is traditionally used to treat disorders such as hepatic cirrhosis caused by fibrosis. Idiopathic pulmonary fibrosis (IPF), one of the most common interstitial lung diseases, is caused by accumulation of fibroblasts in lungs.. In this work we sought to examine the effects of tectorigenin on pulmonary fibroblasts in the IPF animal model and investigated the molecular mechanism (microRNA regulation) of tectorigenin treatment.. A well-known animal disease model of pulmonary fibrosis in rat was established by intratracheally instilling of bleomycin. In vitro cultured pulmonary fibroblasts in bleomycin-treated rats and in controls were treated with or without tectorigenin. Comparative analyses of cell proliferation, apoptosis and cell cycle of pulmonary fibroblasts in bleomycin-treated rats and in controls were performed. Expression of miR-338* and its candidate gene LPA1 related to IPF of tectorigenin-treated pulmonary fibroblasts in bleomycin-treated rats were further investigated.. Tectorigenin significantly inhibited the proliferation of pulmonary fibroblasts in bleomycin-treated rats but not in controls. However, no altered cell cycle and apoptosis of pulmonary fibroblasts in bleomycin-treated rats and in controls was observed after tectorigenin treatment. Tectorigenin remarkably enhanced miR-338* expression of pulmonary fibroblasts in bleomycin-treated rats and downregulated LPA1 in the protein level.. Tectorigenin inhibits the proliferation of pulmonary fibroblasts in vitro and enhances miR-338* expression, which might in turn downregulate LPA1. This indicates a potential inhibitory role of tectorigenin on the pathogenesis of IPF.

Topics: Animals; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Fibroblasts; Gene Expression Regulation; Growth Inhibitors; Isoflavones; Lung; Male; MicroRNAs; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley

To observe the protective effect of tectorigenin on the vascular endothelial cells(VEC) injured by oxidant low density lipoprotein-cholesterol and the expression of MCP-1 and ICAM-1 mRNA, and explore the mechanism of anti-atherosclerosis.. The VEC of rat was cultured in vitro and the 100 mg x L(-1) ox-LDL inducing oxidant injured model was used in this study. Different dosage tectorigenin was added into VEC and the activity of VEC was observed by MTT colorimetry. The expression of MCP-1 and ICAM-1 mRNA in VEC was detected by RT-PCR.. Tectorigenin had significantly protective effect on the VEC injured by ox-LDL and obviously inhibited the excessive expression of MCP-1 and ICAM-1 mRNA in VEC.. It was the critical mechanism of anti-atherosclerosis that tectorigenin prevented the VEC oxidant injured and inhibited the excessive expression of MCP-1 and ICAM-1.

Topics: Animals; Atherosclerosis; Cells, Cultured; Chemokine CCL2; Disease Models, Animal; Endothelial Cells; Gene Expression; Humans; Intercellular Adhesion Molecule-1; Isoflavones; Rats; Rats, Wistar; RNA, Messenger

Belamcanda chinensis (BC) belongs to the family of iridaceae and the isoflavone tectorigenin has been isolated from the rhizome of this plant. Whether this isoflavone has estrogenic, possibly selective estrogen receptor modulator activities and if so, whether they are mediated via the estrogen receptor alpha or beta is unknown at present. Therefore, we performed binding studies with recombinant human ERalpha and ERbeta to show that tectorigenin binds to both receptor subtypes. In ERalpha-expressing MCF7 and ERbeta-expressing MDA-MB231 reporter gene transfected cells tectorigenin causes transactivation. When given intravenously to ovariectomized (ovx) rats, it inhibits pulsatile pituitary LH secretion. In postmenopausal women estrogen-unopposed LH pulses correlate with hot flushes. Therefore, suppression of pulsatile LH secretion may be beneficial in women suffering from hot flushes. Upon chronic application to ovx rats a BC extract containing 5% Belamcanda at a daily dose of 33 mg or 130 mg of the extract had no effect on uterine weight or on estrogen-regulated uterine gene expression while estrogenic effects in the bone, on bone mineral density of the metaphysis of the tibia could be established. Hence, tectorigenin may have antiosteoporotic effects also in postmenopausal women. Immunohistochemical staining of proliferating cell nuclear antigen--a proliferation marker--in the mammary gland did not indicate a mammotrophic effect of the tectorigenin-containing BC extract at both tested doses. In summary, tectorigenin or the B. chinensis extract containing tectorigenin had a strong hypothalamotropic and osteotropic effect but no effect in the uterus or the mammary gland. Therefore, tectorigenin may be in the future a clinically useful selective estrogen receptor modulator.

Topics: Animals; Cell Line; Disease Models, Animal; DNA Primers; Dose-Response Relationship, Drug; Female; Hot Flashes; Immunohistochemistry; Iridaceae; Isoflavones; Ovariectomy; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction; Rhizome; RNA, Messenger; Selective Estrogen Receptor Modulators