Mechanism of triptolide in treating ankylosing spondylitis through the anti?ossification effect of the BMP/Smad signaling pathway.

By London Spine
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Mechanism of triptolide in treating ankylosing spondylitis through the anti‑ossification effect of the BMP/Smad signaling pathway.

Mol Med Rep. 2017 Nov 20;:

Authors: Wang G, Cai J, Zhang J, Li C

Abstract
The present study aimed to examine the mechanism of triptolide in the treatment of ankylosing spondylitis (AS) through the anti‑ossification effect of bone morphogenetic protein (BMP)/small mothers against decapentaplegic (Smad) pathway. Male rats were randomly divided into five groups: Normal rat group; model group; triptolide low dose group (10 mg/kg); triptolide middle dose group (20 mg/kg); triptolide high dose group (40 mg/kg). The spinal joint capsules of each group of rats were collected to perform primary cell culture to determine the levels of cell proliferation. Western blot and reverse transcription‑polymerase chain reaction analyses, and ELISA were used to detect the mRNA and protein expression levels of core‑binding factor α1 (Cbfal), BMP receptor type II (BMPRII), Smad1, Smad4, Smad5 and Smad6, the protein expression of phosphorylation indicators, including phosphorylated (p)Smad1 and pSmad5, the mRNA expression of tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑1β and IL‑6 in rat plasma, and the mRNA expression of BMP/Smads in fibroblasts induced by recombinant human (rh)BMP‑2. The effects on AS in the rats were also examined. The results revealed that, following intervention with triptolide, inflammation was suppressed, and the mRNA expression levels of TNF‑α, IL‑1β and IL‑6 were reduced. The expression levels of Cbfal, BMPRII, Smad1, Smad4 and Smad5 were also reduced, whereas the expression of Smad6 was increased. Following induction by rhBMP‑2, the effects of triptolide weakened, with the most marked effects observed at the highest concentration, suggesting that triptolide functions through the BMP/Smad signaling pathway. Taken together, the results suggested that triptolide may be used to treat AS, the mechanism of which may be through the BMP/Smad pathway.

PMID: 29207198 [PubMed – as supplied by publisher]

Sparstolonin B prevents lumbar intervertebral disc degeneration through toll like receptor 4, NADPH oxidase activation and the protein kinase B signaling pathway.

By Kamruz Zaman
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Sparstolonin B prevents lumbar intervertebral disc degeneration through toll like receptor 4, NADPH oxidase activation and the protein kinase B signaling pathway.

Mol Med Rep. 2017 Nov 06;:

Authors: Ge J, Chen L, Yang Y, Lu X, Xiang Z

Abstract
Intervertebral disc degeneration (IVDD) is the most common pathogeny of lumbago. It is the pathological basis for a series of spinal degenerative diseases. For a long time, the diagnosis and treatment of lumbago have rendered difficult, since the pathogeny has not been identified. Therefore, the present study aimed to investigate the protective effect of Sparstolonin B in preventing lumbar intervertebral disc degeneration, and explored its potential mechanism in rats. Firstly, Sparstolonin B effectively reduced the histological score of disc degeneration and increased endplate porosity of L2 superior endplates in a lumbar IVDD rat model. Sparstolonin B significantly inhibited the IVDD‑induced inflammatory factors tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6, oxidative stress factors (malondialdehyde), and superoxide dismutase and caspase‑3/9 activities. Treatment with Sparstolonin B significantly suppressed toll‑like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor (NF)‑κB protein expression, inhibited NAPDH oxidase 2 protein expression and induced phosphoinositide 3‑kinase and phosphorylated protein kinase B protein expression in the IVDD rat model. These results demonstrated that Sparstolonin B prevents lumbar IVDD‑induced inflammation, oxidative stress and apoptosis through TLR4/MyD88/NF‑κB, NADPH oxidase activation and the phosphoinositide 3‑kinase/protein kinase B signaling pathway. These results implicate Sparstolonin B for use as a therapeutic agent for IVDD in clinical applications.

PMID: 29115481 [PubMed – as supplied by publisher]

Elemene inhibits osteosarcoma growth by suppressing the renin?angiotensin system signaling pathway.

By Kamruz Zaman
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Elemene inhibits osteosarcoma growth by suppressing the renin‑angiotensin system signaling pathway.

Mol Med Rep. 2017 Nov 06;:

Authors: Ding L, Zhang G, Hou Y, Chen J, Yin Y

Abstract
Osteosarcoma remains the most prevalent primary malignant bone tumor in children and young adults globally. Therefore, novel and highly effective antitumor agents are urgently required. Elemene is a natural plant compound extracted from the medicinal Chinese herb, Rhizomazedoariae, which has been employed as an antitumor agent for the treatment of a number of tumors, including osteosarcoma. However, the mechanisms underlying its antitumor effect are currently unclear. The human osteosarcoma cell lines, MG‑63 and U2OS, were employed in the present study. MTT, migration, transwell invasion and terminal deoxynucleotidyltransferase‑mediated deoxy‑UTP‑fluorescein nick end‑labeling assays were performed to evaluate cell viability, migration, invasion and apoptosis, respectively. Western blotting and immunohistochemistry analyses were performed to measure the levels of renin‑angiotensin system (RAS) components. In order to evaluate the effect of elemene on tumor weight and volume, MG‑63 and U2OS cells were injected into mice. Treatment of osteosarcoma cell lines, MG‑63 and U2OS, with elemene led to the inhibition of cell viability, migration and invasion, as well as induction of cell apoptosis. In addition, elemene treatment downregulated the expression of a number of RAS components. The growth of osteosarcoma cell‑transplanted tumors in nude mice and angiotensin II expression were inhibited by elemene treatment. The results of the present study indicate that the antitumor effects of elemene may partly be due to downregulation of the RAS signaling pathway, and that RAS may be a putative pharmacological target for osteosarcoma therapy.

PMID: 29115494 [PubMed – as supplied by publisher]

Astragaloside IV attenuates penicillin-induced epilepsy via inhibiting activation of the MAPK signaling pathway.

By Kamruz Zaman
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Astragaloside IV attenuates penicillin-induced epilepsy via inhibiting activation of the MAPK signaling pathway.

Mol Med Rep. 2017 Oct 26;:

Authors: Zhu X, Chen Y, Du Y, Wan Q, Xu Y, Wu J

Abstract
Astrocytes perform several functions in the brain and spinal cord. Penicillin is commonly used for establishment of experimental epilepsy models. Previous studies have demonstrated that astragaloside IV (3-o-β-d-xylopyranosyl-6-o-β-d-glucopyranosyl-cycloastragenol; AS‑IV) has comprehensive pharmacological functions on the attenuation of inflammation. In the present study, primary astrocyte cell cultures were divided into three groups: Control group, penicillin (2,500 µM) treatment group (epilepsy model), and penicillin+AS‑IV (20, 40, 80 and 160 µmol/l) treatment group. The expression levels of inflammatory factors, including interleukin‑1β and tumor necrosis factor‑α, were determined in the groups using western blot and reverse transcription‑quantitative polymerase chain reaction analyses. The levels of members of the phosphorylated‑mitogen‑activated protein kinase (p‑MAPK) family, including p‑c‑Jun N‑terminal kinase 1/2, p‑extracellular signal‑regulated protein kinase 1/2 and p‑p38, were determined using western blot analysis. Cell viability of the astrocytes was detected using a 3‑(4,5‑dimethyl‑2‑thiazolyl)‑2,5‑diphenyl‑2‑H‑tetrazolium bromide assay and cell proliferation was evaluated using a Cell Counting Kit‑8 assay. The results revealed that AS‑IV significantly suppressed the expression of penicillin‑induced inflammatory factors in the astrocytes at the transcriptional and translational levels, and occurred in a dose‑dependent manner. The penicillin‑induced increase in the protein levels of the the p‑MAPK family were notably decreased by AS‑IV. In addition, the penicillin‑induced downregulation of primary astrocyte viability/cell proliferation was significantly reversed by the administration of AS‑IV. From these results, it was concluded that AS‑IV suppressed the penicillin‑induced upregulation of inflammatory factors and p‑MAPK in astrocytes, ultimately attenuating epilepsy.

PMID: 29115438 [PubMed – as supplied by publisher]