The influence of astragalus polysaccharide and β-elemene on LX-2 cell growth, apoptosis and activation

Zheng, Jiawei; Ma, Li-Tian; Ren, Qin-You; Li, L u; Zhang, Yi; Shi, Heng-jun; Liu, Yi; Li, Chenghua; Dou, Yongqi; Li, Shaodan; Zhang, Hui; Yang, Minghui

doi:10.1186/s12876-014-0224-8

Cited by 22 publications

(14 citation statements)

References 26 publications

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“…Currently, the traditional Chinese medicine β-elemene is widely used in the complementary treatment of different types of malignancies [20,21,22,23,24,25,26,27]. β-Elemene has also been found to inhibit the expression of angiotensin II and RhoA/ROCK signaling in hepatic stellate cells and to delay the progression of hepatic fibrosis [28,29,30,31,32]. It may also be effective in antiosteogenic differentiation of ankylosing spondylitis fibroblasts by inhibiting the BMP/SMAD signal pathway and subsequently blocking the expression of ossification marker genes RUNX2 that initiate osteogenic differentiation [33].…”

Section: Discussionmentioning

confidence: 99%

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Inhibitory Effect of β-Elemene on Human Airway Granulation Tissue in vivo and in vitro

Li¹,

Zeng

Yang

2016

Respiration

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Background: Recurrent airway granulation hyperplasia and scar formation make airway stenosis a clinical challenge. Therefore, a new approach for the treatment of airway stenosis is necessary. Objective: To explore the inhibitory effect of β-elemene on the proliferation of fibroblasts and airway granulation. Methods: In vivo: (1) study of the effect of local β-elemene injection by bronchoscopy. (2) During bronchoscopy, granulation tissues both before and after treatment were obtained. HE staining was performed and the result compared. In vitro: (1) human airway primary fibroblasts were purified and characterized. (2) Fibroblasts were treated with β-elemene and normal saline (NS) and then examined by optical and electron microscopy. (3) Fibroblasts treated with β-elemene or NS were assessed for viability by tetrazolium salt assay. (4) Apoptotic rates were determined by flow cytometry. Results: In vivo: (1) after local injection of β- elemene, airway granulation tissue was reduced. (2) Granulation tissue was found to have less edema, and fibroblasts turned into mature fiber cells. In vitro: (1) human airway primary fibroblasts were successfully purified and cultured. (2) Compared with the control group, fibroblasts of the experimental group became clumped, the plasma granules were increased, and some fibroblasts lost their nucleus and organelles. (3) Compared with the control group, reduction of cell viability was detected with increased concentrations of β-elemene. (4) With increased concentrations of β-elemene, apoptotic rates of the fibroblasts were raised compared with the control group. Conclusions: β-Elemene may induce apoptosis and necrosis of airway primary fibroblasts and inhibit the proliferation of fibroblasts and airway granulation. The results provide a new approach for the treatment of airway stenosis.

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Section: Discussionmentioning

confidence: 99%

“…It has also been shown to reverse multidrug resistance [20,21,22,23,24,25,26,27]. In addition, research has shown that β-elemene can inhibit proliferation of human bone fibroblasts and lens epithelial cells and that it can inhibit liver fibrosis [28,29,30,31,32,33,34]. …”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of β-Elemene on Human Airway Granulation Tissue in vivo and in vitro

Li¹,

Zeng

Yang

2016

Respiration

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“…TGF-β and Col-1 are two important molecules that are secreted by fibroblasts and also induce fibroblasts to promote inflammation and cancer. The TGF-β-induced upregulation of α-SMA and CD44 in LX-2 cells was blocked by βelemene [117]. In addition to CD44, α-SMA is produced when fibroblasts are stimulated and is essential for cell movement, tumor development, and invasion [118,119].…”

Section: β-Elemene Alters Inflammation and Thementioning

confidence: 99%

“…β-Elemene reduces the expression and phosphorylation of Smad3 to inhibit the expression of nuclear transcription factors (such as SNAI1, SNAI2, TWIST, and SIPI1) and block the EMT induced by TGF-β1 in the human breast cancer cell line MCF-7 [116]. TGF-β1 induces the upregulation of α-SMA in human hepatic stellate cells, and its expression and EMT phenotypic transformation can be blocked by β-elemene [117]. TLR4 induces the EMT and the production of antiapoptotic proteins and angiogenesis factors, promoting the survival of cancer cells and inducing immunosuppression [152].…”

Section: β-Elemenementioning

confidence: 99%

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

Xie

Lei

et al. 2020

BioMed Research International

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Inflammatory mediators and inflammatory cells in the inflammatory microenvironment promote the transformation of normal cells to cancer cells in the early stage of cancer, promote the growth and development of cancer cells, and induce tumor immune escape. The monomeric active ingredient β-elemene is extracted from the traditional Chinese medicine Curcuma wenyujin and has been proven to have good anti-inflammatory and antitumor activities in clinical applications for more than 20 years in China. Recent studies have found that this traditional Chinese medicine plays a vital role in macrophage infiltration and M2 polarization, as well as in regulating immune disorders, and it even regulates the transcription factors NF-κB and STAT3 to alter inflammation, tumorigenesis, and development. In addition, β-elemene regulates not only different inflammatory factors (such as TNF-α, IFN, TGF-β, and IL-6/10) but also oxidative stress in vivo and in vitro. The excellent anti-inflammatory and antitumor effects of β-elemene and its ability to alter the inflammatory microenvironment of tumors have been gradually elaborated. Although the study of monomeric active ingredients in traditional Chinese medicines is insufficient in terms of quality and quantity, the pharmacological effects of more active ingredients of traditional Chinese medicines will be revealed after β-elemene.

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“…β-Elemene was found to be effective in inhibiting the viability of fibroblasts cultured from the stiff joints and spines for patients with rheumatoid arthritis [ 9 ] and ankylosing spondylitis [ 10 ], which could slow down the progression of these two diseases. It was also effective in delaying the progression of atherosclerosis [ 11 ] and hepatic fibrosis [ 12 ]. Our previous study also found that β-elemene could effectively inhibit the growth of human airway granulation tissues and fibroblasts cultured from them, which could retard the progression of benign tracheobronchial stenosis [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway

Xue

Li²,

Lin

et al. 2018

Bioscience Reports

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Benign airway stenosis is a clinical challenge because of recurrent granulation tissues. Our previous study proved that a Chinese drug, β-elemene, could effectively inhibit the growth of fibroblasts cultured from hyperplastic human airway granulation tissues, which could slow down the progression of this disease. The purpose of the present study is to find out the mechanism for this effect. We cultured fibroblasts from normal human airway tissues and human airway granulation tissues. These cells were cultured with 160 μg/ml normal saline (NS), different doses of β-elemene, or 10 ng/ml canonical Wnt/β-catenin pathway inhibitor (Dickkopf-1, DKK-1). The proliferation rate of cells and the expression of six molecules involved in canonical Wnt/β-catenin pathway, Wnt3a, glycogen synthase kinase-3β (GSK-3β), β-catenin, α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and Collagen I (Col-I), were measured. At last, we used canonical Wnt/β-catenin pathway activator (LiCl) to further ascertain the mechanism of β-elemene. Canonical Wnt/β-catenin pathway is activated in human airway granulation fibroblasts. β-Elemene didn’t affect normal human airway fibroblasts; however, it had a dose–responsive inhibitive effect on the proliferation and expression of Wnt3a, non-active GSK-3β, β-catenin, α-SMA, TGF-β, and Col-I of human airway granulation fibroblasts. More importantly, it had the same effect on the expression and nuclear translocation of active β-catenin. All these effects were similar to 10 ng/ml DKK-1 and could be attenuated by 10 mM LiCl. Thus, β-elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway. This pathway is possibly a promising target to treat benign tracheobronchial stenosis.

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The influence of astragalus polysaccharide and β-elemene on LX-2 cell growth, apoptosis and activation

Cited by 22 publications

References 26 publications

Inhibitory Effect of β-Elemene on Human Airway Granulation Tissue in vivo and in vitro

Inhibitory Effect of β-Elemene on Human Airway Granulation Tissue in vivo and in vitro

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

β-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/β-catenin pathway

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