Wenyang Huazhuo Tongluo formula inhibits fibrosis via suppressing Wnt/β-catenin signaling pathway in a Bleomycin-induced systemic sclerosis mouse model

Wang, Qian; Zang, Wenhua; Han, Li; Yang, Lei; Ye, Songshan; Ouyang, Jingping; Zhang, Chaoyun; Bi, Yue‐Feng; Zhang, Cuiyue; Bian, Hua

doi:10.1186/s13020-018-0175-z

Cited by 6 publications

(7 citation statements)

References 42 publications

(50 reference statements)

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“…Alkaloid berberine, as a traditional anti-inflammatory Chinese herbal medicine, can inhibit colon tumor formation through inhibition of Wnt/β-catenin signaling [36]. Wenyang Huazhuo Tongluo formula has anti-fibrosis effect in Bleomycin-induced SSc mouse model by inhibiting Wnt/β-catenin signaling pathway [37]. Thus, our study provides a valuable prototype for effective therapeutic agents in tumor treatment by inhibiting Wnt pathway.…”

Section: Discussionmentioning

confidence: 99%

A tannin compound from Sanguisorba officinalis blocks Wnt/β-catenin signaling pathway and induces apoptosis of colorectal cancer cells

Yang

Wang

et al. 2019

Chin Med

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Background: Sanguisorba officinalis, a popular Chinese herb, called DiYu, has been shown to inhibit the growth of many human cancer cell lines, including colorectal cancer cells. The aims of this study were to discover the active compound and molecular mechanism of S. officinalis against Wnt/β-catenin signaling pathway and develop Wnt inhibitors from natural products as anti-colorectal cancer agents. Methods: 1,4,6-TriO -galloyl-β-d-glucopyranose (TGG) was obtained by the preparative HPLC. The effect of DiYu on proliferation of NIH3T3 and HT29 was detected by MTT assay. Luciferase reporter assay was applied to investigate the activity of Wnt/β-catenin signaling in NIH3T3. The expression levels of mRNA and protein were detected by RT-PCR and western blot. Immunofluorescence assay was used to measure the level of β-catenin in cytoplasm and nucleus. Transcriptomic profiling study was performed to investigate the molecular mechanism of DiYu on the Wnt/β-catenin signaling pathway. Results: TGG significantly inhibited the Wnt/β-catenin signaling pathway, down-regulated the expression of β-catenin and Wnt target genes (Dkk1, c-Myc, FGF20, NKD1, Survivin), up-regulated the levels of cleaved caspase3, cleaved PARP and ratio of Bax/Bcl-2, which may explain the apoptosis of HT29. Conclusions: Our study enhanced the discovery of the materials and elucidation of mechanisms that account for the anti-Wnt activity of natural inhibitor (DiYu) and identified the potential of TGG to be developed as anti-colorectal cancer drugs.

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Section: Discussionmentioning

confidence: 99%

A tannin compound from Sanguisorba officinalis blocks Wnt/β-catenin signaling pathway and induces apoptosis of colorectal cancer cells

Yang

Wang

et al. 2019

Chin Med

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“…XAV-939 is one member of a large set of small-molecule inhibitors of the Wnt/β-catenin pathway [28, 39, 40]. Targeting of this pathway in clinical or experimental settings and the applicability of the inhibitors have several limitations, so ongoing drug design is focused on identifying additional specific inhibitors that have fewer side effects [39, 41–43]. Members and proteins of the Wnt/β-catenin signalling or Notch signalling pathways may be new targets for drug development to prevent the progression of AV stenosis, since these signalling pathways are believed to be involved in osteogenesis in human AV disease [4, 9, 17, 33, 44].…”

Section: Discussionmentioning

confidence: 99%

Treatment with XAV-939 prevents in vitro calcification of human valvular interstitial cells

et al. 2018

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The development of a substance or inhibitor-based treatment strategy for the prevention of aortic valve stenosis is a challenge and a main focus of medical research in this area. One strategy may be to use the tankyrase inhibitor XAV-939, which leads to Axin stabilisation and subsequent destruction of the β-catenin complex and dephosphorylation of β-catenin. The dephosphorylated active form of β-catenin (non-phospho-β-catenin) then promotes nuclear transcription that leads to osteogenesis. The aims of the present study were to develop an experimental system for inducing in vitro calcification of human aortic valvular interstitial cells (VICs) to investigate the potential anti-calcific effect of XAV-939 and to analyse expression of the Wnt signalling proteins and Sox9, a chondrogenesis regulator, in this model. Calcification of human VIC cultures was induced by cultivation in an osteogenic medium and the effect of co-incubation with 1μM XAV-939 was monitored. Calcification was quantified when mineral deposits were visible in culture and was histologically verified by von Kossa or Alizarin red staining and by IR-spectroscopy. Protein expression of alkaline phosphatase, Axin, β-catenin and Sox9 were quantified by western blotting. In 58% of the VIC preparations, calcification was induced in an osteogenic culture medium and was accompanied by upregulation of alkaline phosphatase. The calcification induction was prevented by the XAV-939 co-treatment and the alkaline phosphatase upregulation was suppressed. As expected, Axin was upregulated, but the levels of active non-phospho-β-catenin were also enhanced. Sox9 was induced during XAV-939 treatment but apparently not as a result of downregulation of β-catenin signalling. XAV-939 was therefore able to prevent calcification of human VIC cultures, and XAV-939 treatment was accompanied by upregulation of active non-phospho-β-catenin. Although XAV-939 does not downregulate active β-catenin, treatment with XAV-939 results in Sox9 upregulation that may prevent the calcification process.

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“…Male C57/BL6N mice (purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.) aged 8 weeks and weighing 17-20 g were used to construct a bleomycin-induced SSc mouse model as previously described [ 8 ]. Briefy, 100 ul of bleomycin (200 ug/ml) was subcutaneous injected to the restricted area of the upper back each day, which lasted for 3 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous studies have shown that Wenyang Huazhuo Tongluo Formula regulated immune imbalance and exerts anti-fibrosis effects in the treatment of SSc. Wenyang Huazhuo Tongluo Formula exerts it anti-fibrosis effects by regulating the fibroblast cell cycle, inhibiting its proliferation, and reducing collagen synthesis by inhibiting the Wnt/β-catenin signaling pathway [ 8 – 10 ]. Wenyang Huazhuo Tongluo Formula can also inhibit the expression of type I and III collagen by inhibiting the TGF-β1/Smad signaling pathway in SSc fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

Wenyang Huazhuo Tongluo formula alleviates pulmonary vascular injury and downregulates HIF-1α in bleomycin-induced systemic sclerosis mouse model

Wang

et al. 2022

BMC Complement Med Ther

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Background Vascular damage, autoimmune abnormalities, and fibrosis are the three pathological features of systemic sclerosis (SSc).However, pulmonary vascular damage is the main factor affecting the progression and prognosis of SSc. The main purpose of this study was to explore the molecular mechanism of Wenyang Huazhuo Tongluo Formula in alleviating pulmonary vascular injury in bleomycin-induced SSc mouse model. Methods Masson staining and H&E staining were used to analyze the degree of pulmonary vascular fibrosis and the infiltration of leukocyte cells in lung tissue ofbleomycin-induced SSc mouse models treated with saline (BLM group), Wenyang Huazhuo Tongluo Formula (WYHZTL group) and HIF-1α inhibitor KC7F2 (KC7F2 group). Blood vessel exudation was determined by analyzing the cell number and albumin concentration in bronchoalveolar lavage fluid using a cell counter and ELISA assay, respectively. The degree of vascular injury was assessed by measuring the expression levels of vWF, E-selectin, ICAM-1, VCAM-1, VE-cadherin and claudin-5 in serum and pulmonary vascular endothelial cells using ELISA and immunofluorescence staining. Finally, the effect of Wenyang Huazhuo Tongluo Formula on the expression of HIF-1α was detected using immunofluorescence staining. Results Wenyang Huazhuo Tongluo Formula and KC7F2 significantly inhibited bleomycin-induced pulmonary vascular fibrosis and the level of perivascular inflammatory cell infiltration. The number of cells and the concentration of albumin were significantly reduced in the bronchoalveolar lavage fluid of the WYHZTL group and KC7F2 group compared with the BLM group. In addition, treatment with Wenyang Huazhuo Tongluo Formula and KC7F2 significantly downregulated the expression levels of vWF, E-selectin, ICAM-1, VCAM-1 and HIF-1α, but upregulated the expression of VE-cadherin and claudin-5 in serum and pulmonary vascular endothelial cells, compared with treatment with saline. Conclusions This study reveals that Wenyang Huazhuo Tongluo Formula plays a new role in the treatment of SSc by alleviating pulmonary vascular damage. Furthermore, we found that Wenyang Huazhuo Tongluo Formula alleviates pulmonary vascular injury and inhibits HIF-1α expression.

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Wenyang Huazhuo Tongluo formula inhibits fibrosis via suppressing Wnt/β-catenin signaling pathway in a Bleomycin-induced systemic sclerosis mouse model

Cited by 6 publications

References 42 publications

A tannin compound from Sanguisorba officinalis blocks Wnt/β-catenin signaling pathway and induces apoptosis of colorectal cancer cells

A tannin compound from Sanguisorba officinalis blocks Wnt/β-catenin signaling pathway and induces apoptosis of colorectal cancer cells

Treatment with XAV-939 prevents in vitro calcification of human valvular interstitial cells

Wenyang Huazhuo Tongluo formula alleviates pulmonary vascular injury and downregulates HIF-1α in bleomycin-induced systemic sclerosis mouse model

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