Active polypeptides from Hirudo inhibit endothelial cell inflammation and macrophage foam cell formation by regulating the LOX-1/LXR-α/ABCA1 pathway

Lü, Jing; Chen, Xuenan; Xu, Xiaohao; Liu, Jianzeng; Zhang, Zepeng; Wang, Mingxing; Li, Xiangzhu; Chen, Hong; Zhao, Deyu; Wang, Jian; Zhao, Dexi; Cong, Deyu; Li, Xiangyan; Sun, Liwei

doi:10.1016/j.biopha.2019.108840

Cited by 25 publications

(17 citation statements)

References 42 publications

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“…Hirudo is the dried entire body of Whitmania pigra Whitman, Hirudo nipponica Whitman, or W. acranulata Whitman, and is a representative toxic animal-based medicinal material that has been used since the beginning of civilization. It has the efficacy of "breaking blood and expelling stasis", and there is historical evidence of its use in the treatment of endometriosis [22,57,58]. However, it is difficult to confirm the effectiveness of Hirudo against endometriosis, as there were no studies examining only Hirudo.…”

Section: Discussionmentioning

confidence: 99%

Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review

Hwang

Yoon

Sung

et al. 2021

Toxins

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Animal toxins and venoms have recently been developed as cancer treatments possessing tumor cell growth-inhibitory, antiangiogenesis, and proapoptotic effects. Endometriosis is a common benign gynecological disorder in reproductive-age women, and no definite treatment for this disorder is without severe side effects. As endometriosis and malignant tumors share similar characteristics (progressive, invasive, estrogen-dependent growth, and recurrence), animal toxins and venoms are thought to be effective against endometriosis. The objective of this study was to outline studies using toxic animal-based medicinal materials (TMM) as endometriosis treatment and to explore its clinical applicability. Preclinical and clinical studies using TMM were searched for in four databases from inception to October 2020. A total of 20 studies of TMM on endometriosis were included. In eight clinical studies, herbal medicines containing TMM were effective in relieving symptoms of endometriosis, with no side effects. In twelve experimental studies, the main therapeutic mechanisms of TMM against endometriosis were proapoptotic, antiangiogenesis, estrogen level-reducing, and possible anti-inflammatory effects. TMM are thus considered promising sources for the development of an effective treatment method for endometriosis. Further studies are needed to clarify the therapeutic mechanism of TMM against endometriosis and to provide sufficient grounds for clinical application.

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Section: Discussionmentioning

confidence: 99%

Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review

Hwang

Yoon

Sung

et al. 2021

Toxins

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“…The role of ABCA1 in other systems has not been reported yet. Actually, ABCA1 was reported to be an activator in multiple cell pathways such as cell inflammation and macrophage foam cell formation [ 28 ]. Endothelin 1 gene (EDN1) is one of the families of three endothelins that exert their action through two G-protein-coupled receptors [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Expressed Genes and Elucidation of Pathophysiological Relevance of ABCA1 in HaCaT Cells Induced by PM2.5

Peng

Xue

Yang

et al. 2021

Bioinorganic Chemistry and Applications

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Objective. In order to investigate the effects of PM2.5 on proliferation, cell cycle, apoptosis, and potential mechanism of human keratinocyte cell line HaCaT. Methods. HaCaT cells were treated with different concentrations of PM2.5 suspension for 24 hours. Cell viability was detected by the CCK-8 method. Cell cycle distribution and apoptosis were detected by flow cytometry. Microarray analyses were used to find out the microarray gene expression profiling; data processing included gene enrichment and pathway analysis. Western blot was conducted to validate the key pathways and regulators in the microarray analysis. Results. The cell activity decreased, and the cell cycle was significantly inhibited with the increase in PM2.5 concentration. Also, by conducting the gene expression microarray assay, we identified 541 upregulated genes and 935 downregulated genes in PM2.5-treated HaCaT cells. Real-time qPCR and western blot confirmed that PM2.5 treatment could induce the expression of ABCA1 while inhibiting that of END1 and CLDN1. Conclusion. Our results showed that PM2.5 could potentially regulate cell apoptosis and cell cycle arrest via ABCA1-, END1-, ID1-, and CLDN1-mediated pathways in human HaCaT cells, which laid a good foundation for follow-up drug intervention and drug development against skin damage caused by PM2.5 exposure.

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“…Based on this theory, the medicinal materials of GQN, such as Eupolyphaga steleophage and Hirudo , could be used to kill tumor cells because they are believed to be slightly poisonous in Chinese medicine. Previous studies have proven that these two medicinal materials are effective in promoting apoptosis in tumor cells [ 10 , 11 , 19 ]. Therefore, in this paper, the effect of GQN on the mitochondrial apoptotic pathway was determined by documenting the expression of the proapoptotic proteins Bax, Cyt-C, and cleaved Caspase 3 and the antiapoptotic protein Bcl-2 in tumor tissue to explain its antihepatocellular carcinoma effect.…”

Section: Discussionmentioning

confidence: 99%

“…As mentioned above, the main medicines in GQN, such as Eupolyphaga steleophage [ 10 , 11 ] and Hedyotis diffusa [ 13 , 29 ], as well as other medicines, such as Scutellaria barbata [ 17 ], Agrimonia pilosa [ 30 ], and Hirudo [ 19 ], exhibit activity in promoting apoptosis of tumor cells by affecting the mitochondrial apoptotic pathway. Although we do not know exactly which chemical components in GQN play key roles in promoting apoptosis, selected components, such as hirudin of Hirudo [ 31 ], quercetin and methylanthraquinone of Hedyotis diffusa [ 14 , 32 ], scutebarbatine of Scutellaria barbata [ 33 ], and agrimoniin of Agrimonia pilosa [ 34 ], have been confirmed to have antitumor effects.…”

Section: Discussionmentioning

confidence: 99%

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Gan‐Qing‐Ning Formula Inhibits the Growth of Hepatocellular Carcinoma by Promoting Apoptosis and Inhibiting Angiogenesis in H₂₂ Tumor‐Bearing Mice

Zeng

Zhao

Lin

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. Gang-Qing-Ning (GQN) is a traditional Chinese medicine formula that has been used in the treatment of hepatocellular carcinoma (HCC) in the folk population for decades. However, scientific validation is still necessary to lend credibility to the traditional use of GQN against HCC. This study investigates the antitumor effect of GQN on H22 tumor-bearing mice and its possible mechanism. Methods. Fifty H22 tumor-bearing mice were randomly assigned to five groups. Three groups were treated with high, medium, and low dosages of GQN (27.68, 13.84, and 6.92 g/kg, respectively); the positive control group was treated with cytoxan (CTX) (20 mg/kg) and the model group was treated with normal saline. After 10 days’ treatment, the tumor inhibitory rates were calculated. Pathological changes in tumor tissue were observed, and the key proteins and genes of the mitochondrial apoptosis pathway were measured, as well as the mRNA expression levels of VEGF in tumor tissue. Results. The tumor inhibitory rates of high, medium, and low dosages of GQN groups were 47.39%, 38.26%, and 22.17%, respectively. The high dosage of the GQN group significantly increased the protein and mRNA expression levels of Bax, Cyt-C, and cleaved Caspase 3 (or Caspase 3) (P<0.01) but decreased the expression levels of Bcl-2, VEGF, and microvessel density (MVD) (P<0.01). Conclusions. The high dosage of GQN can significantly inhibit the tumor growth in H22 tumor-bearing mice. It exerts the antitumor effect by enhancing proapoptotic factors and inhibiting the antiapoptotic factor of the mitochondrial apoptosis pathway and inhibiting tumor angiogenesis.

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Active polypeptides from Hirudo inhibit endothelial cell inflammation and macrophage foam cell formation by regulating the LOX-1/LXR-α/ABCA1 pathway

Cited by 25 publications

References 42 publications

Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review

Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review

Identification of Differentially Expressed Genes and Elucidation of Pathophysiological Relevance of ABCA1 in HaCaT Cells Induced by PM2.5

Gan‐Qing‐Ning Formula Inhibits the Growth of Hepatocellular Carcinoma by Promoting Apoptosis and Inhibiting Angiogenesis in H₂₂ Tumor‐Bearing Mice

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Active polypeptides from Hirudo inhibit endothelial cell inflammation and macrophage foam cell formation by regulating the LOX-1/LXR-α/ABCA1 pathway

Cited by 25 publications

References 42 publications

Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review

Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review

Identification of Differentially Expressed Genes and Elucidation of Pathophysiological Relevance of ABCA1 in HaCaT Cells Induced by PM2.5

Gan‐Qing‐Ning Formula Inhibits the Growth of Hepatocellular Carcinoma by Promoting Apoptosis and Inhibiting Angiogenesis in H22 Tumor‐Bearing Mice

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Gan‐Qing‐Ning Formula Inhibits the Growth of Hepatocellular Carcinoma by Promoting Apoptosis and Inhibiting Angiogenesis in H₂₂ Tumor‐Bearing Mice