| Peer-Reviewed

Effect of “Nourishing Yin and Qi, Promoting Blood Circulation and Detoxification” on Endoplasmic Reticulum Stress CHOP Apoptotic Bypass in Diabetic Atherosclerosis

Received: 19 September 2019     Accepted: 28 September 2019     Published: 15 October 2019
Views:       Downloads:
Abstract

To explore the mechanism of Huoxue Jiedu Jiangtang Recipe (HJJR) in alleviating endoplasmic reticulum stress (ERS) - inflammation, inhibiting ERS apoptotic bypass of CHOP and alleviating diabetic atherosclerosis (AS). Diabetic AS rats were duplicated by feeding of high lipid diet and intraperitoneal injection of streptozotocin. After diabetes modeled successfully, the rats were randomly divided into model group, low-dose HJJR group (HJJR1), high-dose HJJR group (HJJR2) and western medicine group (Gliquidone+ Benazepril), and accepted corresponding drugs for 2 months respectively. The same batch of rats were taken as normal control group and fed with common diet. The levels of glycosylated hemoglobin (GHb), blood lipid, fasting serum insulin (FINS) and insulin resistance index (IRI) were measured in each group. The contents of inflammatory factors TNF-α and IL-6 were detected by immunohistochemistry. The mRNA transcription of GRP78 and caspase-12 were tested by reverse- transcription polymerase chain reaction (RT-PCR). The apoptotic level of aortic cells was checked by TUNEL. Compared with the model group, all drug groups could significantly reduce GHb, IRI, TG and LDL-C (P<0.05), increase FINS and HDL-C (P<0.05), down-regulate transcription of CHOP and GRP78 (P<0.05), reduce inflammatory factors TNF-a, IL-6, and decreased aortic apoptosis index (AI) (P<0.05). Compared with the western medicine group, the effect of HJJR2 group was more significant (P<0.05). HJJR could alleviate insulin resistance, correct lipid metabolism disorder, depress endoplasmic reticulum stress-induced inflammatory reaction, and inhibit endoplasmic reticulum stress-induced apoptotic bypass of CHOP in arterial cells. The therapeutic effect is dose dependent.

Published in American Journal of Clinical and Experimental Medicine (Volume 7, Issue 5)
DOI 10.11648/j.ajcem.20190705.12
Page(s) 111-118
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

Diabetes, Atherosclerosis, Endoplasmic Reticulum Stress, CCAAT Enhance-Binding Protein Homologous Protein, Huoxue Jiedu Jiangtang Recipe

References
[1] CHEN Yuanyuan, CHEN Yafen, SUN Xueran, et al. Regulation mechanism of AGEs on FSTL1 expression in diabetes with atherosclerosis. International Journal of Cardiovascular Disease, 2019, 46 (1): 31-35.
[2] ZHONG Qiaoqing, ZHU Lingyan, ZHANG Guogang, et al. Atherosclerotic cardiovascular disease in diabetes--mechanisms, clinical represent and management. Chinese Journal of Cardiovascular Review, 2018, 16 (12): 1069-1072.
[3] Fu Xianzhao, Huang Zhenfeng, Huang Wenhua, et al. Review and Prospect of the Preventive Effect of “Supplementing Qi and Nourishing Yin, Activating Blood Circulation and Detoxifying” on Diabetes Mellitus Complicated with Acute Coronary Syndrome. American Journal of Clinical and Experimental Medicine. 2018, 6 (4): 87-93.
[4] Fu Xianzhao, Huang Wenhua, Li Chunyan, et al. Effect of Huoxue Jiedu Jiangtang Formulation on Endoplasmic Reticulum Stress in Diabetic Atherosclerosis. American Journal of Clinical and Experimental Medicine. 2018, 6 (5): 118-124.
[5] Jing G, Xing-zhi W, Tao W, et al. Molecular signal networks and regulating mechanisms of the unfolded protein response. Biomed & Biotechnol, 2017, 18 (1): 1-14.
[6] GUAN Li Ying, XU CaiMin, PAN Hua Zhen. Endoplasmic Reticulum Stress-induced Apoptosis. Progress in Biochemistry and Biophysics, 2007, 34 (11): 1136-1141.
[7] Maamoun H, Abdelsalam SS, Zeidan A, et al. Endoplasmic Reticulum Stress: A Critical Molecular Driver of Endothelial Dysfunction and Cardiovascular Disturbances Associated with Diabetes. Int J Mol Sci. 2019 Apr 3; 20 (7). pii: E1658.
[8] Feng SQ, Zong SY, Liu JX, et al. VEGF antagonism attenuates cerebral ischemia/reperfusion- induced injury via inhibiting endoplasmic reticulum stress-mediated apoptosis. Biol Pharm Bull. 2019 Mar 2. doi: 10.1248/bpb.b18-00628
[9] Chen Y, Zhang B, Cao S, et al. GanDouLing combined with Penicillamine improves cerebrovascular injury via PERK/eIF2α/CHOP endoplasmic reticulum stress pathway in the mouse model of Wilson's disease. Biosci Rep. 2018 Sep 19; 38 (5). pii: BSR20180800.
[10] TIAN JinFan, LIU Yue, LI Li Zhi, et al. reticulum stress, autophagy and their crosstalk: the potential treatment targets for atherosclerosis. Chinese Bulletin of Life Sciences, 2017, 29 (4): 356-362.
[11] ZHANG Wen. Research progress of the relevance between endoplasmic reticulum stress and diabetes associated atherosclerosis. Clinical journal of traditional Chinese medicine, 2018, 27 (11): 1620-1622.
[12] Gong J, Wang XZ, Wang T, et al. Molecular signal networks and regulating mechanisms of the unfolded protein response. J Zhejiang Univ Sci B, 2017, 18 (1): 1-14.
[13] Zhang K, Kaufman RJ. From endoplasmic-retieulum stress to the inflammatory response. Nature, 2008, 454: 455-462.
[14] Seimon T, Tabas I. Mechanisms and consequences of macrophage apoptosis in atherosclerosis [J]. J Lipid Res, 2009, 50: S382-S387.
[15] Jia LX, Zhang WM, Li TT, et al. ER stress dependent microparticles derived from smooth muscle cells promote endothelial dysfunction during thoracic aortic aneurysm and dissection. Clin Sci (Lond). 2017 Jun 7; 131 (12): 1287-1299.
[16] Hu H, Wang C, Jin Y, et al. Catalpol Inhibits Homocysteine-induced Oxidation and Inflammation via Inhibiting Nox4/NF-κB and GRP78/PERK Pathways in Human Aorta Endothelial Cells. Inflammation. 2019 Feb; 42 (1): 64-80. doi: 10.1007/s10753-018-0873-9.
[17] Tabas I, Seimon T, Timmins J, et al. Macrophage apoptosis in advanced atherosclerosis. Ann N Y Acad Sci. 2009, 1173 (Suppl 1): E40-45.
[18] Yuan J, Chen M, Xu Q, et al. Effect of the Diabetic Environment On the Expression of miRNAs in Endothelial Cells: Mir-149-5p Restoration Ameliorates the High Glucose-Induced Expression of TNF-α and ER Stress Markers. Cell Physiol Biochem, 2017, 43 (1): 120-135.
[19] Lim W, Timmins J, Seimon T, et al. Signal transducer and activator of transcription-1 is critical for apoptosis in macrophages subjected to endoplasmic reticulum stress in vitro and in advanced atherosclerotic lesions in vivo [J]. Circulation, 2008. 117 (7): 940-951.
[20] FU Xian-zhao, XU Jing, HUANG WenHua, et al. Strategy of Stasis-resolving and Detoxification on Diabetic Coronary Heart Disease [J]. JETCM, 2014, 23 (11): 2024-2027.
[21] FU Xian-zhao, XU Jing, LI ChunYan, et al. Effects of Huoxue Jiedu Jiangtang formulation on the balance between pro-and anti-inflammatory cytokines in non-revascularization patients with diabetic acute coronary syndrome [J]. Chin J TCM WM Crit Care, 2016, 23 (1): 6-10.
[22] FU Xian-zhao, XU Jing, LI ChunYan, et al. Effect of Huoxue Jiedu Jiangtang formulation on heart remodeling in diabetic patients with acute coronary syndrome after PCI [J]. Chin J TCM WM Crit Care, 2016, 23 (2): 117-121.
Cite This Article
  • APA Style

    Fu Xianzhao, Li Chunyan, Huang Wenhua, Li Xingchan, Qiu Haixian, et al. (2019). Effect of “Nourishing Yin and Qi, Promoting Blood Circulation and Detoxification” on Endoplasmic Reticulum Stress CHOP Apoptotic Bypass in Diabetic Atherosclerosis. American Journal of Clinical and Experimental Medicine, 7(5), 111-118. https://doi.org/10.11648/j.ajcem.20190705.12

    Copy | Download

    ACS Style

    Fu Xianzhao; Li Chunyan; Huang Wenhua; Li Xingchan; Qiu Haixian, et al. Effect of “Nourishing Yin and Qi, Promoting Blood Circulation and Detoxification” on Endoplasmic Reticulum Stress CHOP Apoptotic Bypass in Diabetic Atherosclerosis. Am. J. Clin. Exp. Med. 2019, 7(5), 111-118. doi: 10.11648/j.ajcem.20190705.12

    Copy | Download

    AMA Style

    Fu Xianzhao, Li Chunyan, Huang Wenhua, Li Xingchan, Qiu Haixian, et al. Effect of “Nourishing Yin and Qi, Promoting Blood Circulation and Detoxification” on Endoplasmic Reticulum Stress CHOP Apoptotic Bypass in Diabetic Atherosclerosis. Am J Clin Exp Med. 2019;7(5):111-118. doi: 10.11648/j.ajcem.20190705.12

    Copy | Download

  • @article{10.11648/j.ajcem.20190705.12,
      author = {Fu Xianzhao and Li Chunyan and Huang Wenhua and Li Xingchan and Qiu Haixian and Huang Guangming and Cao Qiuxia and Lu Mian},
      title = {Effect of “Nourishing Yin and Qi, Promoting Blood Circulation and Detoxification” on Endoplasmic Reticulum Stress CHOP Apoptotic Bypass in Diabetic Atherosclerosis},
      journal = {American Journal of Clinical and Experimental Medicine},
      volume = {7},
      number = {5},
      pages = {111-118},
      doi = {10.11648/j.ajcem.20190705.12},
      url = {https://doi.org/10.11648/j.ajcem.20190705.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20190705.12},
      abstract = {To explore the mechanism of Huoxue Jiedu Jiangtang Recipe (HJJR) in alleviating endoplasmic reticulum stress (ERS) - inflammation, inhibiting ERS apoptotic bypass of CHOP and alleviating diabetic atherosclerosis (AS). Diabetic AS rats were duplicated by feeding of high lipid diet and intraperitoneal injection of streptozotocin. After diabetes modeled successfully, the rats were randomly divided into model group, low-dose HJJR group (HJJR1), high-dose HJJR group (HJJR2) and western medicine group (Gliquidone+ Benazepril), and accepted corresponding drugs for 2 months respectively. The same batch of rats were taken as normal control group and fed with common diet. The levels of glycosylated hemoglobin (GHb), blood lipid, fasting serum insulin (FINS) and insulin resistance index (IRI) were measured in each group. The contents of inflammatory factors TNF-α and IL-6 were detected by immunohistochemistry. The mRNA transcription of GRP78 and caspase-12 were tested by reverse- transcription polymerase chain reaction (RT-PCR). The apoptotic level of aortic cells was checked by TUNEL. Compared with the model group, all drug groups could significantly reduce GHb, IRI, TG and LDL-C (P<0.05), increase FINS and HDL-C (P<0.05), down-regulate transcription of CHOP and GRP78 (P<0.05), reduce inflammatory factors TNF-a, IL-6, and decreased aortic apoptosis index (AI) (P<0.05). Compared with the western medicine group, the effect of HJJR2 group was more significant (P<0.05). HJJR could alleviate insulin resistance, correct lipid metabolism disorder, depress endoplasmic reticulum stress-induced inflammatory reaction, and inhibit endoplasmic reticulum stress-induced apoptotic bypass of CHOP in arterial cells. The therapeutic effect is dose dependent.},
     year = {2019}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Effect of “Nourishing Yin and Qi, Promoting Blood Circulation and Detoxification” on Endoplasmic Reticulum Stress CHOP Apoptotic Bypass in Diabetic Atherosclerosis
    AU  - Fu Xianzhao
    AU  - Li Chunyan
    AU  - Huang Wenhua
    AU  - Li Xingchan
    AU  - Qiu Haixian
    AU  - Huang Guangming
    AU  - Cao Qiuxia
    AU  - Lu Mian
    Y1  - 2019/10/15
    PY  - 2019
    N1  - https://doi.org/10.11648/j.ajcem.20190705.12
    DO  - 10.11648/j.ajcem.20190705.12
    T2  - American Journal of Clinical and Experimental Medicine
    JF  - American Journal of Clinical and Experimental Medicine
    JO  - American Journal of Clinical and Experimental Medicine
    SP  - 111
    EP  - 118
    PB  - Science Publishing Group
    SN  - 2330-8133
    UR  - https://doi.org/10.11648/j.ajcem.20190705.12
    AB  - To explore the mechanism of Huoxue Jiedu Jiangtang Recipe (HJJR) in alleviating endoplasmic reticulum stress (ERS) - inflammation, inhibiting ERS apoptotic bypass of CHOP and alleviating diabetic atherosclerosis (AS). Diabetic AS rats were duplicated by feeding of high lipid diet and intraperitoneal injection of streptozotocin. After diabetes modeled successfully, the rats were randomly divided into model group, low-dose HJJR group (HJJR1), high-dose HJJR group (HJJR2) and western medicine group (Gliquidone+ Benazepril), and accepted corresponding drugs for 2 months respectively. The same batch of rats were taken as normal control group and fed with common diet. The levels of glycosylated hemoglobin (GHb), blood lipid, fasting serum insulin (FINS) and insulin resistance index (IRI) were measured in each group. The contents of inflammatory factors TNF-α and IL-6 were detected by immunohistochemistry. The mRNA transcription of GRP78 and caspase-12 were tested by reverse- transcription polymerase chain reaction (RT-PCR). The apoptotic level of aortic cells was checked by TUNEL. Compared with the model group, all drug groups could significantly reduce GHb, IRI, TG and LDL-C (P<0.05), increase FINS and HDL-C (P<0.05), down-regulate transcription of CHOP and GRP78 (P<0.05), reduce inflammatory factors TNF-a, IL-6, and decreased aortic apoptosis index (AI) (P<0.05). Compared with the western medicine group, the effect of HJJR2 group was more significant (P<0.05). HJJR could alleviate insulin resistance, correct lipid metabolism disorder, depress endoplasmic reticulum stress-induced inflammatory reaction, and inhibit endoplasmic reticulum stress-induced apoptotic bypass of CHOP in arterial cells. The therapeutic effect is dose dependent.
    VL  - 7
    IS  - 5
    ER  - 

    Copy | Download

Author Information
  • Clinic Medical College, Youjiang Medical National College, Baise, China

  • Clinic Medical College, Youjiang Medical National College, Baise, China

  • Clinic Medical College, Youjiang Medical National College, Baise, China

  • Clinic Medical College, Youjiang Medical National College, Baise, China

  • Clinic Medical College, Youjiang Medical National College, Baise, China

  • Clinic Medical College, Youjiang Medical National College, Baise, China

  • Clinic Medical College, Youjiang Medical National College, Baise, China

  • Clinic Medical College, Youjiang Medical National College, Baise, China

  • Sections