Berberine inhibits human retinal vascular endothelial cell apoptosis induced by high glucose_Chinese Journal of Ocular Fundus Diseases

Authors：

Wang Shanshan ¹ , Xu Xianzhen ² , Liao Xing ¹ , Lai Meichen ¹ ,  Fu Shuhua ¹

1. Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China;
2. Department of Ophthalmology, Xiushui County Hospital of Traditional Chinese Medicine, Jiujiang 332400, China;

Corresponding?author：

Fu Shuhua, Email: fushuhua1435@163.com

Keywords：

Diabetic retinopathy; Endothelium; vascular; Apoptosis; Berberine

DOI：

10.3760/cma.j.cn511434-20210225-00100

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To observe the inhibitory effect of berberine (BBR) on the apoptosis of human retinal vascular endothelial cells (hREC) under high glucose environment.Methods hREC was divided into blank control group (NC group), high glucose group (HG group), BBR treatment group (BN group), and BBR+high glucose treatment group (BH group). The cells of each group were cultured in Dulbecco's modified eagle medium; 5.5 and 30.0 mmol/L glucose were added to the medium of the NC group and HG group, respectively; 5.0 mmol/L glucose and 5.0 mmol/L BBR was added to the BN group; 30.0 mmol/L glucose and 5.0 mmol/L BBR was added to the medium of the BH group. Flow cytometry was used to observe the apoptosis rate of each group. Western blotting was used to detect the relative expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), and Cytochrome C (Cyt-C) and cysteine aspastic acid-specific protease 3 (Caspase-3) proteins in each group of cells. The difference between the two groups was tested by t test, and the difference among multiple groups was analyzed by one-way analysis of variance. Results The results of flow cytometry showed that compared with the NC group, the apoptosis rate of the HG group significantly increased, and the difference was statistically significant (P＜0.01); compared with the HG group, the apoptosis rate of the BH group significantly reduced, the difference was statistical significance (P＜0.05). Western blot test results showed that, compared with the NC group, the relative expression of Bax and Caspase-3 protein in the HG group increased, and the relative expression of Bcl-2 protein decreased. The difference was statistically significant (P＜0.01). Compared with the HG group, the relative expression of Bax, Cyt-C, and Caspase-3 protein in BH group cells decreased, and the relative expression of Bcl-2 protein increased, and the difference was statistically significant (P＜0.01). Conclusion BBR can inhibit hREC apoptosis by affecting the expression of apoptotic protein under high glucose environment.

Citation： Wang Shanshan, Xu Xianzhen, Liao Xing, Lai Meichen, Fu Shuhua. Berberine inhibits human retinal vascular endothelial cell apoptosis induced by high glucose. Chinese Journal of Ocular Fundus Diseases, 2021, 37(10): 790-794. doi: 10.3760/cma.j.cn511434-20210225-00100 Copy

1.	Cunha-Vaz J, Bernardes R, Lobo C. Blood-retinal barrier[J]. Eur J Ophthalmol, 2011, 21(Suppl 6): S3-9. DOI: 10.5301/EJO.2010.6049.
2.	Daiber A, Steven S, Weber A, et al. Targeting vascular (endothelial) dysfunction[J]. Br J Pharmacol, 2017, 174(12): 1591-1619. DOI: 10.1111/bph.13517.
3.	Wang Y, Yan A, Li S, et al. Efficacy and safety of berberine in the treatment of type 2 diabetes with insulin resistance: protocol for a systematic review[J/OL]. Medicine (Baltimore), 2019, 98(35): e16947[2019-09-30]. https://pubmed.ncbi.nlm.nih.gov/31464934/. DOI: 10.1097/MD.0000000000016947.
4.	萬強, 楊玉萍, 劉中勇. 黃連素抑制ERK1/2途徑減輕大氣細顆粒物對EA.hy926內皮細胞損傷的研究[J]. 中藥材, 2016, 39(7): 1623-1627. DOI: 10.13863/j.issn1001-4454.2016.07.042.Wan Q, Yang YP, Liu ZY. Study of berberine on attenuating PM2.5-induced vascular endothelial cells injury by ERK1/2 signal pathway[J]. Zhong Yao Cai, 2016, 39(7): 1623-1627. DOI: 10.13863/j.issn1001-4454.2016.07.042.
5.	Chang W, Chen L, Hatch GM. Berberine as a therapy for type 2 diabetes and its complications: from mechanism of action to clinical studies[J]. Biochem Cell Biol, 2015, 93(5): 479-486. DOI: 10.1139/bcb-2014-0107.
6.	Hsu YJ, Lin CW, Cho SL, et al. Protective effect of fenofibrate on oxidative stress-induced apoptosis in retinal-choroidal vascular endothelial cells: implication for diabetic retinopathy treatment[J/OL]. Antioxidants (Basel), 2020, 9(8): 712[2020-08-05]. https://pubmed.ncbi.nlm.nih.gov/32764528/. DOI: 10.3390/antiox9080712.
7.	Wang Y, Huang Y, Lam KS, et al. Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase[J]. Cardiovasc Res, 2009, 82(3): 484-492. DOI: 10.1093/cvr/cvp078.
8.	Ong WY, Go ML, Wang DY, et al. Effects of antimalarial drugs on neuroinflammation-potential use for treatment of COVID-19-related neurologic complications[J]. Mol Neurobiol, 2021, 58(1): 106-117. DOI: 10.1007/s12035-020-02093-z.
9.	Samuels IS, Bell BA, Pereira A, et al. Early retinal pigment epithelium dysfunction is concomitant with hyperglycemia in mouse models of type 1 and type 2 diabetes[J]. J Neurophysiol, 2015, 113(4): 1085-1099. DOI: 10.1152/jn.00761.2014.
10.	Simó R, Villarroel M, Corraliza L, et al. The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy[J/OL]. J Biomed Biotechnol, 2010, 2010: 190724[2010-02-17]. https://pubmed.ncbi.nlm.nih.gov/20182540/. DOI: 10.1155/2010/190724.
11.	Cunha-Vaz J, Bernardes R. Nonproliferative retinopathy in diabetes type 2. Initial stages and characterization of phenotypes[J]. Prog Retin Eye Res, 2005, 24(3): 355-377. DOI: 10.1016/j.preteyeres.2004.07.004.
12.	Li C, Miao X, Li F, et al. Oxidative stress-related mechanisms and antioxidant therapy in diabetic retinopathy[J/OL]. Oxid Med Cell Longev, 2017, 2017: 9702820[2017-02-06]. https://pubmed.ncbi.nlm.nih.gov/28265339/. DOI: 10.1155/2017/9702820.
13.	Tan JKS, Wei X, Wong PA, et al. Altered red blood cell deformability-a novel hypothesis for retinal microangiopathy in diabetic retinopathy[J/OL]. Microcirculation, 2020, 27(7): e12649[2020-08-11]. https://pubmed.ncbi.nlm.nih.gov/32663357/. DOI: 10.1111/micc.12649.
14.	Sorrentino FS, Matteini S, Bonifazzi C, et al. Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction[J]. Eye (Lond), 2018, 32(7): 1157-1163. DOI: 10.1038/s41433-018-0032-4.
15.	Warren CFA, Wong-Brown MW, Bowden NA. BCL-2 family isoforms in apoptosis and cancer[J/OL]. Cell Death Dis, 2019, 10(3): 177[2019-02-21]. https://pubmed.ncbi.nlm.nih.gov/30792387/. DOI: 10.1038/s41419-019-1407-6.
16.	Khalilzadeh B, Shadjou N, Kanberoglu GS, et al. Advances in nanomaterial based optical biosensing and bioimaging of apoptosis via caspase-3 activity: a review[J/OL]. Mikrochim Acta, 2018, 185(9): 434[2018-08-29]. https://pubmed.ncbi.nlm.nih.gov/30159750/. DOI: 10.1007/s00604-018-2980-6.
17.	Pazarc? ?, Aydin H, K?l?n? S. Comparison of caspase-8, granzyme B and cytochrome C apoptosis biomarker levels in orthopedic trauma patients[J]. Ulus Travma Acil Cerrahi Derg, 2020, 26(2): 274-279. DOI: 10.14744/tjtes.2019.02680.
18.	Elena-Real CA, Díaz-Quintana A, González-Arzola K, et al. Cytochrome c speeds up caspase cascade activation by blocking 14-3-3epsilon-dependent Apaf-1 inhibition[J/OL]. Cell Death Dis, 2018, 9(3): 365[2018-03-06]. https://pubmed.ncbi.nlm.nih.gov/29511177/. DOI: 10.1038/s41419-018-0408-1.

1. Cunha-Vaz J, Bernardes R, Lobo C. Blood-retinal barrier[J]. Eur J Ophthalmol, 2011, 21(Suppl 6): S3-9. DOI: 10.5301/EJO.2010.6049.
2. Daiber A, Steven S, Weber A, et al. Targeting vascular (endothelial) dysfunction[J]. Br J Pharmacol, 2017, 174(12): 1591-1619. DOI: 10.1111/bph.13517.
3. Wang Y, Yan A, Li S, et al. Efficacy and safety of berberine in the treatment of type 2 diabetes with insulin resistance: protocol for a systematic review[J/OL]. Medicine (Baltimore), 2019, 98(35): e16947[2019-09-30]. https://pubmed.ncbi.nlm.nih.gov/31464934/. DOI: 10.1097/MD.0000000000016947.
4. 萬強, 楊玉萍, 劉中勇. 黃連素抑制ERK1/2途徑減輕大氣細顆粒物對EA.hy926內皮細胞損傷的研究[J]. 中藥材, 2016, 39(7): 1623-1627. DOI: 10.13863/j.issn1001-4454.2016.07.042.Wan Q, Yang YP, Liu ZY. Study of berberine on attenuating PM2.5-induced vascular endothelial cells injury by ERK1/2 signal pathway[J]. Zhong Yao Cai, 2016, 39(7): 1623-1627. DOI: 10.13863/j.issn1001-4454.2016.07.042.
5. Chang W, Chen L, Hatch GM. Berberine as a therapy for type 2 diabetes and its complications: from mechanism of action to clinical studies[J]. Biochem Cell Biol, 2015, 93(5): 479-486. DOI: 10.1139/bcb-2014-0107.
6. Hsu YJ, Lin CW, Cho SL, et al. Protective effect of fenofibrate on oxidative stress-induced apoptosis in retinal-choroidal vascular endothelial cells: implication for diabetic retinopathy treatment[J/OL]. Antioxidants (Basel), 2020, 9(8): 712[2020-08-05]. https://pubmed.ncbi.nlm.nih.gov/32764528/. DOI: 10.3390/antiox9080712.
7. Wang Y, Huang Y, Lam KS, et al. Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase[J]. Cardiovasc Res, 2009, 82(3): 484-492. DOI: 10.1093/cvr/cvp078.
8. Ong WY, Go ML, Wang DY, et al. Effects of antimalarial drugs on neuroinflammation-potential use for treatment of COVID-19-related neurologic complications[J]. Mol Neurobiol, 2021, 58(1): 106-117. DOI: 10.1007/s12035-020-02093-z.
9. Samuels IS, Bell BA, Pereira A, et al. Early retinal pigment epithelium dysfunction is concomitant with hyperglycemia in mouse models of type 1 and type 2 diabetes[J]. J Neurophysiol, 2015, 113(4): 1085-1099. DOI: 10.1152/jn.00761.2014.
10. Simó R, Villarroel M, Corraliza L, et al. The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy[J/OL]. J Biomed Biotechnol, 2010, 2010: 190724[2010-02-17]. https://pubmed.ncbi.nlm.nih.gov/20182540/. DOI: 10.1155/2010/190724.
11. Cunha-Vaz J, Bernardes R. Nonproliferative retinopathy in diabetes type 2. Initial stages and characterization of phenotypes[J]. Prog Retin Eye Res, 2005, 24(3): 355-377. DOI: 10.1016/j.preteyeres.2004.07.004.
12. Li C, Miao X, Li F, et al. Oxidative stress-related mechanisms and antioxidant therapy in diabetic retinopathy[J/OL]. Oxid Med Cell Longev, 2017, 2017: 9702820[2017-02-06]. https://pubmed.ncbi.nlm.nih.gov/28265339/. DOI: 10.1155/2017/9702820.
13. Tan JKS, Wei X, Wong PA, et al. Altered red blood cell deformability-a novel hypothesis for retinal microangiopathy in diabetic retinopathy[J/OL]. Microcirculation, 2020, 27(7): e12649[2020-08-11]. https://pubmed.ncbi.nlm.nih.gov/32663357/. DOI: 10.1111/micc.12649.
14. Sorrentino FS, Matteini S, Bonifazzi C, et al. Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction[J]. Eye (Lond), 2018, 32(7): 1157-1163. DOI: 10.1038/s41433-018-0032-4.
15. Warren CFA, Wong-Brown MW, Bowden NA. BCL-2 family isoforms in apoptosis and cancer[J/OL]. Cell Death Dis, 2019, 10(3): 177[2019-02-21]. https://pubmed.ncbi.nlm.nih.gov/30792387/. DOI: 10.1038/s41419-019-1407-6.
16. Khalilzadeh B, Shadjou N, Kanberoglu GS, et al. Advances in nanomaterial based optical biosensing and bioimaging of apoptosis via caspase-3 activity: a review[J/OL]. Mikrochim Acta, 2018, 185(9): 434[2018-08-29]. https://pubmed.ncbi.nlm.nih.gov/30159750/. DOI: 10.1007/s00604-018-2980-6.
17. Pazarc? ?, Aydin H, K?l?n? S. Comparison of caspase-8, granzyme B and cytochrome C apoptosis biomarker levels in orthopedic trauma patients[J]. Ulus Travma Acil Cerrahi Derg, 2020, 26(2): 274-279. DOI: 10.14744/tjtes.2019.02680.
18. Elena-Real CA, Díaz-Quintana A, González-Arzola K, et al. Cytochrome c speeds up caspase cascade activation by blocking 14-3-3epsilon-dependent Apaf-1 inhibition[J/OL]. Cell Death Dis, 2018, 9(3): 365[2018-03-06]. https://pubmed.ncbi.nlm.nih.gov/29511177/. DOI: 10.1038/s41419-018-0408-1.

Chinese Journal of Ocular Fundus Diseases

Berberine inhibits human retinal vascular endothelial cell apoptosis induced by high glucose

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content