Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway

Author(s): Yunchao Sun, Yongzhang Li*, Xueliang Gao, Limin Gao, Bingqi Yang and Jianing Zhao

Volume 24, Issue 8, 2024

Published on: 22 November, 2023

Page: [918 - 929] Pages: 12

DOI: 10.2174/0118715303251692231112150225

Price: $65

Abstract

Background: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM.

Methods: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks.

Results: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury.

Conclusion: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.

« Previous Next »
Graphical Abstract

[1]
Khosla, S.; Samakkarnthai, P.; Monroe, D.G.; Farr, J.N. Update on the pathogenesis and treatment of skeletal fragility in type 2 diabetes mellitus. Nat. Rev. Endocrinol., 2021, 17(11), 685-697.
[http://dx.doi.org/10.1038/s41574-021-00555-5] [PMID: 34518671]
[2]
Tinajero, M.G.; Malik, V.S. An update on the epidemiology of type 2 diabetes. Endocrinol. Metab. Clin. North Am., 2021, 50(3), 337-355.
[http://dx.doi.org/10.1016/j.ecl.2021.05.013] [PMID: 34399949]
[3]
Niwa, H.; Takahashi, K.; Dannoura, M.; Oomori, K.; Miyoshi, A.; Inada, T.; Miyoshi, H. The association of cardio-ankle vascular index and ankle-brachial index with macroangiopathy in patients with type 2 diabetes mellitus. J. Atheroscler. Thromb., 2019, 26(7), 616-623.
[http://dx.doi.org/10.5551/jat.45674] [PMID: 30487347]
[4]
Liu, Z.; Han, J.; Wang, Y.; Yang, M.; Niu, L.; Shi, B. Association of serum C1Q/TNF-related protein 4 levels with carotid atherosclerosis in subjects with type 2 diabetes mellitus: A cross-sectional study. Clin. Chim. Acta, 2022, 531, 337-341.
[http://dx.doi.org/10.1016/j.cca.2022.04.1004] [PMID: 35525266]
[5]
Yang, Z.; Han, B.; Zhang, H.; Ji, G.; Zhang, L.; Singh, B.K. Association of lower extremity vascular disease, coronary artery, and carotid artery atherosclerosis in patients with type 2 diabetes mellitus. Comput. Math. Methods Med., 2021, 2021, 1-8.
[http://dx.doi.org/10.1155/2021/6268856] [PMID: 34697555]
[6]
Lee, S.H.; Park, S.Y.; Choi, C.S. Insulin resistance: From mechanisms to therapeutic strategies. Diabetes Metab. J., 2022, 46(1), 15-37.
[http://dx.doi.org/10.4093/dmj.2021.0280] [PMID: 34965646]
[7]
Gong, Y.Y.; Peng, H.Y. Correlation analysis of epicardial adipose tissue thickness, C-reactive protein, interleukin-6, visfatin, juxtaposed with another zinc finger protein 1, and type 2 diabetic macroangiopathy. Lipids Health Dis., 2021, 20(1), 25.
[http://dx.doi.org/10.1186/s12944-021-01451-7] [PMID: 33722242]
[8]
Xiang, E.; Han, B.; Zhang, Q.; Rao, W.; Wang, Z.; Chang, C.; Zhang, Y.; Tu, C.; Li, C.; Wu, D. Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis. Stem Cell Res. Ther., 2020, 11(1), 336.
[http://dx.doi.org/10.1186/s13287-020-01852-y] [PMID: 32746936]
[9]
Wang, J.; Ma, Q.; Li, Y.; Li, P.; Wang, M.; Wang, T.; Wang, C.; Wang, T.; Zhao, B. Research progress on traditional chinese medicine syndromes of diabetes mellitus. Biomed. Pharmacother., 2020, 121, 109565.
[http://dx.doi.org/10.1016/j.biopha.2019.109565] [PMID: 31704615]
[10]
Li, B.; Cheng, Y.; Yin, Y.; Xue, J.; Yu, S.; Gao, J.; Liu, J.; Zang, L.; Mu, Y. Reversion of early- and late-stage β-cell dedifferentiation by human umbilical cord-derived mesenchymal stem cells in type 2 diabetic mice. Cytotherapy, 2021, 23(6), 510-520.
[http://dx.doi.org/10.1016/j.jcyt.2021.01.005] [PMID: 33736932]
[11]
Zeng, X.; Zheng, Y.; Luo, J.; Liu, H.; Su, W. A review on the chemical profiles, quality control, pharmacokinetic and pharmacological properties of Fufang Xueshuantong Capsule. J. Ethnopharmacol., 2021, 267, 113472.
[http://dx.doi.org/10.1016/j.jep.2020.113472] [PMID: 33068651]
[12]
Pang, H.; Li, M.; Wang, Y.; Tang, M.; Ma, C.; Huang, J. Effect of compatible herbs on the pharmacokinetics of effective components of Panax notoginseng in Fufang Xueshuantong Capsule. J. Zhejiang Univ. Sci. B, 2017, 18(4), 343-352.
[http://dx.doi.org/10.1631/jzus.B1600235] [PMID: 28378572]
[13]
Peng, M.; Liu, H.; Ji, Q.; Ma, P.; Niu, Y.; Ning, S.; Sun, H.; Pang, X.; Yang, Y.; Zhang, Y.; Han, J.; Hao, G. Fufang xueshuantong improves diabetic cardiomyopathy by regulating the Wnt/β-catenin pathway. Int. J. Endocrinol., 2022, 2022, 1-10.
[http://dx.doi.org/10.1155/2022/3919161] [PMID: 36237833]
[14]
Wu, C.; Chen, R.L.; Wang, Y.; Wu, W.Y.; Li, G. Acacetin alleviates myocardial ischaemia/reperfusion injury by inhibiting oxidative stress and apoptosis via the Nrf-2/HO-1 pathway. Pharm. Biol., 2022, 60(1), 553-561.
[http://dx.doi.org/10.1080/13880209.2022.2041675] [PMID: 35244510]
[15]
Jin, T.; Chen, C. Umbelliferone delays the progression of diabetic nephropathy by inhibiting ferroptosis through activation of the Nrf-2/HO-1 pathway. Food Chem. Toxicol., 2022, 163, 112892.
[http://dx.doi.org/10.1016/j.fct.2022.112892] [PMID: 35278496]
[16]
Gupta, A.; Behl, T.; Sehgal, A.; Bhatia, S.; Jaglan, D.; Bungau, S. Therapeutic potential of Nrf-2 pathway in the treatment of diabetic neuropathy and nephropathy. Mol. Biol. Rep., 2021, 48(3), 2761-2774.
[http://dx.doi.org/10.1007/s11033-021-06257-5] [PMID: 33754251]
[17]
Janhavi, P.; Divyashree, S.; Sanjailal, K.P.; Muthukumar, S.P. DoseCal: A virtual calculator for dosage conversion between human and different animal species. Arch. Physiol. Biochem., 2022, 128(2), 426-430.
[http://dx.doi.org/10.1080/13813455.2019.1687523] [PMID: 31746232]
[18]
Gal, A.; Burchell, R.K. Diabetes mellitus and the kidneys. Vet. Clin. North Am. Small Anim. Pract., 2023, 53(3), 565-580.
[http://dx.doi.org/10.1016/j.cvsm.2023.01.006] [PMID: 36854633]
[19]
Hu, B.; Yin, T.; Zhang, J.; Liu, M.; Yun, H.; Wang, J.; Guo, R.; Huang, J.; Zhou, Y.; Meng, H.; Wang, L. Effect of “maccog” TCM tea on improving glucolipid metabolism and gut microbiota in patients with type 2 diabetes in community. Front. Endocrinol., 2023, 14, 1134877.
[http://dx.doi.org/10.3389/fendo.2023.1134877] [PMID: 36967788]
[20]
Moldovan, R.; Mitrea, D.R.; Florea, A.; David, L.; Mureşan, L.E.; Chiş, I.C.; Suciu, Ş.M.; Moldovan, B.E.; Lenghel, M.; Chiriac, L.B.; Ielciu, I.; Hanganu, D.; Bab, T.; Clichici, S. Effects of gold nanoparticles functionalized with cornus mas l. fruit extract on the aorta wall in rats with a high-fat diet and experimental-induced diabetes mellitus-an imaging study. Nanomaterials, 2023, 13(6), 1101.
[http://dx.doi.org/10.3390/nano13061101] [PMID: 36985995]
[21]
Ren, B.C.; Zhang, W.; Zhang, W.; Ma, J.X.; Pei, F.; Li, B.Y. Melatonin attenuates aortic oxidative stress injury and apoptosis in STZ-diabetes rats by Notch1/Hes1 pathway. J. Steroid Biochem. Mol. Biol., 2021, 212, 105948.
[http://dx.doi.org/10.1016/j.jsbmb.2021.105948] [PMID: 34224859]
[22]
Dos Santos, J.M.; Tewari, S.; Mendes, R.H. The role of oxidative stress in the development of diabetes mellitus and its complications. J. Diabetes Res., 2019, 2019, 1-3.
[http://dx.doi.org/10.1155/2019/4189813] [PMID: 31192263]
[23]
Luca, M.; Di Mauro, M.; Di Mauro, M.; Luca, A. Gut microbiota in Alzheimer’s Disease, depression, and type 2 diabetes mellitus: The role of oxidative stress. Oxid. Med. Cell. Longev., 2019, 2019, 1-10.
[http://dx.doi.org/10.1155/2019/4730539] [PMID: 31178961]
[24]
Liao, Z.; Zhang, J.; Liu, B.; Yan, T.; Xu, F.; Xiao, F.; Wu, B.; Bi, K.; Jia, Y. Polysaccharide from Okra (Abelmoschus esculentus (L.) Moench) improves antioxidant capacity via PI3K/AKT pathways and Nrf2 translocation in a type 2 diabetes model. Molecules, 2019, 24(10), 1906.
[http://dx.doi.org/10.3390/molecules24101906] [PMID: 31108940]
[25]
Darenskaya, M.A.; Kolesnikova, L.I.; Kolesnikov, S.I. Oxidative stress: Pathogenetic role in diabetes mellitus and its complications and therapeutic approaches to correction. Bull. Exp. Biol. Med., 2021, 171(2), 179-189.
[http://dx.doi.org/10.1007/s10517-021-05191-7] [PMID: 34173093]
[26]
Halim, M.; Halim, A. The effects of inflammation, aging and oxidative stress on the pathogenesis of diabetes mellitus (type 2 diabetes). Diabetes Metab. Syndr., 2019, 13(2), 1165-1172.
[http://dx.doi.org/10.1016/j.dsx.2019.01.040] [PMID: 31336460]
[27]
Alshehri, A.S. Kaempferol attenuates diabetic nephropathy in streptozotocin-induced diabetic rats by a hypoglycaemic effect and concomitant activation of the Nrf-2/Ho-1/antioxidants axis. Arch. Physiol. Biochem., 2023, 129(4), 984-997.
[http://dx.doi.org/10.1080/13813455.2021.1890129] [PMID: 33625930]
[28]
Uddandrao, V.V.S.; Parim, B.; Singaravel, S.; Ponnusamy, P.; Ponnusamy, C.; Sasikumar, V.; Saravanan, G. Polyherbal formulation ameliorates diabetic cardiomyopathy through attenuation of cardiac inflammation and oxidative stress via NF-κB/Nrf-2/HO-1 pathway in diabetic rats. J. Cardiovasc. Pharmacol., 2022, 79(1), e75-e86.
[http://dx.doi.org/10.1097/FJC.0000000000001167] [PMID: 34740211]
[29]
Li, H.; Shi, Y.; Wang, X.; Li, P.; Zhang, S.; Wu, T.; Yan, Y.; Zhan, Y.; Ren, Y.; Rong, X.; Xia, T.; Chu, M.; Wu, R. Piceatannol alleviates inflammation and oxidative stress via modulation of the Nrf2/HO-1 and NF-κB pathways in diabetic cardiomyopathy. Chem. Biol. Interact., 2019, 310, 108754.
[http://dx.doi.org/10.1016/j.cbi.2019.108754] [PMID: 31323227]
[30]
Mittal, R.; Kumar, A.; Singh, D.P.; Bishnoi, M.; Nag, T.C. Ameliorative potential of rutin in combination with nimesulide in STZ model of diabetic neuropathy: Targeting Nrf2/HO-1/NF-kB and COX signalling pathway. Inflammopharmacology, 2018, 26(3), 755-768.
[http://dx.doi.org/10.1007/s10787-017-0413-5] [PMID: 29094308]
[31]
Baig, N.; Sultan, R.; Qureshi, S.A. Antioxidant and anti-inflammatory activities of Centratherum anthelminticum (L.) Kuntze seed oil in diabetic nephropathy via modulation of Nrf-2/HO-1 and NF-κB pathway. BMC Complementary Medicine and Therapies, 2022, 22(1), 301.
[http://dx.doi.org/10.1186/s12906-022-03776-x] [PMID: 36401276]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy