Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2024

Open Access 01-12-2024 | Research

Astragalus polysaccharides attenuate rat aortic endothelial senescence via regulation of the SIRT-1/p53 signaling pathway

Authors: Xinyu Miao, Lingjun Rong, Bo Fu, Shaoyuan Cui, Zhaoyan Gu, Fan Hu, Yanhui Lu, Shuangtong Yan, Banruo Sun, Wenli Jiang, Yuting Zhang, Yanping Gong, Chunlin Li

Published in: BMC Complementary Medicine and Therapies | Issue 1/2024

Login to get access

Abstract

Background

Astragalus polysaccharides (APS) have been verified to have antioxidative and antiaging activities in the mouse liver and brain. However, the effect of APS on aortic endothelial senescence in old rats and its underlying mechanism are currently unclear. Here, we aimed to elucidate the effects of APS on rat aortic endothelial oxidative stress and senescence in vitro and in vivo and investigate the potential molecular targets.

Methods

Twenty-month-old natural aging male rats were treated with APS (200 mg/kg, 400 mg/kg, 800 mg/kg daily) for 3 months. Serum parameters were tested using corresponding assay kits. Aortic morphology was observed by staining with hematoxylin and eosin (H&E) and Verhoeff Van Gieson (VVG). Aging-related protein levels were evaluated using immunofluorescence and western blot analysis. Primary rat aortic endothelial cells (RAECs) were isolated by tissue explant method. RAEC mitochondrial function was evaluated by the mitochondrial membrane potential (MMP) measured with the fluorescent lipophilic cationic dye JC‑1. Intracellular total antioxidant capacity (T-AOC) was detected by a commercial kit. Cellular senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal) staining.

Results

Treatment of APS for three months was found to lessen aortic wall thickness, renovate vascular elastic tissue, improve vascular endothelial function, and reduce oxidative stress levels in 20-month-old rats. Primary mechanism analysis showed that APS treatment enhanced Sirtuin 1 (SIRT-1) protein expression and decreased the levels of the aging marker proteins p53, p21 and p16 in rat aortic tissue. Furthermore, APS abated hydrogen peroxide (H2O2)-induced cell senescence and restored H2O2-induced impairment of the MMP and T-AOC in RAECs. Similarly, APS increased SIRT-1 and decreased p53, p21 and p16 protein levels in senescent RAECs isolated from old rats. Knockdown of SIRT-1 diminished the protective effect of APS against H2O2-induced RAEC senescence and T-AOC loss, increased the levels of the downstream proteins p53 and p21, and abolished the inhibitory effect of APS on the expression of these proteins in RAECs.

Conclusion

APS may reduce rat aortic endothelial oxidative stress and senescence via the SIRT-1/p53 signaling pathway.
Literature
1.
Donato AJ, Machin DR, Lesniewski LA. Mechanisms of dysfunction in the Aging vasculature and role in Age-Related Disease. Circul Res. 2018;123(7):825–48.CrossRef
2.
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186(2):243–78.PubMedCrossRef
3.
Luo W, Wang Y, Yang H, Dai C, Hong H, Li J, et al. Heme oxygenase-1 ameliorates oxidative stress-induced endothelial senescence via regulating endothelial nitric oxide synthase activation and coupling. Aging. 2018;10(7):1722–44.PubMedPubMedCentralCrossRef
4.
Zhou Q, Meng G, Teng F, Sun Q, Zhang Y. Effects of astragalus polysaccharide on apoptosis of myocardial microvascular endothelial cells in rats undergoing hypoxia/reoxygenation by mediation of the PI3K/Akt/eNOS signaling pathway. J Cell Biochem. 2018;119(1):806–16.PubMedCrossRef
5.
Liu X, Gu X, Yu M, Zi Y, Yu H, Wang Y, et al. Effects of ginsenoside Rb1 on oxidative stress injury in rat spinal cords by regulating the eNOS/Nrf2/HO-1 signaling pathway. Exp Ther Med. 2018;16(2):1079–86.PubMedPubMedCentral
6.
Li M, Han B, Zhao H, Xu C, Xu D, Sieniawska E, et al. Biological active ingredients of Astragali Radix and its mechanisms in treating cardiovascular and cerebrovascular diseases. Phytomedicine. 2022;98:153918.PubMedCrossRef
7.
Sun S, Yang S, An N, Wang G, Xu Q, Liu J, et al. Astragalus polysaccharides inhibits cardiomyocyte apoptosis during diabetic cardiomyopathy via the endoplasmic reticulum stress pathway. J Ethnopharmacol. 2019;238:111857.PubMedCrossRef
8.
Huang WM, Liang YQ, Tang LJ, Ding Y, Wang XH. Antioxidant and anti-inflammatory effects of Astragalus polysaccharide on EA.hy926 cells. Exp Ther Med. 2013;6(1):199–203.PubMedPubMedCentralCrossRef
9.
Yuan LB, Hua CY, Gao S, Yin YL, Dai M, Meng HY, et al. Astragalus polysaccharides attenuate monocrotaline-induced pulmonary arterial hypertension in rats. Am J Chin Med. 2017;45(4):773–89.PubMedCrossRef
10.
Yang F, Yan G, Li Y, Han Z, Zhang L, Chen S, et al. Astragalus polysaccharide attenuated iron overload-induced dysfunction of mesenchymal stem cells via suppressing mitochondrial ROS. Cell Physiol Biochem. 2016;39(4):1369–79.PubMedCrossRef
11.
Zhang LY, Yong WX, Wang L, Zhang LX, Zhang YM, Gong HX, et al. Astragalus polysaccharide eases G1 phase-correlative bystander effects through mediation of TGF- β R/MAPK/ROS signal pathway after carbon ion irradiation in BMSCs. Am J Chin Med. 2019;47(3):595–612.PubMedCrossRef
12.
Li XT, Zhang YK, Kuang HX, Jin FX, Liu DW, Gao MB, et al. Mitochondrial protection and anti-aging activity of Astragalus polysaccharides and their potential mechanism. Int J Mol Sci. 2012;13(2):1747–61.PubMedPubMedCentralCrossRef
13.
Song J, Chen M, Li Z, Zhang J, Hu H, Tong X, et al. Astragalus polysaccharide extends lifespan via mitigating endoplasmic reticulum stress in the silkworm, bombyx mori. Aging Dis. 2019;10(6):1187–98.PubMedPubMedCentralCrossRef
14.
Miao XY, Zhu XX, Gu ZY, Fu B, Cui SY, Zu Y, et al. Astragalus polysaccharides reduce high-glucose-induced rat aortic endothelial cell senescence and inflammasome activation by modulating the mitochondrial Na+/Ca2+ exchanger. Cell Biochem Biophys. 2022;80(2):341–53.PubMedCrossRef
15.
Leibiger IB, Berggren PO. Sirt1: a metabolic master switch that modulates lifespan. Nat Med. 2006;12(1):34–6. discussion 36.PubMedCrossRef
16.
Liu D, Su J, Lin J, Qian G, Chen X, Song S, et al. Activation of AMPK-dependent SIRT-1 by astragalus polysaccharide protects against ochratoxin A-induced immune stress in vitro and in vivo. Int J Biol Macromol. 2018;120(Pt A):683–92.PubMedCrossRef
17.
Tissenbaum HA, Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature. 2001;410(6825):227–30.PubMedCrossRefADS
18.
Satoh A, Brace CS, Rensing N, Cliften P, Wozniak DF, Herzog ED, et al. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab. 2013;18(3):416–30.PubMedPubMedCentralCrossRef
19.
Chen C, Zhou M, Ge Y, Wang X. SIRT1 and aging related signaling pathways. Mech Ageing Dev. 2020;187:111215.PubMedCrossRef
20.
Donato AJ, Magerko KA, Lawson BR, Durrant JR, Lesniewski LA, Seals DR. SIRT-1 and vascular endothelial dysfunction with ageing in mice and humans. J Physiol. 2011;589(Pt 18):4545–54.PubMedPubMedCentralCrossRef
21.
Huang YF, Lu L, Zhu DJ, Wang M, Yin Y, Chen DX et al. Effects of astragalus polysaccharides on dysfunction of mitochondrial dynamics induced by oxidative stress. Oxid Med Cell Longev. 2016; 2016:9573291.
22.
Lu WW, Jia LX, Ni XQ, Zhao L, Chang JR, Zhang JS, et al. Intermedin1-53 attenuates abdominal aortic aneurysm by inhibiting oxidative stress. Arterioscler Thromb Vasc Biol. 2016;36(11):2176–90.PubMedCrossRef
23.
Zhu XX, Miao XY, Gong YP, Fu B, Li CL. Isolation and culture of rat aortic endothelial cells in vitro: a novel approach without collagenase digestion. J Cell Biochem. 2019;120(8):14127–35.PubMedCrossRef
24.
Ma X, Wang J, Li J, Ma C, Chen S, Lei W, et al. Loading MiR-210 in endothelial progenitor cells derived exosomes boosts their beneficial effects on hypoxia/reoxygeneation-injured human endothelial cells via protecting mitochondrial function. Cell Physiol Biochem. 2018;46(2):664–75.PubMedCrossRef
25.
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A. 1995;92(20):9363–7.PubMedPubMedCentralCrossRefADS
26.
Donato AJ, Walker AE, Magerko KA, Bramwell RC, Black AD, Henson GD, et al. Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice. Aging Cell. 2013;12(5):772–83.PubMedCrossRef
27.
de Picciotto NE, Gano LB, Johnson LC, Martens CR, Sindler AL, Mills KF, et al. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell. 2016;15(3):522–30.PubMedPubMedCentralCrossRef
28.
29.
Feissner RF, Skalska J, Gaum WE, Sheu SS. Crosstalk signaling between mitochondrial Ca2 + and ROS. Front Biosci (Landmark Ed). 2009;14:1197–218.PubMedCrossRef
30.
31.
Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, et al. Cellular senescence: defining a path forward. Cell. 2019;179(4):813–27.PubMedCrossRef
32.
33.
Salmon EE, Breithaupt JJ, Truskey GA. Application of oxidative stress to a tissue-engineered vascular aging model induces endothelial cell senescence and activation. Cells. 2020;9(5):1292.PubMedPubMedCentralCrossRef
34.
Arunachalam G, Yao H, Sundar IK, Caito S, Rahman I. SIRT1 regulates oxidant- and cigarette smoke-induced eNOS acetylation in endothelial cells: role of resveratrol. Biochem Biophys Res Commun. 2010;393(1):66–72.PubMedPubMedCentralCrossRef
35.
Kitada M, Ogura Y, Koya D. The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis. Aging. 2016;8(10):2290–307.PubMedPubMedCentralCrossRef
36.
D’Onofrio N, Vitiello M, Casale R, Servillo L, Giovane A, Balestrieri ML. Sirtuins in vascular diseases: emerging roles and therapeutic potential. Biochim Biophys Acta. 2015;1852(7):1311–22.PubMedCrossRef
37.
Hossain E, Li Y, Anand-Srivastava MB. Angiotensin II-induced overexpression of sirtuin 1 contributes to enhanced expression of Giα proteins and hyperproliferation of vascular smooth muscle cells. Am J Physiol Heart Circ Physiol. 2021;321(3):H496–h508.PubMedCrossRef
38.
Li Y, Hossain E, Arifen N, Srivastava AK, Anand-Srivastava MB. Sirtuin1 contributes to the overexpression of Giα proteins and hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats. J Hypertens. 2022;40(1):117–27.PubMedCrossRef
39.
Alcendor RR, Gao S, Zhai P, Zablocki D, Holle E, Yu X, et al. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res. 2007;100:1512–21.PubMedCrossRef
40.
Peng QH, Tong P, Gu LM, Li WJ. Astragalus polysaccharide attenuates metabolic memory-triggered ER stress and apoptosis via regulation of miR-204/SIRT1 axis in retinal pigment epithelial cells. Biosci Rep. 2020;40(1):BSR20192121.PubMedPubMedCentralCrossRef
41.
Ong ALC, Ramasamy TS. Role of Sirtuin1-p53 regulatory axis in aging, cancer and cellular reprogramming. Ageing Res Rev. 2018;43:64–80.PubMedCrossRef
42.
Lamichane S, Baek SH, Kim YJ, Park JH, Dahal Lamichane B, Jang WB, et al. MHY2233 attenuates replicative cellular senescence in human endothelial progenitor cells via SIRT1 signaling. Oxid Med Cell Longev. 2019;2019:6492029.PubMedPubMedCentralCrossRef
43.
Khanh VC, Zulkifli AF, Tokunaga C, Yamashita T, Hiramatsu Y, Ohneda O. Aging impairs beige adipocyte differentiation of mesenchymal stem cells via the reduced expression of Sirtuin 1. Biochem Biophys Res Commun. 2018;500(3):682–90.PubMedCrossRef
44.
Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey M, Baker M, et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol. 2020;18(7):e3000410.PubMedPubMedCentralCrossRef
Metadata
Title
Astragalus polysaccharides attenuate rat aortic endothelial senescence via regulation of the SIRT-1/p53 signaling pathway
Authors
Xinyu Miao
Lingjun Rong
Bo Fu
Shaoyuan Cui
Zhaoyan Gu
Fan Hu
Yanhui Lu
Shuangtong Yan
Banruo Sun
Wenli Jiang
Yuting Zhang
Yanping Gong
Chunlin Li
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2024
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-024-04387-4

Other articles of this Issue 1/2024

BMC Complementary Medicine and Therapies 1/2024 Go to the issue

Research

Effects of garlic (Allium sativum L) and Citrullus colocynthis (L.) Schrad individually and in combination on male reproductive damage due to diabetes: suppression of the AGEs/RAGE/Nox-4 signaling pathway

Research

Trends in the use of complementary and alternative medicine between 1987 and 2021 in Denmark

Research

Study on the differential hepatotoxicity of raw polygonum multiflorum and polygonum multiflorum praeparata and its mechanism

Research

Development and characterization of a topical gel, containing lavender (Lavandula angustifolia) oil loaded solid lipid nanoparticles

Research

Berberine alleviates ischemia reperfusion injury induced AKI by regulation of intestinal microbiota and reducing intestinal inflammation

Research

Effect of aromatherapy with peppermint essential oil on the gag reflex: a randomized, placebo-controlled, single-blind, crossover study