Citation: | MO Xinhe, WAN Youqiong, WANG Sibu, et al. Ameliorative effect of baicalin nanomedicine on hydrogen peroxide-induced senescence of human umbilical vein vascular endothelial cells[J]. J China Pharm Univ, 2025, 56(1): 110 − 118. DOI: 10.11665/j.issn.1000-5048.2024052101 |
To investigate the effect of baicalin (BAI)-loaded cross-linked lipoic acid nanocapsules (BAI@cLANCs) against hydrogen peroxide (H2O2)-induced senescence in human umbilical vein endothelial cells (HUVECs), this study examined the toxicity of BAI@cLANCs on HUVECs by MTT method. The cell nuclear staining, SA-β-gal staining, and MTT methods were used to assess the optimal concentration of H2O2-induced senescence in HUVECs. The cellular uptake of BAI@cLANCs was evaluated using fluorescence microscopy imaging and flow cytometry. The proportion of cellular senescence was determined by SA-β-gal staining. The level of reactive oxygen species (ROS) in senescent cells was detected by fluorescence microscopy imaging and multifunctional microplate reader. The content of malondialdehyde (MDA) in cells was detected by lipid oxidation detection kit, and the cell cycle was analyzed by flow cytometry with propidium iodide staining. The results showed that BAI@cLANCs had no significant effect on the growth of HUVECs in the range of BAI at 2.80−112 mmol/L. 200 μmol/L and 25 minutes were the ideal conditions for H2O2-induced senescence of HUVECs. cLANCs as drug delivery carriers significantly enhanced the uptake efficiency of BAI in HUVECs. Compared with the normal group, the H2O2 model group showed decreased cell viability, increased positive SA-β-gal staining rate, increased ROS and MDA content, as well as increased percentage of cells blocked in S phase and decreased cells entering G2/M phase. Compared with the H2O2 model group, BAI, cLANCs, BAI + cLANCs, and BAI@cLANCs groups showed increased cell viability, decreased positive SA-β-gal staining rate, decreased ROS and MDA content, decreased percentage of S-phase cells, and increased cells entering G2/M phase, with the best anti-aging effect in the BAI@cLANCs group. In summary, the results above showed that both BAI and cLANCs have anti-aging properties. With cLANCs as drug carriers, the anti-aging benefits of BAI@cLANCs are synergistic and can effectively delay H2O2-induced senescence of HUVECs.
[1] |
Ke YL, Li D, Zhao MM, et al. Gut flora-dependent metabolite Trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress[J]. Free Radic Biol Med, 2018, 116: 88-100. doi: 10.1016/j.freeradbiomed.2018.01.007
|
[2] |
Marian AJ, Bhatnagar A, Bolli R, et al. Introduction to cardiovascular aging compendium[J]. Circ Res, 2018, 123(7): 737-739. doi: 10.1161/CIRCRESAHA.118.313940
|
[3] |
Ogrodnik M, Salmonowicz H, Gladyshev VN. Integrating cellular senescence with the concept of damage accumulation in aging: relevance for clearance of senescent cells[J]. Aging Cell, 2019, 18(1): e12841. doi: 10.1111/acel.12841
|
[4] |
Childs BG, Durik M, Baker DJ, et al. Cellular senescence in aging and age-related disease: from mechanisms to therapy[J]. Nat Med, 2015, 21(12): 1424-1435. doi: 10.1038/nm.4000
|
[5] |
Orrico F, Lopez AC, Saliwonczyk D, et al. The permeability of human red blood cell membranes to hydrogen peroxide is independent of aquaporins[J]. J Biol Chem, 2022, 298(1): 101503. doi: 10.1016/j.jbc.2021.101503
|
[6] |
Ji QS, Liu J, Wang GF, et al. EphA2 overexpression reduces H2O2-induced damage of lens epithelial cells[J]. Genet Mol Biol, 2021, 44(3): e20200414. doi: 10.1590/1678-4685-gmb-2020-0414
|
[7] |
Huang YQ, Sun MY, Yang XF, et al. Baicalin relieves inflammation stimulated by lipopolysaccharide via upregulating TUG1 in liver cells[J]. J Physiol Biochem, 2019, 75(4): 463-473. doi: 10.1007/s13105-019-00698-0
|
[8] |
Pan YT, Chen D, Lu QY, et al. Baicalin prevents the apoptosis of endplate chondrocytes by inhibiting the oxidative stress induced by H2O2[J]. Mol Med Rep, 2017, 16(3): 2985-2991. doi: 10.3892/mmr.2017.6904
|
[9] |
Jia Y, Xu RG, Hu YC, et al. Anti-NDV activity of baicalin from a traditional Chinese medicine in vitro[J]. J Vet Med Sci, 2016, 78(5): 819-824. doi: 10.1292/jvms.15-0572
|
[10] |
Zhang Y, Li X, Ciric B, et al. Therapeutic effect of baicalin on experimental autoimmune encephalomyelitis is mediated by SOCS3 regulatory pathway[J]. Sci Rep, 2015, 5: 17407. doi: 10.1038/srep17407
|
[11] |
Zeng N, Zhang GW, Hu X, et al. Inhibition mechanism of baicalein and baicalin on xanthine oxidase and their synergistic effect with allopurinol[J]. J Funct Foods, 2018, 50: 172-182. doi: 10.1016/j.jff.2018.10.005
|
[12] |
Wang X, Yu JY, Sun Y, et al. Baicalin protects LPS-induced blood-brain barrier damage and activates Nrf2-mediated antioxidant stress pathway[J]. Int Immunopharmacol, 2021, 96: 107725. doi: 10.1016/j.intimp.2021.107725
|
[13] |
Zhao L, Wei YM, Huang Y, et al. Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and in vivo evaluation[J]. Int J Nanomedicine, 2013, 8: 3769-3779.
|
[14] |
Theodosis-Nobelos P, Papagiouvannis G, Tziona P, et al. Lipoic acid. Kinetics and pluripotent biological properties and derivatives[J]. Mol Biol Rep, 2021, 48(9): 6539-6550. doi: 10.1007/s11033-021-06643-z
|
[15] |
Liao CY, Dai X, Chen Y, et al. Biogenic (R)-(+)-lipoic acid only constructed cross-linked vesicles with synergistic anticancer potency[J]. Adv Funct Materials, 2019, 29(3): 1806567. doi: 10.1002/adfm.201806567
|
[16] |
Wang L, Jing P, Tan J, et al. “One-stitch” bioorthogonal prodrug activation based on cross-linked lipoic acid nanocapsules[J]. Biomaterials, 2021, 273: 120823. doi: 10.1016/j.biomaterials.2021.120823
|
[17] |
Huang N, Chen HH, Gong H, et al. SeHed, a novel gene expression system with stress-evoked hydrogen peroxide elimination property and anti-aging effect[J]. Signal Transduct Target Ther, 2022, 7(1): 235. doi: 10.1038/s41392-022-01047-2
|