Salvia miltiorrhiza Prevents Methylglyoxal-Induced Glucotoxicity via the Regulation of Apoptosis-Related Pathways and the Glyoxalase System in Human Umbilical Vein Endothelial Cells
- Authors
- Kim, Jae Sung; Lee, Jae Hyuk; Hong, Seong Min; Cho, Kyo Hee; Kim, Sun Yeou
- Issue Date
- Jan-2022
- Publisher
- PHARMACEUTICAL SOC JAPAN
- Keywords
- Salvia miltiorrhiza extract; methylglyoxal; advanced glycation end-product; endothelial dysfunction; human umbilical vein endothelial cell; apoptosis
- Citation
- BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.45, no.1, pp.51 - 62
- Journal Title
- BIOLOGICAL & PHARMACEUTICAL BULLETIN
- Volume
- 45
- Number
- 1
- Start Page
- 51
- End Page
- 62
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/83261
- DOI
- 10.1248/bpb.b21-00507
- ISSN
- 0918-6158
- Abstract
- Methylglyoxal (MGO), which is produced as a byproduct of glucose metabolism, is the leading to diabetic cardiovascular complications. Salvia miltiorrhiza Bunge (Lamiaceae) has been reported as a potential plant to control diabetes and cardiovascular disease. However, no report exists on the effect of Salvia miltiorrhiza Bunge extract (SME) on MGO-induced glucotoxicity in human umbilical vein endothelial cells (HUVECs). We demonstrated the protective effects of SME (1, 5, and 10 mu g/mL) and its components against MGO-induced endothelial dysfunction in HUVECs. Cytotoxicity was evaluated using the several in vitro experiments. Additionally, the protein expression of receptor of advanced glycation end-products (RAGE), mitogen-activated protein kinase (MAPK) pathway and glyoxalase system were measured. Then, the inhibitory effects of SME and its main components on MGO-induced oxidative stress, radical scavenging, formation of MGO-derived advanced glycation end products (AGEs), and MGO-AGEs crosslinking were evaluated. SME (10 mu g/mL) strongly prevented expressed levels of RAGE, MGO-induced apoptosis and reduced reactive oxygen species (ROS) generation in HUVECs, comparing with 1 mM aminoguanidine. Additionally, SME (5 and 10 mu g/mL) reduced the expression of proteins (e.g., p-extracellular signal-regulated kinase (ERK) and p-p38) in the MAPKs pathway and upregulated the glyoxalase system in HUVECs. SME (0.5-10 mg/mL), dihydrotanshinone (0.4 mM), and rosmarinic acid (0.4 mM) prevented MGO-AGEs formation and broke the MGO-AGE crosslinking. These results show that S. miltiorrhiza has protective effects against MGO-induced glucotoxicity by regulating the proteins involved in apoptosis, glyoxalase system and antioxidant activity. We expect that S. miltiorrhiza is a potential natural resource for the treatment of MGO-induced vascular endothelial dysfunction.
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