Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158

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Salvia miltiorrhiza prevents methylglyoxal-induced glucotoxicity via the regulation of apoptosis-related pathways and the glyoxalase system in human umbilical vein endothelial cells
Jae Sung KimJae Hyuk LeeSeong Min HongKyoHee ChoSun Yeou Kim
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論文ID: b21-00507

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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 µg/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 µg/mL) strongly prevented expressed levels of RAGE, MGO-induced apoptosis and reduced ROS generation in HUVECs, comparing with 1 mM aminoguanidine. Additionally, SME (5 and 10 µg/mL) reduced the expression of proteins (e.g., p-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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