PMID- 31931595 OWN - NLM STAT- MEDLINE DCOM- 20200904 LR - 20200904 IS - 1793-6853 (Electronic) IS - 0192-415X (Linking) VI - 48 IP - 1 DP - 2020 TI - Rhodiola crenulata Suppresses High Glucose-Induced Matrix Metalloproteinase Expression and Inflammatory Responses by Inhibiting ROS-Related HMGB1-TLR4 Signaling in Endothelial Cells. PG - 91-105 LID - 10.1142/S0192415X20500056 [doi] AB - Rhodiola crenulata, a popular folk medicine for anti-altitude sickness in Tibet, has been shown to have protective effects against high glucose (HG)-induced endothelial cell dysfunction in human umbilical vein endothelial cells (HUVECs). However, its mechanisms of action are unclear. Here, we aimed to examine the effects and the mechanisms of action of Rhodiola crenulata extract (RCE) on matrix metalloproteinases (MMPs) and inflammatory responses under HG conditions. HUVECs were pretreated with RCE or untreated and then exposed to 33 mM glucose medium for 24 h. The levels of oxidative stress markers, MMPs, endogenous tissue inhibitors of MMPs (TIMPs), and adhesion molecules were determined. Zymography assays were also carried out. We found that RCE significantly decreased HG-induced increases in reactive oxygen species (ROS) and activation of MAPK and NF-kappaB pathways. In addition, RCE not only significantly reduced the expression and activities of MMPs but also upregulated TIMP protein levels. Consistently, HG-induced activation of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response protein (MyD88) signaling pathway, intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and high mobility group box 1 (HMGB1) as well as endothelial cell apoptosis was inhibited by RCE treatment. RCE exerts protective effects on endothelial cells against HG insult, partially by suppressing the HMGB1/TLR4 axis. These findings indicate that Rhodiola crenulata may be a potential therapeutic agent for diabetes-associated vascular diseases. FAU - Huang, Li-Yen AU - Huang LY AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. AD - Division of Cardiology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan. FAU - Yen, I-Chuan AU - Yen IC AD - School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. FAU - Tsai, Wei-Cheng AU - Tsai WC AD - Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan. FAU - Lee, Shih-Yu AU - Lee SY AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. AD - Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan. LA - eng PT - Journal Article DEP - 20200114 PL - Singapore TA - Am J Chin Med JT - The American journal of Chinese medicine JID - 7901431 RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, human) RN - 0 (Plant Extracts) RN - 0 (Reactive Oxygen Species) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Cells, Cultured MH - Glucose/metabolism MH - HMGB1 Protein/*metabolism MH - Human Umbilical Vein Endothelial Cells/drug effects MH - Humans MH - Matrix Metalloproteinases/*metabolism MH - Oxidative Stress/*drug effects MH - Plant Extracts/*pharmacology MH - Reactive Oxygen Species/metabolism MH - Rhodiola/*chemistry MH - Toll-Like Receptor 4/*metabolism OTO - NOTNLM OT - Endothelial Cells OT - High Glucose OT - High Mobility Group Box 1 OT - Matrix Metalloproteinases OT - Rhodiola crenulata OT - Toll-Like Receptor 4 EDAT- 2020/01/15 06:00 MHDA- 2020/09/05 06:00 CRDT- 2020/01/15 06:00 PHST- 2020/01/15 06:00 [pubmed] PHST- 2020/09/05 06:00 [medline] PHST- 2020/01/15 06:00 [entrez] AID - 10.1142/S0192415X20500056 [doi] PST - ppublish SO - Am J Chin Med. 2020;48(1):91-105. doi: 10.1142/S0192415X20500056. Epub 2020 Jan 14.