Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver
Magnesium lithospermate B (MLB) is the biologically active compound of the water-soluble fraction of Salvia miltiorrhiza. Magnesium lithospermate B exhibits various biological functions, including antidiabetic, neuroprotective, and antioxidant effects. However, its beneficial effects on insulin sens...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-08-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1420-3049/23/9/2098 |
| _version_ | 1828347332552294400 |
|---|---|
| author | Ji won Jeong Bonggi Lee Dae Hyun Kim Hyoung Oh Jeong Kyoung Mi Moon Min Jo Kim Takako Yokozawa Hae Young Chung |
| author_facet | Ji won Jeong Bonggi Lee Dae Hyun Kim Hyoung Oh Jeong Kyoung Mi Moon Min Jo Kim Takako Yokozawa Hae Young Chung |
| author_sort | Ji won Jeong |
| collection | DOAJ |
| description | Magnesium lithospermate B (MLB) is the biologically active compound of the water-soluble fraction of Salvia miltiorrhiza. Magnesium lithospermate B exhibits various biological functions, including antidiabetic, neuroprotective, and antioxidant effects. However, its beneficial effects on insulin sensitivity and related signaling pathways in the liver need to be elucidated. Our previous study reported that MLB is a PPARβ/δ agonist in fibroblasts. Because insulin-sensitizing and anti-inflammatory effects of PPARβ/δ has been reported in the liver, we investigated whether MLB has a beneficial effect on insulin-, ER stress- and inflammasome-related signaling in the livers of aging and obese animal models. Western blotting and protein-ligand docking simulation showed that MLB activated PPARβ/δ and improved glucose tolerance in the livers of aging and obese animal models. MLB supplementation ameliorated aging or obesity-induced disruption of insulin signaling in the liver. Consistently, aging and obesity-induced increase in the protein levels of a gluconeogenic phosphoenolpyruvate carboxykinase was decreased by MLB. When molecular signaling pathways related to insulin signaling were examined in the liver, MLB supplementation suppressed ER stress- and inflammasome-related signaling molecules induced by aging and obesity. These results suggest that MLB may improve insulin resistance in the liver at least partially by suppressing ER stress and inflammasome formation in aging and obese animal models. |
| first_indexed | 2024-04-14T00:38:59Z |
| format | Article |
| id | doaj.art-b39ca2527b064f1c9be8385232f141e4 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-14T00:38:59Z |
| publishDate | 2018-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b39ca2527b064f1c9be8385232f141e42022-12-22T02:22:16ZengMDPI AGMolecules1420-30492018-08-01239209810.3390/molecules23092098molecules23092098Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the LiverJi won Jeong0Bonggi Lee1Dae Hyun Kim2Hyoung Oh Jeong3Kyoung Mi Moon4Min Jo Kim5Takako Yokozawa6Hae Young Chung7Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, KoreaMolecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, KoreaMolecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, KoreaMolecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, KoreaMolecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, KoreaMolecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, KoreaGraduate School of Science and Engineering for Research, University of Toyama, Toyama 930-8555, JapanMolecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, KoreaMagnesium lithospermate B (MLB) is the biologically active compound of the water-soluble fraction of Salvia miltiorrhiza. Magnesium lithospermate B exhibits various biological functions, including antidiabetic, neuroprotective, and antioxidant effects. However, its beneficial effects on insulin sensitivity and related signaling pathways in the liver need to be elucidated. Our previous study reported that MLB is a PPARβ/δ agonist in fibroblasts. Because insulin-sensitizing and anti-inflammatory effects of PPARβ/δ has been reported in the liver, we investigated whether MLB has a beneficial effect on insulin-, ER stress- and inflammasome-related signaling in the livers of aging and obese animal models. Western blotting and protein-ligand docking simulation showed that MLB activated PPARβ/δ and improved glucose tolerance in the livers of aging and obese animal models. MLB supplementation ameliorated aging or obesity-induced disruption of insulin signaling in the liver. Consistently, aging and obesity-induced increase in the protein levels of a gluconeogenic phosphoenolpyruvate carboxykinase was decreased by MLB. When molecular signaling pathways related to insulin signaling were examined in the liver, MLB supplementation suppressed ER stress- and inflammasome-related signaling molecules induced by aging and obesity. These results suggest that MLB may improve insulin resistance in the liver at least partially by suppressing ER stress and inflammasome formation in aging and obese animal models.http://www.mdpi.com/1420-3049/23/9/2098magnesium lithospermate BPPARβ/δER stressinsulin resistanceinflammasomeaging |
| spellingShingle | Ji won Jeong Bonggi Lee Dae Hyun Kim Hyoung Oh Jeong Kyoung Mi Moon Min Jo Kim Takako Yokozawa Hae Young Chung Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver Molecules magnesium lithospermate B PPARβ/δ ER stress insulin resistance inflammasome aging |
| title | Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver |
| title_full | Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver |
| title_fullStr | Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver |
| title_full_unstemmed | Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver |
| title_short | Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver |
| title_sort | mechanism of action of magnesium lithospermate b against aging and obesity induced er stress insulin resistance and inflammsome formation in the liver |
| topic | magnesium lithospermate B PPARβ/δ ER stress insulin resistance inflammasome aging |
| url | http://www.mdpi.com/1420-3049/23/9/2098 |
| work_keys_str_mv | AT jiwonjeong mechanismofactionofmagnesiumlithospermatebagainstagingandobesityinducederstressinsulinresistanceandinflammsomeformationintheliver AT bonggilee mechanismofactionofmagnesiumlithospermatebagainstagingandobesityinducederstressinsulinresistanceandinflammsomeformationintheliver AT daehyunkim mechanismofactionofmagnesiumlithospermatebagainstagingandobesityinducederstressinsulinresistanceandinflammsomeformationintheliver AT hyoungohjeong mechanismofactionofmagnesiumlithospermatebagainstagingandobesityinducederstressinsulinresistanceandinflammsomeformationintheliver AT kyoungmimoon mechanismofactionofmagnesiumlithospermatebagainstagingandobesityinducederstressinsulinresistanceandinflammsomeformationintheliver AT minjokim mechanismofactionofmagnesiumlithospermatebagainstagingandobesityinducederstressinsulinresistanceandinflammsomeformationintheliver AT takakoyokozawa mechanismofactionofmagnesiumlithospermatebagainstagingandobesityinducederstressinsulinresistanceandinflammsomeformationintheliver AT haeyoungchung mechanismofactionofmagnesiumlithospermatebagainstagingandobesityinducederstressinsulinresistanceandinflammsomeformationintheliver |