Antihyperglycemic Effects of Salvia polystachya Cav. and Its Terpenoids: α-Glucosidase and SGLT1 Inhibitors
Abstract
:1. Introduction
2. Results
2.1. In Vivo Assays
2.1.1. Acute Oral Toxicity of the Ethanolic Extract of the Stems from S. polystachya
2.1.2. Acute Effect of Ethanolic Extract of Stems from S. polystachya and its Products over Glycemia in Normal and Diabetic Mice
2.1.3. Oral Sucrose and Starch Tolerance Tests of the Products Obtained from Stems from S. polystachya
2.1.4. Oral Glucose and Galactose Tolerance Tests of the Products Obtained from Stems from S. polystachya
2.2. Ex Vivo Assays
2.2.1. Inhibition of Intestinal Sucrose Hydrolysis of the Products Obtained from the Stems from S. polystachya
2.2.2. Inhibition of Intestinal Glucose Absorption of the Products Obtained from the Stems from S. polystachya
2.3. In Silico Assays
2.3.1. Molecular Docking Studies of Ursolic Acid (UA), Oleanolic Acid (OA) and Acarbose on α-Glucosidase Enzyme
2.3.2. Molecular Docking Studies of Ursolic Acid (UA), Oleanolic Acid (OA) and Canagliflozin on SGLT1 Cotransporter
3. Discussion
4. Materials and Methods
4.1. General Information
4.2. Plant Material
4.3. Preparation of Ethanolic Extracts, Fractionation, and Characterization of Ursolic and Oleanolic Acid
4.4. Experimental Animals
4.5. In Vivo Assays
4.5.1. Acute Toxicity Study
4.5.2. Induction of Experimental Type 2 Diabetes
4.5.3. Acute Effect of Ethanolic Extract from Stems of S. polystachya and Its Products over Glycemia
4.5.4. Oral Sucrose and Starch Tolerance Tests of the Products Obtained from Stems from S. polystachya
4.5.5. Oral Glucose and Galactose Tolerance Tests of the Products Obtained from the Stems from S. polystachya
4.6. Ex Vivo Assays
Determination of the Inhibition of Intestinal Sucrose Hydrolysis and Glucose Absorption of the Products Obtained from the Stems from S. polystachya Cav. and Its Products
4.7. In Silico Assays
4.8. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Group | Dose (mg/kg) | Pancreas (g) | Liver (g) | Kidneys (g) | Stomach (g) |
---|---|---|---|---|---|
Normal | - | 0.8 ± 0.0 | 4.9 ± 0.1 | 1.2 ± 0.05 | 1.4 ± 0.1 |
EESpS | 50 | 0.7 ± 0.0 | 4.5 ± 0.2 | 1.1 ± 0.1 | 2.1 ± 0.1 |
300 | 0.6 ± 0.1 | 5.0 ± 0.3 | 1.2 ± 0.1 | 2.0 ± 0.5 | |
2000 | 0.8 ± 0.2 | 4.8 ± 0.2 | 1.2 ± 0.0 | 1.9 ± 0.5 |
Group | Dose (mg/kg−1) | 0 min | 30 min | 60 min | 90 min | 120 min |
---|---|---|---|---|---|---|
NM control | - | 175.3 ± 1.4 | 174 ± 1.8 | 170.5 ± 2.6 | 172.8 ± 2 | 178.5 ± 1.7 |
DM control | - | 302.5 ± 5.7 | 306 ± 3.7 | 309.4 ± 2.8 | 311.5 ± 1.5 | 294.8 ± 0.6 |
DM + EESpS | 50 | 295.5 ± 5 | 310.3 ± 12 | 290.3 ± 14 | 300 ± 20 | 291.8 ± 1 |
DM + EESpS | 100 | 301.8 ± 1 | 242.3 ± 0.6 * | 258.3 ± 1.2 ** | 241.3 ± 0.8 ■ | 247.3 ± 0.3 ■■ |
DM + EESpS | 200 | 303.3 ± 10 | 320.4 ± 7.3 | 307.8 ± 1.3 | 287 ± 9.5 ■ | 313.3 ± 3.5 |
DM + AqRFr | 50 | 309 ± 2.6 | 268.4 ± 2.7 | 231.6 ± 3.4 | 218.8 ± 1 | 213.3 ± 7.9 |
DM + EtOAcFr | 50 | 300 ± 4.8 | 249 ± 5.9 * | 203.3 ± 1.8 ** | 213 ± 4.4 ■ | 187.5 ± 0.6 ■■ |
DM + SeFr6 | 50 | 293.5 ± 2.5 | 338.8 ± 2.2 | 386 ± 3.9 | 330.3 ± 4.2 | 259.3 ± 5.1 ■■ |
DM + Oleanolic acid | 50 | 283.2 ± 5.2 | 302 ± 11.4 | 302 ± 7.2 | 239.4 ± 3.1 ■ | 252.8 ± 2.9 ■■ |
DM + Ursolic acid | 50 | 268.7 ± 4 | 220.8 ± 5.9 * | 239 ± 6.6 ** | 259.2 ± 4 ■ | 236 ± 5.5 ■■ |
DM + Acarbose | 50 | 308.7 ± 1.6 | 236.8 ± 2.3 * | 237.8 ± 3.4 ** | 249 ± 1.5 ■ | 225 ± 2.5 ■■ |
DM + Glibenclamide | 50 | 307.6 ± 1.8 | 243.5 ± 6.2 * | 247.8 ± 5.4 ** | 268 ± 1.9 ■ | 292 ± 2.3 ■■ |
Treatment | Glucose (mg/dL−1) | Glucose (mg/dL−1) | % of Inhibition | IC50 |
---|---|---|---|---|
0 h | 2 h | |||
Sucrose (15%) | 0 ± 0 | 90.6 ± 5.8 | - | - |
EESpS [200 µgmL−1] | 0 ± 0 | 71.6 ± 1.6 * | 20.8 ± 1.8 | 734.3 µgmL−1 |
EESpS [400 µgmL−1] | 0 ± 0 | 55 ± 2 * | 39.2 ± 2.2 | |
EESpS [800 µgmL−1] | 0 ± 0 | 44 ± 1.8 * | 51.4 ± 2 | |
EtOAcFr [200 µgmL−1] | 0 ± 0 | 65.6 ± 1.2 * | 27.5 ± 1.3 | 573.5 µgmL−1 |
EtOAcFr [400 µgmL−1] | 0 ± 0 | 51 ± 1.4 * | 43.7 ± 1.6 | |
EtOAcFr [800 µg/mL−1] | 0 ± 0 | 35 ± 1.7 * | 61.3 ± 1.8 | |
UA [200 µM] | 0 ± 0 | 59.3 ± 1.8 * | 34.5± 2 | 739.9 µM |
UA [400 µM] | 0 ± 0 | 48.3 ± 1.2 * | 46.6 ± 1.3 | |
UA [800 µM] | 0 ± 0 | 45.3 ± 1.9 * | 49.9± 2.1 | |
OA [200 µM] | 0 ± 0 | 87 ± 3.9 | 3.9 ± 1.6 | 726.3 µM |
OA [400 µM] | 0 ± 0 | 77.3 ± 1.2 * | 14.6 ± 1.3 | |
OA [800 µM] | 0 ± 0 | 50 ± 3.6 * | 44.8 ± 4 | |
Acarbose [200 µM] | 0 ± 0 | 38.2 ± 1.22 * | 57.8 ± 1.3 | |
Acarbose [400 µM] | 0 ± 0 | 13.1 ± 0.75 * | 85.5 ± 0.8 | 173 µM |
Acarbose [800 µM] | 0 ± 0 | 7 ± 0.4 * | 96.7 ± 0.18 |
Treatment | Glucose (mg/dL−1) | Glucose (mg/dL−1) | % Of Inhibition | IC50 |
---|---|---|---|---|
0 h | 1 h | |||
Glucose (5%) | 0 ± 0 | 217.3 ± 6.1 | - | - |
EESpS [200 µg/mL−1] | 0 ± 0 | 216 ± 8.1 | 0.5 ± 3.7 | 1536.3 µg/mL |
EESpS [400 µg/mL−1] | 0 ± 0 | 192.5 ± 3.7 * | 11.4 ± 1.4 | |
EESpS [800 µg/mL−1] | 0 ± 0 | 167.7 ± 9 * | 22.8 ± 4.1 | |
EtOAcFr [200 µg/mL−1] | 0 ± 0 | 175.3 ± 19 * | 19.3 ± 8.7 | 697.3 µg/mL |
EtOAcFr [400 µg/mL−1] | 0 ± 0 | 162.7 ± 1.8 * | 25.1 ± 0.8 | |
EtOAcFr [800 µg/mL−1] | 0 ± 0 | 176.5 ± 7.1 * | 18.7 ± 7.7 | |
UA [200 µM] | 0 ± 0 | 270 ± 31.3 | 0 | 966.6 µM |
UA [400 µM] | 0 ± 0 | 188.3 ± 4 * | 13.3 ± 1.8 | |
UA [800 µM] | 0 ± 0 | 132.3 ± 5.3 * | 39.1 ± 2.4 | |
OA [200 µM] | 0 ± 0 | 189.3 ± 4 * | 12.8 ± 1.8 | 849.3 µM |
OA [400 µM] | 0 ± 0 | 132.3 ± 2.2 * | 39.1 ± 1 | |
OA [800 µM] | 0 ± 0 | 121 ± 6.5 * | 44.3 ± 3 | |
Canagliflozin [200 µM] | 0 ± 0 | 230 ± 13.3 | 0 | |
Canagliflozin [400 µM] | 0 ± 0 | 113.5 ± 7.4 * | 49 ± 3.1 | 834.5 µM |
Canagliflozin [800 µM] | 0 ± 0 | 124 ± 5.7 * | 40.5 ± 1.3 |
Compound | α-Glucosidase | SGLT1 | ||||||
---|---|---|---|---|---|---|---|---|
ΔG (kcal-mol−1) | H-BR | NPI | RMSD | ΔG (kcal-mol−1) | H-BR | NPI | RMSD | |
Oleanolic acid | −6.41 | Leu677 | Asp282, Met519, Phe525, Leu650, Gly651, Ser676, Leu678 | - | −10.55 | Gln451 | Gly272, Ala447, Gln448, Ser449, Asp454, Tyr455, Glu503, Thr508, Cys522, Gly523, Val524, His525, Tyr526 | - |
Ursolic acid | −5.48 | Asp518 | Trp376, Trp481, Met519, Asp616, Phe649, Leu650, His674 | - | −9.65 | Gln451, Gly523 | Asp273, Ala447, Gln448, Ser449, Asp454, Tyr455, Ser458, Thr508, Cys522 | - |
Acarbose | −8.33 | Arg281, Asp282, Ala284, Arg600, Asp616, Gly651, Ser676, Leu678 | Met519, Trp618, Leu650 | 1.87 | - | - | - | - |
Canagliflozin | - | - | - | - | −11.04 | Met283, Thr287, Tyr290, Trp291, Gln 457 | Asn78, His83, Phe101 | 1.44 |
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Ortega, R.; Valdés, M.; Alarcón-Aguilar, F.J.; Fortis-Barrera, Á.; Barbosa, E.; Velazquez, C.; Calzada, F. Antihyperglycemic Effects of Salvia polystachya Cav. and Its Terpenoids: α-Glucosidase and SGLT1 Inhibitors. Plants 2022, 11, 575. https://doi.org/10.3390/plants11050575
Ortega R, Valdés M, Alarcón-Aguilar FJ, Fortis-Barrera Á, Barbosa E, Velazquez C, Calzada F. Antihyperglycemic Effects of Salvia polystachya Cav. and Its Terpenoids: α-Glucosidase and SGLT1 Inhibitors. Plants. 2022; 11(5):575. https://doi.org/10.3390/plants11050575
Chicago/Turabian StyleOrtega, Rocio, Miguel Valdés, Francisco J. Alarcón-Aguilar, Ángeles Fortis-Barrera, Elizabeth Barbosa, Claudia Velazquez, and Fernando Calzada. 2022. "Antihyperglycemic Effects of Salvia polystachya Cav. and Its Terpenoids: α-Glucosidase and SGLT1 Inhibitors" Plants 11, no. 5: 575. https://doi.org/10.3390/plants11050575