Therapeutic Potential of Rosa davurica Pall. Root Extract as an Antidiabetic Agent: A Comprehensive Analysis from Molecular Mechanisms to In Vivo Efficacy
Abstract
:1. Introduction
2. Results
2.1. Polyphenol Content of RDR and Its Antioxidant and Radical Scavenging Activities
2.2. α-Glucosidase Inhibitory Activities of RDR
2.3. Effects of RDR on Glucose Uptake in C2C12 Cells
2.4. Effects of RDR on the PI3K/Akt Signaling Cascade
2.5. Effects of RDR on AMPK Signaling
2.6. Effects of RDR on Glucose Transporter Type 4
2.7. Effect of RDR on Symptoms of Diabetes Mellitus (DM) in STZ-Induced Diabetic Rats
2.8. Effects of RDR on Blood Glucose and Liver and Kidney Functions in STZ-Induced Diabetic Rats
2.9. Effects of RDR on Pancreatic Function in STZ-Induced Diabetic Rats
2.10. Identification of Phytochemical Compounds in RDR through GC–MS Chromatogram
2.11. Molecular Docking Analysis of the Potential Interaction between the Main Components in RDR and GLUT4
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Preparation of R. davurica Pall. Extracts
4.3. Determination of Total Polyphenols
4.4. DPPH Radical Scavenging Assay
4.5. Reducing Power Assay
4.6. Cell Culture and Cytotoxicity Assay
4.7. α-Glucosidase Inhibitory Activities
4.8. Measurement of Glucose Uptake
- (1)
- 10 μL of the samples (or standard) was mixed with 10 μL of 4% phenol acid in an e-tube.
- (2)
- After 5 min, 100 μL of sulfuric acid was added to the e-tube with the mixture, and then the e-tube was placed in a 30 °C water bath for 30 min.
- (3)
- The reaction was adapted to a 96-well format, where 50 μL of the mixture was blended with 50 μL of distilled water, and the absorbance was assessed at 490 nm using a GENios® spectrophotometer (BioTek Instruments, Inc., Winooski, VT, USA). The glucose uptake was quantified based on the standard curve. The results were presented as a fold-increase from their respective controls (vehicle alone).
4.9. Isolation of Cytosolic and Plasma Membrane Fraction Proteins
4.10. Western Blotting
4.11. Animals
4.12. Induction of Diabetes Rat Model and Treatment of RDR
- Group I—Control (normal rats administered with saline)
- Group II—STZ (diabetic rats administered with saline)
- Group III—STZ + RDR (diabetic rats administered with a low dosage of RDR, 100 mg/kg)
- Group IV—STZ + RDR (diabetic rats administered with a high dosage of RDR, 500 mg/kg)
- Group V—STZ + MET (diabetic rats administered with metformin, 200 mg/kg).
4.13. Blood Biochemical Analysis
4.14. Histological Analysis
4.15. GC Analysis
4.16. Molecular Docking Analysis
4.17. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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No. | Retention Time (min) | Compound Name | Molecular Formula | Score (%) | Mass (m/z) | Activity (1) |
---|---|---|---|---|---|---|
1 | 24.358 | 4H-Pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-(=DDMP) | C6H8O4 | 71.94 | 144 | Antioxidant, antidiabetic, antimicrobial, anti-inflammatory |
2 | 35.195 | 1,2,3-Benzenetriol (=Pyrogallol) | C6H6O3 | 94.58 | 126 | Antimicrobial preservative |
3 | 40.980 | D-Allose | C6H12O6 | 79.29 | 180.1 | Antioxidant, antidiabetic, anticancer, |
4 | 55.805 | Dibutyl phthalate | C16H22O4 | 95.45 | 278.2 | Antifouling, antimicrobial |
5 | 56.027 | n-Hexadecanoic acid (=Palmitic acid) | C16H32O2 | 92.52 | 256.2 | Antioxidant, hypocholesterolemic nematicide, pesticide, lubricant, antiandrogenic, flavor, hemolytic 5-alpha reductase inhibitor |
6 | 59.157 | 9,12-Octadecadienoic acid (Z,Z)- (=Linoleic acid) | C18H32O2 | 96.31 | 280.2 | Antioxidant, antidiabetic, anticancer, hypocholesterolemic action |
7 | 59.289 | Oleic acid | C18H34O2 | 89.19 | 282.3 | Anti-inflammatory, anti-androgenic cancer preventive, dermatitigenic hypocholesterolemic, 5-alpha reductase inhibitor, anemia genic insectifuge, flavor |
8 | 59.799 | Octadecanoic acid (=Stearic acid) | C18H36O2 | 89.09 | 284.3 | Antidiabetic, hypocholesterolemic action |
Compound Name | AutoDock Score (kcal/mol) | Hydrogen Bond Interactions | Hydrophobic Interactions |
---|---|---|---|
4H-Pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-(=DDMP) | −5.5 | 384-HIS, 386-LYS, 387-ASN, 480-GLY | 479-ILE |
1,2,3-Benzenetriol (=Pyrogallol) | −5.6 | 36-ASN, 144-ARG | - |
D-Allose | −6.9 | 56-THR, 110-TYR, 400-ARG | - |
Dibutyl phthalate | −5.7 | 56-THR | 110-TYR, 143-TYR, 175-ILE, 327-PRO, 396-LEU, 400-ARG, 402-VAL, 483-PRO |
n-Hexadecanoic acid (=Palmitic acid) | −6.3 | 54-GLY, 436-THR | 70-ILE, 110-TYR, 175-ILE, 327-PRO, 396-LEU, 402-VAL, 459-LEU |
9,12-Octadecadienoic acid (Z,Z)- (=Linoleic acid) | −6.0 | 56-THR | 106-PRO, 110-TYR, 175-ILE, 327-PRO, 396-LEU, 402-VAL, 459-LEU, 483-PRO |
Oleic acid | −5.7 | - | 110-TYR, 327-PRO, 396-LEU, 400-ARG, 402-VAL, 459-LEU, 483-PRO |
Octadecanoic acid (=Stearic acid) | −5.7 | 110-TYR | 175-ILE, 327-PRO, 396-LEU, 400-ARG, 402-VAL, 459-LEU, 483-PRO |
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Hwang, D.H.; Asirvatham, R.D.; Mohan Prakash, R.L.; Kang, C.; Kim, E. Therapeutic Potential of Rosa davurica Pall. Root Extract as an Antidiabetic Agent: A Comprehensive Analysis from Molecular Mechanisms to In Vivo Efficacy. Int. J. Mol. Sci. 2024, 25, 8944. https://doi.org/10.3390/ijms25168944
Hwang DH, Asirvatham RD, Mohan Prakash RL, Kang C, Kim E. Therapeutic Potential of Rosa davurica Pall. Root Extract as an Antidiabetic Agent: A Comprehensive Analysis from Molecular Mechanisms to In Vivo Efficacy. International Journal of Molecular Sciences. 2024; 25(16):8944. https://doi.org/10.3390/ijms25168944
Chicago/Turabian StyleHwang, Du Hyeon, Ravi Deva Asirvatham, Ramachandran Loganathan Mohan Prakash, Changkeun Kang, and Euikyung Kim. 2024. "Therapeutic Potential of Rosa davurica Pall. Root Extract as an Antidiabetic Agent: A Comprehensive Analysis from Molecular Mechanisms to In Vivo Efficacy" International Journal of Molecular Sciences 25, no. 16: 8944. https://doi.org/10.3390/ijms25168944