Lannea coromandelica (Houtt.) Merr. Induces Heme Oxygenase 1 (HO-1) Expression and Reduces Oxidative Stress via the p38/c-Jun N-Terminal Kinase–Nuclear Factor Erythroid 2-Related Factor 2 (p38/JNK–NRF2)-Mediated Antioxidant Pathway
Abstract
:1. Introduction
2. Results
2.1. High-Pressure Liquid Chromatography (HPLC) Analysis of Lannea coromandelica Bark Extract
2.2. Radical-Scavenging Activities of LCB Extract
2.3. LCB Extract Attenuates Cellular Oxidative Stress Induced by 2,2′-Azobis(2-Amidinopropane) Dihydrochloride (AAPH) in RAW 264.7 Cells
2.4. Effects of LCB Extract on Antioxidant Enzyme Expression
2.5. Effects of LCB Extract on Phase II Enzymes through NRF2 Nuclear Translocation
2.6. LCB Extract Activates NRF2 via Phosphorylation of JNK and p38 MAPKs
3. Discussion
4. Experimental Section
4.1. Plant Material and Extraction
4.2. Drugs and Chemicals
4.3. High-Pressure Liquid Chromatography with Diode-Array Detection Analysis
4.4. Radical-Scavenging Activity Assays
4.4.1. 2,2-Diphenyl-1-Picrylhydrazyl Radical-Scavenging Assay
4.4.2. 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) Radical-Scavenging Assay
4.4.3. Superoxide Radical-Scavenging Assay
4.4.4. Hydroxyl Radical-Scavenging Assay
4.4.5. Ferric Reducing Antioxidant Power Assay
4.4.6. Cupric Reducing Antioxidant Capacity
4.4.7. Oxygen Radical Absorbance Capacity
4.5. In Silico Toxic Risk Prediction and Biological Activity Spectrum
4.6. Cell Culture and Cell Viability Assay
4.7. Measurement of Intracellular ROS
4.8. Reverse Transcription-Polymerase Chain Reaction
4.9. Preparation of Cell Lysates and Western Blotting
4.10. Statistical Data Analyses
Acknowledgments
Author Contributions
Conflicts of Interest
References
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ID Substances | Toxic Risk by ACD/Labs 1; admetSAR 2; pkCSM 3; PreADMET 4 | |||||
---|---|---|---|---|---|---|
Phytoconstituents | Mutagenic | Carcinogenic | Cardiotoxic | Skin Irritant | Reproductive System Toxicity 1 | Hepatotoxic |
Gallic acid | N1, | N1, | N3, | N1 | N3 | |
N2, | N2, | (+)2, | ||||
N3, | N4, | N3, | ||||
(+)4 | (+)4 | |||||
EGCG | (+)1, | (+)1, | N3 | N1 | N3 | |
N2, | N2, | (+)2, | ||||
N3, | (+)4, | N3, | ||||
(+)4 | (++)4 | |||||
Cathechin | (+)1, | (+)1, | N3 | (+)1 | N3 | |
N2, | N2, | (+)2, | ||||
N3, | N4, | N3, | ||||
(+)4 | (++)4 | |||||
Chlorogenic acid | (+)1, | N1, | N3 | N1 | (+)3 | |
N2, | N2, | (+)2, | ||||
N3, | (+)4, | N3, | ||||
N4 | (+++)4 | |||||
Caffeic acid | (+)1, | N1, | N3 | N1 | N3 | |
N2, | N2, | (+)2, | ||||
N3, | (+)4, | N3, | ||||
(+)4 | (++)4 |
Phytoconstituents | Main Predicted Properties by PASS Online | Pa # | Pi # |
---|---|---|---|
Gallic acid | Antiseptic | 0.921 | 0.003 |
Astringent | 0.884 | 0.001 | |
Antiinfective | 0.828 | 0.005 | |
Fibrinolytic | 0.823 | 0.004 | |
Mucomembranous protector | 0.814 | 0.015 | |
Mucositis treatment | 0.798 | 0.014 | |
Kidney function stimulant | 0.779 | 0.004 | |
HO-1 expression enhancer | 0.732 | 0.005 | |
EGCG | HMOX1 expression enhancer | 0.985 | 0.001 |
Mucomembranous protector | 0.950 | 0.003 | |
Fibrinolytic | 0.942 | 0.003 | |
Free radical scavenger | 0.934 | 0.001 | |
Astringent | 0.927 | 0.001 | |
Antioxidant | 0.827 | 0.003 | |
Cardioprotectant | 0.822 | 0.003 | |
Hepatoprotectant | 0.820 | 0.004 | |
Antihemorrhagic | 0.794 | 0.002 | |
Antiviral (Influenza) | 0.771 | 0.003 | |
Antihypercholesterolemic | 0.705 | 0.008 | |
Catechin | HO-1 expression enhancer | 0.971 | 0.001 |
Mucomembranous protector | 0.962 | 0.003 | |
Fibrinolytic | 0.959 | 0.002 | |
Antihemorrhagic | 0.926 | 0.002 | |
Astringent | 0.921 | 0.001 | |
Free radical scavenger | 0.850 | 0.002 | |
Antioxidant | 0.828 | 0.003 | |
Chemopreventive | 0.791 | 0.004 | |
Hepatoprotectant | 0.769 | 0.005 | |
Chlorogenic acid | Choleretic | 0.920 | 0.001 |
Free radical scavenger | 0.856 | 0.002 | |
Antioxidant | 0.809 | 0.003 | |
Antieczematic | 0.808 | 0.017 | |
Antineoplastic | 0.785 | 0.014 | |
Mucomembranous protector | 0.752 | 0.034 | |
Caffeic acid | Mucomembranous protector | 0.945 | 0.003 |
Mucositis treatment | 0.873 | 0.008 | |
HO-1 expression enhancer | 0.799 | 0.004 | |
Antiseptic | 0.782 | 0.004 | |
Vasoprotector | 0782 | 0.006 | |
Fibrinolytic | 0.750 | 0.009 | |
Cytoprotectant | 0.722 | 0.039 | |
Antieczematic | 0.702 | 0.005 |
Gene Name | Sequences | |
---|---|---|
Sod1 | Forward | AAGCGGTGAACCAGTTGTGT |
Reverse | GCCAATGATGGAATGCTCTC | |
Sod2 | Forward | AACTCAGGTCGCTCTTCAGC |
Reverse | CTGTAAGCGACCTTGCTCCT | |
Gpx1 | Forward | ACACCGAGATGAACGATCTG |
Reverse | ATGTACTTGGGGTCGGTCAT | |
Cat | Forward | CACCCACGATATCACCAGATAC |
Reverse | GAAGACTCCAGAAGTCCCAGAC | |
Hmox1 | Forward | ACGCATATACCCGCTACCTG |
Reverse | TCCTCTGTCAGCATCACCTG | |
Gclc | Forward | GGAGGCGATGTTCTTGAGAC |
Reverse | GGGTGCTTGTTTATGGCTTC | |
Gclm | Forward | AGTTGCACAGCTGGACTCTG |
Reverse | TCGGGTCATTGTGAGTCAGT | |
Nqo1 | Forward | CTGGCCCATTCAGAGAAGAC |
Reverse | GTCTGCAGCTTCCAGCTTCT | |
Nrf2 | Forward | ACATCCTTTGGAGGCAAGAC |
Reverse | GGGAATGTCTCTGCCAAAAG | |
Gstpi | Forward | GCCCAGATGGATATGGTGAA |
Reverse | ATGGGACGGTTCACATGTTC | |
Keap1 | Forward | GCTACAACCCCATGACCAAC |
Reverse | GCGGAGTTAAGCCGGTTAGT |
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Alam, M.B.; Kwon, K.-R.; Lee, S.-H.; Lee, S.-H. Lannea coromandelica (Houtt.) Merr. Induces Heme Oxygenase 1 (HO-1) Expression and Reduces Oxidative Stress via the p38/c-Jun N-Terminal Kinase–Nuclear Factor Erythroid 2-Related Factor 2 (p38/JNK–NRF2)-Mediated Antioxidant Pathway. Int. J. Mol. Sci. 2017, 18, 266. https://doi.org/10.3390/ijms18020266
Alam MB, Kwon K-R, Lee S-H, Lee S-H. Lannea coromandelica (Houtt.) Merr. Induces Heme Oxygenase 1 (HO-1) Expression and Reduces Oxidative Stress via the p38/c-Jun N-Terminal Kinase–Nuclear Factor Erythroid 2-Related Factor 2 (p38/JNK–NRF2)-Mediated Antioxidant Pathway. International Journal of Molecular Sciences. 2017; 18(2):266. https://doi.org/10.3390/ijms18020266
Chicago/Turabian StyleAlam, Md Badrul, Kyoo-Ri Kwon, Seok-Hyun Lee, and Sang-Han Lee. 2017. "Lannea coromandelica (Houtt.) Merr. Induces Heme Oxygenase 1 (HO-1) Expression and Reduces Oxidative Stress via the p38/c-Jun N-Terminal Kinase–Nuclear Factor Erythroid 2-Related Factor 2 (p38/JNK–NRF2)-Mediated Antioxidant Pathway" International Journal of Molecular Sciences 18, no. 2: 266. https://doi.org/10.3390/ijms18020266