Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction
Abstract
:1. Introduction
2. Chemistry and Biosynthesis of Apigenin
3. Pharmacokinetics of Apigenin
3.1. Absorption
3.2. Distribution
3.3. Metabolism
3.4. Excretion
3.5. Bioavailability
4. Metabolic Syndrome: An Overview
5. Broad-Spectrum Antioxidant Activity of Apigenin with a Main Focus on Dysmetabolic Conditions
5.1. Cardioprotective Potential of Apigenin through Antioxidant Action
Role of Apigenin in Dysmetabolism-Dependent Heart Dysfunction
5.2. Neuroprotective Role of Apigenin through Antioxidant Action
Apigenin in Dysmetabolism-Dependent Brain Alteration
5.3. Renoprotection of Apigenin against Oxidative Stress-Induced Injury
Apigenin in Renal Complication following Dysmetabolism
6. Effects of Apigenin in Metabolic Syndrome
6.1. Peroxisome Proliferator-Activated Receptor γ (PPARγ) as a Main Metabolic Target of Apigenin
6.2. Additional Insight in the Mechanism Underlying Apigenin-Induced Metabolic Effects
7. Does Apigenin Have Potential Clinical Impact in Metabolic Syndrome?
8. Future Perspectives and Limitations
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ARE | Antioxidant response element |
AT II | Angiotensin II |
ATP III | National Cholesterol Education Program’s Adult Treatment Panel III report |
BMI | Body mass index |
CAT | Catalase |
CD36 | Cluster determinant 36 |
CD38 | Cluster of differentiation 38 |
CETP | Cholesterol ester transport protein |
CHD | Coronary heart disease |
Cmax | Maximum concentration |
CVD | Cardiovascular diseases |
EGIR | European Group for the Study of Insulin Resistance |
FFA | Free fatty acids |
GPX | Glutathione peroxidase |
GSH | Glutathione |
HDL | High-density lipoproteins |
HF | Heart failure |
I/R | Ischaemia/reperfusion |
IDF | International Diabetes Federation |
IL | Interleukin |
IL-6 | Interleukin 6 |
ISO | Isoproterenol |
Keap1 | Kelch-like ECH-associated protein 1 |
LDL | Low-density lipoproteins |
M1 | Macrophages 1 |
M2 | Macrophages 2 |
MRP | Multidrug resistance proteins |
MW | Molecular weight |
NAD | Nicotinamide adenine dinucleotide |
NF-kB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
NHANES | National Health and Nutritional Examination Survey |
NO | Nitric oxide |
NAFLD | Non-alcoholic Fatty Liver Disease |
Nrf2 | Nuclear factor erythroid 2-related factor 2 |
PPARγ | Peroxisomes proliferator activated receptor gamma |
SIRT1 | Sirtuin-1 |
SOD | Superoxide dismutase |
STAT 3 | Signal transducer and activator of transcription 3 |
TGs | Triglycerides |
TNF | Tumour Necrosis factor |
TXNRD | Thioredoxin reductase |
VLDL | Very low-density lipoproteins |
VO | Visceral obesity |
WHO | World Health Organization |
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Target Sites | Systemic Effects of Metabolic Syndrome | References |
---|---|---|
Skin | Psoriasis, systemic lupus erythematosus, alopecia, acne inversa, burn-induced insulin resistance, skin cancer | [44] |
Eye | Open angle glaucoma, age-related cataract, oculomotor nerve palsy, central retinal artery occlusion, non-diabetic retinopathy | [42] |
Liver | Hepatic fibrosis, non-alcoholic steatohepatitis, elevated serum transaminase, cirrhosis and non-alcoholic fatty liver | [45] |
Kidney | Glomerulomegaly, microalbuminuria, focal segmental glomerulosclerosis, hyperfiltration, hypofiltration and chronic kidney disorder | [46] |
Cardiovascular System | Myocardial infarction, stroke and coronary heart disease | [47] |
Reproductive System | Erectile dysfunction, polycystic ovarian syndrome and hypogonadism | [48] |
Criteria | WHO (1998) | IDF (2005) | EGIR (1999) | AHA/NHLBI (2009) |
---|---|---|---|---|
Diabetes or Insulin Resistance + Two of the Four Criteria Below | Obesity + Two of the Four Criteria Below | Hyperinsulinemia + Two of the Four Criteria Below | 3 of the Following 5 Risk Factors | |
Hyperglycaemia | Insulin resistance already required | Fasting glucose ≥ 100 mg/dL | Insulin resistance already required | Fasting glucose ≥ 100 mg/dL |
Hypertension | ≥140/90 mmHg | >130 mmHg systolic or >85 mmHg diastolic | ≥140/90 mmHg | ≥130 mmHg systolic or ≥85 mmHg diastolic |
Obesity | Waist/hip ratio: >0.90 (M) > 0.85 (F) or BMI > 30 kg/m2 | Central obesity already required | Waist circumference: ≥94 cm (M) ≥80 cm (F) | * Waist circumference: ≥102 cm (M) ≥88 cm (F) TG ≥ 150 mg/dL |
Dyslipidaemia | TG ≥ 150 mg/dL or HDL-C < 35 mg/dL (M) and <39 mg/dL (F) | TG ≥ 150 mg/dL or Rx | TG ≥ 177 mg/dL or HDL-C < 39 mg/dL | HDL-C < 40 mg/dL (M) and <50 mg/dL (F) |
Organ | Effects of Apigenin through Antioxidant Action | Effects of Apigenin during Dysmetabolic-Dependent Organ Alteration |
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HEART |
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BRAIN |
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KIDNEY |
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Alam, W.; Rocca, C.; Khan, H.; Hussain, Y.; Aschner, M.; De Bartolo, A.; Amodio, N.; Angelone, T.; Cheang, W.S. Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction. Antioxidants 2021, 10, 1643. https://doi.org/10.3390/antiox10101643
Alam W, Rocca C, Khan H, Hussain Y, Aschner M, De Bartolo A, Amodio N, Angelone T, Cheang WS. Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction. Antioxidants. 2021; 10(10):1643. https://doi.org/10.3390/antiox10101643
Chicago/Turabian StyleAlam, Waqas, Carmine Rocca, Haroon Khan, Yaseen Hussain, Michael Aschner, Anna De Bartolo, Nicola Amodio, Tommaso Angelone, and Wai San Cheang. 2021. "Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction" Antioxidants 10, no. 10: 1643. https://doi.org/10.3390/antiox10101643