Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials
Abstract
:1. Introduction
2. Functional Hubs of CGA’s Pharmacological Effects
2.1. Anti-Inflammation and Anti-Oxidation (Figure 1A)
2.2. Glucose and Lipid Metabolic Homeostasis Modulation (Figure 1B)
2.3. Human Subject Studies
3. Cardiovascular Protective Effect
3.1. Hypotensive Effects (Figure 1C)
3.2. Effects of Endothelial Protections and Anti-Atherosclerosis (Figure 1C)
3.3. Cardioprotective Effects (Figure 1C)
3.4. Human Subject Studies for Cardiovascular Protection
4. Mitigative Effects on Diabetes Mellitus (DM)
4.1. Protective Effects on β Cells (Figure 1B)
4.2. Mitigative Effects on DM Complications (Figure 1D)
4.3. Human Subject Studies for Glycemic Control
5. Hepatoprotection
5.1. Hepatoprotection from Metal-, Chemical-, Drug-, and Toxin-Induced Liver Injury (Figure 1E)
5.2. Mitigative Effects on Metabolic-Associated Fatty Liver Disease (MAFLD) (Figure 1E)
5.3. Mitigative Effects on Liver Fibrosis and Hepatocellular Carcinoma (HCC) (Figure 1E)
5.4. Human Subject Studies for Hepatic Protection
6. Neuroprotection
6.1. Protective Effects against Neuronal Injury (Figure 1F)
6.2. Mitigative Effects on Alzheimer’s Disease (AD) (Figure 1F)
6.3. Mitigative Effects on Parkinson’s Disease (PD) (Figure 1F)
6.4. Effects on Ischemia-Induced Brain Injury (Figure 1F)
6.5. Effects on Cognitive Function (Figure 1F)
6.6. Modulation of Neuropathic Pain (Figure 1F)
6.7. Human Subject Studies for Neuroprotection
7. Anticancer Effect
7.1. Breast Cancer
7.2. Colorectal Cancer
7.3. Esophageal Cancer
7.4. Leukemia
7.5. Lung Cancer
7.6. Melanoma
7.7. Brain Glioma
7.8. Osteosarcoma
7.9. Pancreatic Cancer
7.10. Prostate Cancer
7.11. Renal Cell Carcinoma (RCC)
7.12. Human Subject Studies for Cancer Management
8. Skin Protection
8.1. Dermal Protection against Skin Pathologies (Figure 1H)
8.2. Anti-Melanogenesis Effects (Figure 1H)
8.3. Human Subject Studies for Skin Protection
9. Antiviral and Antimicrobial Effects
9.1. Anti-HBV Effects (Figure 1I)
9.2. Inhibitory Effects against Other Viruses (Figure 1I)
9.3. Inhibitory Effects against Bacteria and Fungi (Figure 1I)
9.4. Anti-Allergic Effect
10. Extending Lifespan in Worms
11. Other Protective Roles of CGA
11.1. Lung Protective Effects
11.2. Intestinal Protective Effects
11.3. Ovarian Protective Effects
11.4. Human Subject Studies for Menopausal Symptom Management
12. Summary
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Pathological Conditions/Organs | Pharmacological Effects | Experimental Models | Potential Signaling Pathways/Targets | Compound/Natural Sources |
---|---|---|---|---|
Aging | Mitochondria protection and increasing lifespan (Section 10) | C. elegans [332,333] | DAF-16-regulated insulin/IGF-1 signaling [332]; activation of Nrf2/SKN-1 [333] | CGA |
Cardiovascular system | Hypotensive effect (Section 3.1) | SMCs, SHRs, and cyclosporine-induced hypertensive rats [64,65,66,67] | Elevation of EDRFs, suppression of oxidations and vasoconstrictors, decrease HIF-1α and an enhancement of Shc/Grb2/ERK1/2 signaling [2,64,66,67] | CGA, GCE |
Patients with mild hypertension [7,14,103,104]; patients with borderline or stage 1 hypertension [105]; healthy male adults [106] | Targeting muscarinic acetylcholine receptors [64,65] | CGA; CGA plus HHQ | ||
Endothelial protection and anti-atherosclerosis (Section 3.2) | EC injuries [75,76,79,80,81]; atherosclerosis and HFD rat [68,69,70]; macrophages and ApoE−/− mice [73,86,87] | Upregulating SIRT1 and AMPK/PGC-1 activity [75] suppressing mtROS/JNK/NF-κB and HIF-1α-VEGF signaling [2,82] regulating A2A receptor/AC/cAMP/PKA pathway [84,85]; activating PPARγ–LXRα–ABCA1 signaling [86,87] | CGA; extract of Crataegus pinnatifida Bge. var. major N.E.Br. fruit | |
Cardioprotection (Section 3.3 and Section 3.4) | H9C2 cells; [96] MI animal models induced by ISO, LAD, and CCl4, and LAD-induced myocardial I/R SAMP8 mouse [97,98,99,100,101] | Suppressing NF-κB and JNK pathways, regulating PPARα and PI3K/Akt pathways, lower HIF-1α expression, and suppressing cardiac apoptotic signaling [2,90,91,92,96] | CGA; CGAs-enriched chrysanthemum extracts; CGA-enriched extracts from Lindl. Benth. | |
healthy adults [108,109,110,111,112,113,114]; subjects with metabolic syndrome [115,116] | n.a. | CGA-enriched coffee beverages; nutraceutical containing CGA and luteolin extracts; GCE | ||
Inflammation and oxidation | Anti-inflammatory and oxidative effects (Section 2.1 and Section 2.3) | Macrophage [32]; 3T3-L1 cells [27]; carbon tetrachloride or acetaminophen-induced liver injury in mice [20,23,24] Weaned Pigs, LPS-induced mice, I/R rat liver injury, endotoxic shock-induced acute liver injury [28,30,31,33] | Suppressing TLR4, TNF-α, NF-κB, and MAPK pathways [28,29,30,31]; activation of CD36/AMPK/PGC-1α [32] and Nrf2 signaling [20,34,35,36,37] | CGA; Taraxacum officinale root |
Healthy postmenopausal women [55]; healthy subjects [56] | n.a. | Bioactive yogurt containing curcumin and CGA; polyphenol-rich beverage | ||
Liver | Protection of the liver from injuries (5.1) | Metals, chemicals, and toxins: sodium arsenite [137], Pb [138], Cd [139], aluminum chloride [140], polychlorinated biphenyls [141], TAA [142], CCl4 [143], D-gal [144], L-carnitine [145], LPS [146,147], palmitic acid [148], and aflatoxin B1 [149] | Activating the Nrf2 pathway, promoting mitophagy, and suppressing the TLR4/NF-κB pathway [20,24,150,151,152,153,154,155,156,157,158,159] | CGA |
Decreasing NAFLD injury (Section 5.2 and Section 5.4) | Hepatic cell line HepG2 [162,163]; HFD mice [123,164,165]; α-naphthylisothiocyanate-induced mouse model with cholestatic liver injury [43,174]; rat model of hepatic ischemia/reperfusion injury [175] | Inhibiting JNK signaling [123,164,165]; blocking the LPS-TLR4-MyD88 signaling pathway and Nrf2/PPARα signaling [173]; suppressing sphingosine kinase 1/sphingosine-1-phosphate/TLR4 pathways [171]; suppressing HMGB1/TLR-4/NF-κB and mitochondria-mediated apoptosis [175] | CGA, CGA in combination with metformin or geniposide or telmisartan | |
Human subjects with NDFLD in type 2 DM [185] | n.a. | CGA, CGA plus coffeine | ||
Mitigation of liver fibrosis and HCC (Section 5.3 and Section 5.4) | Schistosoma japonicum cercaria-induced hepatic fibrosis [176]; CCl4-induced liver fibrosis [22,177,178]; DEN/CCl4-caused HCC [184]; diethylnitrosamine (DEN)/CCl4-caused liver fibrosis [183] | Regulating IL-13/miR-21/Smad7 [176]; suppressing miR-21/TGF-β1/Smad7 signaling or inhibiting the TLR4/NF-κB signaling and stimulating the Nrf2 pathway [22,177,178] | CGA; CGA with protocatechuic acid; CGA plus caffeine and trigonelline | |
HCC patients [186] | Targeting AKT/CyclinD1/p21/p27 pathways [186] | FZJDXJ (formononetin, CGA, caffeic acid, luteolin, gallic acid, diosgenin, ergosterol endoperoxide, and lupeol) | ||
Glucose and lipid metabolism | Metabolic homeostasis modulation (Section 2.2 and Section 2.3) | HFD mice [52]; HFD golden hamsters or rats [50,51] | Activation of AMPK pathways [4] | CGA; GCE |
Patients with IGT [57]; healthy subjects [58,61]; overweight dyslipidemic subjects [59]; hypercholesterolemic subjects [60]; overweight subjects [62]; patients with metabolic syndrome [8] | n.a. | CGA; cooked ham (22.5 mg CGA/100 g cooked ham); nutraceutical (containing bergamot, phytosterols, vitamin C, and CGA); green/roasted (35:65) coffee; coffee; GCE | ||
Nervous system | Protection of neuronal injury (Section 6.1) | Neuronal cells and PC12 cells [34,191]; oligodendrocyte [196] and OL cell line M03-13 [193]. granule cells [194]; rat cortical neurons [195] | Suppression of TNFα/NF-kB [193] and PKC and caspase-dependent signaling [196] | CGA |
Neuronal protection in AD and PD (Section 6.2 and Section 6.3) | SH-SY5Y cells and PC12 cells [210,211,212,213]; APP/PS2 mice [216]; SAMP8 mice [217]; molecular docking [220] | Inhibition and binding to AChE [218,219,220]; blockage of the interplay between oxidized dopamine and α-synuclein [221]; anti-apoptotic pathways [226] | CGA; CGA combined with caffeic acid | |
Decreasing ischemia-induced brain injury (Section 6.4) | Cerebral I/R rat models [229,232,233] | Activation of Nrf2 pathways [229,232,233]; Inhibition of the TNF-α pathway [230,233] and the apoptotic pathway [229,230,232]; decrease in the expression of metalloproteinases such as MMP-2 and MMP-9 [198] | CGA | |
Cognitive improvement (Section 6.5 and Section 6.7) | Mouse model of anxiety [234]; sleep-deprived mice activation [235]; LPS-induced neuroinflammation mouse model [236]; diabetic rats [237]; corticosterone-induced depression-like mice [238] | Activation of Nrf2/PPAR [235]; inhibition of the TNFα signaling pathway [236] | CGA | |
Healthy subjects with mild cognitive impairment [269,270,271]; healthy subjects observed [272,273] | n.a. | CGA; CGA-enriched coffee berry extracts | ||
Neuropathic pain (Section 6.6) | A chronic inflammatory pain model of mice and carrageenan-induced rat hind paw edema [255,256]; rat model of CCI [240,241]; trigeminal ganglion inflammations [263,264] sensory ganglions [257,268] | Suppression of peripheral release of pro-inflammatory factors, including TNF-α, NO, and ILs [239,242,243]; activation of GABAA receptors [259,260]; suppression of Kv channels [263,264] and acid-sensing channels [257,268] | Mansoa alliacea extracts; Cheilanthes farinose extracts; CGA | |
Pancreas and DM | Protecting β-cells and improving β-cell function (Section 4.1) | β cells and Langerhans from rat islets [119,120]; mice fed on HFD or high-fat milk, spontaneously obese mice, or rats fed on HFD [121,122,123]; STZ-induced DM rats [126] | Anti-oxidative stress [125] and anti-inflammatory response [126] | CGA; CGA with tetrahydrocurcumin |
Mitigation of DM complications (Section 4.2) | A diabetic nephropathy rat model [127,128]; DM mice [129,130]; diabetic DPN DM mice [132] | Anti-oxidative and anti-inflammatory response [127,128,129,130,132] | CGA; CGA-enriched extracts | |
Glycemic control in human subjects (Section 4.3) | Healthy human subjects [134]; subjects with IFG [136]; patients with metabolic syndrome [8] | n.a. | GTC together with coffee CGA; CGA-rich Cs extracts; GCE | |
Pathogen infections | Anti-viral effects (9.1) | Sowbane mosaic virus, potato virus X, and alfalfa mosaic virus [326]; RSV, HSV-2, ADV-3, ADV-11 [327]; H5N1 [328]; HSV-1 in MDBK cells and in Vero cells [329] | n.a. | CGA |
Anti-bacterial effects (Section 9.2) | A. baumannii, B. subtilis, E. coli, E. faecalis, K. pneumoniae, P. mirabilis, P. aeruginosa, and S. aureus [329] | n.a. | CGA | |
Anti-Fungal effects (Section 9.3) | C. albicans and C. parapsilosis [329] | n.a. | CGA | |
Anti-allergic effects (Section 9.4) | Shrimp food-fed mice [330] | Increase in CPT-1 and AMPK and ACC phosphorylation [330] | CGA | |
Skin | Dermal protection (Section 8.1) | Dermal fibroblasts [303,304]; skin flap survival in rats [306]; epidermal keratinocytes [307]; MRL/lpr mice [309] | Inhibition of MAPK/NF-kb/NLRP3 pathways [305] and KT/mTOR/SREBP signaling [308] | CGA |
Anti-melanogenic effects (Section 8.2) | Molecular docking simulation and in vitro kinetic assay [312,313,314,315] | Inhibition of α-MSH [312,313,314]; inhibition of tyrosinase [315] | CGA | |
Protection of skin barrier and improvement in microcirculation (Section 8.3) | Human female subjects with mildly xerotic skin [317]; | n.a. | Beverage containing coffee polyphenols | |
Tumor | Inhibiting tumor cell proliferation/increasing chemo-sensitivity (Section 7.1, Section 7.2, Section 7.3, Section 7.4, Section 7.5, Section 7.6, Section 7.7, Section 7.8, Section 7.9, Section 7.10 and Section 7.11) | Breast cancer cell line MCF-7 [274,275]; colon cancer cell lines HCT116, HT29 [278], Caco-2 [280]; esophageal cancer cell lines KYSE30/70/140/150/180/510 [282]; leukemia cell lines U937, and HL60 [284,285]; lung cancer cell line A549 [287]; melanoma C32 and B16F10 [288,289]; glioma cells U87 [290]; osteosarcoma cell lines U2OS, MG-63, and Saos-2 [294,295]; pancreatic carcinoma PANC-1 [297,298]; prostate cancer cell DU145 [300]; and RCC A498 cells [301]; tumor-bearing SCID mouse models [282,287] | Increase in p53, Bax, and the ratio of Bax/Bcl-2 [276,277]; blockages of (1) p-STAT-5 and p-CrkL [283,287], (2) the NF-kb pathway [276], (3) the STAT3/Snail pathway [294,295], (4) the PI3K/Akt/mTOR pathway [301], and EMT [276] | CGA |
Cancer management in patients (Section 7.12) | Patients with recurrent high-grade glioma [302] | n.a. | CGA | |
Others | Lung injury protection (Section 11.1) | LPS-induced acute lung injury mouse model [335]; LPS/POLY I:C-induced ALI/ARDS in human epithelial cells [336] | KAT2A inhibitor [335]; targeting of the TLR4/TLR3/NLRP3 inflammasome axis [336] | CGA |
Intestinal protection (Section 11.2) | Broilers induced by necrotic enteritis challenge [337]; a rat model of PI-IBS [338] | Suppression of the mtDNA-cGAS-STING signaling pathway [337]; modulation of gut microbial-released extracellular vesicles [338] | CGA | |
Ovarian protection (Section 11.3) | CDDP-induced ovarian damage in rats [339]; PCOS rats [340] | HIF-1alpha signaling [340] | CGA | |
Menopausal symptom management (Section 11.4) | Human, healthy women [341] | n.a. | CGA |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Nguyen, V.; Taine, E.G.; Meng, D.; Cui, T.; Tan, W. Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials. Nutrients 2024, 16, 924. https://doi.org/10.3390/nu16070924
Nguyen V, Taine EG, Meng D, Cui T, Tan W. Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials. Nutrients. 2024; 16(7):924. https://doi.org/10.3390/nu16070924
Chicago/Turabian StyleNguyen, Vi, Elaine G. Taine, Dehao Meng, Taixing Cui, and Wenbin Tan. 2024. "Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials" Nutrients 16, no. 7: 924. https://doi.org/10.3390/nu16070924