Of Chlorogenic Acid in Widanga (Embelia ribes)
Of
Chlorogenic Acid in Widanga (Embelia ribes)
Introduction
Widanga
(Embelia ribes) contains many pharmacologically active phytochemicals.
One of them is Chlorogenic acid.
Chlorogenic
acid is the ester of caffeic acid. The term "chlorogenic acids"
refers to a related polyphenol family of esters. Despite the word
"chloro", chlorogenic acid does not contain chlorine. Instead the name comes from
the Greek, pertaining to the green color produced when chlorogenic acids are
oxidized. Chlorogenic acid is freely soluble in ethanol and acetone.
Chlorogenic acid is found in coffee and many plants.
Chlorogenic
acid exhibits a pleiotropic pharmacological activity. [1]
Anti-inflammatory
activity
Anti-inflammatory
activity of chlorogenic acid was examined in lipopolysaccharide
(LPS)-stimulated mice. The results showed that chlorogenic acid exerted
anti-inflammatory activity as was evident by lower levels of inflammatory
markers. [2]
In
rats chlorogenic acid at doses 50 and 100 mg/kg body weight exhibited
anti-inflammatory, antinociceptive and antipyretic action within two
hours of experimental procedure.
Chlorogenic acid did not inhibit febrile response induced by lipopolysaccharide
(LPS). The highest tested dose was 200 mg/ kg body weight which did not produce
any untoward side effects nor any toxic effects. [3]
Anti-inflammatory
and antioxidant
Chlorogenic
acid controls oxidative stress and shows anti-inflammatory activity. [4]
Although chlorogenic acid is a good
antioxidative agent it is unstable when exposed to light and heat. However
recently it has been made stable by encapsulating it with β-cyclodextrin
(β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-cyclodextrin). [5]
To evaluate effect of topical
application of 1 % ointment of chlorogenic acid, excision wounds were inflicted
in Wistar rats. The wounds were dressed with 1% ointment of chlorogenic
acid. The anti-inflammatory and antioxidant properties of chlorogenic acid
accelerated the process of wound healing. [6]
As physiological importance of an orally
administered drug depends on its absorption in the intestine and action on
target tissues, an in vivo intestinal ischemia-reperfusion model was
used to evaluate antioxidant activity of chlorogenic acid. The study showed
that chlorogenic acid protected the intestinal tissues
from ischemia-reperfusion injury. [7]
Immunomodulatory activity
Bronchial asthma is a chronic
inflammatory disease characterized by hypersensitivity response, reversible
airway obstruction and remodeling of the airways. Immunomodulatory activity of
chlorogenic acid was investigated in ovalbumin (OVA)-induced allergic bronchial
asthma in mice. The results showed that suppressed the hypersensitivity
response, eosinophilia, expression of interleukin-4
(IL-4), interleukin-5, tumor necrosis factor-α (TNF-α) as well as
total and ovalbumin-specific immunoglobulin E (IgE). [8]
Using in
vitro and in vivo models researchers proved that
chlorogenic acid inhibied compound 48/80-induced systemic anaphylactic shock in
mice and skin vascular permeability in rats. Chlorogenic acid also
inhibited anti-dinitrophenyl (DNP) immunoglobulin E (IgE)-mediated
passive cutaneous anaphylaxix (PCA). Moreover, depending on the dose,
chlorogenic acid reduced histamine and (TNF-α) release from
rat basophilic leukemia 2H3 (RBL2H3) cells. These results suggest that
chlorogenic acid can be used in mast cell dependent allergic and anaphylactic
reactions. [9]
Currently
the popliteal lymphnode is considered a very promising tool for assessing
immunosensitizing potential of low molecular weight compounds (LMWCs). In a
study it was found that chlorogenic acid failed to induce immunoreactivity to
some antigens. The study also showed that chlorogenic acid lacks the intrinsic
capacity to stimulate or dysregulate immune responses to some antigens. [10]
In
response to the controversies of published studies on the potential
sensitization of chlorogenic acid, Mingbao Lin et al, analyzed 108 articles
published from January 1979 to October 2012. They feel much of the data was not
of high quality. More high quality research is necessary to declare the final
conclusion regarding the use of chlorogenic acid in allergic disorders. [11]
Sepsis
is a complex, multifactorial, rapidly progressive disease characterized by an
overwhelming activation of immune system and the countervailing anti-inflammatory response.
In a study chlorogenic acid suppressed progression of the sepsis. [12]
Antibacterial
activity
Chlorogenic
acid increases the outer and plasma membrane permeability, resulting in the
loss of barrier function, disruption of outer membrane leading to death of
many microorganisms. Chlorogenic acid shows bacteriostatic
activity. Chlorogenic acid has antibacterial activity
against Escherichia coli.
In
an in vitro study chlorogenic acid showed antibacterial activity
against Bacillus cereus, Clostridium sporogenes, Micrococcus luteus, Escherichia
coli, Staphylococcus aureus, Pseudomonas flourescens and Salmonella
enterica. [13], [14]
Antiviral
activity
Viral
neuraminidases are implicated in viral replication. By blocking viral
neuraminidases chlorogenic acid exerts antiviral activity against influenza and
parainfluenza viruses. Therefore chlorogenic acid is used for the
treatment viral infections of the upper respiratory tract and influenza. Recently intravenous
injection of 100 mg/kg body weight of chlorogenic acid was found to
alleviate influenza infection caused by H 1 N 1 and H 3 N 2 viruses. [15]
In
a study chlorogenic acid and its compounds were shown to inhibit HepG2.2.15
cells and duck hepatitis virus. [16]
In
China, 20 mg/kg body weight of chlorogenic acid was found to be effective for
the treatment of Enterovirus 71 (EV 71) infection. In laboratory, human rhabdomysarcoma
(RD) cells are used to diagnose enterovirus infection. In experimental study
chlorogenic acid inhibited EV 71 2A transcription and translation in EV
71-infected RD cells. Chlorogenic acid inhibited secretions of IL-6,
TNF- α, interferon
(IFN-γ) and monocyte chemotactic protein (MCP-1) in EV 71-infected RD
cells. [17]
Antifungal
activity
Chlorogenic
acid, by disrupting the structure of cell membrane of many pathological fungi,
showed antifungal activity in vitro. The antifungal activity of
chlorogenic acid did not show any hemolytic effect on human erythrocytes. Thus
chlorogenic acid can be a future candidate for the development of new
antifungal agent. [18]
Chlorogenic
acid showed antifungal and anti-mycotoxigenic activities against Aspergillus
flavus and Aspergillus ochraceus. [19]
Actions
on Hematopoetic System
4-tert-octylphenol
(OP) is a chemical compound from the group of alkylphenols. The
substance is estrogenic and belongs to the chemicals known as
'endocrine disruptors'. In animal studies, 4-tert-octylphenol (OP) induced
significant pnacytopenia, decreased serum levels of sodium, potassium,
chloride, calcium and phosphorus. OP reduces glutathione-S-transferase,
glutathione peroxidase, glutathione reductase, catalase and superoxide
dismutase. More over OP increased serum hepcidin, ferritin, transferrin,
erythropoietin, aspartate aminotransferase, alanine aminotransferase, alkaline
phosphatae, urea, creatinine, selenium, zinc, manganese, copper, iron,
malondialdehyde and protein carbonyl levels.
Treatment with chlorogenic acid corrected anemia, pancytopenia, mineral
disturbances and restored all the disturbed levels to normal values. [20]
Chlorogenic
acid promotes expression of caspase-3,-7,-8,-9 in U 937 cells. Chlorogenic
acid induces cell death in U 937 leukemia cells through caspase dependent and
mitochondria-dependent pathways. [21]
Actions
on the Skin
TPA
(12-O-tetradecanoylphorbol-13-acetate) is used in cancer research to stimulate
division of B-cells during cytogenic diagnosis of B-cell cancers such as
chronic lymphocytic leukemia. Topical application of chlorogenic acid
inhibits epidermal ornithine decarboxylase activity. Thus chlorogenic acid
inhibits TPA (12-O-tetradecanoylphorbol-13-acetate) induced
tumors. [22]
Actions
on Musculo-skeletal System
In
female Sprague-Dawley rats at 27 and 45 mg/kg body weight per day chlorogenic
acid inhibited the decrease of bone density caused by estrogen deficiency.
Furthermore chlorogenic acid was found to promote proliferation of
osteoblast precursors and subsequently differentiation of osteoblasts by
inhibiting Shp-2 gene, phospho-Akt and cyclin D1. Thus chlorogenic acid can
prevent osteoporosis. [23]
Actions
on Endocrine System
Chlorogenic
acid modifies gastrointestinal (GI) hormone secretion and glucose tolerance.
[24]
Actions
on the Breast
Chlorogenic
acid belongs to phenolic acid group. It does exhibit group action. Its
antiproliferative and apoptotic effects show anti-breast cancer activity. This
effect is attributed to the antioxidant property of this compound on T47D human
breast cancer cells. Chlorogenic acid does not interfere with steroid and
adrenergic receptors. [25]
Action
on Nervous system
Chlorogenic
acid is said to be present in human nervous tissue. Chlorogenic acid from
decaffeinated green coffee is highly absorbed
and metabolized in humans. Chlorogenic acid is used as a nutritional
supplement. [26]
Chlorogenic
acid has protective effect against cerebral ischemia. Depending upon the
dose, Chlorogenic acid reduces the volume of infarct, sensory-motor functional deficit,
reduces brain edema, reduces lipid peroxidation (LPO) and inhibits matrix
metalloproteinase (MMP) expressions and activities. These effects of
chlorogenic acid were due to its antioxidant and free radical scavenging
activities. These results suggest that chlorogenic acid has protective
effect against cerebral ischemia. [27]
Recent
evidence suggests that consumption of chlorogenic acid in the diet protects the
brain from neuro-degenerative changes. [28]
The
activated microglia release pro-inflammatory factors in the brain. They
contribute to the progression of neurodegenerative diseases. The anti-inflammatory activity of
chlorogenic acid, by mediating microglial activation protects the brain from
neuro- degenerative diseases. [29]
In
mice chlorogenic acid exerted neuro-protective effect against scopolamine
induced amnesia via improving antioxidant defense mechanism and by decreasing
the activity of acetylcholine esterase. [30]
Chlorogenic
acid and its metabolites evoke neurotrophic respone in hippocampal cells. [31]
Cadmium
induces brain damage due to oxidative stress. Cadmium treated rats displayed
numerous pathological changes in the brain such as inhibition of acetylcholinesterase,
elevated lipid peroxidation, depletion of enzymatic and non-enzymatic
antioxidants, reduction of membrane-bound ATPase activity, mitochondrial
dysfunction and DNA fragmentation. Pretreatment of the rats with
chlorogenic acid attenuated these
ill effects induced by cadmium. This study suggests that chlorogenic acid is
beneficial in the prevention of brain damage and neuropathy due to heavy metal
poisoning. [32]
The
most detrimental effects of alcohol (ethanol) exposure are the loss of neurones
in the hippocampus and neocortex which may be related to the apoptosis and
necrosis due to oxidative stress. By counteracting against oxidative stress
chlorogenic acid prevents alcohol induced neurotoxicity. [33]
The
activated microglia release pro-inflammatory factors in the brain. They might
be responsible for tumorigenesis in the brain. Chlorogenic acid is potent
inhibitor of microsomal glucose 6-phosphate translocase (G6PT). This process is
thought possess cancer chemopreventive properties. A study showed that
chlorogenic acid has thepotential to regulate invasive brain tumor-derived
glioma cells. [34]
Actions
on CVS
Chlorogenic
acid increases the homocysteine level in the blood even in healthy persons
which is detrimental to the heart. Homocysteine is a biomarker for
cardiovascular disease. It is yet unclear whether chlorogenic acid merely
increases the biomarker or it actually increases the cardiovascular risk. [35],
[36]
Chlorogenic
acid and its metabolites exert a potent anti-hypertensive effect. This effect
is attributed to ferulic acid a metabolite of chlorogenic acid. Ferulic
acid is vasodilator. [37], [38], [39]
Chlorogenic
acid is vasodilator, reduces elevated blood pressure, attenuates endothelial
dysfunction and improves endothelial function. Chlorogenic acid reduces
oxidative stress and improves the bioavailability of nitric oxide in
hypertensive subjects. [40]
Anti-inflammatory
and antioxidant activities of chlorogenic acid protect endothelial cells of
the human umbilical vein from the toxic damage induced by
Perfluorooctane Sulphonate. [41]
Several
research papers reported anti-hypertensive activity of chloroenic acid. To
arrive at a definite scientific conclusion on this issue Onakpoya I J et al
undertook a meta-analytical review. Five eligible studies including 364
patients were included. The meta-analysis also showed that chloroenic acid
significantly reduced systolic and diastolic blood pressure. [42]
Antioxidant
activity, better bioavailability of nitric oxide in arterial vasculature and
improvement in endothelial function are the key factors for lowering of blood
pressure by chlorogenic acid. Inclusion of chlorogenic acid in the diet may
hold a promise for providing a non-pharmacological approach for the prevention
and treatment of hypertension. [43]
Actions
on RS
A
study was designed to evaluate protective effects of chlorogenic acid
against lipopolysaccharide (LPS)-induced acute lung injury. The study group
treated mice with chlorogenic acid at doses of 5, 20 and 50 mg/kg body weight
30 minutes or 3 hours after intratracheal administration of
lipopolysaccharide (LPS). The histological study after the treatment with
chlorogenic acid displayed reduction in edema, hemorrhage, vascularity and
alveolar structural damage caused by lipopolysaccharide (LPS). At the dose
of 50 mg/kg body weight chlorogenic acid protected mice from acute lung
injury caused by lipopolysaccharide (LPS). [44]
Actions
on the Pancreas
Chlorogenic
acid in decaffeinated coffee (green coffee) inhibited porcine pancreatic
lipase. [45]
Actions
on Liver
Anti-inflammatory
and antioxidant properties of chlorogenic acid protected the liver from
carbontetrachloride (CCl4) induced hepato-toxicity in male Sprague-Dawley rats.
Chlorogenic acid significantly attenuated the symptoms of liver inflammation
and fibrosis induced by carbontetrachloride (CCl4). Chlorogenic acid
also significantly reduced the elevated liver enzymes. The histological study also
revealed improvement in the structure of the
liver. This is attributed to inhibition of the activation of
toll-like receptor 4 (TLR4/NF-κB) signaling pathway in the liver by
chlorogenic acid. [46]
Methamphetamine
intoxication can cause acute hepatic failure. If treated with chlorogenic acid
before administration of methamphetamine
chlorogenic acid can prevent hepatic injury. [47]
Hepatic
ischemia-reperfusion is accompanied by excessive reactive oxygen species and
hepatic inflammation. Chlorogenic acid has
been shown to exert potent anti-inflammatory, antioxidant and
antimicrobial activities. Thus chlorogenic acid might have potential as an agent for the treatment of hepatic
ischemia-reperfusion injury. [48]
Chlorogenic
acid suppresses the invasion of AH109A, a rat ascites hepatoma cell line at
concentrations of 5-40 µM without altering the cell proliferation. Thus in
future chlorogenic acid can be an important chemical for the treatment of
hepatoma. [49]
5-fluorouracil
(5-FU) inhibits proliferation of heptocellular carcinoma cells. Chlorogenic
acid enhances the effects of 5-fluorouracil. Chlorogenic acid acts as a
chemosensitizer of 5-fluorouracil in the treatment of hepatocellular carcinoma.
This activity is attributed to inhibition of extracellular signal-regulated
kinases by chlorogenic acid [50]
Actions
in Diabetes
Chlorogenic
acid lowered blood sugar in streptozotocin-induced diabetic
rats. Chlorogenic acid also improved memory, prevented neuropathy and improved acetylcholine esterase
(AChE) activity in streptozotocin-induced diabetic rats. [51]
Diabetic
rats treated with chlorogenic acid showed an increase in adenosine
monophosphate hydrolysis in cerebral cortex. Furthermore chlorogenic
acid also reduced the platelet aggregation in the brain. [52]
AMPK
(5' adenosine monophosphate-activated protein kinase) is an enzyme that
plays an important role in cellular energy homeostasis. The net effect
of AMPK activation is stimulation of activation of hepatic fatty acid
oxidation, ketogenesis, stimulation of skeletal muscle fatty acid
oxidation and glucose uptake; inhibition of cholesterol synthesis, triglyceride
synthesis, lipogenesis, inhibition of adepocyte- lipolysis and modulation of
insulin secretion by pancreatic beta-cells. Chlorogenic acid stimulates
glucose uptake in skeletal muscle through activation of 5'
adenosine monophosphate-activated protein kinase (AMPK). [53], [54], [55]
On
Metabolism/Obesity
Disorders
of glucose metabolism and lipid metabolism are closely related. They may result
into diabetes, obesity, hypertension, hepatic steatisis, cardiovascular
disease, neuropathies and cancer. Chlorogenic acid can prevent these events. [56]
Chlorogenic
acid has a significant effect on the absorption and utilization of glucose. Use
of chlorogenic acid for an extended time may reduce body fat and body
mass.
A
study on high fat-fed mice showed that, chlorogenic acid improved body weight,
lipid metabolism and levels of obesity-related hormones in high-fat fed mice.
Chlorogenic acid seemed to be more potent for body weight reduction and
regulation of lipid metabolism than caffeic acid. [57], [58], [59]
To
assess the effects of chlorogenic acid on lipid metabolism in male golden
hamsters, the animals were fed on 15% high fat diet. The animals were treated
with chlorogenic acid 80 mg/kg body weight for eight weeks. The results of the
treatment showed that the levels of fasting serum triglyceride (TG), free fatty
acid (FFA), total cholesterol (TC), low density lipoprotein cholesterol (LDL) glucose and insulin were significantly lower.
Chlorogenic acid also led to higher activity of hepatic lipase (HL), lower
contents of TG (triglyceride) and FFA
(free fatty acid) in the liver. Thus chlorogenic acid can modify lipid and
glucose metabolism [60], [61]
Actions
on Reproductive System
In
the only reported rat study, chlorogenic acid at 5-500 mg/kg body weight per
day induced rib defects in fetuses of 5-12 weeks of gestation. No CNS defects
and fetal or maternal mortality was reported. [62]
Antitumor
Activity
Chlorogenic
acid can prevent lung cancer. Chlorogenic acid induces high levels of
topoisimerase I- and topoisomerase II-DNA complexes in cells. This is responsible
for anticancer activity of chlorogenic acid. The lung cancer cells
(A549) are more sensitive than normal lung fibroblasts (MRC5) to
chlorogenic acid. This and the findings from some other studies suggest
that the cytotoxic activity of chlorogenic acid may be selective
in killing cancer cells. [63]
In
a study, treatment of adenocarcinoma cells of colon with chlorogenic acid and
neochlorogenic acid at concentrations of 150-500 µmol significantly
reduced cell proliferation. The cell morphology of treated cells changed: the
surface of cells became uneven, more rough and irregular in shape. These
changes were dependent on the concentrations used. [64]
Chlorogenic
acid is able to change gene expression involved in immunepathways. Chlorogenic
acid promotes the activation and proliferation of T cells, macrophages and
natural killer cells. Thus by enhancing killing abilities of these cells,
chlorogenic acid can suppress the growth rate of tumor cells.[66]
Chlorogenic
acid upregulates glycogen synthase kinase 3 (GSK-3β) and
antigen-presenting cell (APC) genes which could inhibit free β-catenin into the
nucleus.This disrupts the cell proliferation and causes apoptosis of cancer
cells. [67]
Toxicity
of Cclorogenic acid
High
intake of chlorogenic acid could be responsible for the higher homocysteine
concentration in the blood. This can be a risk for cardiiovascular diseases. [68]
Dose: 120-300 mg
for oral intake [69]
References:
1.
https://en.wikipedia.org/wiki/Chlorogenic_acid
2.
Hwang SJ et al, Anti-inflammatory effects of chlorogenic acid in
lipopolysaccharide-stimualted RAW 264.7 cells. Inflamm Res. 2014 Jan; 63(1):
81-90
3.
Michel David dos Santos et al, Evaluation of the Anti-inflammatory, Analgesic
and Antipyretic Activities of Natural Polyphenol Chlorogenic Acid, Biol. Pharm.
Bull. 29(11) 2236-2240; (2006)
4. Ningjian Liang and David D. Kitts,
Role of Chlorogenic Acids in Controlling Oxidaative and Inflammatory Stress
Conditions, Nutrients, 2016 Jan; 8(1):16
5. Aneela Maalic et al, Chlorogenic
acid: A pharmacologically potent molecule, Acta Poloniae Pharmaceutica-Drug
Research; Volume 73, No.4 pp. 851-854, 2016
6. Chen WC et al, Effect of topical
application of chlorogenic acid on excision wound healing in rats, Planta Med.
2013 May; 79(8): 616-621
7. Sato Y et al, In vitro and in vivo
antioxidant properties of chlorogenic and caffeic acid, International Journal
of Pharmaceutics, Volume 403, Issues 1-2, 17 January 2011, Pages 136-138
8. Kim HR et al, Chlorogenic acid
suppresses pulmonary eosinophilia, IgE production and Th-2 type cytokine
production in an ovalbumin-induced
allergic asthma: activation of STAT-6 and JNK is inhibited by chlorogenic acid,
International Immunopharmacology, 2010
Oct; 10(10:1242-1248
9.
HD Quin et al, Effect of chlorogenic acid on mast cell-dependent anaphylactic
reaction, International Immunopharmacology, 2010 Sept; 10(9): 1135-1141
10.
ZhaohuaLiua, Evaluation of chlorogenic acid using a ploliteal lymph node assay
in BALB/c mice, Food and Chemical Toxicology; Volume 48, Issue 4, April 2010,
Pages 1059-1065
11.
Mingbao Lin et al, Evaluation of the Potential Sensitization of Chlorogenic
Acid: A Meta-Analysis, Evidence-Based Complimentary and Alternative Medicine,
Volume 2013, Article ID 208467, 9 pages
12.
Chan-Ho Lee et al, Chlorogenic Acid Attenuates High Mobility Group Box 1(HMGB
1) and Enhances Host Defense Mechanisms in Murine Sepsis, Mol. Med. 2012;
18(1): 1437-1448
13.
Lou Z et al, Antibacterial activity and mechanism of action of chlorogenic
acid, J Food Science 2011 August 76(6):M398-403
14.
Mirna L et al, Antibacterial activity and Antifungal and Anti-Mitotoxigenic
Activities Against Aspergillus flavus and A. ochraceus of Green Coffee
Chlorogenic acids and Dodecyl Chlorogenates, Journalof Food Safety, 1st August
2013, Volume 33, Issue 3, pages 360-363
15.
Ding Y et al, Antiviral activity of chlorogenic acid against influenza A
(H1N1/H3N2) viruses and its inhibition of neuraminidase, Sci. Rep. 2017 Apr,
10:7:45723
16.
Gui-Feng Wang et al, Anti-hepatitis activity of chlorogenic acid, quinic acid
and caffeic acid in vivo and in vitro, Antiviral Res 2009Aug, 83(2)
186-190
17.Xiang
Li et al, Chlorogenic acid inhibits the Replication and Viability of
Enterovirus 71 in vitro, September 30, 2013,
http://journals.plos.org/plosone
18.
Woo Sang Sung et al, Antifungal action of chlorogenic acid against pathogenic
fungi mediated by membrane disruption,
Pure Appl. Chem., Vol.82, No. 1, pp 219-226, 2010
19.
Mirna L et al, Antibacterial activity and Antifungal and Anti-Mitotoxigenic
Activities Against Aspergillus flavus and A. ochraceus of Green Coffee
Chlorogenic acids and Dodecyl Chlorogenates, Journalof Food Safety, 1st August
2013, Volume 33, Issue 3, pages 360-363
20.
Khaled M et al, The Role of Chhlorogenic Acid Supplementation in Anemia and
Mineral Disturbances Induced by 4-Tert- Octylphenol Toxicity , Journal
of Dietary Supplements
21.
Yang JS et al, Chlorogenic acid induces apoptotic cell death in U 937 leukemia
cells through caspase-and mitochondria- dependent pathways, In Vivo, 2012
November-December; 26(6): 971-8
22.
Mou-Tuan Huang et al, Inhibitory Effect of Curcumin,Chlorogenic Acid and
Ferulic acid on Tumor Promotion in Mouse Skin by
12-O-tetradecanoylphorbol-13-acetate, Cancer Research, 48, 5941-4946, November
1, 1988
23.
Rong Ping Zhou et al, Chlorogenic acid Prevents osteoporosis by Shp-2/PI3K/Akt
Pathway in Ovariectomized Rats, PLOS: Decembe 29, 2016
24.
Kelly L Johnston et al, Chlorogenic acid acutely modifies gastrointestinal
hormone secretion and glucose tolerance in humans:
glycemic effects of chlorogenic acid and caffeine 1'2'3, American J Clin
Nutr.October 2003; 78(4): 728-733
25.
Marilena Kampa et al, Antiproliferative and apoptotic effects of selective
phenolic acids on T47D human breast cancer cells: potential mechanisms of
action, Breast Cancer Research 2003, 6:R63.
[26]
Farah A et al, Chlorogenic acid from green coffee extract are highly
bioavailable in humans, J Nutr. 2008, December; 138(12):2309-2315
27.
Lee K et al, Chlorogenic acid ameliorates brain damage and edema by inhibiting
matrix metalloproteinase-2 and 9 in rat model of focal cerebral ischemia, Eur J
Pharmacol. 2012 Aug 15; 689(1-3): 89-95
28.
Heitman E et al, Cognitive and neuroprotective effects of chlorogenic acid,
Nutr Neurosci 2017 Jan; 20(1):32-39
29.
Shen W et al, Chlorogenic acid inhibits LPS-induced microglial activation and
improves survival of dopaminergic neurones,
Brain Res Bull. 2012 Aug 1; 88(5): 487-494.
30.
Mani Neelakandan et al, (2017), Pharmacological effects of chlorogenic acid: an
overview, Int. J. Res. Pharm. Sci. 8(1): 28-32
31.Hideyuki
ITO et al, Chlorogenic Acid and Its Metabolite m-Counaric Acid Evoke
Neutite Outgrowth in Hippocampal Neuronal Cells, Bioscience, Biotechnology, and
Biochemistry, Volume 72, 2008- Issue 3
32.
Hao ML et al, Therapeutic efficacy of chlorogenic acid on cadmium-induced
oxidative neuropathy in a murine model, Exp.Ther. Med 2015 May; 9(5): 1887-
33.
Fang SQ et al, Beneficial effects of chlorogenic acid on alcohol-induced damage
in PC-12 cells, Biomed Pharmacother, 2016 Apr; 79: 254-62.
34.
Anissa Belkaid et al, The chemopreventive properties of chlorogenic acid
reveal a potential new role for the microsomal glucose-6-phosphate translocase
in brain tumor progression, Cancer Cell Int. 2006 March 27; 6:7
35.
Urgent R et al Heavy coffee consumption and plasma homocysteine: a
randomized controlled trial in healthy volunteers Am J Clin Nutr, 2000
36.
Olthof MR et al, Consumption of high doses of chlorogenic acid present in
coffee or black tea increases plasma total
homocysteine concentrations in humans, Am J Clin Nutr, 2001
37.
Mesas AE et al, The effect of coffee on blood pressure and cardiovascular
disease in hypertensive individuals: a systematic review and
meta-analysis. Am J Clin Nutr. 2011
38.
Kozuma K et al, Antihypertensive effect of green coffee bean extract on mildly
hypertensive subjects, Hypertens Res 2005
39.
Suzuki A et al Green coffee bean extract and its metabolites have a hypotensive
effect in spontaneously hypertensive rats, Hypertens Res. 2002
40.
Suzuki et al, Chlorogenic acid attenuates hypertension and improves endothelial
function in spontaneously hypertensive rats, Journal of Hypertension: June
2006, Volume 24, Issue 6, pp 1065-1073.
41.
Yanyan LiaoSijun Dong et al, Flos Lonicerae Extracts and Chlorogenic Acid
Protect Human Umbilical Vein Endothelial Cells from the Toxic Damage of
Perfluorooctane Sulphonate, Inflammation, June 2013, Volume 36, Issue 3, PP
767-779
42.
Onakpoya I J et al, The effect of chlorogenic acid on blood pressure: a
systematic and meta-analysis of randomized clinical trials, J Hum Hypertens,
2015 Feb; 29(2): 77-81
43.
Zhao Y et al, Antihypertensive effects and mechanisms of chlorogenic acids,
Hypertens Res. 2012 Apr; 35(4):379-374
44.
XuZhanga et al, Chlorogenic acid protects mice against
lipopolysaccharide-induced acute lung injury, Injury, Volume 41, Issue 7, July
2010, Pages 746-752
45.
Narita Y, Inhibitory activity of chlorogenic acids in decaffeinated green
coffee beans against porcine pancreas lipase and effect and effect of a
decaffeinated bean extract on an emulsion of olive oil, Biosci Biotechnol
Biochem 2012, 76(12): 2329-31
46.
Haito Shi et al, Chlorogenic acid reduces liver inflammation and fibrosis
through inhibition of toll-like receptor 4 signaling pathway, Toxicology,
Volume 303, 7 January 2013, Pages 107-114
47.
Khaled M, Chlorogenic and Caffeic Acids in Liver Toxicity and Oxidative Stress
Induced by Methamphetamine, Journal of Toxicology, Volume 2014, Article ID
583494
48.
Nari Yun et al, Protective effects of of chlorogenic acid against
ischemia/reperfusion injury in rat liver: molecular evidence of its antioxidant
and anti-inflammatory properties, The Journal of Nutritional Biochemistry,
Volume 23, Issue 10, October 2012, Pages 1249-1255
49.
Kazumi Yagasaki et al, Inhibitory effects of chlorogenic acid and its
related compounds on the invasion of cells in culture, Cytotechnology 33:
229-235, 2000
50.
Yuan Yan et al, Chlorogenic acid enhances the effects of 5-fluouracil in human
hepatocellular carcinoma cells through the inhibition of extracellular
signal-regulated kinases, Anticancer Drugs, 2015, Jun; 26(5): 540-546
51.
Stefanello N et al, Effects of chlorogenic acid, caffeine and coffee on
behavioral and biochemical parameters of diabetic rats, Mol Cell Biochem, 2014
Mar; 388(1-2) 277-86
52.
Stefanello N et al, Effects of chlorogenic acid, caffeine and coffee on
components of purinergic system of streptozotocin-induced diabetic rats, J Nutr
Biochem, 2016 Dec; 38: 145-153
53.
MF Mcarthy, A chlorogenic acid-induced increase in GLP-1 production may mediate
the impact of heavy coffee consumption on diabetes risk, Medical hypotheses,
2005, Elsevier
54.
Khang Wei Ong et al, Antidiabetic and anti-lipidemic effects of chlorogenic
acid are mediated by ampk activation,
Biochemical Pharmacology, Volume 85, Issue 9, 1 May 2013, Pages
1341-1351
55.
Krishnamoothy Karthikesan et al, Protective effect of tetrahydrocurcumin and
chlorogenic acid against streptozotocin- nicotinamide generated oxidative stress-induceddiabetes,
Journal of Functional Foods, Volume 2, Issue 2, April 2010,
Pages 134-142
56.
Shengxi Meng et al, Roles of Chlorogenic Acid on Regulating Glucose and Lipid
Metabolism: A Review, Evidence-Based Complementary and Alternative Medicine, Volume
2013, Article ID 801457, 11 Pages
57.
Thom E, The effect of chlorogenic acid enriched coffee on glucose absorption in
healthy volunteers and its effect on body mass when used long-term in
overweight and obese people, J Int Med Res. 2007 Nov-Dec, 35(6): 900-8
58.
Onakpoya I et al, The use of green coffee extract as a weight loss supplement:
a systematic review and meta-analysis of randomised clinical trials,
Gastroenterol Res Pract 2011; pii: 38852
59.
Cho AS et al, Chlorogenic acid exhibits anti-obesity property and improves
lipid metabolism in high-fat diet-induced obese mice, Food Chem Toxicol 2010
March; 48(3): 937-43
60.
Li SY et al, Modulating effects of chlorogenic acid on lipids and
glucosemetabolism and expression of hepatic peroxisome proliferator-activated
receptor- in golden hamsters fed on high fat diet, Biomedical and
Environmental Sciences: BES 01 April 2009, 22(2): 122-129
61.
K. Karthikesan et al, Antihyperlipidemic effect of chlorogenic acid and
tetrahydrocurcumin in rats subjected to diabetogenic agents, Chemico-Biological
Interactions, Volume 188, Issue 3, 5 December 2010, Pages 643-650
62.
Errol Zeiger, Toxicological Summary for chlorogenic acid and Caffeic acid,
Review of Toxicological Literature, Triangle Park North Carolina 27709 July
1998
63.
Estefania Burgos-Moron et al, The Coffee Constituent Chlorogenic Acid Induces
Cellular DNA Damage and Formation of Topoisomerase I- and II- DNA Complexes in
Cells, J. Agric. Food Chem., 2012, 60 (3): 7384-7391
64.
Taylor Thurow's thesis, Effect of chlorogenic acid and neochlorogenic acid on
human colon cancer cells, University of Arkansas April 2012.
66.
Kang TY et al, The studies of chlorogenic acid antitumor mechanism by gene chip
detection: the immune pathway gene
expression, J Anal Methods Chem, 2013; 2013: 617243; Epub2013 May 9
67.
Roushi Xu, Atnitumor Molecular Mechanism of Chlorogenic Acid on Inducing
Genes GSK-3β and APC and Inhibiting Gene β-catenin,
Journal of Analytical Methods in Chemistry, Volume 2013, Article ID 951319,
Pages 7.
68.
Olthof MR et al, Consumption of high doses of chlorogenic acid, presennt in
coffee, or of black tea increases plasma total homocysteine concentrations in
humans, Am J Clin Nutr, 2001 March; 73(3): 532-538
69.
https://examine.com/supplements/chlorogenic-acid/
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