Caffeic acid

Antiviral Res. 2009 Aug;83(2):186-90.

Anti-hepatitis B virus activity of chlorogenic acid, quinic acid and caffeic acid in vivo and in vitro.[Pubmed: 19463857 ]

Chlorogenic acid and its related compounds are abundant plant polyphenols that have a diverse antiviral activity.
METHODS AND RESULTS:
In this study, HepG2.2.15 cells and duck hepatitis B virus infection model were used as in vitro and in vivo models to evaluate their anti-HBV activity. In the cell model, all the three compounds inhibited HBV-DNA replication as well as HBsAg production. Chlorogenic acid and Caffeic acid also reduced serum DHBV level in DHBV-infected duckling model. Moreover, the anti-HBV activity of crude extracts of coffee beans, which have a high content of chlorogenic acid, was studied.
CONCLUSIONS:
Both the extracts of regular coffee and that of decaffeinated coffee showed inhibitory effect on HBV replication.

2015 Sep 5;762:313-21

Caffeic acid exhibits anti-pruritic effects by inhibition of multiple itch transmission pathways in mice[Pubmed: 26057691]

Itch is an unpleasant sensation that evokes a desire to scratch. Although often regarded as a trivial 'alarming' sensation, itch may be debilitating and exhausting, leading to reduction in quality of life. In the current study, the question of whether Caffeic acid can be used to alleviate itch sensation induced by various pruritic agents, including histamine, chloroquine, SLIGRL-NH2, and β-alanine was investigated. It turned out that histamine-induced intracellular calcium increase was significantly blocked by Caffeic acid in HEK293T cells that express H1R and TRPV1, molecules required for transmission of histamine-induced itch in sensory neurons. In addition, inhibition of histamine-induced intracellular calcium increase by Caffeic acid was demonstrated in primary cultures of mouse dorsal root ganglion (DRG). When chloroquine, an anti-malaria agent known to induce histamine-independent itch - was used, it was also found that Caffeic acid inhibits the induced response in both DRG and HEK293T cells that express MRGPRA3 and TRPA1, underlying molecular entities responsible for chloroquine-mediated itch. Likewise, intracellular calcium changes by SLIGRL-NH2 - an itch-inducing agent via PAR2 and MRGPRC11 - were decreased by Caffeic acid as well. However, it was found that Caffeic acid is not capable of inhibiting β-alanine-induced responses via its specific receptor MRGPRD. Finally, in vivo scratching behavior tests showed that Caffeic acid indeed has anti-scratching effects against histamine, chloroquine, and SLIGRL-NH2 administration but not by β-alanine. Overall, the current study demonstrated that Caffeic acid has anti-itch effects by inhibition of multiple itch mechanisms induced by histamine, chloroquine and SLIGRL-NH2.

J Pharmacol Exp Ther. 2006 Aug;318(2):476-83

Antihyperglycemic and antioxidant properties of caffeic acid in db/db mice.[Pubmed: 16644902 ]

This study investigated the blood glucose-lowering effect and antioxidant capacity of Caffeic acid in C57BL/KsJ-db/db mice.
METHODS AND RESULTS:
Caffeic acid induced a significant reduction of the blood glucose and glycosylated hemoglobin levels than the control group. The plasma insulin, C-peptide, and leptin levels in Caffeic acid group were significantly higher than those of the control group, whereas the plasma glucagon level was lower. Increased plasma insulin by Caffeic acid was attributable to an antidegenerative effect on the islets. Caffeic acid also markedly increased glucokinase activity and its mRNA expression and glycogen content and simultaneously lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities and their respective mRNA expressions, accompanied by a reduction in the glucose transporter 2 expression in the liver. In contrast to the hepatic glucose transporter 2, adipocyte glucose transporter 4 expression was greater than the control group. In addition, Caffeic acid significantly increased superoxide dismutase, catalase, and glutathione peroxidase activities and their respective mRNA levels, while lowering the hydrogen peroxide and thiobarbituric acid reactive substances levels in the erythrocyte and liver of db/db mice.
CONCLUSIONS:
These results indicate that Caffeic acid exhibits a significant potential as an antidiabetic agent by suppressing a progression of type 2 diabetic states that is suggested by an attenuation of hepatic glucose output and enhancement of adipocyte glucose uptake, insulin secretion, and antioxidant capacity.

Free Radic Res. 2004 Nov;38(11):1241-53.

Caffeic acid derivatives: in vitro and in vivo anti-inflammatory properties.[Pubmed: 15621702]

Caffeic acid and some of its derivatives such as Caffeic acid phenetyl ester (CAPE) and octyl caffeate are potent antioxidants which present important anti-inflammatory actions.
METHODS AND RESULTS:
The present study assessed the in vitro and in vivo effects of five Caffeic acid derivatives (Caffeic acid methyl, ethyl, butyl, octyl and benzyl esters) and compared their actions to those of CAPE. In the model of LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages, the pre-incubation of all derivatives inhibited nitrite accumulation on the supernatant of stimulated cells, with mean IC50 (microM) values of 21.0, 12.0, 8.4, 2.4, 10.7 and 4.80 for methyl, ethyl, butyl, octyl, benzyl and CAPE, respectively. The effects of Caffeic acid derivatives seem to be related to the scavenging of NO, as the compounds prevented SNAP-derived nitrite accumulation and decreased iNOS expression. In addition, butyl, octyl and CAPE derivatives significantly inhibited LPS-induced iNOS expression in RAW 264.7 macrophages. Extending the in vitro results, we showed that the pre-treatment of mice with butyl, octyl and CAPE derivatives inhibited carrageenan-induced paw edema and prevented the increase in IL-1beta levels in the mouse paw by 30, 24 and 36%, respectively. Butyl, octyl and CAPE derivatives also prevented carrageenan-induced neutrophil influx in the mouse paw by 28, 49 and 31%, respectively.
CONCLUSIONS:
Present results confirm and extend literature data, showing that Caffeic acid derivatives exert in vitro and in vivo anti-inflammatory actions, being their actions mediated, at least in part by the scavenging of NO and their ability to modulate iNOS expression and probably that of other inflammatory mediators.

2015 Apr 18;11:18.

The protective effect of caffeic acid on global cerebral ischemia-reperfusion injury in rats[Pubmed: 25907417]

Ischemic stroke is a major cause of death and disability all over the world. Ischemic stroke results from a temporary or permanent reduction of cerebral blood flow that leads to functional and structural damage in different brain regions. Despite decades of intense research, the beneficial treatment of stroke remains limited. In light of this, the search for effective means ameliorating cerebral ischemia-reperfusion injury (CIRI) is one of the major problems of experimental medicine and biology. Recently, the 5-Lipoxygenase (5-LO, a key enzyme metabolizing arachidonic acid to produce leukotrienes) inhibitors have been showed to protect brain against ischemic damage in animal model of cerebral ischemia. Caffeic acid, an inhibitor of 5-LO, is a phenolic compound widely distributed in medicinal plants. The aim of this study was to investigate the effect of Caffeic acid on global cerebral ischemia-reperfusion injury in rats. The study was carried out on 45 rats that were randomly divided into five groups: the sham group (n = 9), I/R non-treated group (n = 9), I/R-Caffeic acid group (10 mg · kg(-1)) (n = 9), I/R-Caffeic acid group (30 mg · kg(-1)) (n = 9) and I/R-Caffeic acid group (50 mg · kg(-1)) (n = 9). Global cerebral ischemia was induced by bilateral carotid artery occlusion for 20 min followed by reperfusion. Spatial learning and memory was evaluated using Morris water maze. Histopathological changes of hippocampus neurons was observed using HE staining. Superoxide dismutase (SOD, the antioxidant enzyme) activities and malondialdehyde (MDA, an oxidative stress biomarker) contents were detected. NF-κBp65 expression was detected by the methods of immunohistochemistry. Caffeic acid markedly reduced the escape latency, relieved hippocampal neurons injury and increased neuron count compared with those of I/R non-treated rat. NF-κBp65 expression and MDA content decreased significantly, and SOD activities increased significantly in hippocampus. Compared with sham group, 5-LO expression increase significantly in I/R non-treated group rat, and Caffeic acid markedly reduced 5-LO expression. The results of the study suggest that Caffeic acid has a significant protective effect on global cerebral ischemia-reperfusion injury in rats. The neuroprotective effects is likely to be mediated through the inhibition of 5-LO.

Biochimie. 2015 Jan;108:178-85.

Anti-fibrillation potency of caffeic acid against an antidepressant induced fibrillogenesis of human α-synuclein: Implications for Parkinson's disease.[Pubmed: 25461276]

Alpha synuclein is a 14 kDa intrinsically disordered, presynaptic protein whose fibrillation is a critical step in the pathogenesis of Parkinson's disease (PD). A structural investigation of the effect of escitalopram (a selective serotonin reuptake inhibitor) on α-synuclein was performed using ANS and ThT assays, CD, turbidity and Rayleigh scattering measurements as well as atomic force and transmission electron microscopy. Analysing the mechanism of α-synuclein fibril formation, helped us in elucidating the passage of an intermediate at 75 μM concentration of escitalopram. Fibrils of α-synuclein were obtained at 100 μM concentration of escitalopram. Inhibition of α-synuclein fibrillation was brought about by a polyphenolic acid known as Caffeic acid which acted in a concentration dependent manner ranging from 10 to 60 μM. Maximum inhibition was achieved at a concentration of 60 μM. Fibrillation of α-synuclein in presence of escitalopram gives us clue for the negative effects of antidepressant. Inhibitory activity of Caffeic acid against α-synuclein fibrillation may guide us in designing novel therapeutic drugs for PD.

Clin Cancer Res. 2015 Feb 17.

Caffeine and caffeic acid inhibit growth and modify estrogen receptor (ER) and insulin-like growth factor I receptor (IGF-IR) levels in human breast cancer.[Pubmed: 25691730]

Epidemiologic studies indicate that dietary factors, such as coffee, may influence breast cancer and modulate hormone receptor status. The purpose of this translational study was to investigate how coffee may affect breast cancer growth in relation to estrogen receptor-α (ER) status.
METHODS AND RESULTS:
The influence of coffee consumption on patient and tumor characteristics and disease-free survival was assessed in a population-based cohort of 1,090 patients with invasive primary breast cancer in Sweden. Cellular and molecular effects by the coffee constituents caffeine and Caffeic acid were evaluated in ER(+) (MCF-7) and ER(-) (MDA-MB-231) breast cancer cells. Moderate (2-4 cups/day) to high (≥5 cups/day) coffee intake was associated with smaller invasive primary tumors (Ptrend = 0.013) and lower proportion of ER(+) tumors (Ptrend = 0.018), compared with patients with low consumption (≤1 cup/day). Moderate to high consumption was associated with lower risk for breast cancer events in tamoxifen-treated patients with ER(+) tumors (adjusted HR, 0.51; 95% confidence interval, 0.26-0.97). Caffeine and Caffeic acid suppressed the growth of ER(+) (P ≤ 0.01) and ER(-) (P ≤ 0.03) cells. Caffeine significantly reduced ER and cyclin D1 abundance in ER(+) cells. Caffeine also reduced the insulin-like growth factor-I receptor (IGFIR) and pAkt levels in both ER(+) and ER(-) cells. Together, these effects resulted in impaired cell-cycle progression and enhanced cell death.
CONCLUSIONS:
The clinical and experimental findings demonstrate various anticancer properties of caffeine and Caffeic acid against both ER(+) and ER(-) breast cancer that may sensitize tumor cells to tamoxifen and reduce breast cancer growth.

Carcinogenesis. 2009 February; 30(2): 321–30.

Caffeic acid, a phenolic phytochemical in coffee, directly inhibits Fyn kinase activity and UVB-induced COX-2 expression[Pubmed: 19073879]

Caffeic acid (3,4-dihydroxycinnamic acid) is a well-known phenolic phytochemical present in many foods, including coffee. Recent studies suggested that Caffeic acid exerts anticarcinogenic effects, but little is known about the underlying molecular mechanisms and specific target proteins.
METHODS AND RESULTS:
In this study, we found that Fyn, one of the members of the non-receptor protein tyrosine kinase family, was required for ultraviolet (UV) B-induced cyclooxygenase-2 (COX-2) expression, and Caffeic acid suppressed UVB-induced skin carcinogenesis by directly inhibiting Fyn kinase activity. Caffeic acid more effectively suppressed UVB-induced COX-2 expression and subsequent prostaglandin E(2) production in JB6 P+ mouse skin epidermal (JB6 P+) cells compared with chlorogenic acid (5-O-caffeoylquinic acid), an ester of Caffeic acid with quinic acid. Data also revealed that Caffeic acid more effectively induced the downregulation of COX-2 expression at the transcriptional level mediated through the inhibition of activator protein-1 (AP-1) and nuclear factor-kappaB transcription activity compared with chlorogenic acid. Fyn kinase activity was suppressed more effectively by Caffeic acid than by chlorogenic acid, and downstream mitogen-activated protein kinases (MAPKs) were subsequently blocked. Pharmacological Fyn kinase inhibitor (3-(4-chlorophenyl)1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine and leflunomide) data also revealed that Fyn is involved in UVB-induced COX-2 expression mediated through the phosphorylation of MAPKs in JB6 P+ cells. Pull-down assays revealed that Caffeic acid directly bound with Fyn and non-competitively with adenosine triphosphate. In vivo data from mouse skin also supported the idea that Caffeic acid suppressed UVB-induced COX-2 expression by blocking Fyn kinase activity.
CONCLUSIONS:
These results suggested that this compound could act as a potent chemopreventive agent against skin cancer.