Protective Effect Of Chlorogenic Acid Research Articles

Protective effect of chlorogenic acid on liver injury in heat‐stressed meat rabbits

Protective effect of chlorogenic acid on liver injury in heat‐stressed meat rabbits

Chlorogenic acid regulates the expression of protein phosphatase 2A subunit B in the cerebral cortex of a rat stroke model and glutamate-exposed neurons

BackgroundIschemic stroke is a serious neurological disorder caused by blockages in cerebral artery. Protein phosphatase 2A (PP2A) is a phosphatase that performs a critical role in cell signaling and growth. PP2A subunit B acts as a neuroprotective agent in the nerve system. Chlorogenic acid, which is mainly found in roasted coffee, has antioxidant, anti-inflammatory, and anti-apoptotic effects. We hypothesized that chlorogenic acid modulates PP2A subunit B expression in ischemic stroke models and glutamate-mediated neurons. Middle artery occlusion (MCAO) surgery was operated and chlorogenic acid (30 mg/kg) or phosphate buffer saline was treated 2 h after MCAO. The cerebral cortex was collected 24 h after surgery and the change of PP2A subunit B expression was analyzed. Glutamate and/or chlorogenic acid were treated in cultured neurons, further study was performed.ResultsA decrease in PP2A subunit B expression in MCAO animals was identified. Chlorogenic acid alleviated this decrease due to ischemic injury. Moreover, the number of PP2A subunit B-positive cells in the ischemic cerebral cortex was significantly decreased, chlorogenic acid alleviated this decrease. We also found protective effects of chlorogenic acid in neurons exposed to glutamate. Glutamate decreased the expression of PP2A subunit B and chlorogenic acid mitigated this decrease. Our results elucidated that chlorogenic acid performs neuroprotective functions and attenuates the reduction of PP2A subunit B by brain damage and glutamate-mediated excitotoxicity.ConclusionsWe showed that chlorogenic acid attenuated the decrease of PP2A subunit B in ischemic injury and neurons exposed to glutamate. Since PP2A subunit B contributes to the protection of brain tissue, we can suggest that chlorogenic acid preserves neurons by modulating PP2A subunit B during ischemic damage.

Chlorogenic acid ameliorates intestinal inflammation by inhibiting NF-κB and endoplasmic reticulum stress in lipopolysaccharide-challenged broilers

Intestinal inflammation is a primary contributor to poor growth performance during poultry production. Chlorogenic acid (CGA) is a natural phenolic acid that exhibits superior anti-inflammatory activity and improved intestinal health. To investigate the protective effects and molecular mechanisms of CGA during intestinal inflammation in lipopolysaccharide (LPS)-challenged broilers, we randomly divided 288 one-day-old male Cobb broilers into 4 groups: a control group fed a basal diet (CON group), a basal diet + LPS group (LPS group), and 2 basal diet groups fed 500 or 750 mg/kg CGA + LPS (CGA_500 or CGA_750 groups). Broilers were injected with LPS or saline at 15, 17, 19, and 21 d old. Chlorogenic acid supplementation improved the growth performance of LPS-challenged broilers by increasing average daily gain (ADG) and reducing feed/gain (F/G) ratios (P < 0.05). CGA also improved intestinal barrier function in LPS-challenged boilers by enhancing jejunum morphology and integrity, decreasing intestinal permeability, and increasing occludin 3, zonula occludens-1, and mucin 2 expression (P < 0.05). CGA supplementation also improved systemic and jejunum antioxidant capacity by significantly enhancing glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities (P < 0.05), and reducing malonaldehyde (MDA) and protein carbonyl (PCO) levels (P < 0.05). Chlorogenic acid supplementation reduced systemic and jejunum pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, and IL-12) and increased anti-inflammatory cytokines (IL-10) in LPS-challenged broilers (P < 0.05) by inhibiting the toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway (P < 0.05). In addition, the protective effects of CGA toward intestinal inflammation and apoptosis appeared to be correlated with inhibited endoplasmic reticulum (ER) stress (P < 0.05). In summary, CGA supplementation improved intestinal morphology and integrity by inhibiting TLR4/NF-κB and ER stress pathways, which potentially reduced oxidative stress and inflammation, and ultimately improved the growth performance of LPS-challenged broilers.

Protective effects of chlorogenic acid against cyclophosphamide induced liver injury in mice

ABSTRACT We investigated possible protective effects of chlorogenic acid (CGA) against cyclophosphamide (CP) induced hepatic injury in mice. We measured aminotransferase alanine transaminase (ALT) and aspartate transaminase (AST) levels in the serum. We assayed catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in hepatic tissue. We assessed expression of nuclear transcription factor 2 (Nrf2) and Kelch sample related protein-1 (keap1) proteins in hepatic tissues using immunohistochemistry. The relative mRNA expression levels of heme oxygenase-1 (HO-1), NADH quinone oxidoreductase 1 (NQO1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Hematoxylin & eosin staining was used to assess liver histopathology. We found that administration of CGA prior to induction of injury by CP decreased serum ALT, AST and MDA expressions in hepatic tissue, while CAT, SOD, GSH and GSH-Px concentrations were increased. We found that hepatocytes of animals administered CGA gradually returned to normal morphology. CGA increased the protein expression of Nrf2 in murine hepatic tissue. Administration of CGA up-regulated mRNA expression levels of HO-1, NQO1, TNF-α and IL-6 in hepatic tissue. CGA exhibited a marked protective effect on CP induced liver injury in mice.

Involvement of miR-27a/smurf1/ TNF-α and mitochondrial apoptotic pathway in apoptosis induced by cerebral ischemia–reperfusion injury in rats: The protective effect of chlorogenic acid

AimsApoptosis may contribute to a considerable proportion of neuron death after acute cerebral ischemia, although the underlying mechanisms remain unknown. The purpose of this research is to investigate the effect of cerebral ischemia–reperfusion on miR-27a/smurf1 axis in rat cerebral cortex alone and in combination with chlorogenic acid. MethodsTo create a model of ischemic brain injury, nylon monofilament occlusion of the common carotid artery (CCAO) was used for 20 min. Chlorogenic acid (30 mg/kg) was given intraperitoneally (ip) 10 min before ischemia and 10 min before reperfusion. ResultsTUNEL staining of cerebral cortex neurons revealed an increase in the number of apoptotic neurons 24 h after reperfusion. At the molecular level, IR damage lowered bcl2 protein expression while simultaneously increasing bax levels and the bax/bcl2 ratio. Also, we observed higher miR-27a gene expression and higher TNF-α protein level as well as lower smurf1 protein expression after 24 h following CCAO. Treatment with chlorogenic acid significantly reduced the apoptotic damage and reversed molecular alterations in cerebral cortex neurons after IR. ConclusionOur findings indicate that miR-27a/smurf1/TNF-α axis may play a regulatory function in cerebral cortex cell death, providing a new target for novel therapeutic approaches during transit ischemic stroke. It was also shown that chlorogenic acid could restore these molecular changes, demonstrating that it is an effective agent against cerebral cortex apoptotic damage after acute IR injury.

Chlorogenic acid enhances PPARγ-mediated lipogenesis through preventing Lipin 1 nuclear translocation in Staphylococcus aureus-exposed bovine mammary epithelial cells

Chlorogenic acid (CGA) as one of the most ubiquitously dietary polyphenolic compounds, has been reported to have various antimicrobial effects and exhibit strong anti-inflammatory ability. Staphylococcus aureus is a gram-positive bacterium that can induce mastitis. However, the mechanism through which S. aureus infection affects lipid synthesis and whether CGA have protective effect on S. aureus reduced lipid synthesis is not fully understood. In this study, the internalization of S. aureus reduced intracellular lipid droplet formation, decreased the levels of intracellular triacylglycerol, total cholesterol and 7 types of fatty acid and downregulated the expression of lipogenic genes FAS, ACC, and DGAT1 in bovine mammary epithelial cells (BMECs). In addition, we found that S. aureus intracellular infection attenuated mTORC1 activation resulting in Lipin 1 nuclear localization. Remarkablely, S. aureus infection-mediated repression of lipid synthesis related to the mTORC1 signaling and Lipin 1 nuclear localization can be alleviated by CGA. Thus, our findings provide a novel mechanism by which lipid synthesis is regulated under S. aureus infection and the protective effects of CGA on lipid synthesis in BMECs.

Chlorogenic Acid Inhibits Ceramide Accumulation to Restrain Hepatic Glucagon Response.

Chlorogenic acid (CGA), a dietary natural phenolic acid, has been widely reported to regulate glucose and lipid metabolism. However, the protective effects and the underlying mechanisms of CGA on glucagon-induced hepatic glucose production remain largely uncharacterized. Herein, we investigated the efficacy of CGA on hepatic gluconeogenesis both in vivo and in vitro. The elevated levels of endogenous glucose production induced by infusion of glucagon or pyruvate were lowered in mice administered with CGA. Furthermore, chronic CGA treatment ameliorated the accumulation of glucose and ceramide in high-fat diet (HFD)-fed mice. CGA also attenuated HFD-fed-induced inflammation response. The protective effect of CGA on glucose production was further confirmed in primary mouse hepatocytes by inhibiting accumulation of ceramide and expression of p38 MAPK. Moreover, CGA administration in HFD-fed mice preserved the decreased phosphorylation of Akt in the liver, resulting in the inhibition of FoxO1 activation and, ultimately, hepatic gluconeogenesis. However, these protective effects were significantly attenuated by the addition of C2 ceramide. These results suggest that CGA inhibits ceramide accumulation to restrain hepatic glucagon response.

Chlorogenic Acid Protects DNA against Double-strand Breaks: Evidence from Single Molecule Observation

A natural polyphenol chlorogenic acid (CGA) is regarded as an antioxidant by preventing oxidative damage. Among the oxidative damages, DNA double-strand breaks (DSBs) are considered the most severe. To study the protective effect of CGA against DSBs, we measured the time-dependent increase of DSBs caused by photo-irradiation through a single molecule observation of DNA (166 kbp) using fluorescence microscopy. The results have been analyzed in relation to the two-step mechanism with single-strand breaks. A major beneficial effect of polyphenols is to prevent oxidative damage in living cells by suppressing the production of reactive oxygen species (ROS). We quantified the protective effect of Chlorogenic acid (Polyphenol) against ROS by calculating the amount of DSBs generated in a genome-size DNA molecule using a single molecular observation technique.

Targeting TLR4/3 using Chlorogenic acid ameliorates LPS+POLY I:C-induced acute respiratory distress syndrome via alleviating oxidative stress-mediated NLRP3/NF-κB axis.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a life-threatening condition caused due to significant pulmonary and systemic inflammation. Chlorogenic acid (CGA) has been shown to possess potent antioxidant, anti-inflammatory, and immunoprotective properties. However, the protective effect of CGA on viral and bacterial-induced ALI/ARDS is not yet explored. Hence, the current study is aimed to evaluate the preclinical efficacy of CGA in lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (POLY I:C)-induced ALI/ARDS models in vitro and in vivo. Human airway epithelial (BEAS-2B) cells exposed to LPS+POLY I:C significantly elevated oxidative stress and inflammatory signaling. Co-treatment with CGA (10 and 50 µM) prevented inflammation and oxidative stress mediated by TLR4/TLR3 and NLRP3 inflammasome axis. BALB/c mice, when chronically challenged with LPS+POLY I:C showed a significant influx of immune cells, upregulation of pro-inflammatory cytokines, namely: IL-6, IL-1β, and TNF-α, and treatment with intranasal CGA (1 and 5 mg/kg) normalized the elevated levels of immune cell infiltration as well as pro-inflammatory cytokines. D-Dimer, the serum marker for intravascular coagulation, was significantly increased in LPS+ POLY I:C challenged animals which was reduced with CGA treatment. Further, CGA treatment also has a beneficial effect on the lung and heart, as shown by improving lung physiological and cardiac functional parameters accompanied by the elevated antioxidant response and simultaneous reduction in tissue damage caused by LPS+POLY I:C co-infection. In summary, these comprehensive, in vitro and in vivo studies suggest that CGA may be a viable therapeutic option for bacterial and viral-induced ALI-ARDS-like pathology.

Chlorogenic acid attenuates liver apoptosis and inflammation in endoplasmic reticulum stress-induced mice.

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER)results in a state known as "ER stress". It can affect the fate of proteins and play a crucial role in the pathogenesis of several diseases. In this study, we investigated the protective effect of chlorogenic acid (CA) on the inflammation and apoptosis of tunicamycin-induced ER stress in mice. We categorized mice into six groups: Saline, Vehicle, CA, TM, CA 20-TM, and CA 50-TM. The mice received CA (20 or 50 mg/kg) before intraperitoneal tunicamycin injection. After 72 hr of treatment, serum biochemical analysis, histopathological alterations, protein and/or mRNA levels of steatosis, and inflammatory and apoptotic markers were investigated by ELISA and/or RT-PCR. We found that 20 mg/kg CA decreased mRNA levels of Grp78, Ire-1, and Perk. Moreover, CA supplementation prevented TM-induced liver injury through changes in lipid accumulation and lipogenesis markers of steatosis (Srebp-1c, Ppar- α , and Fas), and exerted an inhibitory effect on inflammatory (NF- κ B, Tnf- α , and Il-6) and apoptotic markers (caspase 3, p53, Bax, and Bcl2), of liver tissue in ER stress mice. These data suggest that CA ameliorates hepatic apoptosis and inflammation by reducing NF-κB and Caspase 3 as related key factors between inflammation and apoptosis.

Effects of dietary supplementation with chlorogenic acid on growth performance, antioxidant capacity, and hepatic inflammation in broiler chickens subjected to diquat-induced oxidative stress

This study was conducted to investigate the protective effects of chlorogenic acid (CGA) on broilers subjected to (DQ)-induced oxidative stress. In experiment 1, one hundred and ninety-two male one-day-old Ross 308 broiler chicks were distributed into 4 groups and fed a basal diet supplemented with 0, 250, 500, or 1,000 mg/kg CGA for 21 d. In experiment 2, an equivalent number of male one-day-old chicks were allocated to 4 treatments for a 21-d trial: 1) Control group, normal birds fed a basal diet; 2) DQ group, DQ-challenged birds fed a basal diet; and 3) and 4) CGA-treated groups: DQ-challenged birds fed a basal diet supplemented with 500 or 1,000 mg/kg CGA. The intraperitoneal DQ challenge was performed at 20 d. In experiment 1, CGA administration linearly increased 21-d body weight, and weight gain and feed intake during 1 to 21 d (P < 0.05). CGA linearly and/or quadratically increased total antioxidant capacity, catalase, superoxide dismutase, and glutathione peroxidase activities, elevated glutathione level, and reduced malondialdehyde accumulation in serum, liver, and/or jejunum (P < 0.05). In experiment 2, compared with the control group, DQ challenge reduced body weight ratio (P < 0.05), which was reversed by CGA administration (P < 0.05). DQ challenge increased serum total protein level, aspartate aminotransferase activity, and total bilirubin concentration (P < 0.05), which were normalized when supplementing 500 mg/kg and/or 1,000 mg/kg CGA (P < 0.05). DQ administration elevated hepatic interleukin-1β, tumor necrosis factor-α, and interleukin-6 levels (P < 0.05), and the values of interleukin-1β were normalized to control values when supplementing CGA (P < 0.05). DQ injection decreased serum superoxide dismutase activity, hepatic catalase activity, and serum and hepatic glutathione level, but increased malondialdehyde concentration in serum and liver (P < 0.05), and the values of these parameters (except hepatic catalase activity) were reversed by 500 and/or 1,000 mg/kg CGA. The results suggested that CGA could improve growth performance, alleviate oxidative stress, and ameliorate hepatic inflammation in DQ-challenged broilers.

Protective effects of chlorogenic acid on growth, intestinal inflammation, hepatic antioxidant capacity, muscle development and skin color in channel catfish Ictalurus punctatus fed an oxidized fish oil diet

Under oxidative stress condition, the protective effects of dietary chlorogenic acid (CGA) supplementation on liver antioxidant capacity, intestinal inflammation and barrier function, muscle development and skin coloration in channel catfish Ictalurus punctatus were explored in the current study. With that purpose, I. punctatus were fed five experimental diets containing 2% fresh fish oil (FFO, 9.2 meqO2/kg) or 2% oxidized fish oil (OFO, 897.4 meqO2/kg) without or with CGA supplementation (0.02%, 0.04% and 0.08%) for 8 weeks. Upon comparative analysis, the oxidized fish oil consumption significantly lowered weight gain rate, decreased intestinal villi length and muscular thickness values and the tight junction proteins mRNA abundance, augmented the intestinal proinflammatory factors, attenuated hepatic antioxidant enzymes activities and related genes mRNA expression levels, influenced the myogenic regulatory factors expression profile and impacted the myocyte density, myocyte area values as well as the skin pigments contents compared to the FFO treatment. Collectively, long-term feeding of the oxidized fish oil diet suppressed the growth performance, destroyed intestinal structural integrity, caused intestinal inflammation and hepatic oxidative stress, impacted the skeletal development and skin color of I. punctatus. Whereas CGA supplementation in oxidized fish oil diets partially counteracted the negative effects of the oxidized fish oil on I. punctatus in terms of increasing the growth performance, improving the intestinal mucosal structure, alleviating hepatic oxidative stress and intestinal inflammation, recompiling the myogenic regulatory factors expression and improving skin color. In conclusion, CGA has great potential to be an aquatic feed additive.

Chlorogenic acid ameliorates chronic stress-induced prefrontal cortex injury through activating the 5-HT/BDNF signaling pathway in rats

The chlorogenic acid (CGA) has a strong neuroprotective ability and cognitive improvement. The purpose of this study was to investigate the effect and mechanism of CGA on chronic restraint stress (CRS)-induced prefrontal cortex (PFC) injury and depression-like behavior. Rats were restrained for 6 h each day to create a CRS paradigm that lasted for 21 days. One hour prior to constraint, CGA (50 mg/kg, 100 mg/kg and 150 mg/kg) was intragastrically delivered. The results showed that CGA could reduce serum corticosterone (CORT) levels in rats and 100 mg/kg CGA could prevent CRS-induced depression-like behaviors. Histopathological revealed that 100 mg/kg CGA ameliorated CRS-induced PFC microstructural. Furthermore, 5-HT content was also increased. Therefore, 100 mg/kg of CGA will be used to further probe the molecular mechanism of regulating 5-HT. Observations using transmission electron microscopy demonstrated that CGA reduced CRS-induced PFC synaptic damage. CGA promotes cAMP-CREB-BDNF signaling pathway and inhibits indoleamine 2,3-dioxygenase (IDO) and serotonin transporter (SRET). Cellular thermal shift assays (CETSA) and molecular docking studies have shown that IDO, SERT and CGA docking have priority potential targets. Together, a protective effect of CGA is seen in rats with CRS-induced PFC by regulating the expression of IDO and SERT and then affecting the effect of 5-HT on the cAMP-CREB-BDNF signaling pathway.

Efficacy of chlorogenic acid against ethylene glycol-induced renal stone model: The role of NFKB-RUNX2-AP1-OSTERIX signaling pathway

Background and objectiveRenal tissue injuries by free radicals are an essential reason in pathogenesis of urinary tract stones. Ethylene glycol is one of the toxic agents which can causes to the increases in biosynthesis of reactive oxygen species and oxidative stress condition. Natural antioxidants have been reported to protective efficacy against renal stones formation. Accordingly, the aim of the current experiment was to identify the renal protective effect of chlorogenic acid as a well-prominent antioxidant on ethylene glycol-induced renal stone model targeting the NFKB-RUNX2-AP1-OSTERIX signaling pathway. Materials and methodsRenal stones model were established by ethylene glycol (Percent: 0.75) within the daily drinking water for rats. Treatment groups received cystone (750 mg/kg) and chlorogenic acid (100, 200, and 400 mg/kg, day: 15th to 28th, gavage). After 4 weeks, the renal function parameters (calcium, uric acid, creatinine, total protein, oxalate, and citrate) in plasma, urine, and renal tissue were measured. Moreover, oxidative stress factors and gene expression of NFKB, RUNX2, AP1, and OSTERIX were also evaluated. ResultsThe results showed improved renal function in chlorogenic acid-treated groups. The total proteins and creatinine excretion were decreased. Also the gene expression of oxidative stress pathway (NFKB-RUNX2-AP1-OSTERIX) were decreased which caused to increases of antioxidant enzymes. Conclusionsthe antioxidant activity increases by chlorogenic acid treatment may have a critical role in prevention of calcium oxalate formation via inhibition of the NFKB-RUNX2-AP1-OSTERIX signaling pathway.

An evaluation of the protective effects of chlorogenic acid on broiler chickens in a dextran sodium sulfate model: a preliminary investigation

This study was conducted to investigate the protective effects of chlorogenic acid (CGA) on broilers subjected to dextran sodium sulfate (DSS)-induced intestinal damage. One hundred and forty-four 1-day-old male Arbor Acres broiler chicks were allocated into one of 3 groups with 6 replicates of eight birds each for a 21-d trial. The treatments included: 1) Control group: normal birds fed a basal diet; 2) DSS group: DSS-treated birds fed a basal diet; and 3) CGA group: DSS-treated birds fed a CGA-supplemented control diet. An oral DSS administration via drinking water was performed from 15 to 21 d of age. Compared with the control group, DSS administration reduced 21-d body weight and weight gain from 15 to 21 d, but increased absolute weight of jejunum and absolute and relative weight of ileum (P < 0.05). DSS administration elevated circulating D-lactate concentration and diamine oxidase activity (P < 0.05), which were partially reversed when supplementing CGA (P < 0.05). The oral administration with DSS decreased villus height and villus height/crypt depth ratio, but increased crypt depth in jejunum and ileum (P < 0.05). Compared with the control group, DSS administration increased serum glutathione level and jejunal catalase activity and malonaldehyde accumulation, but decreased jejunal glutathione level (P < 0.05). In contrast, feeding a CGA-supplemented diet normalized serum glutathione and jejunal malonaldehyde levels, and increased jejunal glutathione concentration in DSS-administrated birds (P < 0.05). Additionally, CGA supplementation reduced ileal malonaldehyde accumulation in DSS-treated birds (P < 0.05). DSS challenge increased levels of serum interferon-γ and interleukin-6, jejunal interleukin-1β, tumor necrosis factor-α, and interleukin-6, and ileal interleukin-1β and interleukin-6 when compared with the control group (P < 0.05). The elevated serum interferon-γ and ileal interleukin-6 levels were normalized to control values when supplementing CGA (P < 0.05). The results suggested that CGA administration could partially prevent DSS-induced increased intestinal permeability, oxidative damage, and inflammation in broilers, although it did not improve their growth performance and intestinal morphology.

Protective effects of chlorogenic acid against ionizing radiation-induced testicular toxicity

BackgroundTesticular tissues could damage by ionizing radiation (IR) during the treatment of pelvic cancers. The aim of this study was to investigate both the protective and therapeutic effects of chlorogenic acid (CGA) on IR-induced mouse testis tissue damage. MethodsIn this experimental study, 70 mice were divided into 3 groups, including group 1 (normal saline), group 2 (IR + normal saline), and group 3 (IR + 5, 10, 20, 40, and 80 mg/kg) CGA via I.P injection. Animals in groups 2 and 3 received a dose of 2.0 Gy total-body irradiation in a single fraction. At two determined time points (16 h and 35 days after exposure), the testis and caudal part of both epididymis were isolated and underwent subsequent analyses. ResultsThe results showed that irradiation of mice caused massive damage to spermatogenesis, seminiferous tubules, basal lamina, Leydig cells, and sperm parameters. Further biochemical assessment of the data demonstrated that 40 mg/kg CGA almost restored MDA to a normal level. In addition, the level of SOD, TAC, and GSH were significantly increased in the 40 mg/kg CGA treated group. Molecular evidence confirmed the protective effects of CGA and also revealed that the ratio of Bax/Bcl-2 in the presence of 40 mg/kg CGA was significantly decreased compared to IR and some treated groups. ConclusionThe protective and therapeutic effects of CGA on testis were found to be positively correlated with the dose level.

Chlorogenic acid enhances alveolar macrophages phagocytosis in acute respiratory distress syndrome by activating G protein-coupled receptor 37 (GPR 37)

BackgroundImpaired alveolar macrophages phagocytosis can contribute to pathogenesis of acute respiratory distress syndrome (ARDS) and negatively impacts clinical outcomes. Chlorogenic acid (CGA) is a naturally occurring polyphenolic compound with potential anti-inflammatory and antioxidant bioactivities. Studies have shown that CGA plays a protective role in ARDS, however, the precise protective mechanism of CGA against ARDS, is still unclear. PurposeThe aim of this study was to investigate whether CGA enhances alveolar macrophages phagocytosis to attenuate lung injury during ARDS. MethodsRAW264.7 cells were stimulated with lipopolysaccharides (100 μg/ml for 24 h) and treated with CGA (100, 200, and 400 μM CGA for 1 h) to measure pro-inflammatory cytokine levels, GPR37 expression and macrophages phagocytosis. Mouse models of ARDS induced by cecal ligation and perforation (CLP) surgery were treated with CGA (100 or 200 mg/kg) to investigate lung inflammatory injury and alveolar macrophages phagocytosis. Computational modeling was performed to examine potential binding sites of G protein-coupled receptor 37 (GPR37) with CGA, and the results were validated by interfering with the binding sites. ResultIn vitro, CGA notably ameliorated inflammatory response and increased phagocytosis in lipopolysaccharides-induced RAW264.7 cells. In vivo, CGA administration significantly alleviated lung inflammatory injury, decreased the bacteria load in the lung, promoted alveolar macrophages phagocytosis and improved the survival rate in mice with CLP-induced ARDS. Moreover, CGA markedly upregulated the expression of GPR37 in vivo and in vitro. However, the protective effect of CGA against ARDS were reversed after silencing the expression of GPR37. ConclusionCGA has a protective effect against ARDS and may enhance alveolar macrophages phagocytosis and attenuate lung inflammatory injury by upregulating GPR37 expression.

Protective effects of chlorogenic acid on inflammatory responses induced by Staphylococcus aureus and milk protein synthesis in bovine mammary epithelial cells

Staphylococcus aureus (S. aureus) is a major mastitis-causing pathogen in dairy cows. Dairy cows with mastitis suffer from a decrease in milk yield and protein content. Chlorogenic acid (CGA) is a natural product with anti-inflammatory effects. In this study, we examined the function and mechanism of CGA with regard to its anti-inflammatory effects and evaluated its protective function in milk protein synthesis in bovine mammary epithelial cells (BMECs). BMECs were cultured with and without infection by S. aureus and CGA, and extracellular inflammatory cytokines and amino acids in the medium and milk proteins were determined by ELISA. The function of IL-10RA in anti-inflammatory processes and of SF-1 in milk protein synthesis was assessed by gene silencing. The activity of mTORC1, NF-κB, and STAT5 was examined by western blot. S. aureus caused intracellular infection and upregulated TNF-α, IL-1β, IL-6, and IL-8, whereas uptake of amino acids and milk protein synthesis were suppressed. CGA mitigated the S. aureus-induced inflammatory response and milk protein synthesis in vitro and in vivo. CGA alleviated S. aureus-induced inhibition of mTORC1 and STAT5 and upregulated IL-10 and IL-10RA. In addition, SF-1 was predicted to be a transcription factor of the milk protein-encoding genes α-LA, β-LG, and CSN2. S. aureus downregulated SF-1 and CGA reversed the decline in milk protein synthesis due to SF-1 knockdown. Thus, CGA mitigates the inflammatory response that is induced by S. aureus and protects the uptake of amino acids and milk protein synthesis in BMECs.

Protective effects of chlorogenic acid on isoflurane-induced cognitive impairment of aged mice.

Postoperative cognitive dysfunction (POCD) is characterized by impairment in cognitive functions in patients following anesthesia and surgery. Chlorogenic acid (CGA) is a plant‐derived compound possessing numerous bioactive properties. The aim of this study was to investigate the therapeutic potential of CGA in isoflurane (ISO)‐induced cognitive dysfunction of aged mice, and further identify the mechanisms involved in the protective effects of CGA. A total of 80 male C57BL/6 mice, 20‐month‐old, were randomly divided into control group, isoflurane group (ISO), and ISO + 30 mg/kg CGA group and ISO + 60 mg/kg CGA. CGA was given orally once daily for 7 days to the mice and they were exposed to ISO (1.5%; 4 h). The open‐field and Morris water maze tests were used to investigate the cognitive function of mice. Pretreatment with CGA significantly attenuated ISO‐induced cognitive impairment. The levels of IL‐1β, TNF‐α, IL‐6, nuclear p65 NF‐kB, cleaved caspase‐3, and Bax were significantly increased, while the levels of IkBα and Bcl‐2 were decreased in the hippocampus 24 h after the ISO anesthesia. All the mentioned effects induced by ISO were reversed by CGA pretreatment. Furthermore, ISO exposure induced marked downregulation of SOD, CAT, HO‐1, and NQO‐1 and elevation of MDA and nuclear translocation of Nrf2 in the hippocampus tissue. All these parameters were reversed by CGA treatment. Importantly, the higher dose of CGA (60 mg/kg) showed a greater neuroprotective effect. In conclusion, these findings suggest that CGA attenuates the ISO‐induced cognitive impairment via its anti‐inflammatory, anti‐oxidative, and anti‐apoptotic properties in aged mice.

Proteomics reveal the protective effects of chlorogenic acid on Enterococcus faecium Q233 in a simulated pro-oxidant colonic environment

Certain phytochemicals have been found to promote the beneficial effects of probiotic bacteria although the molecular mechanisms of such interactions are poorly understood. The objective of the present study was to evaluate the impact of the exposure to 0.5 mM chlorogenic acid (CA) on the redox status and proteome of Enterococcus faecium isolated from cheese and challenged with 2.5 mM hydrogen peroxide (H2O2). The bacterium was incubated in anaerobic conditions for 48 h at 37 °C. CA exposure led to a more intense oxidative stress and accretion of bacterial protein carbonyls than those induced by H2O2. The oxidative damage to bacterial proteins was even more severe in the bacterium treated with both CA and H2O2, yet, such combination led to a strengthening of the antioxidant defenses, namely, a catalase-like activity. The proteomic study indicated that H2O2 caused a decrease in energy supply and the bacterium responded by reinforcing the membrane and wall structures and counteracting the redox and pH imbalance. CA stimulated the accretion of proteins related to translation and transcription regulators, and hydrolases. This phytochemical was able to counteract certain proteomic changes induced by H2O2 (i.e. increase of ATP binding cassete (ABC) transporter complex) and cause the increase of Rex, a redox-sensitive protein implicated in controlling metabolism and responses to oxidative stress. Although this protection should be confirmed under in vivo conditions, such effects point to benefits in animals or humans affected by disorders in which oxidative stress plays a major role.