Protective effects of chlorogenic acid on acute hepatotoxicity induced by lipopolysaccharide in mice

Xu, Yuexin; Chen, Jingwen; Yu, Xiao; Tao, Weiwei; Fengrong, Jiang; Yin, Zhimin; Liu, Chang

doi:10.1007/s00011-010-0199-z

Cited by 102 publications

(76 citation statements)

References 37 publications

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“…It has been reported that TNF-a and IL-6 are the key pro-inflammatory cytokines to trigger an inflammatory cascade involving massive apoptosis of hepatocytes and nephrocytes, and consequent damages of hepatic and renal functions (Mei & Zheng 2009;Sarkar & Fisher 2006;Xu et al 2010). TNF-a and IL-6 are critical players in liver and kidney damage (Nowak et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…It is one of the important ingredients of green coffee beans (Bekedam et al 2008) and also in many kinds of fruits and vegetables such as apples, cherries, plums, berries, apricots, tomatoes, and potatoes (Heitman & Ingram 2014). Several recent studies have demonstrated that CGA exerts a variety of pharmacological effects, including antioxidative and anti-inflammatory effects (Xu et al 2010;Sato et al 2011). Previous research found that CGA protected mice against lipopolysaccharideinduced inflammatory responses in acute lung injury (Zhang et al 2010).…”

Section: Introductionmentioning

confidence: 99%

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Chlorogenic acid protects d-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice

Feng

Wang

et al. 2016

Pharmaceutical Biology

106

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Context Oxidative stress and inflammation are implicated in the aging process and its related hepatic and renal function decline. Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in the human diet. Recently, CGA has shown in vivo and in vitro antioxidant properties. Objective The current study investigates the effects of protective effects of chlorogenic acid (CGA) on D-galactose-induced liver and kidney injury. Materials and methods Hepatic and renal injuries were induced in a mouse model by subcutaneously injection of D-galactose (D-gal; 100 mg/kg) once a day for 8 consecutive weeks and orally administered simultaneously with CGA included in the food (200 mg/kg of diet). The liver and renal functions were examined. Histological analyses of liver and kidney were done by haematoxylin and eosin staining. The oxidative stress markers and pro-inflammatory cytokines in the liver and the kidney were measured. Results CGA significantly reduced the serum aminotransferase, serum creatinine (SCr) and blood urea nitrogen (BUN) levels in D-gal mice (p50.05). CGA also restored superoxide dismutase, catalase, and malondialdehyde levels and decreased glutathione content in the liver and kidney in D-gal mice (p50.05). Improvements in liver and kidney were also noted in histopathological studies. CGA reduced tumour necrosis factor-a (TNF-a) and interleukin-6 (IL-6) protein levels in the liver and kidney in D-gal mice (p50.05). Discussion and conclusion These findings suggest that CGA attenuates D-gal-induced chronic liver and kidney injury and that this protection may be due to its antioxidative and antiinflammatory activities.ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chlorogenic acid protects d-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice

Feng

Wang

et al. 2016

Pharmaceutical Biology

106

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“…A previous study has also pointed out that the hepatotoxicity of 5-CQA can be markedly increased when the peroxidase/H 2 O 2 oxidation system was added to hepatocyte incubations (Moridani et al, 2001). Regardless of several research groups who have shown the antioxidative property of 5-CQA (Pari et al, 2010;Xu et al, 2010;Sato et al, 2011), the anti-and pro-oxidation properties of 5-CQA are not contradictory. The dose is critical with regards to the metabolic fate of the compound as well as metabolic switching and the route of administration.…”

Section: Xie Et Almentioning

confidence: 99%

Identification of the ortho-Benzoquinone Intermediate of 5-O-Caffeoylquinic Acid In Vitro and In Vivo: Comparison of Bioactivation under Normal and Pathological Situations

Xie¹,

Zhong²,

Chen³

2012

Drug Metab Dispos

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ABSTRACT:5-O-Caffeoylquinic acid (5-CQA) is one of the major bioactive ingredients in some Chinese herbal injections. Occasional anaphylaxis has been reported for these injections during their clinical use, possibly caused by reactive metabolites of 5-CQA. This study aimed at characterizing the bioactivation pathway(s) of 5-CQA and the metabolic enzyme(s) involved. After incubating 5-CQA with GSH and NADPH-supplemented human liver microsomes, two types of GSH conjugates were characterized: one was M1-1 from the 1,4-addition of GSH to ortho-benzoquinone intermediate; the other was M2-1 and M2-2 from the 1,4-addition of GSH directly to the ␣,␤-unsaturated carbonyl group of the parent. The formation of M1-1 was cytochrome P450 (P450)-mediated, with 3A4 and 2E1 as the principal catalyzing enzymes, whereas the formation of M2-1 and M2-2 was independent of NADPH and could be accelerated by cytosolic glutathione transferase. In the presence of cumene hydroperoxide, M1-1 formation increased 6-fold, indicating that 5-CQA can also be bioactivated by P450 peroxidase under oxidizing conditions. Furthermore, M1-1 could be formed by myeloperoxidase in activated human leukocytes, implying that 5-CQA bioactivation is more likely to occur under inflammatory conditions. This finding was supported by experiments on lipopolysaccharideinduced inflammatory rats, where a greater amount of M1-1 was detected. In S-adenosyl methionine-and GSH-supplemented human S9 incubations, M1-1 formation decreased by 80% but increased after tolcapone-inhibited catechol-O-methyltransferase (COMT) activity. In summary, the high reactivities of the orthobenzoquinone metabolite and ␣,␤-unsaturated carbonyl group of 5-CQA to nucleophiles have been demonstrated. Different pathological situations and COMT activities in patients may alter the bioactivation extent of 5-CQA.

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“…Thereby, the lonicerae flos extract is further developed as a drug candidate currently undergoing a phase I trial (Korea Food and Drug Administration, Identifier HSP Injection_101 Version 2.00) for sepsis treatment. Moreover, CGA ameliorates LPS-induced acute hepatotoxicity in D-galactosamine (GalN)-sensitized mice (22). This liver injury is also known as an innate immunity-related disorder, but differs from LPS-induced systemic endotoxemia in that it involves a sudden hepatocellular apoptosis with minimal necrosis (23).…”

mentioning

confidence: 99%

IRAK4 as a Molecular Target in the Amelioration of Innate Immunity–Related Endotoxic Shock and Acute Liver Injury by Chlorogenic Acid

Park

Baek

Yun

et al. 2015

The Journal of Immunology

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Mice lacking the IL-1R–associated kinase 4 (IRAK4) are completely resistant to LPS-induced endotoxic disorder or the TLR9 agonist CpG DNA plus d-galactosamine–induced acute liver injury (ALI), whereas wild-type strains succumb. However, translational drugs against sepsis or ALI remain elusive. Lonicerae flos extract is undergoing the clinical trial phase I in LPS-injected healthy human volunteers for sepsis treatment. In the current study, chlorogenic acid (CGA), a major anti-inflammatory constituent of lonicerae flos extract, rescued endotoxic mortality of LPS-intoxicated C57BL/6 mice, as well as ameliorated ALI of LPS/d-galactosamine–challenged C57BL/6 mice. As a mechanism, CGA inhibited various TLR agonist–, IL-1α–, or high-mobility group box-1–stimulated autophosphorylation (activation) of IRAK4 in peritoneal macrophages from C57BL/6 or C3H/HeJ mice via directly affecting the kinase activity of IRAK4, a proximal signal transducer in the MyD88-mediated innate immunity that enhances transcriptional activity of NF-κB or AP-1. CGA consequently attenuated protein or mRNA levels of NF-κB/AP-1 target genes encoding TNF-α, IL-1α, IL-6, and high-mobility group box-1 in vivo under endotoxemia or ALI. Finally, this study suggests IRAK4 as a molecular target of CGA in the treatment of innate immunity–related shock and organ dysfunction following insult of various TLR pathogens from bacteria and viruses.

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Protective effects of chlorogenic acid on acute hepatotoxicity induced by lipopolysaccharide in mice

Abstract: Our data suggest that CGA has remarkable hepatoprotective effects on LPS-induced liver injury and that the possible mechanism is related to its anti-inflammatory action.

Cited by 102 publications

References 37 publications

Chlorogenic acid protects d-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice

Chlorogenic acid protects d-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice

Identification of the ortho-Benzoquinone Intermediate of 5-O-Caffeoylquinic Acid In Vitro and In Vivo: Comparison of Bioactivation under Normal and Pathological Situations

IRAK4 as a Molecular Target in the Amelioration of Innate Immunity–Related Endotoxic Shock and Acute Liver Injury by Chlorogenic Acid

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