Study on the Anti-Gout Activity of Chlorogenic Acid: Improvement on Hyperuricemia and Gouty Inflammation

2014 ◽  
Vol 42 (06) ◽  
pp. 1471-1483 ◽  
Author(s):  
Zhao-Qing Meng ◽  
Zhao-Hui Tang ◽  
Yun-Xia Yan ◽  
Chang-Run Guo ◽  
Liang Cao ◽  
...  

Gout is a metabolic disorder associated with hyperuricemia resulting in the deposition of monosodium urate (MSU) crystals in joints and tissues. Lowering serum uric acid (Sur) levels and anti-inflammation are highly essential in treating gout. Chlorogenic acid (CA), as one of the most abundant polyphenols in the Chinese medicines, has been rarely reported to have an anti-gout effect. The model of potassium oxonate (PO)-induced hyperuricemia in mice and MSU crystal-induced inflammation in rats has been established in this study. The potential beneficial effects and mechanisms of CA on hyperuricemia and gouty arthritis were elucidated. The results demonstrated that CA significantly decreased the Sur level by inhibiting the xanthine oxidase (XOD) activity but not increasing the urinary uric acid (Uur) level. In addition, CA also exhibited the effect of suppressing paw swelling. Further investigation indicated that CA improved the symptoms of inflammation induced by MSU crystals by inhibiting the production of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The present study suggests that CA may have a considerable potential for development as an anti-gouty arthritis agent for clinical application.

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 278
Author(s):  
Yun Mi Lee ◽  
Eunjung Son ◽  
Dong-Seon Kim

Sam-Myo-Whan (SMW) has been used in Korean and Chinese traditional medicine to help treat gout, by reducing swelling and inflammation and relieving pain. This study compared the effects of SMW extracted by using different solvents, water (SMWW) and 30% EtOH (SMWE), in the treatment of gouty arthritis. To this end, we analyzed the main components of SMWW and SMWE, using high-performance liquid chromatography (HPLC). Anti-hyperuricemic activity was evaluated by measuring serum uric acid levels in hyperuricemic rats. The effects of SMWW and SMWE on swelling, pain, and inflammation in gouty arthritis were investigated by measuring affected limb swelling and weight-bearing, as well as by enzyme-linked immunosorbent assays, to assess the levels of proinflammatory cytokines and myeloperoxidase (MPO). In potassium oxonate (PO)-induced hyperuricemic rats, SMWW and SMWE both significantly decreased serum uric acid to similar levels. In monosodium urate (MSU)-induced gouty arthritis mice, SMWE more efficiently decreased paw swelling and attenuated joint pain compare to SMWW. Moreover, SMWE and SMWW suppressed the level of inflammation by downregulating proinflammatory cytokines (interleukin-1β, tumor necrosis factor-α, and interleukin-6) and MPO activity. HPLC analysis further revealed that berberine represented one of the major active ingredients demonstrating the greatest change in concentration between SMWW and SMWE. Our data demonstrate that SMWE retains a more effective therapeutic concentration compared to SMWW, in a mouse model of gouty arthritis.


2008 ◽  
Vol 68 (2) ◽  
pp. 273-278 ◽  
Author(s):  
E J Giamarellos-Bourboulis ◽  
M Mouktaroudi ◽  
E Bodar ◽  
J van der Ven ◽  
B-J Kullberg ◽  
...  

Objective:Recent studies suggest that crystals of monosodium urate (MSU), deposited in joints of patients with acute gouty arthritis, activate the NACHT domain, leucine-rich repeat and pyrin domain-containing protein (NALP)3 inflammasome. In the present study we have investigated whether production of proinflammatory cytokines by crystals was exacerbated during costimulation with Toll-like receptor (TLR) ligands.Methods:Mononuclear cells of 22 healthy donors were stimulated by various concentrations of MSU crystals in the absence or presence of lipopolysaccharide (LPS), Pam3Cys and flagellin. Production of tumour necrosis factor α (TNFα), interleukin (IL)1β and IL6, as well as the intracellular concentrations of proIL1β were measured by ELISA. mRNA transcripts of TNFα and IL1β were assessed by real-time PCR. Stimulation experiments were also performed with peripheral blood mononuclear cells (PBMCs) of one patient carrying a NALP3 mutation.Results:MSU induced a moderate release of IL1β and IL6, but not of TNFα. Urate crystals amplified IL1β production stimulated by the TLR4 ligand LPS, while no synergy was apparent for IL6 production. In addition, no synergy between urate crystals and Pam3Cys (TLR2 ligand) or flagellin (TLR5 ligand) was apparent. The synergy between urate crystals and LPS was directed at the level of the NALP3 inflammasome, as it was present only when active IL1β was measured, but not at the level of IL1 mRNA or proIL1β. The synergy between LPS and MSU crystals ceased to exist in the presence of a caspase 1 inhibitor.Conclusions:MSU crystals act in synergy with LPS for the induction of enhanced release of IL1β. Increased cleavage of proIL1β by urate-activated caspase 1 is proposed as the underlying mechanism.


Nanomaterials ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 50 ◽  
Author(s):  
Sung Eun Kim ◽  
Somang Choi ◽  
Jae-Young Hong ◽  
Kyu-Sik Shim ◽  
Tae-Hoon Kim ◽  
...  

The purpose of this study was to investigate the effects of lactoferrin (LF)-conjugated nanodiamonds (NDs) in vitro on both anti-oxidant and anti-inflammation activity as well as osteogenic promotion. The application of LF-NDs resulted in sustained release of LF for up to 7 days. In vitro anti-oxidant analyses performed using Dichlorofluorescin diacetate (DCF-DA) assay and cell proliferation studies showed that LF (50 μg)-NDs effectively scavenged the reactive oxygen species (ROS) in MC3T3-E1 cells (osteoblast-like cells) after H2O2 treatment and increased proliferation of cells after H2O2 treatment. Treatment of lipopolysaccharide (LPS)-induced MC3T3-E1 cells with LF-NDs suppressed levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, LF-NDs were associated with outstanding enhancement of osteogenic activity of MC3T3-E1 cells due to increased alkaline phosphatase (ALP) and calcium deposition. Our findings suggest that LF-NDs are an important substrate for alleviating ROS effects and inflammation, as well as promoting osteogenic differentiation of cells.


Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 914
Author(s):  
Vika Guloyan ◽  
Buzand Oganesian ◽  
Nicole Baghdasaryan ◽  
Christopher Yeh ◽  
Manpreet Singh ◽  
...  

Morbidity and mortality of coronavirus disease 2019 (COVID-19) are due in large part to severe cytokine storm and hypercoagulable state brought on by dysregulated host-inflammatory immune response, ultimately leading to multi-organ failure. Exacerbated oxidative stress caused by increased levels of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) along with decreased levels of interferon α and interferon β (IFN-α, IFN-β) are mainly believed to drive the disease process. Based on the evidence attesting to the ability of glutathione (GSH) to inhibit viral replication and decrease levels of IL-6 in human immunodeficiency virus (HIV) and tuberculosis (TB) patients, as well as beneficial effects of GSH on other pulmonary diseases processes, we believe the use of liposomal GSH could be beneficial in COVID-19 patients. This review discusses the epidemiology, transmission, and clinical presentation of COVID-19 with a focus on its pathogenesis and the possible use of liposomal GSH as an adjunctive treatment to the current treatment modalities in COVID-19 patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ramin Goudarzi ◽  
Maryam Eskandarynasab ◽  
Ahad Muhammadnejad ◽  
Ahmad Reza Dehpour ◽  
Alireza Partoazar

Abstract Objective Atopic dermatitis (AD) is a chronic inflammatory skin disease mainly caused by immune stimuli. The current study was conducted to investigate the effects of ROCEN and to compare it with betamethasone (Beta) on mice subjected to AD. Methods First, the safety of topical ROCEN was tested to determine possible sensitization induction in vivo. Then, the mice were subjected to oxazolone (Oxa) to induce chronic AD. Consequently, they underwent treatment with ROCEN and Beta. Scratching and wiping behaviors related to dermatitis were evaluated in treated animals for 35 days. The histopathology and immunohistochemistry (IHC) analysis of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) cytokines were performed on the dorsal skin of the treated mice. Results Topical administration of ROCEN and Beta to the dorsum of sensitized mice for 5 weeks significantly alleviated scratching and wiping symptoms and reduced erythema, scaling, and edema in the skin of the mice with AD. Moreover, histological indices showed that ROCEN effectively reduced leucocyte infiltration and improved skin healing parameters in treated AD mice. Application of ROCEN or Beta reduced IHC markers including IL-8 and TNF-α significantly. Conclusion ROCEN alleviated the AD symptoms similar to betamethasone in an experimental animal model.


2020 ◽  
Vol 8 (A) ◽  
pp. 220-224
Author(s):  
Rachmat Hidayat ◽  
Muhammad Reagan ◽  
Lusia Hayati

BACKGROUND: Gouty arthritis, a chronic inflammatory disease characterized by severe pain and swelling in one or more synovial joints, as a result from joint deposition of monosodium urate (MSU) crystals. Tempuyung (Sonchus arvensis) is a plant that has been extensively studied in the role of shedding kidney stones and diuretics. It is presumed that it also has great potential in shedding MSU crystals in the joints. AIM: This study focused on exploring the anti-inflammatory role of tempuyung extract (ET) on pro-inflammatory cytokines in gout arthritis white rats. METHODS: The extraction of tempuyung was performed to obtain ET. A total of 30 Wistar rats were randomly divided into the following six groups, each containing five rats: Normal control group, MSU group (negative control), MSU + colchicine group (Col; 0.28 mg/kg), and MSU + ET group (at dose of 25 mg/kg, 50 mg/kg, and 100 mg/kg). Gouty arthritis was induced with 50 ml of MSU solution (20 mg/ml), which was injected into the left ankle joint cavity on day 7. Synovial fluid was evacuated for the examination of Western blotting of tumor necrosis factor-α (TNF-α). A portion of synovial tissue was fixed in 4% paraformaldehyde buffer for histopathological examination. Interleukin (IL)-1β levels in the synovial fluid of the joints were examined by IL-1β rat enzyme-linked immunosorbent assay. Statistical analysis was performed with way ANOVA followed by post hoc. RESULTS: The histopathological image of the MSU model group showed a large number of inflammatory cells depicting an inflammatory reaction. This inflammation response decreased in the ET treatment group in dose-dependent manner. ET showed the effect of decreased pro-inflammatory cytokines expression in both IL-1β and TNF-α, as the dose increased. CONCLUSION: Tempuyung extract possessed an anti-gout arthritis effect in white rats induced by MSU, by reducing the inflammatory response in the synovial joint.


2019 ◽  
Vol 244 (5) ◽  
pp. 344-351 ◽  
Author(s):  
Yessica Zamudio-Cuevas ◽  
Javier Fernández-Torres ◽  
Gabriela Angélica Martínez-Nava ◽  
Karina Martínez-Flores ◽  
Adriana Ramírez Olvera ◽  
...  

Synovial cells play a crucial part in gouty arthritis, with different features for the inflammation within the joint. However, there is no information about how the synoviocytes can mediate the activation of inflammation. We hypothesized that the process of monosodium urate (MSU) crystal uptake alters the inflammatory response of synoviocytes through regulation of unknown mechanisms. Synoviocytes were stimulated with MSU crystals, and the phagocytosis index (PhIx) was evaluated by counting of cells with MSU ingested using polarized light microscopy. Additionally, transmission electron microscopy and flow cytometry were performed. Secretion of cytokines was measured by a panel of immunoassays. Changes in gene expression of hypoxia-inducible factor-1 ( HIF1A), von Hippel-Lindau ( VHL), and vascular endothelial growth factor ( VEGF) were evaluated by quantitative real-time PCR (qRT-PCR). Protein levels were detected by ELISA. MSU crystals induced a time-dependent increase in PhIx and the formation of numerous secretory vesicles and cavities located in the cytoplasm. Culture supernatants of MSU-treated cells had high levels of the cytokines IL-1β, IL-6, IL-8, TNF-α, and MCP-1, and the growth factors NGF and HGF. The decrease in HIF1A gene expression was 0.58-fold, and overexpression of VHL and VEGF genes was 1.98- and 4-fold, respectively, in MSU-treated synoviocytes compared to untreated cells. Additionally, VEGF levels were increased. The identification of phagocytosis of MSU crystals triggering an inflammatory cellular state in synoviocytes suggests a possible mechanism of synovial activation in the pathogenesis of crystal-induced arthritis. Impact statement Gout is distinguished by an inflammatory process that is mediated by phagocytosis of monosodium urate (MSU) crystals in synoviocytes by regulation of unknown mechanisms. Here we suggest that the synovial cells play a crucial role in gouty arthritis by activating inflammation by MSU uptake and increasing the secretion of pro-inflammatory cytokines IL-1β, IL-6, IL-8, TNF-α, MCP-1, and the growth factors NGF and HGF. We discuss some co-existing features in synoviocytes, including anomalous morphologies of the cells, and microvesicle formation, dysregulation in VEGF gene expression. We provide evidence that phagocytosis of MSU crystals triggers an inflammatory cellular state in synoviocytes in the pathogenesis of crystal-induced arthritis.


2009 ◽  
Vol 36 (8) ◽  
pp. 1575-1579 ◽  
Author(s):  
ESTELLA MUSACCHIO ◽  
CHIARA VALVASON ◽  
CONSTANTIN BOTSIOS ◽  
FRANCESCA OSTUNI ◽  
ANTONIO FURLAN ◽  
...  

Objective.Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine involved in the pathogenesis of several rheumatic diseases, including rheumatoid arthritis (RA), associated with systemic bone loss and subchondral bone erosions. TNF-α-blocking agents such as infliximab have been successful in treatment of disease-modifying antirheumatic drug-resistant rheumatic diseases. Infliximab therapy in RA also had beneficial effects on local bone destruction and bone mineral density. We assessed effects of infliximab treatment on the bone tissue compartment and cytokine profile expression in vitro.Methods.Osteoblast-like cells were exposed for 24 h to sera of RA patients collected at baseline and after 1 month (T1) and 3 years (T2) of infliximab treatment. Total RNA was extracted, and expression of interleukin 1ß (IL-1ß), IL-6, and osteoprotegerin (OPG) was measured by RT-PCR.Results.IL-1ß gene expression was significantly reduced by the T1 serum, and the same decrease was elicited by the T2 serum. IL-6 downregulation was evident with the T2 serum. OPG was unaffected.Conclusion.The finding of downregulation of inflammatory cytokines was interesting, particularly IL-6, which plays a crucial role in arthritis-related bone loss due to its involvement in osteoclast recruitment and activation. These results may represent a biological explanation and a link for the clinical observation of the beneficial effects of anti-TNF-α agents on the progression of rheumatic diseases at the bone level.


2021 ◽  
Author(s):  
Ramin Goudarzi ◽  
Maryam Eskandarynasab ◽  
Ahad Muhammadnejad ◽  
Ahmad Reza Dehpour ◽  
Alireza Partoazar

Abstract Objective: Atopic dermatitis (AD) is a chronic inflammatory skin disease caused mainly by the immune stimulus. The current study aimed to investigate the effects of liposome containing arthrocen (ROCEN) and its comparison with betamethasone (Beta) on mice subjected to AD. Methods: First of all, the risk assessment of ROCEN sensitization was done, then mice were subjected to oxazolone (Oxa) for chronic AD induction and treatment. Scratching and wiping behaviors related to dermatitis were evaluated in animals treated topically with ROCEN. The histological and immunohistochemistry analysis of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) were conducted to the dorsal skin of treated rats. Results: The results showed that cutaneous administration of ROCEN on sensitized mice for 5 weeks, alleviated significantly scratching and wiping symptoms, erythema, scaling, and edema in animals’ skin. Moreover, histological indices showed that ROCEN reduced effectively leucocyte infiltration and improved skin healing parameters in AD mice. Immunohistochemically markers of IL-8 and TNF-α were hindered significantly by ROCEN in dermal tissues of mice. Conclusion: ROCEN potentiated alleviation of the AD symptoms rather than betamethasone drug in an experimental model.


2017 ◽  
Vol 68 (6) ◽  
pp. 1234-1241
Author(s):  
Adina Octavia Duse ◽  
Delia Berceanu Vaduva ◽  
Mirela Nicolov ◽  
Cristina Trandafirescu ◽  
Marcel Berceanu Vaduva ◽  
...  

Acute gouty arthritis represents an inflammatory response to microcrystals of monosodium urate that precipitate in joint tissues from supersaturated body fluids or are shed from preexisting articular deposits [1]. Gout is a metabolic disease characterized by recurrent episodes of arthritis associated with the presence of monosodium urate crystals in the tissue or synovial fluid during the attack.These forms of crystal-induced arthritis usually affect peripheral joints, including knee, ankle, wrist, and metacarpophalangeal and metatarsophalangeal joints. All of them may be associated with other inflammatory, endocrine diseases [2]. The present study was done to highlight the relationship between increased levels of uric acid and specific laboratory tests in order to possible forecast development of further disease in patients with gouty arthrithis.The present study was done on 34 patients hospitalized in Felix Hospital of Rehabilitation in 2015-2016, with age between 44 and 74, having the main diagnosis of gouty arthritis.We studied the following laboratory tests:urea and other related analysis, like uric acid, creatinine, cholesterol, glutamate pyruvate transaminase and glutamate oxalate transaminase.


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