Extracts of Andrographis paniculata (Burm.f.) Nees Leaves Exert Anti-Gout Effects by Lowering Uric Acid Levels and Reducing Monosodium Urate Crystal-Induced Inflammation

Andrographis paniculata (Burm.f.) Nees has been found to have anti-inflammatory and immunostimulatory effects. This study was to investigate antihyperuricemic and anti-inflammatory effects of A. paniculata leaf extracts. Andrographolide, 14-deoxy-11,12-didehydroandrographolide, and neoandrographolide were quantified in 80% ethanol (EtOH80) and water extracts using High Performance Liquid Chromatography (HPLC) analysis. Antihyperuricemic activity was evaluated using a spectrophotometric in vitro inhibitory xanthine oxidase (XO) assay. The most active extract and andrographolide were further investigated in a hyperuricemic rat model induced by potassium oxonate to determine serum uric acid levels, liver XO activity, followed by Western blot analysis for renal urate transporter URAT1, GLUT9, and OAT1 to investigate the excretion of uric acid via kidney. Anti-inflammatory activity was assessed by in vitro interleukin assay for interleukin (IL-1α, IL-1β, IL-6, IL-8), and tumor necrosis factor (TNF-α) in monosodium urate (MSU) crystal-induced human fibroblast-like synoviocyte (HFLS) cells using ELISA-kits, followed by Western blot analysis for the expression of MyD88, NLRP3, NF-κB p65, and caspase-1 proteins to investigate the inflammation pathway. In vivo assay of the most active extract and andrographolide were performed based on the swelling rate and inhibition of pro-inflammatory mediator release from synovial fluid of a rat knee joint induced by MSU crystals. The results showed that the EtOH80 extract had a greater amount of andrographolide (11.34% w/w) than the water extract (1.38% w/w). In the XO inhibitory activity, none of the samples exhibited greater than 50% inhibition. However, in a rat model, EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg/day) decreased serum uric acid levels and reduced liver XO activity, reduced the protein expression levels of URAT1 and GLUT9, and restored the decrease in OAT1 levels. In the in vitro anti-inflammatory study, EtOH80 extract and andrographolide significantly decreased production of IL-1α, IL-1β, IL-6, and TNF-α, as well as inhibited the synthesis of MyD88, NLRP3, NF-κB p65, and caspase-1 in a concentration-dependent manner, almost comparable to dexamethasone. The EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg) significantly decreased swelling rate and IL-1α, IL-1β, IL-6, and TNF-α in the synovial fluid of rat models in a time-dependent manner, comparable to indomethacin (3 mg/kg/day). In conclusion, the findings show that EtOH80 extract has a substantial anti-gout effect by lowering uric acid levels and suppressing pro-inflammatory mediator production due to the andrographolide content, that might be beneficial in the treatment of gouty-inflammation.

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Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts

Journal of Dental Research ◽

10.1177/154405910608500511 ◽

2006 ◽

Vol 85 (5) ◽

pp. 452-456 ◽

Cited By ~ 1

Author(s):

M.M. Zavarella ◽

O. Gbemi ◽

J.D. Walters

Keyword(s):

Steady State ◽

Connective Tissue ◽

Inflammatory Mediator ◽

Dependent Manner ◽

Gingival Fibroblasts ◽

Temperature Dependent ◽

Tnf Α ◽

Steady State Levels ◽

Inflammatory Drugs ◽

Anti Inflammatory

Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders. We hypothesized that gingival fibroblasts actively accumulate NSAIDs and enhance their levels in gingival connective tissue. Using fluorescence to monitor NSAID transport, we demonstrated that cultured gingival fibroblasts transport naproxen in a saturable, temperature-dependent manner with a Km of 127 μg/mL and a Vmax of 1.42 ng/min/μg protein. At steady state, the intracellular/extracellular concentration ratio was 1.9 for naproxen and 7.2 for ibuprofen. Naproxen transport was most efficient at neutral pH and was significantly enhanced upon cell treatment with TNF-α. In humans, systemically administered naproxen attained steady-state levels of 61.9 μg/mL in blood and 9.4 μg/g in healthy gingival connective tissue, while ibuprofen attained levels of 2.3 μg/mL and 1.5 μg/g, respectively. Thus, gingival fibroblasts possess transporters for NSAIDs that are up-regulated by an inflammatory mediator, but there is no evidence that they contribute to elevated NSAID levels in healthy gingiva.

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Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

Cellular Physiology and Biochemistry ◽

10.1159/000484192 ◽

2017 ◽

Vol 43 (5) ◽

pp. 2074-2087 ◽

Cited By ~ 19

Author(s):

Liling Yang ◽

Xiangjun Zhou ◽

Weijuan Huang ◽

Qin Fang ◽

Jianlan Hu ◽

...

Keyword(s):

Signalling Pathway ◽

Dependent Manner ◽

Zebrafish Model ◽

Lps Challenge ◽

Cell Counts ◽

Tnf Α ◽

Forsythia Suspensa ◽

Anti Inflammatory

Background/Aims: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF-α expression. Conclusion: This study provides a rationale for the clinical application of PHN as an anti-inflammatory agent.

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Anti-inflammatory Effect of the Peptide LKEKK

Journal of Clinical & Experimental Immunology ◽

10.33140/jcei.06.05.02 ◽

2021 ◽

Vol 6 (5) ◽

Keyword(s):

High Specificity ◽

Dependent Manner ◽

Thymosin Α1 ◽

Tnf Α ◽

Normal Human ◽

Anti Inflammatory ◽

Interferon Α2 ◽

Dose Dependent

We have established that the peptide LKEKK (Np5) corresponding to the sequence 16-20 of thymosin-α1 and to the sequence 131-135 of interferon-α2, in the concentration range 50 300 µg/ear reduces in a dose-dependent manner phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin edema in mice .Tested in parallel peptide with inverted sequence (iNp5, KKEKL, 150-300 µg/ear) was inactive, indicating high specificity of the Np5 action. In the concentration range of 5 20 µM Np5 significantly decrease the TNF-α-induced production by normal human keranocytes of pro-inflammatory mediators IL-6 and IL-1β. Thus, Np5t has a pronounced anti-inflammatory activity in vivo and in vitro.

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Anti-Inflammatory Activity of Four Triterpenoids Isolated from Poriae Cutis

Foods ◽

10.3390/foods10123155 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3155

Author(s):

Lijia Zhang ◽

Mengzhou Yin ◽

Xi Feng ◽

Salam A. Ibrahim ◽

Ying Liu ◽

...

Keyword(s):

High Speed ◽

High Performance ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Dependent Manner ◽

Tnf Α ◽

Anti Inflammatory ◽

Dose Dependent

In this study, triterpenoid compounds from Poriae Cutis were separated by high-speed countercurrent chromatography (HSCCC) and identified using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) and nuclear magnetic resonance (NMR). The in vitro anti-inflammatory activities of the purified triterpenoids on RAW 264.7 cells were also investigated. Triterpenoids, poricoic acid B, poricoic acid A, dehydrotrametenolic acid, and dehydroeburicoic acid were obtained; their levels of purity were 90%, 92%, 93%, and 96%, respectively. The results indicated that poricoic acid B had higher anti-inflammatory activity than those of poricoic acid A by inhibiting the generation of NO in lipopolysaccharide (LPS)-induced RAW 264.7 cells. However, dehydrotrametenolic acid and dehydroeburicoic acid had no anti-inflammatory activity. In addition, the production of cytokines (TNF-α, IL-1β, and IL-6) in cells treated with poricoic acid B decreased in a dose-dependent manner in the concentration range from 10 to 40 μg/mL. The results provide evidence for the use of Poriae Cutis as a natural anti-inflammatory agent in medicines and functional foods.

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Protective Effects of Lentinan Against Lipopolysaccharide-Induced Mastitis in Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2021.755768 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huifang Yin ◽

Guanhong Xue ◽

Ailing Dai ◽

Haichong Wu

Keyword(s):

Mammary Epithelial ◽

Economic Losses ◽

Dependent Manner ◽

Protective Effects ◽

Dairy Farmers ◽

Worldwide Production ◽

Tnf Α ◽

Anti Inflammatory

Mastitis is a worldwide production disease in dairy cows, which mainly affects milk yield, causing huge economic losses to dairy farmers. Lentinan is a kind of polysaccharide extracted from Lentinus edodes, which has no toxicity and possesses various pharmacological activities including antibacterial and immunomodulatory effects. Therefore, the anti-inflammatory function of lentinan on LPS-stimulated mastitis was carried out, and the mechanism involved was explored. In vivo, lentinan greatly reduced LPS-stimulated pathological injury, myeloperoxidase (MPO) activity, and the proinflammatory factor production (TNF-α and IL-1β) in mice. Further study was performed to determine the activation of the Wnt/β-catenin pathway during LPS stimulation. These results suggested that LPS-induced activation of the Wnt/β-catenin pathway was suppressed by lentinan administration. In vitro, we observed that the mouse mammary epithelial cell (mMEC) viability was not affected by lentinan treatment. As expected, LPS increased the TNF-α and IL-1β protein secretion and the activation of the Wnt/β-catenin pathway that was inhibited by lentinan administration in a dose-dependent manner in mMECs. Conclusively, lentinan exerts the anti-inflammatory function in LPS-stimulated mastitis via inhibiting the activation of the Wnt/β-catenin pathway. Thus, the results of our study also gave an insight that lentinan may serve as a potential treatment for mastitis.

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Synthesis and In Vitro Anti-inflammatory Activity of C20 Epimeric Ocotillol-Type Triterpenes and Protopanaxadiol

Planta Medica ◽

10.1055/a-0770-0994 ◽

2018 ◽

Vol 85 (04) ◽

pp. 292-301 ◽

Cited By ~ 14

Author(s):

Jianqiang Zhang ◽

Qian Zhang ◽

Yangrong Xu ◽

Huixiang Li ◽

Fenglan Zhao ◽

...

Keyword(s):

Nitric Oxide ◽

Prostaglandin E2 ◽

Interleukin 6 ◽

Inflammatory Mediator ◽

Interleukin 10 ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

Tnf Α ◽

Anti Inflammatory

AbstractGinseng is a perennial herb that contains various medicinal substances. The major active constituents of ginseng are ginsenosides, which have multifarious biological activities. Some pharmacological activities are closely dependent on the stereoisomers derived from the configuration at C20. In this study, the in vitro anti-inflammatory activity of C20 epimeric ocotillol-type triterpenes (2, 3, 9, and 10) and protopanaxadiol [20(S/R)-protopanaxadiol] were investigated. Epimers 2 and 3 were prepared starting from 20(S)-protopanaxadiol. Epimers 9 and 10 were synthesized from 20(R)-3-acetylprotopanaxadiol (7). The anti-inflammatory activity of 2, 3, 9, 10, 20(S)-protopanaxadiol, and 20(R)-protopanaxadiol was evaluated in cultured mouse macrophage RAW 264.7 cells. The MTT assay was used to measure the cytotoxicity. RAW 264.7 cells were stimulated by lipopolysaccharide to release the inflammatory mediators nitric oxide, prostaglandin E2, TNF-α, and interleukin-6 and anti-inflammatory mediator interleukin-10. The effect of the compounds on the overproduction of nitric oxide, prostaglandin E2, TNF-α, interleukin-6, and interleukin-10 was determined using Griess and ELISA methods. The results demonstrated that the in vitro anti-inflammatory activities of C20 epimeric ocotillol-type triterpenes and protopanaxadiol were different. Both the 20S-epimers (2 and 3) and 20R-epimers (9 and 10) inhibited the release of inflammatory mediator nitric oxide, while mainly the 20S-epimers inhibited the release of inflammatory mediator prostaglandin E2, and the 20R-epimers inhibited the release of inflammatory cytokine TNF-α. Both the 20S-epimers [2, 3, and 20(S)-protopanaxadiol] and 20R-epimers [9, 10, and 20(R)-protopanaxadiol] inhibited the release of inflammatory cytokine interleukin-6, but mainly the 20S-epimers [2, 3, and 20(S)-protopanaxadiol] increased the release of anti-inflammatory mediator interleukin-10.

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1-Phenyl-6,7-dihydroxy-isochroman suppresses lipopolysaccharide-induced pro-inflammatory mediator production in human monocytes

British Journal Of Nutrition ◽

10.1017/s0007114510005763 ◽

2011 ◽

Vol 106 (1) ◽

pp. 33-36 ◽

Cited By ~ 12

Author(s):

Giuliana Trefiletti ◽

Anna Rita Togna ◽

Valentina Latina ◽

Carolina Marra ◽

Marcella Guiso ◽

...

Keyword(s):

Olive Oil ◽

Virgin Olive Oil ◽

Extra Virgin Olive Oil ◽

Dependent Manner ◽

Human Monocytes ◽

Beneficial Effects ◽

Tnf Α ◽

Cox 2 ◽

Anti Inflammatory

Extra-virgin olive oil is an integral ingredient of the Mediterranean diet, and it has been suggested that its high consumption has beneficial effects on human health. Its protective effect, in particular against the development of CVD, has been related not only to the high content of oleic acid, but also to the antioxidant and anti-inflammatory properties of polyphenols. In order to verify the anti-inflammatory and anti-atherogenic properties of hydroxy-isochromans, a class of ortho-diphenols present in extra-virgin olive oil, we investigated the potential ability of 1-phenyl-6,7-dihydroxy-isochroman (L137) to modulate the production of key inflammatory mediators by human monocytes, by evaluating its in vitro effects on prostanoid (thromboxane A2 and PGE2) and cytokine (TNF-α) production. Its effect on the protein expression of the inducible form of cyclo-oxygenase-2 (COX-2), a pro-inflammatory enzyme responsible for elevated prostanoid levels, was also explored. The results showed that L137 significantly inhibited both prostanoid and TNF-α production in lipopolysaccharide-primed human monocytes in a dose-dependent manner, by inhibiting the COX activity of COX-2. We also demonstrated that the effects of the isochroman are mediated, at least partly, through the suppression of NF-κB activation leading to the down-regulation of the synthesis of COX-2.

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Cyr61 Promotes Inflammation of a Gouty Arthritis Model in Rats

Mediators of Inflammation ◽

10.1155/2020/8298615 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Mi Zhou ◽

Kan Ze ◽

Liang Hua ◽

Liu Liu ◽

Le Kuai ◽

...

Keyword(s):

Western Blot ◽

Signaling Pathway ◽

Acute Inflammation ◽

Gouty Arthritis ◽

Dependent Manner ◽

Monosodium Urate ◽

Synovial Tissues

Background. Cyr61 is considered a novel proinflammatory factor. Gouty arthritis (GA) is a self-limited inflammatory reaction caused by monosodium urate (MSU) crystals. In this study, we assessed the role of Cyr61 in the inflammatory process of GA. Methods. We investigated the expression of Cyr61 in MSU-induced rat gout models and MSU-stimulated rat fibroblast-like synovial (FLS) cells. After inhibiting the expression of Cyr61, levels of IL-1β, TNF-α, and IL-6 were detected by ELISA, qPCR, western blot, and immunohistochemical methods. We probed the downstream NF-κB signaling pathway using the NF-κB inhibitor PDTC, and levels of NF-κB and p-NF-κB were detected by western blot and qPCR. Results. Our results demonstrate that Cyr61 plays a potent role in the formation of local inflammation in vitro and in vivo. Cyr61 was highly expressed in synovial tissues of gout models, and the expression of Cyr61 protein was also significantly increased in MSU-stimulated FLS cells. Cyr61 promoted MSU-induced acute inflammation via the NF-κB signaling pathway. Conclusions. Our study has revealed that Cyr61 is an important regulatory factor for the initiation of inflammation in GA. The high expression of Cyr61 protein can induce synovial cells to produce many inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, partly in an NF-κB-dependent manner. Thus, inhibition of Cyr61 could be a new target and strategy for the prevention and treatment of GA.

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Anti-inflammatory Effect of the Peptide LKEKK

Journal of Clinical & Experimental Immunology ◽

10.33140/jcei.06.05.01 ◽

2021 ◽

Vol 6 (5) ◽

Keyword(s):

High Specificity ◽

Dependent Manner ◽

Thymosin Α1 ◽

Tnf Α ◽

Normal Human ◽

Anti Inflammatory ◽

Interferon Α2 ◽

Dose Dependent

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Anti-Inflammatory and Antinociceptive Activities of Untreated, Germinated, and Fermented Mung Bean Aqueous Extract

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/350507 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Norlaily Mohd Ali ◽

Hamidah Mohd Yusof ◽

Swee-Keong Yeap ◽

Wan-Yong Ho ◽

Boon-Kee Beh ◽

...

Keyword(s):

Aqueous Extract ◽

Mung Bean ◽

Inflammatory Mediator ◽

Dependent Manner ◽

Antinociceptive Effects ◽

Anti Inflammatory ◽

Dose Dependent ◽

Ear Oedema

Evaluation of anti-inflammatory and antinociceptive activities of untreated mung bean (MB), germinated mung bean (GMB), and fermented mung bean (FMB) was performed on bothin vitro(inhibition of inflammatory mediator, nitric oxide(NO)) andin vivo(inhibition of ear oedema and reduction of response to pain stimulus) studies. Results showed that both GMB and FMB aqueous extract exhibited potent anti-inflammatory and antinociceptive activities in a dose-dependent manner.In vitroresults showed that GMB and FMB were potent inflammatory mediator (NO) inhibitors at both 2.5 and 5 mg/mL. Furtherin vivostudies showed that GMB and FMB aqueous extract at 1000 mg/kg can significantly reduce ear oedema in mice caused by arachidonic acid. Besides, both 200 mg/kg and 1000 mg/kg concentrations of GMB and FMB were found to exhibit potent antinociceptive effects towards hotplate induced pain. With these, it can be concluded that GMB and FMB aqueous extract exhibited potential anti-inflammatory and antinociceptive effects.

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