scholarly journals Anti-Inflammatory and Chondroprotective Effects of Vanillic Acid and Epimedin C in Human Osteoarthritic Chondrocytes

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 932
Author(s):  
Reihane Ziadlou ◽  
Andrea Barbero ◽  
Ivan Martin ◽  
Xinluan Wang ◽  
Ling Qin ◽  
...  

In osteoarthritis (OA), inhibition of excessively expressed pro-inflammatory cytokines in the OA joint and increasing the anabolism for cartilage regeneration are necessary. In this ex-vivo study, we used an inflammatory model of human OA chondrocytes microtissues, consisting of treatment with cytokines (interleukin 1β (IL-1β)/tumor necrosis factor α (TNF-α)) with or without supplementation of six herbal compounds with previously identified chondroprotective effect. The compounds were assessed for their capacity to modulate the key catabolic and anabolic factors using several molecular analyses. We selectively investigated the mechanism of action of the two most potent compounds Vanillic acid (VA) and Epimedin C (Epi C). After identification of the anti-inflammatory and anabolic properties of VA and Epi C, the Ingenuity Pathway Analysis showed that in both treatment groups, osteoarthritic signaling pathways were inhibited. In the treatment group with VA, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling was inhibited by attenuation of the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα) phosphorylation. Epi C showed a significant anabolic effect by increasing the expression of collagenous and non-collagenous matrix proteins. In conclusion, VA, through inhibition of phosphorylation in NF-κB signaling pathway and Epi C, by increasing the expression of extracellular matrix components, showed significant anti-inflammatory and anabolic properties and might be potentially used in combination to treat or prevent joint OA.

2000 ◽  
Vol 279 (4) ◽  
pp. L675-L682 ◽  
Author(s):  
Pierre Farmer ◽  
Jérôme Pugin

In addition to their well-studied bronchodilatory and cardiotonic effects, β-adrenergic agonists carry anti-inflammatory properties by inhibiting cytokine production by human mononuclear cells. In a model of human promonocytic THP-1 cells stimulated with lipopolysaccharide (LPS), we showed that β-agonists inhibited tumor necrosis factor-α and interleukin-8 production predominantly via the β2-adrenergic receptor through the generation of cAMP and activation of protein kinase A. This effect was reproduced by other cAMP-elevating agents such as prostaglandins and cAMP analogs. Activation and nuclear translocation of the transcription factor nuclear factor-κB induced by LPS were inhibited with treatment with β-agonists, an effect that was prominent at late time points (>1 h). Although the initial IκB-α degradation induced by LPS was minimally affected by β-agonists, the latter induced a marked rebound of the cytosolic IκB-α levels at later time points (>1 h), accompanied by an increased IκB-α cytoplasmic half-life. This potentially accounts for the observed nuclear factor-κB sequestration in the cytoplasmic compartment. We postulate that the anti-inflammatory effects of β-agonists reside in their capacity to increase cytoplasmic concentrations of IκB-α, possibly by decreasing its degradation.


Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7642
Author(s):  
Wonmin Ko ◽  
Zhiming Liu ◽  
Kwan-Woo Kim ◽  
Linsha Dong ◽  
Hwan Lee ◽  
...  

We previously investigated the methanolic extract of Morus alba bark and characterized 11 compounds from the extract: kuwanon G (1), kuwanon E (2), kuwanon T (3), sanggenon A (4), sanggenon M (5), sanggenol A (6), mulberofuran B (7), mulberofuran G (8), moracin M (9), moracin O (10), and norartocarpanone (11). Herein, we investigated the anti-inflammatory effects of these compounds on microglial cells (BV2) and macrophages (RAW264.7). Among them, 3 and 4 markedly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide in these cells, suggesting the anti-inflammatory properties of these two compounds. These compounds inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, and the expression of inducible nitric oxide synthase and cyclooxygenase-2 following LPS stimulation. Pretreatment with 3 and 4 inhibited the activation of the nuclear factor kappa B signaling pathway in both cell types. The compounds also induced the expression of heme oxygenase (HO)-1 through the activation of nuclear factor erythroid 2-related factor 2. Suppressing the activity of HO-1 reversed the anti-inflammatory effects caused by pretreatment with 3 and 4, suggesting that the anti-inflammatory effects were regulated by HO-1. Taken together, 3 and 4 are potential candidates for developing therapeutic and preventive agents for inflammatory diseases.


Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 741 ◽  
Author(s):  
Jiwon Jang ◽  
Jong Sub Lee ◽  
Young-Jin Jang ◽  
Eui Su Choung ◽  
Wan Yi Li ◽  
...  

Inflammation is a fundamental process for defending against foreign antigens that involves various transcriptional regulatory processes as well as molecular signaling pathways. Despite its protective roles in the human body, the activation of inflammation may also convey various diseases including autoimmune disease and cancer. Sorbaria kirilowii is a plant originating from Asia, with no anti-inflammatory activity reported. In this paper, we discovered an anti-inflammatory effect of S. kirilowii ethanol extract (Sk-EE) both in vivo and in vitro. In vitro effects of Sk-EE were determined with lipopolysaccharide (LPS)-stimulated RAW264.7 cells, while ex vivo analysis was performed using peritoneal macrophages of thioglycollate (TG)-induced mice. Sk-EE significantly reduced the nitric oxide (NO) production of induced macrophages and inhibited the expression of inflammation-related cytokines and the activation of transcription factors. Moreover, treatment with Sk-EE also decreased the activation of proteins involved in nuclear factor (NF)-κB signaling cascade; among them, Src was a prime target of Sk-EE. For in vivo assessment of the anti-inflammatory effect of Sk-EE, HCl/EtOH was given by the oral route to mice for gastritis induction. Sk-EE injection dose-dependently reduced the inflammatory lesion area of the stomach in gastritis-induced mice. Taking these results together, Sk-EE exerts its anti-inflammatory activity by regulating intracellular NF-κB signaling pathways and also shows an authentic effect on reducing gastric inflammation.


Author(s):  
Rüdiger Horstkorte ◽  
Bettina Büttner ◽  
Kaya Bork ◽  
Navdeep Sahota ◽  
Sarah Sabir ◽  
...  
Keyword(s):  
B Cells ◽  

EBioMedicine ◽  
2020 ◽  
Vol 53 ◽  
pp. 102684 ◽  
Author(s):  
Angelika Schmidt ◽  
Johanna E. Huber ◽  
Özen Sercan Alp ◽  
Robert Gürkov ◽  
Christoph A. Reichel ◽  
...  

2012 ◽  
Vol 90 (2) ◽  
pp. 229-236 ◽  
Author(s):  
Li Wang ◽  
Yunxin Zhang ◽  
Zhiping Wang ◽  
Sijia Li ◽  
Guangning Min ◽  
...  

A previous study reported that ginsenoside-Rd reduced the production of tumor necrosis factor-α by inhibiting nuclear factor-κB in lipopolysaccharide-activated N9 microglia in vitro. The aim of the present study was to confirm the anti-inflammatory effects and mechanisms of ginsenoside-Rd in animal experiments involving acute inflammation. The results indicated that ginsenoside-Rd at doses ranging from 12.5 to 50 mg/kg i.m. significantly inhibited the swelling of hind paws in rats for 1–6 h after the carrageenan injection. The levels of proinflammatory cytokines and proinflammatory mediators were markedly reduced by ginsenoside-Rd. Ginsenoside-Rd, when administered intramuscularly at 12.5, 25, and 50 mg/kg doses, showed signicant inhibition of carrageenan-induced production of interleukin-1β (6.91%, 45.75%, and 55.18%, respectively), tumor necrosis factor-α (37.99%, 56.39%, and 47.38%, respectively), prostaglandin E2 (22.92%, 30.12%, and 36.36%, respectively), and nitric oxide (28.27%, 44.53%, and 53.42%, respectively). In addition, ginsenoside-Rd (12.5, 25, and 50 mg/kg i.m.) effectively decreased the levels of nuclear factor-κB (6.77%, 20.28%, and 41.03%, respectively) and phosphorylation of IκBα (13.23%, 26.92%, and 41.80%, respectively) in the carrageenan-inflamed paw tissues. These results suggest that ginsenoside-Rd has significant anti-inflammatory effects in vivo, which might be due to its blocking of the nuclear factor-κB signaling pathway. Thus, it may be possible to develop ginsenoside-Rd as a useful agent for inflammatory diseases.


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