cardamonin and Inflammation

Nature's pharmacy has undoubtedly served humans as an affordable and safer health-care regime for a long times. Cardamonin, a chalconoid present in several plants has been known for a longtime to have beneficial properties towards human health. In this review, we aimed to highlight the recent advances achieved in discovering the pharmacological properties of cardamonin. Cardamonin is cardamom-derived chalcone, which plays a role in cancer treatment, immune system modulation, inflammation and pathogens killing. Through the modulation of cellular signaling pathways, cardamonin activates cell death signal to induce apoptosis in malignant cells that results in the inhibition of cancer development. Moreover, cardamonin arrests cell cycle by altering the expression of regulatory proteins during malignant cells division. Due to its relatively selective cytotoxic potential against host malignant cells, cardamonin is emerging as a promising novel experimental anticancer agent. The potential of cardamonin to target various signaling molecules, transcriptional factors, cytokines and enzymes, such as mTOR, NF-κB, Akt, STAT3, Wnt/β-catenin and COX-2 enhances the opportunity to explore it as a new multi-target therapeutic agent. The pharmacokinetic and biosafety profile of cardamonin favor it as a potentially safe biomolecule for pharmaceutical drug development.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Line, Tumor; Chalcones; Humans; Immune System; Inflammation; Liver; Neoplasms; Neovascularization, Pathologic; Signal Transduction; STAT3 Transcription Factor

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with a complex pathophysiology primarily affecting exocrine glands, leading to compromised secretory function. Recent studies imply that many inflammatory mediators, such as pro-inflammatory cytokines and nitric oxide, are critical in the development and perpetuation of pSS systemic manifestations. In the current study, we aimed to investigate the ex vivo immunomodulatory effect of cardamonin (C

Topics: Adult; Chalcones; Female; Humans; Inflammation; Interleukin-6; Leukocytes, Mononuclear; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase Type II; Sjogren's Syndrome; Tumor Necrosis Factor-alpha

Osteoarthritis (OA) is a common degenerative joint disease, mainly presented by the deterioration of articular cartilage. Amounts of data demonstrated this deterioration is composed of oxidative stress, pro-inflammation and chondrocyte death events. Ferroptosis is a novel form of cell death that differs from apoptosis and autophagy, recent studies have shown that chondrocyte ferroptosis contributes to the development of osteoarthritis. Cardamonin (CAD) has been demonstrated to possess antioxidant and anti-inflammatory properties in several diseases, whether CAD may influence the OA progression is still obscure. Therefore, we aimed to determine whether CAD alleviates chondrocyte ferroptosis and its effect on OA with potential mechanism. In this study, we found that inflammation, cartilage degradation and ferroptosis induced by interleukin-1β (IL-1β) were significantly alleviated by CAD. Moreover, the administration of the ferroptosis inhibitor, Deferoxamine (DFO) reversed the inflammatory and cartilage degradation effects of IL-1β as well. Chondrocyte mitochondrial morphology and function were alleviated by both CAD and DFO. We found that CAD increased collagen II, p53, SLC7A11 GPX4 expression and decreased MMP13, iNOS, COX2 expression in chondrocytes, further investigation showed that the P53 signaling pathway was involved. In vivo, intra-articular injection of CAD significantly ameliorated cartilage damage in a rat OA model, induced collagen II and SLC7A11 expression by immunohistochemistry. Our study proves that CAD ameliorated OA cartilage degradation by regulating ferroptosis via P53 signaling pathway, suggesting a potential role of CAD in OA treatment.

Topics: Animals; Cartilage, Articular; Chondrocytes; Ferroptosis; Inflammation; Interleukin-1beta; Osteoarthritis; Rats; Tumor Suppressor Protein p53

Topics: Anti-Inflammatory Agents; Antioxidants; Cell Line; Humans; Inflammation; Kelch-Like ECH-Associated Protein 1; Lipopolysaccharides; Microglia; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide

Topics: Animals; Apoptosis; Cardiomyopathies; Cardiotonic Agents; Chalcones; Female; Heart; Inflammation; Lipopolysaccharides; Male; Mice; Myocardial Contraction; Myocardium; Myocytes, Cardiac; NF-E2-Related Factor 2; NF-kappa B p50 Subunit; Oxidative Stress; Signal Transduction

Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain, but effective therapies are still lacking because of its complicated pathology. It has been demonstrated that increased levels of interleukin-1β (IL-1β) may promote the development of IVDD. Cardamonin (CAR) is a chalcone extracted from Alpinia katsumadai and other plants. It exhibits an anti-inflammatory effect in multiple diseases. In the present study, we investigated the protective effects of CAR on rat nucleus pulposus (NP) cells under IL-1β stimulation in vitro and in a puncture-induced rat IVDD model in vivo. We explored the CAR treatment's inhibition of the expression of inflammatory factors such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), nitric oxide (NO), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in rat NP cells. Moreover, the up-regulation of matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) and the degradation of aggrecan and collagen II induced by IL-1β were reversed by CAR. Mechanistically, we demonstrated that CAR inhibited nuclear factor kappa B (NF-κB) signaling by activating the nuclear factor erythroid-derived 2-like 2 (Nrf2) in IL-1β-induced rat NP cells. Furthermore, the protective effect of CAR was shown in the IVDD model through persistent intragastric administration. Taken together, our results revealed that CAR could activate the Nrf2/HO-1 signaling axis and be a novel agent for IVDD therapy.

Topics: Animals; Cell Survival; Cells, Cultured; Chalcones; Inflammation; Interleukin-1beta; Male; NF-E2-Related Factor 2; NF-kappa B; Nucleus Pulposus; Rats; Rats, Sprague-Dawley; Signal Transduction

The clinical application of doxorubicin (DOX) for cancer treatment is limited due to its cardiotoxicity. However, the basic pathophysiological molecular mechanisms underlying DOX-induced cardiomyopathy have not yet been completely clarified, and the disease-specific therapeutic strategies are lacking. The aim of the present study was to investigate the potential cardioprotective effect of cardamonin (CAR), a flavone found in Alpinia plant, on DOX-induced cardiotoxicity in a mouse model. At first, in DOX-treated mouse cardiomyocytes, CAR showed significantly cytoprotective effects through elevating nuclear factor erythroid-2 related factor 2 (Nrf2) signaling, and reducing the degradation of Nrf2. This process then improved the anti-oxidant system, as evidenced by the up-regulated expression levels of haem oxygenase-1 (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT). In contrast, DOX-induced increases in malondialdehyde (MDA) and reactive oxygen species (ROS) were highly inhibited by CAR treatments. Additionally, DOX-induced apoptosis and inflammatory response in cardiomyocytes were diminished by CAR through reducing the Caspase-3 and nuclear factor-κB (NF-κB) signaling pathways, respectively. Then, in the DOX-induced animal model with cardiotoxicity, we confirmed that through improving Nrf2 signaling, CAR markedly suppressed oxidative stress, apoptosis and inflammatory response in hearts of mice, improving cardiac function eventually. Together, our findings demonstrated that CAR activated Nrf2-related cytoprotective system, and protected the heart from oxidative damage, apoptosis and inflammatory injury, suggesting that CAR might be a potential therapeutic strategy in the prevention of DOX-associated myocardiopathy.

Topics: Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Cardiotoxicity; Cell Line; Chalcones; Cytokines; Cytoprotection; Doxorubicin; Inflammation; Male; Mice; Mice, Inbred C57BL; Models, Animal; Myocytes, Cardiac; NF-E2-Related Factor 2; Oxidative Stress; Rats; Signal Transduction

Cardamonin (CAD) is a member of the aromatic ketones family that is closely related to anti-bacterial, anti-inflammatory and anti-cancer effects. Nevertheless, the physiological function of cardamonin in chronic colitis and colon cancer has not been well verified. We found that cardamonin treatment alleviates intestinal disease, including recurring colitis and colitis-associated tumorigenesis, along with the reduced secretion of IL-1β and TNF-α. Further, cardamonin inhibits cell viability and inflammation factors of colorectal cancer cells in vitro. In tumor cells, the inhibitory effect of cardamonin on cell proliferation is closely related to decreased phosphorylation of signal transducers and activators of transcription (STAT) signals. This study reveals the crucial role of cardamonin in sustaining gastrointestinal homeostasis and offers a new strategy for colon cancer therapy.

Topics: Animals; Carcinogenesis; Cell Survival; Chalcones; Colitis; Colon; Colonic Neoplasms; Dextran Sulfate; Disease Models, Animal; HT29 Cells; Humans; Inflammation; Interleukin-1beta; Neoplasm Recurrence, Local; NF-kappa B; Signal Transduction; STAT Transcription Factors; Tumor Necrosis Factor-alpha

Ulcerative colitis (UC) is an inflammatory bowel disease with significant morbidity. Cardamonin is a natural chalcone derivative with considerable anti-inflammatory activity. Herein, the potential protective effect of cardamonin against UC was tested in a rat model.. Rats were given 10 or 30mg/kg/day of cardamonin orally for 14days before induction of UC. On the 14th day of treatment, UC was induced by intrarectal instillation of 2ml 3% acetic acid. Twenty four h after acetic acid instillation, rats were sacrificed and colons were analyzed by macroscopic and histopathological examination. Colon lipid peroxidation was examined by biochemical evaluation of malondialdehyde (MDA). Myeloperoxidase (MPO), iNOS, NF-κB, TNFα levels were measured by ELISA. Moreover, caspase-3 and COX-2 were assessed by immunohistochemical analysis.. Cardamonin at 10 and 30mg/kg decreased the disease activity index and macroscopic damage index scores, and significantly reduced histopathological deterioration. Additionally, cardamonin reduced levels of MPO, iNOS, NF-κB, TNFα and MDA (p<0.05). Immunohistochemistry revealed down-regulation of COX-2 and caspase-3 in groups treated with cardamonin.. Cardamonin has a protective effect against acetic acid-induced colitis. This effect may be due to reducing inflammation, oxidative stress and apoptosis.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Caspase 3; Chalcones; Colitis, Ulcerative; Colon; Cyclooxygenase 2; Inflammation; Lipid Peroxidation; Male; Malondialdehyde; NF-kappa B; Nitric Oxide Synthase Type II; Peroxidase; Protective Agents; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1β, TNF-α, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is partially involved in the pathogenesis of cispaltin-induced nephrotoxicity.

Topics: Animals; Antineoplastic Agents; Apoptosis; Chalcones; Cisplatin; HCT116 Cells; HeLa Cells; Hep G2 Cells; Humans; Inflammation; Kidney; Male; NADH, NADPH Oxidoreductases; NADPH Oxidase 1; Protective Agents; Random Allocation; Rats

In the present study, we investigated the effects of Alpinia katsumadai H(AYATA) (Zingiberaceae) seed ethanolic extract (AKEE) and its three components on the production of inflammatory mediators and some potential underlying mechanisms in lipopolysaccharide (LPS)-induced inflammation RAW264.7 cells. The whole formula, AKEE, and three major component compounds were then evaluated for their effects on inflammation-related parameters using LPS-induced RAW264.7 cells. Production of namely nitric oxide (NO) and cytokine levels were measured by the Griess reagent and ELISA, respectively. To investigate the underlying mechanisms of anti-inflammatory activities of AKEE, protein expression of nitric oxide synthase (inducible nitric oxide synthase, iNOS), heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) were evaluated by western blot analysis. AKEE and the major group of compounds in AKEE (alpinetin, cardamonin, and pinocembrin) complement exert anti-inflammatory effects for NO and PGE(2) production. In addition, AKEE treatment significantly inhibited the LPS-induced production of interleukin-6 and tumor necrosis factor (TNF)-α, as well as the expression of iNOS. AKEE also induced HO-1 expression in RAW264.7 cells and inhibited the nuclear translocation of NF-κB by preventing degradation of the inhibitor kappa B-alpha. We also demonstrated that the effects of AKEE on TNF-α production were partially reversed by the HO-1 inhibitor tin protoporphyrin. These results indicate that AKEE and its major component may have anti-inflammatory activity via induction of HO-1 expression was partly responsible for the anti-inflammatory effects.

Topics: Alpinia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Chalcones; Enzyme Induction; Flavanones; Heme Oxygenase-1; I-kappa B Proteins; Inflammation; Inflammation Mediators; Interleukin-6; Lipopolysaccharides; Macrophages; Metalloporphyrins; Mice; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide; Nitric Oxide Synthase Type II; Plant Extracts; Prostaglandins; Protoporphyrins; Seeds; Tumor Necrosis Factor-alpha

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

In this study we examined the effect of the natural product cardamonin, upon lipopolysaccharide (LPS)-induced inflammatory gene expression in order to attempt to pinpoint the mechanism of action.. Cardamonin was isolated from the Greek plant A. absinthium L. Its effects were assessed on LPS-induced nitrite release and iNOS and COX-2 protein expression in two macrophage cell lines. Western blotting was used to investigate its effects on phosphorylation of the mitogen activated protein (MAP) kinases, ERK, JNK and p38 MAP kinase, and activation of the NFkappaB pathway, at the level of IkappaBalpha degradation and phosphorylation of NFkappaB. Also its effects on NFkappaB and GAS/GAF-DNA binding were assessed by EMSA.. Cardamonin concentration-dependently inhibited both NO release and iNOS expression but had no effect on COX-2 expression. It did not affect phosphorylation of the MAP kinases, degradation of IkappaBalpha or phosphorylation of NFkappaB. However, it inhibited NFkappaB DNA-binding in both LPS-stimulated cells and nuclear extracts of the cells (in vitro). It also inhibited IFNgamma-stimulated iNOS induction and GAS/GAF-DNA binding.. These results show that the inhibitory effect of cardamonin on LPS-induced iNOS induction is not mediated via effects on the initial activation of the NFkappaB or MAP kinase pathways but is due to a direct effect on transcription factor binding to DNA. However, although some selectivity in cardamonin's action is implicated by its inability to affect COX-2 expression, its exact mechanism(s) of action has yet to be identified.

Topics: Animals; Cell Line; Chalcones; Humans; Inflammation; Lipopolysaccharides; Macrophages; Mice; Mitogen-Activated Protein Kinases; NF-kappa B; Signal Transduction; Tumor Necrosis Factor-alpha