MAPKs and NF‑κB pathway inhibitory effect of bisdemethoxycurcumin on phorbol‑12‑myristate‑13‑acetate and A23187‑induced inflammation in human mast cells

  • Authors:
    • Ryong Kong
    • Ok‑Hwa Kang
    • Yun‑Soo Seo
    • Tian Zhou
    • Sang‑A Kim
    • Dong‑Won Shin
    • Dong‑Yeul Kwon
  • View Affiliations

  • Published online on: October 20, 2017
  • Pages: 630-635
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Inflammation‑associated damage may occur in any tissue following infection, exposure to toxins, following ischemia, and in allergic and auto‑immune reactions. Inflammation may also result from mast cell degranulation induced by the intracellular calcium concentration. The inflammatory process may be inhibited by compounds that affect mast cells. Bisdemethoxycurcumin [1,7‑bis(4‑hydroxyphenyl) hepta‑1,6‑diene‑3,5‑dione, BDCM] is the active component of turmeric. It has anticancer, antioxidant and antibacterial properties. To investigate the molecular mechanism associated with the anti‑inflammatory activity of BDCM, human mast cell line 1 (HMC‑1) cells were treated with phorbol‑12‑myristate‑13‑acetate (PMA) and calcium ionophore A23187 (A23187) to induce the inflammatory process. Various HMC‑1 cells were pretreated with BDCM prior to stimulation of inflammation. BDCM inhibited the inflammation‑triggered production of cytokines including interleukin (IL)‑6, IL‑8, and tumor necrosis factor (TNF)‑α. BDCM inhibition extended to the gene level. In activated HMC‑1 cells, phosphorylation levels of extracellular signal‑regulated kinase, c‑jun N‑terminal kinase and p38 mitogen‑activated protein kinase were decreased by treatment with BDCM. BDCM also inhibited nuclear factor‑(NF)‑κB activation and IκB degradation. In conclusion, BDCM suppresses the expression of TNF‑α, IL‑8, and IL‑6 by inhibiting the NF‑κB and mitogen activated protein kinase signaling pathways.


Inflammation-related damage can occur in any tissue following infection, exposure to toxins, after ischemia, and in allergic and auto-immune reactions. Inflammatory processes are systematized by inflammatory cells, such as mast cells (1). Mast cells are widely present in the connective tissues of mammals and other vertebrates and are physically in close proximity to blood vessels (2). The cells are significant effector cells in inflammation as well as allergic reactions, because they secrete various cytokines (3). Regulation of cytokine secretion from mast cells could be a useful therapeutic strategy for allergic inflammatory diseases. The signaling pathway inducing mast cell degranulation has been characterized (4). Mast cell activation induces phosphorylation of tyrosine kinase and migration of calcium ion (Ca2+) in the body (5). Tyrosine phosphorylation is an important event in intracellular signal transduction induced activation of protein kinase C and secretion through Ca2+ influx (6). Calcium acts as a second messenger in mast cell activation, with activation in response to increased intracellular Ca2+ (7). The release of intracellular Ca2+ is essential for the activation of mitogen-activated protein kinase (MAPK) (8,9). MAPK participates in the mast cell regulation of cytokine production in response to particular extracellular stimuli, which subsequently begins the biological responses that drive cell differentiation, proliferation, and apoptosis. These include extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) (10). Phsophorylation-mediated ERK activation regulates cytoplasmic and nuclear targets, and various cell responses including proliferation, migration, differentiation and death (11). JNK is involved in a signaling pathway concerned with the inflammatory response. Activated JNKs affect the formation of the activator protein 1 (AP-1) transcription factor complex that participates in the expression of many inflammatory factors and controls the synthesis of many inflammatory cytokines (12). P38 is involved in the production of pro-inflammatory cytokines by regulating the expression of nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κB) (13). In addition, ERKs, JNKs, and p38 are involved in control of interleukin (IL)-6 mRNA or protein production in response to FcεRI aggregation (14). Activated NF-κB regulates the expression of cytokines, chemokines, and cell adhesion molecules (CAM). The activity of NF-κB occurs when IκB is phosphorylated and disassociated by IκB kinase (IKK) catalysis (15).

Curcuma longa L. is a perennial herb in family Zingiberaceae. It is a traditional medicine used to treat disorders, anorexia, diabetic wounds, hepatic disorders, rheumatism, and sinusitis in China and India (16). The three main ingredients of Curcuma longa L. are curcumin (diferuloylmethane), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), with curcumin being most abundant (17). Curcumin has physiological activities including antioxidant, anti-inflammation, and anticancer activities (1820). However, curcumin is unstable and easily degrades in vivo, so more stable curcuminoids are needed to replace it (21). BDCM is more comparatively stable in vivo, is more readily taken up into the cell nucleus (22,23), and possesses anticancer, antioxidant and antibacterial activities (2426). BDCM has anti-inflammatory activity in lipopolysaccharide-induced RAW 264.7 macrophages, with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and NF-κB. BDCM also suppresses carrageenan-induced paw edema in mice (27,28).

The anti-inflammatory effect of BDCM in human mast cells is unknown. The present study investigated the influence of BDCM on cytokine, MAPK, and NF-κB activity in HMC-1 induced with phorbol-12-myristate-13-acetate (PMA) and A23187.

Materials and methods

Reagents and antibodies

Bisdemethoxycurcumin (Fig. 1) was purchased from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan). PMA and A23187 (calcymycin; C29H37N3O6) were purchased from Sigma-Aldrich (Merck KGaA, Darmstadt, Germany). Iscove's modified Dulbecco's medium (IMDM) was obtained from Welgene (Daegu, Korea). Anti-human tumor necrosis factor-α (TNF-α; 555212), anti-IL-6 (555220), anti-IL-8 (555244), biotinylated anti-human TNF-α (51-26372E), anti-IL-6 (51-26452E), IL-8 (51-26542E), and anti-recombinant human TNF-α (51-26376E), anti-IL-6 (51-26456E), and anti-IL-8 (51-26546E) antibodies were obtained from BD Pharmingen (San Diego, CA, USA). The reverse transcription kit was purchased from Qiagen (Valencia, CA, USA). Nuclear and cytoplasmic extraction reagents were purchased from Thermo Fisher Scientific, Inc., (Waltham, MA, USA). Anti-phosphorylated (p-)ERK1/2 (sc-7383), anti-p-JNK1/2 (sc-6254), anti-p-p38 (sc-7973), anti-ERK1/2 (sc-93), anti-JNK1/2 (sc-571) anti-p38 (sc-535), anti-β-actin (sc-47,778), anti-NF-κB (sc-8008), anti-mouse, and anti-rabbit antibodies were obtained from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA).

Cell culture and cell viability

The human mast cell line 1 (HMC-1) was cultured in IMDM supplemented with 10% fetal bovine serum (FBS), 100 IU/ml penicillin, 50 µg/ml streptomycin, and 1.2 mM α-thioglycerol at 37°C in an incubator with an atmosphere of 5% CO2. Cell viability was evaluated by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] (Promega, Madison, WI, USA) assay following incubation in the presence of 25 or 50 µM BDCM for 24 h at the aforementioned temperature and CO2 conditions using an Epoch microplate spectrophotometer (BioTek, Winooski, VT, USA) at an optical density of 490 nm.

Analysis of cytokine production

The OptEIA human enzyme-linked immunosorbent assay (ELISA; BD Bioscience, San Jose, CA, USA) was used to assay culture supernatants to measure TNF-α, IL-6, and IL-8 secretion. HMC-1 cells were seeded at 5×105 cells per well in 24-well plates and treated with 25 or 50 µM BDCM for 30 min. The cells were then stimulated for 8 h with 50 nM PMA and 1 µM A23187 (Sigma-Aldrich). Cytokines in the supernatant were measured using ELISA. Each well of the 96-well microplate was coated with capture antibody diluted in coating buffer (0.1 M carbonate, pH 9.5). Each plate was sealed and incubated overnight at 4°C. After washing three times with phosphate-buffered saline (PBS) containing 0.05% Tween-20, non-specific binding sites were blocked with PBS containing 10% FBS (pH 7.0) for 1 h. A total of 100 µl of each sample, or TNF-α, IL-6, and IL-8 standards were added to wells and incubated for 2 h at room temperature. A total of 100 µl of detection antibody conjugated with and avidin-horseradish peroxidase (HRP) diluted in assay buffer was applied for 1 h. A total of 100 µl of substrate solution (tetramethylbenzidine, TMB) was added to each wells and incubated for 30 min at room temperature in the dark. A total of 50 µl of stop solution (2 M H2SO4) was added and the absorbance was determined at 450 nm.

RNA extraction and reverse transcription-quantitative polymerase chain reaction (RT-qPCR)

Total RNA was isolated from HMC-1 cells using easy BLUE™ Total RNA Extraction kit (iNtRon, Seongnam, Korea). The total RNA was dissolved in DEPC-treated distilled water. A spectrophotometer (Biotek) was used to evaluate RNA purity by measuring the ratio of the absorbance at 260 and 280 nm. Complementary deoxyribonucleic acid (cDNA) was synthesized using the QuantiTect Reverse Transcription kit (Qiagen, Seoul, Korea) according to the manufacturer's instructions. RT-qPCR was performed in triplicate using power SYBR-Green PCR master mix (Applied Biosystems, Foster City, CA, USA) in a StepOne PLus Real-Time-PCR system (Applied Biosystems). The amplification was 1 cycle of 95°C for 10 min, followed by 40 cycles of 95°C for 15 sec and 60°C for 1 min, followed by 1 cycle 95°C for 15 sec and 60°C for 1 min. The expression levels of the target genes relative to the endogenous reference gene, β-actin, were calculated using the ΔΔCq method using StepOne software v2.3 (Applied Biosystems). The primer sequences are listed in Table I.

Table I.

Sequences of oligonucleotide primers designed for reverse transcription-quantitative polymerase chain reaction.

Table I.

Sequences of oligonucleotide primers designed for reverse transcription-quantitative polymerase chain reaction.

GenePrimer sequence (5′-3′)

[i] TNF, tumor necrosis factor; IL, interleukin.

Western blot analysis

BDCM-pretreated and 1-h PMA and A23187 stimulated cells were collected and lysed with ice-cold lysis buffer (iNtRon). Following centrifugation at 13,000 rpm for 20 min, the supernatant was transferred to a 1.5 ml microtube. A total of 20–30 µl of denatured protein lysate was separated by 12% sodium dodecyl sulfate-polyacrylamide electrophoresis and the resolved proteins were transferred to polyvinylidene fluoride membranes. The membranes were incubated with anti-human-phsopho-ERK antibody, anti-human-phsopho-JNK antibody, or anti-human-phsopho-p38 antibody (Santa Cruz Biotechnology, Inc.) overnight at 4°C. HRP-conjugated antibody against mouse IgG (Santa Cruz Biotechnology, Inc.) diluted 1:2,500 in 3% BSA was used as the secondary antibody. The proteins were detected using EzWestLumi plus luminal substrate (ATTO Co., Tokyo, Japan). After stripping, the membranes were reprobed with anti-human ERK antibody, anti-human JNK antibody, or anti-human p38 antibody (Santa Cruz Biotechnology, Inc.) as respective loading controls.

Cytoplasmic and nuclear protein extraction

Cytoplasmic and nuclear proteins were extracted from BDCM-pretreated and 2-h PMA and A23187 stimulated HMC-1 cells. Nuclear extraction was performed according to the manufacturer's instructions using NE-PER® Nuclear and Cytoplasmic Extraction Reagents (Thermo Fisher Scientific, Inc.). Cell volume of 20 µl corresponded to a volume ratio of CER I:CER II:NER (200:11:100 µl). A tube containing CER I was first vortexed vigorously at the highest speed setting for 1 sec to fully suspend the cell pellet. The tube was then incubated on ice for 10 min. Ice-cold CER II was then added to the tube followed by vortexing for 5 sec at the highest speed setting. The tube was then incubated on ice for 1 min before being vortexed for 5 sec at the highest speed setting. The tube was then centrifuged at 13,000 rpm for 5 min in a microcentrifuge. The supernatant (cytoplasmic extract) was then immediately transferred to a clean and pre-chilled tube and stored until use. Ice-cold NER was added to the pellet and the tube was vortexed for 15 sec at the highest speed setting. The sample was placed on ice and vortexed for 15 sec every 10 min for a total of 40 min. The tube was then centrifuged at 13,000 rpm for 5 min in a microcentrifuge. The supernatant (nuclear extract) was then immediately transferred to a clean and pre-chilled tube. The extracted cytoplasmic and nuclear protein was detected by western blot analysis.

Statistical analysis

Data are presented as the mean ± standard error of the mean. Student's t-test for multiple comparisons was performed using SPSS Ver. 23 software (SPSS, Inc., Chicago, IL, USA). P<0.05 was considered to indicate a statistically significant difference.


Cell viability measurement

MTS assay was performed to measure cell viability of HMC-1 treated with BDCM. BDCM did not affect the viability of HMC-1 cells at concentrations of 10, 25, and 50 µM. The cytotoxicity of BDCM was observed at concentrations of 100 µM (Fig. 2).

Effect of BDCM on production of pro-inflammatory cytokines

ELISA was used to evaluate the effect of BDCM on the production of IL-6, IL-8, and TNF-α. The production of all three cytokines in HMC-1 cells considerably increased after stimulation with PMA and A23187 (Fig. 1). However, the productions of these cytokines were decreased by pretreatment with either concentration of BDCM (Fig. 3).

Effect of BDCM on pro-inflammatory cytokine gene expression

RT-qPCR was used to determine the expression levels of the genes encoding IL-6, IL-8, and TNF-α. Expression of the three genes in HMC-1 cells were significantly increased after stimulation with PMA and A23187, but were suppressed by pretreatment with either concentration of BDCM (Fig. 4).

Effect of BDCM on activation of MAPKs

Western blots were used to investigate the effect of BDMC on activation of MAPKs (ERK, JNK, and p38). Phosphorylation of the three MAPKs was increased by stimulation of PMA and A23187 in HMC-1 cells. Both concentrations of BDCM reduced JNK phosphorylation induced by PMA and A23187. Phosphorylation of ERK and p38 was reduced by BDCM at 50 µM (Fig. 5).

Effects of BDCM on NF-κB activation, IκBα phosphorylation, and degradation

The expression of NF-κB signaling molecules and NF-κB transcriptional activity was investigated at the protein level. NF-κB and p-IκBα expressions in HMC-1 cells were increased by stimulation with PMA and A23187. Expressions of NF-κB and p-IκBα were decreased in BDCM-pretreated cells and IκBα degradation was inhibited (Fig. 6).


Mast cells are influential effector cells in the immune system. The importance of mast cells in allergic diseases, anaphylaxis, and autoimmunity is established. Mast cell-related diseases result from increased mast cell number and/or activity.

Activity of genes encoding several cytokines and their protein production were increased in HMC-1 cells stimulated with by PMA and A23187, as was phosphorylation of MAPKs and activity NF-κB. These observations were consistent with the degranulation of HMC-1 cells in response to increased intracellular Ca2+. The inflammatory reaction caused by the mast cell degranulation was alleviated if HMC-1 cells were first pretreated with BDCM. Phosphorylation of JNK, ERK, and p38 was also inhibited by BDCM as was NF-κB and p-IκBα production.

p38 regulates cell proliferation, apoptosis, environmental stress, and neuropathic pain. It is activated by various stress conditions and inflammatory cytokines, such as ultraviolet irradiation, osmotic and oxidative stress, heat shock, IL-1β, TNF-α, and transforming growth factor-β. The activated p38 transfers from the cytosol into the nucleus or to the other regions of the cell, activates downstream kinases, and regulates inflammatory processes, such as those involving iNOS, TNF-α, IL-1β, and COX-2 (29).

Many recent studies have described the interaction of Curcuma longa L. and NF-κB. Because this transcription factor is closely related to inflammatory and immune responses, Curcuma longa L. mediates its effects, at least in part, through the inhibition of NF-κB activation. NF-κB activation is regulated by MAPK via several mechanisms, but accumulated evidence shows that inhibitory proteins called I-κB regulate NF-κB activation by MAPKs that induce specific phosphorylation. In addition, previous studies have demonstrated a role for NF-κB activation and inflammatory cytokine production regulation in inflammatory responses (30). The expression of TNF-α, IL-6, and IL-8 genes is dependent on the activation of transcription factor NF-κB in mast cells.

This means that BDCM, one of the major components of Curcuma longa L., can inhibit the expression of inflammatory mediators by inhibiting NF-κB activation and I-κB depression in HMC-1. Therefore, BDCM suppressed the nuclear translocation of NF-κB, phosphorylation of I-κB, and degradation of I-κB. These results indicate that the molecular mechanism by which BDCM suppresses the expression of pro-inflammatory cytokines and inflammatory mediators is through NF-κB inactivation. Specifically, I-κB degradation and translocation are blocked. Inhibition of NF-κB and MAPK affects the expression of cytokines and cytokine-associated genes.

In summary, BDCM regulates the expression of IL-6, IL-8, and TNF-α in PMA and A23187-induced HMC-1 cells, and inhibits the ERK, JNK, p38 MAPK, and NF-κB pathways. These results implicate BDCM as a valuable compound to suppress the NF-κB signaling pathway in mast cell-mediated inflammatory diseases.


This study was supported by Wonkwang University 2017.



Jeong HJ, Na HJ, Kim SJ, Rim HK, Myung NY, Moon PD, Han NR, Seo JU, Kang TH, Kim JJ, et al: Anti-inflammatory effect of Columbianetin on activated human mast cells. Biol Pharm Bull. 32:1027–1031. 2009. View Article : Google Scholar : PubMed/NCBI


Galli SJ, Zsebo KM and Geissler EN: The kit ligand, stem cell factor. Adv Immunol. 55:1–96. 1994. View Article : Google Scholar : PubMed/NCBI


Metcalfe DD, Baram D and Mekori YA: Mast cells. Physiol Rev. 77:1033–1079. 1997.PubMed/NCBI


Yoo JM, Yang JH, Kim YS, Yang HJ, Cho WK and Ma JY: Inhibitory effects of viscum coloratum extract on IgE/antigen-activated mast cells and mast cell-derived inflammatory mediator-activated chondrocytes. Molecules. 22:pii: E37. 2016. View Article : Google Scholar : PubMed/NCBI


Spalinger MR, McCole DF, Rogler G and Scharl M: Protein tyrosine phosphatase non-receptor type 2 and inflammatory bowel disease. World J Gastroenterol. 22:1034–1044. 2016. View Article : Google Scholar : PubMed/NCBI


Hamawy MM, Mergenhagen SE and Siraganian RP: Protein tyrosine phosphorylation as a mechanism of signalling in mast cells and basophils. Cell Signal. 7:535–544. 1995. View Article : Google Scholar : PubMed/NCBI


Petrou T, Olsen HL, Thrasivoulou C, Masters JR, Ashmore JF and Ahmed A: Intracellular calcium mobilization in response to ion channel regulators via a calcium induced calcium release mechanism. J Pharmacol Exp Ther. 360:378–387. 2017. View Article : Google Scholar : PubMed/NCBI


Crossthwaite AJ, Hasan S and Williams RJ: Hydrogen peroxide-mediated phosphorylation of ERK1/2, Akt/PKB and JNK in cortical neurones: Dependence on Ca (2+) and PI3-kinase. J Neurochem. 80:24–35. 2002. View Article : Google Scholar : PubMed/NCBI


Wong CK, Tsang CM, Ip WK and Lam CW: Molecular mechanisms for the release of chemokines from human leukemic mast cell line (HMC)-1 cells activated by SCF and TNF-alpha: Roles of ERK, p38 MAPK, and NF-kappaB. Allergy. 61:289–297. 2006. View Article : Google Scholar : PubMed/NCBI


Li L, Zhang XH, Liu GR, Liu C and Dong YM: Isoquercitrin suppresses the expression of histamine and pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-κB in human KU812 cells. Chin J Nat Med. 14:407–412. 2016.PubMed/NCBI


Cagnol S and Chambard JC: ERK and cell death: Mechanisms of ERK-induced cell death-apoptosis, autophagy and senescence. FEBS J. 277:2–21. 2010. View Article : Google Scholar : PubMed/NCBI


Zhao J, Wang L, Dong X, Hu X, Zhou L, Liu Q, Song B, Wu Q and Li L: The c-Jun N-terminal kinase (JNK) pathway is activated in human interstitial cystitis (IC) and rat protamine sulfate induced cystitis. Sci Rep. 6:196702016. View Article : Google Scholar : PubMed/NCBI


Zhou Y, Yang Q, Xu H, Zhang J, Deng H, Gao H, Yang J, Zhao D and Liu F: miRNA-221-3p Enhances the Secretion of Interleukin-4 in Mast Cells through the Phosphatase and Tensin Homolog/p38/Nuclear Factor-kappaB Pathway. PLoS One. 11:e01488212016. View Article : Google Scholar : PubMed/NCBI


Kandere-Grzybowska K, Kempuraj D, Cao J, Cetrulo CL and Theoharides TC: Regulation of IL-1-induced selective IL-6 release from human mast cells and inhibition by quercetin. Br J Pharmacol. 148:208–215. 2016. View Article : Google Scholar


Schuliga M: NF-kappaB signaling in chronic inflammatory airway disease. Biomolecules. 5:1266–1283. 2015. View Article : Google Scholar : PubMed/NCBI


Ooko E, Kadioglu O, Greten HJ and Efferth T: Pharmacogenomic characterization and isobologram analysis of the combination of ascorbic acid and curcumin-two main metabolites of Curcuma longa-in cancer cells. Front Pharmacol. 8:382017. View Article : Google Scholar : PubMed/NCBI


Chearwae W, Anuchapreeda S, Nandigama K, Ambudkar SV and Limtrakul P: Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II and III purified from Turmeric powder. Biochem Pharmacol. 68:2043–2052. 2004. View Article : Google Scholar : PubMed/NCBI


Jagetia GC and Rajanikant GK: Curcumin stimulates the antioxidant mechanisms in mouse skin exposed to fractionated γ-irradiation. Antioxidants (Basel). 4:25–41. 2015. View Article : Google Scholar : PubMed/NCBI


Chin KY: The spice for joint inflammation: Anti-inflammatory role of curcumin in treating osteoarthritis. Drug Des Devel Ther. 10:3029–3042. 2016. View Article : Google Scholar : PubMed/NCBI


Deka SJ, Mamdi N, Manna D and Trivedi V: Alkyl cinnamates induce protein kinase C translocation and anticancer activity against breast cancer cells through induction of the mitochondrial pathway of apoptosis. J Breast Cancer. 19:358–371. 2016. View Article : Google Scholar : PubMed/NCBI


Xu J, Yang H, Zhou X, Wang H, Gong L and Tang C: Bisdemethoxycurcumin suppresses migration and invasion of highly metastatic 95D lung cancer cells by regulating E-cadherin and vimentin expression, and inducing autophagy. Mol Med Rep. 12:7603–7608. 2015. View Article : Google Scholar : PubMed/NCBI


Gordon ON, Luis PB, Ashley RE, Osheroff N and Schneider C: Oxidative transformation of demethoxy- and bisdemethoxycurcumin: Products, mechanism of formation, and poisoning of human topoisomerase IIα. Chem Res Toxicol. 28:989–996. 2015. View Article : Google Scholar : PubMed/NCBI


Ramezani M, Hatamipour M and Sahebkar A: Promising Anti-tumor properties of bisdemethoxycurcumin: A naturally occurring curcumin analogue. J Cell Physiol. Jan 11–2017.(Epub ahead of print). PubMed/NCBI


Xu JH, Yang HP, Zhou XD, Wang HJ, Gong L and Tang CL: Role of wnt inhibitory factor-1 in inhibition of bisdemethoxycurcumin mediated epithelial-to-mesenchymal transition in highly metastatic lung cancer 95D cells. Chin Med J (Engl). 128:1376–1383. 2015. View Article : Google Scholar : PubMed/NCBI


Li YB, Gao JL, Zhong ZF, Hoi PM, Lee SM and Wang YT: Bisdemethoxycurcumin suppresses MCF-7 cells proliferation by inducing ROS accumulation and modulating senescence-related pathways. Pharmacol Rep. 65:700–709. 2013. View Article : Google Scholar : PubMed/NCBI


Haukvik T, Bruzell E, Kristensen S and Tønnesen HH: A screening of curcumin derivatives for antibacterial phototoxic effects studies on curcumin and curcuminoids. XLIII. Pharmazie. 66:69–74. 2011.PubMed/NCBI


Guo LY, Cai XF, Lee JJ, Kang SS, Shin EM, Zhou HY, Jung JW and Kim YS: Comparison of suppressive effects of demethoxycurcumin and bisdemethoxycurcumin on expressions of inflammatory mediators in vitro and in vivo. Arch Pharm Res. 31:490–496. 2008. View Article : Google Scholar : PubMed/NCBI


Kim AN, Jeon WK, Lee JJ and Kim BC: Up-regulation of heme oxygenase-1 expression through CaMKII-ERK1/2-Nrf2 signaling mediates the anti-inflammatory effect of bisdemethoxycurcumin in LPS-stimulated macrophages. Free Radic Biol Med. 49:323–331. 2010. View Article : Google Scholar : PubMed/NCBI


Sun J and Nan G: The mitogen-activated protein kinase (MAPK) signaling pathway as a discovery target in stroke. J Mol Neurosci. 59:90–98. 2016. View Article : Google Scholar : PubMed/NCBI


Blackwell TS, Blackwell TR and Christman JW: Impaired activation of nuclear factor-kappaB in endotoxin-tolerant rats is associated with down-regulation of chemokine gene expression and inhibition of neutrophilic lung inflammation. J Immunol. 158:5934–5940. 1997.PubMed/NCBI

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Kong R, Kang OH, Seo YS, Zhou T, Kim SA, Shin DW and Kwon DY: MAPKs and NF‑κB pathway inhibitory effect of bisdemethoxycurcumin on phorbol‑12‑myristate‑13‑acetate and A23187‑induced inflammation in human mast cells. Mol Med Rep 17: 630-635, 2018
Kong, R., Kang, O., Seo, Y., Zhou, T., Kim, S., Shin, D., & Kwon, D. (2018). MAPKs and NF‑κB pathway inhibitory effect of bisdemethoxycurcumin on phorbol‑12‑myristate‑13‑acetate and A23187‑induced inflammation in human mast cells. Molecular Medicine Reports, 17, 630-635.
Kong, R., Kang, O., Seo, Y., Zhou, T., Kim, S., Shin, D., Kwon, D."MAPKs and NF‑κB pathway inhibitory effect of bisdemethoxycurcumin on phorbol‑12‑myristate‑13‑acetate and A23187‑induced inflammation in human mast cells". Molecular Medicine Reports 17.1 (2018): 630-635.
Kong, R., Kang, O., Seo, Y., Zhou, T., Kim, S., Shin, D., Kwon, D."MAPKs and NF‑κB pathway inhibitory effect of bisdemethoxycurcumin on phorbol‑12‑myristate‑13‑acetate and A23187‑induced inflammation in human mast cells". Molecular Medicine Reports 17, no. 1 (2018): 630-635.