Skip to main content

Advertisement

SpringerLink
Log in

Impact of curcumin on p38 MAPK: therapeutic implications

  • Review
  • Published:
Inflammopharmacology Aims and scope Submit manuscript

Abstract

Curcumin (diferuloylmethane) is a herbal remedy which possesses numerous biological attributes including anti-inflammatory, anti-oxidant and anti-cancer properties. Curcumin has been shown to impact a number of signaling pathways including nuclear factor kappa B (NF-KB), reactive oxygen species (ROS), Wingless/Integrated (Wnt), Janus kinase-signal transducer and activator of mitogen-activated protein kinase (MAPK) and transcription (JAK/STAT). P38 belongs to the MAPKs, is known as a stress-activated MAPK and is involved in diverse biological responses. P38 is activated in various signaling cascades. P38 plays a role in inflammation, cell differentiation, proliferation, motility and survival. This cascade can serve as a therapeutic target in many disorders. Extensive evidence confirms that curcumin impacts the P38 MAPK signaling pathway, through which it exerts anti-inflammatory, neuroprotective, and apoptotic effects. Hence, curcumin can positively affect inflammatory disorders and cancers, as well as to increase glucose uptake in cells. This review discusses the pharmacological and therapeutic effects of curcumin as effected through p38 MAPK.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Availability of data and materials

No novel data were produced in the writing of this review article.

References

  • Abdulmalek S, Eldala A, Awad D, Balbaa M (2021) Ameliorative effect of curcumin and zinc oxide nanoparticles on multiple mechanisms in obese rats with induced type 2 diabetes. Sci Rep 11:1–22

    Article  Google Scholar 

  • Akaishi T, Abe K (2018) CNB-001, a synthetic pyrazole derivative of curcumin, suppresses lipopolysaccharide-induced nitric oxide production through the inhibition of NF-κB and p38 MAPK pathways in microglia. Eur J Pharmacol 819:190–197

    Article  CAS  PubMed  Google Scholar 

  • Akaishi T, Yamamoto S, Abe K (2020) The synthetic curcumin derivative CNB-001 attenuates thrombin-stimulated microglial inflammation by inhibiting the ERK and p38 MAPK pathways. Biol Pharm Bull 43:138–144

    Article  CAS  PubMed  Google Scholar 

  • Asher GN, Spelman K (2013) Clinical utility of curcumin extract. Altern Ther Health Med 19:20–22

    PubMed  Google Scholar 

  • Ashrafizadeh M, Rafiei H, Mohammadinejad R, Afshar EG, Farkhondeh T, Samarghandian S (2020) Potential therapeutic effects of curcumin mediated by JAK/STAT signaling pathway: a review. Phytother Res 34:1745–1760

    Article  CAS  PubMed  Google Scholar 

  • Banerjee B, Chakraborty S, Ghosh D, Raha S, Sen PC, Jana K (2016) Benzo(a)pyrene induced p53 mediated male germ cell apoptosis: synergistic protective effects of curcumin and resveratrol. Front Pharmacol 7:245

    Article  PubMed  PubMed Central  Google Scholar 

  • Belcaro G, Cesarone MR, Dugall M, Pellegrini L, Ledda A, Grossi MG, Togni S, Appendino G (2010) Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients. Altern Med Rev 15:337–344

    PubMed  Google Scholar 

  • Binion DG, Otterson MF, Rafiee P (2008) Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition. Gut 57:1509–1517

    Article  CAS  PubMed  Google Scholar 

  • Binion DG, Heidemann J, Li MS, Nelson VM, Otterson MF, Rafiee P (2009) Vascular cell adhesion molecule-1 expression in human intestinal microvascular endothelial cells is regulated by PI 3-kinase/Akt/MAPK/NF-kappaB: inhibitory role of curcumin. Am J Physiol Gastrointest Liver Physiol 297:G259–G268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai B, Chang SH, Becker EB, Bonni A, Xia Z (2006) p38 MAP kinase mediates apoptosis through phosphorylation of BimEL at Ser-65. J Biol Chem 281:25215–25222

    Article  CAS  PubMed  Google Scholar 

  • Camacho-Barquero L, Villegas I, Sánchez-Calvo JM, Talero E, Sánchez-Fidalgo S, Motilva V, de la Lastra CA (2007) Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. Int Immunopharmacol 7:333–342

    Article  CAS  PubMed  Google Scholar 

  • Chainani-Wu N (2003) Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med 9:161–168

    Article  PubMed  Google Scholar 

  • Chen J, Wang G, Wang L, Kang J, Wang J (2010) Curcumin p38-dependently enhances the anticancer activity of valproic acid in human leukemia cells. Eur J Pharm Sci 41:210–218

    Article  CAS  PubMed  Google Scholar 

  • Cho J-W, Park K, Kweon GR, Jang B-C, Baek W-K, Suh M-H, Kim C-W, Lee K-S, Suh S-I (2005) Curcumin inhibits the expression of COX-2 in UVB-irradiated human keratinocytes (HaCaT) by inhibiting activation of AP-1: p38 MAP kinase and JNK as potential upstream targets. Exp Mol Med 37:186–192

    Article  CAS  PubMed  Google Scholar 

  • Cho KB, Park CH, Kim J, Tin TD, Kwak SH (2020) Protective role of curcumin against lipopolysaccharide-induced inflammation and apoptosis in human neutrophil. Anesth Pain Med (seoul) 15:41–48

    Article  PubMed  Google Scholar 

  • Coulthard LR, White DE, Jones DL, McDermott MF, Burchill SA (2009) p38(MAPK): stress responses from molecular mechanisms to therapeutics. Trends Mol Med 15:369–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuadrado A, Nebreda AR (2010) Mechanisms and functions of p38 MAPK signalling. Biochem 429:403–417

    Article  CAS  Google Scholar 

  • Dutta AK, Ikiki E (2013) Novel drug delivery systems to improve bioavailability of curcumin. J Bioequiv Availab 6:001–009

    Google Scholar 

  • Elad S, Meidan I, Sellam G, Simaan S, Zeevi I, Waldman E, Weintraub M, Revel-Vilk S (2013) Topical curcumin for the prevention of oral. Health Med 19:21–24

    Google Scholar 

  • Epstein J, Docena G, Macdonald TT, Sanderson IR (2010) Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1beta and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease. Br J Nutr 103:824–832

    Article  CAS  PubMed  Google Scholar 

  • Fan C, Song Q, Wang P, Li Y, Yang M, Yu SY (2018) Neuroprotective effects of curcumin on IL-1β-induced neuronal apoptosis and depression-like behaviors caused by chronic stress in rats. Front Cell Neurosci 12:516

    Article  CAS  PubMed  Google Scholar 

  • Fanger GR (1999) Regulation of the MAPK family members: role of subcellular localization and architectural organization. Histol Histopathol 14:887–894

    CAS  PubMed  Google Scholar 

  • Gadekar R, Saurabh MK, Thakur GS, Saurabh A (2012) Study of formulation, characterisation and wound healing potential of transdermal patches of curcumin. Asian J Pharm Clin Res 5:225–230

    CAS  Google Scholar 

  • Ghasemi F, Shafiee M, Banikazemi Z, Pourhanifeh MH, Khanbabaei H, Shamshirian A, Moghadam SA, Arefnezhad R, Sahebkar A, Avan A (2019) Curcumin inhibits NF-kB and Wnt/β-catenin pathways in cervical cancer cells. Pathol Res Pract 215:152556

    Article  CAS  PubMed  Google Scholar 

  • Gopi S, Jacob J, Varma K, Jude S, Amalraj A, Arundhathy C, George R, Sreeraj T, Divya C, Kunnumakkara AB (2017) Comparative oral absorption of curcumin in a natural turmeric matrix with two other curcumin formulations: an open-label parallel-arm study. Phytother Res 31:1883–1891

    Article  CAS  PubMed  Google Scholar 

  • Gorabi AM, Razi B, Aslani S, Abbasifard M, Imani D, Sathyapalan T, Sahebkar A (2021) Effect of curcumin on proinflammatory cytokines: a meta-analysis of randomized controlled trials. Cytokine 143:155541

    Article  CAS  PubMed  Google Scholar 

  • Guimarães MR, Leite FRM, Spolidorio LC, Kirkwood KL, Rossa C Jr (2013) Curcumin abrogates LPS-induced pro-inflammatory cytokines in RAW 264.7 macrophages. Evidence for novel mechanisms involving SOCS-1,-3 and p38 MAPK. Arch Oral Biol 58:1309–1317

    Article  PubMed  PubMed Central  Google Scholar 

  • Gupta J, Nebreda AR (2015) Roles of p38α mitogen-activated protein kinase in mouse models of inflammatory diseases and cancer. FEBS J 282:1841–1857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hann SS, Chen J, Wang Z, Wu J, Zheng F, Zhao S (2013) Targeting EP4 by curcumin through cross talks of AMP-dependent kinase alpha and p38 mitogen-activated protein kinase signaling: the role of PGC-1α and Sp1. Cell Signal 25:2566–2574

    Article  CAS  PubMed  Google Scholar 

  • Harper SJ, Lograsso P (2001) Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38. Cell Signal 13:299–310

    Article  CAS  PubMed  Google Scholar 

  • Hassanzadeh K, Buccarello L, Dragotto J, Mohammadi A, Corbo M, Feligioni M (2020a) Obstacles against the marketing of curcumin as a drug. Int J Mol Sci 21:6619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hassanzadeh S, Read MI, Bland AR, Majeed M, Jamialahmadi T, Sahebkar A (2020b) Curcumin: an inflammasome silencer. Pharmacol Res 159:104921

    Article  CAS  Google Scholar 

  • Hatami M, Abdolahi M, Soveyd N, Djalali M, Togha M, Honarvar NM (2019) Molecular mechanisms of curcumin in neuroinflammatory disorders: a mini review of current evidences. Endocr Metab Immune Disord Drug 19:247–258

    Article  CAS  Google Scholar 

  • He Y, Yue Y, Zheng X, Zhang K, Chen S, Du Z (2015) Curcumin, inflammation, and chronic diseases: how are they linked? Molecules 20:9183–9213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heidari Z, Daei M, Boozari M, Jamialahmadi T, Sahebkar A (2022) Curcumin supplementation in pediatric patients: a systematic review of current clinical evidence. Phytother Res 36:1442–1458

    Article  CAS  PubMed  Google Scholar 

  • Heshmati J, Moini A, Sepidarkish M, Morvaridzadeh M, Salehi M, Palmowski A, Mojtahedi MF, Shidfar F (2021) Effects of curcumin supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial. Phytomedicine 80:153395

    Article  CAS  PubMed  Google Scholar 

  • Hilchie AL, Furlong SJ, Sutton K, Richardson A, Robichaud MR, Giacomantonio CA, Ridgway ND, Hoskin DW (2010) Curcumin-induced apoptosis in PC3 prostate carcinoma cells is caspase-independent and involves cellular ceramide accumulation and damage to mitochondria. Nutr Cancer 62:379–389

    Article  CAS  PubMed  Google Scholar 

  • Hsu C-H, Cheng A-L (2007) Clinical studies with curcumin. Adv Exp Med Biol 471–480

  • Huang P, Han J, Hui L (2010) MAPK signaling in inflammation-associated cancer development. Protein Cell 1:218–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang L, Chen C, Zhang X, Li X, Chen Z, Yang C, Liang X, Zhu G, Xu Z (2018) Neuroprotective effect of curcumin against cerebral ischemia-reperfusion via mediating autophagy and inflammation. J Mol Neurosci 64:129–139

    Article  CAS  PubMed  Google Scholar 

  • Huang R, Zhu Y, Lin L, Song S, Cheng L, Zhu R (2020) Solid lipid nanoparticles enhanced the neuroprotective role of curcumin against epilepsy through activation of Bcl-2 family and P38 MAPK pathways. ACS Chem Neurosci 11:1985–1995

    Article  CAS  PubMed  Google Scholar 

  • Jäger R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM (2014) Comparative absorption of curcumin formulations. Nutr J 13:1–8

    Article  Google Scholar 

  • JAMWAL, R. (2018) Bioavailable curcumin formulations: a review of pharmacokinetic studies in healthy volunteers. J Integr Med 16:367–374

    Article  PubMed  Google Scholar 

  • Jiang J, Wang W, Sun YJ, Hu M, Li F, Zhu DY (2007) Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood–brain barrier damage. Eur J Pharmacol 561:54–62

    Article  CAS  PubMed  Google Scholar 

  • Kawano S-I, Inohana Y, Hashi Y, Lin J-M (2013) Analysis of keto-enol tautomers of curcumin by liquid chromatography/mass spectrometry. Chin Chem Lett 24:685–687

    Article  CAS  Google Scholar 

  • Kazazis C, Vallianou NG, Kollas A, Evangelopoulos A (2014) Curcumin and diabetes: mechanisms of action and its anti-diabetic properties. Curr Top Nutraceutical Res 12:135

    Google Scholar 

  • Keihanian F, Saeidinia A, Bagheri RK, Johnston TP, Sahebkar A (2018) Curcumin, hemostasis, thrombosis, and coagulation. J Cell Physiol 233:4497–4511

    Article  CAS  PubMed  Google Scholar 

  • Khayatan D, Razavi SM, Arab ZN, Niknejad AH, Nouri K, Momtaz S, Gumpricht E, Jamialahmadi T, Abdolghaffari AH, Barreto GE, Sahebkar A (2022) Protective effects of curcumin against traumatic brain injury. Biomed Pharmacother 154:113621

    Article  CAS  PubMed  Google Scholar 

  • Kim SJ, Son TG, Park HR, Park M, Kim MS, Kim HS, Chung HY, Mattson MP, Lee J (2008) Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus. J Biol Chem 283:14497–14505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JH, Park JM, Kim EK, Lee JO, Lee SK, Jung JH, You GY, Park SH, Suh PG, Kim HS (2010) Curcumin stimulates glucose uptake through AMPK-p38 MAPK pathways in L6 myotube cells. J Cell Physiol 223:771–778

    CAS  PubMed  Google Scholar 

  • Kotha RR, Luthria DL (2019) Curcumin: biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules 24:2930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuttan G, Hari Kumar KB, Guruvayoorappan C, Kuttan R (2007) Antitumor, anti-invasion, and antimetastatic effects of curcumin. In: Aggarwal BB, Surh YJ, Shishodia S (eds) The molecular targets and therapeutic uses of curcumin in health and disease. Advances in experimental medicine and biology, vol 595. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-46401-5_6

  • Kurita T, Makino Y (2013) Novel curcumin oral delivery systems. Anticancer Res 33:2807–2821

    CAS  PubMed  Google Scholar 

  • Larasati YA, Yoneda-Kato N, Nakamae I, Yokoyama T, Meiyanto E, Kato J-Y (2018) Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Sci Rep 8:1–13

    Article  CAS  Google Scholar 

  • Li G, Duan L, Yang F, Yang L, Deng Y, Yu Y, Xu Y, Zhang Y (2022) Curcumin suppress inflammatory response in traumatic brain injury via p38/MAPK signaling pathway. Phytother Res 36:1326–1337

    Article  CAS  PubMed  Google Scholar 

  • Man S, Zhang L, Cui J, Yang L, Ma L, Gao W (2018) Curcumin enhances the anti-cancer effects of Paris Saponin II in lung cancer cells. Cell Prolif 51:e12458

    Article  PubMed  PubMed Central  Google Scholar 

  • Marjaneh RM, Rahmani F, Hassanian SM, Rezaei N, Hashemzehi M, Bahrami A, Ariakia F, Fiuji H, Sahebkar A, Avan A, Khazaei M (2018) Phytosomal curcumin inhibits tumor growth in colitis-associated colorectal cancer. J Cell Physiol 233(10):6785–6798. https://doi.org/10.1002/jcp.26538

  • Martinez-Limon A, Joaquin M, Caballero M, Posas F, de Nadal E (2020) The p38 pathway: from biology to cancer therapy. Int J Mol Sci 21:1913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meesarapee B, Thampithak A, Jaisin Y, Sanvarinda P, Suksamrarn A, Tuchinda P, Morales NP, Sanvarinda Y (2014) Curcumin I mediates neuroprotective effect through attenuation of quinoprotein formation, p-p38 MAPK expression, and caspase-3 activation in 6-hydroxydopamine treated SH-SY5Y cells. Phytother Res 28:611–616

    Article  CAS  PubMed  Google Scholar 

  • Menon VP, Sudheer AR (2007) Antioxidant and anti-inflammatory properties of curcumin. Adv Exp Med Biol 105–125

  • Mohajeri M, Sahebkar A (2018) Protective effects of curcumin against doxorubicin-induced toxicity and resistance: a review. Crit Rev Oncol 122:30–51

    Article  Google Scholar 

  • Mohammed ES, El-Beih NM, El-Hussieny EA, El-Ahwany E, Hassan M, Zoheiry M (2020) Effects of free and nanoparticulate curcumin on chemically induced liver carcinoma in an animal model. Arch Med Sci 17(1):218–227. https://doi.org/10.5114/aoms.2020.93739

  • Mokhtari-Zaer A, Marefati N, Atkin SL, Butler AE, Sahebkar A (2018) The protective role of curcumin in myocardial ischemia–reperfusion injury. J Cell Physiol 234:214–222

    Article  PubMed  Google Scholar 

  • Momtazi AA, Sahebkar A (2016) Difluorinated curcumin: a promising curcumin analogue with improved anti-tumor activity and pharmacokinetic profile. Curr Pharm Des 22(28):4386–4397. https://doi.org/10.2174/1381612822666160527113501

  • Momtazi-Borojeni AA, Haftcheshmeh SM, Esmaeili SA, Johnston TP, Abdollahi E, Sahebkar A (2018) Curcumin: a natural modulator of immune cells in systemic lupus erythematosus. Autoimmun Rev 17:125–135

    Article  CAS  PubMed  Google Scholar 

  • Mukhopadhyay CD, Ruidas B, Chaudhury SS (2017) Role of curcumin in treatment of Alzheimer disease. Int J Neurorehabilitation 4(2376–0281):1000274

    Google Scholar 

  • Ortega AMM, Campos MRS (2019) Medicinal plants and their bioactive metabolites in cancer prevention and treatment. Bioact Compd. Elsevier

    Google Scholar 

  • Pan W, Yang H, Cao C, Song X, Wallin B, Kivlin R, Lu S, Hu G, Di W, Wan Y (2008) AMPK mediates curcumin-induced cell death in CaOV3 ovarian cancer cells. Oncol Rep 20:1553–1559

    CAS  PubMed  Google Scholar 

  • Panahi Y, Hosseini MS, Khalili N, Naimi E, Simental-Mendía LE, Majeed M, Sahebkar A (2016) Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: a post-hoc analysis of a randomized controlled trial. Biomed Pharmacother 82:578–582

    Article  CAS  PubMed  Google Scholar 

  • Pancholi V, Smina TP, Kunnumakkara AB, Maliakel B, Krishnakumar IM (2021) Safety assessment of a highly bioavailable curcumin-galactomannoside complex (CurQfen) in healthy volunteers, with a special reference to the recent hepatotoxic reports of curcumin supplements: a 90-days prospective study. Toxicol Rep 8:1255–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parsamanesh N, Moossavi M, Bahrami A, Butler AE, Sahebkar A (2018) Therapeutic potential of curcumin in diabetic complications. Pharmacol Res 136:181–193

    Article  CAS  PubMed  Google Scholar 

  • Rahimi HR, Nedaeinia R, Shamloo AS, Nikdoust S, Oskuee RK (2016) Novel delivery system for natural products: nano-curcumin formulations. Avicenna J Phytomed 6:383

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rahimnia AR, Panahi Y, Alishiri G, Sharafi M, Sahebkar A (2014) Impact of supplementation with curcuminoids on systemic inflammation in patients with knee osteoarthritis: findings from a randomized double-blind placebo-controlled trial. Drug Res 65:521–525

    Article  Google Scholar 

  • Ranjan AP, Mukerjee A, Helson L, Vishwanatha JK (2012) Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy. J Nanobiotechnology 10:1–18

    Article  Google Scholar 

  • Reeta V, Kalia S (2022) Turmeric: a review of its’ effects on human health. J Med Plants Stud 10:61–63

    Google Scholar 

  • Roux PP, Blenis J (2004) ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev 68:320–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sahebkar A (2010) Molecular mechanisms for curcumin benefits against ischemic injury. Fertil Steril 94:e75–e76

    Article  PubMed  Google Scholar 

  • Saiz de Cos P, Pérez-Urria Carril E (2015) Cúrcuma I (Curcuma longa L). Ene 8:42

    Google Scholar 

  • Salh B, Assi K, Templeman V, Parhar K, Owen D, Gómez-Muñoz A, Jacobson K (2003) Curcumin attenuates DNB-induced murine colitis. Am J Physiol Gastrointest Liver Physiol 285:G235–G243

    Article  CAS  PubMed  Google Scholar 

  • Salimi A (2018) Liposomes as a novel drug delivery system: fundamental and pharmaceutical application. Asian J Pharm 12

  • Sanphui P, Goud NR, Khandavilli UR, Bhanoth S, Nangia A (2011) New polymorphs of curcumin. Chem Commun 47:5013–5015

    Article  CAS  Google Scholar 

  • Sarawi WS, Alhusaini AM, Fadda LM, Alomar HA, Albaker AB, Aljrboa AS, Alotaibi AM, Hasan IH, Mahmoud AM (2021) Nano-curcumin prevents cardiac injury, oxidative stress and inflammation, and modulates TLR4/NF-κB and MAPK signaling in copper sulfate-intoxicated rats. Antioxidants (basel) 10:1414

    Article  CAS  PubMed  Google Scholar 

  • Sasaki H, Sunagawa Y, Takahashi K, Imaizumi A, Fukuda H, Hashimoto T, Wada H, Katanasaka Y, Kakeya H, Fujita M (2011) Innovative preparation of curcumin for improved oral bioavailability. Biol Pharm Bull 34:660–665

    Article  CAS  PubMed  Google Scholar 

  • Shao-Ling W, Ying L, Ying W, Yan-Feng C, Li-Xin N, Song-Tao L, Chang-Hao S (2009) Curcumin, a potential inhibitor of up-regulation of TNF-alpha and IL-6 induced by palmitate in 3T3-L1 adipocytes through NF-kappaB and JNK pathway. Biomed Environ Sci 22:32–39

    Article  Google Scholar 

  • Sharifi-Rad J, Rayess YE, Rizk AA, Sadaka C, Zgheib R, Zam W, Sestito S, Rapposelli S, Neffe-Skocińska K, Zielińska D (2020) Turmeric and its major compound curcumin on health: bioactive effects and safety profiles for food, pharmaceutical, biotechnological and medicinal applications. Front Pharmacol 11:01021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shehzad A, Rehman G, Lee YS (2013) Curcumin in inflammatory diseases. BioFactors 39:69–77

    Article  CAS  PubMed  Google Scholar 

  • Shinde UK, Suryawanshi DG, Amin PD (2021) Development of Gelucire® 48/16 and TPGS mixed micelles and its pellet formulation by extrusion spheronization technique for dissolution rate enhancement of curcumin. AAPS PharmSciTech 22:182

    Article  CAS  PubMed  Google Scholar 

  • Soltani S, Boozari M, Cicero AFG, Jamialahmadi T, Sahebkar A (2021) Effects of phytochemicals on macrophage cholesterol efflux capacity: impact on atherosclerosis. Phytother Res 35:2854–2878

    Article  CAS  PubMed  Google Scholar 

  • Subhashini A, Chauhan PS, Dash D, Paul BN, Singh R (2016) Intranasal curcumin ameliorates airway inflammation and obstruction by regulating MAPKinase activation (p38, Erk and JNK) and prostaglandin D2 release in murine model of asthma. Int Immunopharmacol 31:200–206

    Article  CAS  PubMed  Google Scholar 

  • Subhramanyam CS, Wang C, Hu Q, Dheen ST (2019) Microglia-mediated neuroinflammation in neurodegenerative diseases. Semin Cell Dev Biol 94:112–120

    Article  CAS  PubMed  Google Scholar 

  • Tegenge MA, Rajbhandari L, Shrestha S, Mithal A, Hosmane S, Venkatesan A (2014) Curcumin protects axons from degeneration in the setting of local neuroinflammation. Exp Neurol 253:102–110

    Article  CAS  PubMed  Google Scholar 

  • Topcu-Tarladacalisir Y, Akpolat M, Uz YH, Kizilay G, Sapmaz-Metin M, Cerkezkayabekir A, Omurlu IK (2013) Effects of curcumin on apoptosis and oxidoinflammatory regulation in a rat model of acetic acid-induced colitis: the roles of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. J Med Food 16:296–305

    Article  CAS  PubMed  Google Scholar 

  • Trempolec N, Dave-Coll N, Nebreda AR (2013) SnapShot: p38 MAPK signaling. Cell 152(656–656):e1

    Google Scholar 

  • Vaughn AR, Branum A, Sivamani RK (2016) Effects of turmeric (Curcuma longa) on skin health: a systematic review of the clinical evidence. Phytother Res 30:1243–1264

    Article  CAS  PubMed  Google Scholar 

  • Wagner EF, Nebreda AR (2009) Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 9:537–549

    Article  CAS  PubMed  Google Scholar 

  • Wang WZ, Li L, Liu MY, Jin XB, Mao JW, Pu QH, Meng MJ, Chen XG, Zhu JY (2013) Curcumin induces FasL-related apoptosis through p38 activation in human hepatocellular carcinoma Huh7 cells. Life Sci 92:352–358

    Article  CAS  PubMed  Google Scholar 

  • Wang B, Li W, Jin H, Nie X, Shen H, Li E, Wang W (2018) Curcumin attenuates chronic intermittent hypoxia-induced brain injuries by inhibiting AQP4 and p38 MAPK pathway. Respir Physiol Neurobiol 255:50–57

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Yang YH, Zhou L, Ding XL, Meng YC, Han K (2020) Curcumin alleviates OGD/R-induced PC12 cell damage via repressing CCL3 and inactivating TLR4/MyD88/MAPK/NF-κB to suppress inflammation and apoptosis. J Pharm Pharmacol 72:1176–1185

    Article  CAS  PubMed  Google Scholar 

  • Watson JL, Greenshields A, Hill R, Hilchie A, Lee PW, Giacomantonio CA, Hoskin DW (2010) Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling. Mol Carcinog 49:13–24

    Article  CAS  PubMed  Google Scholar 

  • Weir NM, Selvendiran K, Kutala VK, Tong L, Vishwanath S, Rajaram M, Tridandapani S, Anant S, Kuppusamy P (2007) Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. Cancer Biol Ther 6:178–184

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Tang Q, Zhao S, Zheng F, Wu Y, Tang G, Hahn SS (2014) Extracellular signal-regulated kinase signaling-mediated induction and interaction of FOXO3a and p53 contribute to the inhibition of nasopharyngeal carcinoma cell growth by curcumin. Int J Oncol 45:95–103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu M-F, Huang Y-H, Chiu L-Y, Cherng S-H, Sheu G-T, Yang T-Y (2022) Curcumin induces apoptosis of chemoresistant lung cancer cells via ROS-regulated p38 MAPK phosphorylation. Int J Mol Sci 23:8248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia JM, Zhang J, Zhou WX, Liu XC, Han M (2013) Downregulation of p38 MAPK involved in inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin. J Huazhong Univ Sci Technolog Med Sci 33:666–671

    Article  CAS  PubMed  Google Scholar 

  • Xiao Y, Xia J, Wu S, Lv Z, Huang S, Huang H, Su X, Cheng J, Ke Y (2018) Curcumin inhibits acute vascular inflammation through the activation of heme oxygenase-1. Oxid Med Cell Longev 2018:3295807

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang Z, Zhao T, Zou Y, Zhang JH, Feng H (2014) Curcumin inhibits microglia inflammation and confers neuroprotection in intracerebral hemorrhage. Immunol Lett 160:89–95

    Article  CAS  PubMed  Google Scholar 

  • Yao Q, Lin M, Wang Y, Lai Y, Hu J, Fu T, Wang L, Lin S, Chen L, Guo Y (2015) Curcumin induces the apoptosis of A549 cells via oxidative stress and MAPK signaling pathways. Int J Mol Med 36:1118–1126

    Article  PubMed  Google Scholar 

  • Yu X, Zhong J, Yan L, Li J, Wang H, Wen Y, Zhao Y (2016) Curcumin exerts antitumor effects in retinoblastoma cells by regulating the JNK and p38 MAPK pathways. Int J Mol Med 38:861–868

    Article  CAS  PubMed  Google Scholar 

  • Yu Y, Shen Q, Lai Y, Park SY, Ou X, Lin D, Jin M, Zhang W (2018) Anti-inflammatory effects of curcumin in microglial cells. Front Pharmacol 9:386

    Article  PubMed  PubMed Central  Google Scholar 

  • Zambrano LMG, Brandao DA, Rocha FRG, Marsiglio RP, Longo IB, Primo FL, Tedesco AC, Guimaraes-Stabili MR, Rossa-Junior C (2018) Local administration of curcumin-loaded nanoparticles effectively inhibits inflammation and bone resorption associated with experimental periodontal disease. Sci Rep 8:6652

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao X, Fang J, Jia Y, Wu Z, Zhang M, Xia M, Dong J (2022) Synthesis and anti-neuroinflammatory activity of 1,7-diphenyl-1,4-heptadien-3-ones in LPS-stimulated BV2 microglia via inhibiting NF-κB/MAPK signaling pathways. Molecules 27:3537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhong W, Qian K, Xiong J, Ma K, Wang A, Zou Y (2016) Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κB related signaling. Biomed Pharmacother 83:302–313

    Article  CAS  PubMed  Google Scholar 

  • Zou T, Li S, Wang B, Wang Z, Liu Y, You J (2021) Curcumin improves insulin sensitivity and increases energy expenditure in high-fat-diet–induced obese mice associated with activation of FNDC5/irisin. Nutrition 90:111263

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

No funding was received to perform this study.

Author information

Authors and Affiliations

  1. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Hedieh Sadat Shamsnia, Mahtab Roustaei, Danial Ahmadvand, Dorsa Amirlou, Sanam Soltani & Amir Hossein Abdolghaffari

  2. GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Hedieh Sadat Shamsnia, Mahtab Roustaei, Danial Ahmadvand, Dorsa Amirlou & Amir Hossein Abdolghaffari

  3. Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain

    Alexandra E. Butler

  4. Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran

    Saeideh Momtaz

  5. Department of Toxicology and Pharmacology, School of Pharmacy, and Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

    Saeideh Momtaz

  6. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Tannaz Jamialahmadi & Amirhossein Sahebkar

  7. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  8. School of Medicine, The University of Western Australia, Perth, Australia

    Amirhossein Sahebkar

  9. Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

Authors
  1. Hedieh Sadat Shamsnia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mahtab Roustaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danial Ahmadvand
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexandra E. Butler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dorsa Amirlou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sanam Soltani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Saeideh Momtaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tannaz Jamialahmadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Amir Hossein Abdolghaffari
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Amirhossein Sahebkar
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HS, MR and DA studied the literature, analyzed the published data of the relevant topics, wrote the first draft of the paper and created the tables. AEB, DA, SS, SM and TJ edited the manuscript. AHA and AS conceptualized, reviewed and edited the manuscript. All authors reviewed and approved the final version of the manuscript. AS is the guarantor of this work.

Corresponding authors

Correspondence to Amir Hossein Abdolghaffari or Amirhossein Sahebkar.

Ethics declarations

Conflict of interest

No authors have any conflict of interest or competing interests to declare.

Ethical approval and consent to participate

Not applicable to a review article.

Consent for publication

All authors gave their consent for publication.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shamsnia, H.S., Roustaei, M., Ahmadvand, D. et al. Impact of curcumin on p38 MAPK: therapeutic implications. Inflammopharmacol 31, 2201–2212 (2023). https://doi.org/10.1007/s10787-023-01265-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-023-01265-2

Keywords

Search

Navigation