
Action and mechanisms of neferine in inflammatory diseases (Review)
- Authors:
- Qin Zhang
- Qiaoling Zhou
- Huihui Li
-
Affiliations: Department of Nephropathy, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, P.R. China, Department of Nephropathy, Xiangya Hospital Central‑South University, Changsha, Hunan 410028, P.R. China - Published online on: April 16, 2025 https://doi.org/10.3892/mmr.2025.13539
- Article Number: 174
-
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Mukherjee PK, Mukherjee D, Maji AK, Rai S and Heinrich M: The sacred lotus (Nelumbo nucifera)-phytochemical and therapeutic profile. J Pharm Pharmacol. 61:407–422. 2009. View Article : Google Scholar : PubMed/NCBI | |
Sharma BR, Gautam LN, Adhikari D and Karki R: A Comprehensive review on chemical profiling of nelumbo nucifera: Potential for drug development. Phytother Res. 31:3–26. 2017. View Article : Google Scholar : PubMed/NCBI | |
Zhao SH, Jin D, Gu CJ and Lian FG: Professor Tong Xiaolin's experience in using lotus leaf, gordon euryale seed and lotus plumule for clearing and transforming damp-heat symptoms. Jilin J Trad Chin Med. 41:336–338. 2021.(In Chinese). | |
Huang XX, Xie Z, Xie MY and Li S: Mechanism of qinggongtang against generalized anxiety disorder based on Glu/GABA metabolic balance. Chin J Exp Trad Med Formulae. 30:28–35. 2024.(In Chinese). | |
Zheng ZJ, Zhu LZ, Song WC, Hu C, Chen S, You P and Zhou Y: Pharmacological Research Progress of Nelumbinis Plumula in the Treatment of Insomnia from the Traditional Chinese Medicine Perspective ‘Heart Mind’. Shenzhen J Integrated Trad Chin Western Med. 32:125–129. 2022.(In Chinese). | |
Wang Z, Li Y, Ma D, Zeng M, Wang Z, Qin F, Chen J, Christian M and He Z: Alkaloids from lotus (Nelumbo nucifera): Recent advances in biosynthesis, pharmacokinetics, bioactivity, safety, and industrial applications. Crit Rev Food Sci Nutr. 63:4867–4900. 2023. View Article : Google Scholar : PubMed/NCBI | |
Bishayee A, Patel PA, Sharma P, Thoutireddy S and Das N: Lotus (Nelumbo nucifera Gaertn.) and its bioactive phytocompounds: A tribute to cancer prevention and intervention. Cancers (Basel). 14:5292022. View Article : Google Scholar : PubMed/NCBI | |
Marthandam Asokan S, Mariappan R, Muthusamy S and Velmurugan BK: Pharmacological benefits of neferine-A comprehensive review. Life Sci. 199:60–70. 2018. View Article : Google Scholar : PubMed/NCBI | |
Bharathi Priya L, Huang CY, Hu RM, Balasubramanian B and Baskaran R: An updated review on pharmacological properties of neferine-A bisbenzylisoquinoline alkaloid from Nelumbo nucifera. J Food Biochem. 45:e139862021. View Article : Google Scholar : PubMed/NCBI | |
Arulselvan P, Fard MT, Tan WS, Gothai S, Fakurazi S, Norhaizan ME and Kumar SS: Role of antioxidants and natural products in inflammation. Oxid Med Cell Longev. 2016:52761302016. View Article : Google Scholar : PubMed/NCBI | |
Priya LB, Baskaran R, Huang CY and Padma VV: Neferine ameliorates cardiomyoblast apoptosis induced by doxorubicin: Possible role in modulating NADPH oxidase/ROS-mediated NFκB redox signaling cascade. Sci Rep. 7:122832017. View Article : Google Scholar : PubMed/NCBI | |
Jarczak D and Nierhaus A: Cytokine Storm-definition, causes, and implications. Int J Mol Sci. 23:117402022. View Article : Google Scholar : PubMed/NCBI | |
van Loo G and Bertrand MJM: Death by TNF: A road to inflammation. Nat Rev Immunol. 23:289–303. 2023. View Article : Google Scholar : PubMed/NCBI | |
Pan Y, Cai B, Wang K, Wang S, Zhou S, Yu X, Xu B and Chen L: Neferine enhances insulin sensitivity in insulin resistant rats. J Ethnopharmacol. 124:98–102. 2009. View Article : Google Scholar : PubMed/NCBI | |
Baskaran R, Priya LB, Kalaiselvi P, Poornima P, Huang CY and Padma VV: Neferine from Nelumbo nucifera modulates oxidative stress and cytokines production during hypoxia in human peripheral blood mononuclear cells. Biomed Pharmacother. 93:730–736. 2017. View Article : Google Scholar : PubMed/NCBI | |
Min X, Guo Y, Zhou Y and Chen X: Protection against dextran sulfate Sodium-induced ulcerative colitis in mice by neferine, a natural product from Nelumbo nucifera gaertn. Cell J. 22:523–531. 2021.PubMed/NCBI | |
Li J, Chou H, Li L, Li H and Cui Z: Wound healing activity of neferine in experimental diabetic rats through the inhibition of inflammatory cytokines and nrf-2 pathway. Artif Cells Nanomed Biotechnol. 48:96–106. 2020. View Article : Google Scholar : PubMed/NCBI | |
Rietschel ET, Kirikae T, Schade FU, Mamat U, Schmidt G, Loppnow H, Ulmer AJ, Zähringer U, Seydel U, Di Padova F, et al: Bacterial endotoxin: Molecular relationships of structure to activity and function. FASEB J. 8:217–225. 1994. View Article : Google Scholar : PubMed/NCBI | |
Wu X, Guo Y, Min X, Pei L and Chen X: Neferine, a bisbenzylisoquinoline alkaloid, ameliorates dextran sulfate Sodium-induced ulcerative colitis. Am J Chin Med. 46:1263–1279. 2018. View Article : Google Scholar : PubMed/NCBI | |
Guolan D, Lingli W, Wenyi H, Wei Z, Baowei C and Sen B: Anti-inflammatory effects of neferine on LPS-induced human endothelium via MAPK, and NF-κβ pathways. Pharmazie. 73:541–544. 2018.PubMed/NCBI | |
Liu XY, Xu HX, Li JK, Zhang D, Ma XH, Huang LN, Lü JH and Wang XZ: Neferine Protects endothelial glycocalyx via mitochondrial ROS in lipopolysaccharide-Induced acute respiratory distress syndrome. Front Physiol. 9:1022018. View Article : Google Scholar : PubMed/NCBI | |
Tang YS, Zhao YH, Zhong Y, Li XZ, Pu JX, Luo YC and Zhou QL: Neferine inhibits LPS-ATP-induced endothelial cell pyroptosis via regulation of ROS/NLRP3/Caspase-1 signaling pathway. Inflamm Res. 68:727–738. 2019. View Article : Google Scholar : PubMed/NCBI | |
Zhong Y, He S, Huang K and Liang M: Neferine suppresses vascular endothelial inflammation by inhibiting the NF-κB signaling pathway. Arch Biochem Biophys. 696:1085952020. View Article : Google Scholar : PubMed/NCBI | |
Li H, Chen W, Chen Y, Zhou Q, Xiao P, Tang R and Xue J: Neferine attenuates acute kidney injury by inhibiting NF-κB signaling and upregulating klotho expression. Front Pharmacol. 10:11972019. View Article : Google Scholar : PubMed/NCBI | |
Li T, Zhai YX, Zheng T and Xu B: Neferine exerts anti-inflammatory activity in BV-2 microglial cells and protects mice with MPTP-induced Parkinson's disease by inhibiting NF-κB activation. Mol Med Rep. 28:2352023. View Article : Google Scholar : PubMed/NCBI | |
Qi Z, Wang R, Liao R, Xue S and Wang Y: Neferine ameliorates Sepsis-induced myocardial dysfunction through Anti-apoptotic and antioxidative effects by regulating the PI3K/AKT/mTOR signaling pathway. Front Pharmacol. 12:7062512021. View Article : Google Scholar : PubMed/NCBI | |
Savin IA, Zenkova MA and Sen'kova AV: Pulmonary fibrosis as a result of acute lung inflammation: Molecular mechanisms, relevant in vivo models, prognostic and therapeutic approaches. Int J Mol Sci. 23:149592022. View Article : Google Scholar : PubMed/NCBI | |
Zhao L, Wang X, Chang Q, Xu J, Huang Y, Guo Q, Zhang S, Wang W, Chen X and Wang J: Neferine, a bisbenzylisoquinline alkaloid attenuates bleomycin-induced pulmonary fibrosis. Eur J Pharmacol. 627:304–312. 2010. View Article : Google Scholar : PubMed/NCBI | |
Niu CH, Wang Y, Liu JD, Wang JL and Xiao JH: Protective effects of neferine on amiodarone-induced pulmonary fibrosis in mice. Eur J Pharmacol. 714:112–119. 2013. View Article : Google Scholar : PubMed/NCBI | |
Wang Y, Wang S, Wang R, Li S and Yuan Y: Neferine exerts antioxidant and Anti-inflammatory effects on carbon Tetrachloride-induced liver fibrosis by inhibiting the MAPK and NF-κB/IκBα pathways. Evid Based Complement Alternat Med. 2021:41360192021.PubMed/NCBI | |
Joffre J and Hellman J: Oxidative stress and endothelial dysfunction in sepsis and acute inflammation. Antioxid Redox Signal. 35:1291–1307. 2021. View Article : Google Scholar : PubMed/NCBI | |
Hussain T, Tan B, Yin Y, Blachier F, Tossou MCB and Rahu N: Oxidative stress and inflammation: What polyphenols can do for us? Oxid Med Cell Longev. 2016:74327972016. View Article : Google Scholar : PubMed/NCBI | |
Lalitha G, Poornima P, Archanah A and Padma VV: Protective effect of neferine against isoproterenol-induced cardiac toxicity. Cardiovasc Toxicol. 13:168–179. 2013. View Article : Google Scholar : PubMed/NCBI | |
Guan G, Han H, Yang Y, Jin Y, Wang X and Liu X: Neferine prevented hyperglycemia-induced endothelial cell apoptosis through suppressing ROS/Akt/NF-κB signal. Endocrine. 47:764–771. 2014. View Article : Google Scholar : PubMed/NCBI | |
Khan A, Bai H, Shu M, Chen M, Khan A and Bai Z: Antioxidative and antiphotoaging activities of neferine upon UV-A irradiation in human dermal fibroblasts. Biosci Rep. 38:BSR201814142018. View Article : Google Scholar : PubMed/NCBI | |
Khan A, Bai H, Khan A and Bai Z: Neferine prevents ultraviolet radiation-induced skin photoaging. Exp Ther Med. 19:3189–3196. 2020.PubMed/NCBI | |
Nguyen T, Nioi P and Pickett CB: The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 284:13291–13295. 2009. View Article : Google Scholar : PubMed/NCBI | |
Baskaran R, Poornima P, Priya LB, Huang CY and Padma VV: Neferine prevents autophagy induced by hypoxia through activation of Akt/mTOR pathway and Nrf2 in muscle cells. Biomed Pharmacother. 83:1407–1413. 2016. View Article : Google Scholar : PubMed/NCBI | |
Bharathi Priya L, Baskaran R, Huang CY and Vijaya Padma V: Neferine modulates IGF-1R/Nrf2 signaling in doxorubicin treated H9c2 cardiomyoblasts. J Cell Biochem. 119:1441–1452. 2018. View Article : Google Scholar : PubMed/NCBI | |
Liu XD, Li H, Wang CZ, Zhao HD and Xiao P: Mechanism of neferine in antioxidant stress. China J Modern Med. 28:31–36. 2018. | |
Wu C, Chen J, Yang R, Duan F, Li S and Chen X: Mitochondrial protective effect of neferine through the modulation of nuclear factor erythroid 2-related factor 2 signalling in ischaemic stroke. Br J Pharmacol. 176:400–415. 2019. View Article : Google Scholar : PubMed/NCBI | |
Jiang XX, Zhang R and Wang HS: Neferine mitigates angiotensin II-induced atrial fibrillation and fibrosis via upregulation of Nrf2/HO-1 and inhibition of TGF-β/p-Smad2/3 pathways. Aging. 16:8630–8644. 2024. View Article : Google Scholar : PubMed/NCBI | |
Sanz AB, Sanchez-Niño MD, Ramos AM, Moreno JA, Santamaria B, Ruiz-Ortega M, Egido J and Ortiz A: NF-kappaB in renal inflammation. J Am Soc Nephrol. 21:1254–1262. 2010. View Article : Google Scholar : PubMed/NCBI | |
Yu H, Lin L, Zhang Z, Zhang H and Hu H: Targeting NF-κB pathway for the therapy of diseases: Mechanism and clinical study. Signal Transduct Target Ther. 5:2092020. View Article : Google Scholar : PubMed/NCBI | |
Jung HA, Jin SE, Choi RJ, Kim DH, Kim YS, Ryu JH, Kim DW, Son YK, Park JJ and Choi JS: Anti-amnesic activity of neferine with antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1. Life Sci. 87:420–430. 2010. View Article : Google Scholar : PubMed/NCBI | |
Chen S, Chu B, Chen Y, Cheng X, Guo D, Chen L, Wang J, Li Z, Hong Z and Hong D: Neferine suppresses osteoclast differentiation through suppressing NF-κB signal pathway but not MAPKs and promote osteogenesis. J Cell Physiol. 234:22960–22971. 2019. View Article : Google Scholar : PubMed/NCBI | |
Wu F, Wu Z, Ye Z, Niu G, Ma Z and Zhang P: PLGA/BGP/Nef porous composite restrains osteoclasts by inhibiting the NF-κB pathway, enhances IGF-1-mediated osteogenic differentiation and promotes bone regeneration. J Biol Eng. 17:452023. View Article : Google Scholar : PubMed/NCBI | |
Ni B, Huang X, Xi Y, Mao Z, Chu X, Zhang R, Ma X and You H: Neferine inhibits expression of inflammatory mediators and matrix degrading enzymes in IL-1β-treated rat chondrocytes via suppressing MAPK and NF-κB signaling pathways. Inflammation. 43:1209–1221. 2020. View Article : Google Scholar : PubMed/NCBI | |
Luo MC, Zhou SY, Feng DY, Xiao J, Li WY, Xu CD, Wang HY and Zhou T: Runt-related transcription factor 1 (RUNX1) binds to p50 in macrophages and enhances TLR4-triggered inflammation and septic shock. J Biol Chem. 291:22011–22020. 2016. View Article : Google Scholar : PubMed/NCBI | |
Wang MY, Zhang SS, An MF, Xia YF, Fan MS, Sun ZR, Zhang LJ, Zhao YL, Sheng J and Wang XJ: Neferine ameliorates nonalcoholic steatohepatitis through regulating AMPK pathway. Phytomedicine. 114:1547982023. View Article : Google Scholar : PubMed/NCBI | |
Xiong Y, Zhong J, Chen W, Li X, Liu H, Li Y, Xiong W and Li H: Neferine alleviates acute kidney injury by regulating the PPAR-α/NF-κB pathway. Clin Exp Nephrol. 28:969–987. 2024. View Article : Google Scholar : PubMed/NCBI | |
Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X and Zhao L: Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 9:7204–7218. 2018. View Article : Google Scholar : PubMed/NCBI | |
Kim EK and Choi EJ: Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 1802:396–405. 2010. View Article : Google Scholar : PubMed/NCBI | |
Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K and Cobb MH: Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions. Endocr Rev. 22:153–183. 2001. View Article : Google Scholar : PubMed/NCBI | |
Liu X, Song X, Lu J, Chen X, Liang E, Liu X, Zhang M, Zhang Y, Du Z and Zhao Y: Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice. Oncotarget. 7:61703–61715. 2016. View Article : Google Scholar : PubMed/NCBI | |
Ozal SA, Gurlu V, Turkekul K, Guclu H and Erdogan S: Neferine inhibits epidermal growth factor-induced proliferation and migration of retinal pigment epithelial cells through downregulating p38 MAPK and PI3K/AKT signalling. Cutan Ocul Toxicol. 39:97–105. 2020. View Article : Google Scholar : PubMed/NCBI | |
Zhu T, Xiao X, Dong Y and Yuan C: Neferine alleviates ovalbumin-induced asthma via MAPK signaling pathways in mice. Allergol Immunopathol (Madr). 51:135–142. 2023. View Article : Google Scholar : PubMed/NCBI | |
Han Q, Li H, Zhao F, Gao J, Liu X and Ma B: Auricularia auricula peptides nutritional supplementation delays H2O2-induced senescence of hepG2 cells by modulation of MAPK/NF-κB signaling pathways. Nutrients. 15:37312023. View Article : Google Scholar : PubMed/NCBI | |
Yang CC, Hung YL, Ko WC, Tsai YJ, Chang JF, Liang CW, Chang DC and Hung CF: Effect of neferine on DNCB-induced atopic dermatitis in HaCaT cells and BALB/c Mice. Int J Mol Sci. 22:82372021. View Article : Google Scholar : PubMed/NCBI | |
Chiu KM, Hung YL, Wang SJ, Tsai YJ, Wu NL, Liang CW, Chang DC and Hung CF: Anti-allergic and Anti-inflammatory effects of neferine on RBL-2H3 cells. Int J Mol Sci. 22:109942021. View Article : Google Scholar : PubMed/NCBI | |
Wang L and Hauenstein AV: The NLRP3 inflammasome: Mechanism of action, role in disease and therapies. Mol Aspects Med. 76:1008892020. View Article : Google Scholar : PubMed/NCBI | |
Coll RC, Schroder K and Pelegrín P: NLRP3 and pyroptosis blockers for treating inflammatory diseases. Trends Pharmacol Sci. 43:653–668. 2022. View Article : Google Scholar : PubMed/NCBI | |
Wu XL, Deng MZ, Gao ZJ, Dang YY, Li YC and Li CW: Neferine alleviates memory and cognitive dysfunction in diabetic mice through modulation of the NLRP3 inflammasome pathway and alleviation of endoplasmic-reticulum stress. Int Immunopharmacol. 84:1065592020. View Article : Google Scholar : PubMed/NCBI | |
Zhu JJ, Yu BY, Huang XK, He MZ, Chen BW, Chen TT, Fang HY, Chen SQ, Fu XQ, Li PJ, et al: Neferine protects against Hypoxic-ischemic brain damage in neonatal rats by suppressing NLRP3-mediated inflammasome activation. Oxid Med Cell Longev. 2021:66549542021. View Article : Google Scholar : PubMed/NCBI | |
Zheng ZJ, Zhu LZ, Qiu H, Zheng WY, You PT, Chen SH, Hu CL, Huang JR and Zhou YJ: Neferine inhibits BMECs pyroptosis and maintains blood-brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α. Sci Rep. 14:144382024. View Article : Google Scholar : PubMed/NCBI | |
Lin TY, Hung CY, Chiu KM, Lee MY, Lu CW and Wang SJ: Neferine, an alkaloid from lotus seed embryos, exerts antiseizure and neuroprotective effects in a kainic Acid-induced seizure model in rats. Int J Mol Sci. 23:41302022. View Article : Google Scholar : PubMed/NCBI | |
Deretic V: Autophagy in inflammation, infection, and immunometabolism. Immunity. 54:437–453. 2021. View Article : Google Scholar : PubMed/NCBI | |
Xu T, Singh D, Liu J, Li H, Peng S, Rizzolo LJ and Wang SB: Neferine, is not inducer but blocker for macroautophagic flux targeting on lysosome malfunction. Biochem Biophys Res Commun. 495:1516–1521. 2018. View Article : Google Scholar : PubMed/NCBI | |
Sengking J, Oka C, Wicha P, Yawoot N, Tocharus J, Chaichompoo W, Suksamrarn A and Tocharus C: Neferine protects against brain damage in permanent cerebral ischemic rat associated with autophagy suppression and AMPK/mTOR regulation. Mol Neurobiol. 58:6304–6315. 2021. View Article : Google Scholar : PubMed/NCBI | |
Li H, Tang Y, Wen L, Kong X, Chen X, Liu P, Zhou Z, Chen W, Xiao C, Xiao P and Xiao X: Neferine reduces cisplatin-induced nephrotoxicity by enhancing autophagy via the AMPK/mTOR signaling pathway. Biochem Biophys Res Commun. 484:694–701. 2017. View Article : Google Scholar : PubMed/NCBI | |
Jones SA, Mills KH and Harris J: Autophagy and inflammatory diseases. Immunol Cell Biol. 91:250–258. 2013. View Article : Google Scholar : PubMed/NCBI | |
Yang Z, Goronzy JJ and Weyand CM: Autophagy in autoimmune disease. J Mol Med (Berl). 93:707–717. 2015. View Article : Google Scholar : PubMed/NCBI | |
Li H, Gao L, Min J, Yang Y and Zhang R: Neferine suppresses autophagy-induced inflammation, oxidative stress and adipocyte differentiation in Graves' orbitopathy. J Cell Mol Med. 25:1949–1957. 2021. View Article : Google Scholar : PubMed/NCBI | |
Jiang T, Harder B, Rojo de la Vega M, Wong PK, Chapman E and Zhang DD: p62 links autophagy and Nrf2 signaling. Free Radic Biol Med. 88:199–204. 2015. View Article : Google Scholar : PubMed/NCBI | |
Heldin CH, Miyazono K and ten Dijke P: TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature. 390:465–471. 1997. View Article : Google Scholar : PubMed/NCBI | |
Xu P, Liu J and Derynck R: Post-translational regulation of TGF-β receptor and Smad signaling. FEBS Lett. 586:1871–1884. 2012. View Article : Google Scholar : PubMed/NCBI | |
Dumbrava MG, Lacanlale JL, Rowan CJ and Rosenblum ND: Transforming growth factor beta signaling functions during mammalian kidney development. Pediatr Nephrol. 36:1663–1672. 2021. View Article : Google Scholar : PubMed/NCBI | |
Goumans MJ and Ten Dijke P: TGF-β signaling in control of cardiovascular function. Cold Spring Harb Perspect Biol. 10:a0222102018. View Article : Google Scholar : PubMed/NCBI | |
Laudisi F, Stolfi C, Monteleone I and Monteleone G: TGF-β1 signaling and Smad7 control T-cell responses in health and immune-mediated disorders. Eur J Immunol. 53:e23504602023. View Article : Google Scholar : PubMed/NCBI | |
Xia Y, Guo Y, Zhou J, Fan L, Xie J, Wang Y, Du H and Ni X: Neferine mediated TGF-β/ERK signaling to inhibit fibrosis in endometriosis. Am J Transl Res. 15:3240–3253. 2023.PubMed/NCBI | |
Liu CM, Shao Z, Chen X, Chen H, Su M, Zhang Z, Wu Z, Zhang P, An L, Jiang Y and Ouyang AJ: Neferine attenuates development of testosterone-induced benign prostatic hyperplasia in mice by regulating androgen and TGF-β/Smad signaling pathways. Saudi Pharm J. 31:1219–1228. 2023. View Article : Google Scholar : PubMed/NCBI | |
Zeng W, Zhang X, Lu Y, Wen Y, Xie Q, Yang X, He S, Guo Z, Li J, Shen A and Peng J: Neferine ameliorates hypertensive vascular remodeling modulating multiple signaling pathways in spontaneously hypertensive rats. Biomed Pharmacother. 158:1142032023. View Article : Google Scholar : PubMed/NCBI | |
Yu Y, Sun S, Wang S, Zhang Q, Li M, Lan F, Li S and Liu C: Liensinine- and Neferine-induced cardiotoxicity in primary neonatal rat cardiomyocytes and Human-induced pluripotent stem Cell-derived cardiomyocytes. Int J Mol Sci. 17:1862016. View Article : Google Scholar : PubMed/NCBI |