
Exploring the potential of honokiol as a treatment for cardiovascular disease (Review)
- Authors:
- Yao Zeng
- Zishan Li
- Xiaolong Lin
-
Affiliations: Department of Pathology, The Affiliated Huizhou Hospital (Huizhou Third People's Hospital), Guangzhou Medical University, Huizhou, Guangdong 516001, P.R. China, Department of Cardiovascularology, The Affiliated Huizhou Hospital (Huizhou Third People's Hospital), Guangzhou Medical University, Huizhou, Guangdong 516001, P.R. China - Published online on: June 10, 2025 https://doi.org/10.3892/br.2025.2012
- Article Number: 134
-
Copyright: © Zeng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
![]() |
![]() |
![]() |
Podolec P and Matusik PT: New clinical classification of rare cardiovascular diseases and disorders: Relevance for cardiovascular research. Cardiovasc Res. 115:e77–e79. 2019.PubMed/NCBI View Article : Google Scholar | |
Kee PS, Chin PKL, Kennedy MA and Maggo SDS: Pharmacogenetics of statin-induced myotoxicity. Front Genet. 11(575678)2020.PubMed/NCBI View Article : Google Scholar | |
Vinci P, Panizon E, Tosoni LM, Cerrato C, Pellicori F, Mearelli F, Biasinutto C, Fiotti N, Di Girolamo FG and Biolo G: Statin-associated myopathy: Emphasis on mechanisms and targeted therapy. Int J Mol Sci. 22(11687)2021.PubMed/NCBI View Article : Google Scholar | |
Wang J, Zou J, Shi Y, Zeng N, Guo D, Wang H, Zhao C, Luan F, Zhang X and Sun J: Traditional Chinese medicine and mitophagy: A novel approach for cardiovascular disease management. Phytomedicine. 128(155472)2024.PubMed/NCBI View Article : Google Scholar | |
Chen C, Zhang QW, Ye Y and Lin LG: Honokiol: A naturally occurring lignan with pleiotropic bioactivities. Chin J Nat Med. 19:481–490. 2021.PubMed/NCBI View Article : Google Scholar | |
Rauf A, Olatunde A, Imran M, Alhumaydhi FA, Aljohani ASM, Khan SA, Uddin MS, Mitra S, Emran TB, Khayrullin M, et al: Honokiol: A review of its pharmacological potential and therapeutic insights. Phytomedicine. 90(153647)2021.PubMed/NCBI View Article : Google Scholar | |
Prasher P, Fatima R, Sharma M, Tynybekov B, Alshahrani AM, Ateşşahin DA, Sharifi-Rad J and Calina D: Honokiol and its analogues as anticancer compounds: Current mechanistic insights and structure-activity relationship. Chem Biol Interact. 386(110747)2023.PubMed/NCBI View Article : Google Scholar | |
Dai SY, Qin WX, Yu S, Li C, Yang YH and Pei YH: Honokiol and magnolol: A review of structure-activity relationships of their derivatives. Phytochemistry. 223(114132)2024.PubMed/NCBI View Article : Google Scholar | |
Li X, Yuan Z, Wang Y, Wang W and Shi J: Recent advances of honokiol: Pharmacological activities, manmade derivatives and structure-activity relationship. Eur J Med Chem. 272(116471)2024.PubMed/NCBI View Article : Google Scholar | |
Yang R, Cui L, Xu S, Zhong Y, Xu T, Liu J, Lan Z, Qin S and Guo Y: Membrane-targeting amphiphilic honokiol derivatives containing an oxazole moiety as potential antibacterials against methicillin-resistant Staphylococcus aureus. J Med Chem. 67:16858–16872. 2024.PubMed/NCBI View Article : Google Scholar | |
Liu A, Xun S, Zhou G, Zhang Y and Lin L: Honokiol alleviates sepsis-associated cardiac dysfunction via attenuating inflammation, apoptosis and oxidative stress. J Pharm Pharmacol. 75:397–406. 2023.PubMed/NCBI View Article : Google Scholar | |
Wang N, Kong R, Han W, Bao W, Shi Y, Ye L and Lu J: Honokiol alleviates ulcerative colitis by targeting PPAR-γ-TLR4-NF-κB signaling and suppressing gasdermin-D-mediated pyroptosis in vivo and in vitro. Int Immunopharmacol. 111(109058)2022.PubMed/NCBI View Article : Google Scholar | |
Zhou Y, Tang J, Lan J, Zhang Y, Wang H, Chen Q, Kang Y, Sun Y, Feng X, Wu L, et al: Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis. Acta Pharm Sin B. 13:577–597. 2023.PubMed/NCBI View Article : Google Scholar | |
Kim H, Lim CY and Chung MS: Magnolia officinalis and its honokiol and magnolol constituents inhibit human norovirus surrogates. Foodborne Pathog Dis. 18:24–30. 2021.PubMed/NCBI View Article : Google Scholar | |
Qu WM, Yue XF, Sun Y, Fan K, Chen CR, Hou YP, Urade Y and Huang ZL: Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice. Br J Pharmacol. 167:587–598. 2012.PubMed/NCBI View Article : Google Scholar | |
Ferrucci L and Fabbri E: Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 15:505–522. 2018.PubMed/NCBI View Article : Google Scholar | |
Shaito A, Aramouni K, Assaf R, Parenti A, Orekhov A, Yazbi AE, Pintus G and Eid AH: Oxidative stress-induced endothelial dysfunction in cardiovascular diseases. Front Biosci (Landmark Ed). 27(105)2022.PubMed/NCBI View Article : Google Scholar | |
Marchio P, Guerra-Ojeda S, Vila JM, Aldasoro M, Victor VM and Mauricio MD: Targeting early atherosclerosis: A focus on oxidative stress and inflammation. Oxid Med Cell Longev. 2019(8563845)2019.PubMed/NCBI View Article : Google Scholar | |
Aktay I, Bitirim CV, Olgar Y, Durak A, Tuncay E, Billur D, Akcali KC and Turan B: Cardioprotective role of a magnolol and honokiol complex in the prevention of doxorubicin-mediated cardiotoxicity in adult rats. Mol Cell Biochem. 479:337–350. 2024.PubMed/NCBI View Article : Google Scholar | |
Fan S, Li X, Lin J, Chen S, Shan J and Qi G: Honokiol inhibits tumor necrosis factor-alpha-stimulated rat aortic smooth muscle cell proliferation via caspase- and mitochondrial-dependent apoptosis. Inflammation. 37:17–26. 2014.PubMed/NCBI View Article : Google Scholar | |
Yuan Y, Zhou X, Wang Y, Wang Y, Teng X and Wang S: Cardiovascular modulating effects of magnolol and honokiol, two polyphenolic compounds from traditional Chinese medicine-Magnolia officinalis. Curr Drug Target. 21:559–572. 2020.PubMed/NCBI View Article : Google Scholar | |
Liu Y, Cheng P and Wu AH: Honokiol inhibits carotid artery atherosclerotic plaque formation by suppressing inflammation and oxidative stress. Aging (Albany NY). 12:8016–8028. 2020.PubMed/NCBI View Article : Google Scholar | |
Liou KT, Lin SM, Huang SS, Chih CL and Tsai SK: Honokiol ameliorates cerebral infarction from ischemia-reperfusion injury in rats. Planta Med. 69:130–134. 2003.PubMed/NCBI View Article : Google Scholar | |
Liu J, Tang M, Li T, Su Z, Zhu Z, Dou C, Liu Y, Pei H, Yang J, Ye H and Chen L: Honokiol ameliorates post-myocardial infarction heart failure through Ucp3-mediated reactive oxygen species inhibition. Front Pharmacol. 13(811682)2022.PubMed/NCBI View Article : Google Scholar | |
Zhao C and Liu ZQ: Comparison of antioxidant abilities of magnolol and honokiol to scavenge radicals and to protect DNA. Biochimie. 93:1755–1760. 2011.PubMed/NCBI View Article : Google Scholar | |
Wang D, Cao L, Zhou X, Wang G, Ma Y, Hao X and Fan H: Mitigation of honokiol on fluoride-induced mitochondrial oxidative stress, mitochondrial dysfunction, and cognitive deficits through activating AMPK/PGC-1α/Sirt3. J Hazard Mater. 437(129381)2022.PubMed/NCBI View Article : Google Scholar | |
Caballero EP, Mariz-Ponte N, Rigazio CS, Santamaria MH and Corral RS: Honokiol attenuates oxidative stress-dependent heart dysfunction in chronic Chagas disease by targeting AMPK/NFE2L2/SIRT3 signaling pathway. Free Radical Biol Med. 156:113–124. 2020.PubMed/NCBI View Article : Google Scholar | |
Lin A, Miano JM, Fisher EA and Misra A: Chronic inflammation and vascular cell plasticity in atherosclerosis. Nat Cardiovasc Res. 3:1408–1423. 2024.PubMed/NCBI View Article : Google Scholar | |
Guzik TJ, Nosalski R, Maffia P and Drummond GR: Immune and inflammatory mechanisms in hypertension. Nat Rev Cardiol. 21:396–416. 2024.PubMed/NCBI View Article : Google Scholar | |
Boulet J, Sridhar VS, Bouabdallaoui N, Tardif JC and White M: Inflammation in heart failure: Pathophysiology and therapeutic strategies. Inflamm Res. 73:709–723. 2024.PubMed/NCBI View Article : Google Scholar | |
Lee J, Jung E, Park J, Jung K, Lee S, Hong S, Park J, Park E, Kim J, Park S and Park D: Anti-inflammatory effects of magnolol and honokiol are mediated through inhibition of the downstream pathway of MEKK-1 in NF-kappaB activation signaling. Planta Med. 71:338–343. 2005.PubMed/NCBI View Article : Google Scholar | |
Tang X, Yao K, Zhang L, Yang Y and Yao H: Honokiol inhibits H2O2-induced apoptosis in human lens epithelial cells via inhibition of the mitogen-activated protein kinase and Akt pathways. Eur J Pharmacol. 650:72–78. 2011.PubMed/NCBI View Article : Google Scholar | |
Ye JS, Chen L, Lu YY, Lei SQ, Peng M and Xia ZY: SIRT3 activator honokiol ameliorates surgery/anesthesia-induced cognitive decline in mice through anti-oxidative stress and anti-inflammatory in hippocampus. CNS Neurosci Ther. 25:355–366. 2019.PubMed/NCBI View Article : Google Scholar | |
Zhu X, Wang Z, Hu C, Li Z and Hu J: . Honokiol suppresses TNF-α-induced migration and matrix metalloproteinase expression by blocking NF-κB activation via the ERK signaling pathway in rat aortic smooth muscle cells. Acta Histochem. 116:588–595. 2014.PubMed/NCBI View Article : Google Scholar | |
Murakami Y, Kawata A, Seki Y, Koh T, Yuhara K, Maruyama T, Machino M, Ito S, Kadoma Y and Fujisawa S: Comparative inhibitory effects of magnolol, honokiol, eugenol and bis-eugenol on cyclooxygenase-2 expression and nuclear factor-kappa B activation in RAW264.7 macrophage-like cells stimulated with fimbriae of Porphyromonas gingivalis. In Vivo. 26:941–950. 2012.PubMed/NCBI | |
Montecino-Garrido H, Méndez D, Araya-Maturana R, Millas-Vargas JP, Wehinger S and Fuentes E: In vitro effect of mitochondria-targeted triphenylphosphonium-based compounds (Honokiol, Lonidamine, and Atovaquone) on the platelet function and cytotoxic activity. Front Pharmacol. 13(893873)2022.PubMed/NCBI View Article : Google Scholar | |
Seok YM, Cho HJ, Cha BY, Woo JT and Kim IK: Honokiol attenuates vascular contraction through the inhibition of the RhoA/Rho-kinase signalling pathway in rat aortic rings. J Pharm Pharmacol. 63:1244–1251. 2011.PubMed/NCBI View Article : Google Scholar | |
Onselaer MB, Nagy M, Pallini C, Pike JA, Perrella G, Quintanilla LG, Eble JA, Poulter NS, Heemskerk JWM and Watson SP: Comparison of the GPVI inhibitors losartan and honokiol. Platelets. 31:187–197. 2020.PubMed/NCBI View Article : Google Scholar | |
Elbarbry F and Moshirian N: The modulation of arachidonic acid metabolism and blood pressure-lowering effect of honokiol in spontaneously hypertensive rats. Molecules. 27(3396)2022.PubMed/NCBI View Article : Google Scholar | |
Chi Z, Le TPH, Lee SK, Guo E, Kim D, Lee S, Seo SY and Lee SY, Kim JH and Lee SY: Honokiol ameliorates angiotensin II-induced hypertension and endothelial dysfunction by inhibiting HDAC6-mediated cystathionine γ-lyase degradation. J Cell Mol Med. 24:10663–10676. 2020.PubMed/NCBI View Article : Google Scholar | |
Lv D, Luo M, Yan J, Yang X and Luo S: Protective effect of sirtuin 3 on CLP-induced endothelial dysfunction of early sepsis by inhibiting NF-κB and NLRP3 signaling pathways. Inflammation. 44:1782–1792. 2021.PubMed/NCBI View Article : Google Scholar | |
He A, Yu H, Hu Y, Chen H, Li X, Shen J, Zhuang R, Chen Y, Sasmita BR, Luo M and Lv D: Honokiol improves endothelial function in type 2 diabetic rats via alleviating oxidative stress and insulin resistance. Biochem Biophys Res Commun. 600:109–116. 2022.PubMed/NCBI View Article : Google Scholar | |
Tan Z, Liu H, Song X, Ling Y, He S, Yan Y, Yan J, Wang S, Wang X and Chen A: Honokiol post-treatment ameliorates myocardial ischemia/reperfusion injury by enhancing autophagic flux and reducing intracellular ROS production. Chem Biol Interact. 307:82–90. 2019.PubMed/NCBI View Article : Google Scholar | |
Lv L, Kong Q, Li Z and Zhang Y, Chen B, Lv L and Zhang Y: Honokiol provides cardioprotection from myocardial ischemia/reperfusion injury (MI/RI) by inhibiting mitochondrial apoptosis via the PI3K/AKT signaling pathway. Cardiovasc Ther. 2022(1001692)2022.PubMed/NCBI View Article : Google Scholar | |
Wang Y, Zhang ZZ, Wu Y, Zhan J, He XH and Wang YL: Honokiol protects rat hearts against myocardial ischemia reperfusion injury by reducing oxidative stress and inflammation. Exp Ther Med. 5:315–319. 2013.PubMed/NCBI View Article : Google Scholar | |
Pillai VB, Samant S, Sundaresan NR, Raghuraman H, Kim G, Bonner MY, Arbiser JL, Walker DI, Jones DP, Gius D and Gupta MP: Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3. Nat Commun. 6(6656)2015.PubMed/NCBI View Article : Google Scholar | |
Zhong C, Wang C, Li W, Li W, Chen X, Guo J, Feng Y and Wu X: A derivative of honokiol HM568 has an anti-neuroinflammatory effect in Parkinson's disease. Chem Biol Interact. 403(111212)2024.PubMed/NCBI View Article : Google Scholar | |
Qiu L, Xu R, Wang S, Li S, Sheng H, Wu J and Qu Y: Honokiol ameliorates endothelial dysfunction through suppression of PTX3 expression, a key mediator of IKK/IkappaB/NF-ĸB, in atherosclerotic cell model. Exp Mol Med. 47(e171)2015.PubMed/NCBI View Article : Google Scholar | |
Lin X, Zhang H, Chu Y, Zhang Y, Xu C, Xie H, Ruan Q, Lin J, Huang CK and Chai D: Honokiol ameliorates angiotensin II-induced cardiac hypertrophy by promoting dissociation of the Nur77-LKB1 complex and activating the AMPK pathway. J Cell Mol Med. 28(e18028)2024.PubMed/NCBI View Article : Google Scholar | |
Zhu J, Ning RB, Lin XY, Chai DJ, Xu CS, Xie H, Zeng JZ and Lin JX: Retinoid X receptor agonists inhibit hypertension-induced myocardial hypertrophy by modulating LKB1/AMPK/p70S6K signaling pathway. Am J Hypertens. 27:1112–1124. 2014.PubMed/NCBI View Article : Google Scholar | |
Cai X, Jiang X, Zhao M, Su K, Tang M, Hong F, Ye N, Zhang R, Li N, Wang L, et al: Identification of the target protein and molecular mechanism of honokiol in anti-inflammatory action. Phytomedicine. 109(154617)2023.PubMed/NCBI View Article : Google Scholar | |
Huang PP, Fu J, Liu LH, Wu KF, Liu HX, Qi BM, Liu Y and Qi BL: Honokiol antagonizes doxorubicin-induced cardiomyocyte senescence by inhibiting TXNIP-mediated NLRP3 inflammasome activation. Int J Mol Med. 45:186–194. 2020.PubMed/NCBI View Article : Google Scholar | |
Guo Y, Liu N, Zhang J, Yang J, Kang W, Lu T, Guo Y and Yao Y: Application of honokiol in preparation of medicine for treating myocardial infarction. China Patent CN114588136A. Filed April 7, 2022; issued June 7, 2022. | |
Miao GP, Han J, Zhang JF, Tong G and Wu Y: A kind of active ingredient of Chinese herbs composition for treating cardiovascular and cerebrovascular disease China Patent CN109045045A. Filed August 14, 2018; issued December 21, 2018. | |
Li WM, Feng YF, Zhu HN, Yu R and Li Y: A kind of compound and its preparation method and application. China Patent CN108033927A. Filed October 27, 2017; issued May 15, 2018. | |
Guang B, Yang T, Dong RH, Peng X, Liu I, Xie J, Qin L, Xu G and Liao X: The new application of honokiol derivative. China Patent CN109771431A. Filed January 31, 2019; issued May 21, 2019. | |
Zhang P, Liu Y, Zhang Y and Gu J: Application of magnolol or aromatic ring amino substituted derivative of honokiol in preparation of anti-myocardial ischemia drugs and pharmaceutical composition. China Patent CN115581690A. Filed July 5, 2021; issued January 10, 2023. | |
Xian X, Zhao X, Zhou X, Liu H, Li C, Wu X, Chen Y, Ye K, Yang H, Li M, et al: Honokiol attenuates oxidative stress and vascular calcification via the upregulation of heme oxygenase-1 in chronic kidney disease. Toxicol Appl Pharmacol. 499(117318)2025.PubMed/NCBI View Article : Google Scholar |