Kurarinone: From chemistry to pharmacological values–A review

Articles in Press

Document Type : Review Article

Authors

1 Department of Chemistry, Vietnam National University of Forestry, Xuan Mai, Hanoi 10000, Vietnam

2 Faculty of Education, Ha Tinh University, Cam Binh, Hatinh 480000, Vietnam

3 Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Nghia Do, Hanoi 10000, Vietnam

10.22038/ijbms.2026.92633.19997

Abstract

Kurarinone (KRN) is a major prenylated flavanone isolated from Sophora flavescens, widely recognized for its diverse pharmacological activities and growing therapeutic relevance. This review provides a comprehensive and updated overview of KRN, encompassing its botanical occurrence, phytochemical characteristics, structural elucidation, and biotransformation pathways, alongside in-depth analyses of its pharmacological activities, molecular mechanisms, and pharmacokinetic behavior across experimental models. A structured literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar using the keywords “Kurarinone,” “Sophora flavescens flavonoids,” “prenylated flavanones,” and related terms. Studies reporting natural occurrence, chemical isolation, biotransformation, physicochemical properties, pharmacological mechanisms, pharmacokinetics, and toxicity were included. In vitro and in vivo experimental studies and clinical disease models were prioritized, while non-primary sources and incomplete reports were excluded. KRN exhibited a broad pharmacological profile, including anticancer, anti-inflammatory, antibacterial, antiviral, and organ-protective effects, driven by its capacity to orchestrate multiple signaling networks. Mechanistically, KRN regulated pivotal molecular pathways, such as NF-κB, MAPK, JAK2/STAT3, PI3K/Akt, Nrf2/HO-1, and caspase-dependent apoptosis, thereby modulating inflammatory responses, oxidative stress, and cell apoptosis. Biotransformation studies reveal rapid conversion into glucuronide and hydroxyl conjugates. pharmacokinetic evidence indicated poor oral bioavailability (less than 50%), extensive Phase II metabolism, and tissue-specific accumulation, particularly in hepatic compartments. While these characteristics may contribute to therapeutic action, dose-dependent hepatotoxicity has been reported, highlighting critical translational challenges and the need for formulation advances and safety optimization. Future research should emphasize pharmacokinetic-pharmacodynamic modeling, nano-delivery systems, toxicity profiling, and well-designed clinical studies to support its translational development.

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Main Subjects

References

1. Wang ZL, Wang S, Kuang Y, Hu ZM, Qiao X, Ye M. A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis. Pharm Biol 2018; 56: 465-484.
2. Janabi AHM, Kamboh AA, Saeed M, Xiaoyu L, Bibi L, Majeed F, et al. Flavonoid-rich foods (FRF): A promising nutraceutical approach against lifespan-shortening diseases. Iran J Basic Med Sci 2020; 23: 140-153.
3. Kang T-H, Jeong S-J, Ko W-G, Kim N-Y, Lee B-H, Inagaki M, et al. Cytotoxic lavandulyl flavanones from Sophora flavescens. J Nat Prod 2000; 63: 680-681.
4. Liu P, Deng T, Ye C, Qin Z, Hou X, Wang J. Identification of kurarinone by LC/MS and investigation of its thermal stability. J Chil Chem Soc 2009; 54: 80-82.
5. Berghe WV, De Naeyer A, Dijsselbloem N, David J-P, De Keukeleire D, Haegeman G. Attenuation of ERK/RSK2-driven NFκB gene expression and cancer cell proliferation by kurarinone, a lavandulyl flavanone isolated from Sophora flavescens Ait. roots. Endocr Metab Immune Disord Drug Targets 2011; 11: 247-261 
6. Min JS, Kim DE, Jin YH, Kwon S. Kurarinone inhibits HCoV-OC43 infection by impairing the virus-induced autophagic flux in MRC-5 human lung cells. J Clin Med 2020; 9: 2230.
7. Yamahara J, Kobayashi G, Iwamoto M, Chisaka T, Fujimura H, Takaishi Y, et al. Vasodilatory active principles of Sophora flavescens root. J Ethnopharmacol 1990; 29: 79-85.
8. Yazal T, Lee PY, Chen PR, Chen IC, Liu PL, Chen YR, et al. Kurarinone exerts anti-inflammatory effect via reducing ROS production, suppressing NLRP3 inflammasome, and protecting against LPS-induced sepsis. Biomed Pharmacother 2023; 167: 115619.
9. Tang KT, Lin CC, Lin SC, Wang JH, Tsai SW. Kurarinone attenuates collagen-induced arthritis in mice by inhibiting Th1/Th17 cell responses and oxidative stress. Int J Mol Sci 2021; 22: 4002.
10. Liu L, Wang Z, Qi Y, Huang A, He C, Zhan X, et al. Kurarinone alleviates cGAS-STING-triggered inflammatory diseases by targeting STING. Phytother Res 2025; 39: 3450-3465.
11. Ma C. Kurarinone activates the Nrf-2/HO-1 signaling pathway and alleviates high glucose-induced ferroptosis in HK2 cells. J Clin Biochem Nutr 2025; 77: 30-36.
12. Prajapati KS, Kumar S. Kurarinone targets JAK2-STAT3 signaling in colon cancer-stem-like cells. Cell Biochem Funct 2024; 42: e3959.
13. Wang L, Lu G, Wang F, Tao Y, Dai C. Kurarinone attenuates LPS-Induced pneumonia by inhibiting MAPK and NF-kappaB signaling pathways. APMIS 2025; 133: e70013.
14. Chung TW, Lin CC, Lin SC, Chan HL, Yang CC. Antitumor effect of kurarinone and underlying mechanism in small cell lung carcinoma cells. Onco Targets Ther 2019; 12: 6119-6131.
15. Nishikawa S, Itoh Y, Tokugawa M, Inoue Y, Nakashima KI, Hori Y, et al. Kurarinone from Sophora flavescens roots triggers ATF4 activation and cytostatic effects through PERK phosphorylation. Molecules 2019; 24: 3110.
16. Hao L, Luo H, Tan W, Zhong J, Xiong J, Liu Z, et al. Kurarinone mitigates LPS-induced inflammatory osteolysis by inhibiting osteoclastogenesis through the reduction of ROS levels and suppression of the PI3K/AKT signaling pathway. Inflammation 2025; 48: 29856-3005.
17. Chen C, Guo SM, Liu B. A randomized controlled trial of kurorinone versus interferon-alpha2a treatment in patients with chronic hepatitis B. J Viral Hepat 2000; 7: 225-229.
18. Lei H, Niu T, Song H, Bai B, Han P, Wang Z, et al. Comparative transcriptome profiling reveals differentially expressed genes involved in flavonoid biosynthesis between biennial and triennial Sophora flavescens. Ind Crop Prod 2021; 161: 113217.
19. Zhou J, Zhang L, Li Q, Jin W, Chen W, Han J, et al. Simultaneous optimization for ultrasound-assisted extraction and antioxidant activity of flavonoids from Sophora flavescens using response surface methodology. Molecules 2018; 24: 112.
20. Olennikov D. Densitometric HPTLC analysis of kurarinone and sophoraflavanone G in Sophora flavescens root. J Planar Chromat 2011; 24: 121-124.
21. Kim JS, Sang MK, Min CK, Suk WK, Byung HU. Fast identification of flavonoids in the roots of Sophora flavescens by on-flow LC-NMR. J Med Plants Res 2010; 4: 2452-2459.
22. Hatayama K, Komatsu M. Studies on the constituents of Sophora species. V. Constituents of the root of Sophora angustifolia SIEB. et ZUCC. (2). Chem Pharm Bull 1971; 19: 2126-2131.
23. Tan RX, Wolfender JL, Zhang LX, Ma WG, Fuzzati N, Marston A, et al. Acyl secoiridoids and antifungal constituents from Gentiana macrophylla. Phytochemistry 1996; 42: 1305-1313.
24. Jung MJ, Kang SS, Jung HA, Kim GJ, Choi JS. Isolation of flavonoids and a cerebroside from the stem bark of Albizzia julibrissin. Arch Pharm Res 2004; 27: 593-599.
25. Xinhluan W, Zhen L, Zhang G, Wong MS, Qin L, Yao X. Osteogenic effects of flavonoid aglycones from an osteoprotective fraction of Drynaria fortunei-an in vitro efficacy study. Phytomedicine 2011; 18: 868-872.
26. Ming CH, Cheng ZH, Chen DF. Qualitative and quantitative analysis of flavonoids in Sophora tonkinensis by LC/MS and HPLC. Chin J Nat Med 2013; 11: 690-698.
27. Sahlan M, Devina A, Pratami DK, Situmorang H, Farida S, Munim A, et al. Anti-inflammatory activity of Tetragronula species from Indonesia. Saudi J Biol Sci 2019; 26: 1531-1538.
28. Shi YQ, Xin XL, Yuan QP, Wang CY, Zhang BJ, Hou J, et al. Microbial biotransformation of kurarinone by Cunninghamella echinulata AS 3.3400. J Asian Nat Prod Res 2012; 14: 1002-1007.
29. Quang TH, Nhiem NX, Anh HLT, Tai BH, Van Minh C, Kim YH, et al. Flavonoids from the roots of Sophora flavescens. Vietnam J Chem 2015; 53: 77-81.
30. Zhang WM, Li RF, Qiu JF, Zhang ZY, Wang HB, Bian L, et al. Determination of kurarinone in rat plasma by UPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2015; 986-987: 31-34.
31. Naeyer AD, Vanden Berghe W, Pocock V, Milligan S, Haegeman G, De Keukeleire D. Estrogenic and anticarcinogenic properties of kurarinone, a lavandulyl flavanone from the roots of Sophora flavescens. J Nat Prod 2004; 67: 1829-1832.
32. Jiang P, Liang Y, Cui X, Zhang Y, Peng C, Wang Q. Mechanistic research on the anti-hepatocellular carcinoma effect of kurarinone based on network pharmacology and experimental validation. Eur J Integr Med 2023; 62: 102280.
33. Kim SC, Lee JR, Park SJ. Cytoprotective effects of kurarinone against tert-butyl hydroperoxide-induced hepatotoxicity in HepG2 Cells. Herb Formula Sci 2018; 26: 251-259.
34. Kwon M, Oh T, Jang M, Kim GH, Kim JH, Ryu HW, et al. Kurarinone induced p53-independent G0/G1 cell cycle arrest by degradation of K-RAS via WDR76 in human colorectal cancer cells. Eur J Pharmacol 2022; 923: 174938.
35. Kushwaha PP, Shuaib M, Prajapati KS, Singh AK, Kulharia M, Kumar S, et al. Kurarinone, a natural notch signaling inhibitor and modulator of breast cancer stemness. Cancer Res 2023; 83: 4955-4955.
36. Li W, Yin X, Yan Y, Liu C, Li G. Kurarinone attenuates hydrogen peroxide-induced oxidative stress and apoptosis through activating the PI3K/Akt signaling by upregulating IGF1 expression in human ovarian granulosa cells. Environ Toxicol 2023; 38: 28-38.
37. Zhou W, Cao A, Wang L, Wu D. Kurarinone synergizes TRAIL-induced apoptosis in gastric cancer cells. Cell Biochem Biophys 2015; 72: 241-249.
38. Nishikawa S, Inoue Y, Hori Y, Miyajima C, Morishita D, Ohoka N, et al. Anti-inflammatory activity of kurarinone involves induction of HO-1 via the KEAP1/Nrf2 pathway. Antioxidants (Basel) 2020; 9: 842.
39. Ali MY, Choi JS, Huang S, Antunes FTT, Jung HA, Zamponi GW. Kurarinone, a lavandulyl flavanone from Sophora flavescens, inhibits t-type calcium channels and exerts analgesic effects in a mouse model of inflammatory pain. ACS Food Sci Technol 2024; 4: 2355-2364.
40. Park S, Kim J, Shin Y-K, Kim K-Y. Antimicrobial activity of 4-hydroxyderricin, sophoraflavanone G, acetylshikonin, and kurarinone against the bee pathogenic bacteria Paenibacillus larvae and Melissococcus plutonius. J Apic Res 2020; 60: 118-122.
41. Yamaki M, Kashihara M, Takagi S. Activity of Ku Shen compounds against Staphylococcus aureus and Streptococcus mutans. Phytother Res 1990; 4: 235-236.
42. Chen L, Cheng X, Shi W, Lu Q, Go VL, Heber D, et al. Inhibition of growth of Streptococcus mutans, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci by kurarinone, a bioactive flavonoid isolated from Sophora flavescens. J Clin Microbiol 2005; 43: 3574-3575.
43. Weng Z, Zeng F, Wang M, Guo S, Tang Z, Itagaki K, et al. Antimicrobial activities of lavandulylated flavonoids in Sophora flavences against methicillin-resistant Staphylococcus aureus via membrane disruption. J Adv Res 2024; 57: 197-212.
44. An JX, Wang R, Li AP, Zhang W, Nan Z, Jiang WQ, et al. Prenylated Flavonoids isolated from the root of Sophora flavescens as potent antifungal agents against Botrytis cinerea. J Agric Food Chem 2024; 72: 19618-19628.
45. Sato S, Takeo J, Aoyama C, Kawahara H. Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg Med Chem 2007; 15: 3445-3449.
46. Lee S, Chae MR, Lee BC, Kim YC, Choi JS, Lee SW, et al. Urinary bladder-relaxant effect of kurarinone depending on potentiation of large-conductance Ca2+-activated K+ channels. Mol Pharmacol 2016; 90: 140-150.
47. Lee SW, Lee HS, Nam JY, Kwon OE, Baek JA, Chang JS, et al. Kurarinone isolated from Sophora flavescens Ait inhibited MCP-1-induced chemotaxis. J Ethnopharmacol 2005; 97: 515-519.
48. Prajapati R, Seong SH, Paudel P, Park SE, Jung HA, Choi JS. In vitro and in silico characterization of kurarinone as a dopamine D(1A) receptor antagonist and D(2L) and D(4) receptor agonist. ACS Omega 2021; 6: 33443-33453.
49. Xie L, Gong W, Chen J, Xie HW, Wang M, Yin XP, et al. The flavonoid kurarinone inhibits clinical progression of EAE through inhibiting Th1 and Th17 cell differentiation and proliferation. Int Immunopharmacol 2018; 62: 227-236.
50. Jia ZQ, Zuo C, Yue WF. Kurarinone alleviates hemin-induced neuroinflammation and microglia-mediated neurotoxicity by shifting microglial M1/M2 polarization via regulating the IGF1/PI3K/Akt signaling. Kaohsiung J Med Sci 2022; 38: 1213-1223.
51. Wu G, Wu Y. Neuroprotective effect of Kurarinone against corticosterone-induced cytotoxicity on rat hippocampal neurons by targeting BACE1 to activate P13K-AKT signaling - A potential treatment in insomnia disorder. Pharmacol Res Perspect 2023; 11: e01132.
52. Sun CP, Zhou JJ, Yu ZL, Huo XK, Zhang J, Morisseau C, et al. Kurarinone alleviated Parkinson’s disease via stabilization of epoxyeicosatrienoic acids in animal model. Proc Natl Acad Sci U S A 2022; 119: e2118818119.
53. Park SJ, Kim TH, Lee K, Kang MA, Jang HJ, Ryu HW, et al. Kurarinone attenuates BLM-induced pulmonary fibrosis via inhibiting TGF-beta signaling pathways. Int J Mol Sci 2021; 22: 8388.
54. Dong T, Zhao D, Jiang S, Gu Y, Wang C, Yang Q, et al. Kurarinone protects against renal injury and fibrosis after unilateral ureteral obstruction through enhancement of the Nrf-2 signaling pathway. J Mol Histol 2025; 56: 286.
55. Long L, Luo H, Wang Y, Gu J, Xiong J, Tang X, et al. Kurarinone, a flavonoid from Radix Sophorae Flavescentis, inhibits RANKL-induced osteoclastogenesis in mouse bone marrow-derived monocyte/macrophages. Naunyn Schmiedebergs Arch Pharmacol 2024; 397: 7071-7087.
56. Xiong Z, Yang H. Unraveling the pharmacological intricacies of kurarinone in osteoporosis: Insights from a network pharmacology approach. Pharmacog Mag 2024; 20: 1350-1358.
57. Xu X, Dong Q, Zhong Q, Xiu W, Chen Q, Wang J, et al. The flavonoid kurarinone regulates macrophage functions via aryl hydrocarbon receptor and alleviates intestinal inflammation in irritable bowel syndrome. J Inflamm Res 2021; 14: 4347-4359.
58. Pan Y, Deng B, Wang T, Zhou Z, Wang J, Gao C, et al. Kurarinone ameliorates intestinal mucosal inflammation via regulating T cell immunity. Front Immunol 2025; 16: 1587479.
59. Li Z, Lin M, Li Y, Shao J, Huang R, Qiu Y, et al. Total flavonoids of Sophora flavescens and kurarinone ameliorated ulcerative colitis by regulating Th17/Treg cell homeostasis. J Ethnopharmacol 2022; 297: 115500.
60. Li W, Li Y, Qiu Y, Huang R, Niu J, Chen J, et al. Kurarinone and Nor-kurarinone inhibit NLRP3 inflammasome activation and regulate macrophage polarization against ulcerative colitis. Int Immunopharmacol 2025; 157: 114758.
61. Gu C, Liu Y, Lv J, Zhang C, Huang Z, Jiang Q, et al. Kurarinone regulates Th17/Treg balance and ameliorates autoimmune uveitis via Rac1 inhibition. J Adv Res 2025; 69: 381-398.
62. Kim BH, Na KM, Oh I, Song IH, Lee YS, Shin J, et al. Kurarinone regulates immune responses through regulation of the JAK/STAT and TCR-mediated signaling pathways. Biochem Pharmacol 2013; 85: 1134-1144.
63. Ha NM, Son NT. Health benefits of fraxetin: From chemistry to medicine. Arch Pharm 2024; 357: e2400092.
64. Thoa NT, Son NT. Scutellarein: A review of chemistry and pharmacology. J Pharm Pharmacol 2025; 77: 352-370.
65. Ni HTN, Linh NN, Nhung PTT, Dao PTB, Manh VQ, Son NT. Icariside II: Natural occurrence, biotransformation, pharmacological activity, synthetic modification, pharmacokinetics, and bioavailability. J Pharm Pharmacol 2025; 77: 1491-1512.
66. Prete M, Dammacco R, Fatone MC, Racanelli V. Autoimmune uveitis: Clinical, pathogenetic, and therapeutic features. Clin Exp Med 2016; 16: 125-136.
67. YuQing G, GuoGuang S. Changes of peripheral blood T lymphocyte subsets and serum cytokine levels in patients with chronic hepatitis B receiving lamivudine and kurorinone treatment. J Clin Hepatol 2013; 16: 229-231.
68. He X, Zhang M, Yang Z, Ji R, Gong D, Li Y, et al. Natural parkin modulators drive mitophagy and overcome metabolic dysfunction-associated fatty liver disease. Ind Crop Prod 2025; 233: 121404.
69. Huang Y, Lin H, Chen Y, Huang X. Pharmacokinetic and bioavailability study of kurarinone in dog plasma by UHPLC-MS/MS. Biomed Chromatogr 2020; 34: e4945.
70. Yang Z, Zhang W, Li X, Shan B, Liu J, Deng W. Determination of sophoraflavanone G and kurarinone in rat plasma by UHPLC-MS/MS and its application to a pharmacokinetic study. J Sep Sci 2016; 39: 4344-4353.
71. Liu Y, Mo ZX, Wang CG, Huang R, Wang F, Chen L. Identification of metabolites of kurarinone from Sophora flavescens Ait in rat urine by ultra-performance liquid chromatography with linear ion trap orbitrap mass spectrometry. Trop J Pharm Res 2016; 15: 1299-1305.
72. Zhang X, Jiang P, Chen P, Cheng N. Metabolism of kurarinone by human liver microsomes and its effect on cytotoxicity. Pharm Biol 2016; 54: 619-627.
73. Qin Y, Zhu Y, Xue X, Zhou G, Li H, Wang J. An in vitro study for evaluating permeability and metabolism of kurarinone. Evid Based Complement Alternat Med 2020; 2020: 5267684.
74. Jiang P, Zhang X, Huang Y, Cheng N, Ma Y. Hepatotoxicity induced by Sophora flavescens and hepatic accumulation of kurarinone, a major hepatotoxic constituent of Sophora flavescens in rats. Molecules 2017; 22; 1809.
Iranian Journal of Basic Medical Sciences

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Available Online from 21 April 2026

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