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Current advances on the therapeutic potential of scutellarin: an updated review |
| Yifei Xie1, Guotong Sun3, Yue Tao2, Wen Zhang1, Shiying Yang2, Li Zhang2, Yang Lu2, Guanhua Du1 |
1 Beijing City Key Laboratory of Drug Target and Screening Research, National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing 100050, China;
2 Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
3 Pharmaceutical College of Henan University, Kaifeng 475004, China |
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Abstract Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed.
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| Keywords
Scutellarin
Pharmacological action
Experimental study
Model
Mechanism
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| Fund:This funding was supported by National Science Foundation of China (22278443); the Key R&D Program of Shan Dong Province (2021ZDSYS26); Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2022-I2M-1-015, 2022-I2M-1-005);Chinese Pharmacopoeia Commission Drug Standard Promoting Fund (2023Y11); Jiangsu Provincial Agricultural Science and Technology Independent Innovation Fund (2202GH15); Special Fund for Scientific Innovation Strategy-Construction of High-level Academy of Agriculture Science (2022D04016); National Natural Science Foundation of China (882141204). |
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Corresponding Authors:
Li Zhang,E-mail:zhangl@imm.ac.cn;Yang Lu,E-mail:luy@imm.ac.cn;Guanhua Du,E-mail:dugh@imm.ac.cn
E-mail: zhangl@imm.ac.cn;luy@imm.ac.cn;dugh@imm.ac.cn
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Issue Date: 14 June 2024
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1. Qu J, Wang Y, Luo G. Determination of scutellarin in Erigeron breviscapus extract by liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2001;919(2):437–41.
2. Malikov V, Yuldashev M. Phenolic compounds of plants of the Scutellaria Genus. Distribution, structure, and properties. Chem Nat Compd. 2002;38(5):473–519.
3. Xin C, Su Y, Guo L, et al. Phenolic constituents from Conyza sumatrensis. Biochem Syst Ecol. 2008;36(3):216–8.
4. Formisano C, Rigano D, et al. Flavonoids in Subtribe Centaureinae (Cass) Dumort (Tribe Cardueae, Asteraceae): distribution and 13C-NMR Spectral Data. Chem Biodivers. 2012;9:2096–158.
5. Hua Y, Wang H. Chemical Components of Anaphalis sinica Hance. J Chin Chem Soc-Taip. 2004;51(2):409–15.
6. Hasibuan P, Harahap U, Sitorus P, et al. The anticancer activities of Vernonia amygdalina Delile. Leaves on 4T1 breast cancer cells through phosphoinositide 3-kinase (PI3K) pathway. Heliyon. 2020;6(7):e04449.
7. Liu C, Gao M, Guo B. Plant regeneration of Erigeron breviscapus (vant.) Hand. Mazz. and its chromatographic fingerprint analysis for quality control. Plant Cell Rep. 2008;27(1):39–45.
8. Wang A, Cheng G. Determination of Scutellarin in Herba scutellariae Barbata by HPLC. Guangzhou Chem Ind. 2017;45(07):94–5+113.
9. Hong C, Chen J, Lu M, et al. Simultaneous determination of scutellarin and baicalin in the flowers of Scutellaria Baicalensis Georgi by HPLC. Chin J Mod Appl Pharm. 2020;37(11):1320–3.
10. Hu Y, Zhang H, Zhang Z. Determination flavonoids and scutellarin in herbs of Erigeron genu. Chin J Pharm Ana. 2005;25(01):21–3.
11. Liu H, Liu B, Wang G, et al. Studies on the chemical constituents from Conyza canadensis. Chin Med Mat. 2011;34(05):718–20.
12. Fan S, Sui H, Chen X, et al. Determination of phenolic parts in Thymusquinquecostatus Celak by HPLC and UV-Vis. J Beijing Univ TCM. 2019; 42(10):854–61.
13. Gaihre Y, Tsuge K, Hamajima H, et al. The contents of polyphenols in Perilla frutescens (L.) Britton var frutescens (Egoma) leaves are determined by vegetative stage, spatial leaf position, and timing of harvesting during the day. J Oleo Sci. 2021;70(6):855–59.
14. Cattaneo L, Cicconi R, Mignogna G, et al. Anti-proliferative effect of Rosmarinus officinalis L. extract on human melanoma A375 cells. PLoS ONE. 2015;10(7):e0132439.
15. Pisarev D, Novikov O, Novikova M, et al. Flavonoid composition of Juniperus oblonga Bieb. Bull Exp Biol Med. 2011;150(6):714–7.
16. Han X, Wang S, Yang X, et al. Analysis of plasma migration components in Patrinia villosa (Thunb.) Juss. effective parts by UPLC-Q-TOF-MS. Biomed Chromatogr. 2020;34(1):e4701.
17. Wang X, Wei L, Wang L, et al. Scutellarin potentiates vancomycin against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus through dual inhibition of sortase A and caseinolytic peptidase P. Biochem Pharmacol. 2022;199:114982.
18. Fang H, Zhao X, Zhang M, et al. Beneficial effects of flavonoids on cardiovascular diseases by influencing NLRP3 inflammasome. Inflammopharmacology. 2023;31:1–15.
19. Xu H, Wang E, Chen F, et al. Neuroprotective phytochemicals in experimental ischemic stroke: mechanisms and potential clinical applications. Oxid Med Cell Longev. 2021;2021:1–45.
20. Bangar A, Khan H, Kaur A, et al. Understanding mechanistic aspect of the therapeutic role of herbal agents on neuroplasticity in cerebral ischemicreperfusion injury[J]. J Ethnopharmacol. 2023:117153.
21. Tuli H, Bhushan S, Kumar A, et al. Autophagy Induction by Scutellaria Flavones in Cancer: Recent Advances. Pharmaceuticals. 2023;16(2):302.
22. Subedi L, Gaire B. Phytochemicals as regulators of microglia/macrophages activation in cerebral ischemia. Pharmacol Res. 2021;165:105419.
23. Chen H, Jia W, Li H, et al. Scutellarin exerts anti-inflammatory effects in activated microglia/brain macrophage in cerebral ischemia and in activated BV-2 microglia through regulation of MAPKs signaling pathway. Neuromolecular Med. 2020;22(2):264–77.
24. Niu R, Xiong L, Zhou H, et al. Scutellarin ameliorates neonatal hypoxicischemic encephalopathy associated with GAP43-dependent signaling pathway. Chin Med. 2021;16(1):105.
25. Hung Y, Liu Y, Wu B, et al. Cinaciguat prevents postnatal closure of ductus arteriosus by vasodilation and anti-remodeling in neonatal rats. Front Physiol. 2021;12:661171.
26. Lorigo M, Quintaneiro C, Maia C, et al. UV-B filter octylmethoxycinnamate impaired the main vasorelaxant mechanism of humanumbilical artery. Chemosphere. 2021;277:130302.
27. Abdallah H, Hassan N, El-Halawany A, et al. Major flavonoids from Psiadia punctulata produce vasodilation via activation of endothelial dependent NO signaling. J Adv Res. 2020;24:273–9.
28. Shen Z, Zhang Z, Wang X, et al. VEGFB-VEGFR1 ameliorates Ang IIinduced cardiomyocyte hypertrophy through Ca2+-mediated PKG I pathway. J Cell Biochem. 2018;119(2):1511–20.
29. Chen Y, Chen C, Li M, et al. Scutellarin reduces cerebral ischemia reperfusion injury involving in vascular endothelium protection and PKG signal. Nat Prod Bioprospect. 2021;11(6):659–70.
30. Deng M, Sun J, Peng L, et al. Scutellarin acts on the AR-NOX axis to remediate oxidative stress injury in a mouse model of cerebral ischemia/reperfusion injury. Phytomedicine. 2022;103:154214.
31. Meng Z, Wu J, Zhu Y, et al. Revealing the common mechanisms of scutellarin in angina pectoris and ischemic stroke treatment via a network pharmacology Approach. Chin J Integr Med. 2021;27(1):62–9.
32. Jia Q, Chen H, Qi Z, et al. Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway. Sci Rep-Uk. 2023;13(1):1–11.
33. Xie X, Wang F, Ge W, et al. Scutellarin attenuates oxidative stress and neuroinflammation in cerebral ischemia/reperfusion injury through PI3K/Aktmediated Nrf2 signaling pathways. Eur J Pharmacol. 2023;957:175979.
34. Zhang Y, Zhang Z, Wang J, et al. Scutellarin alleviates cerebral ischemia/reperfusion by suppressing oxidative stress and inflammatory responses via MAPK/NF‐κB pathways in rats. Environ Toxicol. 2022;37(12):2889–96.
35. Wang C, Liu Y, Liu X, et al. Scutellarin alleviates ischemic brain injury in the acute phase by affecting the activity of neurotransmitters in neurons. Molecules. 2023;28(7):3181.
36. Chen H, Yang L, Zhang X, et al. Scutellarin acts via MAPKs pathway to promote M2 polarization of microglial cells. Mol Neurobiol. 2023;60(8):4304–23.
37. Zhang T, Wang K, Fan H, et al. Ameliorative effect of scutellarin on acute alcohol brain injury in mice. J Zhejiang Univ-Sc B. 2022;23(3):258–64.
38. Li J, Song Z , Hou X. Scutellarin ameliorates ischemia/reperfusion injury induced cardiomyocyte apoptosis and cardiac dysfunction via inhibition of the cGAS STING pathway. Exp Ther Med. 2023;25(4):1–9.
39. Zhou L, Han Y, Yang Q, et al. Scutellarin attenuates doxorubicin-induced oxidative stress, DNA damage, mitochondrial dysfunction, apoptosis and autophagy in H9c2 cells, cardiac fibroblasts and HUVECs. Toxicol In Vitro. 2022;82:105366.
40. Wang W, Liu X, Ding Y, et al. Scutellarin Protects Myocardial Ischemia-Reperfusion Injury ERK1/2-CREB Regulated Mitophagy. Pharmacogn Mag. 2023:09731296231199860.
41. Fu Y, Sun S, Sun H, et al. Scutellarin exerts protective effects against atherosclerosis in rats by regulating the Hippo-FOXO3A and PI3K/AKT signaling pathways. J Cell Physiol. 2019;234(10):18131–45.
42. Su Y, Fan X, Li S, et al. Scutellarin Improves Type 2 Diabetic Cardiomyopathy by Regulating Cardiomyocyte Autophagy and Apoptosis. Dis Markers. 2022;2022:3058354.
43. Huo Y, Mijiti A, Cai R, et al. Scutellarin alleviates type 2 diabetes (HFD/low dose STZ)-induced cardiac injury through modulation of oxidative stress, inflammation, apoptosis and fibrosis in mice. Hum Exp Toxicol. 2021;40(12):S460–74.
44. Qu D, Feng P, Zhang X, et al. Effects of scutellarin on acute myocardial ischemia/reperfusion injury in isolated rat heart. Eur J Inflamm. 2023;21:1721727X231192289.
45. Yang L, Li Z, Fang J. Scutellarin Alleviates Diabetic Retinopathy via the Suppression of Nucleotide-Binding Oligomerization Domain (NOD)-Like Receptor Pyrin Domain Containing Protein 3 Inflammasome Activation. Curr Eye Res. 2023:1–8.
46. Zeng S, Chen L, Sun Q, et al. Scutellarin ameliorates colitis-associated colorectal cancer by suppressing Wnt/β-catenin signaling cascade. Eur J Pharmacol. 2021;906:174253.
47. Guo X, Li R, Cui J, et al. Induction of RIPK3/MLKL-mediated necroptosis by Erigeron breviscapus injection exhibits potent antitum or effect. Front Pharmacol. 2023;14:1219362.
48. Zeng S, Tan L, Sun Q, et al. Suppression of colitis-associated colorectal cancer by scutellarin through inhibiting Hedgehog signaling pathway activity. Phytomedicine. 2022;98:153972.
49. Deng W, Han W, Fan T, et al. Scutellarin inhibits human renal cancer cell proliferation and migration via upregulation of PTEN. Bio med Pharmacother. 2018;107:1505–13.
50. Derynck R, Budi E. Specificity, versatility, and control of TGF-β family signaling. Sci Signal. 2019;12(570):eaav5183.
51. David C, Massagué J. Contextual determinants of TGFβ action in development, immunity and cancer. Nat Rev Mol Cell Biol. 2018;19(7):419–35.
52. Yao Y, Yuan Y, Lu Z, et al. Effects of Nervilia fordii Extract on Pulmonary Fibrosis Through TGF-β/Smad Signaling Pathway. Front Pharmacol. 2021;12:659627.
53. Zhang G, Chen W, Li X, et al. Scutellarin-induced A549 cell apoptosis depends on activation of the transforming growth factor-β1/smad2/ROS/caspase-3 pathway. Open Life Sci. 2021;16(1):961–8.
54. He G, Xing D, Jin D, et al. Scutellarin improves the radiosensitivity of nonsmall cell lung cancer cells to iodine-125 seeds via downregulating the AKT/mTOR pathway. Thorac Cancer. 2021;12(17): 2352–9.
55. Sun C, Zhu Y, Li X, et al. Scutellarin Increases Cisplatin-Induced Apoptosis and Autophagy to Overcome Cisplatin Resistance in Non-small Cell Lung Cancer via ERK/p53 and c-met/AKT Signaling Pathways. Front Pharmacol. 2018;9:92.
56. Wang F, Bao M, Xu J, et al. Scutellarin inhibits the glioma cell proliferation by downregulating BIRC5 to promote cell apoptosis. J Cell Mol Med. 2023; 27(14):1975–87.
57. Du J, Li J, Tan J, et al. Scutellarin inhibits glioma cell proliferation by upregulating miR-15a expression. Am J Transl Res. 2023;15(3):2156.
58. Chen Y, Li W. Scutellarin inhibits glioblastoma growth in a dose-dependent manner by suppressing the p63 signaling pathway. Dose-Response. 2023;21(3):15593258231197101.
59. Mei X, Ouyang H, Zhang H, et al. Scutellarin suppresses the metastasis of triple-negative breast cancer via targeting TNFα/TNFR2-RUNX1-triggered G-CSF expression in endothelial cells. Biochem Pharmacol. 2023;217:115808.
60. Mei X, Zhang J, Jia W, et al. Scutellarin suppresses triple-negative breast cancer metastasis by inhibiting TNFα-induced vascular end othelial barrier breakdown. Acta Pharmacol Sin. 2022;43(10):2666–77.
61. Liu F, Zu X, Xie X, et al. Scutellarin Suppresses Patient-Derived Xenograft Tumor Growth by Directly Targeting AKT in Esophageal Squamous Cell Carcinoma. Cancer Prev Res (Phila). 2019;12(12):849–60.
62. Hayashi Y, Maysuo Y, Denda Y, et al. Girdin regulates both migration and angiogenesis in pancreatic cancer cell lines. Oncol Rep. 2023;50(3):1–14.
63. Li L, Zou Y, Wang L, et al. Nanodelivery of scutellarin induces immunogenic cell death for treating hepatocellular carcinoma. Int J Pharmaceut. 2023:123114.
64. Luan H, Huo Z, Zhao Z, et al. Scutellarin, a modulator of mTOR, attenuates hepatic insulin resistance by regulating hepatocyte lipid metabolism via SREBP‐1c suppression. Phytotherapy research. 2020;34(6):1455–66.
65. Gao L, Tang H, Zeng Q, et al. The anti-insulin resistance effect of scutellarin may be related to antioxidant stress and AMPKα activation in diabetic mice. Obes Res Clin Pract. 2020;14(4):368–74.
66. Xi J, Rong Y, Zhao Z, et al. Scutellarin ameliorates high glucose-induced vascular endothelial cells injury by activating PINK1/Parkin-mediated mitophagy. J Ethnopharmacol. 2021;271:113855.
67. Li N, Guo XL, Xu M, et al. Network pharmacology mechanism of Scutellarin to inhibit RGC pyroptosis in diabetic retinopathy. Sci Rep-Uk. 2023;13(1):6504.
68. Fan X, Wang Y, Li X, et al. Scutellarin alleviates liver injury in type 2 diabetic mellitus by suppressing hepatocyte apoptosis in vitro and in vivo. Chin Herb Med. 2023;15:542–8.
69. Huang B, Han R, Tan H, et al. Scutellarin ameliorates diabetic nephropathy via TGF-β1 signaling pathway. Biol Pharm Bull. 2023. https://doi.org/10.1248/bpb.b23-00390.
70. Hu X, Teng S, He J, et al. Pharmacological basis for application of scutellarin in Alzheimer’s disease: antioxidation and antiapoptosis. Mol Med Rep. 2018;18(5):4289–96.
71. Zeng Y, Cui Y, Gu J, et al. Scutellarin mitigates Aβ-induced neurotoxicity and improves behavior impairments in AD mice. Molecules. 2018;23(4):869.
72. Huang X, Xu Y, Sui X, et al. Scutellarein suppresses Aβ-induced memory impairment via inhibition of the NF-κB pathway in vivo and in vitro. Oncol Lett. 2019;17(6):5581–9.
73. Shin J, Kweon K, Kim D, et al. Scutellarin ameliorates learning and memory deficit via suppressing β-amyloid formation and microglial activation in rats with chronic cerebral hypoperfusion. Am J Chin Med. 2018;46(6):1203–23.
74. Sheng N, Zhang Z, Zheng H, et al. Scutellarin rescued mitochondrial damage through ameliorating mitochondrial glucose oxidation via the Pdk-Pdc axis. Adv Sci. 2023;10:2303584.
75. Peng L, Wen L, Shi QF, et al. Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial-mesenchymal transition and inflammation. Cell Death Dis. 2020;11(11):978.
76. Bian H, Wang G, Huang J, et al. Scutellarin protects against lipopolysaccharide-induced behavioral deficits by inhibiting neuroinflammation and microglia activation in rats. Int Immunopharmacol. 2020;88:106943.
77. Ye J, Zeng B, Zhong M, et al. Scutellarin inhibits caspase-11 activation and pyroptosis in macrophages via regulating PKA signaling. Acta Pharm Sin B. 2021;11(1):112–26.
78. Luo Z, Hu Z, Bian Y, et al. Scutellarin attenuates the IL-1β-induced inflammation in mouse chondrocytes and prevents osteoarthritic progression. Front Pharmacol. 2020;11:107.
79. Yang H, Wang Z, Wang L, et al. Scutellarin ameliorates osteoarthritis by protecting chondrocytes and subchondral bone microstructure by inactivating NF-κB/MAPK signal transduction. Biomed Pharmacother. 2022;155:113781.
80. Li J, Wang Q, Zhang X. Scutellarin alleviates complete freund’s adjuvantinduced rheumatoid arthritis in mice by regulating the Keap1/Nrf2/HO-1 pathway. Biocell. 2023;47(6):1307–16.
81. Aksit H, Aksit D, Altun E. Protective effects of scutellarin in experimental colitis in rats. Biotech Histochem. 2023;6(98):432–44.
82. Liu Q, Li X, Ouyang X, et al. Dual effect of glucuronidation of a pyrogalloltype phytophenol antioxidant: a comparison between scutellarein and scutellarin. Molecules. 2018;23(12):3225.
83. Hu X, Wu X, Zhao B, et al. Scutellarin protects human retinal pigment epithelial cells against hydrogen peroxide ( H2O2)-induced oxidative damage. Cell Biosci. 2019;9:12.
84. Wang L, Song J, Liu A, et al. Research progress of the antiviral bioactivities of natural flavonoids. Nat Prod Bioprospect. 2020;10:271–83.
85. Wang X, Wei L, Wang L, et al. Scutellarin potentiates vancomycin against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus through dual inhibition of sortase A and caseinolytic peptidase P. Biochem Pharmacol. 2022;199:114982.
86. Miao Z, Lai Y, Zhao Y, et al. Protective property of scutellarin against liver injury induced by carbon tetrachloride in mice. Front Pharmacol. 2021;12:710692.
87. Dai J, Li C, Zhao L, et al. Scutellarin protects the kidney from ischemia/reperfusion injury by targeting Nrf2. Nephrology. 2022;27(8):690–700.
88. Yang Q, Wang Y, Chen H, et al. Protective activities of scutellarin against alcohol-induced acute kidney injury. Chem Biodivers. 2022;19(11): e202200254.
89. Shahmohammadi A, Golchoobian R, Mirahmadi S, et al. Scutellarin alleviates lipopolysaccharide-provoked septic nephrotoxicity via attenuation of inflammatory and oxidative events and mitochondrial dysfunction. Immunopharm Immunot. 2023;45(3):295–303.
90. Zhu J, Sainulabdeen A, Akers K, et al. Oral scutellarin treatment ameliorates retinal thinning and visual deficits in experimental glaucoma. Front Med (Lausanne). 2021;8:681169.
91. Li G, Guan C, Xu L, et al. Scutellarin ameliorates renal injury via increasing CCN1 expression and suppressing NLRP3 inflammasome activation in hyperuricemic mice. Front Pharmacol. 2020;11:584942.
92. Duan J, Wang J, Zhao Q, et al. Anti-convulsant effects of scutellarein in a PTZ kindling model in mice. Pharmacogn Mag. 2023. https://doi.org/10.1155/2017/5148219.
93. Wang L, Ma Q. Clinical benefits and pharmacology of scutellarin: a comprehensive review. Pharmacol Therapeut. 2018;190:105–27.
94. Li X, Sun S, Jiang G. Research progress on quality control of breviscapine in injection form. Mod Chin Med. 2020;22(06):971–8. |
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