木犀草素的生理作用及制剂研究进展

doi:10.3969/j.issn.1001-1803.2023.04.010

摘要/Abstract

摘要：

木犀草素作为一种天然的黄酮类化合物，是一种可用于化妆品的功效原料，在皮肤上具有抗氧化、抗炎、延缓衰老以及美白作用，但存在溶解性差以及生物利用度低的问题，导致其在化妆品中的应用受到了限制。通过固体分散体、环糊精包合物、磷脂复合物、固体脂质纳米粒、纳米结构脂质体、纳米乳、聚合物胶束等制剂技术可以提高其溶解度和生物利用度，进而发挥良好作用。综述了木犀草素在皮肤上的抗氧化、抗炎、延缓衰老和美白作用通路，以及木犀草素应用于不同制剂技术的研究进展，用以改善木犀草素的溶解度和生物利用度差的问题，同时为进一步促进木犀草素制剂研究及化妆品产品应用提供参考。

关键词: 木犀草素, 生理作用, 化妆品, 制剂

Abstract:

Luteolin is a natural flavonoid compound and can be used as cosmetic raw material. Studies have shown that luteolin can provide hydrogen atoms to react with free radicals to generate stable compounds and enhance the activity of antioxidant enzymes to achieve antioxidant effects. It can also inhibit the expression of inflammatory cytokines and inflammatory mediators by affecting multiple inflammatory signaling pathways. It can also delay aging by inhibiting kinases that affect skin aging and whiten the skin by inhibiting enzymes involved in the synthesis of melanin. However, the solubility and bioavailability of luteolin are poor since it is only slightly soluble both in hot water and in cold water. Its solubility and bioavailability can be improved by preparation technologies such as solid dispersion, cyclodextrin inclusion, phospholipid complexation, formation of solid lipid nanoparticles, nanostructured liposomes, nanomilk and polymer micelles, etc. However, some preparation technologies have the problems of high cost, short shelf life, instability, etc., and further research on the action mechanism of luteolin and related preparations is needed. The physiological action mechanisms of luteolin on the skin, as well as the research progress of its various preparation techniques, were reviewed, which could provide a reference for further preparation research and cosmetic product application.

Key words: luteolin, physiological function, cosmetic, preparation

中图分类号:

TQ658

詹鑫, 徐帆, 祝钧, 何一凡, 裴晓静. 木犀草素的生理作用及制剂研究进展[J]. 日用化学工业（中英文）, 2023, 53(4): 437-444.

Zhan Xin, Xu Fan, Zhu Jun, He Yifan, Pei Xiaojing. Research progress on physiological action and preparations of luteolin[J]. China Surfactant Detergent & Cosmetics, 2023, 53(4): 437-444.

图/表 5

参考文献 47

[1]	Wang Lu. Extraction and purification of luteolin from peanut pod shell, preparation of nanoparticles and design and study of its stable Pickering emulsion[D]. Harbin: Northeast Forestry University, 2020.
[2]	Choi J S, Islam Md N, Ali Md Y, et al. The effects of C-glycosylation of luteolin on its antioxidant, anti-Alzheimer’s disease, anti-diabetic, and anti-inflammatory activities[J]. Archives of Pharmacal Research, 2014, 37(10): 1354-1363. doi: 10.1007/s12272-014-0351-3 pmid: 24988985
[3]	Yan M, Liu Z, Yang H, et al. Luteolin decreases the UVA-induced autophagy of human skin fibroblasts by scavenging ROS[J]. Molecular Medicine Reports, 2016, 14(3): 1986-1992. doi: 10.3892/mmr.2016.5517
[4]	Chen G, Shen H, Zang L, et al. Protective effect of luteolin on skin ischemia-reperfusion injury through an AKT-dependent mechanism[J]. International Journal of Molecular Medicine, 2018, 42(6): 3073-3082. doi: 10.3892/ijmm.2018.3915 pmid: 30280183
[5]	Wölfle U, Esser P R, Simon-Haarhaus B, et al. UVB-induced DNA damage, generation of reactive oxygen species, and inflammation are effectively attenuated by the flavonoid luteolin in vitro and in vivo[J]. Free Radical Biology and Medicine, 2011, 50(9): 1081-1093. doi: 10.1016/j.freeradbiomed.2011.01.027 pmid: 21281711
[6]	McGarry T, Biniecka M, Veale D J, et al. Hypoxia, oxidative stress and inflammation[J]. Free Radical Biology and Medicine, 2018, 125: 15-24. doi: S0891-5849(18)30145-X pmid: 29601945
[7]	Yu Qian, Wu Guanzhong. Research progress on anti-inflammatory mechanism of luteolin[J]. Pharmaceutical Research, 2019, 38(2): 108-111, 119.
[8]	Weng Z, Patel A B, Vasiadi M, et al. Luteolin inhibits human keratinocyte activation and decreases NF-κB induction that is increased in psoriatic skin[J]. PLoS ONE, 2014, 9(2): e90739. doi: 10.1371/journal.pone.0090739
[9]	Zhu Deqiu, Liu Kang, Yi Jiali, et al. Luteolin inhibits inflammatory response and improves insulin sensitivity in the endothelium[J]. Biochimie, 2011, 93(3): 506-512. doi: 10.1016/j.biochi.2010.11.002 pmid: 21081149
[10]	Zhu Shan, Zhao Zhiyue, Wang Zijing, et al. Molecular mechanism of skin age and research progress of chinese medicine on prevention and treatment of skin age[J]. Journal of Tianjin University of Traditional Chinese Medicine, 2021, 40(4): 431-439.
[11]	Lim S H, Jung S K, Byun S, et al. Luteolin suppresses UVB-induced photoageing by targeting JNK1 and p90^RSK2[J]. Journal of Cellular and Molecular Medicine, 2013, 17(5): 672-680. doi: 10.1111/jcmm.12050
[12]	Xia H, Tang Y, Huang R, et al. Nanoliposome use to improve the stability of phenylethyl resorcinol and serve as a skin penetration enhancer for skin whitening[J]. Coatings, 2022, 12(3): 362. doi: 10.3390/coatings12030362
[13]	Ren Qianqian, Wu Hua, Jin Jianming. Cosmetic plant materials (Ⅳ): Research and development of plant whitening materials for inhibiting melanin synthesis signaling pathway[J]. Daily Chemical Industry, 2021, 51(7): 590-597.
[14]	Choi M Y, Song H S, Hur H S, et al. Whitening activity of luteolin related to the inhibition of cAMP pathway in α-MSH-stimulated B16 melanoma cells[J]. Archives of Pharmacal Research, 2008, 31(9): 1166-1171. doi: 10.1007/s12272-001-1284-4
[15]	Pasarkar N, Waghmare S, Kamble H. Solid dispersion: a review[J]. Iconic Research and Engineering Journals, 2022, 5(7): 6.
[16]	Deng Xiangtao, Hao Haijun, Chen Xiaofeng, et al. Preparation, characterization and pharmacokinetic of two solid dispersions of luteolin in rat[J]. Chinese Herbal Medicine, 2018, 49(24): 5787-5793.
[17]	Wu Chun, Chen Jinhui. Preparation and optimization of luteolin solid dispersion[J]. Food Industry Technology, 2019, 40(8): 190-195.
[18]	Alshehri S, Imam S S, Altamimi M A, et al. Enhanced dissolution of luteolin by solid dispersion prepared by different methods: physicochemical characterization and antioxidant activity[J]. ACS Omega, 2020, 5(12): 6461-6471. doi: 10.1021/acsomega.9b04075 pmid: 32258881
[19]	Challa R, Ahuja A, Ali J, et al. Cyclodextrins in drug delivery: An updated review[J]. AAPS PharmSciTech, 2005, 6(2): E329-E357. doi: 10.1208/pt060243 pmid: 16353992
[20]	Jambhekar S S, Breen P. Cyclodextrins in pharmaceutical formulations Ⅱ: solubilization, binding constant, and complexation efficiency[J]. Drug Discovery Today, 2016, 21(2): 363-368. doi: 10.1016/j.drudis.2015.11.016 pmid: 26687191
[21]	Han Dongxu, Li Tianle, Miao Ruidan, et al. Study on the solubilization of luteolin by seven-(2, 6-dimethyl)-β-cyclodextrin[J]. Chinese Journal of Modern Applied Pharmacy, 2020, 37(22): 2747-2751.
[22]	Wang X, Hu X, Li S, et al. Preparation of antibacterial nanofibers by electrospinning polyvinyl alcohol containing a luteolin hydroxypropyl-β-cyclodextrin inclusion complex[J]. New Journal of Chemistry, The Royal Society of Chemistry, 2022, 46(5): 2360-2367.
[23]	Long Youqi, Wang Lan, Shang Jingchuan, et al. Pharmacokinetics of luteolin and its inclusion complex with sulfobutyl ether-β-cyclodextrin in rats[J]. Chinese Journal of Pharmaceutical Analysis, 2018, 38(2): 282-287.
[24]	Loftsson T, Masson M. Cyclodextrins in topical drug formulations: theory and practice[J]. International Journal of Pharmaceutics, 2001, 225(1/2): 15-30. doi: 10.1016/S0378-5173(01)00761-X
[25]	Liu D, Mao Y, Ding L, et al. Dihydromyricetin: A review on identification and quantification methods, biological activities, chemical stability, metabolism and approaches to enhance its bioavailability[J]. Trends in Food Science & Technology, 2019, 91: 586-597.
[26]	Zhao X, Shi C, Zhou X, et al. Preparation of a nanoscale dihydromyricetin-phospholipid complex to improve the bioavailability: in vitro and in vivo evaluations[J]. European Journal of Pharmaceutical Sciences, 2019, 138: 104994. doi: 10.1016/j.ejps.2019.104994
[27]	Biswas S, Mukherjee P K, Harwansh R K, et al. Enhanced bioavailability and hepatoprotectivity of optimized ursolic acid-phospholipid complex[J]. Drug Development and Industrial Pharmacy, 2019, 45(6): 946-958. doi: 10.1080/03639045.2019.1583755 pmid: 30767678
[28]	Khan J, Alexander A, Ajazuddin, et al. Luteolin-phospholipid complex: preparation, characterization and biological evaluation: Luteolin-phospholipid complex[J]. Journal of Pharmacy and Pharmacology, 2014, 66(10): 1451-1462. doi: 10.1111/jphp.12280 pmid: 24934881
[29]	Khan J, Saraf S, Saraf S. Preparation and evaluation of luteolin-phospholipid complex as an effective drug delivery tool against GalN/LPS induced liver damage[J]. Pharmaceutical Development and Technology, 2015: 1-12.
[30]	Li Yangjie, Zhou Jing. Preparation, characterization and in vivo pharmacokinetic behavior of luteolin-phospholipid complex[J]. Chinese Patent Drug, 2019, 41(6): 1381-1384.
[31]	Lingayat V J, Zarekar N S, Shendge R S. Solid lipid nanoparticles: a review[J]. Nanoscience and Nanotechnology Research, 2017, 4(2): 67-72.
[32]	Jeong Y M, Ha J H, Park S N. Cytoprotective effects against UVA and physical properties of luteolin-loaded cationic solid lipid nanoparticle[J]. Journal of Industrial and Engineering Chemistry, 2016, 35: 54-62. doi: 10.1016/j.jiec.2015.12.014
[33]	Chen Jinhui, Wu Chun. Determination of entrapment efficiency and antioxidant activity of luteolin solid lipid particle[J]. Journal of Harbin Commercial University (Natural Science Edition), 2017, 33(6): 687-692.
[34]	Dang H, Meng M H W, Zhao H, et al. Luteolin-loaded solid lipid nanoparticles synthesis, characterization, & improvement of bioavailability, pharmacokinetics in vitro and vivo studies[J]. Journal of Nanoparticle Research, 2014, 16(4): 2347. doi: 10.1007/s11051-014-2347-9
[35]	K S R, M D S R, P V. A review on: liposomes[J]. International Journal of Indigenous Herbs and Drugs, 2022, 5(6): 8-11.
[36]	Wu G, Li J, Yue J, et al. Liposome encapsulated luteolin showed enhanced antitumor efficacy to colorectal carcinoma[J]. Molecular Medicine Reports, 2018, 17(2): 2456-2464. doi: 10.3892/mmr.2017.8185 pmid: 29207088
[37]	Liu Miao, Gao Yue, Li Kangfan, et al. Preparation and physicochemical properties of polyethylene glycol modified luteolin liposomes[J]. Modern Food Technology, 2021, 37(10): 118-125, 316.
[38]	Sinha A P. K. S. Enhanced induction of apoptosis in HaCaT cells by luteolin encapsulated in PEGylated liposomes: role of caspase-3/caspase-14[J]. Applied Biochemistry and Biotechnology, 2019, 188(1): 147-164. doi: 10.1007/s12010-018-2907-z
[39]	Li J, Cheng X, Chen Y, et al. Vitamin E TPGS modified liposomes enhance cellular uptake and targeted delivery of luteolin: An in vivo/in vitro evaluation[J]. International Journal of Pharmaceutics, 2016, 512(1): 262-272. doi: S0378-5173(16)30777-3 pmid: 27545748
[40]	Yao Xuechao, Ning Hongxin, Huang Huan, et al. Research progress of luteolin preparation[J]. Chinese Herbal Medicine, 2021, 52(3): 873-882.
[41]	Hu Zexiang, Tong Lei, Geng Yanmeng, et al. Study on DPPH· radical scavenging activity of luteolin nanoemulsion[J]. Journal of Anhui Science and Technology University, 2021, 35(6): 73-76.
[42]	Shin K, Choi H, Song S K, et al. Nanoemulsion vehicles as carriers for follicular delivery of luteolin[J]. ACS Biomaterials Science & Engineering, 2018, 4(5): 1723-1729.
[43]	Qing Weixia. Construction of luteolin and luteolin-glucoside nano-drug loading system[D]. Kaifeng: Henan University, 2016.
[44]	Qing W, Wang Y, Li H, et al. Preparation and characterization of copolymer micelles for the solubilization and in vitro release of luteolin and luteoloside[J]. AAPS PharmSciTech, 2017, 18(6): 2095-2101. doi: 10.1208/s12249-016-0692-y pmid: 28004344
[45]	Huang M, Gao X, Jinfeng Qiu, et al. Preparation and characterization of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles for the solubilization and in vivo delivery of luteolin[J]. International Journal of Nanomedicine, 2013, 8: 3061-3069. doi: 10.2147/IJN.S45062 pmid: 23990719
[46]	Tan L, Liang C, Wang Y, et al. Pharmacodynamic effect of luteolin micelles on alleviating cerebral ischemia reperfusion injury[J]. Pharmaceutics, 2018, 10(4): 248. doi: 10.3390/pharmaceutics10040248
[47]	Gupta V, Mohapatra S, Mishra H, et al. Nanotechnology in cosmetics and cosmeceuticals: a review of latest advancements[J]. Gels, 2022, 8(3): 173. doi: 10.3390/gels8030173