Research Article

Efficacy of phospholipid complex of flavonoids from persimmon leaves on atherosclerosis, and possible mechanism

  • Jinpeng CHEN ,
  • Kexia ZHANG ,
  • Yi LIU ,
  • Song JIN ,
  • Xiaohong GAI ,
  • Tao REN ,
  • Chengwang TIAN
Expand
  • 1 State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin 300301, China
    2 Tianjin Key Laboratory of TCM quality markers, Tianjin 300301, China
    3 Tianjin Institute of Pharmaceutical Research, Tianjin 300301, China
    4 Tianjin Pharmaceutial Research Institute Co. Ltd., Tianjin 300462, China
    5 Sinopharm Group Tianjin Co. Ltd., Tianjin 300040, China
TIAN Chengwang, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin 300301, China; Tianjin Key Laboratory of TCM quality markers, Tianjin 300301, China; Tianjin Institute of Pharmaceutical Research, Tianjin 300301, China. tiancw@tjipr.com,Telephone: +86-13672157582

Received date: 2021-09-10

  Accepted date: 2021-11-15

  Online published: 2022-05-20

Supported by

National Science and Technology Major Project of China (Research on Evaluation Technology of New Traditional Chinese Medicine Based on Big Data of Classical Prescription)(2019ZX09201005);International Cooperation Project of Traditional Chinese Medicine (China-Germany International Cooperation in Innovative Research and Development of Traditional Chinese Medicine and Botanical Medicine)(0610-2140NF020630)

Abstract

OBJECTIVE: To investigate the efficacy of phospholipid complex of flavonoids from persimmon leaves (PLF-PC) on atherosclerosis, and to study its mechanism behind the action.

METHODS: To clarify the constituents of the flavonoids from persimmon leaves (PLF), an ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry method was established. To enhance the anti-atherosclerotic effect of PLF, a newly emerging approach based on the combination of phospholipid complexation technique was employed. PLF-PC was prepared by the solvent-evaporation method then characterized using Fourier transform infrared spectroscopy, Powder X-Ray Diffractometry and Scanning electron microscopy. A model of oxidized low-density lipoprotein-induced injury on human umbilical vein endothelial cells was established to investigate the anti-atherosclerotic effect of PLF-PC versus PLF. The levels of nitric oxide, endothelial nitric oxide synthase, intracellular adhesion molecule-1, reactive oxygen species, superoxide dismutase, tumor necrosis factor-αand nuclear factor-κB were observed via assay kits.

RESULTS: A total of 31 compounds were identified in PLF. PLF-PC showed better anti-atherosclerotic power compared with PLF, moreover, enzyme linked immune-osorbent assay analysis showed that the PLF-PC may effect on endothelial dysfunction and atherosclerosis via antioxidant-related mechanisms.

CONCLUSIONS: Our findings elucidated that PLF-PC significantly enhanced the PLF’s efficacy on atherosclerosis.

Cite this article

Jinpeng CHEN , Kexia ZHANG , Yi LIU , Song JIN , Xiaohong GAI , Tao REN , Chengwang TIAN . Efficacy of phospholipid complex of flavonoids from persimmon leaves on atherosclerosis, and possible mechanism[J]. Journal of Traditional Chinese Medicine, 2022 , 42(3) : 417 -425 . DOI: 10.19852/j.cnki.jtcm.2022.03.008

References

1 Mizuno Y, Jacob RF, Mason RP. Inflammation and the development of atherosclerosis. J Atheroscler Thromb 2011; 18:351-8.
2 Zhang SL, Guo CL, Chen ZG, et al. Vitexin alleviates ox-LDL-mediated endothelial injury by inducing autophagy via AMPK signaling activation. Mol Immunol 2017; 85:214-21.
3 Xiao Y, Wang YC, Li LL, et al. Lactones from Ligusticum chuanxiong Hort. Reduces atherosclerotic lesions in apoE-deficient mice via inhibiting over expression of NF-kB -dependent adhesion molecules. Fitoterapia 2014; 95:240-6.
4 Chistiakov DA, Revin VV, Sobenin IA, et al. Vascular endothelium: functioning in norm, changes in atherosclerosis and current dietary approaches to improve endothelial function. Mini Rev Med Chem. 2015; 15:338-50.
5 Zhang HP, Zheng FL, Zhao JH, et al. Genistein inhibits ox-LDL-induced VCAM-1, ICAM-1 and MCP-1 expression of HUVECs through heme oxygenase-1. Arch Med Res 2013; 44:13-20.
6 Takahashi Y, Zhu H, Yoshimoto T. Essential roles of lipoxygenases in LDL oxidation and development of atherosclerosis. Antioxid Redox Sign 2005; 7:425-31.
7 Pirillo A, Norata GD, Catapano AL. LOX-1, OxLDL, and atherosclerosis. Mediat Inflamm 2013; 2013:15278-86.
8 Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction. Circulation 2007; 115:1285-95.
9 Itabe H. Oxidized low-density lipoprotein as a biomarker of in vivo oxidative stress: from atherosclerosis to periodontitis. J Clin Biochem Nutr 2012; 51:1-8.
10 Bei WJ, Peng WL, Ma Y, et al. NaoXinQing, an anti-stroke herbal medicine, reduces hydrogen peroxide-induced injury in NG108-15 cells. Neurosci Lett 2004; 363:262-5.
11 Akak CM, Djama CM, Nkengfack AE, et al. New coumarin glycosides from the leaves of Diospyros crassiflora (Hiern). Fitoterapia 2010; 81:873-7.
12 Sun L, Zhang J, Fang K, et al. Flavonoids from persimmon (Diospyros kaki) leaves (FPL) attenuate H2O2-induced apoptosis in MC3T3-E1 cells via the NF-κB pathway. Food Funct 2014; 5:471-9.
13 Chen ZP, Sun J, Chen HX, et al. Comparative pharmacokinetics and bioavailability studies of quercetin, kaempferol and isorhamnetin after oral administration of Ginkgo biloba extracts, Ginkgo biloba extract phospholipid complex and Ginkgo biloba extract solid dispersions in rats. Fitoterapia 2010; 81:1045-52.
14 Zhang KX, Zhang YY, Zhang MY, et al. Effects of phospholipid complex of total flavonoids from Persimmon (Diospyros kaki L.) leaves on experimental atherosclerosis rats. J Ethnopharmacol 2016; 191:245-53.
15 Callemien D, Collin S. Use of RP-HPLC-ESI (-)-MS/MS to differentiate various proanthocyanidin isomers in lager beer extracts. J Am Soc Brew Chem 2008; 66:109-15.
16 Zhou XT, Wang L, Han L, et al. Research progress on chemical constituents and pharmacological effects of Diospyros kaki leaves. Chin Herb Med 2014; 45:3195-203.
17 Ruth MLH, Paola QR, Ana A, et al. Polyphenolic profile of persimmon leaves by high resolution mass spectrometry (LC-ESI-LTQ-Orbitrap-MS). J Funct Foods 2016; 23:370-7.
18 Chen G, Xue J, Xu SX, et al. Chemical constituents of the leaves of Diospyros kaki and their cytotoxic effects. J Asian Nat Prod Res 2007; 9:347-53.
19 Xie CY, Xie ZS, Xu XJ, et al. Persimmon (Diospyros kaki L.) leaves: a review on traditional uses, phytochemistry and pharmacological properties. J Ethnopharmacol 2015; 163:229-40.
20 Kawakami K, Nishida H, Tatewaki N, et al. Persimmon leaf extract inhibits the ATM activity during DNA damage response induced by doxorubicin in A549 lung adenocarcinoma cells. Biosci Biotech Bioc 2011; 75:650-5.
21 Chen G, Xu SX, Sha Y. Studies on the constituents of Diospyros kaki leaves. Chinese Journal of Medicinal Chemistry. J Med Chem 2000; 10:298-9.
22 Chen G, Xu SX, Wang HZ, et al. Note: Kakispyrol, a new biphenyl derivative from the leaves of Diospyros kaki. J Asian Nat Prod Res 2005; 7:265-8.
23 Ganfer F, Chapuis JC, Msonthi JD, et al. Cytotoxic naphthoquinones, molluscicidal saponins and flavonols from Diospyros zombensis. Phytochemistry 1987; 26:2501-3.
24 Xue YL, Miyakawa T, Hayashi Y, et al. Isolation and tyrosinase inhibitory effects of polyphenols from the leaves of persimmon, Diospyros kaki. J Agric Food Chem 2011; 59:6011-7.
25 Chen G, Lu H, Wang C, et al. Effect of five flavonoid compounds isolated from leaves of Diospyros kaki on stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils. Clin Chim Acta 2002; 362:169-75.
26 Chen G, Wei SH, Huang J, et al. A novelC-glycosylflavone from the leaves of Diospyros kaki. J Asian Nat Prod Res 2009; 11:503-7.
27 Uc-Cachon AH, Molina SGM, Said FS, et al. A new dimeric naphthoquinone from Diospyros anisandra. Nat Prod Res 2013; 27:1174-8.
28 Higa M, Ogihara K, Yogi S. Bioactive naphthoquinone derivatives from Diospyros maritime Blume. Chem Pharm Bull 1998; 46:1189-93.
29 Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000; 87:840-4.
30 Vallance P, Chan N. Endothelial function and nitric oxide: clinical relevance. Heart 2001; 85:342-50.
31 Wheatcroft SB, Williams IL, Shah AM, et al. Pathophysiological implications of insulin resistance on vascular endothelial function. Diabet Med 2003; 20:255-68.
32 Pober JS. Endothelial activation: intracellular signaling pathways. Arthritis Res 2002; 4:109-18.
33 Steffens S, Mach F. Inflammation and atherosclerosis. Herz 2004; 29:741-8.
34 Sena MC, Pereira AM, Seiça R. Endothelial dysfunction-a major mediator of diabetic vascular disease. Biochim Biophys Acta 2013; 1832:2216-31.
35 Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation 2005; 111:3481-8.
Outlines

/