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

doi:10.19852/j.cnki.jtcm.2022.03.008

Abstract

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.

Key words: flavonoids, chromatography,high pressure liquid, mass spectrometry, phospholipids, lipoproteins,LDL, endothelial cells

CHEN Jinpeng, ZHANG Kexia, LIU Yi, JIN Song, GAI Xiaohong, REN Tao, TIAN Chengwang. 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.

Figures/Tables 5

References 35

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Peak		t_R		Formula		Calculated		Measured		Error (ppm)			Main fragment ions (m/z)		Identification
No.		(min)		Formula		[M-H]^-/[M+H]⁺		[M-H]^-/[M+H]⁺		Error (ppm)			Main fragment ions (m/z)		Identification
1		0.82		C₇H₆O₂		--/123.0446		--/123.0443		-2.4					Benzoic acid
2		0.83		C₁₅H₁₄O₇		305.0661/--		305.0660 /--		-0.3		179.0296[M-H-C₆H₅O₃]^- 125.0239[M-H-C₉H₇O₄]^-			Epigallocatechin¹⁵
3		0.94		C₇H₆O₅		169.0137/--		169.0133 /--		-2.4		125.0230 [M-H-CO₂]^-			Gallic acid¹⁶
4		0.99		C₁₅H₁₄O₇		305.0661/--		305.0660 /--		-0.3		179.0295 [M-H-C₆H₅O₃]^- 125.0237 [M-H-C₉H₇O₄]^-			Gallocatechin¹⁵
5		1.00		C₇H₆O₃		--/139.0395		--/ 139.0390		-3.6		122.0846[M+2H-H₂O]⁺			4-Hydroxybenzoic acid¹⁶
6		1.07		C₇H₆O₄		153.0188/--		153.0184 /--		-2.6		109.0296 [M-H-CO₂]^-			2,5-dihydroxyben-zoic acid¹⁶
7		1.10		C₈H₁₀O₃		153.0552/--		153.0548 /--		-2.6		125.0226 [M-H-CO]^-			Hydroxytyrosol¹⁷
8		1.35		C₁₅H₁₄O₆		289.0712/--		289.0713 /--		0.3		245.0804 [M-H-CO₂]^- 205.0503 [M-H-2C₂H₂O]^-			Catechin
9		1.44		C₇H₆O₃		--/139.0395		--/ 139.0389		4.3		121.0328 [M+H-H₂O]⁺			2-Hydroxybenzoic acid¹⁶
10		2.63		C₂₁H₂₀O₁₃		479.0826/--		479.0842 /--		3.3		317.0219 [M-H-glc]^- 121.0288 [M-H-glc-C₇H₄O₄-CO₂]^-			Myricetin-3-O-glucopyranoside¹⁸
11		2.96		C₁₅H₁₀O₈		--/319.0454		--/ 319.0439		-4.7		303.0418 [M+H-H₂O]⁺ 150.1165 [M+H-H₂O-C₇H₄O₄]⁺			Myricetin¹⁸
12		3.30		C₉H₁₀O₅		197.0450/--		197.0449 /--		-0.5		153.0230 [M-H-CO₂]^-			Syringic acid¹⁶
13^＊		4.66		C₂₁H₂₀O₁₂		463.0877/--		463.0880 /--		0.6		301.0282 [M-H-glu]^- 151.0073 [M-H-glu-C₈H₆O₃]^-			Hyperoside/isoquercetin¹⁹
14^＊		5.06		C₂₈H₂₄O₁₆		615.0986/--		615.0977 /--		-1.5		463.0906 [M-H-C₇H₅O₄]^- 301.0331 [M-H-C₇H₅O₄-glu]^-			Quercetin 3-O-2”-galloylgalactoside/quercetin 3-O-2”- Galloylglucoside²⁰
15		5.62		C₂₀H₁₈O₁₁		433.0771/--		433.0742 /--		-6.7		301.0318 [M-ara]^- 151.0975 [M-ara-C₈H₆O₃]^-			Quercetin-3-O-arabinopyranoside²¹
16		6.14		C₂₁H₂₀O₁₀		--/433.1135		--/ 433.1119		-3.7		313.1023 [M+H-C₄H₉O₄]⁺			Vitexin^{18, 22}
17^＊		6.40		C₂₁H₂₀O₁₁		447.0927/--		447.0917 /--		-2.2		301.0286 [M-H-rha]^-			Quercitrin²³ /Quecretin-3-O-rhamnopyranoside²¹
18^＊		7.02		C₂₁H₂₀O₁₁		447.0927/--		447.0937 /--		2.2		285.0392 [M-glu]^-/[M-gal]^- 151.0069 [M-H-C₈H₆O₂-glu]^-			Kaempferol-3-O-gl-ucopyranoside/Kae-mpferol-3-O-gal-actopyranoside^24,25
19		7.12		C₂₇H₃₁O₁₆		610.1534/--		610.1567 /--		5.4		447.0927 [M-H-glu]^- 301.0321 [M-H-glu-rha]^-			Quercetin-3-O-glucopyranosyl-(6→1)-α-L-rhamnopyranoside²⁵
20^＊		7.22		C₂₈H₂₄O₁₅		599.1037/--		599.1053 /--		2.7		417.0817 [M-H-C₇H₅O₄]^- 285.0393 [M-H-C₇H₅O₄-glu]^-			Kaempferol-3-O-2" -galloylgalactoside/ kaempferol-3-O-2”- galloylglucoside²⁰
21^＊		7.35		C₂₀H₁₈O₁₀		417.0822/--		417.0824 /--		0.5		285.0349 [M-H-xyl]^- 285.0349 [M-H-ara]^-			Kaempferol-3-O-xylopyranoside/kaempferol-3-O- arabinopyranoside²¹
22		7.44		C₂₂H₂₂O₁₂		477.1033/--		477.1030 /--		0.6		315.0492 [M-glu]^- 300.0279 [M-glu-CH₃]^-			Isorhamnetin-3-O-glucopyranoside^{22, 25}
23		7.45		C₁₅H₁₀O₇		--/303.0505		--/ 303.0499		-2.0		153.0092 [M+H-C₈H₆O₃]⁺			Quercetin²⁶
24		7.47		C₁₅H₁₀O₆		285.0399/--		285.0392 /--		-2.5		151.0068 [M-H-C₈H₆O₂]^-			Kaempferol²⁶
25		7.55		C₁₆H₁₂O₇		--/317.0661		--/ 317.0654		-2.2		287.0463 [M+H-CH₃O]⁺ 153.0085 [M+H-C₉H₈O₃]⁺			Isorhamnetin¹⁷
26		8.64		C₁₆H₁₂O₈		--/333.0610		--/ 333.0591		-5.7		318.0304 [M+H-CH₃]⁺ 291.0779 [M+2H-CH₃-CO]⁺			Annulatin²⁶
27		10.41		C₁₅H₁₀O₅		--/271.0606		--/271.0601		-1.8		153.0082 [M+H-C₈H₆O]⁺ 118.0236 [M+H-C₇H₄O₄]⁺			Apigenin¹⁷
Peak	t_R		Formula		Calculated		Measured		Error		main fragment ions (m/z)			Identification
No.	(min)		Formula		[M-H]^-/[M+H]⁺		[M-H]^-/[M+H]⁺		(ppm)		main fragment ions (m/z)			Identification
28^＊	15.72		C₃₀H₅₀O₂		441.3733/--		441.3726 /--		-1.6		304.9840 [M-H-C₉H₁₄O]^-			Betulin/Uvaol²⁷
29	17.22		C₃₀H₅₀O		425.3783/--		425.3775 /--		-1.9		217.0106 [M-H-C₁₄H₂₄O]^-			β-amyrin²⁸
30	20.06		C₃₀H₄₈O₃		455.3525/--		455.3526/--		0.2		202.0042 [M-H-C₁₄H₂₄O-COOH]^- 189.9268 [M-H-C₁₆H₂₄O₂-H₂O]^-			Oleanolic acid²⁸
31	20.52		C₃₀H₄₈O₃		455.3525/--		455.3526/--		0.2		189.9282 [M-H-C₁₆H₂₄O₂-H₂O]^-			Betulinic acid²⁷

Peak		t_R		Formula		Calculated		Measured		Error (ppm)			Main fragment ions (m/z)		Identification
No.		(min)		Formula		[M-H]^-/[M+H]⁺		[M-H]^-/[M+H]⁺		Error (ppm)			Main fragment ions (m/z)		Identification
1		0.82		C₇H₆O₂		--/123.0446		--/123.0443		-2.4					Benzoic acid
2		0.83		C₁₅H₁₄O₇		305.0661/--		305.0660 /--		-0.3		179.0296[M-H-C₆H₅O₃]^- 125.0239[M-H-C₉H₇O₄]^-			Epigallocatechin¹⁵
3		0.94		C₇H₆O₅		169.0137/--		169.0133 /--		-2.4		125.0230 [M-H-CO₂]^-			Gallic acid¹⁶
4		0.99		C₁₅H₁₄O₇		305.0661/--		305.0660 /--		-0.3		179.0295 [M-H-C₆H₅O₃]^- 125.0237 [M-H-C₉H₇O₄]^-			Gallocatechin¹⁵
5		1.00		C₇H₆O₃		--/139.0395		--/ 139.0390		-3.6		122.0846[M+2H-H₂O]⁺			4-Hydroxybenzoic acid¹⁶
6		1.07		C₇H₆O₄		153.0188/--		153.0184 /--		-2.6		109.0296 [M-H-CO₂]^-			2,5-dihydroxyben-zoic acid¹⁶
7		1.10		C₈H₁₀O₃		153.0552/--		153.0548 /--		-2.6		125.0226 [M-H-CO]^-			Hydroxytyrosol¹⁷
8		1.35		C₁₅H₁₄O₆		289.0712/--		289.0713 /--		0.3		245.0804 [M-H-CO₂]^- 205.0503 [M-H-2C₂H₂O]^-			Catechin
9		1.44		C₇H₆O₃		--/139.0395		--/ 139.0389		4.3		121.0328 [M+H-H₂O]⁺			2-Hydroxybenzoic acid¹⁶
10		2.63		C₂₁H₂₀O₁₃		479.0826/--		479.0842 /--		3.3		317.0219 [M-H-glc]^- 121.0288 [M-H-glc-C₇H₄O₄-CO₂]^-			Myricetin-3-O-glucopyranoside¹⁸
11		2.96		C₁₅H₁₀O₈		--/319.0454		--/ 319.0439		-4.7		303.0418 [M+H-H₂O]⁺ 150.1165 [M+H-H₂O-C₇H₄O₄]⁺			Myricetin¹⁸
12		3.30		C₉H₁₀O₅		197.0450/--		197.0449 /--		-0.5		153.0230 [M-H-CO₂]^-			Syringic acid¹⁶
13^＊		4.66		C₂₁H₂₀O₁₂		463.0877/--		463.0880 /--		0.6		301.0282 [M-H-glu]^- 151.0073 [M-H-glu-C₈H₆O₃]^-			Hyperoside/isoquercetin¹⁹
14^＊		5.06		C₂₈H₂₄O₁₆		615.0986/--		615.0977 /--		-1.5		463.0906 [M-H-C₇H₅O₄]^- 301.0331 [M-H-C₇H₅O₄-glu]^-			Quercetin 3-O-2”-galloylgalactoside/quercetin 3-O-2”- Galloylglucoside²⁰
15		5.62		C₂₀H₁₈O₁₁		433.0771/--		433.0742 /--		-6.7		301.0318 [M-ara]^- 151.0975 [M-ara-C₈H₆O₃]^-			Quercetin-3-O-arabinopyranoside²¹
16		6.14		C₂₁H₂₀O₁₀		--/433.1135		--/ 433.1119		-3.7		313.1023 [M+H-C₄H₉O₄]⁺			Vitexin^{18, 22}
17^＊		6.40		C₂₁H₂₀O₁₁		447.0927/--		447.0917 /--		-2.2		301.0286 [M-H-rha]^-			Quercitrin²³ /Quecretin-3-O-rhamnopyranoside²¹
18^＊		7.02		C₂₁H₂₀O₁₁		447.0927/--		447.0937 /--		2.2		285.0392 [M-glu]^-/[M-gal]^- 151.0069 [M-H-C₈H₆O₂-glu]^-			Kaempferol-3-O-gl-ucopyranoside/Kae-mpferol-3-O-gal-actopyranoside^24,25
19		7.12		C₂₇H₃₁O₁₆		610.1534/--		610.1567 /--		5.4		447.0927 [M-H-glu]^- 301.0321 [M-H-glu-rha]^-			Quercetin-3-O-glucopyranosyl-(6→1)-α-L-rhamnopyranoside²⁵
20^＊		7.22		C₂₈H₂₄O₁₅		599.1037/--		599.1053 /--		2.7		417.0817 [M-H-C₇H₅O₄]^- 285.0393 [M-H-C₇H₅O₄-glu]^-			Kaempferol-3-O-2" -galloylgalactoside/ kaempferol-3-O-2”- galloylglucoside²⁰
21^＊		7.35		C₂₀H₁₈O₁₀		417.0822/--		417.0824 /--		0.5		285.0349 [M-H-xyl]^- 285.0349 [M-H-ara]^-			Kaempferol-3-O-xylopyranoside/kaempferol-3-O- arabinopyranoside²¹
22		7.44		C₂₂H₂₂O₁₂		477.1033/--		477.1030 /--		0.6		315.0492 [M-glu]^- 300.0279 [M-glu-CH₃]^-			Isorhamnetin-3-O-glucopyranoside^{22, 25}
23		7.45		C₁₅H₁₀O₇		--/303.0505		--/ 303.0499		-2.0		153.0092 [M+H-C₈H₆O₃]⁺			Quercetin²⁶
24		7.47		C₁₅H₁₀O₆		285.0399/--		285.0392 /--		-2.5		151.0068 [M-H-C₈H₆O₂]^-			Kaempferol²⁶
25		7.55		C₁₆H₁₂O₇		--/317.0661		--/ 317.0654		-2.2		287.0463 [M+H-CH₃O]⁺ 153.0085 [M+H-C₉H₈O₃]⁺			Isorhamnetin¹⁷
26		8.64		C₁₆H₁₂O₈		--/333.0610		--/ 333.0591		-5.7		318.0304 [M+H-CH₃]⁺ 291.0779 [M+2H-CH₃-CO]⁺			Annulatin²⁶
27		10.41		C₁₅H₁₀O₅		--/271.0606		--/271.0601		-1.8		153.0082 [M+H-C₈H₆O]⁺ 118.0236 [M+H-C₇H₄O₄]⁺			Apigenin¹⁷
Peak	t_R		Formula		Calculated		Measured		Error		main fragment ions (m/z)			Identification
No.	(min)		Formula		[M-H]^-/[M+H]⁺		[M-H]^-/[M+H]⁺		(ppm)		main fragment ions (m/z)			Identification
28^＊	15.72		C₃₀H₅₀O₂		441.3733/--		441.3726 /--		-1.6		304.9840 [M-H-C₉H₁₄O]^-			Betulin/Uvaol²⁷
29	17.22		C₃₀H₅₀O		425.3783/--		425.3775 /--		-1.9		217.0106 [M-H-C₁₄H₂₄O]^-			β-amyrin²⁸
30	20.06		C₃₀H₄₈O₃		455.3525/--		455.3526/--		0.2		202.0042 [M-H-C₁₄H₂₄O-COOH]^- 189.9268 [M-H-C₁₆H₂₄O₂-H₂O]^-			Oleanolic acid²⁸
31	20.52		C₃₀H₄₈O₃		455.3525/--		455.3526/--		0.2		189.9282 [M-H-C₁₆H₂₄O₂-H₂O]^-			Betulinic acid²⁷

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