Traditional Chinese medicine in the treatment of high incidence diseases in cold areas: the thrombotic diseases

Xueqing Tang; Xin Liu; Monayo Seth Mikaye; Hongrui Zhao; Yong Zhang

doi:10.2478/fzm-2021-0005

Traditional Chinese medicine in the treatment of high incidence diseases in cold areas: the thrombotic diseases

doi: 10.2478/fzm-2021-0005

Xueqing Tang^{1, #},
Xin Liu^{1, #},
Monayo Seth Mikaye¹,
Hongrui Zhao¹,
Yong Zhang^{1, 2, 3
, ,}

1.
Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China
2.
Research Unit of Noninfectious Chronic Diseases in Frigid Zone, Chinese Academy of Medical Sciences, 2019 Research Unit 070, Harbin, 150081, China
3.
Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, 150081, China

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Corresponding author: Yong Zhang, E-mail: hmuzhangyong@hotmail.com

摘要

Abstract: Thrombotic diseases are the leading causes of death worldwide, especially in cold climates. Traditional Chinese medicine (TCM)-based therapies have gained increasing popularity worldwide, but also raised some concerns about its efficacy, safety profile and exact mechanisms. TCM has been traditionally used in the management of thrombosis and convincingly proven effective in modifying thrombosis progression, particularly the platelet function, coagulation system and fibrinolytic system. This review article focuses on TCM regulation of thrombosis with brief discussion on the fundamental aspects and relevant background information for better understanding of the subject. In addition to its antithrombotic effects, we will dive insight into the cellular and molecular mechanisms of TCM as pharmacological regulators of platelet aggregation, coagulation, and fibrinolysis. With increasing awareness and understanding of the benefits and potentials of TCM, TCM products will in no doubt gain its broader applications in the treatment of thrombosis and associated disorders, which in turn will deepen our understanding of its pharmacological and molecular mechanisms. Finally, current review provides a perspective view on the future directions to TCM research on thrombosis.
- thrombosis /
- Traditional Chinese Medicine /
- platelet /
- coagulation /
- fibrinolysis

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Figure 1. TCMs and their effects on platelet.

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Figure 2. TCMs and their anticoagulation effects.

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Figure 3. TCMs and their effects on fibrinolytic system.

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Figure 4. TCMs and their multiple effects on thrombosis.

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Table 1. Summary of TCMs and their effects on thrombosis.

Common name	Latin name	Active compounds	Mechanism	Reference
Safflower	Carthamus tinctorius	SY, HSYA	Reduced platelet aggregation; inhibited PAF receptor; inhibited serotonin release; decreased intraplatelet Ca²⁺; inhibited TXA₂ production; reduced GP IIb/IIIa expression	25-30
Aconite	Radix Aconiti praeparata	Higenamine	Reduced platelet aggregation; inhibited α₂-adrenergic receptor; inhibited TXA2 receptor	32-34
Andrographis	Andrographis paniculata	AP1, AP3	Reduced platelet aggregation; decreased intraplatelet Ca²⁺; increase cGMP levels	38-40
Hawthorn	Crataegus pinnatifida	Eriodectyol	Reduced platelet aggregation; inhibited TXA₂ production; inhibited serotonin release	42-45
Motherwort	Leonurus japonicus.	Spirolabdane diterpenoids	Reduced platelet aggregation	47-50
-	Angelica pubescens	Coumarin	Reduced platelet aggregation; inhibited 5-LOX and COX-1 activity	52-54
Dong quai	Angelica sinensis	SF, LIG	Reduced platelet aggregation; inhibited TXA₂ and TXB₂ production; suppressed 6-keto PGF_1α generation; reduced vWF antigen and α-granule membrane protein	55-63
Corydalis	Corydalis yanhusuo	DHC, THB	Reduced platelet aggregation; impaired thromboxane formation and phosphoinositides breakdown; decreased intraplatelet Ca²⁺; bound to ADP receptors P2Y₁ and P2Y₁₂, thrombin receptor PAR1	65-67
Hops	Humulus lupulus L.	XN	Reduced platelet aggregation; inhibited TXA₂ production; decreased intraplatelet Ca²⁺; decreased ROS accumulation and platelet mtDNA release	69-71
Liquorice	Glycyrrhiza glabra	Glycyrrhetinic acid, GL	Inhibited thrombin; inhibited FXa	78-80
Feces Trogopterus		Kaempferol coumaroyl rhamnosides	Inhibited thrombin	83, 84
-	Zanthoxylum nitidum var. tomentosum	Toddalolactone	Inhibited PAI-1	92
Pillbug	Porcellio scaber Latreille	PSLTro01	Activated plasminogen	94
Earthworm	Eisenia fetida/Lumbricus rubellus	EfP, LrP	Activated plasminogen; directly degraded fibrin	95-101
Ginkgo	Ginkgo biloba L.	Ginkgolides, BB	Reduced platelet aggregation; inhibited PAF receptor and glycine receptor; decreased intraplatelet Ca²⁺; inhibited TXA₂ production; increase cAMP and cGMP levels	103-106
		Ginkgetin, isoginkgetin, bilobetin, amentoflavone	Inhibited thrombin	107
		EGb761	Increased TM and t-PA expression and activity	108, 109
Asian Ginseng	Panax ginseng	Ginsenoside Rgl, Rp3, Ro, Rp1, gintonin	Reduced platelet aggregation; decreased intraplatelet Ca²⁺; inhibited TXA₂ production; inhibited serotonin release; inhibited ATP release; impaired GPVI signaling	111-116
		Ginsenosides Rg2, Rg3	Inhibited FXa	117
		Ginsenosides Rg1	Increased plasminogen activator secretion	118
Notoginseng	Panax notoginseng	Ginsenoside Rg1, notoginsenoside Fc	Reduced platelet aggregation	119-122
		Notoginsenoside R1	Increased t-PA and u-PA expression; decreased PAI-1 activity	123
Danshen	Salvia miltiorrhiza Bge.	SA	Reduced platelet aggregation; decreased TXB₂ and vWF levels; increased 6-keto-PGF_1α levels; increased cAMP level	125-127
		Tanshinones	Enhanced AT-III and PC activities; inhibited FXa; inhibited thrombin; inhibited FVIIa	127-129
		-	Decreased plasma PAI-1 levels; increased t-PA levels	127
-	Coptis chinensis	BBR	Reduced platelet aggregation; inhibited TXA₂ production; inhibited α₂-adrenergic receptor	132, 133
		BBR	Inhibited thrombin	134
Chuanxiong	Ligusticum wallichii	Tetramethylpyra-zine, SF	Reduced platelet aggregation; inhibited TXA₂ production; reduced GP IIb/IIIa expression; reduced NO production; increased cAMP level	136-139
		-	Inhibited thrombin	140
Ginger	Zingiber officinale	Gingerol, zingerone	Reduced platelet aggregation; inhibited LOX and COX activity; inhibited TXA₂ production; decreased intraplatelet Ca²⁺; reduced P-selectin and PAC-1 expression	142-146
		Zingerone	Inhibited FXa production and activity	146
-	Celastrus orbiculatus	NST-50	Reduced platelet aggregation; inhibited TXB₂ production; increased 6-keto PGF_1α generation	149
		NST-50	Decreased PAI-1 levels; increased t-PA levels	149
Baical skullcap root	Scutellaria baicalensis Georgi	OroA, baicalin, WGN, WGNS	Reduced platelet aggregation	151-154
		OroA, baicalin, WGN, WGNS	Inhibited thrombin production and activity; inhibited FXa production and activity; inhibited vitamin K reductases; inhibited TF production and activity	152-156
		OroA, baicalin, WGN,	Decreased PAI-1 levels WGNS	152-154
-	Dioscorea zingiberensis	TSSN, diosgenin	Reduced platelet aggregation	158-160
		-	Inhibited FVIII	160
Madder	Rubia cordifolia	-	Reduced platelet aggregation; inhibited TXB₂ production; increased 6-keto PGF_1α generation	162
		Purpurin	Inhibited FVII	163
		Purpurin	Increased t-PA levels; activated pro-urokinase	162, 163
Astragalus	Astragalus membranaceus	AGS-IV	Bound to prothrombin and AT-III	165
		AGS-IV	Decreased PAI-1 levels; increased t-PA levels	166
Peony root	Paeoniae lactiflora	Paeoniflorin	Reduced platelet aggregation; inhibited TXA₂ and TXB₂ production; increased 6-keto PGF_1α generation; modulated vWF-GP Ib interaction	167-170
		Paeoniflorin	Increased t-PA activity; increased u-PA levels	169, 171
Turmeric	Curcuma Longa	Curcumin, curdione	Reduced platelet aggregation; inhibited TXB₂ production; decreased intraplatelet Ca²⁺; inhibited dense granule secretion; inhibited P-selectin expression; increased cAMP levels	173-178
		Curcumin	Inhibited thrombin; inhibited FXa; inhibited FVII synthesis	179, 180
		Curcumin	Increased u-PA levels	181
Yellow mealworm	Tenebrio molitor	-	Reduced platelet aggregation; decreased intraplatelet Ca²⁺; inhibited P-selectin and PAC-1 expression; improved NO production; inhibited ET-1 secretion	183
		-	Inhibited FXa production and activity	183
safflower yellow; HSYA: hydroxysafflor yellow A; AP1: andrographolide; AP3: 14-deoxy-11, 12 didehydroandrographolide; PAF: platelet activating factor; TXA₂: thromboxane A₂; GP: glycoprotein; cGMP: cyclic guanosine monophosphate; LOX: lipoxygenase; COX: cyclooxygenase; SF: sodium ferulate; LIG: Z-ligustilide; TXB₂: thromboxane B₂; PG: prostaglandins; vWF: von Willebrand Factor; DHC: dehydrocorydaline; THB: canadine; ADP: adenosine diphosphate; ATP: adenosine triphosphate; XN: xanthohumol; GL: glycyrrhizin; PAI-1: plasminogen activator inhibitor 1; EfP: E. fetida proteases; LrP: L. rubellus proteases; BB: bilobalide; TM: thrombomodulin; t-PA: tissuetype plasminogen activator; u-PA: urokinasetype plasminogen activator; SA: salvianolic acid; BBR: berberine; OroA: oroxylin A; WGN: wogonin; WGNS: wogonoside; TSSN: total steroidal saponin; AGS-IV: astragaloside IV; cAMP: cyclic adenosine monophosphate; AT-III: antithrombin III; PC: protein C; ET-1: endothelin-1

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