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Research progress of main pharmacological action and mechanism of crocetin

Research progress of main pharmacological action and mechanism of crocetin

  • Time of issue:2024-01-22
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Research progress of main pharmacological action and mechanism of crocetin

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  • Time of issue:2024-01-22
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Saffron is the dry stigma of Crocus Crocus sativus L in the Iraceae.saffron is a traditional Chinese medicine for promoting blood circulation and removing blood stasis, with extensive clinical effects.

 

 

Crocetin is one of the main effective components of crocetin. It has polyunsaturated conjugated oleic acid structure and belongs to carotenoid substance. A large number of studies have shown that crocetin has clear biological activities in anti-cardiovascular system diseases, anti-oxidation, anti-atherosclerosis, prevention and treatment of diabetes complications. In this paper, the research progress on the main pharmacological effects of crocetin in recent years was summarized.

 

 

1 Effect of crocetin on cardiovascular system diseases

 

1.1 Protective effects on myocardial ischemia: 

Liu Tongzheng et al. observed the protective effect of crocin on myocardial ischemia in ISO-induced rat model of acute myocardial ischemia. The results showed that crocin prophylactic administration could significantly reduce the release of creatine kinase (CK) and lactate dehydrogenase (LDH) in serum of the model rats. It can also significantly reduce the level of malondialdehyde in serum and myocardial homogenate. It has obvious inhibitory effect on myocardial edema. Protect the activities of glutathione peroxidase (GSH-Px), Na+,K+ -ATPase and Mg2-ATPase; It has significant protective effect on myocardial necrosis. These results indicate that crocetin can protect ISO-induced acute myocardial ischemia by preventing lipid peroxidation, maintaining the integrity of cell membrane and improving the antioxidant capacity of myocardial tissue.

 

The results showed that prophylactic administration of crocetin (25, 50mg/kg) could improve myocardial cell injury in rats with myocardial ischemia-reperfusion injury. It can alleviate the disturbance of myocardial energy metabolism caused by ischemia and reperfusion, and thus play a certain protective role on myocardial ischemia and reperfusion injury in rats. In addition, crocetin also has a good protective effect on myocardial ischemia caused by coronary ligation in rats and dogs.

 

1.2 Effects on cardiac hypertrophy:

Shen Xiangchun et al. prepared a rat model of myocardial hypertrophy by abdominal aortic partial stenosis, and observed the effect of crocetin on myocardial hypertrophy. The results showed that crocetin could significantly reduce the cardiac coefficient and left ventricular coefficient of the model rats, and significantly improve the activities of Na+,K+ -ATPase, Ca²+,Mg²+ -ATPase in myocardial tissue, while decreasing hydroxyproline in myocardial tissue The acid level indicated that crocin could inhibit the increase of collagen in interstitial cells and improve ventricular remodeling in rats with myocardial hypertrophy.

 

The results indicated that crocetin could ameliorate myocardial hypertrophy by inhibiting the activity of matrix metalloproteinases (MMPs). Other studies have observed that crocetin can inhibit myocardial hypertrophy induced by norepinephrine in rats and prevent the development of left ventricular hypertrophy induced by norepinephrine. Decreased the collagen level in myocardial tissue, increased the activity of Na+,K+ -ATPase in myocardial tissue and Ca²+,Mg²+ -ATPase in mitochondria, significantly inhibited the activity of MMP-2 and the expression of MMP-2 and MMP-9.

 

1.3 Protective effect on cardiomyocyte injury:

Yu Weiping et al. showed that crocetin could inhibit H:O: induced cardiomyocyte apoptosis in a dose-dependent manner, and this effect was related to up-regulation of Bc1-2 protein expression and down-regulation of Caspase-3 protein expression in cardiomyocytes. Other studies have also confirmed that crocetin can improve the morphology of cardiomyocytes, reduce LDH activity and intracellular MDA level in culture medium, increase intracellular SOD activity and reduce the cell size

The number of cell death played a significant protective role in oxidative stress injury of cultured cardiomyocytes caused by H₂O₂. Rao Shuyun et al. also observed that crocetin had a significant protective effect on myocardial cell injury caused by sugar deficiency and hypoxia, and it could reduce the level of MDA in injured cells and the activities of LDH and CK in culture medium. The protective effect of crocetin on myocardial cell injury caused by the above factors is mainly achieved through the antioxidant effect.

 

Crocetin can also protect cardiomyocytes from improving energy metabolism and inhibit cardiomyocyte apoptosis induced by NE. In addition, the protective effect of crocetin on cardiomyocytes is also related to Ca²+. Therefore, crocetin protects injured cardiomyocytes through multiple action targets, multiple action pathways and multiple mechanisms.

 

2. Anti-atherosclerotic effect

A large number of animal experiments have confirmed that crocetin has definite anti-atherosclerosis effect. The effect of crocetin on vasodilation in hyperlipidemia rabbits and its mechanism of action showed that crocetin can significantly increase the serum NO level and improve vasodilation function in hyperlipidemia rabbits, and the mechanism is related to increasing the activity and gene expression of endothelial nitric oxide synthase (eNOS) in blood vessel wall. This effect of crocetin has also been demonstrated in atherosclerotic quail models and bovine aortic endothelial cells cultured in vitro.

 

The anti-atherosclerotic effects of crocetin are multifold. High and low doses of crocetin can significantly reduce the levels of serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and MDA, and significantly increase the levels of serum high density lipoprotein cholesterol (HDL-C), SOD activity and anti-atherosclerotic index of atherosclerotic rats. The pathological results showed that crocetin significantly alleviated atherosclerotic injury in model rats.

 

3. Protective effect on diabetic vascular disease

It was found that crocetin can improve insulin resistance in several models of diabetes. On this basis, it was found that crocetin can significantly improve the non-enzymatic glycosylation of proteins in vitro.

 

The effect of crocin on the formation of advanced glycation products and its receptor expression in diabetic rats was further studied. It was initially confirmed that crocin significantly decreased the serum levels of fructosamine and glycosylated hemoglobin, reduced the deposition of advanced glycation end products (AGEs) in aorta and mesenteric vascular bed in model rats, and reduced the expression of AGEs receptor protein, thus indicating crocin bodies It can inhibit non-enzymatic glycosylation of protein and prevent and treat early diabetic vascular disease.

 

4 Others

In addition to the above effects, crocetin also has a strong antioxidant effect. In addition to its great contribution to cardiovascular protection, its antioxidant effect is also reflected in the protection of DNA damage induced by free radical generating system, the reduction of doxorubicin induced cardiotoxicity in rats, and the protection of doxorubicin induced myocardial mitochondrial damage in rats. Other studies have shown that crocetin can improve the survival rate of rats with hemorrhagic shock and reduce liver tissue damage. Crocetin also has anticoagulant and antithrombotic effects.

 

 

The medicinal use of saffron has a long history. Saffron acid is one of its main active components and its pharmacological effects are very extensive. In recent years, its role in the prevention and treatment of cardiovascular diseases has become a focus of research by many scholars. A large number of research results also show that crocetin has a good cardiovascular protection effect, and its role is multi-target and multi-pathway. These research results indicate that crocetin has a good development prospect, and it is very promising to develop into a new drug for the prevention and treatment of cardiovascular diseases, which is worthy of further study.

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