Silibinin augments the effect of clopidogrel on atherosclerosis in diabetic ApoE deficiency mice

Zhang, Jianbo; Shi, Qiyu; Hu, Yuanlong; Li, Xiaohong

doi:10.3233/ch-211279

Cited by 5 publications

(3 citation statements)

References 23 publications

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“…Silibinin has been proven to reduce at a dose-dependent manner the atherosclerotic plaque burden in the arteries of hypercholesterolemic rabbits fed with silymarin extract at daily doses of 100 and 200 mg/kg, demonstrating a higher anti-atherosclerotic efficacy of 200 mg/kg/d over 100 mg/kg/d of silymarin [ 30 ]. Furthermore, silibinin has been proven to augment the effect of clopidogrel on atherosclerosis [ 31 ]. Mice fed with a high fat diet were divided in three groups, Silibinin, Clopidogrel and combined treatment.…”

Section: Resultsmentioning

confidence: 99%

A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin: A New Kid on the Block

et al. 2022

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Silibinin/silymarin has been used in herbal medicine for thousands of years and it is well-known for its hepato-protective properties. The present comprehensive literature review aimed to critically summarize the pharmacological properties of silymarin extract and its main ingredient silibinin in relation to classical cardiovascular risk factors (e.g., diabetes mellitus, etc.). We also assessed their potential protective and/or therapeutic application in cardiovascular diseases (CVDs), based on experimental and clinical studies. Pre-clinical studies including in vitro tests or animal models have predominantly implicated the following effects of silymarin and its constituents: (1) antioxidant, (2) hypolipidemic, (3) hypoglycemic, (4) anti-hypertensive and (5) cardioprotective. On the other hand, a direct amelioration of atherosclerosis and endothelial dysfunction after silymarin administration seems weak based on scarce data. In clinical trials, the most important findings are improved (1) glycemic and (2) lipid profiles in patients with type 2 diabetes mellitus and/or hyperlipidemia, while (3) the anti-hypertensive effects of silibinin/silymarin seem very modest. Finally, the changes in clinical endpoints are not robust enough to draw a firm conclusion. There are significant limitations in clinical trial design, including the great variety in doses and cohorts, the underlying conditions, the small sample sizes, the short duration and the absence of pharmacokinetic/pharmacodynamic tests prior to study commitment. More data from well-designed and high-quality pre-clinical and clinical studies are required to firmly establish the clinical efficacy of silibinin/silymarin and its possible therapeutic application in cardiovascular diseases.

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Section: Resultsmentioning

confidence: 99%

A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin: A New Kid on the Block

et al. 2022

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“…ApoE is an alkaline protein that is rich in arginine; is found in high-density lipoproteins, very low-density lipoproteins and celiac particles; and has an important role in maintaining the structure of the abovementioned lipoproteins ( 37 ). Furthermore, ApoE is an independent risk factor for the formation of atherosclerotic heart disease due to its gene polymorphism, which is involved in various lipid metabolic processes, such as cholesterol efflux, transport and storage.…”

Section: Discussionmentioning

confidence: 99%

Role and mechanism of the zinc finger protein ZNF580 in foam‑cell formation

Zhang¹,

Qin

Liu

et al. 2022

Exp Ther Med

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Coronary atherosclerotic heart disease poses a significant threat to human health. The pathological basis is atherosclerosis and foam-cell formation is the key factor in the initiation of atherosclerosis. In the present study, foam cell models were established using 50 ng/ml oxidized low-density lipoprotein to stimulate in vitro cultures of THP-1 cells for 72 h. The expression of zinc finger protein 580 (ZNF580), a Cys2-His2 zinc finger protein containing 172 amino acids that was originally cloned by screening a human aortic cDNA library, was measured in foam cells and its interaction with various regulatory factors during foam-cell formation was investigated. Oil red O staining was used to observe cell morphology and intracellular lipid levels. Lentivirus transfection was employed to either overexpress or silence ZNF580 in THP-1 cells, and an inverted fluorescence microscope was used to observe the distribution of ZNF580 immunofluorescence to determine the transfection rate. RNA and total protein were extracted and the expression levels of ZNF580, CD36, peroxisome proliferator-activated receptor-γ (PPAR-γ), ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein E (ApoE) were measured by reverse transcription-quantitative PCR. The protein levels were examined by western blot analysis to evaluate the interaction between ZNF580 and associated regulatory factors. ZNF580 was able to significantly increase the expression levels of ApoE and ABCA1 and significantly decrease the expression levels of CD36 and PPAR-γ, suggesting that ZNF580-mediated inhibition of foam-cell formation is associated with the PPAR-γ-CD36 signalling pathway. Based on these findings, ZNF580 may be a potential therapeutic candidate for the treatment of coronary atherosclerotic heart disease.

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“…In a zebrafish model of type 2 diabetes, a treatment with SM combined with metformin was demonstrated to suppress the expression of important inflammatory genes (IL-1β and TNF-α) associated with the amelioration of intestinal inflammation [163]. In an experiment with ApoE−/− mice fed with a high-fat diet, co-administration of SB with Clopidogrel was found to significantly mitigate the inflammation and endothelial dysfunction in aorta roots [164]. In stroke-induced brain ischemia in rats, SB was able to significantly decrease the expression of Bax and NF-κB, simultaneously with the upregulation of Akt, mTOR, HIF-1α and Bcl-2, leading to the mitigation of neurological deficits, reduced infarct volume and suppressed brain oedema [165].…”

Section: Other In Vivo Model Systems and Disease Statesmentioning

confidence: 99%

Silymarin and Inflammation: Food for Thoughts

Surai,

Earle-Payne

2024

Antioxidants

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Inflammation is a vital defense mechanism, creating hostile conditions for pathogens, preventing the spread of tissue infection and repairing damaged tissues in humans and animals. However, when inflammation resolution is delayed or compromised as a result of its misregulation, the process proceeds from the acute phase to chronic inflammation, leading to the development of various chronic illnesses. It is proven that redox balance disturbances and oxidative stress are among major factors inducing NF-κB and leading to over-inflammation. Therefore, the anti-inflammatory properties of various natural antioxidants have been widely tested in various in vitro and in vivo systems. Accumulating evidence indicates that silymarin (SM) and its main constituent silibinin/silybin (SB) have great potential as an anti-inflammation agent. The main anti-inflammatory mechanism of SM/SB action is attributed to the inhibition of TLR4/NF-κB-mediated signaling pathways and the downregulated expression of pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, IL-12, IL-23, CCL4, CXCL10, etc. Of note, in the same model systems, SM/SB was able to upregulate anti-inflammatory cytokines (IL-4, IL-10, IL-13, TGF-β, etc.) and lipid mediators involved in the resolution of inflammation. The inflammatory properties of SM/SB were clearly demonstrated in model systems based on immune (macrophages and monocytes) and non-immune (epithelial, skin, bone, connective tissue and cancer) cells. At the same time, the anti-inflammatory action of SM/SB was confirmed in a number of in vivo models, including toxicity models, nonalcoholic fatty liver disease, ischemia/reperfusion models, stress-induced injuries, ageing and exercising models, wound healing and many other relevant model systems. It seems likely that the anti-inflammatory activities of SM/SB are key elements on the health-promoting properties of these phytochemicals.

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Silibinin augments the effect of clopidogrel on atherosclerosis in diabetic ApoE deficiency mice

Cited by 5 publications

References 23 publications

A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin: A New Kid on the Block

A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin: A New Kid on the Block

Role and mechanism of the zinc finger protein ZNF580 in foam‑cell formation

Silymarin and Inflammation: Food for Thoughts

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