Efficacy of Curcumin on Aortic Atherosclerosis: A Systematic Review and Meta-Analysis in Mouse Studies and Insights into Possible Mechanisms

Lin, Ke; Chen, Huaijun; Chen, Xiaojun; Qian, Jing; Huang, Shushi; Huang, Weijian

doi:10.1155/2020/1520747

Cited by 24 publications

(32 citation statements)

References 61 publications

(85 reference statements)

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Section: Introductionmentioning

confidence: 99%

“…In a recent meta-analysis that proposed to evaluate the therapeutic effect of curcumin in mouse models of atherosclerosis, Lin et al found that curcumin significantly decreases the aortic atherosclerotic lesion area, and the serum lipid levels (TC, TG and LDL-C) and inflammatory markers (TNF-α and IL-1β) [80]. In addition, Lin et al highlighted the dose-response relation between curcumin and its protective effect on atherosclerosis, showing that the effect on decreasing the aortic lesion area is stronger in low and medium dosages (< 207 mg/kg BW/day) and weaker when the dose was more than 207 mg/kg BW/day, becoming pro-atherogenic when the dose reached 347 mg/kg BW/day [80]. Clinical trials focusing on curcumin effects in atherosclerosis progression gave dissimilar results, some of them evidencing that curcumin has no effect on risk factors of atherosclerosis [81,82], while others reporting an atheroprotective effect of curcumin by improvement of the lipidic profile in patients with metabolic syndrome, patients taking curcumin extract capsules (630 mg thrice daily) for 12 weeks [83].…”

Section: Introductionmentioning

confidence: 99%

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Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

et al. 2020

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Atherosclerosis is the main process behind cardiovascular diseases (CVD), maladies which continue to be responsible for up to 70% of death worldwide. Despite the ongoing development of new and potent drugs, their incomplete efficacy, partial intolerance and numerous side effects make the search for new alternatives worthwhile. The focus of the scientific world turned to the potential of natural active compounds to prevent and treat CVD. Essential for effective prevention or treatment based on phytochemicals is to know their mechanisms of action according to their bioavailability and dosage. The present review is focused on the latest data about phenolic compounds and aims to collect and correlate the reliable existing knowledge concerning their molecular mechanisms of action to counteract important risk factors that contribute to the initiation and development of atherosclerosis: dyslipidemia, and oxidative and inflammatory-stress. The selection of phenolic compounds was made to prove their multiple benefic effects and endorse them as CVD remedies, complementary to allopathic drugs. The review also highlights some aspects that still need clear scientific explanations and draws up some new molecular approaches to validate phenolic compounds for CVD complementary therapy in the near future.In the last decade the scientific researchers turned their attention to phytochemicals, as effective, safe and low-cost natural bioactive compounds for CVD treatment.Dyslipidemia consists of increased blood concentrations of total cholesterol (TC), low density lipoproteins-cholesterol (LDL-C) and/or triglycerides (TG), and decreased high density lipoproteins-cholesterol (HDL-C) [6]. The lipid metabolism is complex and the candidate mechanisms that could generate dyslipidemia include: (i) excessive dietary lipid absorption in the small intestine; (ii) packing of exogenous lipids with cholesterol and fatty acids produced de novo in the liver and their secretion as very low density lipoproteins (VLDL); (iii) hydrolysis of TG from VLDL by lipases and their conversion into LDL, which are taken up by the peripheral tissues through LDL receptor (LDL-R) and scavenger receptors; (iv) diminished production of HDL by the liver and small intestine, thereby decreasing reverse cholesterol transport (RCT) from the peripheral tissues to the liver; (v) lowered excess cholesterol excretion from the liver into gallbladder or to the intestinal lumen through the ATP-binding cassette G5 and G8 transporters (ABCG5/G8) that facilitate trans-intestinal cholesterol efflux (TICE). Dyslipidemia is associated with the accumulation of LDL in the sub-endothelium of the artery wall. At this site, LDL undergoes oxidative modifications (oxLDL) that trigger inflammatory responses, and is taken up by the monocyte-derived macrophages infiltrated in the sub-endothelium which thus become lipid-loaded foam cells, the hallmark of atheroma development [7]. Until now, the most effective lipid-lowering treatment for hyperlipidemic patients was the statin therapy. But recen...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

et al. 2020

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“…Curcumin is a polyphenolic compound found primarily in the rhizomes of the ginger plant, and is believed to be one of the most biologically active natural products. It has been shown that curcumin has pharmacological effects in a wide variety of chronic diseases ( 18 , 19 ). Dong et al ( 20 ) speculated that curcumin or food rich in curcumin, have the potential to be a novel therapy for decreasing the risk of AS by increasing the expression levels of ABCA1 and increasing the cholesterol efflux in mouse adipocytes by the peroxisome proliferator activated receptor γ/liver X receptor α signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

“…Lin et al ( 18 ) found that curcumin can inhibit ox-ldl-induced MCP-1 expression of VSMCs via the mitogen activated protein kinases (MAPK) and nuclear transcription factor κB (NF-κB) signaling pathway. Although a number of studies investigated the mechanisms behind the pharmacological activity of curcumin ( 18-20 ), the exact mechanism behind its pharmacological effects still remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Curcumin affects ox‑LDL‑induced IL‑6, TNF‑α, MCP‑1 secretion and cholesterol efflux in THP‑1 cells by suppressing the TLR4/NF‑κB/miR33a signaling pathway

Zhong

Liu²,

Feng

et al. 2020

Exp Ther Med

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The aim of the present study was to study the molecular mechanism of how curcumin decreases the formation of ox-LDL induced human monocyte macrophage foam cells, promotes the efflux of cholesterol and reduces the secretion of inflammatory cytokines. In vitro cultured THP-1 cells were induced to become macrophages using phorbol-12-myristate-13-acetate. The cells were then pre-treated with curcumin before inducing the foam cell model by addition of oxidized low-density lipoprotein (ox-LDL). Western blot assays were used to detect expression levels of toll-like receptor (TLR)4, nuclear factor κB (NF-κB), NF-κB inhibitor α (IκBα), phosphorylated-IκBα and ATP binding cassette transporter (ABC)A1. Reverse transcription-quantitative PCR was employed to examine mRNA levels of TLR4, microRNA (miR)33a and ABCA1. ELISAs were used to detect inflammatory factors, including tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1 and interleukin (IL)-6. ox-LDL successfully induced the foam cell model, promoted phosphorylation of IκBα, promoted nuclear translocation of NF-κB, promoted the expression of TLR4 and miR33a, and promoted the secretion of TNF-α, MCP-1 and Il-6. Additionally, ox-LDL reduced the expression of ABCA1 and cholesterol efflux. However, pretreatment with curcumin increased the expression of ABCA1 and cholesterol efflux and suppressed secretion of TNF-α, MCP-1 and Il-6. TLR4 antibodies, the NF-κB blocker, PDTC, and the miR33a inhibitor also reduced the abnormal transformations induced by ox-LDL. Curcumin promoted cholesterol efflux by suppressing the TLR4/NF-κB/miR33a signaling pathway, and reduced the formation of foam cells and the secretion of inflammatory factors.

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“…Sirt3 located mainly in mitochondria regulates metabolism and oxidative stress [48,49]. The clinical drug metformin [22] and a number of natural bioactive compounds [52][53][54] have been reported to have anti-atherosclerotic effect, including curcumin, quercetin, puerarin, resveratrol, etc. by activating Sirt1 and/or AMPK.…”

Section: Discussionmentioning

confidence: 99%

Atherosclerosis is attenuated by acacetin via Sirt1-mediated activation of AMPK/Sirt3 signals in diabetic ApoE-/- mice

Han¹,

Chen²,

Wang³

et al. 2020

Preprint

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BackgroundThe strategy of decreasing atherosclerotic cardiovascular disorder is imperative to reduce premature death and improve quality of life in patients with diabetes mellitus. The present study was designed to investigate whether the natural flavone acacetin could improve diabetes- accelerated atherosclerotic lesions.MethodsDiabetic model was established in 7-week-old ApoE−/− mice by intraperitoneal injection of STZ (daily 50 mg/kg) for 5 days. Animals of control, control with acacetin treatment, STZ-diabetes, STZ-diabetes with acacetin treatment received acacetin prodrug subcutaneously (20 mg/kg, b.i.d.) or equivolume saline for 12 weeks, and the elasticity of carotid artery and the ability of vascular wall movement were determined with ultrasound and magnetic resonance imaging. Human umbilical vein endothelial cells (HUVECs) were cultured with medium containing 5.5 mM or 33 mM glucose and treated with acacetin or vehicle. Changes of related aortic lesions and signaling molecules were determined by biochemical and molecular approaches in animals and cultured HUVECs.ResultsIt was found that acacetin significantly suppressed atherosclerotic lesions and neointima hyperplasia, improved the elasticity of carotid artery and the ability of vascular wall movement without reducing blood glucose level and reversed the impaired signaling molecules (i.e. SOD, Bcl2, PGC-1α, pAMPK, Sirt3 and Sirt1) in artery tissues in diabetic mice. In cultured HUVECs, high glucose-induced cell viability reduction, ROS over-production, decrease of anti-oxidation, increase of apoptosis, and impairment of mitochondrial function were countered by acacetin (0.3-3 µM) in a concentration-dependent manner. Moreover, acacetin relies on Sirt1 activation by increasing NAMPT and NAD+ followed by Sirt3, pAMPK and PGC-1α activation. Silencing Sirt1 abolished acacetin-induced activation of Sirt3, pAMPK, and PGC-1α.ConclusionsThese results indicate that Sirt1-mediated activation of pAMPK/Sirt3 signals is involved in protective effects of acacetin against atherosclerosis in diabetes by preserving mitochondrial function via reducing mitochondrial apoptosis and ROS production and enhancing its biogenesis, which suggests that acacetin may be a drug candidate for reducing atherosclerotic cardiovascular disorder in patients with diabetes.

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Efficacy of Curcumin on Aortic Atherosclerosis: A Systematic Review and Meta-Analysis in Mouse Studies and Insights into Possible Mechanisms

Cited by 24 publications

References 61 publications

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

Curcumin affects ox‑LDL‑induced IL‑6, TNF‑α, MCP‑1 secretion and cholesterol efflux in THP‑1 cells by suppressing the TLR4/NF‑κB/miR33a signaling pathway

Atherosclerosis is attenuated by acacetin via Sirt1-mediated activation of AMPK/Sirt3 signals in diabetic ApoE-/- mice

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