Anti-atherosclerotic Effects of Spice-Derived Phytochemicals

Abstract

: Cardiovascular diseases are the leading cause of death in the world. Atherosclerosis is characterized by oxidized lipid deposition, and inflammation in the arterial wall and represents a significant problem in public health and medicine. Some dietary spices have been widely used in many countries; however, the mechanism of their action as it relates to the prevention and treatment of atherosclerosis is still poorly understood. In this review, we focus on the properties of various spice-derived active ingredients used in the prevention and treatment of atherosclerosis, as well as associated atherosclerotic risk factors. We provide a summary of the mechanisms of action, epidemiological analyses, and studies of various components of spice used in the clinic, animal models, and cell lines related to atherosclerosis. Most notably, we focused on mechanisms of action by which these spice-derived compounds elicit their lipid-lowering, anti-inflammatory, antioxidant, and immunomodulatory properties, as well as their involvement in selected biochemical and signal transduction pathways. It is suggested that future research should aim to design well-controlled clinical trials and more thoroughly investigate the role of spices and their active components in the prevention/treatment of atherosclerosis. Based on this literature review, it appears that spices and their active components are well tolerated and have few adverse side effects and, therefore, provide a promising adjunctive treatment strategy for patients with atherosclerosis.

Animal Models of Neointimal Hyperplasia and Restenosis

“…Sprague-Dawley and Wistar rats are frequently used strains for atherosclerosis and neointimal hyperplasia research. Rats that mimic certain aspects of cardiovascular pathophysiology, such as the spontaneously hypertensive rat ( 71 ) or the obese rat versus the lean Zucker rat [diabetes type 2 ( 72 )], can be used to study the specific influence of key cardiovascular risk factors on neointimal hyperplasia. These models, combined with angioplasty procedures (eg, stenting), allow for a more translational investigation of cellular and molecular processes of restenosis compared with mere dietary or mechanical injury models ( 73 ).…”

Impact of Phytochemicals on PPAR Receptors: Implications for Disease Treatments

“…A recent study showed that UA (0-50 μ M) may exert antiskin cancer effects by promoting AMPK and PPAR α in Ca3/7 and MT1/2 premalignant and malignant skin cancer cell lines [ 166 ]. Also, ursolic acid in combination with artesunate suppressed hyperlipidemia and atherosclerosis due to increasing low density lipoprotein receptor (LDLR), apolipoprotein A-I (apoA-I), and PPAR α , as well as SREBP1 reduction in a hyperglycemic rabbit model [ 7 ]. Therefore, UA, a PPAR ligand and coactivator ( Table 1 ), could play a role in management of multiple diseases, but future animal or clinical studies are needed to prove its promising properties related to PPARs.…”

“…In addition to the compounds mentioned above, other natural phytochemicals showed potential PPARs ligand activity in research studies ( Table 1 ). Terpenoids such as 1,8-cineole [ 7 , 179 ], gingerol [ 7 ], cinnamaldehyde [ 180 ], carvacrol [ 181 ], zerumbone [ 182 ], oridonin [ 183 ], tanshinone IIA [ 184 ], pedunculoside [ 185 ], and lycopene and β -carotene [ 186 ] acted as dual PPARs activators for exhibiting antiatherosclerotic, antiadipogenic, anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemia effects. Interestingly, betulinic acid (a triterpenoid) had PPAR γ and PPAR α antagonist activity in 3T3-L1 cells to boost glucose uptake and osteogenesis, along with adipogenesis inhibition [ 187 ].…”

“…Curcumin. Curcumin is a natural lipophilic polyphenol from the rhizome of turmeric, Curcuma longa L. (Zingiberaceae), which can modulate a number of signaling pathways in its biological activities, including inflammation, atherosclerosis, and cardiovascular disease [7,8]. Curcumin has been found to remarkably enhance peroxisome proliferatoractivated receptor-α and γ (PPARα and PPARγ) in its antiinflammatory, antioxidant, antihyperglycemic, and insulin sensitizer effects (Table 1) [8][9][10].…”

The effect of nuts consumption on circulating oxidized low‐density lipoproteins: A systematic review and meta‐analysis of randomized controlled trials

“…Recently, many dietary supplements and herbal products have garnered attention owing to their potential effects on ASCVD risk factors, among them are nuts (Ahmadi et al, 2022; Alidadi et al, 2020; Atazadegan et al, 2021; Bagherniya et al, 2021; Enayati et al, 2021; Enayati, Banach, Jamialahmadi, Sahebkar, & endorsed by the International Lipid Expert, 2022; Mahdavi et al, 2020; Ruscica et al, 2021; Shao et al, 2018; Soltani et al, 2021; Talebi et al, 2020; Vahdat‐Lasemi et al, 2021). Nuts (tree nuts) which are fruits and peanuts (which are not fruit but vegetables) are rich sources of antioxidants and phytochemical (including phytosterols, carotenoids, and polyphenols like flavonoids and stilbenes) (Lorenzon dos Santos et al, 2020).…”