Table 3.
Animal experimental studies of antioxidant compounds and other therapeutic options that target OS with potential in CAVD treatment.
| Ref. | Compound | Species and/or Cells Researched | Meaningful Findings |
|---|---|---|---|
| [121] | E06 natural antibody | E06-scFv transgenic mice | -Counteracted the proinflammatory and proatherogenic OxPL effects. |
| [126] | Resveratrol | Ovariectomized rats | -Reduced RUNX2, ALP expression, and aortic calcification. |
| [127] | Resveratrol | Rat vascular smooth muscle cells (RASMCs) | -Prevents vascular calcification and mitochondria dysfunction through SIRT1 and Nrf2. |
| [128] | Resveratrol | Mouse model of uremia | -Fewer aortic atherosclerotic lesions at the site of the ascending aorta. |
| [131] | Resveratrol | Porcine aortic valve interstitial cells (pVICs) | -Inhibition of osteogenic pVIC differentiation through the AKT/SMAD1/5/8 signaling pathway. |
| [129] | PLD the natural precursor of resveratrol | Mice with complete ligatures of the left carotid arteries for 14 days | -Reduced adhesion molecule expression (ICAM-1, VCAM-1), proinflammatory cytokine production (TNF-α, IL-1β), iNOS, NF-κB expression, and BAX, Fas-Ligand activation. |
| [136] | Curcumin | Apolipoprotein E-knockout mice | -Reduced TLR4 expression, macrophage infiltration in atherosclerotic plaque, aortic IL-1β, TNF-α, VCAM-1, ICAM-1 expression, NF-κB activity, and plasma IL-1β, TNF-α, soluble VCAM-1, and ICAM-1 levels; -Reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development. |
| [138] | Curcumin | Different types of mice, all treated with HF and mice fed with a normal chow diet | -Reduced serum lipid levels, TNF-α, IL-1β, and the aortic atherosclerotic lesion area. |
| [141] | Cardamonin | In Vivo: mice model fed with a HF diet | -Inhibition of VIC osteogenic differentiation through the NF-κB/NLRP3 inflammasome pathway. |
| [143] | Ellagic acid | Rat model | -Improved nitric oxide bioavailability and reduced ROS formation. |
| [144] | Gallic acid | Vascular smooth muscle cell | -Inhibition of vascular calcification through the BMP2-SMAD1/5/8 signaling pathway. |
| [149] | Nobiletin | Male Wistar rats | -Increased intracellular cGMP (activation of cGC, opening BK channels and KATP channels). |
| [151] | Quercetin | Adenine-induced chronic renal failure rats | -Modulation of vascular calcification through the iNOS/p38 MAPK pathway. |
| [154] | Anthocyanins | Tac-induced myocardial dysfunction in mice | -Ameliorated Tac-induced myocardial dysfunction, oxidative stress, and apoptosis via the DDAH1/ADMA/no pathway. |
| [155] | Puerarin | In Vitro; rat vascular smooth muscle cells In Vivo; uremic rats |
-Modulated NLRP3/CASPASE1/IL-1β, NF-κB, and ER/PI3K-AK signaling pathways; -Prevents calcium deposition and inhibits the expression of RUNX2 and BMP2. |
| [158] | Puerarin | VSMCs | -Inhibited oxLDL-induced VSMC viability via inhibition of the p38 MAPK and JNK signaling pathways; -Decreased the levels of IL-6 and TNF-α and increased SOD activity. |
| [161] | Diosgenin | Adenine-induced chronic renal failure rats | -Inhibited the c/Akt/ERK, p38 pathway. |
| [162] | 10-DHGD | HCD-fed rabbits | -Alleviated calcium deposition via the downregulation of the BMP2/Wnt3a pathway, OPG/RANK modulation, and raised HDL-C levels. |
| [164] | Vitamin E | Uremic obese rats | -Prevents osteoblastic differentiation in VSMC and inhibits dephosphorylation of Akt. |
| [87] | Fucoxanthin | In Vitro; rat heart VIC In Vivo; dog model | -Inhibition of the Akt/ERK pathway. |
| [172] | Apocynin | VSMCs | -Enhanced expression of α-SMA, reduced expression of BMP2, RUNX2, OPN, suppressed the ERK1/2 pathway and phosphorylation of p47phox (cytosolic NOX2 component). |
| [70] | Celastrol | In Vitro; porcine AVIC In Vivo; rabbit CAVD model | -Inhibition of NADPH Oxidase 2 and the GSK3β/β-catenin pathway |
| [174] | Celastrol | Macrophages in mice | -Attenuated oxLDL-induced excessive expression of LOX-1; -Decreased IkB phosphorylation and degradation, reduced production of iNOS, NO, TNF-α, and IL-6; -Reduced atherosclerotic plaque size. |
| [75] | Glycine | Streptozotocin-induced diabetic rats and HUVECs | -Downregulating the AGE/RAGE signaling pathway by decreasing levels of AGEs, RAGE, NOX4, and NF-κB p65, and by restoring GLO1 function. |
| [182] | MnBuOE | hVIC and murine model of aortic valve sclerosis | -Inhibited aortic valve remodeling and α-SMA upregulation via TGF-β1; -Upregulated MnSOD via activation of Nrf2. |
| [52,85] | Mitoquinone | Male Sprague–Dawley rats and adult C57BL/6J mice | -Reduced vascular calcification through the Nrf2/Keap1 pathway and fibrosis by inhibiting the TGF-β1-NOX4-ROS axis. |
| [184] | DETA NONOate |
PAVEC and aortic VIC PAVIC | -Inhibited VIC osteogenic differentiation and calcification. |
| [186] | L-arginine | Bovine aortic VICs | -Inhibited VIC osteogenic differentiation and remodeling by downregulating ADAMTSL4 and fibrillin-1. |
| [89] | Anagliptin | Eight-week-old male BALB/c mice | -Activated the PI3K/Akt signaling pathway; -Downregulated the expression of MCP-1, ICAM-1, VCAM-1; -Reduced proteolysis via MMP-2/-9 and CatS/K. |
| [122,190] | Sitagliptin | Weaned male low-density lipoprotein receptor knockout mice | -Blocked NADPH activation; -Inhibited calcification by downregulating RAGE expression and NF-κB activation. |
| [189] | Sitagliptin | Rabbit model of CAVD fed with HCD and vitamin D2 | -Reduced osteogenic transformation of VICs by reinstating IGF-1 activity. |
| [198] | Evogliptin | hVIC, endothelial nitric oxide synthase-deficient, male New Zealand white rabbits | -Reduced TNF-α, IL-1β, and IL-6 levels; -Reduced RUNX2 expression. |
| [69] | Pioglitazone | Mice fed a western-type diet | -Attenuated cusp mobility and inhibited valve calcification by reducing TNFα, IL-6, and BMP2. |
| [193] | Pioglitazone | Male New Zealand rabbits | -Reduced RAGE activation and inhibited NF-κB p65 intranuclear translocation. |
High-fat diet (HF); transverse aortic constriction (Tac); vascular smooth muscle cells (VSMCs); 10-dehydrogingerdione (10-DHGD); high cholesterol diet (HCD); MnTnBuOE-2-PyP5+ (MnBuOE); NO donors application (DETA-NONOate); Porcine aortic VEC (PAVEC); aortic VIC (PAVIC); Polydatin (PLD).