Tetrahydrocurcumin-Related Vascular Protection: An Overview of the Findings from Animal Disease Models

Abstract

Tetrahydrocurcumin (THC), one of the major metabolites of CUR, possesses several CUR-like pharmacological effects; however, its mechanisms of action are largely unknown. This manuscript aims to summarize the literature on the preventive role of THC on vascular dysfunction and the development of hypertension by exploring the effects of THC on hemodynamic status, aortic elasticity, and oxidative stress in vasculature in different animal models. We review the protective effects of THC against hypertension induced by heavy metals (cadmium and iron), as well as its impact on arterial stiffness and vascular remodeling. The effects of THC on angiogenesis in CaSki xenografted mice and the expression of vascular endothelial growth factor (VEGF) are well documented. On the other hand, as an anti-inflammatory and antioxidant compound, THC is involved in enhancing homocysteine-induced mitochondrial remodeling in brain endothelial cells. The experimental evidence regarding the mechanism of mitochondrial dysfunction during cerebral ischemic/reperfusion injury and the therapeutic potential of THC to alleviate mitochondrial cerebral dysmorphic dysfunction patterns is also scrutinized and explored. Overall, the studies on different animal models of disease suggest that THC can be used as a dietary supplement to protect against cardiovascular changes caused by various factors (such as heavy metal overload, oxidative stress, and carcinogenesis). Additionally, the reviewed literature data seem to confirm THC’s potential to improve mitochondrial dysfunction in cerebral vasculature during ischemic stroke through epigenetic mechanisms. We suggest that further preclinical studies should be implemented to demonstrate THC’s vascular-protective, antiangiogenic, and anti-tumorigenic effects in humans. Applying the methods used in the presently reviewed studies would be useful and will help define the doses and methods of THC administration in various disease settings.

Positive Tetrahydrocurcumin-Associated Brain-Related Metabolomic Implications

“…In the same direction, Nakmareong et al [7] showed that administration of a THC-containing diet in a rat model of N(omega)-Nitro-L-Arginine Methyl Ester (L-NAME)-induced oxidative stress leads to a significantly reduced production of superoxide (O2•) and malondialdehyde (MDA), followed by increased endogenous synthesis of glutathione (GSH) [8]. Similarly, THC significantly reduced L-NAME-induced aortic wall thickness and stiffness [9]. Ma et al [10], investigating the relationship between the antioxidative brain potential of brain tissue and cognitive impairment in a C57BL/6 mouse model induced by acute hypobaric hypoxia, discovered that THC improved cognitive impairment, accompanied by reduced oxidative stress and increased glucose transporter 1 (GLUT1) protein levels.…”

“…THC reduces cytochrome c homocysteinylation by decreasing oxidative stress and matrix metalloproteinase 9 (MMP9), as well as protecting neurons via autophagic mechanisms. [9]. The BBB could be disrupted in a variety of clinical situations, including I/R injury, which causes increased vascular permeability and the formation of cerebral edema [74].…”

Estimated pulse wave velocity is associated with all-cause mortality and cardiovascular mortality among adults with diabetes

“…Vascular remodeling is thought to be an important feature of human aging, loss of arterial elasticity is common as people age ( 12 , 13 ). But at the individual level, vascular remodeling is actually a dynamic process, influenced by life style, genetic/epigenetic factors, and biological cues ( 14 – 16 ). Diabetes is an important risk factor for vascular remodeling, which can cause extracellular matrix changes, eventually leading to arterial remodeling and arterial stiffness ( 17 , 18 ).…”

Anticarcinogenic Potency of EF24: An Overview of Its Pharmacokinetics, Efficacy, Mechanism of Action, and Nanoformulation for Drug Delivery

“…In comparison to other CUR analogues and some natural products, EF24 offers distinct advantages, primarily stemming from its engineered properties, pro-apoptotic effects, and its potential role as a targeted therapy in the context of cancer treatment [4][5][6][7][8][9]. Actually, it is crucial to acknowledge that most of the mentioned analogues come with certain limitations.…”

“…Actually, it is crucial to acknowledge that most of the mentioned analogues come with certain limitations. These limitations can be attributed to either weak bioavailability or a trade-off between their more pronounced antioxidant or anti-inflammatory effects and their efficacy in combating cancer [4][5][6][7][8][9]. Taking into consideration these inherent characteristics and limitations, EF24 stands out as one of the most suitable and potent options.…”