The protective effects of curcumin against cigarette smoke-induced toxicity: A comprehensive review.

Cigarette smoking (CS) is a crucial modifiable risk of developing several human diseases and cancers. It causes lung, bladder, breast, and esophageal cancers, respiratory disorders, as well as cardiovascular and metabolic diseases. Because of these adverse health effects, continual efforts to decrease the prevalence and toxicity of CS are imperative. Until the past decades, the impacts of natural compounds have been under investigation on the harmful effects of CS. Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant that belongs to the Zingiberaceae family, is the main source of curcumin. This review is an attempt to find out the current knowledge on CS's harmful effects and protective potential of curcumin in the pulmonary, liver, brain, gastrointestinal, and testis organs. According to the present review, simultaneous consumption of curcumin and CS can attenuate CS toxicities including chronic obstructive pulmonary disease, gastrointestinal toxicity, metabolic diseases, testis injury, and neurotoxicity. Moreover, curcumin suppresses carcinogenesis in the skin, liver, lungs, breast, colon, and stomach. Curcumin mediates these protective effects through antioxidant, anti-inflammatory, anti-apoptotic, and anti-carcinogenicity properties.

Zirconium dioxide nanoparticles induced cytotoxicity in rat cerebral cortical neurons and apoptosis in neuron-like N2a and PC12 cell lines.

During recent decades, the application of zirconium dioxide nanoparticles (ZrO2-NP) has been expanded in various fields ranging from medicine to industry. It has been shown that ZrO2-NP has the potential to cross the blood-brain barrier (BBB) and induce neurotoxicity. In the current study, we investigated the in vivo neurotoxicity, as well as, the cellular mechanism of ZrO2-NP toxicity on two neuronal-like cell lines, PC12 and N2a. PC12 and N2a cells were exposed to increasing concentrations of ZrO2-NP (0-2000 µg/ml) for 48 h. The apoptotic effect of ZrO2-NP was determined using annexin V/propidium iodide double staining (by flow cytometry), and western blot analysis of relative apoptotic proteins, including caspase-3, caspase-9, bax, and bcl2. Based on our results, ZrO2-NP at concentrations of 250-2000 µg/mL increased both early and late-stage apoptosis in a concentration-dependent manner. Moreover, the expressions of cleaved-caspase-3 and -9 proteins and the bax/bcl2 ratio were significantly increased. In addition, oral administration of ZrO2-NP (50 mg/kg) to male Wistar rats for 28 days led to the loss of neuronal cells in the cerebral cortex. Taken together, our findings highlighted the role of apoptosis on cytotoxicity induced by ZrO2-NP.

Mephedrone induced apoptosis and impaired neurogenesis in embryonic neural stem/progenitor cells.

Mephedrone, a synthetic derivative of cathinone, is a commonly used psychoactive substance. Our previous study showed that exposure to mephedrone during pegnancy induced antiproliferative and pro-apoptotic effects in hippocampus of mice delivered pups. However, its effects on neural stem/progenitor cells (NS/PC) remain unexplored. The aim of this study is to investigate the effects of mephedrone exposure on the proliferation, differentiation, and apoptosis of rat embryonic NS/PC. NS/PC were isolated from rat fetal ganglionic eminence region at embryonic day 14.5. The effects of mephedrone on cell proliferation, neurosphere formation (colonies of NS/PC), neuronal differentiation, and apoptosis of NS/PC were assessed using MTT, immunocytochemistry, and flow cytometry. Mephedrone at concentrations of 20-640 µM significantly decreased the proliferation of NS/PC, induced cell cycle arrest, and enhanced the percent of apoptotic and necrotic cells. Neurosphere assays revealed a significant reduction in the number and diameter of neurosphere-forming cells. In addition, mephedrone significantly decreased the expressions of DCX and NeuN neuronal markers. Taken together, our results suggeste that exposure to mephedrone decreases the viability and neuronal differentiation of embryonic NS/PC. This study showed that mephedrone exposure during fetal or neonatal life may impair neurogenesis and subsequent brain development.

Everolimus attenuates glutamate-induced PC12 cells death.

BACKGROUND: Glutamate-induced neuronal cell death plays a key role in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Some recent studies reported the potential immunomodulatory and neuroprotective properties of inhibitors of serine-threonine kinase, mTOR (mammalian target of rapamycin). However, no study was conducted about the neuroprotective potential of everolimus (EVR), a selective and potent mTOR inhibitor. Therefore, this study was planned to investigate whether EVR has protective effects against glutamate-induced toxicity in PC12 cells, which are used as model for neurons injury, and to elucidate the underlying mechanism. METHODS: PC12 cells were concurrently treated with glutamate (8 mM) and EVR (0-40 nM) for 24 h. Then, the cells viability, apoptosis rate, and apoptosis-related proteins (caspase-3, bax and bcl-2) were measured using MTT, annexin V/PI and immunoblotting assays. RESULTS: Analyzing the protective effect of different concentrations of EVR (0-40 nM) against glutamate-induced cytotoxicity revealed a significant increase in cell viability in co-treatment regimen (p < 0.01). Also, EVR (40 nM) significantly (p < 0.01) inhibited glutamate-induced apoptosis through depressing the elevation of bax/bcl-2 ratio and expression of cleaved caspase-3, concentration depend. CONCLUSION: The results demonstrated, for the first time, that EVR could protect against glutamate-mediated PC12 cell death via inhibiting apoptosis.

Involvement of the transient receptor potential A1 in morphine-induced conditioned place preference and physical dependence in mice.

The main side effects of opioid use are physiological and psychological dependence. The transient receptor potential channels, including transient receptor potential ankyrin 1 (TRPA1), are involved in various neurological disorders. We aimed to evaluate the effect of TRPA1 inhibition on morphine-induced conditioned place preference (CPP) and physical dependence. For induction of CPP, morphine (10 and 20 mg/kg) was administrated for four consecutive days to male BALB/c mice. The effects of HC030031 (TRPA1 antagonist, 10, 25, and 50 mg/kg) on the expression and reinstatement of morphine-induced CPP were evaluated. For induction of physical dependence, morphine was injected three times a day for 3 days. Withdrawal-related behaviors such as jumping and defecation were precipitated by the administration of naloxone to morphine-dependent mice. The effect of HC030031 on jumping and defecation was assessed. The results showed that 20 mg/kg of morphine elicited a significant CPP. HC030031 reduced the expression of morphine CPP without any change in the locomotor activity. It also decreased the reinstatement of morphine CPP. HC030031 mitigated morphine withdrawal via reducing jumping and defecation. The present study demonstrated that HC030031 decreased morphine-associated CPP and physical dependence. It is presumed that TRPA1 has interaction with the main pharmacological effects of morphine.

Beneficial effects of levetiracetam in streptozotocin-induced rat model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly. In the light of increasing AD prevalence and lack of effective treatment, new strategies to prevent or reverse this condition are needed. Levetiracetam (LEV) is a newer antiepileptic drug that is commonly used to treat certain types of seizures. Researches indicated that LEV has several other pharmacological activities, including improvement of cognitive function. In this study, the recovery effects of chronic (28 days) administration of LEV (50, 100, and 150 mg/kg, ip) on cognitive deficits caused by the intracerebroventricular (icv) injection of streptozotocin (STZ), as a model for sporadic AD, were evaluated in rats. We also considered the protective effects of LEV against hippocampal cell loss, oxidative damage, acetylcholinesterase (AChE) activity, neuroinflammation, and tauopathy caused by STZ. LEV (100 and 150 mg/kg) significantly attenuated the STZ-induced learning and memory impairments in the passive avoidance and Morris water maze (MWM) tasks. In addition, LEV suppressed STZ-induced hippocampal neuronal loss, while restored alterations in the redox status (lipid peroxides and glutathione), AChE activity, proinflammatory cytokines (IL-1ß, IL-6, TNF-α), and hyperphosphorylation of tau linked to STZ administration. In conclusion, our study demonstrated that LEV alleviated hippocampal cell death and memory deficits in STZ-AD rats, through mitigating oxidative damage, suppression of proinflammatory cytokines expression, and inhibition of abnormal tau hyperphosphorylation.

An updated review of protective effects of rosemary and its active constituents against natural and chemical toxicities.

Natural and chemical toxic agents cause severe adverse effects on people's health in a variety of exposing ways. Herbal medications have taken into consideration as alternative safe treatments for toxicities. Rosmarinus officinalis also known as rosemary belongs to the Lamiaceae family. Rosemary and its constituents including carnosic acid, rosmarinic acid, and carnosol have a lot of benefits such as anti-inflammatory, antioxidant, anti-mutagenic, anti-bacterial, antiviral, antinociceptive, and neuroprotective activities. In this literate review, we focused on the protective effects of rosemary and its main compounds against natural and chemical toxicities in both in vitro and in vivo studies. The protective effects of rosemary and its components are mostly mediated through different mechanisms such as the inhibition of oxidative stress, reduction of inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), cyclooxygenase-2 (COX-2) and nuclear factor ĸB (NF-ĸB) as well as the modulation of apoptosis and mitogen-activated protein kinase (MAPK) signaling pathways.

Milk thistle (Silybum Marianum) as an antidote or a protective agent against natural or chemical toxicities: a review.

Biological and chemical agents cause dangerous effects on human health via different exposing ways. Recently, herbal medicine is considered as a biological and safe treatment for toxicities. Silybum marianum (milk thistle), belongs to the Asteraceae family, possesses different effects such as hepatoprotective, cardioprotective, neuroprotective, anti-inflammatory and anti-carcinogenic activities. Several studies have demonstrated that this plant has protective properties against toxic agents. Herein, the protective effects of S. marianum and its main component, silymarin, which is the mixture of flavonolignans including silibinin, silydianin and silychristin acts against different biological (mycotoxins, snake venoms, and bacterial toxins) and chemical (metals, fluoride, pesticides, cardiotoxic, neurotoxic, hepatotoxic, and nephrotoxic agents) poisons have been summarized. This review reveals that main protective effects of milk thistle and its components are attributed to radical scavenging, anti-oxidative, chelating, anti-apoptotic properties, and regulating the inflammatory responses.

Transient receptor potential ankyrin 1 (TRPA1)-mediated toxicity: friend or foe?

Transient receptor potential (TRP) channels have been widely studied during the last decade. New studies uncover new features and potential applications for these channels. TRPA1 has a huge distribution all over the human body and has been reported to be involved in different physiological and pathological conditions including cold, pain, and damage sensation. Considering its role, many studies have been devoted to evaluating the role of this channel in the initiation and progression of different toxicities. Accordingly, we reviewed the most recent studies and divided the role of TRPA1 in toxicology into the following sections: neurotoxicity, cardiotoxicity, dermatotoxicity, and pulmonary toxicity. Acetaminophen, heavy metals, tear gases, various chemotherapeutic agents, acrolein, wood smoke particulate materials, particulate air pollution materials, diesel exhaust particles, cigarette smoke extracts, air born irritants, sulfur mustard, and plasticizers are selected compounds and materials with toxic effects that are, at least in part, mediated by TRPA1. Considering the high safety of TRPA1 antagonists and their efficacy to resolve selected toxic or adverse drug reactions, the future of these drugs looks promising.

The role of ATP-binding cassette transporter G1 (ABCG1) in Alzheimer's disease: A review of the mechanisms.

The maintenance of cholesterol homeostasis is essential for central nervous system function. Consequently, factors that affect cholesterol homeostasis are linked to neurological disorders and pathologies. Among them, ATP-binding cassette transporter G1 (ABCG1) plays a significant role in atherosclerosis. However, its role in Alzheimer's disease (AD) is unclear. There is inconsistent information regarding ABCG1's role in AD. It can increase or decrease amyloid ß (Aß) levels in animals' brains. Clinical studies show that ABCG1 is involved in AD patients' impairment of cholesterol efflux capacity (CEC) in the cerebrospinal fluid (CSF). Lower Aß levels in the CSF are correlated with ABCG1-mediated CEC dysfunction. ABCG1 modulates α-, ß-, and γ-secretase activities in the plasma membrane and may affect Aß production in the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) cell compartment. Despite contradictory findings regarding ABCG1's role in AD, this review shows that ABCG1 has a role in Aß generation via modulation of membrane secretases. It is, however, necessary to investigate the underlying mechanism(s). ABCG1 may also contribute to AD pathology through its role in apoptosis and oxidative stress. As a result, ABCG1 plays a role in AD and is a candidate for drug development.

The role of transient receptor potential (TRP) channels in phagocytosis: A comprehensive review.

When host cells are exposed to foreign particles, dead cells, or cell hazards, a sophisticated process called phagocytosis begins. During this process, macrophages, dendritic cells, and neutrophils engulf the target by expanding their membranes. Phagocytosis of apoptotic cells is called efferocytosis. This process is of significant importance as billions of cells are eliminated daily without provoking inflammation. Both phagocytosis and efferocytosis depend on Ca2+ signaling. A big family of Ca2+ permeable channels is transient receptor potentials (TRPs) divided into nine subfamilies. We aimed to review their roles in phagocytosis. The present review article shows that various TRP channels such as TRPV1, 2, 3, 4, TRPM2, 4, 7, 8, TRPML1, TRPA1, TRPC1, 3, 5, 6 have roles at various stages of phagocytosis. They are involved in the phagocytosis of amyloid ß, α-synuclein, myelin debris, bacteria, and apoptotic cells. In particular, TRPC3 and TRPM7 contribute to efferocytosis. These effects are mediated by changing Ca2+ signaling or targeting intracellular enzymes such as Akt. In addition, they contribute to the chemotaxis of phagocytic cells towards targets. Although a limited number of studies have assessed the role of TRP channels in phagocytosis and efferocytosis, their findings indicate that they have critical roles in these processes. In some cases, their ablation completely abolished the phagocytic function of the cells. As a result, TRP channels are potential targets for developing new therapeutics that modulate phagocytosis.

Differential effects of antiseizure medications on neurogenesis: Evidence from cells to animals.

Neurogenesis, the process of generating functionally integrated neurons from neural stem and progenitor cells, is involved in brain development during embryonic stages but continues throughout life. Adult neurogenesis plays essential roles in many brain functions such as cognition, brain plasticity, and repair. Abnormalities in neurogenesis have been described in many neuropsychiatric and neurological disorders, including epilepsy. While sharing a common property of suppressing seizures, accumulating evidence has shown that some antiseizure medications (ASM) exhibit neuroprotective potential in the non-epileptic models including Parkinson's disease, Alzheimer's disease, cerebral ischemia, or traumatic brain injury. ASM are a heterogeneous group of medications with different mechanisms of actions. Therefore, it remains to be revealed whether neurogenesis is a class effect or related to them all. In this comprehensive literature study, we reviewed the literature data on the influence of ASM on the neurogenesis process during brain development and also in the adult brain under physiological or pathological conditions. Meanwhile, we discussed the underlying mechanisms associated with the neurogenic effects of ASM by linking the reported in vivo and in vitro studies. PubMed, Web of Science, and Google Scholar databases were searched until the end of February 2023. A total of 83 studies were used finally. ASM can modulate neurogenesis through the increase or decrease of proliferation, survival, and differentiation of the quiescent NSC pool. The present article indicated that the neurogenic potential of ASM depends on the administered dose, treatment period, temporal administration of the drug, and normal or disease context.

TRPA1 as a promising target in ischemia/reperfusion: A comprehensive review.

Ischemic disorders, including myocardial infarction, cerebral ischemia, and peripheral vascular impairment, are the main common reasons for debilitating diseases and death in Western cultures. Ischemia occurs when blood circulation is reduced in tissues. Reperfusion, although commanded to return oxygen to ischemic tissues, generates paradoxical tissue responses. The responses include generating reactive oxygen species (ROS), stimulating inflammatory responses in ischemic organs, endoplasmic reticulum stress, and the expansion of postischemic capillary no-reflow, which intensifies organ damage. Multiple pathologic processes contribute to ischemia/reperfusion; therefore, targeting different pathologic processes may yield an effective therapeutic approach. Transient Receptor Potential A1 (TRPA1) belongs to the TRP family of ion channels, detects a broad range of chemicals, and promotes the transduction of noxious stimuli, e.g., methylglyoxal, ROS, and acrolein effects are attributed to the channel's sensitivity to intracellular calcium elevation or phosphoinositol phosphate modulation. Hypoxia and ischemia are associated with oxidative stress, which activates the TRPA1 channel. This review describes the role of TRPA1 and its related mechanisms that contribute to ischemia/reperfusion. Relevant articles were searched from PubMed, Scopus, Web of Sciences, and Google Scholar electronic databases, up to the end of August 2023. Based on the evidence presented here, TRPA1 may have protective or deteriorative functions during the ischemia/reperfusion process. Its function depends on the activation level, the ischemic region, the extent of lesions, and the duration of ischemia.

Effects of morphine on conditioned place preference and pain are independent of uptake­2.

Morphine changes neurotransmitter release, including norepinephrine, dopamine, and serotonin. Decynium­22 (D22) inhibits an alternative neurotransmitter removal pathway, namely uptake­2. Uptake­2 includes plasma membrane monoamine transporter (PMAT) and organic cation transporters that have a low affinity, but high capacity for uptake of various monoamines such as norepinephrine, dopamine, and serotonin. This study was done to assess the effect of uptake­2 inhibition on morphine­induced conditioned place preference (CPP) and analgesia. In this study, the effects of morphine and/or D22 on CPP were evaluated following intraperitoneal injection in mice. Afterward, changes in motor activity were evaluated by the open field test. Using the tail­flick model, the effects of D22 and/or morphine were evaluated on the pain threshold. The results showed that 20 mg/kg of morphine induced a place preference response. D22, at the dose of 0.03 mg/kg, caused place avoidance, while at the dose of 0.3 mg/kg, it produced a notable place preference response. Co­administration of D22 and morphine showed that morphine reversed the CPP aversion induced by D22 at the lowest dose. Motor activity did not alter. In the tail­flick test, morphine, at the dose of 3 mg/kg but not 1 mg/kg, increased the pain threshold. D22 induced significant analgesic responses. Co­administration of D22 and morphine caused considerable analgesic effects. The findings revealed that D22 induced both conditioned aversion and preference depending on the dose while morphine induced CPP. Both drugs produced analgesia.

Role of orphan G-protein coupled receptors in tissue ischemia: A comprehensive review.

Ischemic events lead to many diseases and deaths worldwide. Ischemia/reperfusion (I/R) occurs due to reduced blood circulation in tissues followed by blood reflow. Reoxygenation of ischemic tissues is characterized by oxidative stress, inflammation, energy distress, and endoplasmic reticulum stress. There are still no adequate clinical protocols or pharmacological approaches to address the consequences of I/R damage. G protein-coupled receptors (GPCRs) are important therapeutic targets. They compose a large family of seven transmembrane-spanning proteins that are involved in many biological functions. Orphan GPCRs are a large subgroup of these receptors expressed in different organs. In the present review, we summarized the literature regarding the role of orphan GPCRs in I/R in different organs. We focused on the effect of these receptors on modulating cellular and molecular processes underlying ischemia including apoptosis, inflammation, and autophagy. The study showed that GPR3, GPR4, GPR17, GPR30, GPR31, GPR35, GPR37, GPR39, GPR55, GPR65, GPR68, GPR75, GPR81, and GPR91 are involved in ischemic events, mainly in the brain and heart. These receptors offer new possibilities for treating I/R injuries in the body.

Lipid-lowering drugs and cancer: an updated perspective.

Statins and non-statin medications used for the management of dyslipidemia have been shown to possess antitumor properties. Since the use of these drugs has steadily increased over the past decades, more knowledge is required about their relationship with cancer. Lipid-lowering agents are heterogeneous compounds; therefore, it remains to be revealed whether anticancer potential is a class effect or related to them all. Here, we reviewed the literature on the influence of lipid-lowering medications on various types of cancer during development or metastasis. We also elaborated on the underlying mechanisms associated with the anticancer effects of antihyperlipidemic agents by linking the reported in vivo and in vitro studies.

Type-1 diabetes: Lessons from a decade of preclinical studies on phytotherapy.

BACKGROUND: In recent decades, numerous herbal products have been shown to have antihyperglycemic and beta cell-regenerative effects in animal studies. However, there is no clinical evidence that those products completely cure patients with type-1 diabetes (T1D). Therefore, it seems that most of the phytochemicals do not have a significant impact on human beta cells, and the results of experimental studies conducted on them may not be generalizable to the clinic. PURPOSE: The present work aims to review extensively the methods and results of preclinical studies on phytotherapy of T1D published in the last 10 years. METHODS: This paper critically analyzes the designs of studies, treatment protocols, methods of diabetes induction, characteristics of the studied animals, clinical relevance, reproducibility of research, and other aspects related to conducting preclinical studies on T1D. We discussed limitations that make many of the results of these studies not generalizable to the clinic. Finally, some recommendations were given to improve studies on the phytotherapy of T1D to avoid misleading interpretations about the antidiabetic effect of herbal compounds. CONCLUSION: This paper can be considered a practical guide for researchers interested in the field of phytotherapy of T1D to increase the reliability, reproducibility, and validity of their preclinical studies.

The role of the ATP-Binding Cassette A1 (ABCA1) in neurological disorders: a mechanistic review.

INTRODUCTION: Cholesterol homeostasis is critical for normal brain function. It is tightly controlled by various biological elements. ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that effluxes cholesterol from cells, particularly astrocytes, into the extracellular space. The recent studies pertaining to ABCA1's role in CNS disorders were included in this study. AREAS COVERED: In this comprehensive literature review, preclinical and human studies showed that ABCA1 has a significant role in the following diseases or disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, neuropathy, anxiety, depression, psychosis, epilepsy, stroke, and brain ischemia and trauma. EXPERT OPINION: ABCA1 via modulating normal and aberrant brain functions such as apoptosis, phagocytosis, BBB leakage, neuroinflammation, amyloid ß efflux, myelination, synaptogenesis, neurite outgrowth, and neurotransmission promotes beneficial effects in aforementioned diseases. ABCA1 is a key molecule in the CNS. By boosting its expression or function, some CNS disorders may be resolved. In preclinical studies, liver X receptor agonists have shown promise in treating CNS disorders via ABCA1 and apoE enhancement.

Cannabidiol goes nuclear: The role of PPARγ.

BACKGROUND: Cannabidiol (CBD) is one of the main phytocannabinoids found in Cannabis sativa. In contrast to Δ9-tetrahydrocannabinol, it has a low affinity for cannabinoid receptors CB1 and CB2, thereby it does not induce significant psychoactive effects. However, CBD may interact with other receptors, including peroxisome proliferator-activated receptor gamma (PPARγ). CBD is a PPARγ agonist and changes its expression. There is considerable evidence that CBD's effects are mediated by its interaction with PPARγ. So, we reviewed studies related to the interaction of CBD and PPARγ. METHODS: In this comprehensive literature review, the term 'cannabidiol' was used in combination with the following keywords including 'PPARγ', 'Alzheimer's disease', 'Parkinson's disease', 'seizure', 'multiple sclerosis', 'immune system', 'cardiovascular system', 'cancer', and 'adipogenesis'. PubMed, Web of Science, and Google Scholar were searched until December 20, 2022. A total of 78 articles were used for the reviewing process. RESULTS: CBD, via activation of PPARγ, promotes significant pharmacological effects. The present review shows that the effects of CBD on Alzheimer's disease and memory, Parkinson's disease and movement disorders, multiple sclerosis, anxiety and depression, cardiovascular system, immune system, cancer, and adipogenesis are mediated, at least in part, via PPARγ. CONCLUSION: CBD not only activates PPARγ but also affects its expression in the body. It was suggested that the late effects of CBD are mediated via PPARγ activation. We suggested that CBD's chemical structure is a good backbone for developing new dual agonists. Combining it with other chemicals enhances their biological effectiveness while reducing their dosage. The present study indicated that PPARγ is a key target for CBD, and its activation by CBD should be considered in all future studies.

Dietary carotenoids to improve hypertension.

Hypertension is one of the major risk factors for cardiovascular diseases and the main reason for premature death in older adults. Although antihypertensive medications have been used frequently, hypertension prevalence has increased in the last decade. Lifestyle improvement is a cornerstone of hypertension prevention and control. High dietary consumptions of fruits and vegetables are linked to reduced risks of high blood pressure. Carotenoids are natural tetraterpene pigments produced by bacteria, fungi, algae, some animals, and various plants. Because of their high pharmacological potential and safety, they have been mentioned as unique therapeutic agents for a diverse range of diseases. Carotenoids modulate high blood pressure. They also have several additional benefits for the cardiovascular system, including antioxidative, anti-inflammatory, anti-atherogenic, and antiplatelet effects. They improve endothelial function and metabolic profile, as well. In the present article, we reviewed the literature data regarding carotenoids' influence on hypertension in both preclinical and clinical studies. Furthermore, we reviewed the underlying mechanisms associated with antihypertensive properties derived from in vitro and in vivo studies. Suppressing reactive oxygen species (ROS) production, Inhibiting angiotensin-II, endothelin-1, and oxidized low-density lipoprotein; and also nitric oxide enhancement are some of the mechanisms by which they lower blood pressure. The present article indicated that astaxanthine, ß-carotene, bixin, capsanthin, lutein, crocin, and lycopene have antihypertensive properties. Having significant antioxidant properties, they can decrease high blood pressure and concomitant comorbidities.