Potential Neuroprotective Role of Neurotrophin in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major global health issue that affects millions of people every year. It is caused by any form of external force, resulting in temporary or permanent impairments in the brain. The pathophysiological process following TBI usually involves excitotoxicity, mitochondrial dysfunction, oxidative stress, inflammation, ischemia, and apoptotic cell death. It is challenging to find treatment for TBI due to its heterogeneous nature, and no therapeutic interventions have been approved thus far. Neurotrophins may represent an alternative approach for TBI treatment because they influence various functional activities in the brain. The present review highlights recent studies on neurotrophins shown to possess neuroprotective roles in TBI. Neurotrophins, specifically brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have demonstrated reduced neuronal death, alleviated neuroinflammatory responses and improved neurological functions following TBI via their immunomodulatory, anti-inflammatory and antioxidant properties. Further studies are required to ensure the efficacy and safety of neurotrophins to be used as TBI treatment in clinical settings.

Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson's disease model.

Introduction: Neurotrophin-3 (NT3) is a neuroprotective growth factor that induces the development, maintenance and survival of neurons. This study aims to localize NT3-expressing cells in the adult zebrafish brain and examine the role of NT3 in a zebrafish Parkinson's disease (PD) model. Methods: Cellular localization of NT3 in adult zebrafish brains was conducted using in situ hybridization. Subsequently, adult zebrafish were injected intraperitoneally with 100 µg/g of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and treated with 400 ng/g body weight of recombinant NT3 (rNT3) via intracranial injection 24 h following MPTP injection. The fish were assessed for neurobehavioral, gene expression, immunohistology, and protein analysis on days 3, 5 and 10 post-MPTP injection. Results: Our findings showed that NT3 was extensively expressed throughout the adult zebrafish brain in neurons. Administration of rNT3 has significantly improved locomotor activity, with upregulation of th1, dat, ntf3 and bdnf gene expressions compared to MPTP-induced zebrafish. Dopaminergic neurons were also significantly increased in the zebrafish brain following rNT3 treatment. ELISA analysis reported raised GST and decreased caspase-3 levels on day 3 of assessment. The trophic changes of rNT3, however, decline as the assessment day progresses. Conclusion: This study is the first to examine the role of NT3 in the adult zebrafish PD model. NT3 has remarkable trophic effects in the zebrafish PD model. However, further study is needed to examine the dosage requirements and long-term effects of NT3 in PD.

Essential Oils in Cervical Cancer: Narrative Review on Current Insights and Future Prospects.

Cervical cancer is a prevalent and often devastating disease affecting women worldwide. Traditional treatment modalities such as surgery, chemotherapy, and radiation therapy have significantly improved survival rates, but they are often accompanied by side effects and challenges that can impact a patient's quality of life. In recent years, the integration of essential oils into the management of cervical cancer has gained attention. This review provides an in-depth exploration of the role of various essential oils in cervical cancer, offering insights into their potential benefits and the existing body of research. The review also delves into future directions and challenges in this emerging field, emphasizing promising research areas and advanced delivery systems. The encapsulation of essential oils with solid lipid nanoparticles, nanoemulsification of essential oils, or the combination of essential oils with conventional treatments showed promising results by increasing the anticancer properties of essential oils. As the use of essential oils in cervical cancer treatment or management evolves, this review aims to provide a comprehensive perspective, balancing the potential of these natural remedies with the challenges and considerations that need to be addressed.

Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the pathologic deposition of amyloid and neurofibrillary tangles in the brain, leading to neuronal damage and defective synapses. These changes manifest as abnormalities in cognition and behavior. The functional deficits are also attributed to abnormalities in multiple neurotransmitter systems contributing to neuronal dysfunction. One such important system is the dopaminergic system. It plays a crucial role in modulating movement, cognition, and behavior while connecting various brain areas and influencing other neurotransmitter systems, making it relevant in neurodegenerative disorders like AD and Parkinson's disease (PD). Considering its significance, the dopaminergic system has emerged as a promising target for alleviating movement and cognitive deficits in PD and AD, respectively. Extensive research has been conducted on dopaminergic neurons, receptors, and dopamine levels as critical factors in cognition and memory in AD. However, the exact nature of movement abnormalities and other features of extrapyramidal symptoms are not fully understood yet in AD. Recently, a previously overlooked element of the dopaminergic system, the dopamine transporter, has shown significant promise as a more effective target for enhancing cognition while addressing dopaminergic system dysfunction in AD.

Parkinson's disease model in zebrafish using intraperitoneal MPTP injection.

Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disease that severely affects the quality of life of patients and their family members. Exposure to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to reflect behavioral, molecular, and proteomic features of PD. This study aimed to assess the protocol for inducing PD following MPTP injection in adult zebrafish. Methods: Fish were injected with 100 µg/g of MPTP intraperitoneally once or twice and then assessed on days 1 to 30 post-injection. Results: Between one-time and two-time injections, there was no significant difference in most locomotor parameters, expressions of tyrosine hydroxylase-2 (th2) and dopamine transporter (dat) genes, and dopaminergic neurons (tyrosine hydroxylase positive, TH+ cells) counts. However, caspase-3 levels significantly differed between one- and two-time injections on the day 1 assessment. Discussion: Over a 30-day period, the parameters showed significant differences in swimming speed, total distance traveled, tyrosine hydroxylase-1 (th1) and dat gene expressions, caspase-3 and glutathione protein levels, and TH+ cell counts. Days 3 and 5 showed the most changes compared to the control. In conclusion, a one-time injection of MPTP with delayed assessment on days 3 to 5 is a good PD model for animal studies.

Microarray-based analysis of differential gene expression profile in rotenone-induced Parkinson's disease zebrafish model.

BACKGROUND & OBJECTIVES: Despite much clinical and laboratory research that has been performed to explore the mechanisms of Parkinson's disease (PD), its pathogenesis remains elusive to date. Therefore, this study aimed to identify possible regulators of neurodegeneration by performing microarray analysis of the zebrafish PD model's brain following rotenone exposure. METHODS: A total of 36 adult zebrafish were divided into two groups: control (n = 17) and rotenone-treated (n = 19). Fish were treated with rotenone water (5 µg/L water) for 28 days and subjected to locomotor behavior analysis. Total RNA was extracted from the brain tissue after rotenone treatment. The cDNA synthesized was subjected to microarray analysis and subsequently validated by qPCR. RESULTS: Administration of rotenone has significantly reduced locomotor activity in zebrafish (p < 0.05), dysregulated dopamine-related gene expression (dat, th1, and th2, p < 0.001), and reduced dopamine level in the brain (p < 0.001). In the rotenone-treated group, genes involved in cytotoxic T lymphocytes (gzm3, cd8a, p < 0.001) and T cell receptor signaling (themis, lck, p < 0.001) were upregulated significantly. Additionally, gene expression involved in microgliosis regulation (tyrobp, p < 0.001), cellular response to IL-1 (ccl34b4, il2rb, p < 0.05), and regulation of apoptotic process (dedd1, p < 0.001) were also upregulated significantly. CONCLUSION: The mechanisms of T cell receptor signaling, microgliosis regulation, cellular response to IL-1, and apoptotic signaling pathways have potentially contributed to PD development in rotenone-treated zebrafish.

Honey and Alzheimer's Disease-Current Understanding and Future Prospects.

Alzheimer's disease (AD), a leading cause of dementia, has been a global concern. AD is associated with the involvement of the central nervous system that causes the characteristic impaired memory, cognitive deficits, and behavioral abnormalities. These abnormalities caused by AD is known to be attributed by extracellular aggregates of amyloid beta plaques and intracellular neurofibrillary tangles. Additionally, genetic factors such as abnormality in the expression of APOE, APP, BACE1, PSEN-1, and PSEN-2 play a role in the disease. As the current treatment aims to treat the symptoms and to slow the disease progression, there has been a continuous search for new nutraceutical agent or medicine to help prevent and cure AD pathology. In this quest, honey has emerged as a powerful nootropic agent. Numerous studies have demonstrated that the high flavonoids and phenolic acids content in honey exerts its antioxidant, anti-inflammatory, and neuroprotective properties. This review summarizes the effect of main flavonoid compounds found in honey on the physiological functioning of the central nervous system, and the effect of honey intake on memory and cognition in various animal model. This review provides a new insight on the potential of honey to prevent AD pathology, as well as to ameliorate the damage in the developed AD.

The effects of metallothionein in paraquat-induced Parkinson disease model of zebrafish.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Metallothionein has been shown to act as a neuroprotectant in various brain injury. Thus, this study aims to identify the effects of full-length human metallothionein 2 peptide (hMT2) in paraquat-induced brain injury in the zebrafish. METHODOLOGY: A total of 80 adult zebrafish were divided into 4 groups namely control, paraquat-treated, pre-hMT2-treated, and post-hMT2-treated groups. Fish were treated with paraquat intraperitoneally every 3 days for 15 days. hMT2 were injected intracranially on day 0 (pre-treated group) and day 16 (post-treated group). Fish were sacrificed on day 22 and the brains were collected for qPCR, ELISA and immunohistochemistry analysis. RESULTS: qPCR analysis showed that paraquat treatment down-regulated the expression of genes related to dopamine activity and biosynthesis (dat and th1) and neuroprotective agent (bdnf). Paraquat treatment also up-regulated the expression of the mt2, smtb and proinflammatory genes (il-1α, il-1ß, tnf-α and cox-2). hMT2 treatment was able to reverse the effects of paraquat. Lipid peroxidation decreased in the paraquat and pre-hMT2-treated groups. However, lipid peroxidation increased in the post-hMT2-treated group. Paraquat treatment also led to a reduction of dopaminergic neurons while their numbers showed an increase following hMT2 treatment. CONCLUSION: Paraquat has been identified as one of the pesticides that can cause the death of dopaminergic neurons and affect dopamine biosynthesis. Treatment with exogenous hMT2 could reverse the effects of paraquat in the zebrafish brain.

Zebrafish: A Pharmacological Model for Learning and Memory Research.

Learning and memory are essential to organism survival and are conserved across various species, especially vertebrates. Cognitive studies involving learning and memory require using appropriate model organisms to translate relevant findings to humans. Zebrafish are becoming increasingly popular as one of the animal models for neurodegenerative diseases due to their low maintenance cost, prolific nature and amenability to genetic manipulation. More importantly, zebrafish exhibit a repertoire of neurobehaviors comparable to humans. In this review, we discuss the forms of learning and memory abilities in zebrafish and the tests used to evaluate the neurobehaviors in this species. In addition, the pharmacological studies that used zebrafish as models to screen for the effects of neuroprotective and neurotoxic compounds on cognitive performance will be summarized here. Lastly, we discuss the challenges and perspectives in establishing zebrafish as a robust model for cognitive research involving learning and memory. Zebrafish are becoming an indispensable model in learning and memory research for screening neuroprotective agents against cognitive impairment.

Comparable Benefits of Stingless Bee Honey and Caffeic Acid in Mitigating the Negative Effects of Metabolic Syndrome on the Brain.

There is mounting evidence that metabolic syndrome (MetS) contributes to the development of neurodegenerative disorders such as Alzheimer's disease. Honey, which has been used for generations, is high in antioxidants and has been demonstrated to benefit the brain and mental health by reducing oxidative stress and boosting cognitive outcomes. Honey from the stingless bees of Heterotrigona itama has been found to have higher phenolic content compared to other types of honeys. The aim of this study is to investigate the effects of stingless bee honey (SBH) supplementation and to compare it with a pure form of antioxidant, caffeic acid (CA), on MetS parameters and inflammatory markers in the brains of MetS-induced rats. A total of 32 male Wistar rats were divided equally into groups of control, high-carbohydrate high-fructose (HCHF) diet (MetS), HCHF + SBH supplemented (1 g/kg) (SBH), and HCHF + CA supplemented (10 mg/kg) (CA) groups. The total duration for SBH and CA supplementation was eight weeks. The HCHF diet was found to promote hypertension, hyperglycemia, and hypertriglyceridemia, and to increase brain TNF-α levels. Supplementation with SBH and CA significantly reversed (p < 0.05) the hyperglycemic and hypertensive effects of the HCHF diet. Although both supplemented groups showed no significant changes to serum HDL or TG, SBH significantly reduced (p < 0.05) brain TNF-α levels and increased (p < 0.05) brain BDNF levels. Immunohistochemistry investigations of neurogenesis (EdU) and apoptosis (TUNEL) on the cornu Ammonis 1 (CA1) and dentate gyrus (DG) areas of the hippocampus showed no changes with SBH and CA supplementation compared to the control. These findings suggest that SBH and CA have the potential to mitigate HCHF-induced MetS effects and possess neuroprotective abilities.

Goofballing of Opioid and Methamphetamine: The Science Behind the Deadly Cocktail.

Globally, millions of people suffer from various substance use disorders (SUD), including mono-and polydrug use of opioids and methamphetamine. Brain regions such as the cingulate cortex, infralimbic cortex, dorsal striatum, nucleus accumbens, basolateral and central amygdala have been shown to play important roles in addiction-related behavioral changes. Clinical and pre-clinical studies have characterized these brain regions and their corresponding neurochemical changes in numerous phases of drug dependence such as acute drug use, intoxication, craving, withdrawal, and relapse. At present, many studies have reported the individual effects of opioids and methamphetamine. However, little is known about their combined effects. Co-use of these drugs produces effects greater than either drug alone, where one decreases the side effects of the other, and the combination produces a prolonged intoxication period or a more desirable intoxication effect. An increasing number of studies have associated polydrug abuse with poorer treatment outcomes, drug-related deaths, and more severe psychopathologies. To date, the pharmacological treatment efficacy for polydrug abuse is vague, and still at the experimental stage. This present review discusses the human and animal behavioral, neuroanatomical, and neurochemical changes underlying both morphine and methamphetamine dependence separately, as well as its combination. This narrative review also delineates the recent advances in the pharmacotherapy of mono- and poly drug-use of opioids and methamphetamine at clinical and preclinical stages.

MicroRNAs in Various Body Fluids and their Importance in Forensic Medicine.

MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate gene expression. miRNAs have tissue-specific expression and are also present in various extracellular body fluids, including blood, tears, semen, vaginal fluid, and urine. Additionally, the expression of miRNAs in body fluids is linked to various pathological diseases, including cancer and neurodegenerative diseases. Examination of body fluids is important in forensic medicine as they serve as a valuable form of evidence. Due to its stability, miRNA offers an advantage for body fluid identification, which can be detected even after several months or from compromised samples. Identification of unique miRNA profiles for different body fluids enables the identification of the body fluids. Furthermore, miRNAs profiling can be used to estimate post-mortem interval. Various biochemical and molecular methods used for the identification of miRNAs have shown promising results. We discuss different miRNAs as specific biomarkers and their clinical importance in different pathological conditions, as well as their medicolegal importance.

Treatment of Glaucoma with Natural Products and Their Mechanism of Action: An Update.

Glaucoma is one of the leading causes of irreversible blindness. It is generally caused by increased intraocular pressure, which results in damage of the optic nerve and retinal ganglion cells, ultimately leading to visual field dysfunction. However, even with the use of intraocular pressure-lowering eye drops, the disease still progresses in some patients. In addition to mechanical and vascular dysfunctions of the eye, oxidative stress, neuroinflammation and excitotoxicity have also been implicated in the pathogenesis of glaucoma. Hence, the use of natural products with antioxidant and anti-inflammatory properties may represent an alternative approach for glaucoma treatment. The present review highlights recent preclinical and clinical studies on various natural products shown to possess neuroprotective properties for retinal ganglion cells, which thereby may be effective in the treatment of glaucoma. Intraocular pressure can be reduced by baicalein, forskolin, marijuana, ginsenoside, resveratrol and hesperidin. Alternatively, Ginkgo biloba, Lycium barbarum, Diospyros kaki, Tripterygium wilfordii, saffron, curcumin, caffeine, anthocyanin, coenzyme Q10 and vitamins B3 and D have shown neuroprotective effects on retinal ganglion cells via various mechanisms, especially antioxidant, anti-inflammatory and anti-apoptosis mechanisms. Extensive studies are still required in the future to ensure natural products' efficacy and safety to serve as an alternative therapy for glaucoma.

Neurotrophin-3 and neurotrophin-4: The unsung heroes that lies behind the meninges.

Neurotrophin is a growth factor that regulates the development and repair of the nervous system. From all factors, two pioneer groups, the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), have been widely explored for their role in disease pathogenesis and potential use as therapeutic agents. Nonetheless, neurotrophin-3 (NT3) and neurotrophin-4 (NT4) also have promising potential, albeit less popular than their counterparts. This review focuses on the latter two factors and their roles in the pathogenesis of brain disorders and potential therapies. An extensive literature search of NT3 and NT4 with their receptors, the TrkB and TrkC on the nervous system were extracted and analyzed. We found that NT3 and NT4 are not only involved in the pathogenesis of some neurodegenerative diseases, but also have promising therapeutic potential on injury- and vascular-related nervous system disease, neuropsychiatry, neurodegeneration and peripheral nerve diseases. In conclusion, the role of NT3 and NT4 should be further emphasized, and more studies could be explored on the potential use of these neurotrophins in the human study.

Fish Gelatin: Current Nutritional, Medicinal, Tissue Repair Applications, and as a Carrier of Drug Delivery.

Gelatin is obtained via partial denaturation of collagen and is extensively used in various industries. The majority of gelatin utilized globally is derived from a mammalian source. Several health and religious concerns associated with porcine/bovine gelatin have been reported. Therefore, gelatin from a marine source is widely being investigated for its efficiency and utilization in a variety of applications as a potential substitute for porcine/bovine gelatin. Although fish gelatin is less durable and possesses lower melting and gelling temperatures compared to mammal-derived gelatin, various modifications have been reported to promote its rheological and functional properties to be efficiently employed. The present review describes in detail the current innovative applications of fish gelatin involving the food industry, drug delivery, and possible therapeutic applications. Gelatin bioactive molecules may be utilized as carriers for drug delivery. Due to its versatility, gelatin can be used in different carrier systems, such as microparticles, nanoparticles, fibers, and hydrogels. The present review also provides a perspective on the other potential pharmaceutical applications of fish gelatin, such as tissue regeneration, antioxidant supplementation, and antihypertensive and anticancer treatments.

Discogenic Low Back Pain: Anatomy, Pathophysiology and Treatments of Intervertebral Disc Degeneration.

Intervertebral disc (IVD) degeneration is a major contributing factor for discogenic low back pain (LBP), causing a significant global disability. The IVD consists of an inner core proteoglycan-rich nucleus pulposus (NP) and outer lamellae collagen-rich annulus fibrosus (AF) and is confined by a cartilage end plate (CEP), providing structural support and shock absorption against mechanical loads. Changes to degenerative cascades in the IVD cause dysfunction and instability in the lumbar spine. Various treatments include pharmacological, rehabilitation or surgical interventions that aim to relieve pain; however, these modalities do not halt the pathologic events of disc degeneration or promote tissue regeneration. Loss of stem and progenitor markers, imbalance of the extracellular matrix (ECM), increase of inflammation, sensory hyperinnervation and vascularization, and associated signaling pathways have been identified as the onset and progression of disc degeneration. To better understand the pain originating from IVD, our review focuses on the anatomy of IVD and the pathophysiology of disc degeneration that contribute to the development of discogenic pain. We highlight the key mechanisms and associated signaling pathways underlying disc degeneration causing discogenic back pain, current clinical treatments, clinical perspective and directions of future therapies. Our review comprehensively provides a better understanding of healthy IVD and degenerative events of the IVD associated with discogenic pain, which helps to model painful disc degeneration as a therapeutic platform and to identify signaling pathways as therapeutic targets for the future treatment of discogenic pain.

Marine algae as emerging therapeutic alternatives for depression: A review.

Depression is a complex heterogeneous brain disorder characterized by a range of symptoms, resulting in psychomotor and cognitive disabilities and suicidal thoughts. Its prevalence has reached an alarming level affecting millions of people globally. Despite advances in current pharmacological treatments, the heterogenicity of clinical response and incidences of adverse effects have shifted research focus to identification of new natural substances with minimal or no adverse effects as therapeutic alternatives. Marine algae-derived extracts and their constituents are considered potential sources of secondary metabolites with diverse beneficial effects. Marine algae with enormous health benefits are emerging as a natural source for discovering new alternative antidepressants. Its medicinal properties exhibited shielding efficacy against neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are indicated to underlie the pathogenesis of many neurological disorders. Marine algae have been found to ameliorate depressive-like symptoms and behaviors in preclinical and clinical studies by restoring monoaminergic neurotransmission, hypothalamic-pituitary-adrenal axis function, neuroplasticity, and continuous neurogenesis in the dentate gyrus of the hippocampus via modulating brain-derived neurotrophic factors and antineuroinflammatory activity. Although antidepressant effects of marine algae have not been validated in comparison with currently available synthetic antidepressants, they have been reported to have effects on the pathophysiology of depression, thus suggesting their potential as novel antidepressants. In this review, we analyzed the currently available research on the potential benefits of marine algae on depression, including their effects on the pathophysiology of depression, potential clinical relevance of their antidepressant effects in preclinical and clinical studies, and the underlying mechanisms of these effects.

The role of natural antioxidants in cisplatin-induced hepatotoxicity.

Cisplatin is a potent platinum-based anticancer drug approved by the Food Drug Administration (FDA) in 1978. Despite its advantages against solid tumors, cisplatin confers toxicity to various tissues that limit its clinical uses. In cisplatin-induced hepatotoxicity, few mechanisms have been identified, which started as excess generation of reactive oxygen species that leads to oxidative stress, inflammation, DNA damage and apoptosis in the liver. Various natural products, plant extracts and oil rich in flavonoids, terpenoids, polyphenols, and phenolic acids were able to minimize oxidative stress by restoring the level of antioxidant enzymes and acting as an anti-inflammatory agent. Likewise, treatment with honey and royal jelly was demonstrated to decrease serum transaminases and scavenge free radicals in the liver after cisplatin administration. Medicinal properties of these natural products have a promising potential as a complementary therapy to counteract cisplatin-induced hepatotoxicity. This review concentrated on the protective role of several natural products, which has been proven in the laboratory findings to combat cisplatin-induced hepatotoxicity.

The Hippocampal Vulnerability to Herpes Simplex Virus Type I Infection: Relevance to Alzheimer's Disease and Memory Impairment.

Herpes simplex virus type 1 (HSV-1) as a possible infectious etiology in Alzheimer's disease (AD) has been proposed since the 1980s. The accumulating research thus far continues to support the association and a possible causal role of HSV-1 in the development of AD. HSV-1 has been shown to induce neuropathological and behavioral changes of AD, such as amyloid-beta accumulation, tau hyperphosphorylation, as well as memory and learning impairments in experimental settings. However, a neuroanatomical standpoint of HSV-1 tropism in the brain has not been emphasized in detail. In this review, we propose that the hippocampal vulnerability to HSV-1 infection plays a part in the development of AD and amnestic mild cognitive impairment (aMCI). Henceforth, this review draws on human studies to bridge HSV-1 to hippocampal-related brain disorders, namely AD and aMCI/MCI. Next, experimental models and clinical observations supporting the neurotropism or predilection of HSV-1 to infect the hippocampus are examined. Following this, factors and mechanisms predisposing the hippocampus to HSV-1 infection are discussed. In brief, the hippocampus has high levels of viral cellular receptors, neural stem or progenitor cells (NSCs/NPCs), glucocorticoid receptors (GRs) and amyloid precursor protein (APP) that support HSV-1 infectivity, as well as inadequate antiviral immunity against HSV-1. Currently, the established diseases HSV-1 causes are mucocutaneous lesions and encephalitis; however, this review revises that HSV-1 may also induce and/or contribute to hippocampal-related brain disorders, especially AD and aMCI/MCI.

Caffeic Acid on Metabolic Syndrome: A Review.

Metabolic syndrome (MetS) is a constellation of risk factors that may lead to a more sinister disease. Raised blood pressure, dyslipidemia in the form of elevated triglycerides and lowered high-density lipoprotein cholesterol, raised fasting glucose, and central obesity are the risk factors that could lead to full-blown diabetes, heart disease, and many others. With increasing sedentary lifestyles, coupled with the current COVID-19 pandemic, the numbers of people affected with MetS will be expected to grow in the coming years. While keeping these factors checked with the polypharmacy available currently, there is no single strategy that can halt or minimize the effect of MetS to patients. This opens the door for a more natural way of controlling the disease. Caffeic acid (CA) is a phytonutrient belonging to the flavonoids that can be found in abundance in plants, fruits, and vegetables. CA possesses a wide range of beneficial properties from antioxidant, immunomodulatory, antimicrobial, neuroprotective, antianxiolytic, antiproliferative, and anti-inflammatory activities. This review discusses the current discovery of the effect of CA against MetS.