Resveratrol in the Treatment of Gynecological Cancer: Mechanisms and Therapeutic Potential.

Gynecological cancers, encompassing endometrial, ovarian, and cervical cancer, pose significant challenges in clinical practice, often marked by high mortality rates and treatment resistance. Despite advances in standard therapies, including chemoradiation and surgery, tumor recurrence and metastasis remain formidable obstacles. In this context, there is a pressing need to explore novel therapeutic strategies that offer improved efficacy and reduced side effects. Herbal medicine, particularly compounds like resveratrol, has garnered attention for its diverse biological properties, including anticancer effects. Resveratrol, a multipotential nutraceutical, holds promise in gynecological cancer therapy through its modulation of key cellular and molecular processes. This review aims to provide an overview of the current status, challenges, and opportunities in utilizing resveratrol for gynecological cancer treatment. We discuss its role in miRNA regulation, clinical trial findings, and the development of effective formulations. By elucidating the underlying mechanisms of resveratrol's anticancer effects and exploring innovative delivery systems, we aim to shed light on the potential avenues for optimizing its therapeutic benefits in gynecological cancers.

Astaxanthin as an Anticancer Agent against Breast Cancer: An In Vivo and In Vitro Investigation.

AIM: This study aimed to investigate the antioxidant properties, cytotoxic activity, and apoptotic effects of astaxanthin (ASX) on genes and pathways involved in breast cancer in Balb/c mice models injected with the 4T1 cell line. BACKGROUND: ASX could inhibit some tumor progression by using in vivo and in vitro models. OBJECTIVE: The effect of ASX on breast cancer was not fully understood till now. METHOD: In an in vivo model, 4T1 cells-injected mice were administered with different concentrations of ASX (100 and 200 mg/kg), and histopathological evaluations were done using an optical microscope and the hematoxylin and eosin (H&E) staining. The real- time PCR investigated the expression levels of B-cell lymphoma 2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), and Caspase 3 genes in mice treated with 100 and 200 mg/kg ASX. Also, the level of superoxide dismutase (SOD) and malondialdehyde (MDA) were examined in ASX-treated cancer mice. RESULTS: ASX (200 mg/kg) caused a significant reduction in the mitotic cell count of tumor tissues compared to ASX (100 mg/kg). The antiproliferative effects of different concentrations of ASX were shown based on the MTT results. The treatment of breast tumor mice with both concentrations of ASX, especially 200 mg/kg, elevated the expression of Caspase 3, Bax, and SOD enzyme levels and decreased Bcl-2 expression and MDA enzyme levels. CONCLUSION: ASX can be considered a promising alternative treatment for breast cancer.

Curcumin in treatment of hematological cancers: Promises and challenges.

Hematological cancers include leukemia, myeloma and lymphoma and up to 178.000 new cases are diagnosed with these tumors each year. Different kinds of treatment including radiotherapy, chemotherapy, immunotherapy and stem cell transplantation have been employed in the therapy of hematological cancers. However, they are still causing death among patients. On the other hand, curcumin as an anti-cancer agent for the suppression of human cancers has been introduced. The treatment of hematological cancers using curcumin has been followed. Curcumin diminishes viability and survival rate of leukemia, myeloma and lymphoma cells. Curcumin stimulates apoptosis and G2/M arrest to impair progression of tumor. Curcumin decreases levels of matrix metalloproteinases in suppressing cancer metastasis. A number of downstream targets including VEGF, Akt and STAT3 undergo suppression by curcumin in suppressing progression of hematological cancers. Curcumin stimulates DNA damage and reduces resistance of cancer cells to irradiation. Furthermore, curcumin causes drug sensitivity of hematological tumors, especially myeloma. For targeted delivery of curcumin and improving its pharmacokinetic and anti-cancer features, nanostructures containing curcumin and other anti-cancer agents have been developed.

Nrf2 Mediates Effect of Resveratrol in Ischemia-reperfusion Injury.

Ischemia-Reperfusion Injury (IRI) is a paradoxical phenomenon where removing the source of injury can cause additional damage. Ischemia reduces ATP production and intracellular pH, reducing oxidative reactions, increasing lactic acid release, and activating anaerobic metabolism. Reperfusion restores aerobic respiration and increases ROS production, leading to malfunction of transmembrane transport, activation of proteases, DNA dissolution, and protein denaturation, leading to apoptotic cell death. Nrf2 is a transcription factor that regulates cellular inflammation and oxidative responses. It is activated by oxidants and electrophiles and enhances detoxifying enzyme expression, maintaining redox homeostasis. It also activates ARE, which activates several ARE-regulated genes that favor cell survival by exhibiting resistance to oxidants and electrophiles. Nrf2 regulates the antioxidant defense system by producing phase II and antioxidant defense enzymes, including HO-1, NQO-1, gglutamylcysteine synthetase, and rate-limiting enzymes for glutathione synthesis. Nrf2 protects mitochondria from damage and supports mitochondrial function in stress conditions. Resveratrol is a stilbene-based compound with a wide variety of health benefits for humans, including antioxidant, anticarcinogenic, antitumor, and estrogenic/antiestrogenic. Resveratrol protects against IRI through several signaling pathways, including the Nrf2/ARE pathway. Here, we review the studies that investigated the mechanisms of resveratrol protection against IRI through modulation of the Nrf2 signaling pathway.

Therapeutic Effect of Resveratrol and its Novel Formulations on Lung Cancer: Focus on Biological Aspects and Underlying Pathways.

Lung cancer is a leading cause of mortality and morbidity worldwide. Due to significant advances in therapeutic strategies, patients' survival and life quality have been improved, however there is still an urgent requirement for developing more effective therapeutic methods. Resveratrol, a natural polyphenol with numerous biological potentials, has been widely studied. It has shown therapeutic potetial in various diseases including neurodegenerative diseases, cardiovascular disorders, and cancers through the regulation of key cellular signaling such as apoptosis, as well as molecular pathways such as microRNA modulation. It has been reported that resveratrol acts as an anticancer agent against lung cancer in vivo and in vitro. Resveratrol could combat against lung cancer by modulating various molecular targets and signaling pathways involved in oxidative stress, inflammation, apoptosis and autoghagy and also microRNAs expression. Moreover, novel delivery systems and analogs have recently been introduced to promote the anticancer impacts of resveratrol. In this article, we review current evidence on the anticancer effects of resveratrol and its novel formulations in the treatment of lung cancer with a focus on underlying mechanisms.

Anticancer Properties of Baicalin against Breast Cancer and other Gynecological Cancers: Therapeutic Opportunities based on Underlying Mechanisms.

Gynecological cancers are serious life-threatening diseases responsible for high morbidity and mortality around the world. Chemotherapy, radiotherapy, and surgery are considered standard therapeutic modalities for these cancers. Since the mentioned treatments have undesirable side effects and are not effective enough, further attempts are required to explore potent complementary and/or alternative treatments. This study was designed to review and discuss the anticancer potentials of baicalin against gynecological cancers based on causal mechanisms and underlying pathways. Traditional medicine has been used for thousands of years in the therapy of diverse human diseases. The therapeutic effects of natural compounds like baicalin have been widely investigated in cancer therapy. Baicalin was effective against gynecological cancers by regulating key cellular mechanisms, including apoptosis, autophagy, and angiogenesis. Baicalin exerted its anticancer property by regulating most molecular signaling pathways, including PI3K/Akt/mTOR, NFκB, MAPK/ERK, and Wnt/ß-catenin. However, more numerous experimental and clinical studies should be designed to find the efficacy of baicalin and the related mechanisms of action.

Application of Quercetin and its Novel Formulations in the Treatment of Malignancies of Central Nervous System: An Updated Review of Current Evidence Based on Molecular Mechanisms.

Quercetin, a naturally occurring polyphenolic compound found in abundance in vegetables and fruits, has emerged as a compelling subject of study in cancer treatment. This comprehensive review delves into the significance and originality of quercetin's multifaceted mechanisms of action, with a particular focus on its application in various brain tumors such as glioblastoma, glioma, neuroblastoma, astrocytoma, and medulloblastoma. This review scrutinizes the distinctive facets of quercetin's anti-cancer properties, highlighting its capacity to modulate intricate signaling pathways, trigger apoptosis, impede cell migration, and enhance radiosensitivity in brain tumor cells. Significantly, it synthesizes recent research findings, providing insights into potential structure-activity relationships that hold promise for developing novel quercetin derivatives with heightened effectiveness. By unraveling the unique attributes of quercetin's anti-brain tumor effects and exploring its untapped potential in combination therapies, this review contributes to a deeper comprehension of quercetin's role as a prospective candidate for advancing innovative treatments for brain cancer.

A review of the epidemiological and laboratory evidence of the role of aluminum exposure in pathogenesis of cardiovascular diseases.

The objective of the present study was to review the epidemiological and laboratory evidence on the role of aluminum (Al) exposure in the pathogenesis of cardiovascular diseases. Epidemiological data demonstrated an increased incidence of cardiovascular diseases (CVD), including hypertension and atherosclerosis in occupationally exposed subjects and hemodialysis patients. In addition, Al body burden was found to be elevated in patients with coronary heart disease, hypertension, and dyslipidemia. Laboratory studies demonstrated that Al exposure induced significant ultrastructural damage in the heart, resulting in electrocardiogram alterations in association with cardiomyocyte necrosis and apoptosis, inflammation, oxidative stress, inflammation, and mitochondrial dysfunction. In agreement with the epidemiological findings, laboratory data demonstrated dyslipidemia upon Al exposure, resulting from impaired hepatic lipid catabolism, as well as promotion of low-density lipoprotein oxidation. Al was also shown to inhibit paraoxonase 1 activity and to induce endothelial dysfunction and adhesion molecule expression, further promoting atherogenesis. The role of Al in hypertension was shown to be mediated by up-regulation of NADPH-oxidase, inhibition of nitric oxide bioavailability, and stimulation of renin-angiotensin-aldosterone system. It has been also demonstrated that Al exposure targets cerebral vasculature, which may be considered a link between Al exposure and cerebrovascular diseases. Findings from other tissues lend support that ferroptosis, pyroptosis, endoplasmic reticulum stress, and modulation of gut microbiome and metabolome are involved in the development of CVD upon Al exposure. A better understanding of the role of the cardiovascular system as a target for Al toxicity will be useful for risk assessment and the development of treatment and prevention strategies.

The protective impact of curcumin, vitamin D and E along with manganese oxide and Iron (III) oxide nanoparticles in rats with scrotal hyperthermia: Role of apoptotic genes, miRNA and circRNA.

BACKGROUND: Infertility is one of the major factors affecting most people around the world. Short-term exposure to high temperatures can cause hyperthermia, which is one of the causes of male infertility. The aim of this study was to investigate the protective effect of curcumin, vitamins D and E along with Iron (III) oxide nanoparticles (Fe2O3-NPs) and manganese oxide nanoparticles (MnO2-NPs) on semen parameters and its effect on miRNA21 and circRNA0001518 expression. MATERIAL AND METHODS: In this study, the lower part of the rat was exposed to 43 °C for 5 weeks every other day for 5 weeks. Then the animals were killed. Tissue samples were collected for sperm parameters analysis, and tissue samples were taken for evaluation of apoptosis levels in germ cells, and RNA extraction in order to examine the expression of Bax, Bcl-2, miRNA, and CircRNA genes. RESULTS: The results of this study showed that administration of curcumin, vitamin D, and vitamin E with Fe2O3-NPs and MnO2-NPs can improve the parameters of semen, Bax gene expression, Bcl-2 as well as miRNA and CircRNA in rats with testicular hyperthermia. In addition, curcumin by reducing the toxicity of Fe2O3 nanoparticles was able to reduce its negative effects and also reduce apoptosis in germ cells. This decrease in apoptosis was attributed to decreased Bcl-2 gene expression and increased expression of Bax, miRNA-21, and circRNA0001518. CONCLUSION: All the results of this study confirmed that Fe2O3-NPs and Mno2-NPs containing antioxidants or vitamins are useful in improving fertility in rats due to scrotal hyperthermia. Although Fe2O3-NPs and Mno2-NPs containing both antioxidants and vitamins had a greater effect on improving fertility and reducing the toxic effects of nanoparticles.

miRNAs as short non-coding RNAs in regulating doxorubicin resistance.

The treatment of cancer patients has been prohibited by chemoresistance. Doxorubicin (DOX) is an anti-tumor compound disrupting proliferation and triggering cell cycle arrest via inhibiting activity of topoisomerase I and II. miRNAs are endogenous RNAs localized in cytoplasm to reduce gene level. Abnormal expression of miRNAs changes DOX cytotoxicity. Overexpression of tumor-promoting miRNAs induces DOX resistance, while tumor-suppressor miRNAs inhibit DOX resistance. The miRNA-mediated regulation of cell death and hallmarks of cancer can affect response to DOX chemotherapy in tumor cells. The transporters such as P-glycoprotein are regulated by miRNAs in DOX chemotherapy. Upstream mediators including lncRNAs and circRNAs target miRNAs in affecting capacity of DOX. The response to DOX chemotherapy can be facilitated after administration of agents that are mostly phytochemicals including curcumol, honokiol and ursolic acid. These agents can regulate miRNA expression increasing DOX's cytotoxicity. Since delivery of DOX alone or in combination with other drugs and genes can cause synergistic impact, the nanoparticles have been introduced for drug sensitivity. The non-coding RNAs determine the response of tumor cells to doxorubicin chemotherapy. microRNAs play a key role in this case and they can be sponged by lncRNAs and circRNAs, showing interaction among non-coding RNAs in the regulation of doxorubicin sensitivity.

Advances in RNAi therapies for gastric cancer: Targeting drug resistance and nanoscale delivery.

Gastric cancer poses a significant health challenge, and exploring innovative therapeutic strategies is imperative. RNA interference (RNAi) has employed as an important therapeutic strategy for diseases by selectively targeting key pathways involved in diseases pathogenesis. Small interfering RNA (siRNA), a potent RNAi tool, possesses the capability to silence genes and downregulate their expression. This review provides a comprehensive examination of the potential applications of small interfering RNA (siRNA) and short hairpin RNA (shRNA), supplemented by an in-depth analysis of nanoscale delivery systems, in the context of gastric cancer treatment. The potential of siRNA to markedly diminish the proliferation and invasion of gastric cancer cells through the modulation of critical molecular pathways, including PI3K, Akt, and EMT, is highlighted. Besides, siRNA demonstrates its efficacy in inducing chemosensitivity in gastric tumor cells, thus impeding tumor progression. However, the translational potential of unmodified siRNA faces challenges, particularly in vivo and during clinical trials. To address this, we underscore the pivotal role of nanostructures in facilitating the delivery of siRNA to gastric cancer cells, effectively suppressing their progression and enhancing gene silencing efficiency. These siRNA-loaded nanoparticles exhibit robust internalization into gastric cancer cells, showcasing their potential to significantly reduce tumor progression. The translation of these findings into clinical trials holds promise for advancing the treatment of gastric cancer patients.

Therapeutic Effects of Berberine against Urological Cancers: Biological Potentials Based on Cellular Mechanisms.

Urological cancers, including prostate, kidney, and bladder cancer are problematic human diseases worldwide. Current strategies for the treatment of these cancers are chemotherapy, radiotherapy, surgery, or a combination of mentioned therapies. Due to the high mortality and morbidity rate of urological cancers and possible side effects of available standard treatments, searching for more effective and safe treatments is a critical issue. The beneficial properties of natural compounds, such as berberine, have been widely investigated in human diseases. Moreover, the anticancer potential of this agent has been extensively documented, especially in experimental studies. In this review, we have tried to discuss the effect of berberine against urological cancers, focusing on cellular and molecular mechanisms.

Targeting the NF-E2-related factor 2 pathway for overcoming leukemia.

Leukemia is cancer of the body's blood-forming tissues, including the bone marrow and the lymphatic system. There are many types of leukemia that some of them occur in children and the others are more common in adults. Currently, there are many different chemotherapy agents for leukemia while chemoresistance increases the survival of the leukemic cells. One of the main reasons of chemoresistance, is a transcription factor called Nuclear factor erythroid 2-Related Factor 2 (NRF2). An increase in NRF2 expression in leukemic cells which are being treated with chemotherapy agents, can increase the survival of these cells in the presence of therapeutics. Accordingly, the inhibition of NRF2 by different methods as a cotreatment with classical chemotherapy agents, can be a promising procedure in leukemia treatment. In this study we focus on the association of NRF2 and leukemia and targeting it as a new therapeutic method in leukemia treatment.

A state-of-art of underlying molecular mechanisms and pharmacological interventions/nanotherapeutics for cisplatin resistance in gastric cancer.

The fourth common reason of death among patients is gastric cancer (GC) and it is a dominant tumor type in Ease Asia. One of the problems in GC therapy is chemoresistance. Cisplatin (CP) is a platinum compound that causes DNA damage in reducing tumor progression and viability of cancer cells. However, due to hyperactivation of drug efflux pumps, dysregulation of genes and interactions in tumor microenvironment, tumor cells can develop resistance to CP chemotherapy. The current review focuses on the CP resistance emergence in GC cells with emphasizing on molecular pathways, pharmacological compounds for reversing chemoresistance and the role of nanostructures. Changes in cell death mechanisms such as upregulation of pro-survival autophagy can prevent CP-mediated apoptosis that results in drug resistance. Moreover, increase in metastasis via EMT induction induces CP resistance. Dysregulation of molecular pathways such as PTEN, PI3K/Akt, Nrf2 and others result in changes in CP response of GC cells. Non-coding RNAs determine CP response of GC cells and application of pharmacological compounds with activity distinct of CP can result in sensitivity in tumor cells. Due to efficacy of exosomes in transferring bioactive molecules such as RNA and DNA molecules among GC cells, exosomes can also result in CP resistance. One of the newest progresses in overcoming CP resistance in GC is application of nanoplatforms for delivery of CP in GC therapy that they can increase accumulation of CP at tumor site and by suppressing carcinogenic factors and overcoming biological barriers, they increase CP toxicity on cancer cells.

Anticancer activity of thymoquinone against breast cancer cells: Mechanisms of action and delivery approaches.

The rising incidence of breast cancer has been a significant source of concern in the medical community. Regarding the adverse effects and consequences of current treatments, cancers' health, and socio-economical aspects have become more complicated, leaving research aimed at improved or new treatments on top priority. Medicinal herbs contain multitarget compounds that can control cancer development and advancement. Owing to Nigella Sativa's elements, it can treat many disorders. Thymoquinone (TQ) is a natural chemical derived from the black seeds of Nigella sativa Linn proved to have anti-cancer and anti-inflammatory properties. TQ interferes in a broad spectrum of tumorigenic procedures and inhibits carcinogenesis, malignant development, invasion, migration, and angiogenesis owing to its multitargeting ability. It effectively facilitates miR-34a up-regulation, regulates the p53-dependent pathway, and suppresses Rac1 expression. TQ promotes apoptosis and controls the expression of pro- and anti-apoptotic genes. It has also been shown to diminish the phosphorylation of NF-B and IKK and decrease the metastasis and ERK1/2 and PI3K activity. We discuss TQ's cytotoxic effects for breast cancer treatment with a deep look at the relevant stimulatory or inhibitory signaling pathways. This review discusses the various forms of polymeric and non-polymeric nanocarriers (NC) and the encapsulation of TQ for increasing oral bioavailability and enhanced in vitro and in vivo efficacy of TQ-combined treatment with different chemotherapeutic agents against various breast cancer cell lines. This study can be useful to a broad scientific community, comprising pharmaceutical and biological scientists, as well as clinical investigators.

Anti-gout and urate-lowering potentials of curcumin: A review from bench to beside.

BACKGROUND: Gouty arthritis is a complex form of inflammatory arthritis, triggered by the sedimentation of monosodium urate crystals in periarticular tissues, synovial joints, and other sites in the body. Curcumin is a natural polyphenol compound, isolated from the rhizome of the plant Curcuma longa, possessing countless physiological features, including antioxidant, anti-inflammatory, and anti-rheumatic qualities. OBJECTIVE: This study aimed to discuss the beneficial impacts of curcumin and its mechanism in treating gout disease. METHODS: Ten English and Persian databases were used to conduct a thorough literature search. Studies examining the anti-gouty arthritis effects of curcumin and meeting the inclusion criteria were included. RESULTS: According to the studies, curcumin has shown xanthine oxidase and urate transporter-1 inhibitory properties, uric acid inhibitory characteristics, and antioxidant and anti-inflammatory effects. However, some articles found no prominent reduction in uric acid levels. CONCLUSION: In this review, we emphasized the potency of curcumin and its compounds against gouty arthritis. Despite the potency, we suggest an additional well-designed evaluation of curcumin, before its therapeutic effectiveness is completely approved as an anti-gouty arthritis agent.

The Role of Resveratrol in Aging and Senescence: A Focus on Molecular Mechanisms.

Resveratrol (Res), a polyphenol found in red wine, has been shown to decelerate aging, the progressive loss of physiological integrity and cellular senescence, characterized by the inability to progress through the cell cycle. No successful clinical trials have yet to be completed in humans on dose limitations. Yet, the potent anti-aging and anti-senescence efficacy of Res has been documented in several in vivo animal models. In this review, we highlight the molecular mechanisms of Res efficacy in anti-aging disorders, such as diabetes, neurodegenerative disorders, eye diseases, and cardiovascular diseases.

Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene.

BACKGROUND: Triple-negative breast cancer (TNBC) is one of the subtypes of breast cancer (BC) that is associated with poor survival rates and failure to respond to hormonal and targeted therapies. OBJECTIVE: The aim of this study was to identify a specific gene at the expression level for TNBC and targeting of this type of breast cancer based on it. Using TCGA database, genes that are particularly high expression in TNBC subtypes compared to other BC subtypes (in terms of receptor status) and normal samples were identified and their sensitivity and specificity were evaluated. Using PharmacoGX and Drug Bank data, drug sensitivity and drug-appropriate genes were identified, respectively. The effects of the identified drug on triple-negative cell lines (MDA-MB-468) were evaluated in comparison with the cell line of other subtypes (MCF7) by apoptosis and MTS tests. RESULTS: Data analyzes showed that the expression level of KCNG1 gene in the TNBC subgroup was significantly higher compared to other BC subtypes from the KCN gene family and ROC results showed that this gene had highest sensitivity and specificity in TNBC subtype. The results of drug resistance and sensitivity showed that an increase in the expression level of KCNG1 was associated with sensitivity to Cisplatin and Oxaliplatin. Moreover, Drug Bank results showed that Guanidine hydrochloride (GuHCl) was a suitable inhibitor for KCNG1. In vitro results showed that the expression level of KCNG1 was higher in MDA-MB-468 compared to MCF7. In addition, the rate of apoptosis in response to GuHCl treatment in MDA-MB-468 cell line as TNBC cell model was higher than MCF7 in the same concentration. CONCLUSION: This study revealed that GuHCl could be a suitable treatment for TNBC subtype by targeting of KCNG1.

Oncogenic alterations of metabolism associated with resistance to chemotherapy.

Metabolic reprogramming in cancer cells is a strategy to meet high proliferation rates, invasion, and metastasis. Also, several researchers indicated that the cellular metabolism changed during the resistance to chemotherapy. Since glycolytic enzymes play a prominent role in these alterations, the ability to reduce resistance to chemotherapy drugs is promising for cancer patients. Oscillating gene expression of these enzymes was involved in the proliferation, invasion, and metastasis of cancer cells. This review discussed the roles of some glycolytic enzymes associated with cancer progression and resistance to chemotherapy in the various cancer types.

Protective effects of curcumin and its analogues via the Nrf2 pathway in metabolic syndrome.

Metabolic Syndrome (MetS) refers to a set of medical conditions including insulin resistance, central obesity, atherogenic dyslipidemia, and hypertension. Due to these dysregulations, if not treated, MetS could increase the risk of CVA, CVD, and diabetes. As described by WHO, CVD is the leading cause of mortality in the world which motivates researchers to investigate the management of its risk factors, especially MetS. It is reported that oxidative stress secondary to the abundant generation of free radicals oxygen species (ROS) and the ensuing altered redox status play an important role as a mediator in MetS. As a result, using new antioxidant agents with higher bioavailability has been proposed as an efficient treatment. Curcumin (a polyphenol of the diarylheptanoids class), which is used as a traditional medicine for various diseases including cardiovascular diseases and diabetes, is characterized by its antioxidant properties which, at least in part, are mediated via the activation of the Nrf2/ARE signaling pathway. Nrf2 is a transcription factor that plays a key role in regulating internal defense systems and increases antioxidant levels to decrease oxidative damage and cell apoptosis. Nrf2 expression and stability are enhanced by curcumin, leading to a higher rate of Nrf2 migration to the cell nucleus to regulate ARE gene expression, thus protecting cells against oxidative stress. In this article, we provide a comprehensive review of the molecular effect of curcumin and its derivatives via Nrf2 regulation in several conditions, such as diabetes, hypertension, dyslipidemia, and obesity.