Oxidative stress results after an imbalance between the antioxidant and oxidant systems. Under normal physiological state, cells contain low oxidants and oxygen radical concentrations, which modulate cellular equilibrium, differentiation, mitosis, survival, and signaling (Bagheri et al., 2016). Oxidative stress has been associated with genesis and etiology of various disorders, including ischemic myocardial injury (Yang Y. et al., 2013). Recent studies have validated that Cur has strong antioxidant activity which can prevent or reduce ischemia-reperfusion (I-R) injury. Cur induces silent information regulator 1 (SIRT1) signaling, which promotes the overexpression of Bcl-2 and the downregulation of Bax, thereby mitigating mitochondrial insufficiency after myocardial I-R (Zhang et al., 2024). Cur may also maintain the redox potential of the mitochondria by markedly enhancing the activity of the superoxide dismutase (SOD) enzyme and reducing the production of MDA and hydrogen peroxide within the mitochondria (Yang Y. et al., 2013). Furthermore, it also promotes the activation of nuclear factor erythroid-derived 2 (Nrf2)- a nuclear basic leucine zipper transcription factor that belongs to the NF-E2 family, and controls the expression of several genes involved in pro-oxidative stimuli detoxification (Fisher et al., 2007). A clinical experiment investigated the beneficial effect of curcuminoids in reducing myocardial I-R damage after CABG. Curcuminoids (4 g/day) were supplemented beginning 3 days following CABG and before 5 days. The results reported a significantly lower incidence (17%) of in-hospital MI in the curcuminoids group as compared to placebo. Plasma concentrations of MDA (biochemical indicator of oxidative stress and lipid peroxidation), C-reactive protein (diagnostic of systemic inflammation), and N-terminal pro-B-type natriuretic peptide were reduced after curcuminoids consumption (Wongcharoen et al., 2012). Schematic diagram illustrating the role of Cur in mitigating oxidative stress and MI is depicted in Figure 2.

Apoptosis has been extensively studied and occurs naturally in multicellular organisms. However, specific diseases can trigger apoptotic pathways, leading to unintended cell necrosis. For example, cardiac I-R initiates the apoptotic pathways, leading to cardiomyocyte death (Wang Y. et al., 2014). Duan et al. investigated rat hearts and indicated that curcumin protects against the harmful effects of myocardial I-R (Duan et al., 2012). Knockdown of the JAK kinase-specific inhibitor AG490 revealed that curcumin alleviated the I–R damage caused by the JAK2–STAT3 signaling pathway activation, which was reflected in the overexpression of Bcl-2 and downregulation of caspase-3 (Duan et al., 2012). In addition, Jeong et al. revealed that curcumin inhibits numerous prosurvival kinases to protect against regional myocardial I-R damage (Jeong et al., 2012). Curcumin has been observed to significantly enhance the antiapoptotic cascade kinases glycogen synthase kinase-3β (GSK-3β), Akt, phosphoinositide 3-kinase (PI3K), and extracellular signal-regulated kinase 1/2 (ERK1/2) were all phosphorylated. p38 MAPKS is one of the most significant signaling pathways that regulate cellular stressors and diverse pathological states, such as cardiac I-R (Jeong et al., 2012) and cell death. Cur therapy decreased p38 MAPK and c-Jun NH2-terminal protein kinase (JNK) phosphorylation levels (Wang J. et al., 2023).

Autophagy is essential for cardiomyocytes to maintain cellular homeostasis (Huang et al., 2015). During physiological conditions, the basal autophagy level in the cardiovascular system is sufficient to protect cells from energy constraints and eliminate damaged organelles and superfluous proteins. Natural components in food, including Cur regulate autophagy by inducing cardioprotective effects which shields mouse cardiomyocytes from oxidative stress (Salabei and Conklin, 2013; Han et al., 2012). Several studies indicated protective autophagy is associated with the activation of the early myocardial ischemia stages and the AMPK pathway (Yang K. et al., 2013). Cur has been observed to prevent I-R damage in H9c2 myocytes by inhibiting increased autophagy and apoptosis, and downregulating the expression of SIRT1, Beclin-1, Bax, BNIP3, and Bcl-2 (Huang et al., 2015).

Complex processes modulate inflammatory reactions and are essential components of host defense. Leukocytes infiltrate the infarcted myocardial area, triggering inflammatory response (Biswas, 2016). However, excessive inflammatory response can damage heart perfusion (Pashkow, 2011). A study indicated that NF-κB signaling is an essential proinflammatory signaling route implicated in cardiac I-R damage. Fiorillo et al. revealed that besides antioxidant protective mechanism, Cur promotes its cardioprotective effects via multiple pathways including NF-κB and JNK pathways (Fiorillo et al., 2008). Cur has been observed to reduce pathological alterations associated with I-R used before or after I-R therapy. Kim et al. showed that pretreatment with Cur (300 mg/kg/day) for 7 days in SD rats decreased the expressions of TLR2 and MCP-1 in cardiomyocytes after I-R damage, inhibited activation of TNF-α, reduced fibrotic response, and inhibited macrophage infiltration (CD68) in cardiac tissues (Kim et al., 2012). The summary of the main molecular mechanisms of curcumin in MI is given in Table 1.

Liposomes are spherical vesicles that mimic cell membranes, made up of one or more phospholipid bilayers (Bozzuto and Molinari, 2015). Nanoparticles encapsulating liposomes are employed in nano-drug formulations. Liposomes have many advantages including enhanced solubility, controlled dispersion, ease of manufacturing, high stability, minimal toxicity, and targeting ability of distinct cells (Tiwari et al., 2012). Several studies indicated that liposomal curcumin provides the best delivery system for treating heart failure (Jiang et al., 2017; Çağdaş et al., 2014). Recently, liposomes have been synthesized to co-deliver atorvastatin calcium and Cur to treat atherosclerosis (Li et al., 2019). Cur as a safe adjunct, has been found to reduce the harmful effects of atorvastatin calcium while enhancing its anti-atherosclerotic properties. To enhance the effectiveness of this treatment, specific ligands have been integrated into the liposome membrane to facilitate targeted delivery. The combined action of these two active ingredients leads to a reduction in pro-inflammatory factors and the formation of atherosclerotic plaques (Li et al., 2019). Moreover, liposomes co-encapsulating resveratrol and Cur have indicated increased encapsulation efficiency, reduced polydispersity index (PDI), and smaller particle size (Huang et al., 2019). Consistently, the literature has indicated that curcumin loaded liposomes possess anti-inflammatory, antioxidant, and cardio-protective properties (Salehi et al., 2020; Basnet et al., 2012).

Liposomal scaffolds are an effective tool for platelet targeting in CVD diagnosis and treatment. It has shown that the natural peptides on the liposomal surface can help target damaged or diseased tissues and facilitate the transfer of active pharmaceutical drugs. Several research studies have indicated that atherosclerosis, MI, aneurysms, angiogenesis, and other CVD outcomes support nano-technology in theranostics (Pala et al., 2021). Figure 3 represents how liposomes act as advanced drug carriers for treating various cardiovascular conditions, highlighting the co-delivery of curcumin and atorvastatin and the targeting of specific tissues through functionalized vesicles.

Solid lipid, polymer, gold, magnetic, and albumin-based nanoparticles have been used to increase the therapeutic applications of curcumin (Danhier et al., 2012). Biocompatible polymeric nanoparticles can stay in the bloodstream for long periods. Various natural and synthetic polymers are employed to form nanoparticles such as polyvinyl alcohol (PVA), polyethylene glycol, silk fibroin, hydrophobic compounds modified starch, and low-density chitosan (Fredenberg et al., 2011). Boarescu et al. investigated the effect of pretreating rats with free Cur and CurNP to treat isoproterenol-induced MI. Doses of 100, 150, and 200 mg/kg were administered in rats for 15 days, and on the 13th day, MI was induced (Boarescu et al., 2019a). Blood samples were collected during studies to assess the antioxidant, cardio-protective, and anti-inflammatory properties of the CCNP by measuring the oxidative stress indices, as well as several enzymes (CK and CK-MB). It was observed that all doses of Cur and CCNP prevent CK-MB outburst from cardiomyocytes, suggesting its cardio-protective effect. A study indicated that rats orally administered with nanoparticles of hydroxyapatite (HAPNPs) had cardiac toxicity (Yousef et al., 2021). This was evident from the increased serum MI markers, such as CK-MB, changes in routine blood factors, increased serum inflammatory markers, P53 expression (apoptotic protein), and interleukin-6 (IL-6), as well as decreased glutathione and cardiac antioxidant enzyme levels. Significant histopathological and histochemical changes were observed in the rats’ hearts, along with lipid peroxidation and nitric oxide. However, the co-administration of Cur and chitosan nanoparticles effectively alleviated these changes (Mosa et al., 2021).

Solid lipid nanoparticles (SLNs) are colloidal submicron particles made of lipids. They are biodegradable, readily scalable drug delivery systems with a high drug-to-fat ratio, which enables poorly soluble substances to become more soluble. SLNs can increase the solubility of natural Cur and decrease the lipopolysaccharide (LPS)-induced activity of pro-inflammatory mediators, such as NO, PGE2, and IL-6, by blocking NF-κB activation (Ganugula et al., 2017). Zhang et al. created Cur loaded nanoparticles (Cur-PEG-PDLLA) and assessed their impact on palmitate-induced cardiomyocyte death. It was observed that Cur-PEG-PDLLA reduced cardiomyocyte death, decreased Bax (a crucial mitochondria target), and increased Bcl-2 (an antiapoptotic protein that prevents Bax from oligomerizing) (Zhang et al., 2019). Therefore, the authors hypothesized that Bcl-2/Bax ratio modulation might be associated with the cardioprotective effect of Cur-PEG-PDLLA. Furthermore, Cur-PEG-PDLLA-treated cardiomyocytes had decreased ROS generation. According to their later study, these effects were associated with the modulation of particular downstream protein expression and the activation of the AMP-mediated protein kinase signaling pathway (Salehi et al., 2020).

Metallic nanoparticles (e.g., Fe, Zn, Ag, etc.) are inexpensive to prepare having special physical qualities. In a recent study, Lijuan Tan created a modern cardioprotective drug (eco-friendly, Zn NPs of Curcumin) to address the MI (iso-preterinol induced) in mice, focus on the PPAR-γ/NF-κB pathway (Tan, 2024). In mice with myocardial infarction, ZnNPs reduce cardiac inflammation. ZnNPs increase ventricular wall infarction, reduce mortality, and lower myocardial injury indicators. ZnNPs significantly attenuated the ST segment depression in mice with myocardial infarction. The mice with myocardial infarction in the pre + post-isoproterenol group showed more cardioprotective benefits from ZnNPs than those in the post-isoproterenol group. ZnNPs significantly reduced cell death and inflammatory cytokine expression in vitro. the results showed that ZnNPs may have favorable effects by normalizing gene expression for PPAR-γ/NF-κB/IκB-α/IKKα/β and phosphorylating PPAR-γ. This study found that ZnNPs protect against isoproterenol-induced myocardial infarction may be due to PPAR-γ activation and NF-κB signaling inhibition. In another recent study, Bourang et al. constructed iron oxide (Fe₃O₄) nanoparticles of cur and assessed them for colorectal cancer treatment in vitro (Bourang et al., 2024). Their study showed that the nanoparticles had high cytotoxicity on colorectal cancer cells and little damage on non-cancerous cells, indicating a well-targeted drug delivery strategy for future colorectal cancer treatments, suggesting the safety of use in other conditions. Moreover, natural compound-coated nanoparticles with magnetic properties have demonstrated their effectiveness in CVD imaging. Suzuki et al. established an animal model via arterial thrombus and elastase-induced vascular damage. They reported that ultra-small superparamagnetic iron oxide nanoparticles were more effective than specific polysaccharides-coated MRI materials. Another example includes effective detection of MI using gold nanoparticles (AuNPs) as contrast agents. The technique relies on collagen-conjugated designed AuNPs, which have been shown to detect myocardial and ischemic damage with great resolution and provide appropriate therapeutic tool (Suzuki et al., 2015). Figure 4 illustrates the effects of metallic nanoparticles on myocardial infarction (MI).

Curcumin oral bioavailability and solubility can be enhanced by conjugating with small molecules and hydrophilic polymers. According to Manju and Sreenivasan, conjugating curcumin with hyaluronic acid enhances its water solubility and stability as well as reduces the impact of the effect of AuNPs (Manju and Sreenivasan, 2011). A conjugate of Cur to a food-derived hydrophilic hydroxyethyl starch (HES) with an acid labile ester linker was used in a study to create amphiphilic conjugates (Chen et al., 2020). The conjugate’s self-assembly produced homogenous micellar nanoparticles (HES-CUR NPs) with significant colloidal and storage stability, an acid-responsive release mechanism, and a favorable drug loading efficacy (Xu et al., 2018). Moreover, this nanoparticle enhanced Cur solubility hundreds of times than its free form and protected the loaded curcumin from UV radiation-induced deterioration. In addition, the in vitro cytotoxicity assays and radical scavenging investigations have indicated that HES-Cur NP’s increased solubility, stability, and bioavailability, considerably increased Cur cytocompatibility, anticancer, and antioxidant activity. Therefore, HES-Cur NPs can be used for creating functional food products or drug formulations that prevent or treat various illnesses, including cancer and inflammatory disorders (Wichitnithad et al., 2011).

Solid dispersion is the molecular dispersion of two different substances (Ford, 1986). The solid dispersions are dissolved as tiny colloidal particles in an aqueous medium to release the medication (Okonogi et al., 1999). Solid dispersions can be made using solvent-based, fusion-melt techniques as well as hybrid techniques that combine the two. Li et al. established a curcumin-Eudragit^® PO solid dispersion via a solution mixing method to improve curcumin’s aqueous solubility and stability. Moreover, an in vitro transdermal study validated Cur@EPO’s suitability as a Cur delivery system for medical applications. In addition, several studies revealed spray-dried CUR-Gelucire^®50/13 solid dispersion increased (3,600-fold) water solubility compared with the native Cur (Li et al., 2015).

A micelle comprises amphiphilic surfactants that form a spherical vesicle when dissolved in a solvent. Micelle is commonly used as a drug delivery system for poor water soluble substances like curcumin (Gong et al., 2013). A recent clinical trial indicated that coronary angioplasty patients had improved lipid profiles and oxidative and inflammatory indicators after Cur nano-micelle treatment (80 mg/day), compared to Cur alone (500 mg/day) (Helli et al., 2021). Furthermore, curcumin nano-formulation significantly reduced the levels of TNF-α, triacylglycerol (TG), malondialdehyde, and SOD (Huang et al., 2019). Another study revealed that hemodialysis patients had reduced proinflammatory adhesion molecules, VCAM-1 and ICAM-1, as well as serum CRP levels after nano-Cur treatment (120 mg/day) (Vafadar afshar et al., 2020). Curcumin nano-micelle also significantly improved the levels of TG in patients with metabolic syndrome but failed to ameliorate other biochemical parameters such as TC, LDL-C, HDL-C, fasting blood sugar (FBS), hemoglobin A1c (HbA1c), homeostatic model assessment (HOMA) for insulin resistance (HOMA-IR), and pancreatic β cell function (HOMA-β) (Bateni et al., 2021). The research revealed that curcumin co-delivered with resveratrol (Cur-Res-mP127) significantly enhanced its aqueous solubility, approximately 1617-fold more than the solubility of the free Cur. Experimental results demonstrated that Cur-Res-mP127 provided cardio protection in rat embryonic cardiomyocytes (H9C2) treated with doxorubicin hydrochloride by reducing apoptosis and ROS (Carlson et al., 2014).

Increase in L-type Ca2+ channel-mediated ROS production and ischemia-reperfusion damage can cause CVD. Scientists assessed the effectiveness of poly (glycidyl methacrylate) nanoparticles enclosed Cur in (Cur-PGMA) and their amalgamation with a peptide that focuses on the α-interacting domain of L-type Ca2+ channels (Cur-AID-PGMA) in rat hearts that were exposed to ischemia-reperfusion. This study aimed to validate these formulations reduced the negative impact of ischemia-reperfusion by inhibiting ROS production and Ca2+ influx (Hardy et al., 2015). The average Cur-AID-PGMA nanoparticles diameter was 152 nm, and PDI was 0.062, suggesting a limited size availability. Cur loading efficiency in the nanoparticles was 11.8% (w/w). It was observed that after ischemia-reperfusion injury, both the Cur-PGMA and Cur-AID-PGMA formulations exerted protective effects against oxidative stress and myocardial injury, indicating their potential therapeutic utility in treating ischemia-reperfusion injury. Based on these results, a study comprehensively investigated the effectiveness of these formulations and highlighted that Cur-loaded nanoparticles reduced myocardial damage and targeted oxidative stress, thereby mitigating the negative effects of ischemia-reperfusion injury (Mohamadian et al., 2022). These data provide the basis for the possible clinical use of Cur-based nanoparticles for the treatment of heart conditions. Ray et al. (2016) showed that while keeping curcumin’s bioactivity, its encapsulation in carboxymethyl chitosan nanoparticles (Cur-CMC), bioavailability is enhanced. Furthermore, Cur-CMC suppressed the heart hypertrophy in rat model’s. Similar to free Cur nano formulation enabled the observation of advantageous effects at a low dose (5 mg/kg body weight).

Microcapsules have an exterior polymeric shell and an internal core. S Manna et al. synthesized selenium nanoparticles encapsulating poly (lactide-co-glycolide) nanospheres using Cur and assessed them against Alzheimer’s disease, suggesting the use of this carrier system for cur delivery (Huo et al., 2019). Hydrophilic drug carriers with a positively charged surface are important for increasing Cur permeability across biological barriers such as the blood-brain barrier. Recently, a cationic polymer, N, N, N-Trimethyl Chitosan (TMC), which is a quaternized chitosan derivative, was established. The TMC synthesis was validated via infrared spectroscopy (FTIR) and nuclear magnetic resonance (1H-NMR). A nano-emulsion technique was employed to synthesize TMC-based nano-spheres for loading Cur (Manna et al., 2023). These studies suggest the use of such curcumin formulations in cardiovascular diseases like MI.

Natural antioxidants in the human diet, such as Cur and resveratrol are employed to treat and prevent various oxidative stress-related illnesses. Lipid-core nano-capsules comprising Cur and resveratrol were prepared to enhance the antioxidant properties of Cur and resveratrol. Physical and chemical properties were assessed and compared with formulations comprising each polyphenol separately. The nano-technological properties of all formulations showed a mean diameter of approximately 200 nm, a low PDI, and nearly 100% encapsulation efficiency without any significant impact from co-encapsulation. It was also observed that resveratrol and Cur were more photo-stable when nanoencapsulated, whereas resveratrol indicated higher photostability when co-encapsulated. The in vitro antioxidant activity of polyphenols against OH radical was enhanced by nanoencapsulation, and a better effect was observed after their co-nano encapsulation. Moreover, both nanocapsulated polyphenols indicated a regulated release profile. Overall, it was observed that co-encapsulating Cur and resveratrol can enhance their therapeutic and preventive efficacy against oxidative stress-related illnesses (Coradini et al., 2014).

Nano-formulations of piperine as a cofactor for MI therapy represent a promising approach to improve the bioavailability and therapeutic efficacy of bioactive compounds (Tagde et al., 2021). It significantly improves curcumin’s pharmacokinetics and absorption and overcomes its poor bioavailability, facilitating delivery to ischemic myocardial tissue. The administration of This synergy may decrease oxidative stress, inflammation, and apoptosis and promote cardiomyocyte survival and tissue repair (Tagde et al., 2021). Piperine has also been found to promote angiogenesis and, therefore, support tissue regeneration. Several studies have used the co-delivery strategy of Piperine and curcumin for enhacing the curcumin’s bioavailability with good results (Moorthi et al., 2012; Tu et al., 2014; Baspinar et al., 2018; Ahmadi et al., 2023). These nanoformulations, however, present challenges in ensuring stability, targeted delivery, and safe long term effects, which will need further experimental and clinical investigation before clinical application (Wang Z. et al., 2023).

In recent years, injectable hydrogel systems have significantly progressed in biological applications. These biomaterials offer numerous benefits of targeted administration, controlled release, and improved mechanical qualities (Caillaud et al., 2018). Researchers assessed if a magnetic hydrogel nanocomposite loaded with Cur could effectively treat heart hypertrophy. They induced cardiac failure in 10 rats by administering 2.5 mg/kg of doxorubicin for 2 weeks. The rats weighed between 150 and 200 g. Then, Cur-loaded magnetic hydrogel nanocomposite was administered to the test groups, whereas the control group was only administered with Cur (Namdari and Eatemadi, 2017). After 2 weeks of the last dosage, the levels of MDA and GPX enzymes were observed. Furthermore, the expression of three heart failure markers, including beta major histology complex (β-MHC), B-type natriuretic peptide (BNP), and atrial natriuretic peptide (ANP), was examined. The expression of these markers decreased as Cur concentration increased (p < 0.05). In cardiac tissue, Cur decreased the raised level of MDA and increased the levels of SOD and GPX. Altogether, it was inferred that this combination could be employed to treat hypertension and heart failure (Namdari and Eatemadi, 2017). These studies suggest the use of local administration of curcumin could significantly enhance its therapeutic potentials in MI. Table 2 shows some prominent studies of curcumin in cardiovascular diseases.

Recent advances in nanomedicine have significantly facilitated drug delivery, diagnosis, and treatment, especially for neurological, cardiovascular, and cancerous conditions. Targeted medication delivery is improved by stimuli-responsive nanoparticles and surface-modified nanocarriers, which release drugs in response to specific stimuli or deliver them directly to diseased tissues (Hesari et al., 2021). Nanoparticles have transformed mRNA and CRISPR delivery in gene therapy, increasing efficacy and safety. Nanotechnology has significantly improved liquid biopsies and immediate diagnostics, enabling quicker and more precise disease diagnosis. Bio-degradable nanoparticles reduce toxicity, while personalized nanomedicine tailored therapies to individual genetic profiles. Advances in immune nanomedicine like nanorobotics offer the potential for transformative minimally invasive treatments (Scafa Udriște et al., 2024). Rachmawati et al. employed 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and acetylcholinesterase (ACE) assay kits to evaluate the antihypertensive and anti-hypercholesterolemic properties of Cur nano-emulsion in vitro. They revealed that nano-emulsified Cur inhibit ACE more than pure Cur (Rachmawati et al., 2016). When Cur/P was administered in vivo, cardiac cells’ serum levels of H2S and Ca2+ content increased, and their expression of the calcium-sensing receptor, calmodulin, and cystathionine-γ-lyase was upregulated. Moreover, Cur and Cur/P alleviated the pathological and morphological loss of cardiac cells and substantially reduced diabetic cardiomyopathy. Two Cur nano-formulations were studied against ischemia-reperfusion injury in rat hearts: 1) Cur-PGMA and 2) Cur combined with a peptide targeting the α-interacting domain of L-type Ca2+ channel (Cur-AIDPGMA). It was observed that both these nano-formulations were effective against ischemia-reperfusion-induced oxidative stress and myocardial injury (Ray et al., 2016). CCNPs (50 mg/kg) were employed for treating monocrotaline-induced pulmonary arterial hypertension in the rat model. It was revealed that CCNP treatment attenuated the development of right ventricular hypertrophy, decreased right ventricle weight to body weight ratio, decreased right ventricle mRNA expression of TNF-α and IL-1β, and diminished oxidative stress (Boarescu et al., 2019b).

A study utilized isoproterenol hydrochloride (ISO) to induce MI in rats and then investigated the effects of the administration of nano cur (Nc) and CUR solutions. Pre- and post-ISO treatment rats indicated that Cur and Nc did not affect the diastolic and systolic blood pressures. Before being treated with ISO, rats that received varied of Cur and Nc showed a decrease in heart rate and extended RR interval. However, how Cur lowered heart rate remains undetermined. The highest dose of Cur and Nc (200 mg/kg/body weight) was more effective for cardioprotection (Boarescu et al., 2019b). Lipid peroxidation, nitric oxide, myocardial MDA levels, and overall oxidative state decreased after Cur and Nc pretreatment. Rats that received Nc pretreatment indicated reduced nitric oxide levels, whereas Cur and Nc-treated ISO-induced rats had reduced blood LDH, ALT, and AST levels. However, Nc had more potential effects (Boarescu et al., 2019b). Hybrid Cur lipopolymer nanoparticles are also employed as a QT prolongation preventive measure (Ranjan et al., 2013). Boarescu et al. indicated that pretreatment with Cur and Nc decreased necrosis, myofibrillar degeneration, interstitial edema, and significant cardiac damage to tissue. Therefore, it was recommended that Nc should be administered to inhibit the progression of cardiac tissue damage in cases of acute MI (Boarescu et al., 2019b).

An antimicrobial peptide called nisin reduced the number of squamous carcinomas of the head and neck cells while inducing an arrest of the cell cycle and apoptosis (Joo et al., 2012). In mammals, Cur-nisin nanoparticles (CurNisNp) have been observed to be absorbed well without any toxicity. The preliminary treatment of ISO-induced guinea rats with CurNisNp before MI resulted in elevated ECG patterns and decreased ROS and MDA levels, serum myeloperoxidase activity, and cardiac troponin I. Cur enhanced the reduced transverse striations, necrosis, myofibril thickness, and hypertrophic index (Nabofa et al., 2018). Moreover, a novel drug delivery system of Curcumin was prepared and its administration significantly increased rats’ cardiac output and reduced their posterior wall thickness (Yadav et al., 2019; Sunagawa et al., 2012).

Rats were used to test the effectiveness of Cur-loaded mesoporous silica nanoparticles (MSNs) against doxorubicin-induced cardiac toxicity. The preliminary Cur-MSNs treatment reduced MDA levels but increased SOD and catalase levels in cardiac cells, thereby protecting the heart from the deleterious effects of recurrent doxorubicin delivery. The cardiac tissue histology of Cur, MSNs, and doxorubicin-treated patients indicated enhanced myofibrils and cytoplasm vacuolization. Moreover, the cardioprotective effects of Cur-MSNs might be because of their anti-inflammatory and antioxidant abilities, as well as their increased bioavailability (Yadav et al., 2019). Liu et al. found that cardiomyocytes exposed to CCNPs had lower levels of intracellular ROS, Rac1 activation, and cell death. Moreover, NP treatment also reduced the expression of palmitate-induced gp91phox, inhibited ROS production, and enhanced SOD activity or suppressed NADPH isoforms. In addition, it stopped apoptosis. It was determined that stress-associated inflammation of the endoplasmic signaling system inhibits NADPH-induced oxidative stress. Therefore, CCNPs were proposed as a potential formulation to ameliorate cardiac harm caused by lipid toxicity. CCNPs may promote these effects by modulating the expression of particular proteins and initiating the adenosine monophosphate-activated protein kinase signaling pathway (Liu et al., 2019). The impact of a magnetic hydrogel composite loaded with doxorubicin-induced MI in rats was also studied. Cur-NIPAAM-MAA-NP’s reduced the expression of the heart failure indicators β-myosin heavy-chain gene, B-type natriuretic peptide, and atrial natriuretic peptide, thereby validating its cardioprotective efficacy (Daya et al., 2022). In addition, the injection of lipid nano-emulsions loaded with Cur (CmLN) and coupled with a nano-arginine peptide (R9CmLN) indicated little cytotoxic and hemolytic effects on human endothelial cells (Simion et al., 2016). A recent investigation revealed that PLGA-CCNPs can increase the oral bioavailability of Cur and decrease liver fat accumulation, thereby improving cardiovascular responses. Another study indicated that CCNPs stopped cardiomyocyte CK-MB leakage in an ISO-induced MI rat. After MI induction, no increase in the circulation levels of IL-1α, MCP-1, IL-6, IL-1β, and TNF-α was observed. In a study using rats, the injection of PLGA nanoparticles co-loaded with gold and capped with Cur prevented heart hypertrophy by enhancing bioavailability, solubility, and absorption, as well as by resisting enzymatic breakdown and medication delivery effectiveness (Hesari et al., 2021). In addition, the antioxidant, antiapoptotic, and anti-inflammatory properties of CAu-PLGA Nps improved survival rates, maintained cardiac output, and protected rodents from cardiac toxicity and heart failure (Xie et al., 2011). These studies suggest that nanoformulations of curcumin could offer more safer and better therapeutic option for cardiovascular ailments like MI.