It has been observed that curcumin can modulate a wide range of molecular targets that are associated with the underlying causes of numerous human disorders. Figure 1 illustrates the therapeutic potential of curcumin across major categories of medical illnesses. The multifaceted properties of curcumin are emphasized, underscoring its relevance in the treatment and prevention of various diseases. Curcuma longa Linnaeus, commonly known as turmeric (Family: Zingiberaceae; Genus: Curcuma; Species: longa) within the Plantae kingdom and the Magnoliophyta division (Rai et al., 2015), has been widely studied for its medicinal value. Curcumin, the principal bioactive compound of Curcuma longa, has been reported to possess diverse therapeutic applications, ranging from the treatment of cancer to the management of coughs and colds (Mundekkad & Cho, 2023). Studies on curcumin-based formulations Table 1 have demonstrated that Curcuma longa exhibits multiple pharmacological benefits and exerts significant anticancer activities against various cell lines.

Curcumin has been reported to produce significant outcomes, including an increased percentage of drug sensitivity, in overcoming medication resistance frequently observed in breast, ovarian, lung, and other cancer types (Amaroli et al., 2024). In breast cancer cell lines, the overexpression of flap endonuclease 1 (FEN1) has been associated with increased resistance to the chemotherapeutic drug cisplatin. It has been discovered that curcumin enhances the sensitivity of breast cancer cells to cisplatin through the downregulation of FEN1 expression in vitro (Zou et al., 2018). Apoptosis was also observed in MCF-7 and MCF-7-DDP cells treated with curcumin. In cells exposed to 2 μg/mL cisplatin combined with 20 μmol/L curcumin, a significantly higher degree of apoptosis was recorded in the combination treatment group compared to cisplatin treatment alone (P < 0.05). These findings suggest that the combined use of cisplatin and curcumin may enhance the susceptibility of breast cancer cells to cisplatin (Ke et al., 2014). Similarly, it has been demonstrated that curcumin, when used together with cisplatin, can overcome cisplatin resistance in lung cancer by promoting apoptosis and inhibiting cell proliferation (Priyadarsini, 2014).

With an IC₅₀ at the micromolar level, it was observed that curcumin significantly suppressed the proliferation of several cancer cell lines, including T47D, MCF7, and MDA-MB-231 (p < 0.001). These findings indicate that curcumin possesses strong anticancer properties. Cell cycle arrest at the G2/M phase was reported following curcumin treatment, as determined through a comprehensive investigation of its mechanism of action (Shan et al., 2018). Among the numerous biological effects of curcumin, its ability to stimulate the production of phase II and antioxidant enzymes through Nrf2-dependent pathways has been highlighted. Due to its rapid metabolism and low bioavailability, curcumin has been extensively investigated in several clinical trials (Deck et al., 2018).

The outcomes were found to demonstrate modest hemolytic and cytotoxic activities against eukaryotic cells, along with enhanced antibacterial and anticancer properties (Adahoun et al., 2017). It was also discovered that neither the extract nor the synthetically prepared gold nanoparticles (GNPs) exhibited any cytotoxic effects on the HeLa or L929 cell lines (Das et al., 2024).

According to a study, in both scratch and Transwell migration tests, the curcuzederone molecule, a phytocompound of C. longa, was found to significantly inhibit the migration of MDA-MB-231 cells (P < 0.05) and reduce cancer cell proliferation (Al-Amin et al., 2021). Based on these reported studies, curcumin is believed to exhibit anticancer properties through multiple mechanisms, including anti-angiogenic effects, induction of apoptosis, disruption of tumor cells, and prevention of tumor invasion into healthy tissues.

By improving mitochondrial function, reducing reactive oxygen species (ROS), and modulating antioxidant enzyme activity, curcumin has been shown to alleviate conditions associated with oxidative stress and mitochondrial dysfunction (Roohi et al., 2017). Recent studies have demonstrated that disorders related to mitochondrial dysfunction and oxidative stress can be mitigated by curcumin. It has been indicated that curcumin may provide therapeutic benefits for certain metabolic disorders(Sathyabhama et al., 2022). At low and intermediate doses, curcumin has been reported to decrease ROS either by upregulating Nrf2 protein levels or by enhancing the activities of SOD, CAT, and GSH-Px. The resulting increase in cellular capacity to eliminate ROS contributes to the preservation of oxidative stress resistance, potentially reducing apoptosis and improving cell survivability (Lin et al., 2020). In clinical models of neuroinflammation, diabetes, and cardiovascular disease, curcumin has been observed to significantly lower oxidative stress enzymes and ROS levels by directly scavenging free radicals and enhancing endogenous antioxidant defenses (Karamalakova et al., 2019).

In untrained, healthy men, oxidative damage is caused by sudden, intense exercise. Oral administration of curcumin for one week has been shown to reduce lipid peroxidation and potentially enhance the intracellular antioxidant system (Roohi et al., 2017). Antioxidant activity in the study was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical–scavenging assay. The ethanolic extract of Chittagong’s mura was found to contain the highest concentrations of ascorbic acid (0.09 mg/100 g), polyphenols (16.07%), and flavonoids (9.66%) (Tanvir et al., 2017).

Several strategies can be employed to achieve this goal, in addition to using micelles for targeting curcumin to mitochondria. For instance, the introduction of various nanocarriers and the development of curcumin derivatives that specifically target mitochondria have been explored (Hu et al., 2024). The growth of stomach tumor cells has been inhibited by curcumin micelles both in vivo and in vitro. This effect is believed to involve increased reactive oxygen species (ROS) production, disruption of redox homeostasis, and modulation of mitochondrial bioenergetics (Lin et al., 2020). Numerous studies have reported reductions in various inflammatory indicators, and the anti-inflammatory and antioxidant properties of curcumin are considered to mediate its beneficial effects on stress markers, inflammatory markers, ulcers, and osteoarthritis.

Curcumin has been proposed as a potential protective agent against inflammatory diseases, including cancer and ulcers. These biological effects are attributed to its antioxidant, antimicrobial, and anti-inflammatory properties. Based on the literature, it can be concluded that gastrointestinal ulcers are prevented by curcumin, and that the compound represents a unique therapeutic option for ulcer treatment (Yadav et al., 2013).

When compared to the control groups, the growth and colony formation of gastric tumor cells were dramatically reduced by curcumin micelles, and apoptosis was induced (Panda et al., 2017). n the repair of indomethacin-induced gastric ulcers (GU), an oral administration of a chitosan-curcumin mixture was found to be more effective than curcumin, chitosan, or lansoprazole, a conventional antiulcer drug (Kuadkaew et al., 2021). n a separate study, no acute toxicity was observed in rats treated with a metal-curcumin complex (MCC). The results indicated that MCC acted as a more efficient scavenger than curcumin. At an oral dose of 100 mg/kg, gastro-protective efficacy against ethanol-induced ulcers in rats was demonstrated by MCC (Joshi et al., 2023). Further investigation revealed that curcumin micelles affected mitochondrial proteins in gastric tumor cells, altering mitochondrial function and influencing mitochondrial bioenergetics (Panda et al., 2017).

The antioxidant properties of curcumin are believed to prevent CCl₄-induced secondary hepatic cytochrome P450 (CYP) damage. It has been reported that curcumin functions as an antioxidant and inhibits NF-κB activation, thereby preventing liver injury caused by CCl₄ (Perrone et al., 2015). Except at a concentration of 5 g/kg/day, no significant changes in hepatic cytochrome P450 levels or activity were observed following curcumin administration, according to a previous study (Sugiyama et al., 2006). In contrast, the activity of these isoenzymes, particularly cytochrome P450 2E1 (CYP2E1), was significantly reduced (P < 0.05) by CCl₄, resulting in elevated free radical production. Pretreatment with curcumin at a dose of 0.5 g/kg/day markedly inhibited the effects of CCl₄. Liver protection was conferred by Curcuma longa L. (CLL) extract, which also significantly decreased plasma bilirubin (BL), gamma-glutamyl transpeptidase (GGT), and lipid peroxidation levels. Consequently, the CLL extract may be utilized as an antioxidant in the treatment of chronic hepatotoxicity (Karamalakova et al., 2019). Furthermore, compared to free curcumin (100 mg/kg), silymarin (25 mg/kg), and self-recovery groups, curcumin-loaded solid lipid nanoparticles (C-SLNs) at 12.5 mg/kg significantly (P < 0.001) reduced histological alterations and oxidative stress (Xu et al., 2020).

Hepatotoxicity was evidenced by histological alterations in the liver induced by arsenic, which also elevated serum aspartate and alanine aminotransferase activities. In the liver, arsenic decreased the activities of glutathione reductase, catalase, and glutathione peroxidase, while increasing lipid peroxidation and depleting reduced glutathione. The effects of arsenic were mitigated by curcumin and its nanoparticle-encapsulated form (CUR-NP) in a preclinical trial, with the amelioration being more pronounced in the CUR-NP treatment. These findings indicate that curcumin administered in nano-encapsulated form produces greater protective effects than free curcumin (Lin et al., 2020). With stronger protective benefits demonstrated by CUR-NP, hepatotoxicity can be substantially reduced through restoration of antioxidant enzyme activity, reduction of lipid peroxidation, and improvement of liver histology. The bioactive potential of curcumin in preventing hepatotoxicity may be further elucidated through carefully designed clinical trials (Perrone et al., 2015). Moreover, in the context of ulcer and cancer treatment, such trials could provide critical insights into the optimal therapeutic use of curcumin, ultimately enhancing patient outcomes and overall well-being.

Blood coagulation occurs within arteries under various conditions, which can disrupt blood flow or cause internal bleeding that may occasionally be fatal. Therefore, anticoagulants are typically administered to prevent blood clotting in such situations. Additionally, inflammation has been shown to increase the risk of blood coagulation by activating molecules that promote clot formation (Chopra et al., 2021). In clinical trials, curcumin’s anticoagulant activity was demonstrated by comparing thromboplastin time and thrombin time analyses with control blood samples, revealing that curcumin prolongs blood clotting times. Both curcumin and its derivative, bisdemethoxycurcumin, were found to significantly extend prothrombin time and activated partial thromboplastin time while inhibiting the activities of activated factor X and thrombin (Sirisidthi et al., 2016).

Similarly, the anticoagulant effect of curcumin has been investigated, revealing that the presence of its hydrophobic groups contributes to a reduction in clotting time in both prothrombin time (PT) and activated partial thromboplastin time (APTT) assays. The ortho-methoxy group, also present in curcumin, has been shown to enhance its anticoagulant activity. Furthermore, a decrease in white blood cell (WBC) count was observed, which consequently reduced platelet aggregation and inhibited the formation of fibrin deposits in the kidneys. Therefore, curcumin, when combined with nanotechnology, is considered a potential anticoagulant and preventive agent for thrombotic disorders (Keihanian et al., 2018).

It has been suggested that effective prophylaxis is highly desirable, as neuroprotective strategies are most effective when applied prior to the onset of damage (Nebrisi, 2021). Among its pleiotropic actions, curcumin exhibits anti-inflammatory properties, a favorable safety profile, and potential neuroprotective efficacy (Cole et al., 2007). The pharmaco-therapeutic potential of curcumin in cerebral ischemia, including its molecular mechanisms of neuroprotection, has been reviewed in animal models, and it has been observed that curcumin represents a promising therapeutic candidate for cerebral ischemia, demonstrating significant improvements in biochemical parameters (Lalita & Bhakta, 2021).

Gold nanoparticles functionalized with curcumin have been shown to effectively interact with amyloid proteins and peptides, inhibit amyloid fibrillation, and disintegrate amyloid fibrils by acting as synthetic molecular chaperones (Yallapu et al., 2015). The desolvation technique was successfully employed to produce curcumin-loaded α-lactalbumin (α-LA) nanoparticles, targeting a particle size range of 100 - 150 nm. The resulting formulation, α-LA-Curcumin, has been demonstrated to provide protection against permethrin-induced neurotoxicity. Upon application of α-LA-Curcumin, the generation of ROS induced by permethrin was reduced, thereby mitigating cellular damage (Paulpandi et al., 2023). NF-κB mRNA expression was significantly downregulated following administration of caffeine-mediated nano-curcumin (N-CUR), while TNF-α and IL-6 levels, as well as SOD activity, were significantly improved. N-CUR has been reported to exert mild to moderate beneficial effects on caffeine-induced inflammatory responses, oxidative stress, and apoptosis in the brain (Morsy et al., 2024). The neuroprotective effects of curcumin are believed to be mediated through multiple mechanisms, including modulation of oxidative stress, excitotoxicity, neuroplasticity, hypothalamic-pituitary-adrenal axis imbalances, and neurotransmitter levels (Nebrisi, 2021).

The effectiveness of the curcumin formulation was evaluated using assessments of grip strength, locomotor activity, and brain chemistry (Yallapu et al., 2015). Improvements in outcomes following brain injury have been reported to be potentially mediated by curcumin through the regulation of Th17 cell development. Twenty-four hours after the onset of stroke, T cells, which play a detrimental role in the ischemic response, were observed to infiltrate the region of ischemic damage. The endogenous apoptosis pathway was shown to be directly influenced by the p53 signaling pathway through interactions with multi-domain members of the Bcl-2 family (Du et al., 2023)(Marques et al., 2020).

In a study, therapeutic potential in cerebral stroke was demonstrated by the epigenetic agent curcumin, which was delivered via 200 nm-sized exosomes. Behavioral, oxidative stress, and physiological parameters were effectively reduced by curcumin, indicating its protective effects against cerebral ischemic insult (Yallapu et al., 2015). Although curcumin has shown promise in animal stroke models, the mechanisms by which it influences microglial polarization and promotes long-term stroke recovery remain unclear. It was observed that, three days after dMCAO, cerebral ischemic damage was markedly reduced following curcumin post-treatment (Liu et al., 2017).

Lysosomes represent a significant class of membrane-bound organelles within the intracellular membrane system. They are involved in immunological modulation, cellular metabolism, and programmed cell death, among other biological processes that influence tumor development and progression. Lysosomal activity has been shown to be modulated by curcumin, thereby affecting drug resistance, immune function, invasion, metastasis, and tumor proliferation (Zeng et al., 2020). Tumor growth can be effectively inhibited by curcumin. The transcription of ribosomal DNA (rDNA) into ribosomal RNA (rRNA), which promotes cell growth and proliferation, is regulated upstream by mTORC1. Curcumin has been demonstrated to inactivate mTORC1 through the suppression of mTOR lysosomal localization(Xu et al., 2020).

The encapsulation of curcumin in Eudragit S100 polymer nanoparticles has been shown to influence cellular uptake and to enhance anti-cancer potential two-fold in the HT-29 human colorectal cell line. Innovative formulations have enabled a multi-theranostic strategy, incorporating both therapeutic and imaging functions (Yallapu et al., 2015). Furthermore, chemo-resistance in tumor cells has been demonstrated to be re-sensitized by curcuminoids through the downregulation of Bcl-2 and DNA repair enzymes (Lin et al., 2020). Additionally, further efforts should be devoted to the development of multimodal anticancer therapy strategies in future research by combining standard chemotherapy regimens with curcumin derivatives, analogs, and nano-formulations (Mohamadian et al., 2022).

The synthesis, characterization, and application of curcumin-capped magnetic nanoparticles have been investigated. It has been demonstrated that the interaction between curcumin and magnetic nanoparticles, which occurs through the carbonyl groups of the polyphenol structure, alters the structural, photochemical, and magnetic properties of the polyphenols using various analytical methods. This novel material has been shown to possess the potential to photo-inactivate Gram-positive bacteria, including Staphylococcus aureus (Cañon-Ibarra et al., 2023).

Compared to Escherichia coli and Bacillus cereus, a greater antibacterial activity in vitro has been exhibited by curcumin nanoparticles (curcumin-NPs) against Staphylococcus aureus. Pathogens in chicken fingers were successfully suppressed by curcumin-NPs during storage for up to 27 days. After storage, reductions in total volatile basic nitrogen (TVB-N) levels were observed in chicken samples treated with curcumin-NPs. The bioactive properties, antioxidant capacity, antibacterial activity, and chemical indicators of these experiments validated the efficacy of nano-curcumin at a dose of 10 μg/g (Morsy et al., 2023). Overall, nanotechnology has been shown to enhance material efficacy and address issues associated with the use of natural additives in the meat industry, which could otherwise alter the sensory qualities of meat products. Consequently, improvements in the microbiological quality of poultry meat, including extended shelf life and reduced lipid oxidation, have been demonstrated by curcumin-NPs (Morsy et al., 2023). Although the signaling pathways utilized by curcumin nanoformulations to treat human diseases are well characterized, appropriate human dosage evaluations remain unavailable and should be prioritized. The therapeutic efficacy of curcumin-containing nanocomposites has been shown to surpass that of nanocurcumin or free curcumin (Chopra et al., 2021). Numerous conceptual preclinical studies have been published; however, these findings should be verified through higher-level animal studies or clinical trials.