This method is a top-down technique to produce nanoparticles by exposing metallic wire to a high density current pulse in a liquid, air or gaseous media (Kotov 2003; Cho et al. 2007; Lázár et al. 2018). In this method, AuNPs are formed by exposing 0.1 mm of gold wire to 3 kV voltage in distilled water (Sul et al. 2010). In the initial phase, the wire is melted and disintegrated into either small droplets or even evaporated atoms within a few microseconds (Lázár et al. 2018). Subsequently, a highly dispersed suspension of AuNPs is formed. Several advantages have been noted for electrical explosion wire in a liquid media as compared to the air or gas media: (1) a non-oxide metal powder can be generated without resorting to the vacuum process, (2) it is feasible to retain the non-oxide phase in the concluding stages of applications, and (3) high dispersibility of the nanopowder in dispersive liquids (Cho et al. 2007). The AuNPs obtained from this method were reported to exhibit a remarkable antioxidant activity by reducing the generation of ROS in response to Receptor Activator of Nuclear Factor-B Ligand (RANKL) and upregulated RANKL-induced glutathione peroxidase-1 (Gpx-1) in the bone marrow-derived macrophages (BMM) of mice (Sul et al. 2010).

The antioxidant AuNPs can be synthesized through a combination of electrochemical and chemical techniques. In the first phase, electrochemical process is conducted in a three-compartment cell at room temperature and the process is controlled by a potentiostat. The cell is consisted of a bulk of Au substrates as the working electrode, a platinum sheet as the counter electrode and a KCL-saturated silver-silver chloride (Ag/AgCl) rod as the reference electrode. The electrolyte solution used is a deoxygenated aqueous solution containing salt and natural chitosan (Yu et al. 2011).

Following the initial phase, the cyclic voltammetry method is applied to the electrochemical cell with a specific voltage and deposition cycle. After this electrochemical process, complexes of AuCl₄- are present in the electrolyte solution. The subsequent phase involves a chemical technique to obtain pure AuNPs by boiling the solution. During this stage, the AuNPs are formed. After cooling, the solution containing these AuNPs is purified by placing it in an ultrasonic bath and then centrifuging it for a certain period of time. In this method, chitosan plays a crucial role in obtaining zerovalent AuNPs. In a study that employed this method, the resulting AuNPs with a size of 10 nm was found to exhibit a comparable antioxidant activity to vitamin C (Yu et al. 2011).

The chemical method consists of reduction process and stabilization (Herizchi et al. 2016). Examples of reducing agents are citric and oxalic acid, borohydrides, polyols, sulfites, and hydrogen peroxide. Reducing agents provide electrons to reduce gold ions (Au³⁺ and Au⁺) to the electric state of nanoparticles (Au⁰). Meanwhile, stabilizing agents work by introducing a repulsive force to control the rate, final size or geometric shape of nanoparticles, thereby preventing their aggregation. Several chemical substances, including sulfur ligands (especially thiolates), phosphorus ligands, trisodium citrate dihydrate, polymers, surfactants, and other agents, are employed as stabilizing agents. Moreover, the stabilizing agents can be the same substance as the reducing agents (Daruich De Souza et al. 2019; Jamkhande et al. 2019).

Limited studies evaluated antioxidant activity of chemically synthesized AuNPs using both electrochemically reduction and chemical reduction methods. In the electrochemical reduction method, AuNPs as antioxidant agent were successfully synthesized by varying the deposition potential (Suliasih et al. 2024) and scan rate (Suliasih et al. 2023). This technique is recognized for its facile and cost-effective nature in metallic nanoparticles preparation (Budi et al. 2010, 2016, 2020), making it a promising approach for future fabrication of AuNPs. Regarding the chemical reduction method, to our best knowledge, only Turkevich method has been used in synthesizing AuNPs for the purpose of obtaining antioxidant activity. This method was first developed by Turkevich in 1951 and since then, it has been modified by several other researchers (Kimling et al. 2006; Pong et al. 2007; Ojea-Jiménez et al. 2011; Herizchi et al. 2016). The method involves the reaction between hydrogen tetrachloroaurate (HAuCl₄) and citrate in boiling water. Citrate acts as an agent for reducing gold ions into AuNPs and stabilizing the resultant nanoparticles from further particle growth, preventing the formation of large particle aggregates (Yeh et al. 2012). This agent can also be replaced with ascorbic acid and tannic acid (Hussain et al. 2020). Strictly controllable process parameters such as concentration, pH and temperature have been noted as one of its drawbacks (Hussain et al. 2020). Recently, this method has been demonstrated to successfully produce AuNPs with the particle size of 2.7 nm and exhibited a high antioxidant activity of approximately 73% inhibition as determined by the DPPH method (Beurton et al. 2019). In a different study, the production of AuNPs with the size of 10.3 nm and 31.3 nm AuNPs exhibited notable antioxidant properties as evaluated by the DPPH method. The IC₅₀ values for these nanoparticles were found to be 6.201 × 10^–9 and 2.217 × 10^–10 mol/L, respectively (Li et al. 2023b).

Biological methods have been widely applied for synthesizing AuNPs for their antioxidant activity. This method, also known as biosynthetic or green synthesis method, involves the use of biological agents, ranging from plant extracts, bacteria, fungi, and algae. This approach has gained significant attention due to its benefits, including high biocompatibility for medical purposes, environmentally friendly characteristics, use of non-toxic solvents, pollution-free operation, and absence of toxic and hazardous substances (Nasrollahzadeh et al. 2015; Katas et al. 2018; Kalimuthu et al. 2020; Ying et al. 2022). However, the biological method faces limitations related to the availability of biological materials, lengthy synthesis time, challenges in controlling the growth of living organisms, and high variability in particle size. These factors collectively pose obstacles for large-scale production (Jamkhande et al. 2019; Ying et al. 2022). In general, this method involves two key techniques (Fig. 3):

Bioreduction: This process aims to reduce metal ions into a biologically stable form using reducing agents found in microorganisms or plant extracts such as amino acids, flavonoids, aldehydes, sugars, amines, ketones, phenols, carboxylic acids, proteins, pigments, alkaloids, terpenoids and other reducing agents (Kanchi and Ahmed 2018). The obtained nanoparticles can be harvested from the contaminated sample to produce stable and inert nanoparticles.

Biosorption: This technique involves the binding of metal cations to the cell wall of certain bacteria, fungi and plants in aqueous media prior to the reduction of metal ion in the presence of enzymes (Kanchi and Ahmed 2018). However, several pieces of evidence have shown that this biosorption technique is mainly applied for biological synthesis using bacteria and fungi (Pantidos 2014; Jamkhande et al. 2019; Qamar and Ahmad 2021).

Plant extracts

Generally, several processes are involved in preparing plants prior to AuNPs synthesis. These include the procurement of various parts of plants, cleaning to remove contaminants, drying, pulverizing to acquire fine powder, aqueous extraction, filtering to remove large particles and obtain fine grained particles and synthesis (Fig. 4). One of the protocols that is commonly used is one-pot hydrothermal chemical reduction method. This method is commonly applied in preparing plant-AuNPs as antioxidants. This involves mixing a plant extract and metal salt (HAuCl₄) to form plant-AuNPs with different morphologies. This process typically takes from a few minutes to several hours. Variation in certain reaction conditions can be applied, including changes in pH and temperature, as well as adjustments to the amount of HAuCl₄ and plant extracts (Chen et al. 2019; Qiao and Qi 2021).

Plant extracts serve as both reducing and stabilizing agents in the fabrication of metal nanoparticles. Common phytochemicals in the plant extracts with these roles include polysaccharides, polyphenols, alkaloids, flavonoids, reducing sugars, phenols, amino acids, vitamins, ketones, and proteins. In this reaction, the phytochemicals in the plant extracts will reduce Au³⁺ to Au⁰ and then mediate and stabilize the resulting AuNPs by covering the outer surface of the AuNPs to prevent agglomeration (Qiao and Qi 2021).

Moreover, pH of the plant extract solution significantly influences the yield of AuNPs synthesis. Evidence has shown that a higher pH induces easier reduction of Au³⁺, resulting in a higher yield of AuNPs (Oueslati et al. 2020). The nature and ratio of the phytochemical fractions play an important role for the formation of nanoparticles, in addition to the pH of reaction medium. Furthermore, the type of plant extract may influence the shape of the obtained AuNPs. For example, the use of hydrosoluble crude extracts produced nanoflower shaped particles, whereas the concentrate of flavonoid produced smaller monodispersed spherical nanoparticles (Ben Haddada et al. 2020; Kalimuthu et al. 2020).

The reduction of gold ions requires high temperatures. Previous studies have indicated that the optimal reduction of gold ions occurs at the temperature range of 80–90 °C. Higher temperatures have been shown to significantly decrease nanoparticle size, whereas lower temperatures result in larger particles (Mohammed Fayaz et al. 2009; Wang et al. 2016). The concentration of gold ions may also influence the characteristics of AuNPs, with a higher concentration of gold ions capable of increasing both particle size and distribution (Wu and Chen 2010).

Table 1 presents a list of antioxidant activity of AuNPs synthesized using plant extracts as the reducing and stabilizing agents, employing one-pot hydrothermal chemical reduction method. The majority of AuNPs were spherical in shape, with particle sizes ranging from 2 to 64 nm. The antioxidant activities are commonly expressed as IC₅₀, a value indicating the concentration of antioxidant required to effectively scavenge 50% of the initial DPPH radicals (Olugbami et al. 2014; Francis et al. 2018).

The obtained IC₅₀ values for antioxidant activity ranged from 1,96 – 725,93 μg/mL. The antioxidant activity of AuNPs is reported to be higher than that of the plant extract alone because the antioxidant compounds from plant extracts are adsorbed onto the active surface of nanoparticles (Reddy et al. 2015; Godipurge et al. 2016; Vinosha et al. 2019; Sunayana et al. 2020; Liu et al. 2021b; Mobaraki et al. 2021; Muniyappan et al. 2021). The surface reaction and the high surface area-to-volume ratio of a nanoparticle may also influence the interaction and scavenging activity of free radicals, resulting in a higher antioxidant activity (Kumar et al. 2021). Contrarily, some studies showed the opposite effect, as the antioxidant activity of the plant extract alone was higher than that of AuNPs. This phenomenon was expected to be due to the reduction of bioactive phytochemical concentration, such as alkaloids, flavonoids and phenolic compounds present in the extract during nanoparticle formation, thus decreasing the free radical scavenging activity of the nanoparticles (Kuppusamy et al. 2015; Nakkala et al. 2016; Chahardoli et al. 2018; Abdoli et al. 2021).

Bacteria

In this method, the synthesis of nanoparticles involves extracellular biologically active substances of bacteria (Manivasagan et al. 2015). The excellent properties of bacteria, such as being easy to cultivate, manipulate and facilitate rapid multiplication, are also useful for the synthesis of AuNPs (Jamkhande et al. 2019). However, only a small number of bacteria can be used for selectively reducing metal ions (Kalimuthu et al. 2020). Enterococcus species have been demonstrated to produce AuNPs with spherical-shaped particles with the particle size range of 8–50 nm. The AuNPs also exhibited a significant antioxidant activity (33.24–51.47% inhibition at concentration of 1–40 μg/ml) (Oladipo et al. 2017). A similar result was reported by Markus et.al., who synthesized AuNPs with Lactobacillus kimchicus (Markus et al. 2016).

Furthermore, AuNPs demonstrated greater antioxidant activity when compared to ascorbic acid, particularly the highest level of activity was observed in AuNPs characterized by spherical particles with an average size of 11.57 ± 124 nm, which were synthesized using Nocardia sp. (Manivasagan et al. 2015). Nocardia sp. GTS18 has also been used to synthesize AuNPs with a particle size of 40–45 nm and DPPH radical scavenging activity ranging from 26.81 ± 6.3% to 60.90 ± 2.9% at the concentration ranging from 100 to 2000 μg/mL (Könen-Adigüzel et al. 2018). Similar to plant extracts, the antioxidant activity of AuNPs is expected to be enhanced with the increasing particle surface area that facilitates the catalytic reaction involving protein molecules from bacteria (Oladipo et al. 2017).

Fungi

Fungi have been used for AuNPs synthesis, as the fungal mycelial mesh can withstand higher flow pressure and agitation in bioreactors or other chambers compared to other microbial systems (Kalimuthu et al. 2020). Due to their extensive secretory components, fungi can produce nanoparticles extracellularly and support the reduction and capping of nanoparticles (Gericke and Pinches 2006). Moreover, biosynthesis with fungi is more effective than the one with bacteria due to the advantages, including the presence of mycelia, which provides an increased surface area. Furthermore, the fact is that fungi secrete significantly higher amounts of proteins compared to bacteria, thereby it enhances the synthesis productivity (Pantidos 2014).

AuNPs produced from this method exhibited a comparable antioxidant activity to the strong antioxidant, ascorbic acid. Elegbede et al. reported that the antioxidant activity of AuNPs, fabricated using Aspergillus niger and Trichoderma longibrachiatum, displayed the inhibition rates ranging from 42.91% to 53.79% at concentrations of 10–100 µg/ml. This result was compared to the antioxidant activity of ascorbic acid, which ranged from 39.03% to 64.42% at concentrations of 2–10 µg/ml. The observed antioxidant activity of AuNPs could be attributed to the functional groups of bioreductant molecules attached to the nanoparticle surfaces (Elegbede et al. 2020). In a different study, the antioxidant activity of AuNPs synthesized by the marine endophytic fungus (Penicillium citrinum) was also found to be comparable to that of the standard ascorbic acid (Manjunath et al. 2017).

Algae

AuNPs can be also synthesized using algae. Marine algae could produce highly stable AuNPs extracellularly in a relatively shorter time compared to other biological methods (Kalimuthu et al. 2020). This method has successfully produced AuNPs with considerably higher antioxidant activity than the algae extract alone. The AuNPs were mostly in triangular and spherical nanostructures, with an average particle size of 16 nm, and they were well dispersed without any presence of agglomeration (Vinosha et al. 2019). In a different study, biosynthesized AuNPs were produced using an edible freshwater epilithic red algae, Lemanea fluviatilis (L.). The AuNPs exhibited polydispersity, with nearly spherical particles ranging in size from 5 to 15 nm. Nevertheless, these AuNPs remarkably demonstrated strong antioxidant activity, with an SC50 (the sample weight required to scavenge 50% of DPPH) measured at 18.10 mg (Sharma et al. 2014). In summary, algae and its compounds exhibit robust antioxidant properties. When combined with AuNPs and other antioxidants from diverse sources, such as plant extracts, a potent synergistic antioxidant effect is anticipated.

This method applies the same underlying principle as the DPPH assay, but it focuses on distinct radical species and is commonly referred to as the Trolox Equivalent Antioxidant Capacity (TEAC) assay. In this assay, the effectiveness of antioxidants in neutralizing the stable radical cation ABTS is assessed. The ABTS radical is subsequently transformed into a colorless product. The extent of this transformation is quantified by measuring the discoloration of a blue-green chromophore at a wavelength of 734 nm (Shahidi and Zhong 2015). The TEAC value is determined by comparing the degree of discoloration caused by a compound to that induced by Trolox (Arts et al. 2004). When employing the ABTS assay for gold nanoparticles (AuNPs), the measurement relies on the AuNPs’ capacity to donate electrons, thereby neutralizing the ABTS radical species. The green-synthesized AuNPs with a peel extract of sweet lime fruit (Citrus limetta Risso) showed a remarkable antioxidant activity, as evaluated by the ABTS method, revealing an IC₅₀ of 54.39 µg/ml (Sivakavinesan et al. 2022). Moreover, an IC₅₀ of 44.81 µg/ml was obtained from mycosynthesized AuNPs produced using Aspergillus terreus (BalaKumaran et al. 2022).

This method belongs to the same group of radical scavenging assays as the two previously mentioned. The antioxidant’s scavenging activity is assessed by measuring the reduction in absorption of H₂O₂ molecules at a wavelength of 230 nm (Gulcin 2020). This method is effective for measuring the antioxidant capacity of AuNPs, owing to their intrinsic catalase-like activity, which involves donating electrons to H₂O₂ molecules, leading to the decomposition of H₂O₂ and the production of oxygen (He et al. 2013; Sivakavinesan et al. 2022). AuNPs fabricated through the green synthesis of fungal xylanases from Aspergillus niger and Trichoderma longibrachiatum exhibited inhibition percentages ranging from 74% to 96% at concentrations of 1–40 µg/ml. Furthermore, other biosynthesized AuNPs by the peel extract of sweet lime (Citrus limetta Risso) also demonstrated an excellent antioxidant activity, with a 50% H₂O₂ scavenging activity observed at a concentration of 56.58 µg/ml (Elegbede et al. 2020; Sivakavinesan et al. 2022).

In this method, the antioxidant activity was assessed by measuring the antioxidant ability to prevent the production of NO· through the nitration of 4,5-diaminofluorescein. The scavenging values are calculated as the percentage inhibition of the oxidation of 4,5-diaminofluorescein, which is directly proportional to the concentration of the NO· scavenging compound (Gulcin 2020). Biosynthesized AuNPs using Vitex negundo leaf extract have been discovered as potent scavengers of nitric oxide, exhibiting an inhibition value of 83% at a concentration of 100 µg/ml. This phenomenon demonstrates the ability of AuNPs to donate electrons to NO·, supported by a dehydrated environment (Sunayana et al. 2020). Meanwhile, another researcher emphasized the influence of phenolic groups, such as flavonoids and flavanols, present in the Vitex negundo leaf extract used to synthesize the AuNPs. This study revealed an IC₅₀ value of 70.45 µg/ml for the AuNPs (Veena et al. 2019).

The antioxidant effect of AuNPs on the early stage of collagen-induced arthritis has been studied in rats. In this study, the antioxidant action of intraarticularly injected 13 nm or 50 nm AuNPs significantly increased the cellular catalase activity without causing negative effects on hematological indices. These AuNPs reduced the production of malondialdehyde (MDA). This MDA is the end product of polyunsaturated fatty acid peroxidation in cells, and its level serves as a standard indicator of oxidative stress (Mehanna et al. 2022). In addition, these AuNPs also significantly up-regulated the activity of CAT, the primary antioxidant responsible for the direct elimination of ROS (Kirdaite et al. 2019). The antioxidant effects of AuNPs have also shown great impact on diabetes and wound healing on male albino rats that were induced with a single intraperitoneal injection of streptozotocin (Ponnanikajamideen et al. 2019).

Toxicological evaluation was also carried out for different sizes of AuNPs (10 and 50 nm) for the exposure duration of 3 days (Abdelhalim and Moussa 2013). AuNPs were intraperitoneally administered in rats for evaluating their effects on the liver and kidneys by monitoring several biochemical parameters including aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alanine transaminase (ALT), alkaline phosphatase (ALP), urea (UREA) and creatinine (CREA). Based on the results obtained, AuNPs altered the liver enzymes to a certain extent, suggesting the need for liver protection during the treatment with AuNPs. In contrast, UREA and CREA showed no significant alterations, indicating no toxicity effects were detected for the kidneys. In a more recent study, biodistribution of different sizes AuNPs (10, 30 and 60 nm) were investigated in Wistar rats and the organ distribution (liver, spleen, kidneys and intestine) was dependent on the particle size (Lopez-Chaves et al. 2018). Higher toxicity effects were observed for the smallest particles due to the high accumulation that led to the overproduction of free radicals and ROS from protein carbonylation, lipid peroxidation and DNA damages.

The antioxidant effect of AuNPs in restraining hyperglycemic conditions has been explored in diabetic mice models. This finding showed the significant inhibitory effect of AuNPs against ROS generation during hyperglycemia induced oxidative stress. In addition, the diabetic mice treated with AuNPs showed a significant decrease in lipid peroxidation compared with diabetic control group mice, indicating an additional benefit of using AuNPs in treating hyperglycemia (BarathManiKanth et al. 2010). Studies have shown that lipid peroxidation can lead to the production of reactive lipid species, which in turn may cause damage to cellular structures. (Zamboni 2008). Another study reported a significant anti-inflammatory and antioxidative effects of AuNPs in mice suffering from asthma. In the study, researchers found evidence that AuNPs could reduce catalase activity and malondialdehyde (MDA) levels in the lung tissues. This reduction in catalase activity and MDA levels is associated with the occurrence of oxidative tissue injury in mice. The study highlights the potential impact of AuNPs on lung health and oxidative stress. (Serra et al. 2022). Moreover, Ok Joo-Sul, et.al found that AuNPs could inhibit Receptor Activator of Nuclear Factor-kB Ligand (RANKL) induced osteoclast (OC) formation in vitro by decreasing ROS production and upregulating the antioxidant enzyme Gpx-1 in mice. RANKL is a key differentiation factor for OC, and has been reported to induce the production of ROS via the RANK-TRAF6 signal pathway (Sul et al. 2010).

For toxicological evaluation in mice, AuNPs (12.5 nm) were considered as a non-toxic agent after repeated administration intraperitoneally for 8 days at 40, 200, and 400 μg/kg/day (Lasagna-Reeves et al. 2010). Despite AuNPs were accumulated the most in the liver followed by kidneys and spleen, no significant organ abnormalities were detected. More recently, the subchronic toxicity study revealed the non-toxicity of AuNPs (53 nm) at 0.2, 2, and 20 mg/kg after repeated dose of oral administration to mice for 90 days. Other than minor infiltration in the kidneys and altered platelet indices at the highest dose in the male and female mice respectively, no obvious abnormalities, mortality and adverse effects were seen (Sun et al. 2021). When coating with other polymers such as polyethyleneimine (PEI) and polyethylene glycol (PEG), the level of distribution was significantly enhanced, with the highest accumulation observed in the liver and spleen after a single dose was administered to the mice (5 mg/kg) (Ozcicek et al. 2021). Middle levels of accumulation of these nanoparticles (50 nm) were seen in the blood tissues, kidneys and heart while the least were seen in the brain.

Gold nanorods (AuNRs), sized at 50 nm, exhibited remarkable antioxidant activity in male rabbits after intravenous repeated-dose treatment over a 15-day period. This was evidenced by the elevated levels of SOD, GPx and CAT, coupled with a reduction in MDA levels. Therefore, it is concluded that these AuNRs could effectively inhibit the elevated ROS generation and lipid peroxidation (Mehanna et al. 2022). The remarkable antioxidant effect of AuNPs on dry eye disease in a rabbit model has been also reported (Li et al. 2019). In a different study involving New Zealand White rabbits, the acute toxicity and biodistribution of AuNPs were investigated. These rabbits, with implanted liver Vx2 tumours, received intravenous injections of 5 nm and 25 nm AuNPs. The results showed no evidence of renal, hepatic, pulmonary, or other organ dysfunction. On the other hand, after administration of 25 nm AuNP, white blood cell concentration was observed to be increased, while most other blood parameters remained unchanged. AuNPs also accumulated in the spleen, liver, and Vx2 tumours, but not in other tissues. In summary, smaller AuNPs were more evenly distributed throughout tissues, suggesting their potential as effective tools for medical therapy (Glazer et al. 2011).

AuNPs have been proposed as regulators of lipoprotein levels. They can facilitate the replication of high-density lipoprotein (HDL) and synthesize HDL-like molecules. These applications hold potential for both diagnosis and treatment of atherosclerosis (Younis et al. 2021). AuNPs also demonstrated a remarkable ability to restore the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in RAW264.7 cells treated with high glucose. Furthermore, they effectively inhibited radical production in macrophage cells exposed to high glucose. This capacity holds significant promise in minimizing atherosclerosis and managing diabetic disease (Rizwan et al. 2017).

Immune cells become activated during inflammation, leading to continuous production and release of free radicals, resulting in oxidative stress. AuNPs, acting as enzymatic antioxidants, effectively inhibit the generation of free radicals in phagocytes (Agarwal et al. 2019; Li et al. 2023a). Research has shown that AuNPs-embedded ceria nanoparticles (Au/CeO2) successfully treat inflammatory bowel disease in mice due to their enzymatic catalytic antioxidant properties (Li et al. 2023a). Additionally, AuNPs synthesized from Suaeda japonica leaf extract exhibit excellent effectiveness in reducing proinflammatory cytokines and inflammatory mediator production (Kwak et al. 2022). Moreover, the antioxidant effect of AuNPs makes them valuable for diseases related to inflammation, such as rheumatoid arthritis (Hornos Carneiro and Barbosa 2016; Jaaffer and Al-Ogaidi 2022). In animal and human models, AuNPs also significantly suppress inflammation in the early stages of erosive immune-mediated polyarthritis (Kirdaite et al. 2019).

In neurodegenerative diseases, it has been observed that AuNPs have the capacity to inhibit the pro-inflammatory reactions in a cell line of microglia. This property of AuNPs is advantageous in promoting the repair and regeneration of the central nervous system (Mikhailova 2021). Another study observed the advantageous effects of AuNPs in the treatment of Alzheimer’s disease (AD), one of the neurodegenerative diseases. In this case, AuNPs have the ability to regulate antioxidant levels in the brain, facilitate mitochondrial repair, and enhance the removal of ROS within the mitochondria. This mechanism ultimately leads to a reduction in oxidative stress in the brains of patients with Alzheimer’s disease (Aili et al. 2023).

AuNPs have been found to play a role in reducing bone loss by inhibiting osteoclast formation. Osteoclasts are specialized cells responsible for breaking down bone tissue, which is crucial for normal bone remodelling. However, in pathological conditions, these cells can contribute to bone loss due to their heightened resorptive activity (Boyce et al. 2009). Recent evidence suggests that AuNPs achieve this effect by interfering with the production of RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand). RANKL is a key player in osteoclast differentiation and has been linked to increased production of ROS. By reducing ROS production and enhancing the expression of the antioxidant enzyme Gpx-1, AuNPs may offer protection against bone loss associated with post-menopause (Sul et al. 2010).

The potential application of AuNPs (Fig. 7) in preventing oxidative stress and their adverse effects, induced at hyperglycemic conditions has opened up ways for a new resource of cost economic alternative in the treatment of diabetic progression (BarathManiKanth et al. 2010). Diabetes mellitus disease is characterized by inadequate insulin secretion and variable levels of insulin resistance, leading to elevated blood glucose concentrations. This high glucose levels have been observed to induce the production of ROS, which are implicated in the development of metabolic dysregulation and chronic complications. AuNPs as antioxidant agent has been proven to have capability to scavenge ROS and inhibit ROS production by increasing antioxidant defence enzyme in streptozotocin induced diabetic mice (BarathManiKanth et al. 2010). Evidence of the ability of AuNPs bioconjugated with aminoguanidine to inhibit glycation reactions in diabetic rats has also been reported (Ahmad et al. 2021). Several studies have also reported the remarkable activity of AuNPs in diabetic animal models, particularly in relation to their antioxidant activity (Ponnanikajamideen et al. 2019; Nor Azlan et al. 2020a; Sekar et al. 2022). Moreover, AuNPs possess significant anti-oxidative properties on several chronic pathological conditions, including cancers (Mobaraki et al. 2021; Jiang et al. 2023), sepsis (Di Bella et al. 2021), heart disease (Chouke et al. 2022) and asthma (Al-Radadi 2023).