Carnosine is a dipeptide composed of β‑alanine and L‑histidine, linked by peptide bonds, and is widely distributed in muscle tissue, the central nervous system (including the brain) and various other organs. As an endogenous bioactive molecule, carnosine plays a crucial role in cellular metabolism and physiological regulation. In recent years, advancements in molecular biology, biochemistry and pharmacology have gradually unveiled the multiple biological functions of carnosine, leading to increased interest in its potential applications for disease therapy. Carnosine exhibits considerable antioxidant and anti‑glycation properties, while also demonstrating unique pharmacological effects related to neuroprotection, anti‑inflammatory responses and immune regulation. These attributes position carnosine as a significant intervention with therapeutic value across various pathophysiological processes associated with different diseases. This review systematically summarizes recent progress on the application of carnosine in disease therapy, focusing on its mechanisms of action and therapeutic roles in neurodegenerative diseases, metabolic disorders, cardiovascular diseases, several types of cancer and ophthalmic conditions. By reviewing existing studies on this topic, this review aims to further explore the diversity of carnosine's roles along with potential mechanisms involved in disease treatment. Ultimately, it aims to provide a theoretical foundation and direction for future research.
Since its discovery in the early 20th-century, the biological function of carnosine has increasingly garnered interest. One of the most significant functions of carnosine is its antioxidant effect. Oxidative stress serves as a common pathological basis for numerous diseases. By scavenging free radicals, chelating metal ions and enhancing endogenous defenses, carnosine reduces oxidative stress. It further inhibits lipid peroxidation, protein oxidation and DNA damage, thereby preserving cellular integrity. Furthermore, the anti-glycation properties of carnosine offer novel insights into the prevention and treatment of diabetes mellitus and its complications by inhibiting the formation of advanced glycation end products (AGEs). The accumulation of AGE is closely associated with diabetes, cardiovascular disease and aging; carnosine competes with sugars to bind proteins to reduce AGEs formation by inhibiting glycosylation processes. In terms of neuroprotection, carnosine demonstrates potential therapeutic value for neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). AD is characterized by β-amyloid protein (Aβ) deposition along with neuronal loss. Studies have shown that carnosine can inhibit Aβ aggregation and toxicity while reducing oxidative damage and inflammation in neurons, thus delaying AD progression. PD is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Evidence indicates that carnosine may protect these neurons from damage induced by oxidative stress and inflammatory responses; consequently, it has the potential to delay the progression of PD. Carnosine exerts anti-inflammatory and immunomodulatory effects by suppressing pro-inflammatory mediators and regulating immune cell activity, supporting its potential in chronic inflammatory and autoimmune diseases. Research demonstrates that carnosine can inhibit the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), among other inflammatory mediators, thereby reducing inflammation. Furthermore, carnosine also plays a role in regulating immune cell functions such as those of macrophages and T cells, enhancing the body's overall anti-inflammatory capacity.
In the treatment of cancer, the role of carnosine is also gradually revealed. Carnosine may delay cancer progression by reducing oxidative stress and inflammation in tumor cells, while also inhibiting proliferation and migration, and inducing apoptosis. In addition, carnosine protects normal cells from damage caused by oxidative stress and inflammatory responses, thereby reducing side effects in cancer treatment.
Although carnosine has shown a wide range of potential applications in disease therapy, it still faces several challenges for clinical use. First, carnosine has low bioavailability in vivo and is readily degraded by enzymes, which affects its efficacy. Studies have explored various strategies to address this. Nanotechnology-based delivery systems, such as liposomes and polymeric nanoparticles, have been developed to protect carnosine from rapid hydrolysis by carnosinase and to facilitate targeted delivery to specific tissues. For instance, liposomal encapsulation has been shown to enhance the stability of carnosine. In addition, derivatization and conjugation strategies (such as cyclodextrins and trehalose) have been employed to enhance the stability of carnosine against carnosinase-mediated degradation as well as its pharmacological activity. Secondly, the efficacy of carnosine is dose-dependent, and high doses may result in certain side effects. In addition, the current clinical research data on carnosine remain insufficient and there is a lack of large-scale clinical trials on this drug. Therefore, it is necessary to improve the bioavailability and stability of carnosine through chemical modification or nanotechnology and develop novel carnosine-based drugs. Similarly, when combined with precision medicine, a personalized carnosine treatment program may be feasible to improve efficacy and reduce side effects. In addition, conducting large-scale clinical trials to verify the safety and effectiveness of carnosine in disease treatment is also an important direction for future research. By systematically reviewing the multiple biological functions of carnosine and its application in the treatment of diseases, this review aims to provide comprehensive theoretical support and practical guidance for researchers in related fields and promote the wider application of carnosine in the medical field.
Carnosine is a powerful antioxidant capable of scavenging free radicals [such as reactive oxygen species] through a variety of mechanisms to protect cells from oxidative stress. Oxidative stress is a common pathological basis for a variety of diseases such as neurodegenerative diseases, cardiovascular diseases and cancer, and the antioxidant effects of carnosine provide a scientific basis for its application in these diseases. Studies have shown that carnosine can inhibit lipid peroxidation, protein oxidation and DNA damage, thereby protecting the structural and functional integrity of cells. The antioxidant effect of carnosine is primarily achieved through several mechanisms: i) Direct removal of free radicals: Carnosine can react directly with free radicals to neutralize their activity, thereby reducing the damage of free radicals to cells. Free radicals are the primary mediators of oxidative stress, capable of attacking cell membranes, proteins and DNA, leading to the destruction of cell structure and function. Carnosine, through its histidine residues in its molecular structure, can effectively trap and neutralize free radicals, thereby protecting cells from oxidative damage. ii) Chelating metal ions: Carnosine can bind to metal ions (such as copper and iron) and inhibit the oxidation reaction catalyzed by metal ions. Metal ions play an important role in oxidative stress, which can catalyze the formation of free radicals and the oxidation reaction. Carnosine can form stable complexes with metal ions through carboxyl and amino groups in its molecular structure, thus inhibiting the oxidation reaction catalyzed by metal ions and reducing the generation of free radicals. iii) Enhancing the endogenous antioxidant system: Carnosine can enhance the levels of endogenous antioxidants such as glutathione (GSH) in the cell, thereby improving the antioxidant capacity of the cell. GSH is one of the most important antioxidants in the cell, which can directly remove free radicals and participate in the regulation of redox reactions. Carnosine enhances the function of the intracellular antioxidant system by promoting the synthesis and regeneration of GSH, thereby improving the resistance of cells to oxidative stress.
In addition, carnosine can further enhance the antioxidant capacity of cells by regulating the activity of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase (GPx). These antioxidant enzymes can catalyze the breakdown and removal of free radicals, thereby protecting cells from oxidative damage. By regulating the activity of these enzymes, carnosine can effectively reduce the damage to cells caused by oxidative stress.
Carnosine has been shown to play a significant role in the field of anti-glycation, effectively inhibiting the non-enzymatic reaction of proteins and sugars (glycation reaction), thereby reducing the formation of AGEs. Glycosylation is a non-enzymatic reaction between proteins, lipids or nucleic acids and reducing sugars, and the accumulation of AGEs in the body is closely associated with a variety of diseases, such as diabetes, cardiovascular disease and age-related diseases. The anti-glycation effect of carnosine is of great significance in delaying aging and preventing diabetic complications (such as vasculopathy and neuropathy), and its mechanism primarily includes the following aspects: i) Inhibition of glycosylation: Carnosine can compete with sugars to bind proteins, thereby inhibiting the occurrence of glycosylation. At the heart of the glycosylation reaction is the reduction of sugars (such as glucose) with free amino groups in proteins (such as lysine and arginine residues) to form unstable Schiff bases, which, in turn, rearrange into stable AGEs. Carnosine, through the amino and carboxyl groups in its molecular structure, can compete with sugars to bind the free amino group of proteins, blocking the initial step of the glycosylation reaction, thereby reducing the production of AGEs. ii) Elimination of AGE precursors: Carnosine can eliminate the precursor substances of AGEs, such as α-dicarbonyl compounds (such as methylglyoxal and glyoxal), thereby reducing the formation of AGEs. α-dicarbonyl compounds are important intermediates in glycation reactions, which are highly reactive and
