Carnosine targets multiple pathways and molecules. It acts as an antioxidant by scavenging reactive oxygen species (ROS) and reactive aldehydes produced during lipid peroxidation. It inhibits the formation of advanced glycation end-products (AGEs). It chelates transition metal ions such as copper (Cu²⁺) and zinc (Zn²⁺). Additionally, carnosine inhibits soluble guanylyl cyclase (sGC) by interacting with the heme iron to form a chelate complex.

L-Carnosine is a dipeptide composed of the amino acids beta-alanine and histidine that has the ability to inhibit many of the metabolic changes associated with aging[1]. L-carnosine also has some antioxidant properties. L-Carnosine's antioxidant mechanism is attributed to its ability to chelate metal ions, have superoxide dismutase (SOD)-like activity, and scavenge ROS and free radicals[2].
In vitro, carnosine exhibits potent antioxidant activity, scavenging free radicals and protecting cells and tissues from oxidative damage. It effectively blocks nonenzymatic glycosylation and protein cross-linking induced by reactive aldehydes. Carnosine has also demonstrated anticonvulsant, antitumor, and neuroprotective effects in various in vitro models. It serves as an intracellular pH buffer, helping to maintain acid-base balance within cells.

In vivo, carnosine has shown neuroprotective effects, particularly in animal models of ischemic stroke. It significantly reduces infarct volume and improves functional outcomes in mouse models of focal cerebral ischemia. Carnosine also exhibits anti-aging properties and has been studied for its potential to improve cognitive function and exercise performance. It is actively marketed as a dietary supplement for these purported benefits.

The in vitro antioxidant activity of carnosine can be assessed using cell-free assays. For example, its ability to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) or ABTS radicals can be measured spectrophotometrically. Its metal chelating activity is evaluated using assays such as the ferrozine-Fe²⁺ complex formation inhibition assay. The inhibition of sGC can be studied by measuring the reduction in cGMP production in cell-free systems containing purified sGC enzyme and its substrate GTP.

In vitro cellular assays for carnosine typically involve treating cultured neuronal cells (e.g., SH-SY5Y or PC12 cells) with oxidative stressors like hydrogen peroxide or glutamate in the presence or absence of carnosine. Cell viability is then measured using MTT or LDH release assays to assess its neuroprotective effects. Its anti-glycation activity is evaluated in cell culture by measuring the accumulation of AGEs in proteins after prolonged exposure to high glucose concentrations.

In vivo animal studies for carnosine often use rodent models of disease. For stroke research, the transient or permanent middle cerebral artery occlusion (MCAO) model is commonly used. Carnosine is administered intraperitoneally (IP) or intravenously (IV) either before or after the ischemic insult. Neurological scores, infarct volume, and markers of oxidative stress are then assessed. For aging studies, carnosine is often administered orally via drinking water or diet for extended periods.

Absorption, Distribution and Excretion
Sano et al. investigated the intestinal absorption of L-CAZ in rats using compounds labeled with 14C and 65Zn. They proposed that L-CAZ dissociates into its constituents L-carnosine and zinc during intestinal absorption. This study used compounds labeled with 14C and 65Zn to examine the intestinal absorption of this drug. Paleprozinc is metabolized into its constituents L-carnosine and zinc during intestinal absorption. The study found that after a single administration of 14C-labeled L-CAZ to rats, the excretion rate was 4.1% in urine, 13.3% in feces, and 38.8% in exhalation. The study using 65Zn-labeled Paleprozinc showed an excretion rate of 0.3% in urine and 85.0% in feces. The zinc absorption rate was estimated to be approximately 11%.

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Metabolism/Metabolites
Following a single dose in rats, the excretion rates of pipprecinol zinc were: 4.1% in urine, 13.3% in feces, and 38.8% in exhalation when using 14C-labeled pipprecinol; and 0.3% in urine and 85.0% in feces when using 65Zn-labeled L-CAZ. The zinc absorption rate is estimated to be approximately 11%.

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Biological Half-Life
Studies in rats have shown that the half-life of pipprecinol zinc is approximately 2 hours.
Carnosine's pharmacokinetics in humans are characterized by rapid absorption and elimination. After oral ingestion, peak plasma concentrations occur within the first hour. However, its bioavailability is limited due to rapid hydrolysis by serum carnosinase (CN1) in the bloodstream. Little circulating carnosine is detectable beyond 4 hours post-dose. In mice, the maximum plasma concentration (Cmax) after intraperitoneal injection can be very high (~1082 µg/mL), achieved at 0.25 hours (Tmax). In the brain, concentrations increase at 1 hour but return to baseline by 5 hours.

Protein Binding
It has been observed that a high-protein diet accelerates zinc absorption, meaning that low-molecular-weight amino acids may carry zinc into the circulatory system through complexation.
Carnosine is generally considered safe and well-tolerated at moderate doses. However, at high doses (e.g., 15 g), the frequency of adverse events becomes unacceptably high, with 77% of participants experiencing side effects. Common side effects include headache (43.5%), nausea (21.7%), and paresthesia (21.7%). Due to its rapid hydrolysis by carnosinase, high doses are required to achieve systemic effects, which may contribute to these side effects.

[1]. Would carnosine or a carnivorous diet help suppress aging and associated pathologies? Ann N Y Acad Sci. 2006 May;1067:369-74.

[2]. Carnosine may reduce lung injury caused by radiation therapy. Med Hypotheses. 2006;66(5):957-9.

Carnosine is a dipeptide, an N-(β-alanyl) derivative of L-histidine. It possesses anticonvulsant, antioxidant, antitumor, human metabolic, large flea metabolic, mouse metabolic, neuroprotective, and anti-aging effects. It is the conjugate acid of carnosine and also a tautomer of carnosine zwitterions.
Polyprezin is a chelate of zinc and L-carnosine. It was the first zinc-related drug approved in Japan and has been used clinically to treat gastric ulcers. Studies have shown that polyprezin may be effective in treating pressure ulcers. A 2013 study showed that concurrent administration of polyprezin may be effective in combating small intestinal mucosal damage caused by long-term aspirin use.
Carnosine has been investigated for the treatment of Gulf War syndrome.
Carnosine has been reported to be found in water fleas, soybeans, and several other organisms with relevant data.
Polyprezin is a highly bioavailable oral chelate composed of zinc and L-carnosine, possessing potential gastric protective, antioxidant, anti-ulcer, and anti-inflammatory activities. After administration, pipprecinol can increase the expression of various antioxidant enzymes in the gastric mucosa, such as superoxide dismutase 1 (SOD-1), SOD-2, heme oxygenase-1 (HO-1), glutathione S-transferase (GST), glutathione peroxidase (GSH-px), peroxide reductase-1 (PRDX1; PRXI), and PRXD5 (PRXV). These enzymes protect cells from damage caused by reactive oxygen species (ROS). Furthermore, this drug can inhibit the activity of the transcription factor nuclear factor-κB (NF-κB) and reduce the expression of various pro-inflammatory cytokines, such as interleukin (IL) 1β, IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Zinc polyprene can also increase the expression of various growth factors, such as platelet-derived growth factor-B (PDGF-B), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), as well as various heat shock proteins (HSPs), including HSP90, HSP70, HSP60, HSP47, HSP27, and HSP10. This helps protect the gastric mucosa from damage and accelerate its healing. Carnosine is a dipeptide composed of β-alanine and 3-methyl-L-histidine, found in dietary red meat, and has potential antioxidant, metal chelating, and anti-glycation activities. Carnosine can scavenge reactive oxygen species (ROS) and unsaturated aldehydes produced by cell membrane lipid peroxidation. In addition, this dipeptide can reduce the rate of formation of advanced glycation end products (AGEs). In summary, this may help protect cells from oxidative damage. Furthermore, carnosine can chelate toxic metals. A naturally occurring dipeptide neuropeptide found in muscle. Indications: Peptic ulcers, dyspepsia.

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Mechanism of Action
Polyprezinc increases the expression of multiple antioxidant enzymes, including superoxide dismutase 1 (SOD-1), SOD-2, heme oxygenase-1 (HO-1), glutathione S-transferase (GST), glutathione peroxidase (GSH-px), peroxide reductase-1 (PRDX1; PRXI), and PRXD5 (PRXV). This process occurs in the gastric mucosa, protecting mucosal cells from reactive oxygen species. The drug inhibits the activity of the transcription factor nuclear factor-κB (NF-κB) and reduces the expression of multiple inflammatory cytokines, including interleukin (IL) 1β, IL-6, IL-8, and tumor necrosis factor-α (TNF-α).
Polyprene zinc also promotes the expression of various growth factors, including platelet-derived growth factor-B (PDGF-B), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), as well as various heat shock proteins (HSPs), including HSP90, HSP70, HSP60, HSP47, HSP27, and HSP10. This process promotes tissue growth and protects the gastric mucosa from damage.

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Pharmacodynamics
Used to treat/control peptic ulcers or gastrointestinal inflammation, it promotes tissue healing by scavenging free radicals.
Carnosine is a naturally occurring compound found in high concentrations in skeletal muscle and brain tissue. It is widely available as a dietary supplement and is used in cosmetic and healthcare products for its anti-aging properties. It is also used as a biochemical reagent in research. Despite its popularity as a supplement, it has not been approved by the FDA as a drug for treating any specific disease. Its primary mechanisms of action are antioxidant, antiglycation, and pH buffering.

C9H14N4O3

226.23

226.106

305-84-0

305-84-0;5852-99-3 (HCl);

439224

White to off-white solid powder

1.4±0.1 g/cm3

656.2±55.0 °C at 760 mmHg

253 °C (dec.)(lit.)

350.7±31.5 °C

0.0±2.1 mmHg at 25°C

1.591

Endogenously produced metabolite: Disease markers Endocrine diseases
Endogenously produced metabolite: Disease markers Nervous System Disorder
Endogenously produced metabolite: Human Gut Microbiota Metabolites

-2.17

121.1

4

5

6

16

259

1

C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)CCN

CQOVPNPJLQNMDC-ZETCQYMHSA-N

InChI=1S/C9H14N4O3/c10-2-1-8(14)13-7(9(15)16)3-6-4-11-5-12-6/h4-5,7H,1-3,10H2,(H,11,12)(H,13,14)(H,15,16)/t7-/m0/s1

(2S)-2-(3-aminopropanoylamino)-3-(1H-imidazol-5-yl)propanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~83.33 mg/mL (~368.34 mM)

Solubility in Formulation 1: 100 mg/mL (442.03 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)