IngredientsAntirrhinin is an anthocyanin and specifically the 3-rutinoside of cyanidin. It belongs to the broader flavonoid superfamily, within the subclass of anthocyanins — water-soluble plant pigments responsible for red, purple, and blue coloration in many fruits and flowers. Within the scientific literature, antirrhinin is more commonly referenced by its systematic chemical name, cyanidin-3-O-rutinoside, abbreviated as C3R. It is also known by the synonym keracyanin (or keracyanin chloride in its salt form).
Keracyanin (antirrhinin) is the pigment originally isolated from the fruit of the cherry. The compound's CAS registry number is 18719-76-1. Cyanidin-3-O-rutinoside chloride is an anthocyanidin compound containing a chloride structure, and it presents as a reddish-purple crystalline powder, soluble in water and slightly soluble in ethanol and alcohol solvents.
As a subgroup of polyphenolic flavonoids, anthocyanins make up the largest group of water-soluble pigments in the plant kingdom, and are responsible for producing the red, purple, and blue hues that color many fruits, vegetables, grains, and flowers. The backbone structure of anthocyanidins consists of an aromatic ring bonded to an oxygen-containing heterocyclic ring called the flavylium ion, which enables visible light absorption from 500 to 550 nm, with another aromatic ring carrying various hydroxyl, methoxy, and hydrogen substituents, to which sugar residues link to form the glycosylated anthocyanin pigments.
Cyanidin (the aglycone of antirrhinin) has a characteristic reddish-purple color, though this can change with pH; solutions of the compound are red at pH <3, violet at pH 7–8, and blue at pH >11.
In antirrhinin specifically, the rutinoside sugar moiety — a disaccharide composed of rhamnose and glucose — is attached at the 3-position of the cyanidin flavylium core. The enzyme cyanidin 3-O-rutinoside 5-O-glucosyltransferase uses UDP-glucose and cyanidin 3-O-rutinoside (antirrhinin) to produce UDP and cyanidin 3-O-rutinoside 5-O-beta-D-glucoside, indicating that antirrhinin itself serves as a biosynthetic substrate for further glycosylation in certain plant species.
The molecular formula of cyanidin-3-O-rutinoside chloride is C₂₇H₃₁O₁₅Cl, with a molar mass of 630.98 g/mol and a melting point of 175°C.
Antirrhinin is an anthocyanin found in Antirrhinum majus (common snapdragon), from which it takes its common name, as it is the 3-rutinoside of cyanidin. Antirrhinum majus, the common snapdragon, is a species of flowering plant belonging to the genus Antirrhinum, placed in the family Plantaginaceae following a revision of its prior classical family, Scrophulariaceae.
The plant is native to southern-central France and the eastern Pyrenees to north-eastern Spain and the Balearic Islands, and often grows in crevices and walls. It is perennial but usually cultivated as an annual plant, and the species has been in culture since the 15th century.
Antirrhinin can be found in blackcurrant, açaí, black raspberry, litchi pericarp, and common fig. Cyanidin-3-rutinoside is widely distributed in a high number of dietary sources, such as blackberry, mulberry, and black raspberry.
Cyanidin-3-rutinoside (also antirrhinin) has been detected, together with peonidin-3-glucoside, in lower amounts in purple-pigmented rice cultivars including 'Violet Nori', 'Artemide', and 'Nerone'. Antirrhinin (cyanidin-3-rutinoside or 3-C-R) is also found in black raspberry.
Antirrhinin is only one of many bioactive compounds found in its namesake plant. Amino acids, pigments, oils, anthocyanidins, flavonols, flavones, aurones, flavanones, cinnamic acids, and a variety of other compounds have been found in Antirrhinum majus. Its active ingredients include mucilages, gallic acid, resins, pectin, and bitters. Fruit proanthocyanidins, flavonols, and anthocyanins have been measured during fruit growth and ripening. Proanthocyanidins and total flavonol concentrations were highest in flower ovaries and early fruit development stages. Proanthocyanidins decreased rapidly during ovary development and growth, then increased slightly during fruit ripening. Flavonols showed a less pronounced decline from levels in flowers and early fruit set stages, and also increased slightly during fruit ripening.
Antirrhinum majus, the plant source from which antirrhinin takes its name, has a rich history in traditional medicine spanning several cultures. Historically, this vibrant flowering plant was valued not only for its ornamental beauty but also for its therapeutic properties. In European folk medicine, snapdragon flowers were used to create soothing infusions and poultices, remedies believed to aid in treating inflammatory skin conditions such as hemorrhoids and abscesses by leveraging the plant's mild astringent and anti-inflammatory effects.
The plant was used traditionally as a diuretic, for treatment of scurvy, liver disorders, and tumors. The leaves and flowers were used as antiphlogistic, resolvent, stimulant, and poultices on tumours and ulcers.
In the Middle Ages, it was considered a plant that warded off evil and was planted at the entrances to houses, and in folk medicine, its juice was used to treat skin diseases.
The plant's actions are described as topically emollient, antiphlogistic, astringent, antiscorbutic, hepatic, and diuretic. It is considered effective against inflammations and has been used for haemorrhoids, in gargles against ulcerations of the oral cavity, and internally for colitis and heartburn. Externally, it has been applied as poultices on erythemas.
Additionally, snapdragon extracts were sometimes applied to relieve minor burns, rashes, and insect bites, and internally, snapdragon was occasionally used in teas for its purported ability to support digestion and alleviate mild headaches.
The above-ground parts are harvested in the summer when in flower and dried for later use. The leaves and flowers are antiphlogistic, bitter, resolvent, and stimulant, and can be used in poultices on skin tumours and ulcers. The plant is effective in the treatment of all kinds of inflammation and is also used on haemorrhoids. The flowers are edible and can be added to green salad rather than infused.
It is important to note that historical uses described above reflect the whole plant (Antirrhinum majus) rather than specifically isolated antirrhinin/cyanidin-3-rutinoside. No traditional medical system specifically isolated or identified antirrhinin as a discrete therapeutic agent prior to modern chemical characterization.
The compound exerts potent antioxidant properties. This mechanism of action is largely attributed to its ability to donate hydrogen atoms or electrons, stabilizing reactive oxygen species.
At concentrations of 5, 10, and 20 μg/mL, anthocyanins (including cyanidin-3-rutinoside) significantly reduced H₂O₂-induced cytotoxicity in stimulated RAW264.7 murine macrophage cells. Incubation with cyanidin-3-rutinoside significantly decreased intracellular reactive oxygen species and DNA damage, and the cellular ferric reducing antioxidant power also increased, compared with control cells.
Advanced glycation end-products (AGEs) play a significant role in the development and progression of vascular complications in diabetes, and anthocyanins have been reported to possess antiglycating activity. Specifically, this has been studied with cyanidin-3-rutinoside to determine whether it inhibits methylglyoxal (MG)-induced protein glycation and oxidative protein and DNA damage, using C3R at concentrations of 0.125–1 mM incubated with bovine serum albumin and MG (1 mM) for 2 weeks.
Nitric oxide production in LPS-stimulated RAW264.7 cells treated with cyanidin-3-rutinoside was reduced by 34.4%. In addition, LPS-induced prostaglandin E₂ production was significantly inhibited by cyanidin-3-rutinoside (58.6%), compared with LPS-stimulated control cells.
Research has also explored the role of antirrhinin/keracyanin on the NF-κB pathway. Anti-inflammatory effects of the anthocyanin keracyanin alone and in combination with oleic acid were studied, including effects on monocyte and macrophage responses and the NF-κB pathway (published in Food Function, 2021).
Cyanidin-3-rutinoside (C3R) possesses anti-oxidant, anti-inflammatory, and anti-glycation properties. In isolated rat vasculature, C3R induced vasorelaxation concentration-dependently in aortic rings (92% maximum relaxation; EC₅₀: 2.43 ± 0.57 μM) and in perfused-mesenteric arterial bed (61% maximum relaxation; EC₅₀: 25.0 ± 1.26 μM) pre-contracted with noradrenaline. The vasorelaxation actions of C3R were endothelium-dependent and mediated primarily via nitric oxide (NO) as evidenced by the absence of relaxation in endothelium-denuded preparations.
A study investigated the effect of cyanidin-3-rutinoside against methylglyoxal (MG)-advanced glycation end-products (AGEs)-mediated cardiovascular abnormalities in rats. In the rats, plasma MG level rose following oral administration of MG (60–120 mg/rat/day) for 8 weeks, accompanied by a buildup of MG-derived AGE in aortic tissue, both of which were decreased by co-treatment with C3R (30 and 100 mg/kg/day). MG-impaired vascular contraction and relaxation responses were normalized by C3R with concomitant upregulation of endothelial nitric oxide synthase mRNA expression. In the whole animal subjected to coronary artery ligation, C3R (100 mg/kg/day) reduced ventricular extra beats and ventricular tachycardia precipitated during acute ischemic episodes. The authors suggest that C3R reduces formation and accumulation of AGEs via direct trapping of MG and upregulation of mRNA expression of glyoxalase I.
C3R has demonstrated promising benefits for reduction of postprandial glucose through inhibition of pancreatic α-amylase and intestinal α-glucosidase. In vitro data support the underlying mechanism and indicate that C3R might modulate postprandial glycemia by inhibiting carbohydrate digestive enzymes and decreasing glucose transport in the small intestine. C3R also regulated glucose uptake and increased GLUT4 expression in 3T3-L1 adipocytes through activation of the PI3K/Akt pathways.
C3R was shown to be a mixed-type competitive inhibitor of pancreatic lipase with an IC₅₀ value of 59.4 ± 1.41 μM. Furthermore, C3R (0.125–1 mM) inhibited pancreatic cholesterol esterase by approximately 5–18%. In addition, C3R inhibited the formation of cholesterol micelles and bound to primary and secondary bile acid. In Caco-2 cells, C3R (12.5–100 μM) exhibited a significant reduction in cholesterol uptake in both free cholesterol (17–41%) and mixed micelles (20–30%). Finally, C3R (100 μM) was able to suppress mRNA expression of NPC1L1 in Caco-2 cells after 24 h incubation, suggesting that C3R acts as a lipid-lowering agent through inhibition of lipid digestion and absorption.
Exposure to high levels of glucose may cause glucotoxicity, leading to pancreatic β cell dysfunction, including cell apoptosis and impaired glucose-stimulated insulin secretion. A study explored the effect of cyanidin-3-rutinoside on glucotoxicity-induced apoptosis in INS-1 pancreatic β cells. Glucose (30 mM) treatment induced INS-1 β cell death, but glucotoxicity and apoptosis significantly decreased in cells treated with 50 μM C3R compared to that observed in 30 mM glucose-treated cells. Furthermore, hyperglycemia increased intracellular reactive oxygen species, lipid peroxidation, and nitric oxide levels, while C3R treatment reduced these in a dose-dependent manner. C3R also increased the activity of antioxidant enzymes, markedly reduced the expression of pro-apoptotic proteins (such as Bax, cytochrome c, caspase 9, and caspase 3), and increased the expression of the anti-apoptotic protein Bcl-2 in hyperglycemic cells.
Cyanidin-3-rutinoside has been shown to stimulate insulin secretion by activating L-type voltage-dependent calcium channels and the phospholipase C-inositol 1,4,5-trisphosphate (PLC-IP3) pathway in pancreatic β-cells.
Antirrhinin/keracyanin is able to inhibit host- and bacteria-derived proteinases.
Evidence type: In vitro enzymatic assays and animal (rodent) studies. No published human clinical trials specifically on isolated antirrhinin/C3R were identified at the time of this review.
The inhibitory activity on intestinal α-glucosidase by cyanidin-3-rutinoside was examined both in vitro and in vivo. The IC₅₀ values of cyanidin-3-rutinoside against intestinal maltase and sucrase were 2,323 ± 14.8 and 250.2 ± 8.1 μM, respectively. Kinetic analysis revealed that intestinal sucrase was inhibited by cyanidin-3-rutinoside in a mixed-type manner.
Synergistic inhibition was also found in the combination of cyanidin-3-rutinoside with acarbose against intestinal maltase and sucrase. Oral administration of cyanidin-3-rutinoside (100 and 300 mg/kg) plus maltose or sucrose to normal rats markedly suppressed postprandial plasma glucose at 30–90 min after loading. Normal rats treated with acarbose and cyanidin-3-rutinoside (30 mg/kg) showed greater reduction of postprandial plasma glucose than the group treated with acarbose alone.
These results suggest that cyanidin-3-rutinoside retards absorption of carbohydrates by inhibition of α-glucosidase, which may be useful as a potential inhibitor for prevention and treatment of diabetes mellitus.
Strength of evidence: The evidence is preliminary and limited to in vitro and preclinical (rat) models. No randomized controlled human trials have been published specifically for isolated antirrhinin.
Evidence type: In vitro cell studies and ex vivo isolated tissue preparations (rat). No published human clinical trials for isolated C3R were identified.
Epidemiological studies suggest that the increased consumption of anthocyanins lowers the risk of cardiovascular diseases. For isolated cyanidin-3-rutinoside specifically, the purified anthocyanin C3R caused vasorelaxation in isolated rat blood vessel preparations (aortic rings and mesenteric vascular bed).
Regarding lipid lowering, clinical evidence has revealed that supplementation of anthocyanins (as a class) reduced total cholesterol, triglyceride, and the level of low-density lipoprotein cholesterol (LDL-C) and increased the level of high-density lipoprotein cholesterol (HDL-C) in patients with dyslipidemia. However, this evidence applies to mixed anthocyanin extracts, not isolated antirrhinin. A previous study reported that consumption of purified mulberry anthocyanins containing cyanidin-3-rutinoside (C3R) effectively decreased serum lipid levels in high-fat fed mice, although the specific mechanisms of action by which C3R decreases serum lipid level are still unknown.
Strength of evidence: Preliminary. Data are from in vitro and animal (rodent) models, with translational human benefit not yet confirmed for isolated antirrhinin specifically.
Evidence type: In vitro (bovine serum albumin model, Caco-2 cells) and in vivo rodent studies.
A study investigated the effect of C3R against methylglyoxal-AGEs-mediated cardiovascular abnormalities in rats. In the rats, plasma MG level rose following oral administration of MG (60–120 mg/rat/day) for 8 weeks, accompanied by buildup of MG-derived AGE in aortic tissue, both of which were decreased by co-treatment with C3R (30 and 100 mg/kg/day).
Studies found that C3R inhibited monosaccharide- and methylglyoxal-induced protein glycation in bovine serum albumin.
Strength of evidence: Preclinical only. No human trials have evaluated antirrhinin's anti-glycation effects.
Evidence type: In vitro cell line studies (leukemic, lymphoma, and colon cancer cell lines). No human clinical evidence.
The effects and mechanisms of cyanidin-3-rutinoside were studied in several leukemia and lymphoma cell lines. Cyanidin-3-rutinoside extracted and purified from the black raspberry cultivar Jewel induced apoptosis in HL-60 cells in a dose- and time-dependent manner. Paradoxically, this compound induced the accumulation of peroxides involved in the induction of apoptosis in HL-60 cells. In addition, cyanidin-3-rutinoside treatment resulted in reactive oxygen species (ROS)-dependent activation of p38 MAPK and JNK, which contributed to cell death by activating the mitochondrial pathway mediated by Bim.
Down-regulation of Bim or overexpression of Bcl-2 or Bcl-x(L) considerably blocked apoptosis, confirming the mechanistic pathway.
Cyanidin-3-rutinoside can inhibit the motility of RKO human colon cancer cells, as demonstrated by a wound-healing assay.
Strength of evidence: In vitro only. Results from cancer cell lines cannot be extrapolated to clinical outcomes without human trial data. The evidence is at an early, exploratory stage.
Evidence type: In vitro (cell culture) studies.
The antioxidant and anti-inflammatory effects of cyanidin-3-rutinoside were determined using RAW264.7 murine macrophage cells. As noted above, nitric oxide production in LPS-stimulated RAW264.7 cells treated with C3R was reduced by 34.4%, and LPS-induced prostaglandin E₂ production was significantly (p<0.05) inhibited by C3R (58.6%), compared with LPS-stimulated control cells.
Strength of evidence: Preliminary in vitro evidence only. The extent to which these effects translate to relevant human conditions has not been established in clinical trials.
Cherry fruit anthocyanins cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside have been studied for protection against blue light-induced cytotoxicity in HaCaT cells (published in Applied Biological Chemistry, 2023). This research area remains at the in vitro cell line stage.
Strength of evidence: Preliminary in vitro only.
Antirrhinin/cyanidin-3-rutinoside is not currently available as a standardized, approved pharmaceutical preparation. In research contexts, it has been used as a purified compound extracted from plant materials. The preparation method for cyanidin-3-O-rutinoside chloride is generally obtained by extracting from natural plants, followed by a series of isolation and purification steps to obtain pure products.
The following dosages have been reported specifically in published preclinical studies:
No standardized human clinical dosage for isolated antirrhinin has been established in the published peer-reviewed literature identified for this article.
Antirrhinin exists naturally in commonly consumed berries, fruits, and vegetables, and dietary exposure through these food sources is generally considered part of a normal human diet. There are no severe side effects linked to snapdragons when used as directed; however, consuming the plant in large quantities, especially by those sensitive to bitter substances, might cause mild digestive upset.
Dietary supplementation with purified keracyanin has been reported to suppress body weight gain in high-fat diet fed mice, suggesting metabolic effects at supplemental doses in animal models, though safety in humans at concentrated supplemental levels has not been formally evaluated in clinical trials identified in this review.
No clinical toxicological profile for isolated, purified antirrhinin has been established in humans based on peer-reviewed evidence available at the time of this writing. The evidence base consists primarily of cell culture and rodent studies, which limits direct safety extrapolation to humans.
Antirrhinum majus has antimicrobial, insecticidal, cytotoxic, antioxidant, central and peripheral nervous system effects, and many other biological activities according to recent studies. The cytotoxic activities documented for whole-plant extracts underscore that extrapolation of plant-source safety to purified antirrhinin requires caution.
Synergistic inhibition was found in the combination of cyanidin-3-rutinoside with acarbose against intestinal maltase and sucrase. This indicates a pharmacodynamic interaction with the anti-diabetic drug acarbose in preclinical models — a consideration for individuals using α-glucosidase-inhibiting medications. No human data on this interaction are currently available.
Antirrhinin (cyanidin-3-O-rutinoside) has been the subject of a growing body of laboratory and preclinical research. Anthocyanins have been a target of many studies due to the presence of catechol, pyrogallol, and methoxy groups in their chemical structure, which confer notable scavenging, anti-apoptotic, and anti-inflammatory activities, and are already recommended as supplementation to mitigate or even attenuate certain disorders such as diabetes, cancer, and cardiovascular and neurological pathologies. However, the evidence for isolated antirrhinin specifically remains almost entirely preclinical — derived from in vitro cell culture systems and rodent models. Scientific investigation into the nutritional and therapeutic benefits of antirrhinin's primary botanical source is still emerging. No large, well-controlled randomized human clinical trials focused on isolated antirrhinin have been identified in the peer-reviewed literature. Broader clinical evidence exists for mixed anthocyanin extracts from berries that contain antirrhinin alongside other compounds, but these results cannot be attributed solely to antirrhinin. Claims about its therapeutic benefits in humans must therefore be considered preliminary and hypothesis-generating at this stage.
Health conditions that Antirrhinin may help support.
Body systems that Antirrhinin may help support.
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