Antirrhinum majus

Antirrhinum majus (Common Snapdragon): A Comprehensive Reference

1. Identity and Botanical Classification

1.1 Nomenclature and Taxonomy

Antirrhinum majus, the common snapdragon (often — especially in horticulture — simply "snapdragon"), is a species of flowering plant belonging to the genus Antirrhinum. The plant was placed in the family Plantaginaceae following a revision of its prior classical family, Scrophulariaceae. The genus name carries a precise etymological origin: the term Antirrhinum comes from the Greek anti (αντι), meaning "in front," and rhín, rhínos, meaning "nose" — a reference to the end of the flower's throat, which resembles a nose. The specific epithet majus means "larger."

The common name "snapdragon" originates from the flowers' reaction to having their throats squeezed, which causes the "mouth" of the flower to snap open like a dragon's mouth.

Within the genus, Section Antirrhinum comprises 19 Old World species of relatively large-flowered perennial plants, including the type species Antirrhinum majus, mostly native to the western Mediterranean region with a focus on the Iberian Peninsula.

1.2 Native Range and Habitat

Antirrhinum majus, commonly known as the snapdragon or garden snapdragon, is a species of herbaceous flowering plant in the family Plantaginaceae, native to the rocky slopes and scrublands of the Mediterranean region in southwestern Europe. More precisely, its native range extends from south-central France and the eastern Pyrenees to north-eastern Spain and the Balearic Islands, and the plants often grow in crevices and walls.

A. majus was probably domesticated in northeastern Spain or southwestern France from Antirrhinum pseudomajus (also known as Antirrhinum majus subspecies pseudomajus), from which it differs by having more darkly pigmented flowers, although traits such as flower color variation might have been introduced by introgression from other species.

The species is now found, cultivated or naturalized, on every continent except Antarctica. It is perennial but usually cultivated as an annual plant. The species has been in culture since the 15th century.

1.3 Morphology

It is an herbaceous perennial plant, growing to 0.5–1 m tall, rarely up to 2 m. The leaves are spirally arranged, broadly lanceolate, 1–7 cm long and 2–2.5 cm broad. It features glossy, lanceolate leaves arranged alternately or oppositely along the stems and dense terminal spikes of showy, bilabiate (two-lipped) tubular flowers measuring 1–2 inches (2.5–5 cm) long. The fruit is an ovoid capsule 10–14 mm in diameter shaped like a skull, containing numerous small seeds.

The flowers bloom from early summer to fall and display a wide color palette including white, yellow, pink, red, orange, purple, and bicolors.

1.4 Common Forms and Preparations

In medicine, the leaves (collected in spring before flowering) and the flowers that have just opened are used. These plant parts are dried and then used as infusions. The plant is harvested in summer when it is in flower, dried for later use, and consumed in the form of an infusion. Beyond dried herb and infusion, in European folk medicine, snapdragon flowers were used to create soothing infusions and poultices. Scientific studies have evaluated aqueous, ethanol, and hexane extracts of the aerial parts, as well as cold-pressed seed oil. The flowers are among the most popular edible flowers and are frequently introduced in different preparations of foods and drinks, such as salads, desserts, soups, teas, and liquors, for decorative and flavor-enhancing purposes.

2. Traditional and Historical Use

2.1 Overview of Traditional Use

Antirrhinum majus 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.

2.2 European Folk Medicine

It was used traditionally as a diuretic, for treatment of scurvy, liver disorders, and tumors. The leaves and flowers were used as antiphlogistic (anti-inflammatory), resolvent, stimulant, and as poultices on tumors and ulcers.

In European folk medicine, snapdragon flowers were used to create soothing infusions and poultices. These remedies were believed to aid in treating inflammatory skin conditions, such as hemorrhoids and abscesses, by leveraging the plant's mild astringent and anti-inflammatory effects. Additionally, snapdragon extracts were sometimes applied to relieve minor burns, rashes, and insect bites, helping to calm irritation and promote healing.

Internally, snapdragon was occasionally used in teas for its purported ability to support digestion and alleviate mild headaches.

In ancient times, Antirrhinum majus was also used for its cosmetic properties; and from an industrial perspective, it was possible to obtain dyes from it (dark green and gold).

Traditionally, this plant is also associated with an increase in diuresis and sweating, and it was used to obtain an antihistamine effect.

2.3 Broader Historical Context

The flowers and leaves of snapdragon have been used as traditional herbal medicine for treating several symptoms and diseases, including watery eyes, gum scurvy, hemorrhoids, ulcers, liver disorder, and tumors.

Antirrhinum majus (Snapdragon) is a perennial Mediterranean-native plant that is commonly used for mass display. Only a few reports have acknowledged the traditional use of A. majus for its medicinal and therapeutic effects.

Snapdragon (Antirrhinum majus L.) has been cultivated for its cut flowers and as ornamental garden plants for more than 2,000 years.

3. Key Chemical Constituents

3.1 General Phytochemical Profile

Antirrhinum majus (common snapdragon) contains a variety of chemical constituents such as amino acids, pigments, oils, anthocyanidins, flavonols, flavones, aurones, flavanones, cinnamic acids, and others. More specifically, the plant's chemical composition includes a significant number of bioactive compounds: amino acids, sugars, flavonoids (such as anthocyanidins, aurones, chalcones), and terpenoid compounds (iridoids, carotenoids).

3.2 Flavonoids and Polyphenols

Using high-performance liquid chromatography (HPLC), 15 chemical compounds were identified in studied raw materials, including sugars (glucose and fructose), free amino acids (phenylalanine, tryptophan), flavonoids (auronolin, quercetin-3-galactoside, quercetin-3-arabinofuranoside, quercetin-3-rhamnoside, apigenin 7,4′-diglucuronide, luteolin 7-glucuronide), carotenoids (lutein, β-carotene), chalcononaringenin 4′-glucoside, cyanidin, and antirrhinoside.

Five flavones present in flowers of Antirrhinum majus have been identified: apigenin 7,4′-diglucuronide, luteolin 7-glucuronide, chrysoeriol 7-glucuronide, kaempferol 3-glucoside, and kaempferol 3,7-diglucoside.

3.3 Aurones and Chalcones

Antirrhinum majus is an emblematic example of 4-hydroxyaurone-based flower coloration, since the plant contains several derivatives in large amounts, such as aureusidin, the glucoside aureusin, and the bracteatin glucoside. A new aurone, bracteatin 6-glucoside, has also been found. Three chalcones were discovered in A. majus yellow flowers, two of which were identified as chalcononaringenin 4′-glucoside and 3,4,2′,4′,6′-pentahydroxychalcone 4′-glucoside.

3.4 Iridoids

The four iridoids found in Antirrhinum majus cultivars are antirrhinoside, antirrhide, 5-glucosyl-antirrhinoside, and linarioside. Their total content varies seasonally and diurnally, with a distinct bimodal distribution showing high total values (around 100 mg/g dry matter) early and late in the season, and a very low total iridoid content coinciding with the onset of flowering at the beginning of August. The total iridoid content ranged from 9.16 to 107.98 mg/g dry weight. The amounts of antirrhinoside, antirrhide, 5-Glc-antirrhinoside, and linarioside also varied, at percentages of 69.87–93.33%, 2.57–19.84%, and 1.61–14.19%, respectively.

3.5 Seed Oil Lipid Constituents

A. majus seeds are a good source of oil (12.3%). The amounts of neutral lipids in the oil were the highest, followed by glycolipids and phospholipids. Linoleic and oleic acids accounted for 88% of the total fatty acids. Snapdragon seed oil is characterized by a relatively high amount of phytosterols, wherein the sterol marker was β-sitosterol. All tocopherol isomers were present, wherein γ-tocopherol constituted 81% of the total tocopherol content followed by β-tocopherol (approximately 14.3%).

3.6 Other Compounds

The n-hexane extract of Antirrhinum majus was found to contain a range of volatile and lipophilic compounds including 1-methoxybutane, 3-methylcyclohexanone, eicosane, hexadecanoic acid methyl ester, octadecanoic acid ethyl ester, and protoverine. Protoverine is an alkaloid that has been previously reported to have hypotensive and cytotoxic activities.

4. Established and Proposed Mechanisms of Action

4.1 Antioxidant Activity

The radical scavenging activity (RSA) toward DPPH radicals and galvinoxyl radicals of A. majus oil were higher than those of extra virgin olive oil. In cellular studies, AME (Antirrhinum majus extract) showed high radical-scavenging ability. The flower macerate extract revealed the highest antioxidant activity and total phenolic content, results believed to be due to the flowers' high content of flavonoids and phenolics.

4.2 Anti-inflammatory Mechanisms

LPS-induced nitric oxide (NO) production was decreased by treatment with 0–300 µg/ml AME in a concentration-dependent manner. AME pretreatment significantly inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a concentration-dependent manner. AME also considerably inhibited the mRNA and protein expression of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6).

4.3 Antimicrobial Mechanisms

Results from antimicrobial research suggest that cold maceration of A. majus fresh aerial parts gave higher flavonoid and phenolic content, contributing to its antimicrobial properties. These flavonoids and phenolic compounds are predicted to have a crucial role in inhibiting fungal sterol 14-demethylase, and bacterial dihydropteroate synthase and gyrase B subunit proteins.

Regarding specific compounds, a molecular docking screen of verbascoside isolated from the aerial parts of Antirrhinum majus showed a high binding affinity to C. albicans sterol 14-demethylase (binding energy −9.40 kcal/mol), forming two hydrogen bonds with the amino acids HIS468 and MET508 of the enzyme.

4.4 Cytotoxic and Anti-cancer Mechanisms

Cell cycle analysis and Annexin V staining assay revealed that snapdragon flower extract (SFE) caused cell cycle arrest at G2/M phase and induction of apoptosis, indicating the growth inhibition by SFE is attributed to its G2/M cell cycle-arresting and apoptosis-inducing activities. SFE dose-dependently enhanced generation of intracellular reactive oxygen species (ROS) and reduced mitochondrial membrane potential in H1299 cells.

5. Scientific Evidence by Area of Use

5.1 Anti-inflammatory Activity

Evidence level: Preclinical (in vitro only); no human clinical trials identified.

Antirrhinum majus has attracted attention as a rich source of phytochemicals beneficial for human health. However, the anti-inflammatory effects of AM had not been studied scientifically prior to the 2020 publication. Researchers investigated the antioxidative properties and anti-inflammatory effects of AM extract (AME) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.

Viability of RAW 264.7 cells was not significantly altered by AME at concentrations of 0–300 µg/ml. LPS-induced nitric oxide (NO) production was decreased by treatment with 0–300 µg/ml AME in a concentration-dependent manner. AME pretreatment significantly inhibited the protein expression of iNOS and COX-2 in a concentration-dependent manner. These findings were described as providing a foundation for further studies and use of AM in nutraceuticals.

This in vitro work is preliminary. The study design, using a murine macrophage cell line, cannot be extrapolated to human therapeutic efficacy without further animal and ultimately clinical studies.

5.2 Wound Healing

Evidence level: Preclinical (in vivo animal model); no human clinical trials identified.

A study scrutinized the Mediterranean-native perennial plant Antirrhinum majus for its antioxidant activity and total phenolic content in order to test for the plant's wound-healing capability. The traditional uses of this plant to treat gum scurvy, various tumors, ulcers, and hemorrhoids were the main idea behind this study. Leaves and flowers of A. majus were extracted by maceration.

The in vivo wound-healing capability study was conducted using 30 Wistar strain albino rats. This study revealed that the healing power of the flowers' extract ointment (5% w/w) was superior compared to the leaves' extract (5% w/w) and the positive-control ointments (MEBO) (1.5% w/w) (p ≤ 0.001).

All three methods used for the assessment of wound-healing activity (visual examination, wound-length measurement, and estimation of hydroxyproline content) indicated better wound closure and healing in the active group rather than the control group. This wound-healing effect of the flowers and leaves of A. majus was related to their antioxidant activity.

While this animal study produced statistically significant results, it cannot be directly applied to humans. No randomized controlled trials in human subjects have been located in the literature.

5.3 Antimicrobial Activity

Evidence level: Preclinical (in vitro and in silico); no human clinical trials identified.

A small number of studies have reported this plant to have a high antioxidant capacity as well as potential antimicrobial activity. A 2022 PubMed-indexed study investigated the antimicrobial activity of A. majus aerial parts through laboratory testing combined with molecular docking. Results suggest that cold maceration of A. majus fresh aerial parts gave higher flavonoid and phenolic content contributing to its antimicrobial properties. These flavonoids and phenolic compounds are predicted to have a crucial role in inhibiting fungal sterol 14-demethylase, and bacterial dihydropteroate synthase and gyrase B subunit proteins.

For E. coli's gyrase B subunit, five compounds showed low energy binding values: kaempferol-3-glucoside, quercetin-3-(6''-benzoyl)-β-galactoside, quercetin-3-(6''-coumaroyl)-β-galactoside, quercetin-3-glucoside, and quercetin 3-rutinoside. These five flavonoids were able to bind through an average of four hydrogen bonds. Quercetin 3-rutinoside had a superior binding energy of −10.67 kcal/mol.

All currently available antimicrobial data are in vitro and computational (molecular docking). No clinical studies have confirmed antimicrobial efficacy in humans.

5.4 Cytotoxic / Anticancer Activity

Evidence level: Preclinical (in vitro cell lines only); no human clinical trials identified.

A study examined inhibitory effects of snapdragon flower extract (SFE) against the distinctive properties of cancer cells — stimulated growth and activated metastasis — using H1299 lung cancer and HCT116 colon cancer cell lines. SFE treatment at 100–1,000 μg/ml for 24–72 hr resulted in a time- and dose-dependent growth inhibition in H1299 and HCT116 cells.

Cell cycle analysis and Annexin V staining assay further revealed that SFE caused cell cycle arrest at G2/M phase and induction of apoptosis, indicating the growth inhibition by SFE is attributed to its G2/M cell cycle-arresting and apoptosis-inducing activities.

Despite rich uses of the flower in medicinal and food products, only a small number of studies have reported its antioxidant, antimicrobial, hemolytic, and wound-healing activities; information on other biological activities remains limited.

These cancer cell-line experiments are preliminary screening studies. Cell-line results do not constitute evidence of anticancer efficacy in humans and must be followed by animal models and, ultimately, clinical trials before any therapeutic conclusions can be drawn.

5.5 Antioxidant Activity

Evidence level: Preclinical (in vitro); no human clinical trials identified.

The radical scavenging activity (RSA) toward DPPH radicals and galvinoxyl radicals of A. majus oil were higher than those of extra virgin olive oil in comparative in vitro testing. Scientific interest in Antirrhinum majus has increased in recent years, particularly regarding its secondary metabolites such as flavonoids, phenolic acids, and anthocyanins.

5.6 Effects on the Central and Peripheral Nervous Systems

Evidence level: Described in review literature only; specific study data not available from current sources.

Recent research has revealed that Antirrhinum majus has a wide range of pharmacological activities, including antimicrobial, insecticidal, cytotoxic, antioxidant, genome evolution, and central and peripheral nervous system effects, as well as a variety of other biological activities. The specific mechanisms and experimental models underlying the stated CNS/PNS effects are referenced in pharmacological reviews but individual study details were not available from accessed sources; this area should be treated with caution until primary study data can be verified.

5.7 Insecticidal Activity

Evidence level: Referenced in review literature; specific study data limited in accessed sources.

Recent research has revealed that Antirrhinum majus has a wide range of pharmacological activities, including insecticidal effects, among other biological activities. The insecticidal activity has been attributed in part to the plant's flavonoid and phenolic content, although primary experimental data from controlled studies were not fully accessible in the sources retrieved.

6. Body Systems and Health Areas Associated with Antirrhinum majus

• Integumentary system (skin and wound healing): Due to the presence of its bioactive substances, the plant exhibits anti-inflammatory, wound-healing, antimicrobial, and antioxidant properties, which have been empirically confirmed.
• Immune and inflammatory system: Seeds, leaves, and flowers are used as herbal medicines, and AM is known to have anti-inflammatory, analgesic, and diuretic effects.
• Urinary system: It was traditionally used as a diuretic.
• Hepatic / liver system: It was traditionally used to treat liver problems.
• Oncology (preclinical): In vitro studies examined inhibitory effects of snapdragon flower extract against cancer cell growth and metastasis using H1299 lung cancer and HCT116 colon cancer cell lines.
• Microbial defense: Flavonoid and phenolic content extracted from aerial parts contributes to antimicrobial properties.
• Nutritional / lipid health: The biological wound-healing effect is probably a result of β-sitosterol and tocopherol isomers, both identified in the seed oil of A. majus.

7. Dosage Forms and Reported Dosages

No standardized or approved therapeutic dosages for human use have been established for Antirrhinum majus, and no human clinical trials with defined dosing regimens have been identified in the accessed peer-reviewed literature. The following dosages reflect only those reported in specific experimental studies:

• Topical wound-healing ointment (animal study): The flowers' extract ointment at a concentration of 5% w/w was tested in 30 Wistar strain albino rats and was found superior to the leaves' extract at 5% w/w and the positive-control ointment (MEBO at 1.5% w/w).
• In vitro anti-inflammatory extract concentrations: Cell viability measurement after treatment with 50, 100, 150, 300, and 500 μg/ml of AME showed cell viability of ≥90% up to the concentration of 300 μg/ml, revealing no cytotoxicity, whereas 500 μg/ml AME showed cell viability of <90%.
• In vitro anticancer extract concentrations: SFE treatment at 100–1,000 μg/ml for 24–72 hr resulted in a time- and dose-dependent growth inhibition in H1299 and HCT116 cells.
• Traditional infusion preparation: The plant is harvested in summer when it is in flower and dried for later use; it is consumed in the form of an infusion. No quantitative dose for traditional infusion use is specified in available peer-reviewed sources.

8. Safety Considerations

8.1 General Tolerability in Experimental Contexts

Sample concentrations with cell viability of ≥90% relative to the control group were considered safe, non-toxic concentrations. Cell viability measurement after treatment with 50, 100, 150, 300, and 500 μg/ml of AME showed cell viability of ≥90% up to the concentration of 300 μg/ml, indicating no cytotoxicity at those concentrations in the RAW 264.7 macrophage model, whereas 500 μg/ml AME showed cell viability of <90%.

8.2 Edibility and Oral Ingestion

The flowers are edible, but their taste is quite bitter, so they are mostly used as garnish rather than for flavor. Consuming the plant in large quantities, especially by those sensitive to bitter substances, might cause mild digestive upset. People with sensitivities should avoid excessive consumption, as the flowers are known to be bitter.

8.3 Alkaloid Content

Protoverine, an alkaloid found in the n-hexane extract of A. majus, has been previously reported to have hypotensive and cytotoxic activities. This finding is relevant to safety considerations at higher concentrations or doses, particularly given that the hypotensive effect of this alkaloid could interact with medications affecting blood pressure.

8.4 Absence of Clinical Safety Data

Despite rich uses of the flower in medicinal and food products, only a small number of studies have reported its antioxidant, antimicrobial, hemolytic, and wound-healing activities; information on other biological activities remains limited. No systematic safety evaluations, controlled human studies, or pharmacovigilance data for Antirrhinum majus as a dietary supplement or medicinal preparation were identified in the accessed sources. The absence of such data means that formal drug interaction profiles, contraindications, and upper safety limits cannot be defined from current evidence.

8.5 Evidence Limitations Summary

The totality of evidence for Antirrhinum majus as a medicinal or dietary supplement ingredient is preliminary. Antirrhinum majus has antimicrobial, insecticidal, cytotoxic, antioxidant, central and peripheral nervous system effects, and many other biological activities, according to recent studies. However, all pharmacological studies identified are either in vitro cell-based models or a single animal wound-healing experiment. Although AM is known to have anti-inflammatory, analgesic, and diuretic effects, scientific studies on the physiological activity of AM are still lacking. No controlled human clinical trials have been identified for any indication. Accordingly, all reported biological activities should be classified as preliminary and hypothesis-generating until confirmed by adequately powered clinical research.

References

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