IngredientsVasicine (peganine) is a quinazoline alkaloid and the major phytochemical component of the plant Adhatoda vasica. The compound is known under several synonyms: it is officially designated by the IUPAC-derived name (β)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-3-ol, and is recorded in chemical databases under the identifier CAS 6159-55-3. The name peganine was applied independently when the same molecule was isolated from a different botanical source. This quinazoline alkaloid was first isolated from the leaves of Adhatoda vasica Nees by Hooper and subsequently discovered in Peganum harmala under the name peganine.
The first known quinazoline alkaloid was vasicine (peganine), isolated in 1888 from Adhatoda vasica, and later from other species. The base is optically inactive, although Spath and Kesztler have reported the isolation of the (β)-form from the fresh leaves of A. vasica, and Rosenfeld and Kolesnikov have obtained the same form from the flowers and stems of Peganum harmala.
*Adhatoda vasica* (L.), Nees, belonging to the family Acanthaceae, is a shrub with opposite ascending branches. The plant has been used in the indigenous system of medicine in India for approximately 2,500 years, and is a well-known plant drug in Ayurvedic and Unani medicines. The plant is common throughout the Indian peninsula and can be seen up to an altitude of 1,300 m. It is also known by the synonyms Adhatoda zeylanica Medic. and Justicia adhatoda L., and by the common names Malabar nut tree and the Sanskrit name Vasaka.
Vasicine and its structural analog vasicinone were also isolated from another medicinal plant, Peganum harmala or Syrian rue. This herb is also known to be a popular ingredient in Middle Eastern and North African folk medicine formulations. *Adhatoda vasica* Nees belongs to the Acanthaceae family and is characterized by its distinctive lance-shaped leaves, which are rough and pubescent. The plant typically grows to a height of 2 to 4 meters and bears clusters of tubular flowers that vary in color from white to purple.
Several phytochemical analyses have been carried out on different parts of A. vasica, including leaf, root, bark, wood, flower, fruit, and even on the whole plant. The two major alkaloids present in the leaves of the plant are vasicine (0.85%) and vasicinone (0.027%). Alkaloid quantification studies of vasaka leaf juice revealed the presence of the quinazoline alkaloid vasicine within the range of 0.3β5.93 mg/mL. Vasicinone has also been isolated from the roots of this plant.
Vasicine undergoes auto-oxidation to form its structural analog vasicinone when exposed to light. The alkaloid vasicinone has been found to be a much weaker base than vasicine, an alkaloid already known to be present in this plant. The molecular weight (Rast) of vasicinone was found to be about 210, with molecular formula CββHββNβOβ. The alkaloid was found to be identical with 2,3-(Ξ±-hydroxytrimethylene)-4-quinazolone, which had been prepared earlier by the oxidation of vasicine with 30 percent hydrogen peroxide.
Important chemical constituents of the leaf include pyrroloquinazoline alkaloids: vasicine, vasicol, adhatonine, vasicinone, vasicinol, and vasicinolone. The new alkaloids vasicoline, vasicolinone, and adhatodine and anisotine are found only in young plants of Adhatoda vasica, in very low yield.
In Ayurvedic preparations, Vasaka leaf juice (Vasa swarasa) is incorporated in more than 20 formulations, including Vasarishta, Mahatiktaka ghrita, Triphala ghrita, Vasavaleha, Vasakasava, Mahatriphalaghrita, Panchatiktaghritaguggulu, and Panchatikta ghrita. The classical method for extracting Vasaka juice is an elaborate process that involves subjecting a bolus of crushed fresh leaf to heat. This method is not applicable to large-scale extraction of juice for commercial purposes. Modern pharmaceutical preparations include isolated vasicine as a reference standard, vasicine acetate as a semi-synthetic derivative, and standardized dry extracts of A. vasica leaves standardized to a defined vasicine content.
Adhatoda vasica, commonly known as Vasaka in Ayurveda, belongs to the family Acanthaceae. This plant has been used in the indigenous system of medicine in India for over 2,000 years. Its Sanskrit name "Vasa" appears in ancient Ayurvedic texts, where the leaves, flowers, roots, and bark have been used to address a range of ailments, especially respiratory complaints. In Ayurveda, the plant is revered as a "Rasayana" for the lungs and was used in treating cough, asthma, tuberculosis, and even bleeding disorders. Ancient texts recommend Vasaka for clearing "Kapha" (mucus) from the body, strengthening the lungs, and restoring ease of breathing.
In Ayurveda, a preparation made from Vasaka flowers, known as gulk, is used to treat tuberculosis. Traditionally it was used for the treatment of various acute and chronic diseases and showed strong pharmacological activity particularly for bronchial infections, cough, bacterial infections, reproductive disorders, cardiac diseases, and many more.
Adhatoda vasica has emerged as an important medicinal herb well known for its applications in different traditional medicinal systems such as Ayurveda, Siddha, and Unani. In Unani and Siddha medicine, the plant was traditionally formulated for respiratory conditions, expectorant syrups, and as a remedy for bleeding (hemostatic properties).
*Peganum harmala* (the secondary source of vasicine, known as peganine) is also a well-known and effective herbal medicine in Turkey, Iran, Algeria, and Morocco. Quinazoline alkaloids from this plant are known to exert bronchodilator and abortifacient actions, and could contribute to such effects reported in P. harmala.
The leaves of Adhatoda vasica are most commonly used in respiratory disorders in Ayurveda. An herbal tea of expectorant action was traditionally prepared with Adhatoda vasica leaves, and the prepared herbal tea is considered a good expectorant. Fresh Vasica leaves have traditionally been ingested by yogis or sadhus, sometimes in conjunction with ginger, because of the plant's stimulating impact on the respiratory system.
The plant has been used in India for 2,000 years for the treatment of respiratory ailments and for its abortifacient activities. In the 1980s, the WHO also included A. vasica in The Special Programme of Research in Human Reproduction as a plant worthy of study for fertility regulation.
Adhatoda vasica mainly consists of alkaloids containing a pyrroloquinazoline ring β derivatives like vasicine, vasicol, and vasicinone, along with other minor constituents. Vasicine is the major bioactive alkaloid of A. vasica, which contains the pyrroloquinazoline ring. Vasicine, an alkaloid, is one of the major components of the plant and is responsible for most of its activities, including its antioxidant, anti-inflammatory, and bronchodilatory qualities.
Vasicine was reported to have bronchodilatory, respiratory stimulant, and uterine stimulant effects. Vasicinone was shown to have bronchodilatory, weak cardiac stimulant, and antianaphylactic action. Both alkaloids in combination (1:1) showed pronounced bronchodilatory activity in vivo and in vitro. Both alkaloids are also respiratory stimulants. Vasicine has a cardiac-depressant effect, while vasicinone is a weak cardiac stimulant; the effect can be normalized by combining the alkaloids.
Vasicine has been compared to theophylline both in vitro and in vivo. Theophylline's principal mechanism of bronchodilation involves nonselective phosphodiesterase (PDE) inhibition, particularly of PDE type III and IV isoenzymes. The alkaloids vasicine and vasicinone present in the leaves possess respiratory stimulant activity.
Bromhexine, a derivative of vasicine, has been shown to possess mucus-liquefying/expectorant activity. Ambroxol, a widely used secretolytic agent also developed from vasicine, was shown to inhibit IgE-dependent mediator secretion from human mast cells and basophils β the principal effectors of allergic inflammation. As compared to vasicine, ambroxol showed a greater effect in lowering basophil IL-4 and IL-13 secretions. It was also reported to reduce IgE-dependent p38 mitogen-activated protein kinase (MAPK) phosphorylation in basophils.
The uterotonic action of vasicine was investigated in-depth both in vitro and in vivo, using uteri from various species of animals with diverse hormonal effects. Similar to oxytocin and methyl ergometrine, uterotonic action was observed. Under the priming impact of estrogens, the abortifacient action of vasicine, as well as its uterotonic effect, was more pronounced. Vasicine works by releasing prostaglandins (PGs).
Vasicine (VAS), a potential natural cholinesterase inhibitor, exhibited promising anticholinesterase activity in preclinical models and has been investigated for the treatment of Alzheimer's disease. This mechanism is separate from its respiratory actions and represents an emerging area of pharmacological interest.
Previous studies have reported that VAS could be metabolized into vasicinone (VAO), deoxyvasicine (DVAS), deoxyvasicinone (DVAO), 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-3-Ξ²-D-glucuronide (VAS-3-G), and vasicinone-3-O-glucuronide (VAO-3-G) in rats after an oral dose of 20 mg/kg. Six key metabolites were isolated from rat urine and elucidated as vasicinone, vasicinol, vasicinolone, and three conjugate forms. The metabolic pathway of VAS in vivo and in vitro mainly involved monohydroxylation, dihydroxylation, trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. When administered intravenously, approximately 55% of the excreted product within the first 18β22 hours consisted of vasicine. Oral administration resulted in approximately 18% of the excreted product being vasicine within the first 24 hours. These figures indicate that oral bioavailability is substantially lower than intravenous bioavailability, an important pharmacokinetic consideration.
*Adhatoda vasica* leaves showed antitussive activity against the guinea pig similar to that of codeine against coughing induced by irritant aerosols. A 2015 study published in Phytomedicine investigated the antitussive, expectorant, and bronchodilating effects of vasicine and related alkaloids from Peganum harmala using animal models. The three quinazoline alkaloids (vasicine, deoxyvasicine, and vasicinone) were tested for antitussive activity on cough models in mice and guinea pigs. VAS, VAO, and DVAS were orally administered at dosages of 5, 15, and 45 mg/kg. Cough in these models was induced by ammonia, capsaicin, and citric acid. Phenol red secretion experiments in mice were performed to evaluate the expectorant activity of the alkaloids. Bronchodilating effects were evaluated using a bronchoconstriction model induced by acetylcholine chloride and histamine in guinea pigs. The conclusion was that quinazoline alkaloids vasicine, vasicinone, and deoxyvasicine have significant antitussive, expectorant, and bronchodilating activities, and may be used to treat respiratory disease.
The respiratory evidence for vasicine in isolation consists primarily of animal (in vivo) and in vitro studies. Principal clinical research studies were primarily developed in an era when stringent methodological approaches were less consistently applied. No large, controlled randomized human clinical trials specifically on isolated vasicine for respiratory outcomes have been identified in the peer-reviewed literature. The evidence base must therefore be characterized as preliminary to moderate, resting on animal models, in vitro data, and historically conducted human studies of variable methodological quality.
Around 1977 it was discovered that vasicine possesses uterine stimulating activity with similar effect as oxytocin. After this discovery and due to the great need for new drugs for fertility regulation, substantial efforts were put into research to develop vasicine as a new abortifacient agent.
Vasicine-induced abortion in rats, guinea pigs, hamsters, and rabbits was investigated. To evaluate the abortifacient effect of vasicine in oestradiol-primed guinea pigs, pre-treatment was done with oestradiol, and then further reduced with indomethacin and aspirin due to the release of prostaglandins that was mediated by vasicine. Abortifacient activity was observed in more than half of the animals after parenteral administration, while no activity was observed after oral administration.
Studies on human subjects have shown that the alkaloid vasicine has significant uterotonic activity. A clinical pharmacology study examined vasicine in hospital in-patients. Investigations on clinical pharmacology were carried out on 24 human volunteers with 0.5β16 mg doses of vasicine injected intravenously in 500 mL saline over 3 hours, with the objective of determining acute human toxicity, tolerance, pharmacological action, any untoward effect, and the safe dosage range. Vasicine tried up to a 16 mg dose on hospital in-patients on the 2nd to 8th day of normal puerperium was well tolerated and showed no undesirable effect in clinical observations, haematological and biochemical investigations, and kidney and liver function tests carried out before, during, and after vasicine treatment. However, the uterus became firm and contracted after vasicine treatment, which indicated its effectiveness as an oxytocic and supported its abortifacient activity.
The uterotonic and abortifacient evidence is supported by convergent preclinical data across multiple animal species and a small human clinical study. The mechanism via prostaglandin release is consistent across studies. However, the clinical study had a small sample size and was performed in postpartum women, not in early pregnancy. The overall evidence is moderate for uterotonic activity but requires further controlled trials for definitive characterization in obstetric applications.
Vasicine acetate, a semi-synthetic derivative, exhibited a good zone of inhibition against bacteria: 10 mm against E. aerogenes, 10 mm against S. epidermidis, and 10 mm against P. aeruginosa. Vasicine acetate showed minimum inhibitory concentration values against bacteria: M. luteus (125 ΞΌg/mL), E. aerogenes (125 ΞΌg/mL), S. epidermidis (125 ΞΌg/mL), and P. aeruginosa (125 ΞΌg/mL).
The benzylamines bromhexine and ambroxol, widely used as mucolytics and semi-synthetic derivatives of vasicine, have a pH-dependent growth-inhibitory effect on Mycobacterium tuberculosis. As these compounds are concentrated in macrophages, they might exert a clinically useful effect on intracellular tubercle bacilli. This, combined with indirect effects including enhancement of lysozyme levels in bronchial secretions and levels of rifampicin in lung tissue and sputum, and possibly clearance of bacilli-laden mucus, suggests a potentially useful adjunctive function in the therapy of tuberculosis.
Antimicrobial evidence for vasicine itself is confined to in vitro studies. Data for its pharmacologically derived analogs (bromhexine, ambroxol) are more developed but involve structurally distinct compounds. No human clinical trials have evaluated vasicine as a primary antimicrobial agent. Evidence should be characterized as preliminary, in vitro only.
Vasicine acetate showed prominent cytotoxic activity in vitro against A549 lung adenocarcinoma cancer cell line. The antiproliferative effect of the closely related vasicinone was investigated against A549 lung carcinoma cells. The A549 cells upon treatment with various doses of vasicinone (10, 30, 50, 70 ΞΌM) for 72 hours showed significant decrease in cell viability. Vasicinone treatment also showed DNA fragmentation, LDH leakage, and disruption of mitochondrial potential, and lower wound healing ability in A549 cells. Annexin V/PI staining showed disrupted plasma membrane integrity and permeability of PI in treated cells.
Anticancer activity has been demonstrated only in cell-culture models for vasicine and vasicinone. There are no animal tumor models or human clinical trials evaluating vasicine as an anticancer agent. This area of research is strictly preliminary and in vitro.
Vasicine (VAS), as a potential natural cholinesterase inhibitor, has exhibited promising anticholinesterase activity in preclinical models and has been in development for the treatment of Alzheimer's disease. A study systematically investigated the in vitro and in vivo metabolism of VAS in rat using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. A total of 72 metabolites were identified based on detailed NMR and mass spectrometry data. This work supports the pharmacological tractability of vasicine as a lead compound for cholinesterase inhibitor development, but no human clinical trials have been conducted in this indication. Evidence is preclinical only.
Compounds derived from A. vasica have shown biological activities including antiseptic, anti-asthmatic, diuretic, antispasmodic, antipyretic, diaphoretic, analgesic, and sedative effects. Antimicrobial, anti-inflammatory, antioxidant, bronchodilatory, antitussive, and abortifacient effects have been reported for vasicine. The radical scavenging activity of vasicine acetate was the maximum at 1,000 ΞΌg/mL (66.15%). These findings are from in vitro assays and preclinical models; no controlled human studies specifically assessing the anti-inflammatory or antioxidant effects of isolated vasicine have been identified.
The following dosages appear in the peer-reviewed literature and should not be construed as recommendations:
No standardized human oral dosage for isolated vasicine as a dietary supplement has been established in controlled clinical trials. Typical traditional preparations (leaf juice, decoctions, and standardized extracts) are dosed at the level of the whole botanical rather than by isolated alkaloid content.
Several scientific reports on oxytocic and abortifacient effects of vasicine and alkaloids derived from the plant have appeared over the past two decades. This leads to questions concerning the safety of A. vasica as a herbal medicine. Under the priming impact of estrogens, the abortifacient action of vasicine, as well as its uterotonic effect, was more pronounced. Important questions arise concerning the safety of A. vasica when used as a medicinal plant in a tea, as an extract, or prepared as a herbal medicine in tablets, pills, or tinctures. The major question is: does A. vasica produce an abortifacient effect or toxic effects in human beings?
Abortifacient activity was observed in more than half of the animals after parenteral administration, while no activity was observed after oral administration. When administered intravenously, approximately 55% of the excreted product within the first 18β22 hours consisted of vasicine. On the other hand, oral administration resulted in approximately 18% of the excreted product being vasicine within the first 24 hours. These findings suggest that the lower oral bioavailability of vasicine may reduce, but not necessarily eliminate, uterotonic risk when ingested orally.
Vasicine has a cardiac-depressant effect, while vasicinone is a weak cardiac stimulant; the effect can be normalized by combining the alkaloids. This cardiovascular activity means that preparations containing vasicine, particularly in high doses or parenterally, could theoretically affect cardiac function.
Vasicine tried up to a 16 mg dose on hospital in-patients on the 2nd to 8th day of normal puerperium was well tolerated and showed no undesirable effects in clinical observations, haematological and biochemical investigations, and kidney and liver function tests carried out before, during, and after vasicine treatment. This represents the most direct human safety data available, but it was conducted in postpartum women and at a single intravenous dose level; it does not establish safety for other populations or for chronic oral use.
Computational toxicity analysis predicted that vasicine may exhibit adverse effects such as shivering and panic hypotension. These are computational (in silico) predictions and have not been confirmed in controlled clinical trials.
Seeds extracts of Peganum harmala containing both quinazoline and Ξ²-carboline alkaloids potently inhibited human monoamine oxidase (MAO)-A. However, quinazoline alkaloids did not contribute to MAO inhibition, which was due to Ξ²-carbolines, suggesting that MAO-related psychoactive or toxic actions do not arise from quinazolines. This indicates that vasicine itself does not carry the MAO-inhibitory risk associated with other Peganum harmala alkaloids. However, given vasicine's uterotonic mechanism and potential cardiac effects, interactions with uterotonics, bronchodilators, and cardiovascular drugs are pharmacologically plausible and deserve caution.
During the last 20 years, several scientific reports on oxytocic and abortifacient effects of vasicine and alkaloids derived from the plant have appeared. This leads to questions concerning the safety of A. vasica as a herbal medicine. No definitive large-scale genotoxicity study specifically on isolated vasicine in humans has been identified in the peer-reviewed literature reviewed here.
A 2007 survey on demand and supply of medicinal plants in India by the National Medicinal Plants Board, New Delhi, listed Adhatoda vasica under the top 36 medicinal plant species in high trade, consumed in volumes exceeding 100 MT per year. The plant and its preparations are used widely within traditional medicine systems in South Asia, but isolated vasicine as a standardized dietary supplement ingredient does not, as of the available literature, have an established regulatory approval or monograph from major Western pharmacopeial bodies (USP, European Pharmacopoeia) in the same category as its pharmaceutical derivatives bromhexine and ambroxol, which are approved drugs in many countries.
Health conditions that Vasicine may help support.
Vasicine is a quinazoline alkaloid from Adhatoda vasica (Malabar nut/Justicia adhatoda) with documented bronchodilatory activity both in vitro and in vivo comparable to theophylline. It has antispasmodic, expectorant, and anti-inflammatory effects demonstrated in preclinical studies. The semi-synthetic derivative ambroxol, developed from vasicine, is a globally-approved mucolytic/secretolytic agent used in bronchitis treatment. Vasicine has been used in Ayurvedic and Unani medicine for over 2,000 years for bronchitis and asthma.
Vasicine is the primary alkaloid of Adhatoda vasica (Malabar nut) with demonstrated bronchodilatory, expectorant, and anti-tussive activities in vitro and in vivo. It is the pharmacopoeial active constituent in Vasaka syrup (Indian Pharmacopoeia) specifically for bronchitis. It is the structural precursor of bromhexine, a widely used pharmaceutical mucolytic for bronchitis.
Vasicine is an alkaloid from Adhatoda vasica (Malabar nut) with demonstrated bronchodilatory, expectorant, and anti-inflammatory properties so potent it was the basis for synthesizing the pharmaceutical mucolytics bromhexine and ambroxol. In vitro and animal studies show it relaxes tracheal muscles, increases bronchial secretions, and facilitates phlegm expulsion.
Body systems that Vasicine may help support.
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