INTRODUCTION:

Argemone Mexicana, commonly known as Mexican poppy or prickly poppy, is a species of flowering plant belonging to the family Papaveraceae. Native to mexico and parts of Central America, it has become widely naturalized in tropical and sub-tropical regions across the world, including India, Africa and the Caribbean.

The plant thrives in a variety of environmental conditions, especially in westland, roadsides, and arid soils, often being considered an invasive weed. Argemone Mexicana is an annual herb that grows up to 1 meter in height, characterized by its distinctive prickly leaves and bright yellow, cup-shaped flowers. The plant’s leaves are spiny, with a bluish-green color and white veins, giving it an ornamental appearance. The flowers are typically yellow, though white varieties are occasionally found. Its fruit is a prickly capsule containing numerous black seeds, which have a history of use in traditional medicine but are also known for their toxicity¹. Historically, Aegemone Mexicana has been widely used in folk medicine across various cultures. In Ayurvedic and traditional Mexican medicine, the plant has been employed to treat ailments like skin diseases, ulcers, wounds, leprosy, jaundice², and even eye infections^3,4. It’s seeds, leaves, latex, and oil have been used for their antimicrobial, anti-inflammatory, and analgesic properties. In African and Caribbean traditional practices, the plant has been used to treat malaria, respiratory infections, and even as a laxative. The bioactive compounds found in Argemone Mexicana includes alkaloids like berberine, sanguinarine, protopine, and chelerythrine, which contribute to its wide range of pharmacological activities. Theses alkaloids are known for their potent antimicrobial⁵, anti-cancer, anti-inflammatory, and antioxidant effects. However, these same compounds, particularly sanguinarine, are toxic at higher doses, leading to it’s controversial use in both traditional and modern medical practices. Recent scientific studies have validated some of the plant's traditional uses. Research has shown that Argemone Mexicana exhibits a broad spectrum of biological activities, including antimicrobial⁶, antifungal, antiviral, anti-cancer⁷, hepatoprotective, and analgesic effects. Its efficacy in treating skin conditions, gastrointestinal disorders, and microbial infections has garnered interest in the pharmaceutical world, especially in developing countries where access to modern healthcare is limited. Despite its medicinal potential, Argemone mexicana is also known for its toxic properties. The seeds and oil contain toxic alkaloids, which can cause serious health issues when consumed in large amounts. One of the most notable cases of toxicity is epidemic dropsy, a condition caused by the consumption of adulterated mustard oil with Argemone oil, leading to symptoms like edema, glaucoma, cardiac failure, and even death. These toxicological risks have led to regulations limiting the use of Argemone mexicana in food and medicine. Argemone mexicana is classified as an invasive species in many parts of the world due to its ability to rapidly colonize disturbed habitats and outcompete native vegetation. This has made it a target for control measures in agricultural and conservation areas. However, its ability to thrive in poor soils and its potential use in bioremediation has prompted interest in its ecological role. Argemone mexicana stands as a plant of both great medicinal promise and considerable toxicological risk. While it has long been revered in traditional medicine for its therapeutic properties, modern science is beginning to explore its pharmacological potential. However, its toxicity remains a significant concern, necessitating careful regulation and further research into safe medicinal applications⁸.

Morphological Description:

Argemone mexicana is an erect, herbaceous annual or perennial plant that can reach heights of 1 to 1.5 meters. It often appears bushy due to multiple branching. The plant has a well-developed taproot that can penetrate deeply into the soil, allowing it to access moisture and nutrients. The stems are robust, often with a slightly woody base. They are usually green but can take on a purplish hue in some individuals. The stems are covered in a waxy coating and can have a glabrous or pubescent texture. Stems are typically armed with sharp, pointed spines, contributing to the plant’s defensive mechanisms. The leaves are alternate and can be quite large, measuring 10 to 30cm in length and 5 to 20cm in width. They are deeply lobed or divided, with irregular margins that can appear serrated or jagged. The upper surface is dark green and may have a glossy appearance, while the undersides are lighter green, often with a slightly hairy texture. The leaves have a prominent venation pattern, contributing to their distinctive lobed appearance. Flowers are borne singly or in small clusters on long, slender pedicels. Each flower is typically 7 to 12cm in diameter, with 4 to 6 large, crinkled petals that can be white, yellow, or pale purple. The center contains numerous stamens with bright yellow anthers, which are prominent and attract pollinators. The calyx consists of 2 green sepals that are typically hairy and can be spiny. The fruit is a capsule (silique) that is elongated and can be up to 5cm long. It splits open when mature, releasing several small, dark seeds that are glossy and about 1-2 mm in diameter. The seeds are covered with a mucilaginous coating, which may help in water retention and germination. Seeds are small, flat, and oval-shaped, typically measuring around 1-2mm in diameter. The seeds are dark brown in nature or say black with a shiny aapearance.⁹ Argemone mexicana is commonly found in disturbed areas, roadsides, fields, and wastelands, adapting well to a variety of soil types. While often considered a weed, it has traditional medicinal uses in some cultures, particularly in treating skin ailments¹⁰.

Taxonomical Description

Table.1 Showing the taxanomy of argemone Mexicana

Kingdom	Plantae
Sub-kingdom	Tracheobionta
Division	Magnoliophyta
Super-division	Spermatophyta
class	Magnoliopsida
Sub-class	Magnoliidae
order	Papaverales
Family	Papaveraceae
Genus	Argemone
species	Argemone Mexicana L.

Fig. 1: It represents the stem, fruit, leaves of Argemone Mexicana

Fig.2: Shows the flower of the Argemone Mexicana

Fig.3: Shows the seed of the plant argemone Mexicana

Argemone Mexicana Vernacular names^11,12

Table.2 Different names of Argemone Mexicana in different regions

Different regions	Name
Mexico	Papalotl or Papalote
United States	Mexican Poppy or California Poppy
India	Satyanashi
Pakistan	Bhangra
South Africa	African Prickly Poppy
Caribbean	Prickly Poppy

Table.3 Common names in different languages.

Sr. No.	Languages	Common names
1.	Hindi	Satyanashi
2.	Marathi	Daruri
3.	Bengali	Barashil-kantal
4.	Gujrati	Gondli
5.	Punjabi	Satyanasi
6.	Tamil	Agaram
7.	Telugu	Brahmadandi
8.	Malayalam	Kantankattiri
9.	Sanskrit	Swarnakshiri

Phytoconstituents:

Argemone mexicana is a plant renowned for its rich phytochemical profile, characterized by a variety of bioactive compounds that contribute to its traditional medicinal uses. The most prominent constituents are alkaloids, including sanguinarine, chelerythrine, and protopine^13,14,15 which are known for their diverse pharmacological activities. Sanguinarine, in particular, has demonstrated significant antimicrobial and anti-inflammatory properties, making it a focus of research in the field of natural medicine. Flavonoids, such as quercetin and kaempferol, further enrich its phytochemistry; these compounds are recognized for their potent antioxidant effects, which help combat oxidative stress and may offer protective benefits against chronic diseases. Additionally, Argemone mexicana contains various terpenoids and phenolic compounds, contributing to its overall therapeutic potential. Essential oils derived from the plant possess volatile compounds that may exhibit antimicrobial and anti-inflammatory properties, enhancing its efficacy in traditional remedies. The combination of these phytochemicals not only underscores the plant's historical use in treating ailments like skin disorders, digestive issues, and inflammation but also highlights the need for caution, as some alkaloids can be toxic in higher concentrations. Ongoing research continues to explore the specific mechanisms of action of these compounds, revealing the complex interplay between the plant's chemistry and its therapeutic applications.

Table.4 Phyto-constituents present in Argemone Mexican in different parts.^16-18

Type of compound	Chemical constituents	Derived from
Flavonoids	Rutin	Whole plant, Aerial part
	Quercetin	Aerial parts
	Isorhamnetin	Flowers
	Luteolin	seeds
	Isorhamnetin-7-O-β-Ddiglucopyanoside	Flowers
	Eriodictoyl	seeds
	Isorhamnetin-3-O-β-Dglucopyanoside	Flowers
	Isorhamnetin-3-7-O-β-Ddiglucopyanoside	Flowers
Terpenoids	β –amyrin	Leaves
Terpenoids	trans-phytol	Aerial
Steroids	β –sitosterol	Roots
Carbohydrate	Arabinose	Roots
Amino acids	Cysteine	Leaves
Amino acids	Phenylalanine	Leaves
Alcohols(long-chain)	Stearic acid	oil
	Palmitic acid	oil
	Myristic acid	oil
	Oleic acid	oil
Aromatic acids	Vannilic acid	Flower
	Tannic acid	Leaves
	5,7-dihydroxy chromone-7-neohesperidoside	Seeds
Alkaloids	Beberine	Seeds
	Sanguinarine	Seeds
	Pancorine	Aerial parts
	Jatrorrhizine	Whole plant
	Oxyhydrastinine	Whole plants
	Dehydrochorydalmine	Whole plant
	Chelerythrine	Whole plant
	Protopine	Apigeal parts, seeds
	Allocryptopine	Apigeal parts
	Reticuline	Apigeal parts
	Muramine	Whole plant
	Isocorydine	Apigeal parts
	Protomexicine	Aerial parts

Table. 5 This table shows the different chemical constituents of argemone Mexicana derived from different parts with their pharmacological activities.

S. No.	Plant parts	Chemical constituents	Pharmacological activities	Ref.
1.	Roots	β- Sitosterol	It shows anti-fungal activity and effective against leprosy inflammation as well as a potent antioxidant.	19
2.	seeds	sanguinarine	Used in dental products for prevention and treatment of gingivitis.	20
3.	Tissue	Dihydrochelerythrine	Cell cycle arrest and gives cytotoxic effect.	21
4.	Flowers	Isorhamnetin	Acts as an anti-oxidant	22
5.	Leaves	β- amyrin	Analgesic activity.	23
6.	Leaves	Berberin	Anti-bacterial, Anti-fertility, anti-inflammatory, also used in high cholesterol level and diabetes.	24
7.	Leaves	cysteine	Reduce aging on skin	25
8.	Whole plant	Dehydrocheilanthifoline	Anti-Hepatitis activity	26
9.	Whole plant	Dehydrochorydalmine	Used as a protective agent towards fungal infections.	27
10.	Roots	Arabinose	Used in treatment of some skin diseases.	28
11.	Leaves	Phenylalanine	Used in body to synthesize neurotrasmitters dopamine and nor-epinephrine.	25
12.	Aerial parts	Protomexicine	Cytotoxic activity	29
13.	Aerial parts	13-oxoprotopine	Used in treatment of neurodegenerative diseases	30
14.	Aerial parts	Higenamine	It shows activities like anti-inflammatory, anti-apoptosis, anti-fibrotic, lipid-lowering.	31
15.	Apigeal part	Isocorydine	Used as Anti-cancer	32
16.	Apigeal part	Reticuline	Anti-inflammatory and anti-cancer activities	33
17.	Apigeal part	Allocryptopine	Cell cycle arrest and anti-inflammatory activities	34
18.	Whole plant	Jatrorrhizine	Activity against hypercholesterolemia and rectal cancer also it promotes gastric motility.	35
19.	Whole plant	oxyhydrastinine	Treatment in leprosy, jaundice, dropsy.	36
20.	Aerial part	Quercetin	Anti-oncology activity, anti-parasitic properties, anti-immunosuppression activity.	37

Therapeutic effect of Argemone Mexicana:

Anti-cancer:

The extract of Argemone mexicana has shown notable anti-cancer activity in various studies, primarily attributed to its rich composition of bioactive compounds such as alkaloids, flavonoids, and saponins. Research indicates that these extracts possess significant cytotoxic effects against multiple cancer cell lines, including breast, lung, and liver cancers. For instance, studies done by Elizondo et al.,³⁸ and Gali et al.,³⁹ have reported that methanolic and ethanolic extracts of specific alkaloids from the leaves of Argemone Mexicana plant can induce apoptosis, or programmed cell death, in cancer cells like HEP-G2, L5178Y-R, MCF-7, HeLa while sparing healthy cells, which is crucial for effective cancer treatment. Additionally, extracts have been found to inhibit cell proliferation and metastasis by disrupting critical signaling pathways involved in tumor growth.

Anti-Bacterial:

Argemone mexicana exhibits notable antibacterial activity, primarily due to its diverse array of phytochemicals, including alkaloids, flavonoids, and tannins. The extracts most commonly studied for their antibacterial properties are the Methanolic, chloroform, n-hexane and aqueous. More N et al.,⁴⁰ took leaf methanolic extract of the plant Argemone Mexicana and also aqueous leaf extract and tested both the extracts against some bacteria like E. coli, Staphylococcus aureus, Bcillus aureus, Pseudomonas aeruginosa, both the extract was poured into the the plate in which the bacterial culture was grown and kept aside for 24hr at 37ᵒC. After 24hr it was found that both aqueous and methanolic extracts have shown significant result and this proves that the leaves extract of the Argemone Mexicana has antibacterial activity.

Anti-Malarial:

The investigation of antiplasmodial compounds from Argemone mexicana, a member of the Papaveraceae family, has garnered interest due to its traditional use in folk medicine and the increasing resistance of malaria parasites to conventional treatments. Research has focused on isolating and characterizing bioactive compounds from various extracts of the plant, particularly methanolic and ethanolic extracts from its leaves and seeds. Simoes Avello et al.,⁴¹ Studied had revealed that Argemone mexicana contains a variety of alkaloids, flavonoids, and other phytochemicals that exhibit antiplasmodial activity. Specific alkaloids, such as allocryotopin, protopine and berberine have been identified as potent inhibitors of Plasmodium falciparum, the parasite responsible for the most severe form of malaria. In vitro assays have demonstrated that these compounds can significantly reduce parasite viability, with effective concentrations often ranging from 50 to 200µg/mL. Additionally, the mechanism of action appears to involve interference with the parasite's metabolic pathways, possibly by inducing oxidative stress or disrupting mitochondrial function.

Anti-Fungal:

The antifungal activity of quaternary alkaloids isolated from Argemone mexicana has been a subject of significant interest due to the plant's traditional use in managing fungal infections. Research done by Sarita singh et al.,⁴² has focused on characterizing a mixture of these alkaloids, which include compounds such as sanguinarine, chelerythrine, and others. Studies have demonstrated that these quaternary alkaloids exhibit notable antifungal properties against various phytopathogenic fungi, including species of Fusarium, Aspergillus, and Candida. The antifungal efficacy of these alkaloids is attributed to their ability to disrupt fungal cell membranes, inhibit spore germination, and interfere with fungal growth and reproduction. In laboratory assays, the minimum inhibitory concentrations (MICs) of the alkaloid mixtures have been found to be effective at concentrations typically ranging from 50 to 300µg/mL, depending on the specific fungal species. Moreover, the mechanism of action often involves inducing oxidative stress within the fungal cells, leading to cellular damage and eventual cell death. The synergistic effects of the alkaloids may also enhance their overall antifungal activity. While results are promising, further studies are necessary to explore the pharmacological potential, optimal formulations, and safety profiles of these quaternary alkaloids for practical applications in agriculture and medicine. This could pave the way for developing natural antifungal agents that are effective against resistant fungal strains.

Anti-Inflammatory:

Mengine Ayele T et al.,⁴³ did evaluation of in vivo anti-inflammatory activities of solvent fractions from the fruits of Argemone mexicana has revealed promising results in mitigating inflammation. Various solvent extraction methods, such as methanol, ethanol, and aqueous extraction, have been employed to isolate the bioactive compounds present in the fruit. These extracts are rich in phytochemicals, including alkaloids, flavonoids, and phenolic compounds, known for their potential therapeutic effects. In preclinical studies, these solvent fractions have been tested in animal models of inflammation, such as paw edema induced by carrageenan or formalin. Results indicate that the extracts significantly reduce inflammatory markers and symptoms, including swelling and pain, compared to control groups. The mechanisms underlying these anti-inflammatory effects are believed to involve the inhibition of pro-inflammatory cytokines and enzymes, such as cyclooxygenase (COX) and lipoxygenase (LOX), which play critical roles in the inflammatory response. Dosing studies have shown that the effectiveness of the extracts varies, with optimal anti-inflammatory activity observed at specific concentrations, often within the range of 100 to 400 mg/kg body weight. Additionally, histopathological evaluations have demonstrated a reduction in inflammatory cell infiltration and tissue damage in treated animals.

Anti-Asthmatic Effect:

The evaluation of the anti-asthmatic activity of the ethanolic extract of Argemone mexicana stems has gained attention due to the plant's traditional use in treating respiratory ailments. Rohit et al.,⁴⁴ has found that on assessing the extract's efficacy in alleviating asthma-related symptoms through various experimental models. In studies involving animal models, the ethanolic extract and chloroform extract are typically administered to subjects experiencing asthma-like conditions, often induced by agents such as histamine or allergen exposure. The extract is observed for its effects on parameters such as bronchoconstriction, airway hyperresponsiveness, and inflammatory cell infiltration in lung tissues. Key findings indicate that the ethanolic extract exhibits significant bronchodilatory effects, helping to relax the bronchial smooth muscles and improve airflow. This is believed to be mediated through the inhibition of inflammatory mediators such as leukotrienes and prostaglandins, which are critical in the pathophysiology of asthma. Additionally, the extract may enhance the activity of antioxidant enzymes, reducing oxidative stress in the airways, which is often elevated in asthmatic conditions. Furthermore, histopathological studies of lung tissues from treated animals typically show a reduction in inflammation, mucus hypersecretion, and structural remodeling associated with chronic asthma. The effective dosage for achieving significant anti-asthmatic activity often falls within the range of 200 to 500mg/kg body weight. Overall, the ethanolic extract of Argemone mexicana stems demonstrates considerable potential as a natural anti-asthmatic agent.

Anti-HIV:

Chang et al.,²¹ discovered two new protopines, argemexicaines A and B, alongside the anti-HIV alkaloid 6-acetonyldihydrochelerythrine, from Formosan Argemone mexicana adds significant value to the understanding of this plant's pharmacological potential. Argemexicaines A and B are newly identified protopine alkaloids. Protopines are a class of alkaloids known for various biological activities, including antimicrobial and anti-inflammatory properties. 6-Acetonyldihydrochelerythrine. a known benzo[c] phenanthridine alkaloid with demonstrated anti-HIV activity, this alkaloid has shown significant anti-HIV effects in vitro, with an EC50 value of 1.77μg/mL and a therapeutic index of 14.6, indicating its potential as a candidate for further development in HIV treatment. The presence of these alkaloids supports the potential of Argemone mexicana as a source of new therapeutic agents, particularly for viral infections like HIV.Sudeep et al.,⁴⁵researches into Argemone Mexicana potential anti-HIV activity has gained interest due to its phytochemical composition. Studies done by them suggested that compounds in Argemone mexicana may interfere with the HIV life cycle, potentially inhibiting reverse transcriptase and protease enzymes that are crucial for viral replication. The antioxidant activity of the phytochemicals may protect immune cells from oxidative stress, which is crucial in HIV-positive individuals.

Anti-Fertility:

Gupta RS et al.,⁴⁶ founded that Argemone mexicana contains several isoquinoline alkaloids, such as sanguinarine, chelerythrine, and others, thry got to know that the Isoquinoline alkaloids may interfere with the hypothalamic-pituitary-gonadal (HPG) axis, leading to altered secretion of reproductive hormones like estrogen and progesterone. This disruption can affect the regularity of the menstrual cycle and ovulation. Studies have shown that these alkaloids can induce ovarian dysfunction, potentially leading to conditions such as anovulation. Changes in follicular development and corpus luteum function may also occur. Alkaloids from Argemone mexicana may cause changes in uterine morphology and function, impacting the endometrium and potentially reducing implantation success. In male studies, isoquinoline alkaloids have been shown to affect spermatogenesis, leading to decreased sperm count and motility, which can contribute to infertility. Various studies on animal models (like Wistar rats, dogs) have demonstrated that administration of isoquinoline alkaloids can lead to significant reductions in fertility parameters, including decreased ovulation rates and changes in estrous cycles. The effects of isoquinoline alkaloids are often dose-dependent, with higher concentrations leading to more pronounced antifertility effects. The duration of exposure also plays a critical role in the extent of these effects. Isoquinoline alkaloids from Argemone mexicana exhibit significant antifertility effects through hormonal disruption, impacts on ovarian and uterine function, and alterations in spermatogenesis.

Hepatoproptective:

The hepatoprotective effect of Argemone mexicana Linn has been studied due to its traditional use in herbal medicine for liver-related ailments. Ali SA et al.,⁴⁷ did the evaluation of the hepatoprotective action of Argemone mexicana Linn, specifically they used root bark, in assessing its potential to protect the liver from damage caused by various hepatotoxic agents, for that they collected and dried the root bark of Argemone mexicana. Prepare an ethanolic or aqueous extract using appropriate solvent extraction methods. Divided Wistar rats into several groups, Control group (no treatment), Hepatotoxic group (exposed to a known hepatotoxin, e.g., carbon tetrachloride {CCl₄}), Treatment group (receiving the extract at various doses). Administer the extract for a specific duration, typically 4-8weeks, alongside the hepatotoxic agent. Measured serum levels of liver enzymes (ALT, AST, ALP), bilirubin, and other markers of liver function. Analyzed liver tissue samples for signs of damage, such as necrosis, fatty infiltration, and inflammation. Assessed levels of antioxidant enzymes (e.g., superoxide dismutase, catalase) and malondialdehyde (MDA) to evaluate oxidative stress. The extract lead to reduced levels of liver enzymes in treated rats compared to the hepatotoxic group, indicating protective effects on liver function.

Wound Healing:

Saravanan R et al.,⁴⁸ founded that the leaves of Argemone mexicana when subjected to various extraction methods, such as maceration with solvents like ethanol and water gives those extracts which helps in wound healing. To assess the wound healing activity, they did in-vivo studies using animal models, typically Wistar rats. The rats were divided into groups, with one group receiving the leaf extract topically on induced wounds, while the control group received a standard treatment or no treatment. The application of Argemone mexicana leaf extract significantly enhanced the rate of wound closure compared to the control group. Measurements taken at regular intervals indicated faster healing in the treated group. Tissue samples from the wound site were analyzed microscopically. The treated group showed increased fibroblast proliferation, collagen deposition, and reduced inflammation, indicating effective tissue regeneration. Levels of oxidative stress markers were assessed, showing that the extract significantly reduced oxidative damage in the wound tissue. Increased levels of antioxidant enzymes were also observed, supporting the extract's role in mitigating oxidative stress. The preliminary phytochemical investigation confirmed that the leaves of Argemone mexicana contain various bioactive compounds that contribute to their pharmacological potential. The wound healing activity demonstrated significant improvement in wound closure rates and tissue regeneration in animal models. These findings support the traditional use of Argemone mexicana in wound care and suggest that its leaf extract could be a promising natural agent for enhancing wound healing.

Anti-Diabetic:

Chanda P et al.,⁴⁹ evaluated the hypoglycemic activity of the Argemone Mexicana plant by taking the ethanolic or aqueous extract of the aerial part of the plant, for this Diabetic rat models, typically induced by streptozotocin (STZ) or alloxan, are commonly used to evaluate the antidiabetic activity of Argemone mexicana extracts. Rats are divided into groups: a control group (diabetic without treatment), a standard treatment group (administered with a known antidiabetic drug), and one or more groups receiving various doses of Argemone mexicana extract. Aerial parts of the plant are harvested, dried, and extracted using solvents such as ethanol or water. The extract is then administered orally or intraperitoneally for a specified duration (e.g., 4-8 weeks). Dose of 200mg/kg to 400mg/kg of Argemone Mexicana aerial parts extract decreases the blood glucose level in experimentally induced diabetic rats. Extract treatment may enhance insulin sensitivity, leading to better glucose uptake in peripheral tissues. Increased insulin levels have been observed in studies. Treated rats frequently exhibit improved lipid profiles, with reductions in total cholesterol and triglycerides, indicating a positive effect on metabolic health. Adult male Wistar rats are induced with diabetes using alloxan (typically at a dose of 150-200mg/kg). The aerial parts of Argemone mexicana are harvested, dried, and extracted using suitable solvents (e.g., ethanol, water) through maceration or soxhlet extraction. Rats treated with Argemone mexicana extracts show a significant decrease in fasting blood glucose levels compared to the control group, indicating effective glycemic control.

Antioxidant:

Reactive Oxygen Species (ROS) are highly reactive molecules derived from oxygen that play critical roles in various biological processes. While they are essential for normal cellular functions, their excessive accumulation can lead to oxidative stress, contributing to a variety of diseases. ROS act as secondary messengers in various signaling pathways, influencing processes like cell growth and apoptosis. They play a role in the immune response by helping to eliminate pathogens. ROS are involved in regulating metabolic pathways and cellular homeostasis. Excessive ROS can overwhelm the body’s antioxidant defenses, leading to oxidative stress, which is implicated in Conditions like diabetes, cardiovascular diseases, and cancer. ROS contribute to the pathophysiology of diseases like Alzheimer’s and Parkinson’s. Reactive Oxygen Species are crucial for various biological processes but can cause significant cellular damage when produced in excess. To get rid of this problem naturally Perumal P et al.,⁵⁰ performed an experiment in which he collected, washed, and dried, roots of Argemone Mexicana. The dried roots are then ground into a powder and extracted using solvent 95% ethanol through method soxhlet extraction. Various assays employed to evaluate the antioxidant activity of the extracts, DPPH Radical Scavenging Assay, ABTS Assay, and H₂O₂ assay. DPPH Radical Scavenging Assay, measures the ability of the extract to donate electrons to the DPPH radical, leading to a color change. The percentage inhibition is calculated to assess antioxidant capacity. ABTS Assay, similar to the DPPH assay, this measures the scavenging ability of the extract against the ABTS radical cation. Extracts from the roots of Argemone mexicana typically demonstrate a significant capacity to scavenge DPPH radicals, with percentage inhibition correlating with the concentration of the extract. The results from the ABTS assays further confirm the antioxidant potential of the root extracts, showing effective reducing power and radical scavenging capabilities.

Vasoconstrictor and Vasorelaxant:

Alkaloids in Argemone mexicana may activate alpha-adrenergic receptors on vascular smooth muscle, leading to vasoconstriction. This process involves increased intracellular calcium levels, resulting in muscle contraction. Compounds may enhance calcium influx or release from intracellular stores in vascular smooth muscle cells, promoting contraction and vasoconstriction. The plant's extracts may affect endothelial cells, leading to altered production of vasoconstrictors like endothelin. Magos-Guerrero et al.,⁵¹ isolated rat aorta preparations and found that Argemone mexicana extracts can induce significant contractions, particularly at higher concentrations. Animal models have demonstrated increased blood pressure or vascular resistance following administration of the plant extracts, indicating vasoconstrictor effects. Flavonoids and other compounds may enhance the release of endothelium-derived relaxing factors (e.g., nitric oxide), promoting vasodilation. Some constituents may inhibit calcium channels in vascular smooth muscle, leading to relaxation. The presence of antioxidants can neutralize reactive oxygen species (ROS) that promote vasoconstriction, thus facilitating relaxation. In isolated vascular preparations, extracts of Argemone mexicana have shown the ability to relax pre-contracted vessels, indicating vasorelaxant properties. These effects may be concentration-dependent. Animal studies may reveal a decrease in blood pressure or improved blood flow following administration of the plant, suggesting beneficial vasorelaxant effects. Lower concentrations may exhibit vasorelaxant effects, while higher concentrations could lead to vasoconstriction. The vasoconstrictor and vasorelaxant activities of Argemone mexicana suggest its potential utility in managing cardiovascular conditions.

Effect on electrically induced contractions of isolated Guinea-pig ileum:

Sonia P et al.,⁵² did experiment on Guinea pigs in which Guinea pigs are euthanized, and segments of the ileum are isolated. The ileal tissues are prepared and placed in an organ bath filled with physiological saline, maintained at a constant temperature. Electrical stimulation is applied to the ileum to induce contractions. The contractile responses are recorded using a force transducer connected to a computer for data acquisition. Different concentrations of alkaloids (e.g., sanguinarine, chelerythrine) are administered to the organ bath before or during electrical stimulation to assess their effects on contraction amplitude and frequency. The amplitude, frequency, and duration of contractions are measured and compared to control responses (saline). Sanguinarine is observed to enhance the amplitude of electrically induced contractions in a dose-dependent manner. This suggests a stimulatory effect on smooth muscle activity, likely involves increased calcium influx or enhanced sensitivity of the muscle to calcium. Chelerythrine may exhibit a more complex effect, potentially inhibiting contractions at higher concentrations. This could indicate a dual role depending on the concentration used. This alkaloid might block calcium channels, reducing muscle contractility. A general trend is noted where lower concentrations may stimulate contractions while higher concentrations may inhibit them, suggesting a biphasic response to isoquinoline alkaloids. Isoquinoline alkaloids from Argemone mexicana demonstrate diverse effects on electrically induced contractions of the isolated guinea pig ileum. Sanguinarine typically enhances contraction, while chelerythrine may inhibit it at higher doses.

Nematicidal:

Nematodes induce galls on plant roots, leading to nutrient and water uptake issues. They are widespread agricultural pests. They form cysts in the soil and can cause significant damage to crops like soybeans and potatoes. They invade roots, causing lesions and leading to plant stress and reduced yields. Decreased crop quality and production lead to financial losses for farmers. Infestations can cause stunting, yellowing, and wilting of plants. Disruption of soil ecosystems, as harmful nematodes can alter microbial communities and soil health. In humans, parasitic nematodes can cause gastrointestinal disturbances, malnutrition, and other health complications. Animal infections can lead to severe health issues, affecting livestock productivity and pet health. Shahid Shaukat et al.,⁵³ founded that the alkaloids in Argemone mexicana can penetrate the nematode cuticle, leading to paralysis or death. Sanguinarine, in particular, has shown promising nematicidal effects by disrupting metabolic processes. Some alkaloids may interfere with the nervous system of nematodes, impairing their movement and ability to feed, which can lead to mortality. The presence of certain phytochemicals may deter nematodes from feeding(Anti-feedant) property on plant roots, reducing their overall impact on crop health. Laboratory assays using nematodes, such as Meloidogyne and Heterodera, have demonstrated significant mortality rates when exposed to extracts of Argemone mexicana. Dose-response experiments indicate that higher concentrations of the extracts correlate with increased nematicidal activity. Field trials have shown that incorporating Argemone mexicana extracts into soil can reduce nematode populations, leading to improved plant health and crop yields.

Larvicidal:

Larvae, the juvenile stage of many insects and other arthropods. Many larvae, such as those of moths and beetles, feed on crops, leading to significant agricultural losses. They can cause damage by eating leaves, stems, roots, and fruits. Larvae can cause extensive defoliation, reducing photosynthesis and ultimately affecting plant health and yield. Mosquito larvae (e.g., Aedes aegypti, Culex quinquefasciatus) can develop into adults that transmit diseases such as malaria, dengue fever, Zika virus, and West Nile virus. Larvae, like those of the caterpillar species, can sting or bite, causing skin irritation, allergic reactions, or even severe pain. Carlos A Granados et al.,⁵⁴ studied and found that the flower extract of the plant Argemone mexicana can penetrate the larvae's cuticle, leading to mortality. Sanguinarine has been particularly noted for its toxicity against mosquito larvae. Alkaloids may affect the nervous system of the larvae, leading to paralysis or impaired movement. Laboratory assays have demonstrated that flower extract extracts of Argemone mexicana exhibit significant larvicidal activity against various species, such as Aedes aegypti and Culex quinquefasciatus. Mortality rates are often evaluated after exposure to different concentrations of the extract over specific time periods. Higher concentrations of the extracts generally correlate with increased larval mortality, indicating a dose-dependent effect. Argemone mexicana demonstrates promising larvicidal activity, primarily attributed to its alkaloid and phytochemical content. Its effectiveness against mosquito larvae makes it a potential candidate for sustainable pest control strategies.

Mollucicidal:

Molluscs are a diverse group of invertebrates belonging to the phylum Mollusca. This phylum includes a wide variety of organisms, such as snails, clams, squids, and octopuses. The defining feature of mollusks is their soft bodies, which are often protected by a hard shell. Molluscs can cause Schistosomiasis, Fascioliasis, Foodborne Illness. Certain molluscs, especially terrestrial and freshwater snails, can damage crops by feeding on plants. They can lead to reduced crop yields and economic losses for farmers. Compounds from Argemone mexicana can penetrate the soft bodies of snails, leading to paralysis and death as per the study done by Afroz A et al.,⁵⁵ and Sunanda K et al.,⁵⁶. Sanguinarine has been particularly noted for its effectiveness in this regard. The alkaloids may affect the respiratory systems of snails, impairing their ability to breathe and resulting in asphyxiation. Saponins and other phytochemicals can compromise cellular integrity, leading to leakage of cellular contents and eventual death. Exposure to the plant's extracts may disrupt normal growth and reproductive functions in molluscs, reducing their populations over time. Argemone mexicana exhibits significant molluscicidal activity, primarily attributed to its alkaloid and phytochemical content. Its effectiveness against freshwater snails highlights its potential as a natural control agent for managing disease vectors.

Table.6 Researchers and their findings on Argemone Mexicana

S. No	Researcher/year	Findings	Ref.
1.	Elizondo et al., 2024	In Vitro Effect of Methanolic Extract of Argemone mexicana Against Trichomonas vaginalis. Trichomonas vaginalis is a flagellated protozoan parasite responsible for trichomoniasis, a common sexually transmitted infection. Conventional treatments often face challenges such as drug resistance and side effects, prompting interest in alternative therapies, including plant-based remedies like Argemone mexicana. Methanolic extract leaves are taken in concentration (0.5, 1, 3, 5)mg/ml. Methanolic extract of Argemone mexicana shows significant inhibitory effects on T. vaginalis growth in a dose-dependent manner. Higher concentrations of the extract lead to increased mortality and reduced motility of the protozoa.	57
2.	Ojija F et al., 2023	The results show that the Argemone Mexicana L crude extracts inhibited the germination of both P. vulgaris and Z. mays at higher concentrations 75% and 100%,.Fewer seeds of these two species germinated at these concentrations compared to the lower concentrations (25% and 50%) and the control group (0%). This suggests that as the concentration of AmL crude extract increased, the germination of Z. mays and P. vulgaris seeds decreased. Overall, compared to seeds germinating at higher concentrations (P. vulgaris: F(4,20) = 5.28, p = 0.0046; Z. mays: F(4,20) = 21.57, p < 0.0001), fewer seeds germinated at lower concentrations (i.e., 25% and 50%) and in the control.	58
3.	Fawehinmi AB et. al. 2022	The anti-microbial potential of Argemone mexicana is evaluated against various microorganisms, including bacteria and fungi, common pathogens such as Escherichia coli, Staphylococcus aureus, and Salmonella typhi, Candida albicans and Aspergillus niger. Methanolic extracts are prepared by soaking the plant material in the solvent and filtering the solution. Filter paper discs soaked in the extract are placed on agar plates inoculated with the target microorganisms. Zones of inhibition are measured to assess the anti-microbial activity. The extract typically shows varying degrees of effectiveness against bacterial strains, with Staphylococcus aureus often being particularly susceptible. The extract may exhibit antifungal properties, with significant inhibition of growth observed for fungi like Candida albicans.	59
4.	Nayeli MB et al. 2021	This overview explores Argemone Mexicana impact on local edema and lipopolysaccharide (LPS)-induced neuroinflammation. Lipopolysaccharides (LPS), found in the outer membrane of Gram-negative bacteria, can trigger an inflammatory response in the nervous system, leading to neuroinflammation and associated neurodegenerative conditions. Leaves of Argemone mexicana are collected, dried, and subjected to extraction using solvents ethanol. Local edema is often induced in animal models rats through subcutaneous injection of an irritant (e.g., carrageenan). Neuroinflammation is induced by administering LPS intraperitoneally. Animals are divided into groups, including control, LPS-treated, and those treated with varying doses of Argemone mexicana extract. The degree of swelling is measured at specific time intervals after induction. Tissue samples are analyzed for cytokine levels, oxidative stress markers, and histopathological changes. Argemone mexicana extracts significantly reduces the volume of edema compared to control groups. The extract shows a marked decrease in levels of pro-inflammatory cytokines in brain tissue. Histological examinations reveal reduced signs of inflammation, such as microglial activation and neuronal damage. The reduction in cytokine levels and oxidative stress markers supports the anti-inflammatory potential of the extract.	60
5.	Pandeya et al. 2020	Study was done on Natural RNA-dependent RNA polymerase (RdRp) inhibitors are crucial in the development of antiviral therapies, particularly against RNA viruses. The alkaloids present in Argemone mexicana have shown potential biological activity that could be explored for this purpose. Obtained the 3D structure of RdRp from databases like the Protein Data Bank (PDB). Analyzed known binding sites or perform site-directed mutagenesis to identify key residues involved in RNA synthesis. Molecular docking studies of biologically active alkaloids from Argemone mexicana provided valuable insights into their potential as therapeutic agents, particularly against RNA viruses like HCV or SARS-CoV-2.	61
6.	Haruna Y et al. 2019	The characterization of antioxidant activity in methanol extracts of Argemone mexicana leaves involves several key steps. First, the leaves are extracted using methanol, followed by phytochemical screening to identify active compounds such as flavonoids and phenolics. Antioxidant activity is assessed through various assays, including the DPPH radical scavenging assay, ABTS radical cation assay, and Ferric Reducing Antioxidant Power (FRAP) assay, with results expressed in terms of IC50 values and total phenolic and flavonoid content. The findings suggest that the methanol extract possesses significant antioxidant properties, potentially due to its rich phytochemical composition, indicating its usefulness for further research and potential health applications.	62
7.	Castro-Rios R et al. 2018	The in vitro study of the antiamoebic activity of methanol extracts from Argemone mexicana focuses on their effects against the trophozoites of Entamoeba histolytica HM1-IMSS, the causative agent of amoebic dysentery. The study involves preparing methanol extracts from the leaves of Argemone mexicana and assessing their efficacy against E. histolytica trophozoites through various concentration gradients. The viability of trophozoites is evaluated using methods such as trypan blue exclusion or MTT assays, allowing researchers to determine the extract's inhibitory concentration (IC50) and the mechanism of action. Results indicate that the extracts exhibit significant antiamoebic activity, potentially due to the presence of bioactive compounds such as alkaloids and flavonoids, which may disrupt trophozoite metabolism or integrity. This research highlights the potential of Argemone mexicana as a natural therapeutic option for treating amoebic infections and encourages further exploration of its active constituents and mechanisms of action.	63
8.	Gabriela JD et al. 2017	The in-vitro assessment of Argemone mexicana against Haemonchus contortus, a significant gastrointestinal nematode affecting livestock, investigates the efficacy of its extracts on both nematode eggs and infective third-stage larvae (L3). Utilizing methanol extracts from the leaves of Argemone mexicana, researchers conduct assays to evaluate the nematicidal properties of the compounds present. The study involves exposing H. contortus eggs and L3 larvae to varying concentrations of the extract, followed by monitoring egg hatchability and larval motility. Results indicate that the extract significantly inhibits the hatching of nematode eggs and reduces the motility of L3 larvae in a dose-dependent manner, suggesting a potent anthelmintic effect. Phytochemical analysis reveals the presence of alkaloids and flavonoids, which may contribute to the observed nematicidal activity. The findings highlight the potential of Argemone mexicana as a natural anthelmintic agent, offering an alternative to synthetic drugs in managing parasitic infections in livestock. This study underscores the need for further research into the active constituents of the plant and their mechanisms of action to develop effective, sustainable strategies for controlling Haemonchus contortus and other nematodes.	64
9.	Arcos-Martinez et al. 2016	The study investigates the anxiolytic-like effects of ethanolic extracts of Argemone mexicana, a plant known for its medicinal properties, and its alkaloids in Wistar rats. The research aims to evaluate how these extracts influence anxiety-related behaviors. By administering varying doses of the extract and its isolated alkaloids, the study assesses their impact on animal models using established anxiety tests, such as the elevated plus maze and the open field test. Results indicate a significant reduction in anxiety-like behaviors, suggesting that Argemone mexicana and its alkaloids may possess anxiolytic properties. This study contributes to the understanding of natural compounds in anxiety management, potentially offering alternative therapeutic options in psychiatric care. The only extracts that produced anxiety-reducing effects similar to a 2 mg/kg dose of diazepam in the Elevated Plus Maze (EPM) test were the ethanolic extract at 200 mg/kg and the alkaloid-enriched extract at 200 µg/kg. These extracts did not affect the movement of the subjects. However, the anxiety-reducing effects of the plant's alkaloid-enriched extract were blocked when picrotoxin was administered.	65
10.	Bapna S et al. 2015	The study examines the antiplasmodial activity of Argemone mexicana through both in vivo and in vitro approaches. Researchers aimed to evaluate the effectiveness of the plant's extracts against the malaria-causing parasite Plasmodium, particularly focusing on its active compounds. In vitro assays assessed the direct effects of the extracts on parasite viability, while in vivo experiments involved administering the extracts to infected animal models to observe reductions in parasitemia and associated symptoms. The findings reveal significant antiplasmodial activity, indicating that Argemone Mexicana may inhibit the growth and proliferation of the malaria parasite. These results support the potential use of this plant as a natural remedy for malaria treatment, highlighting the need for further studies to isolate specific active compounds and understand their mechanisms of action. This research contributes to the search for alternative antimalarial therapies, especially in regions where resistance to conventional drugs is prevalent.	66
11.	Namkeleja et al. 2014	This review examines the allelopathic effects of Argemone mexicana on the growth of native plant species, focusing on the allelochemicals produced by the plant and their impact on seed germination, seedling development, and chlorophyll content. Argemone mexicana, a widely studied invasive species, is known to release secondary metabolites that can inhibit the growth of surrounding flora. The review synthesizes findings from various studies highlighting the specific allelochemicals identified in Argemone mexicana, such as salicylic acid, Vanillic acid, cinnamic acid, and p-hydroxybenzoic acid. The review discusses how these allelochemicals affect seed germination by inhibiting enzyme activity and altering hormonal balance in native plant species, leading to reduced germination rates and delayed emergence. Furthermore, the impact of these compounds on seedling growth is explored, revealing that exposure to Argemone mexicana extracts can stunt root and shoot development, decrease biomass accumulation, and affect overall plant vigor. The review also emphasizes the correlation between allelochemical exposure and chlorophyll content, noting that native species exposed to these compounds often exhibit reduced chlorophyll levels, which can impair photosynthesis and further hinder growth. the review underscores the ecological implications of Argemone mexicana’s allelopathic effects, particularly in ecosystems where it is invasive. By negatively affecting native plant species, it can disrupt local biodiversity and alter habitat dynamics. The authors call for more in-depth research into the specific mechanisms of allelochemical action, as well as strategies for managing Argemone mexicana in affected areas, to preserve native flora and maintain ecological balance.	67
12.	Warikoo R et al. 2013	The researchers focus on the impact of Argemone mexicana extracts on the cidal, morphological, and behavioral responses of the dengue vector, Aedes aegypti L. The study highlights the growing concern over dengue fever and the need for sustainable vector control methods, particularly in light of increasing resistance to conventional insecticides. In their review they systematically examine various extracts from Argemone mexicana, including ethanolic, aqueous, and methanolic extracts, and their effects on different life stages of Aedes aegypti, such as larvae, pupae, and adults. Results indicate that these extracts possess significant larvicidal and adulticidal properties, effectively reducing mosquito populations. The review discusses the concentration-dependent efficacy of the extracts, with higher concentrations yielding greater mortality rates. Morphological alterations in the mosquitoes exposed to Argemone mexicana extracts are also addressed. The review details observed changes in larval and pupal structures, including deformities in appendages and pigmentation, which may hinder development and survivability. These morphological changes suggest that the extracts disrupt normal physiological processes, further contributing to their cidal effects. Additionally, the review explores the behavioral responses of Aedes aegypti to the extracts. Exposure to Argemone mexicana has been shown to affect feeding behavior, locomotion, and mating patterns, potentially leading to decreased reproductive success and population dynamics. The authors note that these behavioral changes may enhance the effectiveness of the extracts as a natural control strategy.	68
13.	Sourabie TS et al. 2012	This study evaluates the anti-icterus effect of the crude powdered leaf of Argemone mexicana L. (family: Papaveraceae) in the context of carbon tetrachloride (CCl₄)-induced liver injury in rats. CCl₄ is commonly used to induce liver damage in experimental models, mimicking conditions such as hepatitis and liver fibrosis, which often result in jaundice (icterus). The research aimed to assess whether the administration of Argemone mexicana could mitigate liver injury and its associated symptoms. The study involved a controlled experimental setup where Wistar rats were divided into several groups: a control group, a CCl₄-treated group, and groups treated with varying doses of the powdered leaf extract after CCl₄ exposure. Key findings of the study included significant reductions in serum markers of liver injury, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), in rats treated with the Argemone mexicana extract compared to the untreated CCl₄ group. These biochemical markers are indicative of hepatocellular damage, and their normalization suggests a protective effect of the plant extract on liver function. Histopathological analyses revealed that rats receiving the extract exhibited less severe liver damage, with reduced inflammatory cell infiltration and preservation of liver architecture compared to the CCl₄ group. Additionally, the extract showed antioxidant properties, evidenced by increased levels of reduced glutathione (GSH) and decreased lipid peroxidation, which collectively contribute to the hepatoprotective effect. The study also explored the potential mechanisms underlying the anti-icterus effect of Argemone mexicana, suggesting that its bioactive compounds may exert hepatoprotective activities by modulating oxidative stress and inflammation. At last, the findings support the traditional use of Argemone mexicana in herbal medicine as a remedy for liver-related ailments. The study underscores its potential as a natural therapeutic agent against CCl₄-induced liver injury, warranting further investigation into its active constituents and mechanisms of action for potential applications in hepatoprotection and liver health.	69
14.	Anarthe S et al. 2011	The neuropharmacological study of Argemone mexicana Linn. investigates the plant's effects on the central nervous system, aiming to understand its potential therapeutic applications for neurological disorders. Argemone mexicana, known for its traditional medicinal uses, has garnered interest for its bioactive compounds, including alkaloids and flavonoids, which may exert neuroprotective, anxiolytic, or analgesic effects. The study typically involves a range of experimental models to evaluate the plant's impact on various neuropharmacological parameters. Researchers often employ behavioral tests to assess anxiolytic and antidepressant activities, utilizing models such as the elevated plus maze, open field test, and forced swim test. Findings from these tests suggest that extracts from Argemone mexicana can significantly reduce anxiety-like behaviors and depressive symptoms, indicating its potential use as a natural anxiolytic or antidepressant. In addition to behavioral assessments, the study often examines the effects of Argemone mexicana on neurochemical markers. Researchers analyze changes in neurotransmitter levels, such as serotonin, dopamine, and norepinephrine, which are critical for mood regulation and anxiety responses. The plant's extracts may enhance the availability of these neurotransmitters, contributing to its therapeutic effects. Furthermore, the study explores the antioxidant properties of Argemone mexicana, assessing its ability to reduce oxidative stress in neural tissues. Oxidative stress is implicated in various neurodegenerative diseases, and the plant’s bioactive compounds may help mitigate damage by scavenging free radicals and enhancing antioxidant defenses. Histopathological examinations may also be included, where brain tissues from treated and untreated groups are analyzed to observe structural changes. These analyses help elucidate the neuroprotective effects of the extracts, showing potential reductions in neuronal damage and inflammation. Overall, the neuropharmacological study of Argemone mexicana provides evidence supporting its traditional use in managing neurological conditions. The findings suggest that this plant may possess promising anxiolytic, antidepressant, and neuroprotective properties.	70
15.	Osho A et al. 2010	The study on the antimicrobial activity of the essential oil of Argemone mexicana Linn. explores its potential as a natural antimicrobial agent against various pathogenic microorganisms. Argemone mexicana, recognized for its traditional medicinal uses, has drawn scientific interest due to the bioactive compounds present in its essential oil, which may exhibit significant antimicrobial properties. The research typically begins with the extraction of essential oil from the leaves or flowers of Argemone mexicana using methods such as steam distillation or hydro-distillation. The chemical composition of the essential oil is analyzed using techniques like gas chromatography-mass spectrometry (GC-MS) to identify the specific compounds present, such as alkaloids, terpenes, and phenolic compounds, which are often responsible for antimicrobial activity. The antimicrobial efficacy of the essential oil is then evaluated against a range of pathogenic microorganisms, including bacteria (both gram-positive and gram-negative), fungi, and possibly viruses. Commonly tested pathogens might include Staphylococcus aureus, Escherichia coli, Candida albicans, and Pseudomonas aeruginosa. The study employs standard methods such as the disk diffusion method, broth dilution method, or agar well diffusion method to determine the minimum inhibitory concentration (MIC) and the zone of inhibition for the essential oil against these microorganisms. Results from the study often demonstrate that the essential oil exhibits significant antimicrobial activity, with varying degrees of effectiveness depending on the type of microorganism tested. For example, the oil may show stronger activity against gram-positive bacteria compared to gram-negative bacteria, which is commonly attributed to the structural differences in their cell walls. The review may also delve into the mechanisms by which the essential oil exerts its antimicrobial effects. These mechanisms could include disruption of microbial cell membranes, interference with metabolic pathways, or inhibition of biofilm formation, which is critical for the survival and virulence of many pathogens. In addition to antimicrobial tests, the study may assess the safety and toxicity of the essential oil through cytotoxicity assays to ensure its potential for use in therapeutic applications. The review also considers the implications of using Argemone mexicana essential oil as a natural preservative in food or a complementary treatment in clinical settings, given the growing resistance to synthetic antibiotics.	71
16.	Bhalke RD et al. 2009	In their article they explained about how Argemone Mexicana stem extracts gives anti-stress and anti-allergic effect in asthama. Asthma is a chronic respiratory disease characterized by inflammation and narrowing of the airways, often triggered by allergens, stress, and environmental factors. Traditional asthma treatments focus on bronchodilation and anti-inflammatory effects, but many patients seek complementary therapies due to limitations and side effects associated with conventional medications. Argemone mexicana, a plant used in various traditional medicine systems, has gained attention for its potential pharmacological properties. The review begins by highlighting the relationship between stress and asthma, noting that stress can trigger or worsen asthma symptoms. The active compounds in Argemone mexicana stems, such as alkaloids and flavonoids, may possess anxiolytic properties, helping to reduce stress and promote relaxation. Animal studies indicate that extracts from the plant can lower levels of stress hormones and modulate neurotransmitter activity, which could alleviate stress-induced asthma exacerbations. The antiallergic effects of Argemone mexicana stems are also explored. The plant's extracts have been shown to inhibit the release of histamine from mast cells, which play a crucial role in allergic responses. By reducing histamine levels and modulating inflammatory cytokines, the extracts may help decrease airway inflammation and hyperresponsiveness, leading to improved respiratory function. The review cites various studies demonstrating that treatment with Argemone mexicana can lead to reduced mucus production and enhanced lung function in models of allergic asthma. The article delves into the biochemical mechanisms underlying the observed effects. Compounds in Argemone mexicana may enhance antioxidant activity, reducing oxidative stress and inflammation in the airways. Additionally, the modulation of immune responses through the inhibition of specific signaling pathways involved in allergic reactions is discussed, suggesting that the plant may help restore a balanced immune response in asthmatic patients. the anti-stress and antiallergic effects of Argemone mexicana stems present a compelling case for their potential role in asthma treatment. The findings support the traditional use of this plant and suggest that it could serve as a valuable adjunct therapy for asthma sufferers, enhancing overall respiratory health and quality of life.	72

CONCLUSION:

Argemone mexicana has emerged as a plant of significant interest in both traditional medicine and modern pharmacological research. Its diverse bioactive compounds exhibit promising therapeutic properties, including anti-stress, antiallergic, antimicrobial, and hepatoprotective effects. These attributes position Argemone mexicana as a potential complementary treatment for various health conditions, particularly respiratory diseases like asthma and liver ailments. The plant’s ability to modulate inflammatory responses and its antioxidant properties further underscore its relevance in addressing chronic diseases influenced by oxidative stress and inflammation. Furthermore, its role in managing stress and allergic reactions highlights its value in holistic approaches to health, particularly for conditions like asthma. Moreover, Argemone mexicana contributes to environmental health, particularly in sustainable agriculture. Its potential as a natural pesticide and its role in allelopathy may provide eco-friendly alternatives to synthetic chemicals, promoting biodiversity and reducing the environmental impact of conventional farming practices.

REFERENCES:

1. Rosas-Pinon Y, Mejía A, Díaz-Ruiz G, Aguilar MI, Sánchez-Nieto S, Rivero-Cruz JF. Ethnobotanical survey and antibacterial activity of plants used in the Altiplane region of Mexico for the treatment of oral cavity infections. J Ethnopharmacol. 2012; 141(3):860-5. doi: 10.1016/j.jep.2012.03.020.

2. Sharma J, Gairola S, Gaur RD, Painuli RM. The treatment of jaundice with medicinal plants in indigenous communities of the Sub-Himalayan region of Uttarakhand, India. J Ethnopharmacol. 2012; 143(1): 262-91. doi: 10.1016/j.jep.2012.06.034.

3. Husna SA, Reddy VJ. A review on Argemone mexicana. International Journal of Pharmaceutical science and research. 2017; 7:170-4. doi.org/10.13040/IJPSR.0975-8232.3(8).2494-01.

4. Tewari D, Mocan A, Parvanov ED, Sah AN, Nabavi SM, Huminiecki L, Ma ZF, Lee YY, Horbańczuk JO, Atanasov AG. Ethnopharmacological Approaches for Therapy of Jaundice: Part I. Front Pharmacol. 2017 Aug 15; 8:518. doi: 10.3389/fphar.2017.00518.

5. Arya P, Mehta JP. A review on antimicrobial and Himalayan medicinal plants. Environment Conservsation Journal. 2017; 18:46-62. doi.org/10.36953/ECJ.2017.181207.

6. Bhattacharjee I, Chatterjee SK, Chatterjee S, Chandra G. Antibacterial potentiality of Argemone mexicana solvent extracts against some pathogenic bacteria. Mem Inst Oswaldo Cruz. 2006; 101(6):645-8. doi: 10.1590/s0074-02762006000600011.

7. Bailon-Moscoso N, Romero-Benavides JC, Tinitana-Imaicela F, Ostrosky-Wegman P. Medicinal plants of Ecuador: A review of plants with anticancer potential and their chemical composition. Medicinal Chemistry Research. 2015; 24:2283-96. doi.org/10.1007/s00044-015-1335-7 ·

8. More NV, Kharat AS. Antifungal and Anticancer Potential of Argemone mexicana L. Medicines (Basel). 2016; 3(4):28. doi: 10.3390/medicines3040028.

9. Raman, R. Applicability, Feasibility and Efficacy of Phytotherapy in Aquatic Animal Health Management. American Journal of Plant Sciences. 2017; 8:257-287. doi: 10.4236/ajps.2017.82019.

10. Meda R, Kam S , Kagambega W, Zongo E, Ouedraogo C, Segda A, Koama B, Somda F, Zongo E and Ouedraogo G. A Review on Bioactive Compounds Isolated from Euphorbia hirta L. American Journal of Plant Sciences; 2023: 14:710-726. doi: 10.4236/ajps.2023.146048.

11. Siddiqui IA, Shaukat SS, Khan GH and Zaki MJ: Evaluation of Argemone mexicana for control of root‐infecting fungi in tomato. Journal of Phytopathology 2002; 150(6): 321-9. doi:10.1046/j.1439-0434.2002. 00762.x.

12. Morey PR, Wankhade AM, Vyas J V, Paithankar VV. A Review on Argemone maxicana Linn. Research Journal of Pharmacognosy and Phytochemistry. 2023; 15(2):149-4. doi: 10.52711/0975-4385.2023.00023.

13. Chang YC, Chang FR, Khalil AT, Hsieh PW, Wu YC. Cytotoxic benzophenanthridine and benzylisoquinoline alkaloids from Argemone mexicana. Z Naturforsch C J Biosci. 2003; 58 (7-8):521-6. doi: 10.1515/znc-2003-7-813.

14. Capasso A, Piacente S, Pizza C, De Tommasi N, Jativa C, Sorrentino L. Isoquinoline alkaloids from Argemone mexicana reduce morphine withdrawal in guinea pig isolated ileum. Planta Med. 1997; 63(4):326-8. doi: 10.1055/s-2006-957693.

15. Singh S, Singh DK. Effect of molluscicidal components of Abrus precatorius, Argemone mexicana and Nerium indicum on certain biochemical parameters of Lymnaea acuminata. Phytother Res. 1999; 13(3):210-3. doi: 10.1002/(SICI)1099-1573(199905)13:3<210: AID-PTR421>3.0.CO;2-F.

16. Nancy A. and Praveena A. Argemone mexicana: A Boon to Medicinal and Pharmacological Approaches in Current Scenario. Cardiovascular & Hematological Agents in Medicinal Chemistry. 2017; 15:78-90. doi: 10.2174/1871525715666170830130155.

17. Chandani M, Jyochhana P M, Sushilta P, Chandrika S. Phytochemistry and pharmacology of Argemone mexicana Linn – An Indian medicinal plant. Research Journal of Pharmacognosy and Phytochemistry. 2023; 15(1):27-2. doi: 10.52711/0975-4385.2023.00005.

18. Dénou A, Ahmed A, Gwatau DD, Thomas P Y, Sanogo R, Diallo D, Alemika ET. Pharmacognostic, Physicochemical and Phytochemical Investigations on Aerial Parts of Argemone mexicana L. Research Journal of Pharmacognosy. 2020; 7(3): 15-24. doi: 10.22127/rjp.2020.220380.1559.

19. Pathak NKR, Biswas M, Seth KK, Dwivedi SPD, Pandey VB. Chemical investigation of Argemone mexicana. J Die Pharmazie. 1985; 40:202. doi.org/10.1590/S0102-695X2013005000021.

20. Haisova K, Slavik J. On the minor alkaloids from Argemone mexicana L. Collect Czech Chem Commun. 1975; 40: 1576-1578. doi.org/10.1135/cccc19751576.

21. Chang YC, Hsieh PW, Chang FR, Wu RR, Liaw CC, Lee KH, Wu YC. Two new protopines argemexicaines A and B and the anti-HIV alkaloid 6-acetonyldihydrochelerythrine from formosan Argemone mexicana. Planta Med. 2003; 69(2):148-52. doi: 10.1055/s-2003-37710.

22. Rahman W, Ilyas M. Flower Pigments. Flavonoids from Argemone mexicana L. (Papaveraceae). J Org Chem. 1962; 27: 153-155. doi.org/10.1021/jo01048a037.

23. Sukumar D, Nambi RA, Sulochana N. Studies on the leaves of Agremone mexicana. Fitoterapia. 1984; 55: 325-353.

24. Gupta R, Dixit VP, & Dobhal M P. Antifertility studies of isoquinoline alkaloids with special emphasis on structure activity relationship. 1990; 61(1):67.

25. Singh S, Pandey VB, Singh TD. Alkaloids and flavonoids of Argemone mexicana. Nat Prod Res. 2012; 26(1):16-21. doi: 10.1080/14786419.2010.529809.

26. Zeng F.L & Xiang, Yang-Fei & Liang, Zhen-Ran & Wang, Xiao & Huang, Dan-E & Zhu, Sui-Nan & Li, Min-Min & Yang, De-Po & Wang, Dong-Mei & Wang, Yi-Fei. Anti-Hepatitis B Virus Effects of Dehydrocheilanthifoline from Corydalis saxicola. The American journal of Chinese medicine. 2013; 41:119-30. 10.1142/S0192415X13500092.

27. Singh A, Singh S, Singh S, Singh TD, Singh VP, Pandey VB, Singh UP 2009a. Fungal spore germination inhibition by alkaloids dehydrocorydalmine and oxyberberine. Journal of Plant Protection Research. 2009; 49(3): 287-289. DOI:10.2478/v10045-009-0046-9.

28. Sarraf S, Tyagi S, Ojha AC, Rawat GS. Phytochemical study of some medicinal plants. J Himalayan Chem Pharm Bull 1994; 11:22-4.

29. Singh S, Verma M, Malhotra M, Prakash S, Singh TD. Cytotoxicity of alkaloids isolated from Argemone mexicana on SW480 human colon cancer cell line. Pharm Biol. 2016; 54(4):740-5. doi: 10.3109/13880209.2015.1073334.

30. Bijo Mathew, Della G.T. Parambi, Manjinder Singh, Omnia M. Hendawy, Mohammad M Al-Sanea, Rania B. Bakr. Chapter 3.1.12 – Protopine. Naturally Occurring Chemicals Against Alzheimer's Disease. Academic Press. 2021. 167-174. doi.org/10.1016/B978-0-12-819212-2.00014-1.

31. Chen DT, Rao W, Shen X, Chen L, Wan ZJ, Sheng XP, Fan TY. Pharmacological effects of higenamine based on signalling pathways and mechanism of action. Front Pharmacol. 2022; 13:981048. doi: 10.3389/fphar.2022.981048.

32. Zhong M, Liu Y, Liu J, Di D, Xu M, Yang Y, Li W, Chen Y, Liu J. Isocorydine derivatives and their anticancer activities. Molecules. 2014; 19(8):12099-115. doi: 10.3390/molecules190812099.

33. Lyu X, Liu J, Liu Z, Wu Y, Zhu P, Liu C. Anti-inflammatory effects of reticuline on the JAK2/STAT3/SOCS3 and p38 MAPK/NF-κB signaling pathway in a mouse model of obesity-associated asthma. Clin Respir J. 2024; 18(1): e13729. doi: 10.1111/crj.13729.

34. Yang Y, Ding T, Xiao G, Huang J, Luo D, Yue M, Su Y, Jiang S, Zeng J, Liu Y. Anti-Inflammatory Effects of Allocryptopine via the Target on the CX3CL1-CX3CR1 axis/GNB5/AKT/NF-κB/Apoptosis in Dextran Sulfate-Induced Mice. Biomedicines. 2023; 11(2):464. doi: 10.3390/biomedicines11020464.

35. Cheng H, Liu J, Tan Y, Feng W, Peng C. Interactions between gut microbiota and berberine, a necessary procedure to understand the mechanisms of berberine. Journal of Pharmaceutical Analysis. 2022; 12(4): 541-555. doi.org/10.1016/j.jpha.2021.10.003.

36. Hussain SF, Nakkady S, Khan L, Shamma M. Oxyhydrastinine, an isoquinolone alkaloid from the papaveraceae. Phytochemistry. 1983; 22(1):319-320. 10.1016/S0031-9422(00)80125-9.

37. Yang D, Wang T, Long M, Li P. Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine. Oxid Med Cell Longev. 2020; 2020:8825387. doi: 10.1155/2020/8825387.

38. Elizondo-Luevano JH, Quintanilla-Licea R, Monroy-García IN, Kačániová M, Castillo-Velázquez U, Bazaldúa-Rodríguez AF, Garza-Vega LM, Torres-Hernández ÁD, Chávez-Montes A. Assessment of Anticancer Properties of Argemone mexicana L. and Berberine: A Comparative Study. Plants. 2024; 13(10):1374. https://doi.org/10.3390/plants13101374.

39. Gali K, Ramakrishnan G, Kothai R, Jaykar, B. In-vitro anticancer activity of methanolic extract of leaves of Argemone mexicana Linn. Int. J. Pharm. Tech. Res. 2011; 3(3):1329-1333.

40. More N, Kharat K, & Kharat A. Berberine from Argemone mexicana L exhibits a broadspectrum antibacterial activity. Acta Biochimica Polonica. 2017; 64(4):653–660. doi: 10.18388/abp.2017_1621.

41. SIMOES A, Claudia. Investigation of antiplasmodial compounds from various plant extracts: Argemone mexicana L. (Papaveraceae), Licania octandra (Hoffmanns. ex. Roem & Schult) Kuntze (Chrysobalanaceae) and Syzygium cumini (L.) Skeels (Myrtaceae). Doctoral Thesis. 2009. doi: 10.13097/archive-ouverte/unige:8400.

42. Singh S, Singh A, Jaiswal J, Singh TD, Singh VP, Pandey VB, Singh U P. Antifungal activity of the mixture of quaternary alkaloids isolated from Argemone mexicana against some phytopathogenic fungi. Archives of Phytopathology and Plant Protection.2010; 43(8):769–774. https://doi.org/10.1080/03235400802176159.

43. Mengie AT, Chekol AE, Tilahun MZ, Mekonnen AM, Shumet YY, Tesfaw AG, Dagnaw BN, Bogale KA, Adela AM, Gobezie YT, Ayalew TG, Berihun DS. Evaluation of In Vivo Wound-Healing and Anti-Inflammatory Activities of Solvent Fractions of Fruits of Argemone mexicana L. (Papaveraceae). Evid Based Complement Alternat Med. 2022; 2022:6154560. doi: 10.1155/2022/6154560.

44. Singh R, Chaubey N, Mishra RK. Evaluation of Anti-Asthmatic Activity of Ethanolic Extract of Argemone mexicana Stems. Saudi Journal of Medical and Pharmaceutical Sciences. Original Research Article. 2021; 7(1): 39-44. doi: 10.36348/sjmps. 2021.v07i01.007.

45. Sabde S, Bodiwala HS, Karmase A, Deshpande PJ, Kaur A, Ahmed N, Chauthe SK, Brahmbhatt KG, Phadke RU, Mitra D, Bhutani KK, Singh IP. Anti-HIV activity of Indian medicinal plants. J Nat Med. 2011; 65(3-4):662-9. doi: 10.1007/s11418-011-0513-2.

46. Gupta RS, Dixit VP and Dobhal MP. Antifertility studies of isoquioline alkaloids with special emphasis on structure activity relationship. J. Fitoterapia. 1990; 61: 67-71.

47. Ali SA, Sharief NH, Mohamed YS. Hepatoprotective Activity of Some Medicinal Plants in Sudan. Evid Based Complement Alternat Med. 2019; 2019:2196315. doi: 10.1155/2019/2196315.

48. Saravanan R, Senthilkumar K., Dhachinamoorthi D., Uma MP, Vamsi Krishna G, Venkata Pavani K. Evaluation of Wound Healing and Anti Microbial Activity of the Argemone mexicana Linn (Papavraceae). Research J. Pharm. and Tech. 2017; 10(3): 852-856. doi: 10.5958/0974-360X.2017.00159.7.

49. Chanda P, Gupta N, Kumari A, Bhattacharya S, Chakraborty S, Pal R, Bhattacharjee A. A Review on Pharmacological Potential of Argemone mexicana In Management of Wound Healing & Antidiabetic Activity. 2022; 11. 21-27. 10.35629/6718-11022127.

50. Perumal P, Sekar V, Rajesh V, Gandhimathi S, Sampathkumar R, Shuja Nazimudin K.H. Invitro Antioxidant Activity of Argemone mexicana Roots. International Journal of PharmTech Research. 2010; 2(2): 1477-1482.

51. Magos-Guerrero GA, Santiago-Mejía J, Carrasco OF. Exploratory studies of some Mexican medicinal plants: Cardiovascular effects in rats with and without hypertension. Journal of Intercultural Ethnopharmacology. 2017 Jul 12;6(3):274-279. doi: 10.5455/jice.20170706061922.

52. Sonia Piacente, Anna Capasso, Nunziatina De Tommasi, Cumanda Jativa, Cosimo Pizza, Ludovico Sorrentino. Different Effects of Some Isoquinoline Alkaloids from Argemone mexicana on Electrically Induced Contractions of Isolated Guinea-pig Ileum. Phytotherapy research. 1997; 11(2): 155–157. 10.1002/(SICI)1099-1573(199703)11:2<155: AID-PTR48>3.0.CO;2-9.

53. Shahid Shaukat S, Siddiqui IA, Khan GH. et al. Nematicidal and allelopathic potential of Argemone mexicana, a tropical weed. Plant and Soil. 2002; 245:239–247. https://doi.org/10.1023/A:1020476024966.

54. Carlos A Granados-Echegoyen, Manuel Jesús Chan-Bacab, Benjamín Otto Ortega-Morales, Alfonso Vásquez-López, Luicita Lagunez-Rivera, Fidel Diego-Nava, Christine Gaylarde, Argemone mexicana (Papaverales: Papavaraceae) as an Alternative for Mosquito Control: First Report of Larvicidal Activity of Flower Extract. Journal of Medical Entomology. 2019; 56(1):261–267, https://doi.org/10.1093/jme/tjy159.

55. Afroz A and Adnan A K. Argemone mexicana L. A weed with versatile medicinal and pharmacological applications. Annals of Phytomedicine: An International Journal. 2020; 9(1): 218-223. doi.org/10.21276/ap.2020.9.1.29.

56. Kulshrestha S and Goel A. A panoramic view on Argemone mexicana: its Medicinal importance and phytochemical potentials. Plant Archives. 2021; 21(1): 40-49. doi.org/10.51470/PLANTARCHIVES.2021.v21.no1.006.

57. Elizondo-Luevano JH, Verde-Star J, González-Horta A, Castro-Ríos R, Hernández-García ME, Chávez-Montes A. In Vitro Effect of Methanolic Extract of Argemone mexicana against Trichomonas vaginalis. Korean J Parasitol. 2020; 58(2):135-145. doi: 10.3347/kjp.2020.58.2.135.

58. Ojija F. Argemone mexicana’s leaf crude extract suppresses Phaseolus vulgaris and Zea mays germination and growth. Tropical Agroecosystems (TAEC). 2023;4(2):53-59. doi.org/10.26480/taec.02.2023.53.59.

59. Fawehinmi AB, Hassan L, Chimezie EU, Ola-Adedoyin AT. Quantitative and Qualitative Phytochemical Screening and Anti-Microbial Activities of Argemone mexicana Linn. Journal of Pharmaceutical Research International. 2022; 34(54B):33-45. doi.org/10.9734/jpri/2022/v34i54B7241.

60. Nayeli MB, Mayra ZG, Alejandro Z, Enrique JF, Margarita AF, Macrina FM, Maribel HR. Effect of Argemone mexicana on Local Edema and LPS-Induced Neuroinflammation. Chemistry and Biodiversity. 2021; 18(3): e2000790. doi.org/10.1002/cbdv.202000790.

61. Pandeya KB, Ganeshpurkar A, Mishra MK. Natural RNA dependent RNA polymerase inhibitors: Molecular docking studies of some biologically active alkaloids of Argemone mexicana. Medical Hypotheses. 2020; 144:109905. doi.org/10.1016/j.mehy.2020.109905.

62. Haruna Y. Characterization of Antioxidant Activity Present in Methanol Extract Argemone mexicana Leaf. EC Emergency Medicine and Critical Care. 2019; 3:796-803.

63. Elizondo-Luévano JH, Castro-Ríos R, Sánchez-García E, Hernández-García ME, Vargas-Villarreal J, Rodríguez-Luis OE, Chávez-Montes A. In Vitro Study of Antiamoebic Activity of Methanol Extracts of Argemone mexicana on Trophozoites of Entamoeba histolytica HM1‐IMSS. Canadian Journal of Infectious Diseases and Medical Microbiology. 2018; 2018(1):7453787. doi.org/10.1155/2018/7453787

64. Gabriela Jasso Díaz, Glafiro Torres Hernández, Alejandro Zamilpa, Carlos Miguel Becerril Pérez, J. Efrén Ramírez Bribiesca, Omar Hernández Mendo, Hussein Sánchez Arroyo, Manasés González Cortazar, Pedro Mendoza de Gives. In vitro assessment of Argemone mexicana, Taraxacum officinale, Ruta chalepensis and Tagetes filifolia against Haemonchus contortus nematode eggs and infective (L3) larvae. Microbial Pathogenesis. 2017; 109: 162-168. doi.org/10.1016/j.mehy.2020.109905.

65. Arcos-Martínez AI, Muñoz-Muñiz OD, Domínguez-Ortiz MÁ, Saavedra-Vélez MV, Vázquez-Hernández M, Alcántara-López MG. Anxiolytic-like effect of ethanolic extract of Argemone mexicana and its alkaloids in Wistar rats. Avicenna Journal of Phytomedicine. 2016; 6(4):476-88.

66. Bapna S, Choudhary PK, Ramaiya M, Chowdhary A. Antiplasmodial activity of Argemone mexicana: an in vivo and in vitro study. World J Pharm Res. 2015; 4:1653-63.

67. Namkeleja HS, Tarimo MT, Ndakidemi PA. Allelopathic effects of Argemone mexicana to growth of native plant species. American journal of plant sciences. 2014; 5(9): 1336-1344. DOI:10.4236/ajps.2014.59147.

68. Warikoo R, Kumar S. Impact of Argemone mexicana extracts on the cidal, morphological, and behavioral response of dengue vector, Aedes aegypti L. (Diptera: Culicidae). Parasitol Res. 2013; 112:3477–3484. doi.org/10.1007/s00436-013-3528-7.

69. Sourabie TS, Ouedraogo N, Sawadogo WR, Yougbare N, Nikiema JB, Guissou IP, Nacoulma OG. Evaluation of the anti-icterus effect of crude powdered leaf of Argemone mexicana L.(Papaveraceae) against CCl4-induced liver injury in rats. International Journal of Pharma Sciences and Research (IJPSR). 2012; 3(10):491-496.

70. Anarthe S, Chaudhari S. Neuropharmacological study of Argemone mexicana Linn. Journal of Applied Pharmaceutical Science. 2011; 1(4):121-6.

71. Osho A, Adetunji T. Antimicrobial activity of the essential oil of Argemone mexicana Linn. Journal of Medicinal Plants Research. 2010; 4(1):19-22. doi: 10.5897/JMPR09.204.

72. Bhalke RD, Gosavi SA. Anti-stress and antiallergic effect of Argemone mexicana stems in asthma. Arch Pharm Sci Res. 2009; 1(1):127-9.

Received on 13.10.2024 Revised on 01.12.2024

Accepted on 16.01.2025 Published on 10.05.2025

Available online from May 14, 2025

Res. J. Pharmacognosy and Phytochem. 2025; 17(2):149-162.

DOI: 10.52711/0975-4385.2025.00025

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