Bishop's weed

Bishop's Weed: A Comprehensive Reference Article

Nomenclature and Taxonomic Identity

The common name "bishop's weed" is shared by several distinct plants, which has historically caused — and continues to cause — significant confusion in both botanical and medical literature. Bishop's weed is a common name for several plants, nearly all belonging to the family Apiaceae: Aegopodium podagraria (ground elder, an invasive perennial weed of temperate regions), Ammi majus (commonly known as bullwort or laceflower), Houttuynia cordata (fish mint, of the family Saururaceae), Trachyspermum ammi (known also as ajwain or carom), and Visnaga daucoides (bisnaga or khella). This article covers the two species most prominently described as "bishop's weed" in medical and pharmacological literature: Trachyspermum ammi (ajwain/carom) and Ammi majus (greater ammi). A related species, Ammi visnaga (khella), is sometimes conflated with Ammi majus and is noted where relevant.

Trachyspermum ammi (Ajwain / Carom)

The ajowan, Trachyspermum ammi (L.) Sprague ex Turrill, belonging to the family Apiaceae, is an important seed spice known as bishop's weed, carum seed, or carum ajowan. Common botanical synonyms include Trachyspermum copticum Linn, Carum copticum Benth and Hook, Ammi copticum Linn., Ptychotis coptica DC, and Ligusticum ajowain Roxb. The correct generic placement of this spice has been a matter of uncertainty; Boissier placed it in the genus Ammi (where Linnaeus originally put it), and per Genera Plantarum it has been referred to Carum; in more recent taxonomy it was placed in the section Trachyspermum, which includes about 14 species.

Ajwain or ajowan (Trachyspermum ammi) — also known as ajowan caraway, thymol seeds, bishop's weed, or carom — is an annual herb in the family Apiaceae. Both the leaves and the seed-like fruit (often mistakenly called seeds) of the plant are consumed by humans. Ajwain's small, oval, seed-like fruits are pale brown schizocarps, which resemble the seeds of other plants in the family Apiaceae such as caraway, cumin, and fennel. They have a bitter and pungent taste, with a flavor similar to anise and oregano, and smell like thyme because they also contain thymol, but are more aromatic and less subtle in taste.

Ajowan is indigenous to India and Egypt. It is an annual, aromatic, and herbaceous plant, profusely branched with a height of 60–90 cm, small, erect, with soft fine hair.

Ammi majus (Greater Ammi / Bullwort)

The scientific name is Ammi majus L. Its common names in English include bishop's weed and Queen Anne's lace. Its Arabic names include Khillah and Khillah shytani; in Latin and German it is known as Ammi; and in French as Ammi commun. A member of the family Apiaceae, Ammi majus is native to Egypt and widely distributed in Europe, the Mediterranean, and West Asia. The plant thrives in regions including Iraq, Egypt, the Mediterranean basin, West Africa, and Iran.

Note that bishop's weed is also a widely used common name for other Apiaceae family plants, such as goutweed, known as bishop's goutweed (Aegopodium podagraria L.), and khella (Ammi visnaga). Care should be taken not to confuse Ammi majus with its related species, khella (Ammi visnaga).

Morphology and Natural Source

Both Trachyspermum ammi and Ammi majus are annual herbs of the Apiaceae family, characterized by compound umbel flower heads. Ajwain (T. ammi) is profusely branched with a height of 60–90 cm, erect with soft fine hair, and has many branched leafy stems, feather-like leaves 2–3 pinnately divided, with linear segments and flowers that are terminal and compound.

Cultivation of T. ammi extends across a broad geographic range. Cultivated extensively in regions such as Egypt, Iran, Afghanistan, Pakistan, and India, T. ammi has drawn attention due to its rich essential oil content, prominently thymol. For Ammi majus, specific regions include the Nile River Valley in Egypt, countries of the Mediterranean area (including Morocco, Algeria, Tunisia, Libya, Italy, Spain, Albania, Cyprus, and Turkey), and further regions including Iran, Iraq, Lebanon, Syria, Palestine, Saudi Arabia, Oman, and Yemen.

Common Forms and Preparations

Trachyspermum ammi

Both the leaves and the seed-like fruit (often mistakenly called seeds) of T. ammi are consumed by humans. As a spice, seeds are dry-roasted or fried in oil to enhance curries, breads, and snacks, with a flavor profile that is sharp, slightly bitter, and peppery. In herbal medicine, both seeds and essential oil are used therapeutically for digestive, respiratory, and joint support. Modern preparations include capsules, tinctures, and concentrated oils, often standardized for their active compounds.

Ajwain oil, a brown-colored oil, is present in the seeds in a concentration of 2–4.4%. Intestinal issues, loss of appetite, and bronchial problems are traditionally treated with thymol, the active ingredient in this oil.

Ammi majus

For Ammi majus, the fruits, stems, leaves, and roots are all utilized to treat illness. The most significant pharmaceutical preparations derived from Ammi majus are those containing its isolated furanocoumarin compounds. Worldwide, many pharmaceutical products contain A. majus extract or the active principle xanthotoxin, marketed under the trade names 'Oxsoralen', 'Methoxsalen', or 'Meladinine' by many pharmaceutical companies in different dosage forms in various countries; suntan lotions also incorporate it, as does Lukoskin ointment and oral liquid (an Ayurvedic proprietary preparation). Two pharmacopoeial preparations — Majoon Aatrilal and Dawae Bars — are used in the Unani system of medicine.

Traditional and Historical Use

Ammi majus: Ancient Egypt and the Islamic Medical Tradition

For more than three thousand years, it has been known that plants combined with natural sunlight can be used to treat vitiligo. In Ancient Egypt and India, physicians and herbalists used the plant species Ammi majus Linnaeus in Egypt and Psoralea corylifolia L. in India for repigmentation of vitiligo. In 1947, several crystalline compounds, including ammoidin (8-methoxypsoralen) and bergapten (5-methoxypsoralen), were isolated from the powder of Ammi majus L., and El Mofty showed that 8-methoxypsoralen was useful in the treatment of vitiligo.

In Egypt around 2000 BC, the juice of Ammi majus was rubbed on patches of vitiligo, after which patients were encouraged to lie in the sun. In the 13th century, vitiligo was treated with a tincture of honey and the powdered seeds of a plant called "aatrillal," which was abundant in the Nile River Valley. This plant has since been identified as A. majus, but the trade name Aatrillal is still used today to refer to the yellowish-brown powder made from its seeds.

In Egyptian folk medicine, the plant served as a diuretic for urinary tract disorders, an emmenagogue to regulate menstruation, and a remedy for psoriasis, asthma, and kidney stones. Similar traditional applications persisted in regions like Oman and Iraq for skin conditions including vitiligo and tinea, as well as menstrual regulation.

In the Unani system of medicine, A. majus has been used for the treatment of various dermatological disorders, particularly vitiligo, for ages. In traditional medicine, fruits are used as an emmenagogue as well as a diuretic, blood purifier and to treat leprosy, urinary and digestive disorders.

Trachyspermum ammi: Ayurvedic, Unani, and South Asian Traditions

Commonly known as Ajwain or Carom seeds, T. ammi is a versatile medicinal plant of the Apiaceae family, widely utilized in traditional medicine systems including Ayurveda, Unani, and Siddha. Seeds of T. ammi are widely used in India and eastern Asia, both in diet and in traditional medicine.

Evidence of T. ammi use dates back to the Ebers Papyrus (1500 BCE), where it was recommended for digestive ailments. In classical Sanskrit texts such as the Charaka Samhita (c. 400 CE), Ajwain is praised as a carminative and expectorant, particularly under vata-pacifying and kapha-reducing therapies.

The fruit has a long history of medicinal usage because of its antispasmodic, stimulant, and carminative action. It has been used to manage conditions including flatulence, atonic dyspepsia, diarrhea, abdominal tumors, piles, bronchial troubles, nausea, vomiting, asthma, and other respiratory problems.

In the Unani tradition, ajwain is used as an anti-inflammatory agent, liver tonic, and for relieving paralysis. In Ayurveda, renowned Ayurvedic physician Charaka advocated that this herb is useful in relieving urticaria and has anticolic and antiflatulent properties.

Key Constituents and Active Compounds

Trachyspermum ammi

Ajwain fruits yield 2% to 4% brownish essential oil, with thymol as the major constituent (35% to 60%). The non-thymol fraction (thymene) contains para-cymene, γ-terpinene, α- and β-pinenes, dipentene, α-terpinene, and carvacrol.

Fiber (11.9%), carbohydrates (24.6%), tannins, glycosides, moisture (8.9%), protein (17.1%), fat (21.1%), saponins, flavones, and other components (7.1%) — involving calcium, phosphorous, iron, cobalt, copper, iodine, manganese, thiamine, riboflavin, and nicotinic acid — are among the reported phytochemical constituents.

Several studies have reported the chemical composition of ajwain oil with different major constituents including thymol, γ-terpinene, and p-cymene. The plant's populations can be classified into two chemotypes: thymol/p-cymene/γ-terpinene type and thymol/carvacrol type.

Ajwain seeds, characterized by their bioactive components such as thymol and carvacrol, exhibit a broad spectrum of pharmacological properties, including antioxidant, anti-inflammatory, antimicrobial, antihypertensive, and antidiabetic effects.

Ammi majus

The major constituents of Ammi majus are the furanocoumarins, which include xanthotoxin (methoxsalen, 8-methoxypsoralen, ammoidin; up to 1.15%), imperatorin (ammidin; up to 0.75%), and bergapten (heraclin, majudin, 5-methoxypsoralen; up to 1.88%), as well as marmesin (0.25%), isoimperatorin (0.01%), heraclenin (0.07%), and isopimpinellin (0.01%).

Ammi species, part of the Umbelliferae family, contain significant bioactive compounds, particularly coumarins and flavonoids, renowned for their biological activities. Ammi majus L. harbors several active ingredients including xanthotoxin, bergapten, imperatorin, isoimperatorin, isopimpinellin, and marmesinin.

Additional constituents documented in Ammi majus include phenolic acids such as caffeic acid, chlorogenic acid, cinnamic acid, ferulic acid, gallic acid, tannic acid, and vanillic acid, as well as oxypeucedanin.

Mechanisms of Action

Thymol (from T. ammi)

Thymol has antioxidant properties by preventing chelating metal ions and free radicals and boosting endogenous antioxidants. Additionally, the non-phenolic monoterpene terpinene exhibits antioxidant effects.

The therapeutic mechanism of methoxsalen (derived from A. majus) involves the compound's absorption into skin cells, where UVA irradiation activates it to intercalate between DNA base pairs and form covalent photoadducts, predominantly with thymine residues, resulting in DNA cross-linking that inhibits replication and transcription, thereby reducing hyperproliferative epidermal activity.

Furanocoumarins (from A. majus)

Methoxsalen is defined as a photoactive toxic substance used in conjunction with ultraviolet light to treat skin disorders such as psoriasis, vitiligo, and cutaneous T-cell lymphoma, while also being recognized as a carcinogen. It occurs naturally in several plant species and was originally isolated from bishop's weed (Ammi majus) in 1947.

Extracts of these fruits and seeds have been used since ancient times as dermal sensitizing agents in the treatment of vitiligo. Topical application of psoralen extracts, followed by irradiation with light, results in stimulation of melanin production, producing a dermal "tanning" effect. In more recent years, psoralens have been utilized in the photochemotherapy of psoriasis: psoralens are administered orally or topically, then the skin is exposed to ultraviolet radiation, and a high percentage of disease remissions follow such treatment.

Furanocoumarins are widely applied due to their photosensitizing effect, as well as their anticoagulant, antimicrobial, and microsomal oxidation-inducing properties in the liver and intestines.

Scientific Evidence by Area of Use

1. Skin Disorders: Vitiligo and Psoriasis (Ammi majus)

This is the area of greatest clinical significance and the most extensively developed therapeutic application of bishop's weed.

Bishop's weed contains psoralens, which are substances that react with ultraviolet (UV) light and darken the skin. Psoralens are currently used together with UV light therapy to treat skin disorders such as psoriasis and vitiligo. Oral 8-methoxypsoralen, a drug made from bishop's weed, has been described as the drug of choice in photochemotherapy for vitiligo and psoriasis.

Photochemotherapy use was resumed in 1947 when the active ingredients of Ammi majus — 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP) — were isolated. The first trials with 8-MOP and sun exposure were performed in vitiligo patients by El-Mofty in Egypt in 1947. Various publications by Parrish, Fitzpatrick, Tanenbaum, and Pathak subsequently reported the beneficial effect of UVA tube therapy in combination with oral 8-MOP in the treatment of psoriasis.

Clinical efficacy is evidenced by clearance rates exceeding 80% in psoriasis patients after 20–30 PUVA sessions, though relapse often necessitates maintenance therapy.

The use of psoralen baths followed by UVA exposure (bath PUVA) originated in Scandinavia and is still in use, as it avoids 8-MOP side effects such as nausea and dizziness. However, topical and bath PUVA did not gain as much popularity as the oral form.

Evidence strength: There is currently insufficient evidence available in humans to support the use of crude Ammi majus preparations for any medical condition. High-quality human studies are needed before any strong conclusion can be made about the safety and effectiveness of the whole plant. However, the isolated active principle, methoxsalen (8-MOP), has an established, well-documented clinical record as part of PUVA therapy under pharmaceutical supervision.

2. Anticancer Activity (Ammi majus)

A PMC-indexed in vitro study aimed to evaluate the anticancer properties of Ammi majus fruit methanol extract (AME) against liver cancer. Three fractions (Hexane, CH₂Cl₂, and EtOAc) were tested for anticancer activities against the HepG2 cell line. Among the AME fractions, the CH₂Cl₂ fraction revealed the most potent cytotoxic activity, and xanthotoxin (Compound 1) was found to have the strongest cytotoxic activity against HepG2 cells (IC₅₀ 6.9 ± 1.07 µg/mL).

Treating HepG2 cells with 6.9 µg/mL of xanthotoxin induced significant changes in the DNA cell cycle (increases in apoptotic pre-G1 and G2/M phases and a decrease in the S-phase). Xanthotoxin induced a significant increase in Annexin-V-positive HepG2 cells at both early and late stages of apoptosis, as well as a significant decrease in autophagic flux. In silico analysis revealed strong interaction with topoisomerase II, implying potential broad-spectrum anticancer activity. The results indicate that xanthotoxin exhibits anticancer effects with good biocompatibility toward normal human cells, though further studies are needed to optimize its antitumor efficacy, toxicity, solubility, and pharmacokinetics.

Evidence strength: All anticancer data for Ammi majus are currently limited to in vitro cell-line and in silico studies. No human clinical trials have been published demonstrating anticancer efficacy.

3. Gastrointestinal Health (Trachyspermum ammi)

The oil of T. ammi is known for various medicinal applications, particularly addressing bronchial issues, gastrointestinal troubles, and loss of appetite. The roots possess diuretic properties, while the seeds exhibit aphrodisiac qualities. The oil's thymol content (35%–60%) is effective against bronchial problems, poor appetite, and gastrointestinal disorders.

Ajwain's ability to raise bile acid, stomach acid, and digestive enzyme activity has been established. The length of the meal transit may be shortened as well. Ajwain increases pancreatic lipase and amylase activity as an enzyme modulator.

Trachyspermum ammi has demonstrated potent anti-ulcer properties in experimental settings.

Evidence strength: The gastrointestinal effects of T. ammi have been well characterized in preclinical (animal and in vitro) studies and are supported by centuries of traditional use, but robust, well-powered randomized controlled human trials specifically confirming these effects remain limited.

4. Cardiovascular and Antihypertensive Effects (Trachyspermum ammi)

From a therapeutic perspective, ajwain has been demonstrated in preclinical settings to exhibit a wide range of pharmacological activities, including antioxidant, antimicrobial, antifungal, hypolipidaemic, and antihypertensive effects.

One randomized controlled trial specifically tested the cardiovascular effects of ajwain. Ajwain (T. ammi), a traditional medicinal herb, has reported autonomic benefits; one trial aimed to evaluate its effect as an adjunct to routine antihypertensive medicines on heart rate variability (HRV) in patients with stage 1 hypertension. This was a randomized controlled trial in which 99 subjects with stage 1 hypertension were allocated to an intervention group (ajwain 3 g twice daily along with routine antihypertensive medication, n=50) or a control group (routine antihypertensive medication only, n=49). The intervention lasted 21 days. Within-group analysis showed that both groups demonstrated significant improvement in HRV measures (RMSSD and pRR50). Ajwain supplementation for 21 days showed no added cardio-autonomic benefits beyond standard antihypertensive care. Longer, standardized, and polyherbal-focused trials are needed to clarify ajwain's cardio-autonomic effects in hypertension.

Evidence strength: Preclinical evidence suggests antihypertensive activity, but the single published randomized controlled trial found no significant added benefit of ajwain over standard antihypertensive medication alone. Evidence in humans is currently insufficient.

5. Antimicrobial Activity (Trachyspermum ammi)

The oil of T. ammi showcases anti-aggregatory and anti-microbial properties in humans. Rich in essential oils, phenolic compounds, and flavonoids, T. ammi has demonstrated remarkable pharmacological activities including analgesic, antibacterial, antifungal, anti-inflammatory, and antioxidant properties. Its active compounds, primarily thymol, contribute to its efficacy against various pathogens.

Ammi majus has also demonstrated larvicidal impact on mosquito larvae and is reported to possess antibiotic, antifungal, and antioxidant properties in laboratory settings.

Evidence strength: Antimicrobial and antifungal properties of both T. ammi and Ammi majus are primarily supported by in vitro and preclinical data. Human clinical trials in this area are lacking.

6. Analgesic and Neuropathic Pain (Trachyspermum ammi)

A clinical trial with a topical formulation has been published. Petramfar et al. conducted a study published in Neurological Sciences (2016) titled "Trachyspermum ammi 10% topical cream versus placebo on neuropathic pain" — a randomized, double-blind, placebo-controlled trial.

Evidence strength: A single published double-blind, placebo-controlled trial exists for topical ajwain cream on neuropathic pain; independent replication in larger populations is required before conclusions can be drawn.

7. Neurological Effects (Trachyspermum ammi)

Thymol in Trachyspermum ammi seed extract has been shown in preclinical work to exhibit neuroprotection, learning, and memory enhancement in a scopolamine-induced Alzheimer's disease mouse model. In primary hippocampal cultures, T. ammi seed extract (TASE) at 75 and 100 µg/mL and thymol at 10 and 20 µM enhanced neuronal polarity, early neurite arborization, and maturation of hippocampal neurons in a dose-dependent manner. The stimulatory activities on neurite extension involved TrkB signaling. TASE and thymol also rescued nocodazole-induced blunted neurite extension, suggesting a role as a potent microtubule-stabilizing agent. These findings demonstrate the potential capacities of TASE and thymol in promoting neuronal development and reconstruction of neuronal circuitry, which are often compromised in neurodegenerative diseases and acute brain injuries.

Emerging evidence highlights the plant's potential role in combating neurodegenerative diseases, cancer, and metabolic disorders, but further studies on pharmacokinetics, bioavailability, and clinical efficacy are essential.

Evidence strength: All neurological evidence is currently from in vitro and animal model studies only. No human clinical trials have been conducted.

8. Antidiabetic Effects (Trachyspermum ammi)

Ajwain seeds, characterized by their bioactive components such as thymol and carvacrol, exhibit a broad spectrum of pharmacological properties, including antidiabetic effects.

Evidence strength: Antidiabetic evidence for T. ammi derives from in vitro and animal studies. No well-designed human clinical trials specifically for blood glucose management have been identified in the literature.

Body Systems and Health Areas

• Integumentary system (skin): Ammi majus — vitiligo, psoriasis, cutaneous T-cell lymphoma (via isolated methoxsalen/PUVA therapy); T. ammi — reported use for urticaria and joint inflammation.
• Gastrointestinal system: T. ammi — carminative, antispasmodic, anti-ulcer, enzyme-stimulating effects; traditional use for flatulence, dyspepsia, colic, and diarrhea.
• Respiratory system: T. ammi possesses bronchodilatory and antispasmodic properties, with traditional use for bronchial complaints and asthma.
• Cardiovascular system: Preclinical data suggest antihypertensive and hypolipidemic effects; one human trial produced a null result for cardio-autonomic outcomes.
• Immune and microbial defense: Both species show antimicrobial, antifungal, and antioxidant activities in vitro.
• Nervous system: Preclinical (animal/cell culture) data only for neuroprotection and memory enhancement.
• Urinary system: Ammi majus traditionally used as a diuretic; an aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin were shown to prevent cell damage caused by oxalate in renal epithelial cells in a study published in Phytomedicine (2010).
• Endocrine/metabolic system: Preclinical evidence for antidiabetic and lipid-lowering activity.

Dosage Forms and Reported Dosages

Trachyspermum ammi — Reported in Studies and Traditional Practice

Parts used are the fruits. Traditional Ayurvedic dosage ranges reported are: fruit powder — 1–3 grams; oil — 1–3 drops; distillate (Ajamoda arka) — 5–10 drops; decoction — 15–30 ml.

In the published randomized controlled trial on hypertension and heart rate variability, the intervention dose was ajwain 3 g twice daily along with routine antihypertensive medication, administered over 21 days.

For neuropathic pain, the published clinical trial used a Trachyspermum ammi 10% topical cream formulation versus placebo.

Ammi majus — Pharmaceutical Forms

In modern clinical settings, Ammi majus-derived 8-MOP (methoxsalen) is administered as a tablet or topical lotion before UVA therapy, with doses standardized and carefully managed by phototherapy specialists.

8-Methoxsalen (8-MOP) is used in the treatment of psoriasis, mycosis fungoides, vitiligo, and other hyperproliferative skin disorders, delivered through systemic (oral administration) and topical routes. Various topical preparations available in the market include creams, ointments, and lotions.

Safety Considerations

Phototoxicity and Dermatitis (Ammi majus)

Bishop's weed (Ammi majus) has been known to induce toxic phytophotodermatitis. Early evidence suggests that psoralen compound 8-methoxypsoralen (8-MOP) from Ammi majus may help treat vitiligo, but case reports also mention potential phototoxic skin damage, phototoxic dermatitis, and pigmentary retinopathy caused by Ammi majus.

Higher doses of oral methoxsalen (such as for PUVA therapy) can, with exposure to sunlight or ultraviolet irradiation, cause serious sunburn or premature aging of the skin.

Long-Term Carcinogenic Risk

A 1997 prospective cohort study of 1,380 psoriasis patients treated with oral methoxsalen and UVA reported a dose-dependent elevation in melanoma risk, with a relative risk of 2.3 overall and up to 5.4 for those receiving over 250 treatments, observed approximately 15 years post-initiation.

Livestock Photosensitization

Ammi majus causes primary photosensitization due to the presence of furocoumarins. Poisonings have been reported in Brazil, Uruguay, and Argentina. The plant is most toxic during seed production, when photodynamic compounds are concentrated.

Allergic Reactions

IgE-mediated rhinitis and contact urticaria caused by exposure to bishop's weed have been described in clinical case reports, including in a 31-year-old atopic female florist.

Contraindications (Ammi majus)

Fructus Ammi Majoris is contraindicated in diseases associated with photosensitivity, cataract, invasive squamous-cell cancer, and known sensitivity to xanthotoxin (psoralens), and in children under the age of 12 years. The fruits are also contraindicated in pregnancy, nursing, tuberculosis, liver and kidney diseases, HIV infections, and other autoimmune diseases.

Drug Interactions

Furanocoumarins possess microsomal oxidation-inducing properties in the liver and intestines, which is relevant to potential interactions with drugs metabolized by the same hepatic enzyme systems. The use of oral khellin (from the related Ammi visnaga) is limited by its potential for toxicity including elevated liver enzymes, phototoxicity, and dermatitis.

Safety of Trachyspermum ammi

The pharmacological activities of T. ammi include hepatoprotective, antibacterial, antioxidant, antihypotensive, abortifacient, estrogenic, insecticidal, and antiulcer properties. The abortifacient classification warrants caution regarding use during pregnancy. Abortifacient activity of T. ammi has been noted in the pharmacological literature.

Summary of Evidence Quality

For Ammi majus: The isolated pharmaceutical compound methoxsalen (8-MOP), originally derived from bishop's weed, has well-established clinical evidence for use in PUVA phototherapy for vitiligo and psoriasis. However, as a whole plant or crude extract preparation, human clinical evidence is classified as insufficient by evidence-based reviews. There is currently insufficient evidence available in humans to support the use of Ammi majus as a whole plant for any medical condition, and high-quality human studies are needed before strong conclusions can be made.

For Trachyspermum ammi: The field emphasizes integrating traditional knowledge with modern research, advocating for further clinical studies, standardization, and advanced delivery systems to enhance its therapeutic application. The preponderance of pharmacological evidence remains preclinical (in vitro and animal model), with very few human clinical trials having been published.

References

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