Hygrophila

Hygrophila (Hygrophila auriculata): A Comprehensive Reference

1. Identity: Botanical Classification, Nomenclature, and Natural Source

1.1 Accepted Name, Synonyms, and Taxonomic Position

The accepted botanical name is Hygrophila auriculata (Schumach.) Heine, and the species has been known under several synonyms, including Hygrophila schulli (Buch.-Ham.) M.R. Almeida & S.M. Almeida, Asteracantha longifolia (L.) Nees, Hygrophila spinosa T. Anderson, and Barleria auriculata Schumach. & Thonn. The species was initially described as Barleria auriculata by Schumacher and Thonning in their 1827 work, based on specimens from Guinea, and was transferred to the genus Hygrophila by Heine in 1962, reflecting a reclassification within the Acanthaceae family.

This species has also been published as Hygrophila schulli by M.R. Almeida and S.M. Almeida, though that name has been declared invalid by the International Plant Names Index. In the scientific literature, the names H. auriculata, H. spinosa, and Asteracantha longifolia are frequently used interchangeably to refer to the same plant, and many published pharmacological studies use these names synonymously.

Its full taxonomic classification is: Kingdom: Plantae; Order: Lamiales; Family: Acanthaceae; Genus: Hygrophila; Species: H. auriculata. The generic name Hygrophila means "water-loving," derived from the Greek hygros (moist or humid) and philos (love or friend), describing the plant's preferred wet habitat, while the species epithet auriculata means "eared" or "having an ear-like appendage," derived from the Latin for "little ear."

1.2 Common Names and Vernacular Designations

In Ayurveda, the plant is known as Kokilaaksha (also spelled Kokilaksha), Ikshuraka, and Ikshura. In the Unani tradition it is called Taalmakhaanaa. In Tamil and Siddha medicine it is known as Neermulli, while in Assam and Bengal it is commonly called Kulekhara, and in Hindi, Talmakhana. The Ayurvedic epithet Kokilasha means "having eyes like the Kokila or the Indian cuckoo."

1.3 Morphology and Natural Habitat

It is an erect semiwoody plant found in moist places of India, nearby the banks of stagnant or fresh water ditches and swampy grounds, many times mixed with sedges and marshy grasses. It is a stout herb with stems that are fasciculate, subquadrangular, erect, 0.6–1.5 m tall, thickened at the nodes, hispid with long hairs, bearing axillary spines; leaves approximately 9 × 1 cm, hairy, oblanceolate, growing in whorls. Flowers are 2–3 cm long, purple-blue, bilabiate, borne in whorls. The fruits are capsules, 8 mm long, with 4–8 seeds. The seeds are black in colour and swell and become slimy when they come into contact with water or saliva.

The plant is believed to be indigenous to India, from the Himalayas to Sri Lanka, Myanmar, Malaysia, and Nepal. It is distributed in tropical and subtropical climates around the world, including India, Malaysia, Indonesia, Brazil, Africa, and many parts of Southeast Asia and Central America.

1.4 Plant Parts Used and Common Preparations

The medicinal applicability of the plant — its seeds, roots, leaves, and the panchang (a combination of root, flowers, stem, fruits, and leaves burnt together as ash) — are well documented in Ayurveda. The extract can be made from almost any section of the plant.

Traditional preparations documented in Ayurvedic practice include:

• Decoction of the root, given in a dose of 10 ml to treat jaundice and swelling of the body.
• Powder of the seed, given in a dose of 2–4 g with milk to treat impotence, low sperm count, and general debility.
• Ash prepared by burning the dried plant (Kshara), given with a decoction of Tribulus terrestris to treat renal calculi.
• Cold infusion of the seed, given in a dose of 25–30 ml to treat hepatomegaly and bloating of the abdomen.

In modern supplement contexts, the plant is prepared as standardised dry powders, aqueous extracts, ethanolic extracts, hydroalcoholic extracts, and encapsulated seed or whole-plant powders. Decoctions, cold infusions, and seed pastes are the classical forms, while commercial preparations most often use methanol or ethanol extraction, typically reported in research at concentrations yielding aqueous, ethanolic, or total alkaloid fractions.

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2. Traditional and Historical Use

2.1 Ayurvedic Medicine (India)

H. auriculata has been used in various medicinal systems such as Ayurveda, Unani, Siddha, and folk medicine for its anti-inflammatory, hepatoprotective, diuretic, and aphrodisiac properties. It was traditionally used to prepare ancient Indian Ayurvedic medicines for treating chronic disorders.

Various ethnomedicinal writings document the use of the plant or its parts for the treatment of jaundice, oedema, gastrointestinal ailments, diarrhoea, dysentery, urinogenital disorders, gall stones, urinary calculi, kidney stones, leucorrhoea, rheumatism, tuberculosis, anaemia, body pain, constipation, skin disease, and as an aphrodisiac.

According to Ayurvedic characterisation, the plant is classified as having a sweet taste (Madhura Rasa), heavy and slimy qualities (Guru, Snigdha Guna), cold potency (Sheeta Veerya), and sweet post-digestive effect (Madhura Vipaka), with pharmacological actions described as diuretic, hepatoprotective, respiratory stimulant, antispasmodic, and hypotensive.

Traditional Ayurvedic uses include: Vrushya (aphrodisiac, improving vigour), Balya (improving strength and immunity), and Ruchya (improving taste, relieving anorexia).

2.2 Siddha Medicine (Tamil Nadu)

In Siddha/Ayurvedic medicine, the plant is referred to as Seethaveryam or Mathuravipaka and is used to treat premeham (diabetes) and athisaram (dysentery). In Tamil usage, the plant (known as Neermulli) is a documented component of formulations directed at urinary stone expulsion, kidney disorders, and liver disease.

2.3 Unani Medicine

In Ayurvedic and Unani literature, Hygrophila spinosa (syn. H. auriculata) is noted for its diuretic and aphrodisiac properties. The Unani designation Taalmakhaanaa applies to seed preparations used for genitourinary conditions.

2.4 Folk and Tribal Medicine

From the tribe Ruellieae, Hygrophila auriculata (local name: Su padang) is traditionally used to treat malaria in Myanmar. Aerial parts of the plant are used ethnobotanically for the treatment of body pain, jaundice, and malaria, while the seeds are used for treatment of impotence and thus as an aphrodisiac.

Its use in different pathophysiological conditions such as jaundice, rheumatism, renal stones, gonorrhoea, and hepatic disorders is documented in Indian system medicine and other standard literature, and it is also used to prevent anaemia during pregnancy. The sweet leaves are used in Bengali cooking, particularly along with small fried fish, while adding lemon or lime juice and honey.

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3. Key Phytochemical Constituents

3.1 Flavonoids

The plant has been reported to contain flavonoids including apigenin, luteolin, ellagic acid, gallic acid, and quercetin. The leaves contain sterols (beta-sitosterol, hydroxy-sitosterol), flavonoids (rutin, kaempferol, quercetin), minerals (calcium, potassium), tannins, acids (salicylic acid, malic acid), and amines (histamine).

3.2 Alkaloids

The plant's alkaloid fraction includes asteracanthine and asteracanthicine. These plant-specific alkaloids have been the focus of hepatoprotective activity research. The total alkaloid fraction has been isolated from leaf methanol extracts in several experimental studies.

3.3 Triterpenes and Sterols

Triterpenes identified include lupeol, lupenone, hentricontane, and betulin; sterols include stigmasterol and asterol. Aerial parts of Hygrophila auriculata have been specifically reported to contain lupeol, stigmasterol, and butelin, while the seeds are reported to contain mainly fatty acids.

Analysis of seed oil showed that alpha-tocopherol constitutes the dominant tocopherol fraction (91%) in H. auriculata, and that Δ5-stigmasterol (50%) dominates the sterol fraction, distinguishing it from most other aquatic plants in which beta-sitosterol predominates.

3.4 Additional Bioactive Compounds

The plant contains various groups of phytoconstituents including phytosterols, fatty acids, minerals, polyphenols, proanthocyanins, mucilage, alkaloids, enzymes, amino acids, carbohydrates, hydrocarbons, flavonoids, terpenoids, vitamins, and glycosides. The plant is also abundant in sodium, potassium, iron, fibre, vitamin C, and β-carotene.

The mucilage found in the seeds of H. auriculata has been linked to its use in treating respiratory disorders, while the potassium salts are believed to contribute to its diuretic effects.

GC-MS analysis of the entire H. auriculata plant extracted with diethyl ether revealed the presence of several compounds including tetradecanoic acid, diundecyl phthalate, 2-furancarboxaldehyde, hydroxymethyl, ellipticine, 2-hydroxycyclopentadecane, 1-octadecene, quercetin, and 2,3-dihydrobenzofuran.

3.5 Proposed Mechanisms of Action

The presence of bioactive sterols such as stigmasterol, β-sitosterol, and lupeol underscores the plant's medicinal properties, particularly in relation to its anti-inflammatory and hepatoprotective activities. Flavonoids and alkaloids may exert hypoglycaemic action; specific phytochemical compounds such as asteracanthine, luteolin, apigenin, asteracanthicine, lupeol, betulin, and β-sitosterol have been identified as potentially playing important roles in lowering elevated blood glucose levels.

The bioactive compounds are linked to phytopharmaceutical properties including antioxidant, cardioprotective, anti-diabetic, diuretic, hepatoprotective, androgenic, haematinic, anti-cancer, and anti-inflammatory activities.

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4. Scientific Evidence by Area of Use

Important note on evidence quality: The overwhelming majority of evidence for Hygrophila auriculata is preclinical — derived from in vitro cell studies and in vivo animal (rodent) models. Very few randomised controlled trials or well-designed human clinical studies exist. Where human data is referenced, this is noted explicitly. The following summaries represent the state of the evidence as reported in peer-reviewed publications.

4.1 Hepatoprotective Activity

Hepatoprotective and antioxidant effects of Hygrophila auriculata root extract (syn. Asteracantha longifolia, Acanthaceae) were studied in experiments widely used in Indian systems of medicine for the treatment of various liver ailments. The hepatoprotective activity of the aqueous extract of the roots was studied on CCl₄-induced liver toxicity in rats, assessed by monitoring liver function tests including alanine transaminase, aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, and total bilirubin, with hepatic tissues also subjected to histopathological studies. The root extract was studied for in vitro antioxidant activity using ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods, and exhibited significant hepatoprotective and antioxidant activities.

A published study in PMC found that the antihepatotoxic effect of the total alkaloid fraction was observed in freshly isolated rat hepatocytes at concentrations of 80–40 µg/ml. A dose-dependent increase in percentage viability was observed when CCl₄-exposed HepG2 cells were treated with different concentrations of the total alkaloid fraction. Its in vivo hepatoprotective effect at 80 mg/kg body weight was comparable with that of the standard silymarin at 250 mg/kg body weight. The total alkaloid fraction was able to normalise the biochemical levels that were altered due to CCl₄ intoxication.

Hepatoprotective potential of the aerial parts, roots, and whole plant has been studied using multiple models, including carbon tetrachloride-induced hepatotoxicity, paracetamol and thioacetamide intoxication, and galactosamine-induced liver dysfunction in rats.

Evidence strength: Moderate for preclinical (animal and cell-based) hepatoprotection. No published randomised controlled human clinical trials have been identified for this indication.

4.2 Diuretic and Anti-Urolithiatic (Kidney Stone) Activity

In the last four decades, various research teams have conducted experiments with Hygrophila spinosa (syn. H. auriculata) to screen the plant for hepatoprotective, anti-urolithiasis, diuretic, anti-hypertensive, anti-diabetic, chemoprotective, and anticancer activities. In the Ayurvedic system of medicine, Pashanabheda group plants are claimed to be useful in the treatment of urinary stones. Pashanabheda is the Sanskrit term for a group of plants with diuretic and antiurolithiatic activities (Pashana = stone; Bheda = break), within which H. auriculata is included.

Leaves, roots, and seeds are used as diuretics and for diseases of the urinogenital tract, spermatorrhoea. Preclinical diuretic studies have used rodent models in which extracts were compared against reference diuretics such as frusemide. For these experiments, male Wistar albino rats were utilised, with the first group administered frusemide (10 mg/kg, p.o.) as the reference comparator.

Evidence strength: Preliminary; evidence is from animal studies and traditional case records. No formal human clinical trial data are available for the diuretic or antiurolithiatic claims.

4.3 Anti-Inflammatory and Antinociceptive Activity

Extracts of ethanol and distilled water of Hygrophila auriculata were shown to have significant anti-inflammatory activity at a dose of 400 mg/kg body weight against carrageenan-induced inflammations in rats and mice, when compared with the standard drugs diclofenac sodium and metamizole.

Using acetic acid writhing test (chemical method) and hot plate and tail flick tests (thermal methods), both extracts at doses of 100 and 200 mg/kg p.o. inhibited abdominal constrictions induced by acetic acid and also increased the pain threshold of mice toward thermal sources in a dose-dependent manner.

Crude extract (CrE) induced significant antinociceptive activity of 50 and 57.28% at doses of 150 and 300 mg/kg, respectively.

Evidence strength: Preliminary; all evidence is animal-based (rodent models of acute inflammation and chemical/thermal nociception). No human clinical trial data exist for this indication.

4.4 Antidiabetic and Hypoglycaemic Activity

Hygrophila auriculata has been shown to possess hypoglycaemic activity in human subjects (Fernando et al., 1989) — this represents one of the few references to human data in the literature, though the original study dates to 1989 and cannot be evaluated without access to the full report's methodology and sample size.

Intake of H. auriculata extract at 100–250 mg/kg body weight for three weeks was shown to lower TBARS (thiobarbituric acid reactive substances), blood glucose, and hydroperoxide in diabetic rats.

A study examined the antihyperglycaemic effect in a rat model of diabetes induced by the alloxan method, using dried flower powder of H. auriculata and Cordia macleodii, both alone and in combination. Five hours after oral treatment, the investigation showed that a mixture of dried flower powder of H. auriculata and C. macleodii significantly reduced blood sugar levels.

Evidence strength: Weak-to-preliminary for human use. One older reference to human hypoglycaemic activity exists but lacks detailed methodology in the published record; all recent controlled evidence is from animal (alloxan-induced diabetic rat) models.

4.5 Hematopoietic Activity (Blood Formation)

The aerial parts of the plant are used in traditional medicine to treat blood disorders, and the plant has attributed medicinal properties that include hematopoietic activity. It is also described as preventing anaemia during pregnancy. Hematopoietic potential has been linked to the plant's notable iron content, and laboratory investigations have evaluated erythropoietic effects in animal models.

Evidence strength: Preliminary; based on in vivo animal studies and traditional use. No peer-reviewed human clinical trial data are available.

4.6 Androgenic and Anabolic Activity

Anabolic and androgenic activities of H. auriculata were reported by Jayatilak et al. (1976). The plant's seeds, in particular, are used in Ayurvedic practice as an aphrodisiac and for male reproductive health. Research into androgenic effects has been conducted in animal models. The plant has been attributed pharmacological activities including androgenic and anabolic properties, among others.

Evidence strength: Very preliminary; largely based on old animal studies. No modern randomised human clinical trials are available.

4.7 Antitumour Activity

Antitumour activity of Hygrophila spinosa (syn. H. auriculata) was reported by Mazmudar et al. on Ehrlich ascites carcinoma and sarcoma 180 induced in mice (Indian Journal of Experimental Biology, 1997). Results showed that the hydroalcoholic extract of H. spinosa possesses anti-tumour activity in these animal cancer models.

Evidence strength: Very preliminary; confined to in vitro and murine tumour models. No human oncology trials have been reported.

4.8 Antioxidant Activity

Crude extract (CrE) and ethyl acetate extract (EAE) showed potent activity in scavenging DPPH with IC₅₀ values of 9.14 ± 1.88 and 44.3 ± 0.85 µg/mL, respectively. Ethyl acetate, crude, butanol, and hexane fractions displayed greater than 80% activity in inhibition of β-carotene oxidation, while the ethyl acetate extract had an IC₅₀ of 0.87 ± 0.02 mg/mL in a hydroxyl radical scavenging assay.

Evidence strength: Moderate for in vitro radical scavenging; clinical relevance of in vitro antioxidant findings has not been established in human trials.

4.9 Antimicrobial Activity

Extracts and bioactive compounds from the plant have been found to possess antimicrobial activity across various pathogens in laboratory settings. Research using standard MIC (minimum inhibitory concentration) methods and zone-of-inhibition assays has demonstrated activity against various bacterial strains.

Evidence strength: Preliminary; all evidence is in vitro. No clinical trial data in humans are available.

4.10 Nephroprotective Activity

A study calculated the safe dose of ethanolic leaf extract (EHAE) using OECD 420 guidelines, finding no signs of toxicity or mortality at a maximum dose of 2000 mg/kg body weight, and chose doses of 250 and 500 mg/kg body weight for subsequent study. Results from all three drug-induced nephrotoxicity models (cisplatin, paracetamol, gentamycin) indicated a significant and dose-dependent reduction of serum biomarkers upon EHAE administration.

Evidence strength: Preliminary; preclinical rodent study only. No human data available.

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5. Body Systems and Health Areas Associated with Hygrophila

Based on the sum of traditional documentation and published experimental research, the following body systems and health areas are associated with H. auriculata:

• Hepatobiliary system: Medicinal systems use it to treat a number of liver disorders; roots and seeds have special application in medicines for jaundice and other hepatic obstruction.
• Genitourinary system: Parts of the plant are widely used in traditional medicine for the treatment of various disorders including diseases of the urinogenital tract, dropsy from chronic Bright's disease, vesical calculi, leukorrhoea, and gonorrhoea.
• Haematopoietic system (blood): Used for anaemia, blood purification, and hematopoiesis, with iron content and erythropoietic activity described in the ethnobotanical literature.
• Musculoskeletal / inflammatory system: Used for rheumatism, body pain, and oedema; anti-inflammatory and antinociceptive activities studied in rodents.
• Endocrine / metabolic system: Anti-diabetic and hypoglycaemic activities investigated in animal models and one older human reference.
• Reproductive system: Seeds are used for treatment of impotence and as an aphrodisiac.
• Gastrointestinal system: Used for diarrhoea, dysentery, flatulence, and constipation in traditional practice, with preclinical anti-diarrhoeal and antimotility evidence.
• Immune / antimicrobial: In vitro antimicrobial and potential immunomodulatory activity.
• Nervous system / neuroprotection: Antinociceptive properties tested in animal models; neuroprotective attributes are attributed in the literature but remain unvalidated in humans.
• Cardioprotective: Bioactive compounds are linked to cardioprotective properties, though human clinical evidence is absent.

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6. Dosage Forms and Reported Dosages

The following dosages are drawn strictly from published research and classical Ayurvedic references, as reported in sources found. They relate to experimental and traditional contexts and do not represent clinical recommendations.

6.1 Classical Ayurvedic Dosages

• Root decoction: 10 ml for jaundice and body swelling.
• Seed powder: 2–4 g with milk for impotence, low sperm count, and debility.
• Cold infusion of seeds: 25–30 ml for hepatomegaly and abdominal bloating.

6.2 Dosages Used in Preclinical Research

• Extract at 100–250 mg/kg body weight for three weeks in diabetic rat models for antihyperglycaemic and antioxidant effects.
• Total alkaloid fraction at 80 mg/kg body weight (in vivo), comparable in hepatoprotection to silymarin at 250 mg/kg in rat models.
• Ethanolic and aqueous extracts at 400 mg/kg body weight in rat/mouse models of carrageenan-induced inflammation.
• Extracts at doses of 100 and 200 mg/kg p.o. for antinociceptive activity in mice.
• Ethanolic leaf extract at doses of 250 and 500 mg/kg body weight, selected based on OECD 420 acute toxicity guidelines, for nephroprotective studies.
• Methanolic seed extract at 100 and 200 mg/kg body weight in chronic toxicity studies, producing no significant changes in biochemical parameters of liver and kidney or haematological parameters.
• Crude extract at 150 and 300 mg/kg for antinociceptive studies in rodents.

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7. Safety, Toxicity, and Interactions

7.1 Acute Toxicity

Acute and chronic toxicity profiles were studied with methanolic extract (MHA) of seeds of Hygrophila auriculata in rats. In acute toxicity studies, MHA did not produce any toxic manifestations up to the dose of 2000 mg/kg p.o. body weight.

An acute toxicity study investigated the methanol extract of leaves of H. auriculata on albino rats at a dose of 2000 mg/kg body weight, using a sighting study conducted stepwise using fixed doses of 5, 50, 300, and 2000 mg/kg body weight, with animals observed for 14 days. The single oral dose of the extract did not produce mortality or significant changes in body weight, food, and water consumption.

One study reported the acute toxicity of an aqueous aerial parts extract was above 2000 mg/kg body weight, which is classified as "slightly toxic" according to standard classification criteria.

7.2 Subacute and Chronic Toxicity

In chronic toxicity studies, the effect of the methanolic seed extract on biochemical parameters of liver and kidney, as well as haematological parameters, was studied. The extract did not produce any significant changes in the above parameters at doses of 100 and 200 mg/kg p.o. body weight.

The findings of a subacute (28-day repeated dose oral) toxicity study suggest that the Hygrophila spinosa extract and its combination can be used for the studied duration without any adverse effect in rodents.

Toxicological assessments indicate that the plant is generally safe at therapeutic levels. However, these conclusions are derived exclusively from animal studies, and long-term human safety data are absent.

7.3 Limitations of Available Safety Data

Formal toxicity study of the Hygrophila auriculata leaves extract is still lacking in comprehensive and standardised form. The absence of Phase I human safety trials, established LD₅₀ values in humans, or multi-centre safety monitoring data means that assessments of safety in human populations cannot be made with confidence from current evidence alone.

7.4 Interactions

More research is still needed to connect existing literature with contemporary pharmacology, including potential herb-drug interactions. Aqueous and ethyl acetate fractions of the plant showed significant percentages of clot lysis (35.15% and 30.08%, respectively), and crude, hexane, and ethyl acetate extracts inhibited blood clotting even after 3 hours in in vitro experiments — findings that suggest potential interaction with anticoagulant medications, though this has not been examined in human pharmacokinetic studies.

The plant's diuretic activity, confirmed in animal models, raises a theoretical concern for additive effects with pharmaceutical diuretics and potential electrolyte disturbance with long-term use, though no formal human interaction studies have been conducted. Given its documented hypoglycaemic effects in animal models and one older human reference, concurrent use with antidiabetic medications warrants attention.

7.5 Populations Requiring Caution

There is limited information on the safety of Hygrophila auriculata during pregnancy and lactation. The plant's traditional use in pregnancy to prevent anaemia is recorded, but no controlled safety data exist for this population. No formal paediatric safety data are available.

7.6 Evidence Gaps and Research Needs

The mechanisms underlying the plant's pharmacological effects remain largely unexplored, and prioritising efforts toward standardisation and thorough characterisation of its constituents is crucial to unlocking its full therapeutic potential. Future research should focus on isolated phytoconstituents and clinical trials to confirm efficacy. Preclinical research has validated pharmacological advantages; nonetheless, more investigation, including clinical trials, is required to fully realise its promise in contemporary medicine.

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