Alisma

Alisma (Rhizoma Alismatis, Ze Xie): A Comprehensive Reference

1. Identity and Botanical Characterization

1.1 Taxonomic Classification and Accepted Names

Rhizoma alismatis, known as "Zexie" in Chinese, is a perennial aquatic herb of the genus Alisma (Alismataceae), predominantly inhabiting temperate and subtropical marshlands across the Northern Hemisphere. Among 12 globally recognized Alisma species, six are endemic to China, with Alisma plantago-aquatica L. and A. plantago-aquatica subsp. orientale (Sam.) Sam holding particular medicinal significance.

Alisma plantago-aquatica, also known as European water-plantain, common water-plantain, or mad-dog weed, is a perennial flowering aquatic plant widespread across most of Europe and Asia, and apparently spread elsewhere in both the Old and New World. Alisma orientale, commonly known as Asian water plantain, is a flowering plant species in the genus Alisma found in Asia, and is sometimes treated as a variety of Alisma plantago-aquatica (Alisma plantago-aquatica var. orientale).

Chinese medicine Rhizoma Alismatis (RA) is the dried rhizome of the fresh plant Alisma plantago-aquatica L. subsp. orientale Sam., Alismataceae, which is mainly distributed in China, Russia, Japan, Mongolia, and North India. The tubers of A. orientale are additionally known in Japanese Kampo medicine as Takusha, and in Korean traditional medicine as Taeksa.

1.2 Botanical Description

Alisma plantago-aquatica is a hairless plant that grows in shallow water, consists of a fibrous root, several basal long-stemmed leaves 15–30 centimetres long, and a triangular stem up to 1 metre tall. It has a branched inflorescence bearing numerous small flowers, 1 cm across, with three round or slightly jagged, white or pale purple petals. The flowers open in the afternoon, and there are three blunt green sepals and six stamens per flower.

1.3 Medicinal Part and Common Preparations

The dried tubers of Alisma orientale, commonly referred to as Alismatis rhizome (AR), have long been used in traditional Chinese medicine to treat a variety of diseases. The 2020 edition of the Pharmacopoeia of the People's Republic of China includes two specifications: AR (standard rhizome) and salt-processed AR (SAR). The ability of salt-processed Alismatis Rhizoma (SAR) to nourish Yin and promote urination is considered stronger than that of unprocessed Alismatis Rhizoma (AR).

The rhizome is dug and collected in winter when the tuber and leaves become yellow; it has a slight smell and a slightly bitter taste. The product produced in Fujian and Jiangxi provinces, called Jian Ze Xie, is considered to be of good quality. The big, firm, white-yellow rhizome with much powder is preferred. It is sliced and used unprocessed, or baked with bran or salty water.

Alismatis rhizoma is a diuretic agent of key importance, whose diuretic effect is related to the season of harvest, the medicinal parts, the processing method, the route of administration, and the species of the tested organism. Moreover, the diuretic effect of genuine Alismatis rhizoma is strongest when collected in winter, while spring collection results in a slightly reduced effect.

Common commercial and clinical preparation forms include:

• Water decoctions (the traditional "Tang" preparation)
• Powdered dried rhizome
• Standardized ethanolic extracts and triterpene-enriched extracts
• Standardized tablets and capsules as part of multi-herb formulas
• Aqueous extracts used in research contexts

2. Traditional and Historical Use

2.1 Traditional Chinese Medicine (TCM)

These species were first documented in the Book of Songs · Wei Feng (ca. 11th–7th century BCE) and subsequently classified as a superior-grade (shang pin) botanical drug in the Shennong's Herbal Classic (ca. 200–300 CE) for their dampness-resolving, diuretic, and kidney-tonifying properties.

In China, RA was mentioned and recorded as a high-grade drug for the first time in the drug monograph Shen Nong's Herbal Classic (Shen Nong Ben Cao Jing), dated back to the Han dynasty. These points were inherited in the Compendium of Materia Medica and Huiyan of Materia Medica, though divergent perspectives also emerged as recorded in Bencao Yanyi and Bencao Yueyan. While maintaining consensus on diuretic and dampness-removal efficacy, debates arose regarding its tonifying effects, and some texts described nourishing of the five viscera organs and yin deficiency supplementation. In the Qing Dynasty and into the modern era, the effect of R. alismatis on diuresis was discussed in depth in "Herbal Reading," "Herbal Justice," "Ten Lectures on Medication Experience," and the 2020 edition of the Pharmacopoeia of the People's Republic of China.

Traditional Chinese medicine holds that Rhizoma alismatis has the effects of promoting water and dampness and venting heat. In TCM classification, it is sweet and bland in flavor, cold in temperature, and enters the kidney and bladder meridians, with the principal actions of inducing diuresis, draining dampness, and purging heat.

As a traditional medicine in China, RA is an important part of many prescriptions and has been commonly used for treating a wide range of ailments related to dysuria, edema, nephropathy, hyperlipidaemia, diabetes, inflammation, and tumor in clinical applications.

The rhizomes, which possess versatile bioactivities, are commonly used to treat oliguria, edema, gonorrhea with turbid urine, leukorrhea, diarrhea, and dizziness.

2.2 Classical Formulas Incorporating Alisma

In Traditional Chinese Medicine (TCM), Alisma is a key ingredient in the classic formula Liu Wei Di Huang Wan (Six-Ingredient Rehmannia Pill), where it works synergistically with other herbs to nourish the kidneys and balance yin and yang energies.

Alismatis Rhizoma Decoction (ARD), comprised of the rhizomes of Alisma orientale (Sam.) Juzep. (AR) and the rhizomes of Atractylodes macrocephala Koidz. (AMR) at a ratio of 5:2, was first described by Zhongjing Zhang in Jingui Yaolue. Alismatis Rhizoma Decoction (ARD) is a classical TCM formula for treatment of vertigo with a long history of successful clinical effect. The formula of ARD originated from the Jin Gui Yao Lve written by Zhongjing Zhang, a famous doctor of the Han Dynasty (ca. 220 CE) in ancient China.

Alisma is also a key component of Wuling San (Five-Ingredient Powder with Poria), a classical formula for water metabolism disorders. Alismatis Rhizoma (AR) is the dried tuber of Alisma plantago-aquatica L., a traditional diuretic used in China with a long history of use for treating edema, as seen in formulations like Wulingsan, Baizhusan, and Zexie Decoction.

2.3 Use in Japanese Kampo and Korean Medicine

The rhizome of the plant is also a herb used in Kampo Japanese medicine. RA has been extensively used in China, Japan, and many other countries for several centuries. In Korean traditional medicine, the herb is referred to as Taeksa and similarly employed in diuretic and anti-inflammatory preparations.

2.4 European Folk Use

According to Flora of the U.S.S.R. (1934), "a powder prepared from dried roots is used in popular medicine as a cure for rabies and crushed leaves are used against mammary congestion; fresh leaves are employed in homeopathy." A. plantago-aquatica is also known as mad-dog weed, as if it could be used to cure rabies, though it should not be confused with Scutellaria lateriflora (mad-dog skullcap).

3. Key Constituents and Active Compounds

3.1 Overall Phytochemical Profile

Rhizoma alismatis encompasses numerous chemical constituents, of which 262 metabolites have been identified thus far. According to their structure, these metabolites can be primarily classified into seven categories: terpenoids, sugars, nitrogen-containing compounds, phenylpropanoids, flavonoids, steroids, and phenolic acids.

Previous chemical studies on A. plantago-aquatica reported the identification of triterpenes, diterpenes, sesquiterpenes, steroids, alkaloids, and phenolic acid. Terpenes and phenolic acid are regarded as major secondary metabolites from this medicinal plant.

Systematic phytochemical studies have revealed that the active components of Zexie (Alismatis Rhizoma) are primarily triterpenoids, along with sesquiterpenes, polysaccharides, sterols, alkaloids, phenolic acids, and lignans, which form the material basis for its pharmacological activities.

3.2 Terpenoids: The Principal Bioactive Class

Among the terpenoids, triterpenoids, sesquiterpenes, and diterpenes are particularly abundant; triterpenes are considered to be the main active ingredients of Rhizoma alismatis. The structure of triterpenoids is mostly prototerpene tetracyclic triterpenoids, including alisol A, alisol B, alisol C, and alisol B 23-acetate.

In phytochemical aspects, the main bioactive constituents are protostane-type triterpenes and guaiane-type sesquiterpenes. Approximately 70 protostane triterpenes have been identified.

Approximately 120 compounds have been isolated from A. orientale. Terpenoids have been identified as A. orientale's characteristic constituents, which include protostane triterpenoids and guaiane sesquiterpenoids.

The most pharmacologically prominent compounds isolated from Rhizoma Alismatis include:

• Alisol A and Alisol A 24-acetate (C₃₂H₅₂O₆; MW 532.75 g/mol) — protostane-type triterpenes
• Alisol B and Alisol B 23-acetate (C₃₂H₅₀O₅; MW 514.8 g/mol) — considered chemotaxonomic markers of the genus
• Alisol C 23-acetate
• Alisol F (C₃₀H₄₈O₅; MW 488.7 g/mol) and Alisol F 24-acetate
• Alisol G
• Alismol (C₁₅H₂₄O; MW 220.356 g/mol) — a guaiane sesquiterpene

These include Alisol A 24-acetate (C₃₂H₅₂O₆, molecular weight of 532.75 g/mol), Alisol B 23-acetate (C₃₂H₅₀O₅, MW of 514.8 g/mol), Alisol F (C₃₀H₄₈O₅, MW of 488.7 g/mol), and Alismol (C₁₅H₂₄O, MW of 220.356 g/mol).

In the Chinese Pharmacopoeia, the content of alisol B 23-acetate in Rhizoma Alismatis should be not less than 0.050%.

3.3 Other Notable Constituents

Recent advancements in the isolation and identification of chemical constituents have highlighted a diverse array of compounds, including flavonoids, tannins, and polysaccharides, contributing to its therapeutic efficacy. Phenolic acids are additionally present; a new phenolic acid, plantain A, along with four known phenolic compounds were isolated and identified from A. plantago-aquatica by extensive chromatographic and spectrometric methods.

4. Mechanisms of Action

4.1 Diuretic Mechanism

Triterpene total extract (TTE) presented a notable diuretic effect by increasing Na⁺, K⁺, and Cl⁻ displacements. The most suitable triterpene component compatibility (TCC) for diuretic activity was validated, and triterpenes were confirmed as the material basis for the diuretic activity of AR.

Animal experiments showed that the diuretic effect of 80% ethanol extract of R. alismatis was stronger than that of water extract.

4.2 Lipid-Lowering (Hypolipidemic) Mechanism

Alisol acetates lower total cholesterol (TC) levels via inhibiting the activity of HMG-CoA reductase, which may exhibit an inhibition effect by directly and competitively binding to HMG-CoA. The side chain of the alisol acetate was the steering group as shown by molecular simulation.

A. orientale, including Alisol A 24-acetate and Alisol A 23-acetate, hindered hepatic de novo lipogenesis and accelerated β-oxidation via AMPK and PPARα activation by adiponectin, leading to the inhibition of hepatic triglyceride accumulation and increased lipid output from the liver. In addition, A. orientale suppressed hepatic gluconeogenesis by regulating hepatic expression of glucogenic genes like PEPCK and G6Pase via AMPK-SREBP1c signaling.

Alisol B 23-acetate intervened the downstream regulators of FXR such as SREBP1c, PPARα, and genes involved in triglyceride metabolism (ApoC-II, ApoC-III, and angiopoietin-like ANGPTL3), contributing to the improvement of hyperlipidemia as well as hepatic steatosis.

The triterpenoid contents in the ethanolic extract of A. orientale were identified as alisol A, alisol A 24-acetate, alisol B, alisol B 23-acetate, alisol C 23-acetate, alisol F, alisol F 24-acetate, and alisol G. The hypolipidemic effect of the triterpenoids is mediated mainly through alteration of gut microecology and the regulation of genes involved in cholesterol metabolism, especially Insig1.

4.3 Anti-Inflammatory Mechanism

In a rat study of chronic prostatitis, treatment with isolated phenolic compounds at 50 mg/kg produced a significant decrease in TNF-α, IL-1β, COX-2, PGE2, and TGF-β1 cytokine levels. The anti-chronic non-bacterial prostatitis effect was attributed to their anti-inflammatory properties.

Alisols have shown a series of biological activities, including anticancer, lipid-regulating, anti-inflammatory, antibacterial, antiviral, and diuretic activities.

4.4 Farnesoid X Receptor (FXR) Activation

FXR activation suppresses the expression of ER stress markers (PERK, EIF2α, and ATF4) and CHOP signaling, thereby reducing hepatocellular ER stress. Alisma orientalis can restore the hepatocellular ER homeostasis by stimulating FXR activation, particularly through Alisol A 24-acetate and Alisol B 23-acetate.

4.5 Anticancer Signaling Pathways

Recent evidence has demonstrated that the Alismatis rhizome extract showed pharmacological activities to effectively reverse cancer-related molecular targets. In particular, triterpenes naturally isolated from AR have been found to exhibit antitumor activity. Biological activities and plausible signaling cascades involve cancer-related physiology and pathology. In terms of anticancer activity, it exhibits proliferation inhibition and apoptosis induction in various tumor cells such as liver, lung, and colon cancers.

5. Scientific Evidence by Area of Use

5.1 Diuretic and Fluid Metabolism Effects

The diuretic activity of Rhizoma Alismatis is the most extensively studied and best-supported pharmacological property. Alismatis rhizoma (AR), the dried rhizoma of Alisma orientale Juzepzuk (Alismataceae), is a traditional Chinese medicine and is an important part of many prescriptions, commonly used as a diuretic agent in Asia.

One study evaluated the diuretic effects of total triterpene extract (TTE) and triterpene component compatibility (TCC, comprising alisol B 23-acetate, alisol B, alisol A 24-acetate, alisol A, and alisol C 23-acetate) in saline-loaded rats. The optimal diuretic TCC was optimized using a uniform design. Different doses (5, 20, and 40 mg/kg) of TTE and TCC groups were orally administered to rats. Urinary excretion rate, pH, and electrolyte excretion were measured. Results showed that TTE doses increased urine volume and electrolyte excretion compared with the control group.

Evidence strength for diuretic effect: Reasonably well-supported in preclinical (animal) models with identification of the triterpene constituents responsible, but robust prospective human clinical trials specifically examining Rhizoma Alismatis as a standalone diuretic agent are limited. Its presence in the Chinese Pharmacopoeia reflects a long clinical consensus.

5.2 Lipid-Lowering and Cholesterol Effects

Modern pharmacology studies have indicated that A. orientalis possesses diuretic, antiplasmodial, anti-HBV, hypolipidemic, and hyperglycemic activities.

Alismatis Rhizoma Decoction (ARD) is a classical TCM formula with a long history of successful clinical use in treatment of vertigo. Chen et al. found the anti-hyperlipidemia effect of a modified ARD formula was similar to that of Lovastatin in essential hyperlipidemia patients. However, this comparison was cited in a review paper rather than being a primary clinical report accessible for detailed assessment, and its methodology is not fully characterizable from available abstracts. The evidence from this specific human comparison should therefore be considered preliminary.

Molecular docking demonstrated that three key compounds could bind to FXR and were potential FXR agonists for the treatment of hyperlipidemia. This study elucidated the effective components and potential molecular mechanism of action of Alismatis Rhizoma Decoction for treating hyperlipidemia.

Evidence strength for lipid-lowering effects: Predominantly preclinical (in vitro and animal models). Proposed mechanisms (HMG-CoA reductase inhibition, FXR agonism, AMPK pathway activation) are biologically plausible and supported by experimental data, but rigorous, large-scale, randomized human clinical trials are lacking. Existing human evidence is largely drawn from traditional use claims and small or uncontrolled studies.

5.3 Nonalcoholic Fatty Liver Disease (NAFLD) and Hepatic Steatosis

A. orientale and its chemical substances can contribute to the treatment of NAFLD and metabolic syndrome based on their pharmacological activities such as antisteatotic, antioxidant, antilipoapoptotic, hepatoprotective, anti-inflammatory, antifibrotic, hypolipidemic, antiobesity, and hypoglycemic effects. In particular, A. orientale regulated effectively lipid and glucose metabolism in the liver and controlled liver injury like oxidative stress, inflammation, and fibrosis. Moreover, A. orientale was involved in hyperglycemia, obesity, or hyperlipidemia, representative comorbidities of NAFLD.

Chronic administration of Alisol B alleviated hepatic steatosis, along with decreased inflammatory cytokine expression and improved lipid peroxidation in murine NASH models. Alisol A 24-acetate and Alisol B 23-acetate were reported to ameliorate NASH via stimulating autophagy and regulating AMPK/mTOR signaling or activating FXR, respectively. Alisol B also uncovered novel molecular mechanisms on hepatic steatosis and lipotoxicity via regulating the RARα-PPARγ-CD36 transcriptional cascade.

A. orientale prevented hepatic triglyceride accumulation through suppressing de novo lipogenesis and increasing lipid export. In addition, it controlled oxidative stress markers, lipoapoptosis, liver injury panels, and inflammatory and fibrotic mediators, eventually influencing steatohepatitis and liver fibrosis. Moreover, it exhibited pharmacological activities against hyperlipidemia, obesity, and hyperglycemia as well as appetite.

Taken together, A. orientale might be an effective candidate agent for the treatment of NAFLD and its comorbidities, although further assessment of its standardization, safety test, and clinical trials is consistently required.

Evidence strength for NAFLD: Mechanistic understanding is advancing based on preclinical (in vitro and animal) studies. No published randomized controlled trials in human NAFLD populations have been identified. Evidence is currently preclinical only and cannot be extrapolated to clinical recommendations without formal human trials.

5.4 Anti-Inflammatory Effects and Chronic Prostatitis

Previous studies on this plant revealed that the water extract of A. plantago-aquatica showed significant anti-chronic prostatitis activity in rats. Phenolic compounds isolated from A. plantago-aquatica markedly decreased inflammatory factors expression and showed significant anti-chronic prostatitis activity in rats at doses of 50 mg/kg in that study.

Evidence strength for anti-inflammatory/prostatitis effects: Limited to animal models at this time. Results are biologically interesting but insufficient to draw clinical conclusions without human trial data.

5.5 Antidiabetic and Glycemic Effects

A. orientale stimulated adiponectin and subsequently suppressed hepatic de novo lipogenesis and accelerated fatty acid oxidation via AMPK and PPARα activation, resulting in decreased hepatic triglyceride contents and lipid output acceleration from the liver. In addition, A. orientale regulated hepatic gluconeogenesis by lowering PEPCK and G6Pase mRNA via AMPK-SREBP1c signaling.

The dried tubers of A. orientale have long been used in traditional Chinese medicine to treat a variety of diseases, including dysuria, diarrhea, edema, stranguria, diabetes, and hyperlipidemia.

Evidence strength for antidiabetic effects: Primarily preclinical (animal models with diabetic induction). Mechanistic studies in vitro support glucose metabolism modulation, but clinical human evidence is absent from the peer-reviewed literature examined.

5.6 Antiurolithiasis (Kidney Stone) Effects

The antiurolithiasis effect of Alismatis Rhizoma has been clearly linked to inhibiting the crystallization of stone components and promoting stone expulsion; its renal protective effect can ameliorate kidney injury by reducing oxidative stress and suppressing inflammatory responses in renal tissues.

Modern pharmacology has demonstrated its kidney stone protective, lipid-lowering, hypoglycemic, liver-protecting, and antibacterial activity. Modern pharmacological studies have shown that it also has a variety of biological activities, such as diuretic inhibition of kidney stone formation, anti-inflammatory and antioxidant effects, blood lipid regulation, hypoglycemic, liver protection and antibacterial, anti-tumor effects.

Evidence strength for antiurolithiasis: Animal and in vitro data exist. The proposed mechanism (inhibition of stone component crystallization) is plausible, but clinical human evidence is not established.

5.7 Anticancer Activity

Alisols have shown a series of biological activities including anticancer, lipid-regulating, anti-inflammatory, antibacterial, antiviral, and diuretic activities. Alisol B 23-acetate in particular exhibits significant anti-tumor activity.

Alismatis rhizome has long been used to treat inflammatory diseases, hyperlipidemia, diabetes, bacterial infection, edema, oliguria, diarrhea, and dizziness. Recent evidence has demonstrated that its extract showed pharmacological activities to effectively reverse cancer-related molecular targets. In particular, triterpenes naturally isolated from AR have been found to exhibit antitumor activity.

Evidence strength for anticancer activity: Evidence is in vitro and animal-model based. Proliferation inhibition and apoptosis induction have been demonstrated for liver, lung, and colon cancer cell lines in laboratory settings, but no human clinical oncology trials have been identified. This area is exploratory.

5.8 Cardiovascular and Anti-Atherosclerotic Effects

A. orientale was found to have divergent biological actions that include diuretic, antiurolithiasis, antinephritic, hepatoprotective, anti-atherosclerotic, and immunomodulatory activities.

Liu-wei-Di-huang (LWDH), a classical Chinese medicine prescription containing tubers of Alisma orientale as one of its six components, reduces serum lipid, Hcy, CHOP, and Caspase-3 levels in ovariectomized (Ovx) ApoE⁻/⁻ mice, suggesting that LWDH may exert a preventive and therapeutic effect on atherosclerosis. However, this was demonstrated in an animal model and the contribution of Alisma specifically versus the whole formula cannot be isolated from this study design.

Evidence strength for cardiovascular effects: Preliminary. Multi-herb formula animal data exist, and individual compound studies at the cellular level demonstrate relevant molecular activity, but human clinical cardiovascular trial data attributable specifically to Alisma are not available.

6. Body Systems and Health Areas Associated with Alisma

• Urinary system: Diuretic effects, reduction of dysuria, edema, and urinary stranguria; kidney stone inhibition
• Hepatic/biliary system: Hepatoprotective activity; anti-NAFLD effects via lipid metabolism regulation and FXR agonism
• Metabolic/endocrine system: Lipid-lowering, hypoglycemic, and anti-obesity effects via AMPK, PPARα, and FXR pathways
• Renal system: Nephroprotective effects at therapeutic doses; potential nephrotoxicity at overdose
• Immune and inflammatory system: Anti-inflammatory activity via reduction of TNF-α, IL-1β, COX-2, and PGE2
• Oncological: In vitro antitumor activity (liver, lung, colon cancer cell lines)
• Cardiovascular: Anti-atherosclerotic potential, cholesterol regulation

7. Dosage Forms and Reported Dosages

In TCM decoction practice, the standard recommended dose is 5–10 g of the dried rhizome, decocted in water.

In preclinical research studies, the following doses have been reported:

• Different doses of 5, 20, and 40 mg/kg of total triterpene extract (TTE) were administered orally to saline-loaded rats in diuretic efficacy experiments.
• In the chronic prostatitis rat model, isolated phenolic compounds were administered at 50 mg/kg.
• In the 90-day subchronic toxicity study, Sprague-Dawley rats received doses of 0, 360, 720, and 1440 mg/kg/day of triterpene-enriched extract for 90 days.
• In the 90-day aqueous extract safety study, ARAE was administered orally to male and female rats for 90 days at 0 (control), 500, 1,000, and 2,000 mg/kg/day.

In the context of classical TCM formulas, Zhibai Dihuang pill, a well-known formula, includes Alisma orientale at a dose proportion ratio of 3 parts (alongside Rehmannia glutinosa at 8, Dioscorea batatas at 4, Cornus officinalis at 4, Poria cocos at 3, Paeonia moutan at 3, and Anemarrhena asphodeloides at 2).

Note: No standardized dosage for isolated alisol compounds has been established for human use in the peer-reviewed clinical literature reviewed. Reported dosages above are drawn from traditional pharmacopoeia guidelines and preclinical experimental contexts only.

8. Safety Considerations

8.1 General Safety Profile

Alismatis Rhizoma has been generally considered safe at recommended doses. However, overdosage may induce hepatotoxicity and/or nephrotoxicity. The safety of its water-soluble fraction has been confirmed by some recent studies.

The safety of the lipid-soluble fraction of Alismatis Rhizoma containing various triterpenes has not been fully scientifically established.

8.2 Preclinical Toxicology Studies

In a 90-day repeated oral dose toxicity study of Alismatis Rhizoma aqueous extract (ARAE) in Sprague-Dawley rats, ARAE was administered at 0 (control), 500, 1,000, and 2,000 mg/kg/day (n = 10 per sex per dose group). An additional recovery group was observed for a 28-day recovery period. Treatment-related effects including an increase in red blood cells, hemoglobin, hematocrit, albumin, total protein, and urine volume were observed in males of the 2,000 mg/kg/day group. However, these hematological and serum biochemical changes were attributed primarily to the diuretic effect of ARAE. The oral no-observed-adverse-effect level (NOAEL) of ARAE was determined to be greater than 2,000 mg/kg/day in both genders, and no target organs were identified for toxicity.

A separate study on the triterpene-enriched extract found no chronic toxicity at the dose of 1440 mg/kg/day in both sexes in rats. However, a study found that components of RA possessed nephrotoxicity at higher doses.

8.3 Hepatotoxicity and Nephrotoxicity Risk

RA was once commonly considered to be a traditional medicine with little toxicity. High-dose or long-term use of RA can lead to water-electrolyte imbalance, hematuria, and even acidosis. However, overdose or long-term usage of RA may result in hepatotoxicity or nephrotoxicity.

Toxicology studies on Alisma orientale have revealed that chronic administration may induce mild nephrotoxicity and hepatotoxicity, emphasizing the need to verify the toxicity and safety profile of its compounds and their molecular mechanisms.

Network toxicology analysis illustrated that the triterpenoids were the main therapeutic compounds and emodin was identified as a potential main toxic compound of Alisma orientale.

8.4 Fresh Plant Toxicity

The distinction between fresh and processed plant material is clinically relevant. The raw, fresh rhizome and leaves of Alisma plantago-aquatica may carry distinct risks that are mitigated by traditional processing methods including drying, baking with bran, or salt-water processing.

8.5 Quality Control Marker

In the Chinese Pharmacopoeia, the content of alisol B 23-acetate in RA should be not less than 0.050% — a regulatory quality standard that reflects the importance of ensuring adequate and consistent levels of the principal bioactive triterpene in commercial preparations.

8.6 Drug Interactions

No formal pharmacokinetic drug-interaction studies in humans were identified in the peer-reviewed literature reviewed. Given Alisma's known involvement in CYP-mediated pathways and its FXR agonist properties, interactions with drugs that are FXR ligands or substrates of hepatic metabolism pathways are pharmacologically plausible but have not been clinically characterized. The documented in vitro inhibition of human carboxylesterase 2 by protostane triterpenoids from Alisma orientale has been noted in the scientific literature, which could theoretically affect the metabolism of drugs processed by that enzyme.

References

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• Frontiers in Pharmacology (2025): Botany, traditional uses, phytochemistry, pharmacology, toxicology and processing of Rhizoma alismatis: a review
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