Sparganium

Sparganium (Sparganium stoloniferum Buch.-Ham.): A Comprehensive Reference

1. Identity and Botanical Classification

Taxonomy and Nomenclature

Sparganii Rhizoma (SR; Chinese: 三棱), a widely used gynecological drug in traditional Chinese medicine (TCM), is the dried tuberous rhizome of Sparganium stoloniferum Buch.-Ham. (Family: Sparganiaceae). The family Sparganiaceae contains about 20 species in temperate regions of both the Northern and Southern Hemispheres. The drug is most commonly known in English as bur-reed rhizome or common bur-reed tuber. In pinyin Chinese it is rendered Sān Léng (三棱); in Korean practice it is called samreung.

Common names include Sparganium Rhizome, Rhizoma Sparganii Stoloniferi, Bur Reed Rhizome, and Scirpus. The full accepted botanical binomial is Sparganium stoloniferum (Graebn.) Buch.-Ham. ex Juz., and the drug-specific Latin designation used in Chinese pharmacopoeial and scholarly literature is Rhizoma Sparganii or Rhizoma Sparganii Stoloniferi.

The name "San Leng" (三棱, "Three Edges") refers to the sharply three-angled stem of the original plant source (the sedge Scirpus yagara). Over time, there has been considerable botanical confusion: the Ben Cao Tu Jing (Illustrated Classic of Materia Medica) described three forms based on tuber shape (flat like a crucian carp, round like a dark plum, or hooked like a chicken's claw), noting that "all three are one substance, differing only in the strength of their action." The Chinese Pharmacopoeia now designates the Sparganiaceae species Sparganium stoloniferum (known as "Hei San Leng" botanically) as the official source, while the sedge family species (Scirpus yagara, confusingly called "Jing San Leng" in commerce) is a commonly encountered substitute.

Botanical Description and Geographic Distribution

S. stoloniferum is a perennial aquatic or marsh herb, distributed in wet valley areas of East Asia (China, Japan and Korea), Europe and Africa. The plant is an aquatic marsh species found in the shallows of lakes, rivers, ponds, and similar environments in temperate climes around the world. Primary production areas in China include Jiangsu, Henan, Shandong, Jiangxi, Liaoning, Anhui, Zhejiang, Sichuan, and Hubei.

Commercial Forms and Preparations

The tubers of this plant are collected in the winter months after the aerial parts have finished their growth cycle for the season and withered. They are cleaned, peeled, dried, and then sliced for use as medicine. The decocting pieces are thin transverse slices, revealing the creamy white interior, which turns darker after processing with vinegar. Firm rhizomes with the outer skin completely removed and a pale-yellow outer surface are considered highest quality.

In commerce and clinical practice, Sparganii Rhizoma is available in the following principal forms:

• Raw, dried slices (crude SR): Cut or sliced transverse pieces for preparation of water decoctions.
• Vinegar-processed (Cu Sanleng / SR-CR): Slices stir-fried with rice vinegar; the history of Sparganium stoloniferum processing from the Tang Dynasty to the Qing Dynasty has been documented and summarized in classic TCM literature and successive editions of the Chinese Pharmacopoeia.
• Aqueous extract: An aqueous extract of RS (RS-W) is widely used in the treatment of blood stasis, amenorrhea, functional dyspepsia, and early stages of tumors, especially hysteromyoma, in China.
• Total flavonoid fraction (SRF): An isolated fraction employed in pharmacological research.
• Standardized granules and capsules: Modern pharmaceutical preparations used in contemporary TCM practice, often in combination with Curcumae Rhizoma.

2. Traditional and Historical Use

East Asian Medical History

SR was first recorded as a medicinal herb in a classic TCM book named Ben Cao Shi Yi (Tang Dynasty, A.D. 739), and it has been used to treat dysmenorrhea, mass in the abdomen, amenorrhea due to blood stasis, and abdominal distension in TCM for hundreds of years. San Leng was first recorded as a medicinal herb in the Ben Cao Shi Yi (Supplement to the Materia Medica) by Chen Cangqi during the Tang Dynasty (739 CE).

SR is often used together with Curcumae Rhizoma (CR) to get a better therapeutic effect, which was first recorded in Jing Yan Liang Fang (Qing Dynasty, A.D. 1842). It is mentioned in "Records of Chinese Medicine with Reference to Western Medicine" that Zhang Xichun often used this herbal combination in clinical practice and called it "the most important medicine for blood quickening."

Traditional Chinese Medicine Theory and Applications

According to TCM theory, SR possesses the following properties: bitter and pungent in flavor (味苦、辛), neutral in property (性平), attributive to the liver and spleen meridians (归肝脾经). Its functions are to eliminate blood stasis, promote the flow of Qi (破血行气), remove the retention of undigested food and relieve pain (镇痛消积).

SR is a gynecological drug which is often used to treat dysmenorrhea, mass in the abdomen, amenorrhea due to blood stasis, and abdominal distension in TCM. San Leng breaks blood stasis in severe cases characterized by palpable masses and severe, stabbing pain that is relatively fixed in its location. San Leng disperses qi stagnation and addresses epigastric and abdominal pain, often with indigestion.

In modern TCM practice, it is mainly used to treat common gynecological diseases such as uterine myoma, hyperplasia of mammary glands, ovarian cysts, endometriosis, infertility, and dysmenorrhea. Its main actions according to TCM include strongly breaking up Blood Stagnation, invigorating Blood and Qi, relieving pain, regulating menstruation, removing food stagnation, and promoting lactation.

Korean and Japanese Traditional Use

Sparganii Rhizoma is called "samreung" in Korea and has been used as a traditional Korean medicine to treat patients with gynecological diseases such as uterine fibroids, blood stasis, and dysmenorrhea. The herb has also featured in traditional Japanese Kampo medicine, typically in formulas addressing gynecological stasis and pain syndromes, though SR as a primary single ingredient is more prominent in Chinese and Korean traditions.

3. Key Chemical Constituents and Active Compounds

Phytochemical Overview

Approximately 180 compounds have been identified from SR, including phenylpropanoids, flavonoids, anthraquinones, organic acids, alkaloids, steroids, volatile oils, diarylheptanes, and others. A 2017 review reported a somewhat higher tally: phytochemical studies have revealed the presence of a total of 233 compounds belonging to alkaloids, nucleosides, organic acids, polysaccharides, volatile oils, and related classes.

Phenylpropanoids

The chemical components of SR have been identified as phenylpropanoids (such as ferulic acid, p-coumaric acid, caffeic acid), flavonoids (such as kaempferol, rutin, formononetin), coumarins (such as sparstolonin B), volatile oils (β-pinene, eucalyptol, myrtenol), and others. The isolation and structure elucidation of three phenylpropanoid glycosides along with three known phenylpropanoid glycerides from Chinese folk medicine "Sân Léng" (Sparganium stoloniferum Buch.−Hamil.) have been described, with structures elucidated by chemical and spectroscopical evidence including 2D-NMR studies. A 2023 study isolated four new ferulic acid sucrose esters together with four known phenylpropanoids from the rhizome of Sparganium stoloniferum.

Flavonoids

Key flavonoids isolated from SR include kaempferol, rutin, formononetin, and acacetin. The total flavonoids of SR (SRF) were active ingredients which exhibited anti-cancer and analgesic activities. Flavonoid compounds from SR showed significant anti-platelet aggregation activities. On the basis of chemical and biological data, the material basis of ACE inhibitory activity was the phenolic constituents, whereas the flavonoid compounds were responsible for the anti-platelet aggregation.

Coumarins — Sparstolonin B (SsnB)

The structure of sparstolonin B is 8,5′-dihydroxy-4-phenyl-5,2′-oxidoisocoumarin (i.e., a novel isocoumarin). Sparstolonin B (SsnB) selectively blocks TLR2- and TLR4-mediated inflammatory signaling. SsnB was isolated from Sparganium stoloniferum; its structure was determined by NMR spectroscopy and X-ray crystallography. SsnB has become the single most extensively studied isolated compound from SR, attracting broad interest across inflammation, oncology, and cardiovascular pharmacology.

Alkaloids and Other Notable Compounds

An aluminum complex alkaloid-glycoside (grailsine-Al-glycoside) was isolated from SR, and the aluminum element was identified as an active component of SR in the treatment of stomach diseases. A network pharmacology analysis identified seven main active ingredients in SR: acacetin, sanleng acid, ferulic acid, methyl 3,6-dihydroxy-2-[(2-hydroxyphenyl)ethynyl]benzoate, caffeic acid, adenine nucleoside, and azelaic acid.

A polysaccharide named SpaTA, described as a novel selective estrogen receptor modulator, was isolated from water extraction of SR. Compounds such as flavonoids, saponins, phenylpropanoids, and organic acids are the predominant pharmacodynamic basis of Sanleng.

4. Mechanisms of Action

Anti-inflammatory Mechanisms

SsnB effectively inhibited inflammatory cytokine expression in mouse macrophages induced by lipopolysaccharide (LPS, a TLR4 ligand), Pam3CSK4 (a TLR1/TLR2 ligand), and Fsl-1 (a TLR2/TLR6 ligand), but not by poly(I:C) (a TLR3 ligand) or ODN1668 (a TLR9 ligand). It suppressed LPS-induced cytokine secretion from macrophages and diminished phosphorylation of Erk1/2, p38α, IκBα, and JNK in these cells. SsnB may block TLR2- and TLR4-triggered inflammatory signaling by inhibiting the recruitment of MyD88 to the TIR domains of TLR2 and TLR4.

SsnB upregulated HO-1 production, inhibited luciferase-NF-κB interaction, and lowered COX-2/PGE2 and iNOS/NO, which led to the reduction of STAT-1 phosphorylation. SsnB found in Sparganium stoloniferum effectively suppresses the expressions of IL-1, IL-6, and TNF-α in response to LPS stimulation.

Antithrombotic and Antiplatelet Mechanisms

New ferulic acid sucrose esters isolated from S. stoloniferum exhibited obvious inhibitory effects on ADP-induced platelet aggregation. Total flavonoids of Sparganium stoloniferum (RS-F) have anti-platelet and anti-thrombotic actions in SD rats. The pharmacological effects of Sanleng include improvement of blood rheology, antiplatelet aggregation, and antithrombotic activity.

Estrogen Antagonism and Anti-angiogenic Mechanisms

The pharmacological mechanism of the aqueous extract of RS could be related to anti-angiogenesis and anti-estrogen activity. When Sparganii Rhizoma was studied in mice, there was a significant decrease in FGF-1 and VEGF levels, suggesting that Sparganii Rhizoma may have an effect on angiogenesis.

Bone Metabolism

SR inhibited osteoclast differentiation and decreased the expression of TNF receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells 1 (NFATc1), and c-Fos pathway. In addition, SR stimulates osteoblast differentiation and increased protein expression of the bone morphogenetic protein 2 (BMP-2)/SMAD signaling pathway. Among the constituent compounds, kaempferol, rutin, formononetin, ferulic acid, p-coumaric acid, and caffeic acid were previously found to inhibit osteoclast differentiation.

Anti-tumor Mechanisms

Seven active ingredients — including acacetin, sanleng acid, ferulic acid, caffeic acid, adenine nucleoside, and azelaic acid — were identified by molecular docking as having good affinity for hub gene proteins in gastric cancer. These seven active ingredients may be the material basis for SR to exert therapeutic efficacy in gastric cancer. Enrichment analyses found that the mechanism of action of the Sparganii Rhizoma–Curcumae Rhizoma combination in lung cancer mainly involved mitochondrial-mediated caspase-dependent cell apoptosis signaling pathways.

Cardiovascular Effects

SsnB suppressed vascular smooth muscle cell (VSMC) proliferation and migration induced by PDGF. SsnB significantly suppressed the expression of MCP-1, TNFα, and IL-6 in VSMCs. Erk1/2 and Akt signaling pathways were activated by LPS or PDGF stimulation, and SsnB significantly inhibited their activation. SsnB also substantially suppressed intracellular cholesterol accumulation in VSMCs loaded with acetylated LDL.

5. Scientific Evidence by Area of Use

5.1 Anti-inflammatory Activity

Nature of evidence: Preclinical (in vitro and animal); no published human clinical trials specifically on SR as an anti-inflammatory agent.

Blockade of excessive Toll-like receptor (TLR) signaling is a therapeutic approach being actively pursued for many inflammatory diseases. SsnB selectively blocks TLR2- and TLR4-mediated inflammatory signaling. The landmark in vitro and in vivo characterization study, published in the Journal of Biological Chemistry (2011), established that SsnB is a selective TLR2 and TLR4 antagonist. Additional preclinical work showed that as a selective TLR antagonist, SsnB showed significant pharmacological activities such as anti-tumour, anti-obesity, and anti-inflammatory effects in various inflammatory disorders. SsnB also plays a protective role in mouse models with LPS-induced lung disease.

These results are from mouse macrophage and rodent in vivo models. Translation to human clinical applications has not yet been established in peer-reviewed trials.

5.2 Antithrombotic and Cardiovascular Activity

Nature of evidence: Preclinical (in vitro and animal); no published standalone human clinical trials for SR as an antithrombotic agent.

In a study using rat left ventricular tissue slices, SsnB protected tissue from hypoxic injury by inhibiting the myocardial inflammatory response. Incubation with SsnB (15 and 30 μM) significantly reduced by 20 and 40%, respectively, the amount of LDH released from hypoxic LV slices. In atherosclerosis-relevant cell models, SsnB inhibited VSMC proliferation and migration induced by PDGF. The pharmacological effects of Sanleng include protection of cardiovascular and cerebrovascular vessels. All evidence to date in this domain is from animal or cell-based studies.

5.3 Anti-tumor Activity

Nature of evidence: Predominantly in vitro and network pharmacology; limited in vivo animal data; no randomized controlled human trials for SR as a standalone anti-cancer agent.

Sparganii Rhizoma has potential therapeutic effects on gastric cancer, but its main active ingredients and possible anticancer mechanism are still unclear. A study published in Scientific Reports (2021) employed HPLC-Q-TOF–MS/MS and network pharmacology to identify candidate active ingredients: forty-one compounds were ultimately identified: nine phenylpropanoids, eight organic acids, four flavonoids, four amino acids, two alkaloids, and fourteen other compounds. Molecular docking confirmed binding affinity of active ingredients for hub oncogenic proteins.

SsnB was isolated from an aquatic Chinese herb, Sparganium stoloniferum, and tubers of this herb have been used in traditional Chinese medicine for the treatment of several inflammatory diseases and cancers. Cell viability and morphological analysis indicated that SsnB at 10 µM concentration significantly inhibited the growth of both N-myc amplified (SK-N-BE(2), NGP, and IMR-32 cells) and N-myc nonamplified (SH-SY5Y and SKNF-1 cells) neuroblastoma cells.

The herbal combination Sparganii Rhizoma–Curcumae Rhizoma (HCSC) has been clinically used to relieve the symptoms of patients with tumors, especially gynecological ones. However, systematic, high-quality, randomized controlled clinical trial evidence specifically attributing anti-cancer efficacy to SR as a single agent is not currently available in the published English-language literature.

5.4 Gynecological Conditions (Uterine Fibroids, Endometriosis, Dysmenorrhea)

Nature of evidence: Preclinical animal studies; some limited clinical data in Chinese-language literature as part of multi-herb formulas; no high-quality English-language RCTs for SR as a monotherapy.

SR has been reported to exhibit therapeutic effects on thrombus, solid tumor, and endometriosis. It is usually used to treat endometriosis and chronic atrophic gastritis, while its underlying mechanisms are poorly delineated. It has been reported to exhibit therapeutic effects on thrombus, solid tumor, and endometriosis.

Among the most frequently prescribed herbs for uterine fibroids in TCM are Sparganii Rhizoma and Curcumae Rhizoma. Studies have been conducted on the effect of this herb pair on UF rats. When Sparganii Rhizoma was studied in mice, it was observed that there was a significant decrease in FGF-1 and VEGF levels, suggesting that Sparganii Rhizoma may have an effect on angiogenesis.

5.5 Osteoporosis and Bone Loss

Nature of evidence: Preclinical in vitro and animal (ovariectomized rat model); no human clinical data.

A study published in Frontiers in Pharmacology (2022) investigated the effect of SR on bone metabolism: SR inhibited osteoclast differentiation and decreased the expression of TRAF6, NFATc1, and c-Fos. In addition, SR stimulates osteoblast differentiation and increased protein expression of the BMP-2/SMAD signaling pathway. Moreover, SR protected against bone loss in OVX-induced rats. These results demonstrate the potential role of SR as an osteoclastogenesis-inhibiting and osteogenesis-promoting herbal medicine for the treatment of postmenopausal osteoporosis.

In the in vivo experiment, SR was orally administered to rats for 8 weeks. After 8 weeks, the levels of TRAP were significantly decreased in the SR-H (high dose) group. These findings are preliminary and confined to animal models.

5.6 Liver Inflammation (NASH)

Nature of evidence: Animal model only.

SsnB, a novel TLR4 antagonist derived from Sparganium stoloniferum, was investigated as a possible drug to mitigate early inflammation in NASH using an early steatohepatitic injury model in high-fat-fed mice. SsnB was administered for 1 week along with bromodichloromethane, an inducer of CYP2E1-mediated oxidative stress. Results showed that SsnB administration attenuated inflammatory morphology and decreased elevation of the liver enzyme ALT. Mice administered SsnB also showed decreased mRNA expression of proinflammatory cytokines TNF-α, IFN-γ, IL-1β, and IL-23. No human clinical data exist for this application.

6. Body Systems and Health Areas Associated with Sparganium

• Cardiovascular and Hematological System: SR has been used for eliminating blood stasis, promoting the flow of Qi, removing the retention of undigested food, and relieving pain in China for hundreds of years. Antiplatelet and antithrombotic effects have been documented in preclinical studies.
• Gynecological and Reproductive System: SR is mainly used to treat common gynecological diseases such as uterine myoma, hyperplasia of mammary glands, ovarian cysts, endometriosis, infertility, and dysmenorrhea.
• Gastrointestinal System: San Leng disperses qi stagnation and addresses epigastric and abdominal pain, often with indigestion. The herb is also used in the context of chronic atrophic gastritis.
• Immune and Inflammatory System: Via TLR2/TLR4 antagonism by sparstolonin B; suppression of NF-κB, COX-2, and proinflammatory cytokines.
• Musculoskeletal / Bone System: SR has demonstrated osteoclast-inhibiting and osteoblast-promoting effects in preclinical models.
• Oncological Applications (Investigational): SR and its isolated compounds have shown antiproliferative activity in cell-based cancer models across multiple malignancy types.
• Hepatic System: SsnB has shown preclinical evidence of attenuating liver inflammation in NASH animal models.

7. Dosage Forms and Reported Dosages

In TCM clinical practice, the preparation is as follows: collect the tuber or rhizome, clean, remove skin and dry. The dosage used is 3–10 g. This range refers specifically to the dried crude rhizome used in water decoctions.

In animal studies and preclinical experiments, the following dosages have been reported:

• Reproductive toxicity studies tested 100, 200, and 400 mg/kg RS extract in pregnant ICR mice.
• Incubation with SsnB at 15 and 30 μM concentrations was tested in the cardiac hypoxia model.
• In the OVX-induced bone loss model, SR was orally administered to rats for 8 weeks, with reference to low-dose (SR-L) and high-dose (SR-H) groups, though the exact mg/kg figures are not specified in the available abstracts.
• SsnB at 10 µM concentration significantly inhibited the growth of multiple neuroblastoma cell lines in vitro.

No standardized or regulatory-approved dosage exists outside of TCM frameworks. No human clinical trial has established a pharmacologically effective dose for any indication.

8. Safety Considerations and Drug Interactions

Reproductive Toxicity

Although no toxicity has been reported in normal animal studies with RS, it still has a potential reproductive toxicity because of its gynecological indications. The offspring of treated mice (100, 200, and 400 mg/kg RS extract) during pregnancy had various pathological conditions, suggesting an abnormal FGF signaling phenomenon during pregnancy. Embryos from the 400 mg/kg group had significantly depressed levels of FGF-1 (P < 0.01) and VEGF (P < 0.05) expression levels as compared to controls.

Intragastric administration of high-dose extracts of SR (400 mg/kg/d) in the teratogenic sensitive period of mouse pregnancy (10.0–19.0 days post-coitum) significantly shortened the pregnant period of mice. SR also has reproductive toxicity based on these animal findings.

Pharmacopeial Contraindications

San Leng precautions include: do not use if pregnant or nursing; do not use in cases of excessive bleeding. These contraindications reflect both TCM classical teaching and the mechanistic findings from reproductive toxicity studies.

Potential Drug Interactions — Anticoagulants and Antiplatelets

Given the documented antiplatelet and antithrombotic activity of SR's flavonoid and phenylpropanoid fractions, San Leng should be used with caution in persons taking anticoagulant medications such as heparin, warfarin (Coumadin), and enoxaparin (Lovenox), or antiplatelet drugs such as aspirin. This represents an additive pharmacodynamic interaction risk, mechanistically supported by the ADP-induced platelet aggregation inhibition demonstrated for SR's constituent phenylpropanoids.

Quality Control and Standardization

Quality control and evaluation, in-depth pharmacological mechanism, and toxicological effects of SR require further detailed research. The presence of a botanically distinct commercial substitute (Scirpus yagara, marketed as "Jing San Leng") introduces a real-world authentication challenge: the two sources have distinct chemical profiles, and lot-to-lot variation in products not authenticated per the Chinese Pharmacopoeia standard may affect both efficacy and safety assessments.

Estrogen Receptor Modulation

A polysaccharide named SpaTA, described as a novel selective estrogen receptor modulator, was isolated from SR. The pharmacological mechanism of the aqueous extract of RS could be related to anti-angiogenesis and anti-estrogen activity. This raises theoretical concerns in populations with hormone-sensitive conditions, though human data confirming clinically significant estrogenic or anti-estrogenic effects are currently absent.

Overall Evidence Characterization

The crude extracts and isolated components of SR have been reported to have anti-tumor, antithrombotic, estrogen antagonistic, anti-inflammatory, analgesic, antioxidant, anti-organ fibrosis, and other pharmacological activities. However, quality control and evaluation, in-depth pharmacological mechanism, and toxicological effects of SR require further detailed research. The totality of evidence for SR remains predominantly preclinical — in vitro cell studies and animal models — with a paucity of high-quality, adequately powered, randomized human clinical trials. Its pharmacological plausibility is strong and mechanistically coherent, but clinical efficacy and safety in humans have not been established to the standard required for regulatory approval in Western contexts.

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