Trillium Uses, Benefits & Dosage - Drugs.com Herbal Database

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# Trillium

Scientific Name(s): Trillium erectum L., Trillium govanianum Wall., Trillium grandiflorum (Michaux) Salisb., Trillium tschonoskii Maxim.
Common Name(s): Bethroot, Birthroot, Cough root, Great white trillium, Ground lily, Indian balm, Jew's harp, Purple trillium, Red trillium, Snake bite, Stinking Benjamin, Trillium, Trillium pendulum, Wake-robin, White wake-robin

Medically reviewed by Drugs.com. Last updated on Jan 1, 2022.

## Clinical Overview

### Use

Trillium has a history of use for various gynecological conditions and for controlling postpartum bleeding. Trillium may have a role in topical control of bleeding and provide relief from insect bites and skin irritations. However, there are no clinical trial data supporting use for any indication.

### Dosing

There is no clinical evidence to guide trillium dosing.

### Contraindications

Contraindications have not been identified.

### Pregnancy/Lactation

Avoid use. Adverse effects (emmenagogue and uterine stimulant) have been documented.

### Interactions

None well documented.

### Adverse Reactions

Although not clinically observed, trillium may have potential membrane-irritating effects and induce cardiac activity.

### Toxicology

While trillium leaves are considered edible, the possibility of toxicity from plant parts exists.

## Scientific Family

- Liliaceae (lily)
- Melanthiaceae alt. Trilliaceae

## Botany

The Trillium genus comprises approximately 48 interrelated species. T. erectum is a low-growing perennial that reaches a height of 40 to 45 cm and is native to North America. It has 3 dark-green, diamond-shaped leaves about 18 cm in length. From April to June, the plant produces a solitary, odiferous, yellow to reddish-brown flower; the common name "stinking Benjamin" derives from the unpleasant smell of the flower. T. erectum produces only 1 fruit per plant. T. grandiflorum is found in the Virginian mountains in the United States; T. tschonoskii in Bhutan, Japan, Korea, and China; and T. govanianum in Bhutan, India, Nepal, China, and Pakistan.(Chevallier 1996, Duke 2002, Lapointe 1998, Ur Rahman 2017)

## History

Various Trillium species have been used by American Indians to treat gynecological conditions (including irregular menstrual periods, menstrual pain, and excessive vaginal discharge) and to aid childbirth (hence the name birthroot). Other traditional uses include as an expectorant and for treatment of diarrhea. Topical preparations have been used to relieve insect bites and skin irritations. T. erectum is a popular folk remedy for treatment of bleeding, snakebites, and skin irritations. The leaves have been used as a potherb or salad green.(Chevallier 1996, USDA 2021) In China, T. tschonoskii has been used for hypertension and neurasthenia for thousands of years and is used clinically to treat traumatic brain injury and headache.(Li 2018, Yang 2021)

## Chemistry

Trillium species are rich sources of bioactive steroids, saponin derivatives, and flavonoids.(Ur Rahman 2017) Tertiary literature documents a fixed and volatile oil, a saponin (trillarin, which is a diglycoside of diosgenin), a glycoside resembling convallamarin, tannic acid, a resin, and considerable starch.(Chevallier 1996, Hufford 1988, Spoerke 1980) Steroidal saponins (ie, spirostanol, furostanol) have been identified, some of which may possess cytotoxic, antifungal, antioxidant, and cyclooxygenase-2 (COX-2) inhibitory activities.(Hayes 2009, Ur Rahman 2017, Yokosuka 2008)

## Uses and Pharmacology

Limited pharmacological data exist regarding T. erectum. Reviews of tertiary literature suggest the medicinal component of the plant is the rhizome. Although trillium has a long history of use as an herbal means of controlling postpartum bleeding as well as other uterine bleeding conditions, a clear mechanism for this systemic effect has not been identified.(Duke 2002, Osol 1955) The plant may have astringent properties that account for its ability to limit topical bleeding and irritation. This action was the basis for its historic use in diarrhea.(Osol 1955, USDA 2021) No chemical basis has been identified for its traditional use as an expectorant.

The saponin glycosides have been shown to have antifungal activity.(Hufford 1988) Steroidal saponins have been identified, some of which may possess cytotoxic activity.(Hayes 2009, Yokosuka 2008)

### Analgesic activity

#### Animal data

In mice, a methanolic extract of T. govanianum rhizomes and various fractions (ie, diosgenin, pennogenin, borassoside E) at 50 mg/kg and 100 mg/kg doses exhibited antinociceptive activity comparable to diclofenac sodium (P<0.05 to P<0.001). Results were similar for both tonic visceral and thermal nociception testing.(Ur Rahman 2016)

### Anti-inflammatory effects

#### Animal and in vitro data

Anti-inflammatory activity has been demonstrated with a T. govanianum rhizome methanol extract as well as a steroidal saponin extracted from T. tschonoskii rhizomes.(Ur Rahman 2016, Yan 2016) In a mouse paw edema model, a methanol extract of T. govanianum rhizome and various fractions (ie, diosgenin, pennogenin, borassoside E) at doses of 50, 100, and 200 mg/kg exhibited acute anti-inflammatory activity comparable to diclofenac sodium. The mechanism appeared to be related to inhibition of reactive oxygen species from whole blood.(Ur Rahman 2016) Furotrilliumoside is a steroidal saponin fraction extracted from the roots and rhizomes of T. tschonoskii that has been shown to have strong anti-inflammatory activity; in a mouse macrophage cell line, this fraction inhibited nitrite, tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) production, and COX-2 protein expression in a dose-dependent manner without affecting cell viability.(Yan 2016)

### Cancer

#### Animal and in vitro data

Six compounds isolated from the roots and rhizomes of T. tschonoskii were evaluated for effects on 6 cancer cell lines. One compound, identified as chonglouosid, exhibited significant toxicity in the 6 human tumor cell lines.(Yan 2021) A steroidal saponin (Paris saponin VII) was associated with several beneficial activities in human non–small cell lung cancer cell lines, including induction of apoptosis and autophagosome formation, activation of autophagy (via AMPK/mTOR signaling), and inhibition of proliferation.(Xiang 2021)

### Hepatoprotection

#### Animal data

In an acute liver injury rat model, hepatomegaly and increases in liver enzymes and liver index were reduced with administration of a T. tschonoskii ethanolic extract for 5 days. The effects resulted from a reduction in inflammatory markers (ie, TNF-alpha, IL-6) and inhibition of hepatocyte apoptosis in a dose-dependent manner.(Wu 2016)

### Neuroprotection

#### Animal data

Neuroprotection by T. tschonoskii rhizome extract and/or its active fractions has been demonstrated in rat models of Alzheimer disease, spinal cord injury, and brain aging.(Chen 2018, Luo 2018, Wang 2018) Spatial memory deficit and tau phosphorylation were significantly reduced with a T. tschonoskii aqueous extract given for 7 days in an Alzheimer disease model (P<0.05). The number of dendritic spines on pyramidal neurons in the hippocampus were preserved with the extract (P<0.05). Efficacy was similar to the positive control (vitamin B12 plus folate).(Luo 2018) In an acute spinal cord injury rat model, administration of a T. tschonoskii major bioactive saponin (diosgenin glucoside) significantly decreased structural damage and promoted functional recovery (P<0.05), as well as attenuated apoptosis caused by the spinal cord injury (P<0.01).(Chen 2018) In a brain-aging rat model, diosgenin improved learning and memory capacity (P<0.05) via mechanisms that involved inhibition of hippocampal neuron apoptosis and decreased dysfunctional autophagy in hippocampal tissue.(Wang 2018)

### Stroke

#### Animal data

In a rat ischemic stroke model, effects of oral T. tschonoskii rhizome (at human clinically equivalent doses of 33, 65, and 130 mg/kg for 15 days) on neurological function and survival rate were assessed. The 65 mg/kg dose consistently demonstrated maximal improvement in survival rates and neurobehavioral outcomes (P<0.05 and P<0.01), often with similar results to the positive control. Cerebral infarct volume was also markedly reduced with the T. tschonoskii rhizome 65 mg/kg dose (P<0.01), as was the grey and white matter injury (P<0.05 or P<0.01). Improvements in arterial occlusion and cerebral blood flow were also documented. Axonal microstructure in the ischemic stroke model was preserved, axonal reorganization improved, and axonal remyelination appeared to be promoted by T. tschonoskii rhizome saponins.(Li 2018)

## Dosing

There is no clinical evidence to guide trillium dosing.

## Pregnancy / Lactation

Avoid use. Adverse effects (emmenagogue and uterine stimulant) have been documented.(Lapointe 1998, USDA 2021)

## Interactions

None well documented.

## Adverse Reactions

Although not clinically observed, trillium may have potential membrane-irritating effects and induce cardiac activity.(Spoerke 1980)

## Toxicology

While trillium leaves are considered edible, the possibility of toxicity from plant parts exists. Saponin has potential membrane-irritating effects, and the convallamarin-like glycoside could induce cardiac activity, although neither of these events has been observed clinically.(Spoerke 1980)

In mice, the methanolic extract of T. govanianum rhizomes exhibited maximum mortality at 6,000 mg/kg, while no deaths were observed at 500 mg/kg. The median lethal dose was 2,030.4 mg/kg.(Ur Rahman 2016)

## References

## Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Chen XB, Wang ZL, Yang QY, et al. Diosgenin glucoside protects against spinal cord injury by regulating autophagy and alleviating apoptosis. Int J Mol Sci. 2018;19(8):2274. doi:10.3390/ijms1908227430072674
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Duke JA, Bogenschutz-Godwin MJ, duCellier J, Duke PK. Handbook of Medicinal Herbs. 2nd ed. CRC Press; 2002.
Hayes PY, Lehmann R, Penman K, Kitching W, De Voss JJ. Steroidal saponins from the roots of Trillium erectum (Beth root). Phytochemistry. 2009;70(1):105-113. doi:10.1016/j.phytochem.2008.10.01919091359
Hufford CD, Liu SC, Clark AM. Antifungal activity of Trillium grandiflorum constituents. J Nat Prod. 1988;51(1):94-98. doi:10.1021/np50055a0133373231
Lapointe L. Fruit development in trillium. Dependence on stem carbohydrate reserves. Plant Physiol. 1998;117(1):183-188. doi:10.1104/pp.117.1.1839576787
Li M, Ouyang J, Zhang Y, et al. Effects of total saponins from Trillium tschonoskii rhizome on grey and white matter injury evaluated by quantitative multiparametric MRI in a rat model of ischemic stroke. J Ethnopharmacol. 2018;215:199-209. doi:10.1016/j.jep.2018.01.00629309860
Luo HB, Shang N, Xie WZ, et al. Trillium tschonoskii maxim extract attenuates abnormal Tau phosphorylation. Neural Regen Res. 2018;13(5):915-922. doi:10.4103/1673-5374.23248729863023
Osol A, Farrar GE Jr, eds. The Dispensatory of the United States of America. 25th ed. J.B. Lippincott; 1955.
Spoerke DG. Herbal Medications. Woodbridge Press; 1980.
Trillium. USDA, NRCS. 2021. The PLANTS Database (http://plants.usda.gov, 16 November 2021). National Plant Data Team, Greensboro, NC 27401-4901 USA.
Ur Rahman S, Adhikari A, Ismail M, et al. Beneficial effects of Trillium govanianum rhizomes in pain and inflammation. Molecules. 2016;21(8):1095. doi:10.3390/molecules2108109527556434
Ur Rahman S, Ismail M, Khurram M, Ullah I, Rabbi F, Iriti M. Bioactive steroids and saponins of the genus trillium. Molecules. 2017;22(12):2156. doi:10.3390/molecules2212215629206216
Wang L, Du J, Zhao F, et al. Trillium tschonoskii maxim saponin mitigates D-galactose-induced brain aging of rats through rescuing dysfunctional autophagy mediated by Rheb-mTOR signal pathway. Biomed Pharmacother. 2018;98:516-522. doi:10.1016/j.biopha.2017.12.04629287199
Wu H, Qiu Y, Shu Z, et al. Protective effect of Trillium tschonoskii saponin on CCl4-induced acute liver injury of rats through apoptosis inhibition. Can J Physiol Pharmacol. 2016;94(12):1291-1297. doi:10.1139/cjpp-2016-022827598942
Xiang YC, Shen J, Si Y, et al. Paris saponin VII, a direct activator of AMPK, induces autophagy and exhibits therapeutic potential in non–small-cell lung cancer. Chin J Nat Med. 2021;19(3):195-204. doi:10.1016/S1875-5364(21)60021-333781453
Yan T, Wang A, Hu G, Jia J. Chemical constituents of Trillium tschonoskii Maxim. Nat Prod Res. 2021;35(20):3351-3359. doi:10.1080/14786419.2019.170024531928348
Yan T, Yu X, Sun X, Meng D, Jia JM. A new steroidal saponin, furotrilliumoside from Trillium tschonoskii inhibits lipopolysaccharide-induced inflammation in Raw264.7 cells by targeting PI3K/Akt, MARK and Nrf2/HO-1 pathways. Fitoterapia. 2016;115:37-45.
Yang L, Li CY, Ouyang JY, et al. Trillium tschonoskii rhizomes' saponins induces oligodendrogenesis and axonal reorganization for ischemic stroke recovery in rats. J Ethnopharmacol. 2021;279:114358. doi:10.1016/j.jep.2021.11435834166736
Yokosuka A, Mimaki Y. Steroidal glycosides from the underground parts of Trillium erectum and their cytotoxic activity. Phytochemistry. 2008;69(15):2724-2730. doi:10.1016/j.phytochem.2008.08.00418822438

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