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 Dec 22, 2023.
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
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