Trillium

Generic name: Trillium Erectum L., Trillium Govanianum Wall., Trillium Grandiflorum (Michaux) Salisb., Trillium Tschonoskii Maxim.
Brand names: 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

Usage of Trillium

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)

Trillium side effects

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

Before taking Trillium

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

How to use Trillium

There is no clinical evidence to guide trillium dosing.

Warnings

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)

What other drugs will affect Trillium

None well documented.

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