Scientific Name(s): Polygala senega L.
Common Name(s): Milkwort, Mountain flax, Polygalae radix, Rattlesnake root, Seneca snakeroot, Tenuigenin
Medically reviewed by Drugs.com. Last updated on Dec 21, 2021.
Senega has been traditionally used as an antitussive and has also demonstrated hypoglycemic, immunologic, and anticancer effects. However, there are no clinical trials to support these uses.
Root: 1 to 3 g/day. Fluid extract: 1.5 to 3 g/day or 0.3 to 1 mL/day. Tincture: 2.5 to 7.5 g/day or 2.5 to 5 mL/day.
Pregnancy, peptic ulcer disease, or inflammatory bowel disease.
Avoid use. Emmenagogue and uterine stimulant action has been documented.
None well documented.
High doses of powdered senega root or tincture are emetic and irritating to the GI tract.
When investigated for their immunological potential as adjuvants in vaccinations, saponin fractions of P. senega were less toxic than those of Quillaja saponaria.
- Polygalaceae (milkwort)
Senega root is an uncommon perennial herb found throughout eastern North America(van Wyk 2004); it has "endangered" status in Connecticut, Maine, and New Jersey and "threatened" status in Maryland.(USDA 2016) The plant grows to approximately 0.5 m in height and has unbranched stems arising from a branched root.(van Wyk 2004, WHO 2004) The leaves are small, alternate, and narrowly lanceolate. Numerous pinkish-white or greenish-white flowers are crowded on a terminal spike. The root is twisted and has an irregular, knotty crown with a distinctive ridge. Senega's faint, sweet scent is similar to that of methyl salicylate.(WHO 2004) The variety P. senega var. latifolia Torr. & Gray has been distinguished; it grows in the same habitat but differs from P. senega in the size of its leaves and flowers and in its slightly later flowering period. Related species include Polygala tenuifolia Willd., Polygala reinii Franch., Polygala glomerata Lour., and Polygala japonica Houtt., all of which are used in Asia in a similar manner to P. senega.
Senega root was used by eastern American Indian tribes, including the Seneca tribe (from whom its name is derived), to treat rattlesnake bites(van Wyk 2004); however, early European observers gave little credence to this use. Colonists and Europeans used senega root as an emetic, cathartic, diuretic, and diaphoretic, and in treatment of pulmonary diseases (such as pneumonia, asthma, and pertussis), gout, and rheumatism.(Erichsen-Brown 1979) Its main use in the 19th century was as an expectorant cough remedy. It was included in the US Pharmacopeia from 1820 to 1936 and in the National Formulary from 1936 to 1960.
Seneca snakeroot contains a series of saponins constructed from the 2,3,27-trihydroxy-oleanane 23,28-dioic acid triterpene skeleton (presenegenin), with a single sugar attached at position 3 and a 4- to 6-sugar chain appended at position 28. A variety of methoxy-cinnamate esters are attached at the internal sugar of the C-28 chain.(Akada 1971, Shoji 1971, Shoji 1971, Shoji 1972, Tsukitani 1973, Yoshikawa 1995, Yoshikawa 1996, Yoshikawa 1995) These saponins have been named senegins Ι through ΙV and senegasaponins A through C. The triterpene senegenin, also known as tenuigenin, is considered a major bioactive compound. The senegins can be analyzed by high-performance liquid chromatography.(Kanazawa 1993, Lacaille-Dubois 2020) Several other species of Polygala (see Botany) contain distinct but very similar saponins based on the same sapogenin.(Zhang 1998) An extensive series of ester oligosaccharides, senegoses A through O, have been isolated from P. senega var. latifolia.(Saitoh 1993, Saitoh 1993, Saitoh 1994) The root also contains a small amount of methyl salicylate, which is responsible for its characteristic wintergreen scent.
Uses and Pharmacology
The antitussive effect of senega root has generally been attributed to the saponin content of the plant, which is consistent with the general detergent property of saponins in breaking up phlegm.(van Wyk 2004) In addition, senega is thought to act by irritation of the gastric mucosa followed by a reflex action, which stimulates an increase in bronchial mucous gland secretion. However, most of the available information about senega's antitussive properties is anecdotal.
Animal and in vitro data
In a study of anesthetized dogs, senega syrup dosed orally at 3 mL/kg (about 90 mg/kg) increased the volume output of respiratory tract fluid within 5 minutes of administration; the increase continued at 30 minutes following administration.(Misawa 1980)
In one study, a fluid extract of senega root reduced mucus viscosity in patients with bronchiectasis.(WHO 2004)
Animal and in vitro data
In mice inoculated with sarcoma S180 cells, the senega saponin senegin III dosed at 2.5 mg/kg inhibited tumor growth in a manner similar to cisplatin. In addition, the combination of senegin III with cisplatin resulted in greater growth inhibition compared with the control group.(Arai 2011)
In in vitro and an in vivo models in mice, P. senega was beneficial in the treatment of lung cancer. Administration of senega 50 and 100 mg/kg in mice with long-term exposure to a carcinogen modulated the expression of signal proteins.(Paul 2010) Similarly, an ethanolic root extract of P. senega reduced DNA damage as well as tumor nodules and tumor growth in mice with benzo[a]pyrene-induced lung cancer.(Paul 2011) Nanoencapsulation of an ethanolic root extract of P. senega was associated with greater inhibition of cancer cell growth, better bioavailability, and increased cellular entry compared with the non-nanoencapsulated ethanolic root extract of P. senega.(Paul 2011)
Animal and in vitro data
In studies evaluating the hypoglycemic effects of senega saponins in mice with and without diabetes, hypoglycemic activity was observed in normal and diabetic mice, but not in mice with streptozotocin-induced diabetes.(Kako 1995, Kako 1996, Kako 1997, Yoshikawa 1995, Yoshikawa 1995, Yoshikawa 1996) Thus, these compounds have activity relevant to non–insulin-dependent diabetes. This activity is most potent when the saponins are injected intraperitoneally but can also be detected with higher oral doses. The same saponins also substantially reduced alcohol absorption when given orally to rats 1 hour before alcohol consumption.(Yoshikawa 1995, Yoshikawa 1996, Yoshikawa 1995)
In a study investigating an aqueous extract of the related species P. tenuifolia, a potent blocking effect on inflammatory processes in cultured mouse astrocytes was observed. Substance P– and lipopolysaccharide-induced production of tumor necrosis factor and interleukin-1 (IL-1) was blocked by a P. tenuifolia extract at low concentrations.(Kim 1998) It is possible that a systemic anti-inflammatory effect may be the result of a similar mechanism.
No biological activity has been reported for the oligosaccharides of senega root. Senegose A was inactive in the previously described hypoglycemia model.(Kako 1997)
Animal and in vitro data
In a murine model, P. senega saponins increased antibody response to ovalbumin antigens in mice. These effects were similar to those of saponins from Q. saponaria but were less toxic, suggesting a potential role as an adjuvant in vaccines.(Katselis 2007) Another study demonstrated similar effects in mice immunized with ovalbumin, with no P. senega saponin effect detected 10 days after immunization; in another arm of this study, P. senega saponins increased the immunoglobulin G response to rotavirus in immunized hens.(Estrada 2000) In an in vitro study, senega saponins exerted antiangiogenic activity against human umbilical vein endothelial cells.(Arai 2011)
A cell-screening assay of several P. senega extracts revealed dose-dependent anti-inflammatory effects, such as reductions in levels of IL-1beta, IL-6, and tumor necrosis factor alpha.(Van 2009)
Tenuigenin, the major active component of P. senega and other Polygala species, has been shown to be a significant inhibitor of NF-kappaB and capable of preventing IL-1beta-induced inflammation in human osteoarthritis chondrocytes. Significant decreases in many other pro-inflammatory cytokines (ie, TNF-alpha, IL-1beta, IL-6, IL-12, PGE-2) and enzymes (ie, iNOS, COX-2) have also been observed with tenuigenin, P. japonica, P. sabulosa, P. molluginifolia, and other species. Findings in animal models of neuroinflammation, pleurisy, peritonitis, pneumonia, liver, and kidney injury further support the anti-inflammatory effects of Polygala species and extracts.(Lacaille-Dubois 2020)
Neuroprotection against degeneration of dopaminergic neurons in a mouse model of Parkinson disease was documented for tenuigenin, which also improved neuroplasticity in vitro by potentiating basic synaptic transmission via regulation of presynaptic intracellular calcium. In an Alzheimer murine model, tenuigenin significantly improved memory-related behaviors and cognitive dysfunction via dose-dependent antioxidant effects in the hippocampus. Improvements in memory and cognitive function were also demonstrated with tenuigenin in a menopausal mouse model.(Lacaille-Dubois 2020)
1 to 3 g/day.(Blumenthal 1998, Claus 1956)
1.5 to 3 g/day(Brinker 1998) or 0.3 to 1 mL/day.(van Wyk 2004)
2.5 to 7.5 g/day(Blumenthal 1998) or 2.5 to 5 mL/day.(van Wyk 2004)
Pregnancy / Lactation
Avoid use. Emmenagogue and uterine stimulant action has been documented.(Brinker 1998, Ernst 2002)
None well documented.
High doses of powdered senega root (more than 1 g) or tincture are emetic and irritating to the GI tract.(Blumenthal 1998) The use of senega root is contraindicated during pregnancy, and in peptic ulcer disease or inflammatory bowel disease.(Grieve 1931) Senega may exacerbate inflammatory conditions of the GI tract.
When investigated for their immunological potential as adjuvants in vaccinations, saponin fractions of P. senega were less toxic than those from Q. saponaria, which have traditionally been used as adjuvants for veterinary vaccines.(Estrada 2000)
- Polygala glomerata Lour.
- Polygala japonica Houtt.
- Polygala reinii Franch.
- Polygala senega var. latifolia Torr. & Gray
- Polygala tenuifolia Willd.
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