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Senega Root

Scientific Name(s): Polygala senega L.
Common Name(s): Milkwort, Mountain flax, Polygalae radix, Rattlesnake root, Seneca snakeroot

Clinical Overview

Use

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.

Dosing

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.

Contraindications

Pregnancy, peptic ulcer disease, or inflammatory bowel disease.

Pregnancy/Lactation

Avoid use. Emmenagogue and uterine stimulant action has been documented.

Interactions

None well documented.

Adverse Reactions

High doses of powdered senega root or tincture are emetic and irritating to the GI tract.

Toxicology

When investigated for their immunological potential as adjuvants in vaccinations, saponin fractions of P. senega were less toxic than those of Quillaja saponaria.

Botany

Senega root is an uncommon perennial herb found throughout eastern North America1; it has "endangered" status in Connecticut, Maine, and New Jersey and "threatened" status in Maryland.2 The plant grows to approximately 0.5 m in height and has unbranched stems arising from a branched root.1, 3 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.3 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.

History

Senega root was used by eastern American Indian tribes, including the Seneca tribe (from whom its name is derived), to treat rattlesnake bites1; 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.4 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.

Chemistry

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.5, 6, 7, 8, 9, 10, 11, 12 These saponins have been named senegins Ι through ΙV and senegasaponins A through C. The senegins can be analyzed by high-performance liquid chromatography.13 Several other species of Polygala (see Botany) contain distinct but very similar saponins based on the same sapogenin.14 An extensive series of ester oligosaccharides, senegoses A through O, have been isolated from P. senega var. latifolia.15, 16, 17 The root also contains a small amount of methyl salicylate, which is responsible for its characteristic wintergreen scent.

Uses and Pharmacology

Antitussive effects

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.1 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.18

Clinical data

In one study, a fluid extract of senega root reduced mucus viscosity in patients with bronchiectasis.3

Hypoglycemic effects

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.10, 11, 12, 19, 20, 21 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.10, 11, 12

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.22 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.21

Clinical data

Research reveals no clinical data regarding the use of senega root for its hypoglycemic effects.

Immunological effects

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.23 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.24 In an in vitro study, senega saponins exerted antiangiogenic activity against human umbilical vein endothelial cells.25

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.26

Clinical data

Research reveals no clinical data regarding the use of senega root for its immunological effects.

Anticancer effects

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.25

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.27 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.28 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.29

Clinical data

Research reveals no clinical data regarding the use of senega root for its anticancer effects.

Dosing

Root

1 to 3 g/day.30, 31

Fluid extract

1.5 to 3 g/day31 or 0.3 to 1 mL/day.1

Tincture

2.5 to 7.5 g/day31 or 2.5 to 5 mL/day.1

Pregnancy / Lactation

Avoid use. Emmenagogue and uterine stimulant action has been documented.32, 33

Interactions

None well documented.

Adverse Reactions

High doses of powdered senega root (more than 1 g) or tincture are emetic and irritating to the GI tract.31 The use of senega root is contraindicated during pregnancy, and in peptic ulcer disease or inflammatory bowel disease.34 Senega may exacerbate inflammatory conditions of the GI tract.

Toxicology

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.24

References

1. van Wyk BE, Wink M, eds. Medicinal Plants of the World: an Illustrated Scientific Guide to Important Medicinal Plants and Their Uses. 1st ed. Portland, OR: Timber Press Inc; 2004.
2. Polygala senega L. USDA, NRCS. 2016. The PLANTS Database (http://plants.usda.gov, 21 September 2016). National Plant Data Team, Greensboro, NC 27401-4901 USA. Accessed September 21, 2016.
3. Radix Senegae. In: WHO Monographs on Selected Medicinal Plants. Vol. 2. Geneva: World Health Organization; 2004. http://apps.who.int/medicinedocs/en/d/Js4927e/27.html. Accessed September 23, 2016.
4. Erichsen-Brown C. Medicinal and Other Uses of North American Plants. Dover, NY: Dover Publications; 1979:359-362.
5. Shoji J, Kawanishi S, Tsukitani Y. Studies on the constituents of Senegae radix. Ι. Isolation and qualitative analysis of the glycosides [in Japanese]. Yakugaku Zasshi. 1971;91(2):198-202.5102349
6. Akada Y, Yuki H, Takiura K. Studies on glycon moiety of Senega saponins. I. Isolation and purification of the Senega saponins [in Japanese]. Yakugaku Zasshi. 1971;91(11):1178-1181.5169124
7. Shoji J, Kawanishi S, Tsukitani Y. On the structure of senegin-ΙΙ of Senegae Radix. Chem Pharm Bull (Tokyo). 1971;19(8):1740-1742.
8. Shoji J, et al. Structure of senegin-ΙΙΙ of Polygala senega root. Chem Pharm Bull. 1972;20:424.
9. Tsukitani Y, et al. Constituents of Senegae Radix. ΙΙΙ. Structures of senegin-III and -IV, saponins from Polygala senega var. latifolia. Chem Pharm Bull (Tokyo). 1973;21:1564.
10. Yoshikawa M, Murakami T, Ueno T, et al. Bioactive saponins and glycosides. I. Senegae radix. (1): E-senegasaponins a and b and Z-senegasaponins a and b, their inhibitory effect on alcohol absorption and hypoglycemic activity. Chem Pharm Bull (Tokyo). 1995;43(12):2115-2122.8582013
11. Yoshikawa M, Murakami T, Matsuda H, et al. Bioactive saponins and glycosides. II. Senegae Radix. (2): Chemical structures, hypoglycemic activity, and ethanol absorption-inhibitory effect of E-senegasaponin c, Z-senegasaponin c, and Z-senegins II, III, IV. Chem Pharm Bull (Tokyo). 1996;44(7):1305-1313.8706138
12. Yoshikawa M, Murakami T, Ueno T, et al. E-senegasaponins A and B, Z-senegasaponins A and B, Z-senegins II and III, new type inhibitors of ethanol absorption in rats from senegae radix, the roots of Polygala senega L. var. latifolia Torrey et Gray. Chem Pharm Bull (Tokyo). 1995;43(2):350-352.7728939
13. Kanazawa H, Nagata Y, Matsushima Y, Tomoda M, Takai N. Determination of acidic saponins in crude drugs by high-performance liquid chromatography on octadecylsilica porous glass. J Chromatogr. 1993;630(1-2):408-414.8445006
14. Zhang D, Miyase T, Kuroyanagi M, Umehara K, Noguchi H. Polygalasaponins XLII-XLVI from roots of Polygala glomerata. Phytochemistry. 1998;47(3):459-466.9433820
15. Saitoh H, Miyase T, Ueno A. Senegoses A-E, oligosaccharide multi-esters from Polygala senega var. latifolia Torr. et Gray. Chem Pharm Bull (Tokyo). 1993;41(6):1127-1131.8370112
16. Saitoh H, Miyase T, Ueno A. Senegoses F-I, oligosaccharide multi-esters from the roots of Polygala senega var. latifolia Torr. et Gray. Chem Pharm Bull (Tokyo). 1993;41(12):2125-2128.8118905
17. Saitoh H, Miyase T, Ueno A, Atarashi K, Saiki Y. Senegoses J-O, oligosaccharide multi-esters from the roots of Polygala senega L. Chem Pharm Bull (Tokyo). 1994;42(3):641-645.8004714
18. Misawa M, Yanaura S. Continuous determination of tracheobronchial secretory activity in dogs. Jpn J Pharmacol. 1980;30(2):221-229.7452972
19. Kako M, Miura T, Usami M, et al. Effect of senegin-II on blood glucose in normal and NIDDM mice. Biol Pharm Bull. 1995;18(8):1159-1161.8535417
20. Kako M, Miura T, Nishiyama Y, Ichimaru M, Moriyasu M, Kato A. Hypoglycemic effect of the rhizomes of Polygala senega in normal and diabetic mice and its main component, the triterpenoid glycoside senegin-II. Planta Med. 1996;62(5):440-443.8923811
21. Kako M, Miura T, Nishiyama Y, Ichimaru M, Moriyasu M, Kato A. Hypoglycemic activity of some triterpenoid glycosides. J Nat Prod. 1997:60(6):604-605.9214731
22. Kim HM, Lee EH, Na HJ, et al. Effect of Polygala tenuifolia root extract on the tumor necrosis factor-alpha secretion from mouse astrocytes. J Ethnopharmacol. 1998;61(3):201-208.9705011
23. Katselis GS, Estada A, Gorecki DK, Barl B. Adjuvant activities of saponins from the root of Polygala senega L. Can J Physiol Pharmacol. 2007;85(11):1184-1194.18066120
24. Estrada A, Katselis GS, Laarveld B, Barl B. Isolation and evaluation of immunological adjuvant activities of saponins from Polygala senega L. Comp Immunol Microbiol Infect Dis. 2000;23(1):27-43.10660256
25. Arai M, Hayashi A, Sobou M, et al. Anti-angiogenic effect of triterpenoidal saponins from Polygala senega.J Nat Med. 2011;65(1):149-156.21042868
26. Van Q, Nayak BN, Reimer M, Jones PJ, Fulcher RG, Rempel CB. Anti-inflammatory effect of Inonotus obliquus, Polygala senega L., and Viburnum trilobum in a cell screening assay. J Ethnopharmacol. 2009;125(3):487-493.19577624
27. Paul S, Mandal SK, Bhattacharyya SS, Boujedaini N, Khuda-Bukhsh AR. In vitro and in vivo studies demonstrate anticancer property of root extract of Polygala senega.J Acupunct Meridian Stud. 2010;3(3):188-196.20869020
28. Paul S, Bhattacharyya SS, Samaddar A, Boujedaini N, Khuda-Bukhsh AR. Anticancer potentials of root extract of Polygala senega against benzo[a]pyrene-induced lung cancer in mice. Zhong Xi Yi Jie He Xue Bao. 2011;9(3):320-327.21419086
29. Paul S, Bhattacharyya SS, Boujedaini N, Khuda-Bukhsh AR. Anticancer potentials of root extract of Polygala senega and its PLGA nanoparticles-encapsulated form. Evid Based Complement Alternat Med. 2011;2011.2095343110.1155/2011/517204
30. Claus E, ed. Pharmacognosy. 3rd ed. Philadelphia, PA: Lea & Febiger; 1956.
31. Blumenthal M, Busse WR, eds. 1st ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston, MA: Integrative Medicine Communications; 1998.
32. Brinker FJ. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications; 1998.
33. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235.11950176
34. Senega. In: Grieve M. A Modern Herbal. 1931. http://www.botanical.com/botanical/mgmh/s/senega41.html. Accessed January 30, 2016.

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