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Pokeweed

Scientific Name(s): Phytolacca americana L.
Common Name(s): American nightshade, Cancer jalap, Cancerroot, Chongras, Coakum, Crowberry, Garget, Inkberry, Pigeonberry, Poke, Pokeberry, Red ink plant, Scoke

Clinical Overview

Use

Young pokeweed leaves and berries may be eaten as food, but only after being cooked properly by boiling in several changes of water. Clinical trials are lacking; however, applications for observed antiviral activity are being investigated.

Dosing

At doses of 1 g, dried pokeweed root is emetic and purgative. At lower doses of 60 to 100 mg/day, the root and berries have been used to treat rheumatism and for immune stimulation; however, there are no clinical trials that support these uses or doses.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Documented adverse effects. Avoid use. Uterine stimulant with toxic constituents; is reputed to affect menstrual cycle.

Interactions

None well documented.

Adverse Reactions

GI distress, possibly leading to severe toxicities (see Toxicology).

Toxicology

Ingestion of poisonous parts of the plant may cause severe stomach cramping, nausea with persistent diarrhea and vomiting, slow and difficult breathing, weakness, spasms, hypotension, severe convulsions, and death.

Scientific Family

  • Phytolaccaceae

Botany

Pokeweed is an ubiquitous plant found in areas such as fields, along fences, and in damp woods. Pokeweed is indigenous to eastern North America, and widely naturalized in Europe, the West Indies, and Asia. This vigorous shrub-like perennial can grow up to 4 m from a heavy tap root. The reddish stem has large pointed leaves that taper at both ends. The flowers are numerous, in small and greenish-white racemes, developing into clusters of juicy, purple-black berries that mature from July to September.1, 2

History

Pokeweed leaves and roots have been used in folk medicine for the treatment of chronic rheumatism and arthritis, and as an emetic and purgative.3 The plant has also been used to treat edema4 skin cancers, catarrh, dysmenorrhea, mumps, ringworm, scabies, tonsillitis, and syphilis. Poke greens, the young immature leaves, are commercially canned and sold under the name "poke salet." The juice of the berries has been employed as an ink, a dye, and as a coloring agent in wine.5

Chemistry

The toxic components of the plant are saponins based on the triterepene genins phytolaccagenin, jaligonic acid, phytolaccagenic acid (phytolaccinic acid), esculentic acid, and pokeberrygenin.4 These include phytolaccosides A, B, D, E, and G, and phytolaccasaponins B, E, and G.6, 7 The saponins are present in cell culture as well.8 The free triterpenes also have been isolated from different plant parts.4, 9 In addition, poke root has been found to contain sterols, including alpha-spinasterol.10

Several neolignans have been isolated from seeds, including americanins A, B, and D11, 12; americanol A; isoamericanol A13; and the methyl esters and ethers of the latter compounds.14

A 4 kDa antifungal peptide, PAFP-s, has been elucidated from the seeds15 and its solution structure as a knottin-type peptide determined by nuclear magnetic resonance.16, 17

Numerous proteins of poke have been studied for a variety of reasons. The cysteine proteases phytolacains G and R are found in fruits and are 25 and 23 kDa in size, respectively.18, 19, 20 Mitogenic proteins with the ability to bind specific carbohydrates (di-N-acetylchitobiose) have been recognized and isolated from poke roots for decades.21 The pokeweed lectins C, D1, and D2 have been thoroughly characterized by x-ray crystallography and contain multiple chitin-binding domains.22, 23

The most medically interesting group of proteins from poke are pokeweed antiviral proteins (PAP). Different isoforms of PAP are present in seeds and in leaves at different growth stages. All proteins are approximately 30 kDa in size and are homologous to ribosome inactivating proteins such as ricin.24

Uses and Pharmacology

Antiviral activity

PAPs have been extensively studied for their biochemical mechanism and antiviral activity. They are able to enzymatically depurinate adenine (A4324) and several other residues of ribosomal RNA via a specific RNA N-glycosidase activity. The consequence of this activity in a living cell is cessation of protein synthesis. The proteins are bound within the plant cell wall matrix and do not interfere with the plant's ribosomes unless the cell is injured.25 PAP isoforms are also able to depurinate viral RNA of HIV-1, which blocks replication of the virus within host cells26 a property not shared by all ribosome-inactivating proteins. Ricin, for example, is inactive as an antiviral, but PAPs are active against a broad spectrum of plant and animal viruses, including poliovirus, herpes simplex, influenza, cytomegalovirus, and HIV.26 The specificity for viral versus host cell RNA appears to reside in PAP's ability to bind to RNA cap structures.27 It has been shown that cap binding and rRNA depurination can be uncoupled because mutation of a conserved asparagine residue blocks rRNA depurination but not cap binding.28 The same study showed that PAP is retrotranslocated through the endoplasmic reticulum into the cellular cytosol. High resolution x-ray crystallogrphic structures of PAP-III and PAP-S have been published.29, 30

The antiviral properties of PAP have prompted its development as a microbicide for sexually transmitted diseases such as HIV. PAP-I had no adverse effects on semen used for artificial insemination of rabbits, and pups born via insemination with treated semen were entirely normal.31 Likewise, neither human spermatazoa nor female genital tract epithelial cells were adversely affected by PAP.32 As a topical microbicide, PAP would be administered vaginally in a gel formulation. Consequently, PAP was evaluated in a 13-week subchronic and reproductive toxicity study in mice. No adverse effects on the vaginal mucosa or on reproductive success were found in examination of numerous end points.33 However, in rabbits, moderate to marked vaginal irritation was noted in some animals, but it was not dose-dependent in intensity.34

It should be emphasized that the above studies were conducted on purified proteins and that crude extracts of poke cannot be substituted in therapy because of their acutely toxic properties. Studies related to pokeweed antiviral proteins are ongoing.35, 36, 37, 38

Other uses

The saponins showed anti-inflammatory activity in a rat paw edema model at doses 10-fold lower than the LD50; however, the toxicity of the saponins precludes their use in inflamation.39 Poke extracts were found to have inhibitory activity in a model of diabetic nephropathy.40 The sterol alpha-spinasterol was isolated as the active principle.10 Some of the neolignans of poke promote neurite outgrowth in rat cortical neuron cultures.13, 14 Antiproliferative and antitumor activities have been described for the component americanin A,41 as well as acetylcholinesterase inhibitory activity from the leaf extract.42

Dosing

At doses of 1 g, dried pokeweed root is emetic and purgative. At lower doses of 60 to 100 mg/day, the root and berries have been used to treat rheumatism and for immune stimulation. However, there are no clinical trials that support these uses or doses.43, 44, 45

Pregnancy / Lactation

Documented adverse effects. Avoid use. Uterine stimulant with toxic constituents; is reputed to affect menstrual cycle.46

Interactions

None well documented.

Adverse Reactions

GI distress, possibly leading to severe toxicities, can occur (see Toxicology).

Toxicology

Pokeweed poisonings were common in eastern North America during the 19th century, especially from the use of tinctures as antirheumatic preparations and from ingestion of berries and roots that were mistaken for parsnip, Jerusalem artichoke, or horseradish.43

All parts of pokeweed are toxic except the aboveground leaves sprouting in the early spring. The poisonous principles are found in highest concentrations in the rootstock, less in the mature leaves and stems, and least in the fruits. Young leaves, if collected before acquiring a red color, are edible if boiled for 5 minutes, rinsed, and reboiled. Berries are toxic when raw but edible when cooked.

Ingestion of poisonous parts of the plant may cause severe stomach cramping, nausea with persistent diarrhea and vomiting, slow and difficult breathing, weakness, spasms, hypotension, severe convulsions, and death.47 However, less than 10 uncooked berries are generally harmless to adults. Several investigators have reported deaths in children following the ingestion of uncooked berries or pokeberry juice.47, 48 Severe poisonings have been reported in adults who ingested mature pokeweed leaves49 and following the ingestion of tea brewed from one-half teaspoonful of powdered pokeroot.43

A case of toxicity in campers who ingested properly cooked young shoots has been reported by the Centers for Disease Control and Prevention. Sixteen of the 51 cases exhibited case-definitive symptoms (vomiting followed by any 3 of the following: nausea, diarrhea, stomach cramps, dizziness, headache). These symptoms persisted for up to 48 hours (mean, 24 hours).50 Poisoning also may occur when the toxic components enter the circulatory system through cuts and abrasions in the skin. Symptoms of mild poisoning generally last 24 hours. In severe cases, gastric lavage, emesis, and symptomatic and supportive treatment have been suggested.47 The FDA classifies pokeweed as an herb of undefined safety that has demonstrated narcotic effects.

References

1. Phytolacca americana. USDA, NRCS. 2017. The PLANTS Database (http://plants.usda.gov, March 2017). National Plant Data Team, Greensboro, NC 27401-4901 USA. Accessed March 2017.
2. Reader's Digest. Magic and Medicine of Plants. Pleasantville, NY: Reader's Digest Association, Inc; 1986.
3. Dejey MA, Bianchini F, Carbetta F. Health Plants of the World: Atlas of Medicinal Plants. New York, NY: Newsweek Books; 1977.
4. Kang SS, Woo WS. Triterpenes from the berries of Phytolacca americana. J Nat Prod. 1980;43:510-513.6448759
5. Duke JA. CRC Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press; 1985.
6. Tang W, Eisenbrand G. Chinese Drugs of Plant Origin: Chemistry, Pharmacology, and Use in Traditional and Modern Medicine. New York, NY: Springer-Verlag; 1992:765.
7. Suga Y, Maruyama Y, Kawanishi S, Shoji J. Studies on the constituents of phytolaccaceous plants. I. On the structures of phytolaccasaponin B, E and G from the roots of Phytolacca americana L. Chem Pharm Bull. 1978;26:520-525.
8. Takahashi H, Namikawa Y, Tanaka M, Fukuyama Y. Triterpene glycosides from the cultures of Phytolacca americana. Chem Pharm Bull. 2001;49:246-248.
9. Woo WS, Wagner H. 3-Acetylaleuritolic acid from the seeds of Phytolacca americana. Phytochemistry. 1977;16:1845-1846.
10. Jeong SI, Kim KJ, Choi MK, et al. alpha-Spinasterol isolated from the root of Phytolacca americana and its pharmacological property on diabetic nephropathy. Planta Med. 2004;70:736-739.
11. Woo WS, Kang SS, Wagner H, Chari VM. The structure of americanin, a new neolignan from Phytolacca americana [in German]. Tetrahedron Lett. 1978;35:3239-3242.
12. Woo WS, Kang SS, Seligmann O, Chari VM, Wagner H. The structure of new lignans from the seeds of Phytolacca americana. Tetrahedron Lett. 1980;21:4255-4258.
13. Fukuyama Y, Hasegawa T, Toda M, Kodama M, Okazaki H. Structures of americanol A and isoamericanol A having a neurotrophic property from the seeds of Phytolacca americana. Chem Pharm Bull. 1992;40:252-254.1576680
14. Takahasi H, Yanagi K, Ueda M, Nakade K, Fukuyama Y. Structures of 1,4-benzodioxane derivatives from the seeds of Phytolacca americana and their neuritogenic activity in primary cultured rat cortical neurons. Chem Pharm Bull. 2003;51:1377-1381.14646313
15. Shao F, Hu Z, Xiong YM, et al. A new antifungal peptide from the seeds of Phytolacca americana: characterization, amino acid sequence and cDNA cloning. Biochim Biophys Acta. 1999;1430:262-268.10082954
16. Gao GH, Liu W, Dai JX, et al. Solution structure of PAFP-S: a new knottin-type antifungal peptide from the seeds of Phytolacca americana. Biochemistry. 2001;40:10973-10978.11551192
17. Gao GH, Liu W, Dai JX, et al. Molecular scaffold of a new pokeweed antifungal peptide deduced by 1H nuclear magnetic resonance. Int J Biol Macromol. 2001;29:251-258.11718821
18. Uchikoba T, Arima K, Yonezawa H, Shimada M, Kaneda M. Amino acid sequence and some properties of phytolacain G, a cysteine protease from growing fruit of pokeweed, Phytolacca americana. Biochim Biophys Acta. 2000;1523:254-260.11042392
19. Sussner U, Abel G, Schulte R, Kreis W. Isolation and characterisation of a cysteine protease (phytolacain G), from Phytolacca americana roots. Planta Med. 2004;70:942-947.15490323
20. Yonezawa H, Uchikoba T, Arima K, Shimada M, Kaneda M. Amino acid sequence and some properties of phytolacain R, a cysteine protease from full-growth fruits of pokeweed, Phytolacca americana. J Biochem. 1999;126:26-33.
21. Yokoyama K, Terao T, Osawa T. Carbohydrate-binding specificity of pokeweed mitogens. Biochim Biophys Acta. 1978;538:384-396.620075
22. Hayashida M, Fujii T, Hamasu M, Ishiguro M, Hata Y. Crystallization and preliminary X-ray analysis of lectin C from the roots of pokeweed (Phytolacca americana). Acta Crystallogr D Biol Crystallogr. 2003;59(Pt 7):1249-1252.12832775
23. Fujii T, Hayashidi M, Hamasu M, Ishiguro M, Hata Y. Structures of two lectins from the roots of pokeweed (Phytolacca americana). Acta Crystallogr D Biol Crystallogr. 2004;60:665-673.15039554
24. Ready M, Wilson K, Piatak M, Robertus JD. Ricin-like plant toxins are evolutionarily related to single-chain ribosome-inhibiting proteins from Phytolacca. J Biol Chem. 1984;259:15252-15256.6511792
25. Ready MP, Brown DT, Robertus JD. Extracellular localization of pokeweed antiviral protein. Proc Natl Acad Sci U S A. 1986;83:5053-5056.3523481
26. Rajamohan F, Venkatachalam TK, Irvin JD, Uckun FM. Pokeweed antiviral protein isoforms PAP-I, PAP-II, and PAP-III depurinate RNA of human immunodeficiency virus (HIV)-1. Biochem Biophys Res Commun. 1999;260:453-458.10403789
27. Hudak KA, Bauman JD, Tumer NE. Pokeweed antiviral protein binds to the cap structure of eukaryotic mRNA and depurinates the mRNA downstream of the cap. RNA. 2002;8:1148-1159.12358434
28. Parikh BA, Baykal U, Di R, Tumer NE. Evidence for retro-translocation of pokeweed antiviral protein from endoplasmic reticulum into cytosol and separation of its activity on ribosomes from its activity on capped RNA. Biochemistry. 2005;44:2478-2490.15709760
29. Zeng ZH, He XL, Li HM, Hu Z, Wang DC. Crystal structure of pokeweed antiviral protein with well-defined sugars from seeds at 1.8A resolution. J Struct Biol. 2003;141:171-178.12615543
30. Kurinov IV, Uckun FM. High resolution X-ray structure of potent anti-HIV pokeweed antiviral protein-III. Biochem Pharmacol. 2003;65:1709-1717.12754107
31. D'Cruz OJ, Uckun FM. Effect of pretreatment of semen with pokeweed antiviral protein on pregnancy outcome in the rabbit model. Fertil Steril. 2001;76:830-833.11591423
32. D'Cruz OJ, Uckun FM. Pokeweed antiviral protein: a potential nonspermicidal prophylactic antiviral agent. Fertil Steril. 2001;75:106-114.11163824
33. D'Cruz OJ, Waurzyniakt B, Uckun FM. A 13-week subchronic intravaginal toxicity study of pokeweed antiviral protein in mice. Phytomedicine. 2004;11:342-351.15185849
34. D'Cruz OJ, Waurzyniakt B, Uckun FM. Mucosal toxicity studies of a gel formulation of native pokeweed antiviral protein. Toxicol Pathol. 2004;32:212-221.15200159
35. Di R, Tumer NE. Pokeweed antiviral protein: its cytotoxicity mechanism and applications in plant disease resistance. Toxins (Basel). 2015 Mar 6;7(3):755-72.25756953
36. Domashevskiy AV, Goss DJ. Pokeweed antiviral protein, a ribosome inactivating protein: activity, inhibition and prospects. Toxins (Basel). 2015 Jan 28;7(2):274-98.25635465
37. Ishag HZ, Li C, Huang L, Sun MX, Ni B, Guo CX, Mao X. Inhibition of Japanese encephalitis virus infection in vitro and in vivo by pokeweed antiviral protein. Virus Res. 2013 Jan;171(1):89-96.23142554
38. Krivdova G, Hudak KA. Pokeweed antiviral protein restores levels of cellular APOBEC3G during HIV-1 infection by depurinating Vif mRNA. Antiviral Research 2015;122: 51-54.26275799
39. Woo WS, et al. Constituents of Phytolacca species. I. Antiinflammatory saponins. Soul Taehakkyo Saengyak Yonguso Opjukjip. 1976;15103.
40. Jeong SI, Kim KJ, Choo YK, Keum KS, Choi BK, Jung KY. Phytolacca americana inhibits the high glucose-induced mesangial proliferation via suppressing extracellular matrix accumulation and TGF-beta production. Phytomedicine. 2004;11:175-181.15070169
41. Jung C, Hong JY, Bae SY, Kang SS, Park HJ, Lee SK. Antitumor activity of Americanin A isolated from the seeds of Phytolacca americana by regulating the ATM/ATR signaling pathway and the Skp2-p27 axis in human colon cancer cells. J Nat Prod. 2015;78(12):2983-2993.26595875
42. Zheleva-Dimitrova DZ. Antioxidant and acetylcholinesterase inhibition properties of Amorpha fruticosa L. and Phytolacca americana L. Pharmacogn Mag. 2013;9(34):109-113.23772105
43. Lewis WH, Smith PR. Poke root herbal tea poisoning. JAMA. 1979;242:2759-2760.501875
44. Claus E, ed. Pharmacognosy. 3rd ed. Philadelphia, PA: Lea & Febiger; 1956.
45. Gruenwald J, ed. PDR for Herbal Medicines. 2nd ed. Montvale, NJ: Medical Economics; 2000:602-603.
46. Newall CA, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-Care Professionals. 2nd ed. London: Pharmaceutical Press; 1996.
47. Hardin JW, Arena JM. Human Poisoning from Native and Cultivated Plants. 2nd ed. Durham, NC: Duke University Press; 1974.
48. Toxic reactions to plant products sold in health food stores. Med Lett Drugs Ther. 1979;21:29-32.460042
49. Stein ZL. Pokeweed-induced gastroenteritis. Am J Hosp Pharm. 1979;36:1303.507065
50. Centers for Disease Control (CDC). Plant poisonings—New Jersey. Morb Mortal Wkly Rep. 1981;30:65-67.

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