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Chinese Cucumber

Scientific Name(s): Trichosanthes kirilowii Maxim.
Common Name(s): Chinese cucumber, Chinese snake gourd, Compound Q, Gua-lou, Radix trichosanthis, Tian-hua-fen, Tolidostena japonica

Clinical Overview

Use

Chinese cucumber root extract has been traditionally used to induce abortion. Antiviral activity and potential application in cancer therapy is being investigated; however, a lack of clinical trials and toxicity of the plant’s root limit use.

Dosing

In traditional Chinese medicine, Chinese cucumber is most commonly administered as part of a polyherbal preparation. In a clinical trial in HIV patients, trichosanthin 1.2 mg intravenously (IV) weekly, then monthly, was used. In another study, the plant seeds (20 g of seed kernels per day for 28 days) were eaten as a dietary source of conjugated linolenic acid.

Contraindications

Pregnancy.

Pregnancy/Lactation

Avoid use. Extracts of the root possess abortifacient activity and are toxic to the fetus.

Interactions

None well documented.

Adverse Reactions

Available published clinical studies are limited. However, one trial reported myalgia, fever, elevated liver function tests, and mild to moderate anaphylactic reactions.

Toxicology

Extracts of the Chinese cucumber are extremely toxic (death has occurred), particularly with parenteral use.

Botany

The Chinese cucumber is one of more than 40 recognized species of Trichosanthes, including the snake or serpent gourd, Trichosanthes cucumerina. It is a member of the gourd family, and the root, fruit, seeds, stems, and peel have been traditionally used. While T. kirilowii is the plant of this species most often referred to in Chinese Materia Medica, a number of related species are often used as adulterants.1, 2

History

T. kirilowii has a long history in traditional Chinese medicine and has been used to reduce fever, swelling, and cough. A starch extracted from the root is used for abscesses, amenorrhea, jaundice, and polyuria. Modern Chinese medicinal uses include the management of diabetes and use as an abortifacient. The plant has been used for centuries in the treatment of tumors.2, 3

Chemistry

The most studied component of T. kirilowii is the protein trichosanthin, which is found in the root of the plant. At least 2 ribosome-inactivating proteins, the trichosanthins, have been identified (sometimes referred to as "compound Q"), with T. kirilowii appearing to have the highest content. A highly purified form of trichosanthin has been investigated under the name GLQ-223. The trichosanthins possess abortifacient activity and are toxic to the fetus. The plant seeds contain hydroxylated sterols, fatty acids, and lignans.3, 4, 5, 6, 7, 8

Uses and Pharmacology

Antiviral

Animal data

Studies in rats and guinea pigs demonstrated antiviral activity of trichosanthin.9 In vitro studies demonstrated activity against herpes simplex virus, HIV, and hepatitis B.10, 11 In vitro studies to determine potential applications are ongoing.12

Clinical data

Early interest in trichosanthin as an agent in HIV treatment appears to have lost momentum. The compound was reported to block HIV replication and destroy HIV-infected macrophages. A single clinical trial published findings on the addition of trichosanthin to standard therapy, which resulted in a median gain of 1.1 CD4+ cells/mm3/month.8

Cancer

Animal data

Multiple in vitro studies have investigated both trichosanthin and cucurbitacin D using human cancer cell lines,13, 14, 15, 16 with much interest focusing on breast cancer.17, 18, 19, 20, 21, 22 Other tumor cell lines used include hepatoma and lung tumor.23, 24, 25

In vivo animal studies included use in lung, nasopharyngeal, and cervical cancers, among others.26, 27, 28, 29

Clinical data

Trichosanthin was reported to have been used to treat choriocarcinoma and cervical cancer, but clinical studies are lacking.29

Immune system

Animal data

In rodent and in vitro experiments, trichosanthin and cucurbitacin D demonstrated an inhibitory effect on lymphocytes, upregulation of CD4 T cells, and modulation of macrophages.30, 31, 32 In a study in mice, trichosanthin delayed allograft rejection.32 Anti-inflammatory effects of the related T. cucumerina against induced paw edema have also been demonstrated in rats.33

Clinical data

Research reveals no clinical data regarding the use of T. kirilowii for immune suppression, such as preventing graft-versus-host disease.

Other uses

Antioxidant

Antioxidant activity has been demonstrated in vitro and in vivo in rodents.34, 35, 36, 37

Diabetes

Extracts from the related T. cucumerina plant demonstrated antidiabetic and hypolipidemic activity in rats.38, 39

Dietary

In rats, the seed oil is a source of linolenic acid,40 while in a clinical study, T. kirilowii seeds (20 g of seed kernels per day for 28 days) were eaten as a dietary source of conjugated linolenic acid.41

Gastroprotective

Extracts from the related T. cucumerina plant were gastroprotective in rats.42

Dosing

In traditional Chinese medicine, Chinese cucumber is most commonly administered as part of a polyherbal preparation.

In a clinical trial in HIV patients, trichosanthin 1.2 mg IV weekly, then monthly, was used.8

In a clinical study, T. kirilowii seeds (20 g of seed kernels per day for 28 days) were eaten as a dietary source of conjugated linolenic acid.41

Pregnancy / Lactation

Avoid use. Extracts of the root possess abortifacient activity and are toxic to the fetus. For this reason, trichosanthin has been used to resolve ectopic pregnancy in place of management via salpingectomy.43, 44

Interactions

None well documented.

Adverse Reactions

Available published clinical studies are limited. However, one trial reported myalgia, fever, elevated liver function tests, and mild to moderate anaphylactic reactions.8 Allergy and sensitization to trichosanthin have been reported.2

Toxicology

Extracts of the Chinese cucumber are extremely toxic, particularly if administered parenterally. Acute pulmonary edema, cerebral edema and hemorrhage, myocardosis, and death have been reported.2 Extracts of the root possess abortifacient activity and are toxic to the fetus.43

References

1. Trichosanthes cucumerina. USDA. NRCS. 2014. The PLANTS database (http://plants.usda.gov, December 2014). National Plant Data Center, Greensboro, NC 27401-4901 USA. Accessed January 7, 2015.
2. Duke JA. Handbook of Medicinal Herbs. 2nd ed. Boca Raton, FL: CRC Press; 2002.
3. Fan XM, Chen G, Sha Y, et al. Chemical constituents from the fruits of Trichosanthes kirilowii. J Asian Nat Prod Res. 2012;14(6):528-532.22587792
4. Duke J. Dr. Duke's Phytochemical and Ethnobotanical Databases. Agricultural Research Service website. http://www.ars-grin.gov/duke. Updated June 13, 1996. Accessed December 15, 2014.
5. Lian L, Fan XM, Chen G, et al. Two new compounds from the fruits of Trichosanthes kirilowii maxim. J Asian Nat Prod Res. 2012;14(1):64-67.22263595
6. Lee DH, Seong S, Kim SS, Han JB. A case of stage IV non-small cell lung cancer treated with Korean medicine therapy alone. Case Rep Oncol. 2013;6(3):574-578.24348396
7. de Virgilio M, Lombardi A, Caliandro R, Fabbrini MS. Ribosome-inactivating proteins: from plant defense to tumor attack. Toxins (Basel). 2010;2(11):2699-2737.22069572
8. Byers VS, Levin AS, Malvino A, Waites L, Robins RA, Baldwin RW. A phase II study of effect of addition of trichosanthin to zidovudine in patients with HIV disease and failing antiretroviral agents. AIDS Res Hum Retroviruses. 1994;10(4):413-420.7915124
9. Shaw PC, Lee KM, Wong KB. Recent advances in trichosanthin, a ribosome-inactivating protein with multiple pharmacological properties. Toxicon. 2005;45(6):683-689.15804517
10. He D, Zheng Y, Tam S. The anti-herpetic activity of trichosanthin via the nuclear factor-ΚB and p53 pathways. Life Sci. 2012;90(17-18):673-681.22498878
11. Wong KL, Wong RN, Zhang L, et al. Bioactive proteins and peptides isolated from Chinese medicines with pharmaceutical potential. Chin Med. 2014;9:19.25067942
12. Fang EF, Ng TB, Shaw PC, Wong RN. Recent progress in medicinal investigations on trichosanthin and other ribosome inactivating proteins from the plant genus Trichosanthes. Curr Med Chem. 2011;18(28):4410-4417.21861819
13. Yin D, Wakimoto N, Xing H, et al. Cucurbitacin B markedly inhibits growth and rapidly affects the cytoskeleton in glioblastoma multiforme. Int J Cancer. 2008;123(6):1364-1375.18561312
14. Dat NT, Jin X, Hong YS, Lee JJ. An isoaurone and other constituents from Trichosanthes kirilowii seeds inhibit hypoxia-inducible factor-1 and nuclear factor-kappaB. J Nat Prod. 2010;73(6):1167-1169.20469887
15. Mi SL, An CC, Wang Y, et al. Trichomislin, a novel ribosome-inactivating protein, induces apoptosis that involves mitochondria and caspase-3. Arch Biochem Biophys. 2005;434(2):258-265.15639225
16. Li CT, Lin CH, Kao TY, et al. The mechanisms of action of Tianhua on antitumor activity in lung cancer cells. Pharm Biol. 2010;48(11):1302-1309.20738166
17. Yang L, Wu S, Zhang Q, Liu F, Wu P. 23,24-dihydrocucurbitacin B induces G2/M cell-cycle arrest and mitochondria-dependent apoptosis in human breast cancer cells (Bcap37). Cancer Lett. 2007;256(2):267-278.17681423
18. Duangmano S, Sae-Lim P, Suksamrarn A, Domann FE, Patmasiriwat P. Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation. BMC Complement Altern Med. 2012;12:185.23062075
19. Duangmano S, Dakeng S, Jiratchariyakul W, Suksamrarn A, Smith DR, Patmasiriwat P. Antiproliferative effects of cucurbitacin B in breast cancer cells: down-regulation of the c-Myc/hTERT/telomerase pathway and obstruction of the cell cycle. Int J Mol Sci. 2010;11(12):5323-5338.21614210
20. Dakeng S, Duangmano S, Jiratchariyakul W, U-Pratya Y, Bögler O, Patmasiriwat P. Inhibition of Wnt signaling by cucurbitacin B in breast cancer cells: Reduction of Wnt-associated proteins and reduced translocation of galectin-3-mediated β-catenin to the nucleus. J Cell Biochem. 2012;113(1):49-60.21866566
21. Promkan M, Dakeng S, Chakrabarty S, Bögler O, Patmasiriwat P. The effectiveness of cucurbitacin B in BRCA1 defective breast cancer cells. PLoS One. 2013;8(2):e55732.23393598
22. Kim SR, Seo HS, Choi HS, et al. Trichosanthes kirilowii ethanol extract and cucurbitacin D inhibit cell growth and induce apoptosis through inhibition of STAT3 activity in breast cancer cells. Evid Based Complement Alternat Med. 2013;2013:975350.24194785
23. Shin JW, Son JY, Kang JK, Han SH, Cho CK, Son CG. Trichosanthes kirilowii tuber extract induces G2/M phase arrest via inhibition of tubulin polymerization in HepG2 cells. J Ethnopharmacol. 2008;115(2):209-216.18022775
24. Takahashi N, Yoshida Y, Sugiura T, Matsuno K, Fujino A, Yamashita U. Cucurbitacin D isolated from Trichosanthes kirilowii induces apoptosis in human hepatocellular carcinoma cells in vitro. Int Immunopharmacol. 2009;9(4):508-513.19185617
25. Cai Y, Xiong S, Zheng Y, Luo F, Jiang P, Chu Y. Trichosanthin enhances anti-tumor immune response in a murine Lewis lung cancer model by boosting the interaction between TSLC1 and CRTAM. Cell Mol Immunol. 2011;8(4):359-367.21572449
26. Li M, Li X, Li JC. Possible mechanisms of trichosanthin-induced apoptosis of tumor cells. Anat Rec (Hoboken). 2010;293(6):986-992.20225201
27. Liu F, Wang B, Wang Z, Yu S. Trichosanthin down-regulates notch signaling and inhibits proliferation of the nasopharyngeal carcinoma cell line CNE2 in vitro. Fitoterapia. 2012;83(5):838-842.22808524
28. Kabir SR, Islam MF, Alom MJ, Abu Zubair M, Absar N. Purification, characterizations of a snake guard seeds lectin with antitumor activity against Ehrlich ascites carcinoma cells in vivo in mice. Protein Pept Lett. 2012;19(3):360-368.22185504
29. Sha O, Niu J, Ng TB, Cho EY, Fu X, Jiang W. Anti-tumor action of trichosanthin, a type 1 ribosome-inactivating protein, employed in traditional Chinese medicine: a mini review. Cancer Chemother Pharmacol. 2013;71(6):1387-1393.23377374
30. Wang BL, Su H, Chen Y, Wang J, Xu GL. A role for trichosanthin in the expansion of CD4CD25 regulatory T cells. Scand J Immunol. 2010;71(4):258-266.20384869
31. Zhou X, Yang N, Lu L, et al. Up-regulation of IL-10 expression in dendritic cells is involved in trichosanthin-induced immunosuppression. Immunol Lett. 2007;110(1):74-81.17467810
32. Song Y, Ding N, Kanazawa T, Yamashita U, Yoshida Y. Cucurbitacin D is a new inflammasome activator in macrophages. Int Immunopharmacol. 2013;17(4):1044-1050.24140411
33. Arawwawala M, Thabrew I, Arambewela L, Handunnetti S. Anti-inflammatory activity of Trichosanthes cucumerina Linn. in rats. J Ethnopharmacol. 2010;131(3):538-543.20654707
34. Sathesh Kumar S, Ravi Kumar B, Krishna Mohan G. Hepatoprotective effect of Trichosanthes cucumerina Var cucumerina L. on carbon tetrachloride induced liver damage in rats. J Ethnopharmacol. 2009;123(2):347-350.19429383
35. Chen Y, Miao Y, Huang L, et al. Antioxidant activities of saponins extracted from Radix Trichosanthis: an in vivo and in vitro evaluation. BMC Complement Altern Med. 2014;14:86.24597831
36. Seo CS, Kim TW, Kim YJ, et al. Trichosanthes kirilowii ameliorates cisplatin-induced nephrotoxicity in both in vitro and in vivo [published online September 4, 2014]. Nat Prod Res.2518582210.1080/14786419.2014.952229
37. Shah SL, Mali VR, Zambare GN, Bodhankar SL. Cardioprotective activity of methanol extract of fruit of Trichosanthes cucumerina on doxorubicin-induced cardiotoxicity in Wistar rats. Toxicol Int. 2012;19(2):167-172.22778516
38. Kirana H, Srinivasan BP. Trichosanthes cucumerina Linn. improves glucose tolerance and tissue glycogen in non insulin dependent diabetes mellitus induced rats. Indian J Pharmacol. 2008;40(3):103-106.20040935
39. Saha SS, Chakraborty A, Ghosh S, Ghosh M. Comparative study of hypocholesterolemic and hypolipidemic effects of conjugated linolenic acid isomers against induced biochemical perturbations and aberration in erythrocyte membrane fluidity. Eur J Nutr. 2012;51(4):483-495.21814874
40. Yuan GF, Yuan JQ, Li D. Punicic acid from Trichosanthes kirilowii seed oil is rapidly metabolized to conjugated linoleic acid in rats. J Med Food. 2009;12(2):416-422.19459746
41. Yuan G, Sinclair AJ, Xu C, Li D. Incorporation and metabolism of punicic acid in healthy young humans. Mol Nutr Food Res. 2009;53(10):1336-1342.19753607
42. Arawwawala LD, Thabrew MI, Arambewela LS. Gastroprotective activity of Trichosanthes cucumerina in rats. J Ethnopharmacol. 2010;127(3):750-754.19963056
43. Xiang DJ, Chen LM, Gu JS, Stone P, Chen Q. Trichosanthin, a Chinese medicine for the medical treatment of ectopic pregnancy with high levels of β-hCG. Reprod Sci. 2012;19(5):534-538.22267541
44. Lu PX, Jin YC. Ectopic pregnancy treated with trichosanthin. Clinical analysis of 71 patients. Chin Med J (Engl). 1989;102(5):365-367. 2509159

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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