Goji Berry

Scientific Name(s): Lycium barbarum L. and Lycium chinense Mill. Family: Solanaceae (potato). Synonyms: Lycium halimifolium Mill.; Lycium vulgare Dunal

Common Name(s): Barbary wolfberry , Chinese desert thorn , Chinese wolfberry , desert-thorn , Duke of Argylls tea tree , Fructus Lycii Chinensis , goji , goji berry , Gou Qi Zi , Gouqizi , Himalayan goji , kuko , LYCH , matrimony vine , Ningxia , red diamonds , Tibetan goji , wolfberry

Uses

Limited quality clinical trials exist to support therapeutic claims. In vitro and animal experiments suggest antioxidant, hypoglycemic, immune-enhancing, and neuro-, hepato-, and ophthalmic-protective effects.

Dosing

Data are lacking to guide dosage in the clinical setting.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Case reports of interactions with warfarin exist.

Adverse Reactions

Clinical trials report few or no adverse reactions. Information is limited.

Toxicology

Information is lacking.

Botany

Two closely related species, L. barbarum and L. chinense , collectively produce the berries considered to be goji, wolfberries, or Gou Qi Zi. They are botanically related to the tomato and are deciduous woody perennials. Primarily cultivated in China, these species grow from 1 to 3 m in height; the L. barbarum tends to be the taller of the two. 1 The 5-petaled flowers are lavender to light-purple in color, and the lanceolate/ovate leaves appear alternately or in bundles on the shoot. The tender, oblong berries, which must be picked carefully or shaken from the vine when ripe, are a bright orange-red color and contain between 10 to 60 yellow seeds. The berries ripen from July to October in the Northern Hemisphere. A process of slow drying is undertaken to preserve the fruit, which then appear similar in size and texture to a raisin. 2 The leaves are used to make tea, and the bark is extensively used in traditional Chinese medicines. 1

History

Gou Qi Zi is listed in the Pharmacopeia of the People's Republic of China (2000), 3 and use of the berries dates back 2,300 years. Traditional use has included preventing conditions such as diabetes, hyperlipidemia, cancer, hepatitis, immune disorders, thrombosis, and male infertility. 4 , 5 In traditional Chinese medicine it is used for its anti-aging properties and tranquilizing and thirst quenching effects, as well as its ability to increase stamina. Goji is a core ingredient in most herbal eye remedies. Further uses have included nourishing the blood, enriching the yin, and as a tonic for the liver, kidneys, and lungs. 6 , 7 , 8 , 9

Chemistry

Major compounds isolated from the berries include the carotenoids beta-carotene, lutein, lycopene, zeaxanthin, zeaxanthin dipalmitate, polysaccharides (comprising 30% of the pulp), vitamins (ascorbic acid, glucopyranosyl ascorbic acid, tocopherol), fatty acids, betaine, and peptidoglycans. 7 , 9 , 10 , 11 , 12

Neutral volatile compounds identified include steroids, glycolipids (including the cerebrosides), glycosides, glucopyranosides, and alkaloids (spermine alkaloid, polyhydroxylated alkaloids). 13 , 14 Flavonoids, phenolic amides, cyclic peptides, and sesquiterpenes have also been described. 14 Additionally, rutin, chlorogenic acid, and lyciumosides have been identified in the leaf, 15 and phenolic amides identified in the root bark. 16 , 17

The berries contain dietary amounts of calcium, potassium, iron, zinc, and selenium, as well as riboflavin and vitamin C. Concern has been raised about the amount of atropine present in berries; only trace amounts were found and at levels considered insignificant (up to a maximum of 19 ppb w/w). 3

Uses and Pharmacology

High quality, clinical trials are lacking.

Antioxidant effects

Potent superoxide anion scavenging activity has been demonstrated for the polysaccharide extract of Goji berries. 4 , 14 , 18 Activity of polysaccharide extract 500 mg has been estimated to be greater than vitamin C 500 mg. 4

In older mice, the decreased activity of enzymes in the brain, liver, and heart consequent to oxidative stress was enhanced by administration of polysaccharides extracted from Lycium fruits, lending support to the traditional anti-aging use of Gou Qi Zi. 4

Lycium fruit has been used traditionally to treat infertility. In mice with heat- and time-damaged seminiferous tubules, the polysaccharide extract of the berries inhibited apoptosis and reversed morphological damage. 8 , 19 , 20 Protection against DNA-induced seminiferous tubule damage was also demonstrated in mice, and these actions are attributed to anti-oxidative activity. 8 Doxorubicin-induced cardiac oxidative stress was decreased in rats pretreated with the aqueous extract of L. barbarum , 21 and anti-oxidative effects on human dermal fibroblasts have been demonstrated. 22

Diabetes

Healthy mice fed L. barbarum extract maintained normal blood glucose levels, while streptozocin- and alloxan-induced diabetic rats and rabbits showed decreases in blood glucose levels. 23 , 24

A hypolipidemic effect was also observed. 24 Improved insulin resistance has been demonstrated in non-insulin dependent diabetic rats. 10 , 25

Hepatoprotective effect

Pretreatment with an aqueous extract of the L. chinense fruits decreased hepatic enzyme levels (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) in rats with carbon tetrachloride-induced hepatic injury. Histological changes were also decreased. 26 Similar results were obtained for zeaxanthin extract against induced hepatic fibrosis in rats. 11 Lycium compounds with potential hepato-protective (possibly antioxidant) effects have been identified. 5 , 17 , 26

Immune/anticancer activity

Experiments investigating the potential of L. barbarum and L. chinense in cancer treatment focus on immune-enhancing and direct effects. The weight of the thymus and spleen in rats was increased, as was macrophage activity, with administration of a polysaccharide extract. 4 , 27 , 28 Increased cytotoxic T lymphocyte and tumor necrosis factor activity have occurred in animal experiments and in human mononuclear cells in vitro. 8 , 27 , 29 Protection from the effects of myelosuppression has been reported. 30

Aqueous extracts inhibit proliferation and induce apoptosis in hepatocellular cancer in rats and human hepatoma cell lines. 31 , 32 Growth of sarcoma in mice was suppressed 28 , 29 while an observational study suggested a benefit for cancer patients taking L. barbarum polysaccharides. 29

CNS

Experiments investigating the effect of berry polysaccharides have found enhanced spontaneous electrical activity in the hippocampus, and a decreased stroke index and neurological score in ischemia and reperfusion models. 8 Neuronal death and apoptosis have been prevented, in animal experiments. 8 In rats, beta-amyloid peptide neurotoxicity has been prevented, suggesting a role for the berry in Alzheimer disease. 7 , 33

Inhibition of monoamine oxidase B, which is elevated in neurodegenerative disease and aging, has been demonstrated with Lycium . 34

Ophthalmic effects

Effects on the eye are thought to be related to antioxidant activity. 8 , 23 The berries are rich in zeaxanthin and increased plasma zeaxanthin levels have been demonstrated with berry consumption. 2 , 8 Lutein content in the berries is somewhat lower. 2 , 9 Fifteen grams of berries per day for 28 days increased total and lipid-standardized plasma zeaxanthin levels. 2 Bioavailability of zeaxanthin is variable and experiments have been conducted to increase the availability using milk-based and emulsion formulations. 12 , 35

Increased survival of retinal ganglion cells has been demonstrated in experiments in rats with induced glaucoma. 23 No effect on ocular pressure was found. The effect did not appear to be dose-dependent, and a prolonged effect (4 weeks) was demonstrated. 8

Other effects

Antifungal ( Candida albicans ) and antimicrobial (methicillin-resistant Staphylococcus aureus ) properties have been described for extracts of the root bark. 16 , 36

Dosage

Data are lacking to guide dosage in the clinical setting. Fifteen grams of berries per day increased plasma zeaxanthin levels in healthy adults. 2

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

There are case reports of elevated international normalized ratio values in patients taking warfarin. 29 , 37 In these reports, the patients consumed herbal tea made from the berries or bark of L. barbarum estimated to equate to 6 to 18 g of berries/day. 37

In vitro experiments suggest the potential for monoamine oxidase B inhibition, the clinical importance of which is unknown. 34

Adverse Reactions

Clinical trials report few or no adverse reactions. 2 , 12 , 35 , 38 Information is limited.

Toxicology

Data are lacking.

Bibliography

1. Lycium barbarum L. USDA, NRCS. 2007 The PLANTS Database ( http://plants.usda.gov , May 2008). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Cheng CY, Chung WY, Szeto YT, Benzie IF. Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial. Br J Nutr . 2005;93(1):123-130.
3. Adams M, Wiedenmann M, Tittel G, Bauer R. HPLC-MS trace analysis of atropine in Lycium barbarum berries. Phytochem Anal . 2006;17(5):279-283.
4. Li XM, Ma YL, Liu XJ. Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice. J Ethnopharmacol . 2007;111(3):504-511.
5. Jung K, Chin YW, Kim YC, Kim J. Potentially hepatoprotective glycolipid constituents of Lycium chinense fruits. Arch Pharm Res . 2005;28(12):1381-1385.
6. Yeh YC, Hahm TS, Sabliov CM, Lo YM. Effects of Chinese wolfberry ( Lycium chinense P. Mill.) leaf hydrolysates on the growth of Pediococcus acidilactici . Bioresour Technol . 2008;99(5):1383-1393.
7. Yu MS, Leung SK, Lai SW, et al. Neuroprotective effects of anti-aging oriental medicine Lycium barbarum against beta-amyloid peptide neurotoxicity. Exp Gerontol . 2005;40(8-9):716-727.
8. Chang RC, So KF. Use of anti-aging herbal medicine, Lycium barbarum , against aging-associated diseases. What do we know so far? Cell Mol Neurobiol . 2008;28(5):643-652.
9. Peng X, Tian G. Structural characterization of the glycan part of glycoconjugate LbGp2 from Lycium barbarum L. Carbohydr Res . 2001;331(1):95-99.
10. Zhao R, Li Q, Xiao B. Effect of Lycium barbarum polysaccharide on the improvement of insulin resistance in NIDDM rats. Yakugaku Zasshi . 2005;125(12):981-988.
11. Kim HP, Lee EJ, Kim YC, et al. Zeaxanthin dipalmitate from Lycium chinense fruit reduces experimentally induced hepatic fibrosis in rats. Biol Pharm Bull . 2002;25(3):390-392.
12. Breithaupt DE, Weller P, Wolters M, Hahn A. Comparison of plasma responses in human subjects after the ingestion of 3R,3R'-zeaxanthin dipalmitate from wolfberry ( Lycium barbarum ) and non-esterified 3R,3R'-zeaxanthin using chiral high-performance liquid chromatography. Br J Nutr . 2004;91(5):707-713.
13. Asano N, Kato A, Miyauchi M, et al. Specific alpha-galactosidase inhibitors, N-methylcalystegines--structure/activity relationships of calystegines from Lycium chinense . Eur J Biochem . 1997;248(2):296-303.
14. Han SH, Lee HH, Lee IS, Moon YH, Woo ER. A new phenolic amide from Lycium chinense Miller. Arch Pharm Res . 2002;25(4):433-437.
15. Toyoda-Ono Y, Maeda M, Nakao M, Yoshimura M, Sugiura-Tomimori N, Fukami H. 2-O-(beta-D-Glucopyranosyl)ascorbic acid, a novel ascorbic acid analogue isolated from Lycium fruit. J Agric Food Chem . 2004;52(7):2092-2096.
16. Lee DG, Park Y, Kim MR, et al. Anti-fungal effects of phenolic amides isolated from the root bark of Lycium chinense . Biotechnol Lett . 2004;26(14):1125-1130.
17. Chin YW, Lim SW, Kim SH, et al. Hepatoprotective pyrrole derivatives of Lycium chinense fruits. Bioorg Med Chem Lett . 2003;13(1):79-81.
18. Wu SJ, Ng LT, Lin CC. Antioxidant activities of some common ingredients of traditional chinese medicine, Angelica sinensis , Lycium barbarum and Poria cocos . Phytother Res . 2004;18(12):1008-1012.
19. Luo Q, Li Z, Huang X, Yan J, Zhang S, Cai YZ. Lycium barbarum polysaccharides: protective effects against heat-induced damage of rat testes and H2O2-induced DNA damage in mouse testicular cells and beneficial effect on sexual behavior and reproductive function of hemicastrated rats. Life Sci . 2006;79(7):613-621.
20. Wang Y, Zhao H, Sheng X, Gambino PE, Costello B, Bojanowski K. Protective effect of Fructus Lycii polysaccharides against time and hyperthermia-induced damage in cultured seminiferous epithelium. J Ethnopharmacol . 2002;82(2-3):169-175.
21. Xin YF, Zhou GL, Deng ZY, et al. Protective effect of Lycium barbarum on doxorubicin-induced cardiotoxicity. Phytother Res . 2007;21(11):1020-1024.
22. Zhao H, Alexeev A, Chang E, Greenburg G, Bojanowski K. Lycium barbarum glycoconjugates: effect on human skin and cultured dermal fibroblasts. Phytomedicine . 2005;12(1-2):131-137.
23. Chan HC, Chang RC, Koon-Ching Ip A, et al. Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma. Exp Neurol . 2007;203(1):269-273.
24. Luo Q, Cai Y, Yan J, Sun M, Corke H. Hypoglycemic and hypolipidemic effects and antioxidant activity of fruit extracts from Lycium barbarum . Life Sci . 2004;76(2):137-149.
25. Wu H, Guo H, Zhao R. Effect of Lycium barbarum polysaccharide on the improvement of antioxidant ability and DNA damage in NIDDM rats. Yakugaku Zasshi . 2006;126(5):365-371.
26. Ha KT, Yoon SJ, Choi DY, Kim DW, Kim JK, Kim CH. Protective effect of Lycium chinense fruit on carbon tetrachloride-induced hepatotoxicity. J Ethnopharmacol . 2005;96(3):529-535.
27. Gan L, Zhang SH, Liu Q, Xu HB. A polysaccharide-protein complex from Lycium barbarum upregulates cytokine expression in human peripheral blood mononuclear cells. Eur J Pharmacol . 2003;471(3):217-222.
28. Gan L, Hua Zhang S, Liang Yang X, Bi Xu H. Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum . Int Immunopharmacol . 2004;4(4):563-569.
29. Lycium barbarum . J Soc Integr Oncol . 2007;5(3):130. No abstract available.
30. Hai-Yang G, Ping S, Li JI, Chang-Hong X, Fu T. Therapeutic effects of Lycium barbarum polysaccharide (LBP) on mitomycin C (MMC)-induced myelosuppressive mice. J Exp Ther Oncol . 2004;4(3):181-187.
31. Chao JC, Chiang SW, Wang CC, Tsai YH, Wu MS. Hot water-extracted Lycium barbarum and Rehmannia glutinosa inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells. World J Gastroenterol . 2006;12(28):4478-4484.
32. Zhang M, Chen H, Huang J, Li Z, Zhu C, Zhang S. Effect of Lycium barbarum polysaccharide on human hepatoma QGY7703 cells: inhibition of proliferation and induction of apoptosis. Life Sci . 2005;76(18):2115-2124.
33. Ho YS, Yu MS, Lai CS, So KF, Yuen WH, Chang RC. Characterizing the neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity. Brain Res . 2007;1158:123-134.
34. Lin RD, Hou WC, Yen KY, Lee MH. Inhibition of monoamine oxidase B (MAO-B) by Chinese herbal medicines. Phytomedicine . 2003;10(8):650-656.
35. Benzie IF, Chung WY, Wang J, Richelle M, Bucheli P. Enhanced bioavailability of zeaxanthin in a milk-based formulation of wolfberry (Gou Qi Zi; Fructus barbarum L.). Br J Nutr . 2006;96(1):154-160.
36. Lee DG, Jung HJ, Woo ER. Antimicrobial property of (+)-lyoniresinol-3alpha-O-beta-D-glucopyranoside isolated from the root bark of Lycium chinense Miller against human pathogenic microorganisms. Arch Pharm Res . 2005;28(9):1031-1036.
37. Leung H, Hung A, Hui AC, Chan TY. Warafarin overdose due to the possible effects of Lycium barbarum L. Food Chem Toxicol . 2008;46(5):1860-1862.
38. Amagase H, Nance DM. A randomized, double-blind, placebo-controlled, clinical study of the general effects of a standardized Lycium barbarum (Goji) Juice, GoChi. J Altern Complement Med . 2008;14(4):403-412.

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