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Goji Berry

Scientific Name(s): Lycium barbarum L., Lycium chinense Mill., 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

Clinical Overview

Use

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. A meta-analysis of several low-quality randomized controlled trials suggest a beneficial reduction in cardiometabolic risk factors may be provided for subjects at least 60 years of age who supplemented for at least 3 months.

Dosing

Data are lacking to guide dosage in the clinical setting. A dose of 150 mg twice daily was effective as an antidiabetic in a small clinical trial.

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

Anaphylaxis and varying degrees of hypersensitivity reactions have been reported. 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 Synonyms are Lycium halimifolium Mill.; Lycium vulgare Dunal.

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 leaf15 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.

Antifungal/Antimicrobial effects

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

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. barbarum21 and anti-oxidative effects on human dermal fibroblasts have been demonstrated.22

Cardiometabolic risk factors

A meta-analysis of randomized controlled trials investigating the effects of L. barbarum on cardiometabolic risk factors identified 7 trials (N=548) that met eligibility criteria. The majority of the studies were of low-quality and were conducted in healthy subjects in China; however, 2 were conducted in patients with type 2 diabetes. Interventions included the fruit, fruit juice, and the polysaccharide extract. Overall, no significant differences were found on risk factors of noncommunicable diseases but when stratified by age and duration of intervention, significant improvements were noted. In participants at least 60 years of age or when the duration of the intervention was not less than 3 months, L. barbarum supplementation resulted in significant reductions in total cholesterol and triglycerides. Compared to healthy subjects, those with type 2 diabetes exhibited more of a reduction in fasting glucose.41

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

Diabetes

Animal studies

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

Clinical data

A double-blind, randomized, placebo-controlled trial enrolling 67 adults with type 2 diabetes was conducted by the Nanjing Center for Disease Control and Prevention in China to evaluate the hypoglycemic effect of L. barbarum polysaccharide (LBP), used traditionally in Chinese medicine to treat various diseases that manifest with frequent drinking and urination. Administration of 300 mg/day of LBP for 3 months resulted in significant improvements in glucose area under the curve, insulinogenic index, serum glucose, and high-density lipoprotein levels; however, these effects were only significant in patients not currently taking hypoglycemic medications. Insulin response to a meal was not changed and no significant changes were noted for other lipid parameters or adipokines (ie, toxic necrosis factor [TNF]-alpha, leptin, interleukin-6). No adverse events were reported.40

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.11Lycium 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 suppressed28, 29 while an observational study suggested a benefit for cancer patients taking L. barbarum polysaccharides.29

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

Dosing

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.

Varying degrees of hypersensitivity reactions have been reported, including a case report of anaphylaxis. A 37-year-old Italian man, with known allergies to pollen since childhood, experienced goji berry-dependent exercise-induced anaphylaxis that was effectively treated with epinephrine, fluids, and corticosteroids. Subsequent skin prick tests were positive for grass, ragweed, mugwort, pellitory, birch, olive tree, tomato, peanut, and hazelnut.39

Toxicology

Data are lacking.

References

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):504-511.17224253
5. Jung K, Chin YW, Kim YC, Kim J. Potentially hepatoprotective glycolipid constituents of Lycium chinense fruits. Arch Pharm Res. 2005;28(12):1381-1385.16392672
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):1383-1393.17383176
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):716-727.16139464
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):643-652.17710531
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):981-988.16327243
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):390-392.11913541
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):707-713.15137922
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):296-303.9346281
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):433-437.12214850
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):2092-2096.15053557
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):1125-1130.15266117
17. Chin YW, Lim SW, Kim SH, et al. Hepatoprotective pyrrole derivatives of Lycium chinense fruits. Bioorg Med Chem Lett. 2003;13(1):79-81.12467621
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):1008-1012.15742346
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):613-621.16563441
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):1020-1024.17622973
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):529-535.15619574
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):217-222.12826241
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):563-569.15099534
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):181-187.15724837
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):4478-4484.16874858
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):2115-2124.15826878
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):650-656.14692725
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):154-160.16870004
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):1031-1036.16212233
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):1860-1862.18281140
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):403-412.18447631
39. Zauli D, Mirarchi MG. Anaphylaxis induced by goji berries. Ann Allergy Asthma Immunol. 2015;114(6):522-536.25935431
40. Cai H, Liu F, Zuo P, Huang G, Song Z, Wang T, Lu H, Guo F, Han C, Sun G. Practical application of antidiabetic efficacy of Lycium barbarum polysaccharide in patients with type 2 diabetes. Med Chem. 2015;11(4):383-390.25381995
41. Guo XF, Li ZH, Cai H, Li D. The effects of Lycium barbarum L. (L. barbarum) on cardiometabolic risk factors: a meta-analysis of randomized controlled trials. Food Funct. 2017;8(5):1741-1748.28401234

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