Goji (Lycium barbarum and L. chinense): Phytochemistry, Pharmacology and Safety in the Perspective of Traditional Uses and Recent Popularity

Abstract

Since the beginning of this century, Goji berries and juice are being sold as health food products in western countries and praised in advertisements and in the media for well-being and as an anti-aging remedy. The popularity of Goji products has rapidly grown over the last years thanks to efficient marketing strategies. Goji is a relatively new name given to Lycium barbarum and L. chinense, two close species with a long tradition of use as medicinal and food plants in East Asia, in particular in China. While only L. barbarum is officinal, the fruit (fructus Lycii) and the root bark (cortex Lycii radicis) of both species are used in the folk medicine. We review here the constituents, pharmacology, safety, and uses of L. barbarum and L. chinense with consideration to the different parts of the plant. Investigations of the fruit have focused on proteoglycans, known as “Lycium barbarum polysaccharides”, which showed antioxidative properties and some interesting pharmacological activities in the context of age related diseases such as atherosclerosis and diabetes. As to the root bark, several compounds have demonstrated a hepatoprotective action as well as inhibitory effects on the rennin/angiotensin system which may support the traditional use for the treatment of hypertension. While there are no signs of toxicity of this plant, two cases of possible interaction with warfarin point to a potential risk of drug interaction. In view of the available pharmacological data and the long tradition of use in the traditional Chinese medicine, L. barbarum and L. chinense certainly deserve further investigation. However, clinical evidences and rigorous procedures for quality control are indispensable before any recommendation of use can be made for Goji products.

Goji - wolfberry - Lycium barbarum - Lycium chinense - Solanaceae - Novel Food

References

• 1 Potterat O, Hamburger M. Goji juice: a novel miraculous cure for longevity and well being? A review of composition, pharmacology, health-related claims and benefits.  Schweiz Zschr Ganzheitsmedizin. 2008;  20 399-405
• 2 Zhang K Y B, Leung H W, Yeung H W, Wong R N S. Differentiation of Lycium barbarum from its related Lycium species using random amplified polymorphic DNA.  Planta Med. 2001;  67 379-381
• 3 Hänsel R, Keller K, Rimpler H, Schneider G. Hagers Handbuch der pharmazeutischen Praxis, Vol 5: Drogen E – O. Berlin, Heidelberg, New York; Springer Verlag 1993
• 4 Sze S C W, Song J X, Wong R N S, Feng Y B, Ng T B, Tong Y, Zhang K Y B. Application of SCAR (sequence characterized amplified region) analysis to authenticate Lycium barbarum (wolfberry) and its adulterants.  Biotechnol Appl Biochem. 2008;  5 15-21
• 5 Genaust H. Etymologisches Wörterbuch der botanischen Pflanzennamen, 3. Auflage. Basel; Birkhäuser Verlag 1996
• 6 Qian J, Liu D, Huang A. The efficiency of flavonoids in polar extracts of Lycium chinense Mill. fruits as free radical scavenger.  Food Chem. 2004;  87 283-288
• 7 Stuart G A, Smith F P. Chinese Materia Medica. Shanghai; American Presbyterian Mission Press 1911: 250
• 8 Bich D H, Tap N, Toan T, Hung T, Hien P V, Lo V N, Man P K, Dan N V, Nhu D T, Mai P D. Selected medicinal plants in Vietnam, volume 2. Hanoi; Science and Technology Publishing House 1999
• 9 [no authors listed.]. Pharmacopoeia of the People's Republic of China, English edition. Beijing; Chemical Industry Press 2000
• 10 Burke D S, Smidt C R, Vuong L T. Momordica cochichinensis, Rosa roxburghii, wolfberry, and sea buckthorn – highly nutritional fruits supported by tradition and science.  Curr Top Nutraceutical Res. 2005;  3 259-266
• 11 Zhufan X. Practical traditional Chinese medicine. Beijing; Foreign Language Press 2000
• 12 Bensky D, Clavey S, Stöger E. Chinese herbal medicine, 3rd edition. Materia Medica. Seattle; Eastland Press, Inc. 2004
• 13 Chen J K, Chen T T. Chinese medical herbology and pharmacology. City of Industry, CA; Art of Medicine Press, Inc. 2004
• 14 Zhu Y P. Chinese Materia Medica – chemistry, pharmacology and applications. Amsterdam; Harwood Academic Publishers 1998
• 15 Reid D P. Chinesische Heilkunde. Stuttgart; Thieme Hippokrates Enke 1995: 155,224
• 16 Reid D. Handbuch der chinesischen Heilkräuter. München; Droemersche Verlagsanstalt Th Knaur Nachf 1998
• 17 Huang K C. The pharmacognosy of Chinese herbs. Boca Raton; CRC Press 1999: 333-334
• 18 Yin G, Dang Y. Optimization of extraction technology of the Lycium barbarum polysaccharides by Box-Behnken statistical design.  Carbohydr Polym. 2008;  74 603-610
• 19 Peng X, Tian G. Structural characterization of the glycan part of glycoconjugate LbGp2 from Lycium barbarum L.  Carbohydr Res. 2001;  331 96-99
• 20 Huang L, Lin Y, Tian G, Ji G. Isolation, purification and physicochemical properties of immunoactive glycoconjugates from fruit of Lycium barbarum L.  Yaoxue Xuebao. 1998;  33 512-516
• 21 Huang L, Tian G Y, Ji G Z. Structure elucidation of glycan of glycoconjugate LbGp3 isolated from the fruit of Lycium barbarum L.  J Asian Nat Prod Res. 1999;  1 259-267
• 22 Peng X, Huang J, Qi C, Zhang Y X, Tian G Y. Studies on chemistry and immuno-modulating mechanism of a glycoconjugate from Lycium barbarum L.  Chin J Chem. 2001;  19 1190-1197
• 23 Peng X, Qi C, Tian G, Zhang X X. Physico-chemical properties and bioactivities of a glycoconjugate LbGp5B from Lycium barbarum L.  Chin J Chem. 2001;  19 842-846
• 24 Gan L, Zhang S H, Yang X L, Xu H B. Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum.  Int Immunopharmacol. 2004;  1 563-569
• 25 Zhao C J, He Y Q, Li R Z, Cui G H. Chemistry and pharmacological activity of petidoglycan from Lycium barbarum.  Chin Chem Lett. 1996;  11 1009-1010
• 26 Zhao C, Li R, He Y, Chui G. Studies on chemistry of Gouqi polysaccharides.  Yie Daxue Xuebao. 1997;  29 231-232 240 (CAN 129: 120129)
• 27 Chen Z, Tan B K H, Chan S H. Activation of T lymphocytes by polysaccharide-protein complex from Lycium barbarum L.  Int Immunopharmacol. 2008;  8 1663-1671
• 28 Duan C, Qiao S, Wang N, Zhao Y, Qi C, Yao X. Studies on active polysaccharides from Lycium barbarum.  Yaoxue Xuebao. 2001;  36 196-199
• 29 Wang C C, Chang S C, Chen B H. Chromatographic determination of polysaccharides in Lycium barbarum Linneaus.  Food Chem. 2009;  116 595-603
• 30 Li X, Zhou A G, Li X M. Inhibition of Lycium barbarum polysaccarides and Ganoderma lucidum polysaccharides against oxidative injury induced by γ-irradiation in rat liver mitochondria.  Carbohydr Polym. 2007;  69 172-178
• 31 Piao M, Murata Y, Zhu B, Shimoishi Y, Tada M. Changes in carotenoid content and its composition during maturation of Fructus lycii fruits.  Jpn J Food Chem. 2005;  12 35-39 (CAN 144: 169735)
• 32 Weller P, Breithaupt D E. Identification and quantification of zeaxanthin esters in plants using liquid chromatography-mass spectrometry.  J Agric Food Chem. 2003;  51 7044-7049
• 33 Peng Y, Ma C, Li Y, Leung K S Y, Jiang Z H, Zhao Z. Quantification of zeaxanthin dipalmitate and total carotenoids in Lycium fruits (Fructus lycii).  Plant Foods Hum Nutr. 2005;  60 161-164
• 34 Inbaraj B S, Lu H, Hung C F, Wu W B, Lin C L, Chen B H. Determination of carotenoids and their esters in fruits of Lycium barbarum Linnaeus by HPLC-DAD-APCI-MS.  J Pharm Biomed Anal. 2008;  47 812-818
• 35 Molnar P, Pfander H, Olah P, Deli J, Toth G. Carotenoid composition of Lycium barbarum L. seeds of Chinese and Hungarian origin.  Olaj, Szappan, Kozmetika. 2003;  52 50-55 (CAN 140: 108103)
• 36 Qi Z, Li S, Wu J, Qu R, Yang Y, Zhang L, Yang X. Chemical constituents of Fructus lycii and Folium lycii – nutrients in Fructus lycii and Folium lycii.  Zhongyao Tongbao (Beijing, China). 1986;  11 169-171
• 37 Toyoda-Ono Y, Maeda M, Nakao M, Yoshimura M, Sugiura-Tomimori N, Fukami H. 2-O-(β-D-Glucopyranosyl)ascorbic acid, a novel ascorbic acid analogue isolated from Lycium fruit.  J Agric Food Chem. 2004;  52 2092-2096
• 38 Le K, Chiu F, Ng K. Identification and quantification of antioxidants in Fructus lycii.  Food Chem. 2007;  105 353-363
• 39 Altintas A, Kosar M, Kirimer N, Baser K H, Demirci B. Composition of the essential oils of Lycium barbarum and Lycium ruthenicum fruits.  Chem Nat Comp. 2006;  41 24-25
• 40 Gao Z, Ali Z, Khan I A. Glycerogalactolipids from the fruit of Lycium barbarum.  Phytochemistry. 2008;  69 2856-2861
• 41 Chen S, Wang Q, Gong S, Wu J, Yu X, Lin S. Analysis of amino acid in Fructus lycii.  Zhongguo Yaoke Daxue Xuebao. 1991;  22 53-55 (CAN 115: 15369)
• 42 Cao Y, Zhang X, Chu Q, Fang Y, Ye J. Determination of taurine in Lycium barbarum L. and other foods by capillary electrophoresis with electrochemical detection.  Electroanalysis. 2003;  15 898-902
• 43 Wang Q, Qiu Y, He S P, Chen Y Y. Chemical constituents of the fruit of Lycium barbarum L.  J Chin Pharm Sci. 1988;  7 218-220
• 44 Zou C, Zhao Q, Chen C X, He Y N. New dopamine derivative from Lycium barbarum.  Chin Chem Lett. 1999;  10 131-132
• 45 Hiserodt R D, Adedeji J, John T V, Dewis M L. Identification of monomenthyl succinate, monomenthyl glutarate, and dimenthyl glutarate in nature by high performance liquid chromatography-tandem mass spectrometry.  J Agric Food Chem. 2004;  52 3536-3541
• 46 Harsh M L. Tropane alkaloids from Lycium barbarum Linn., in vivo and in vitro.  Curr Sci. 1989;  58 817-818
• 47 Adams M, Wiedenmann M, Tittel G, Bauer R. HPLC-MS trace analysis of atropine in Lycium barbarum berries.  Phytochem Anal. 2006;  17 279-283
• 48 Qin X, Yamauchi R, Aizawa K, Inakuma T, Kato K. Isolation and characterization of arabinogalactan-protein from the fruit of Lycium chinense. Mill.  J Appl Glycosci. 2000;  47 155-160
• 49 Qin X, Yamauchi R, Aizawa K, Inakuma T, Kato K. Structural features of arabinogalactan-proteins from the fruit of Lycium chinense Mill.  Carbohydr Res. 2001;  333 79-85
• 50 Qin X, Lin H. Isolation and characteristics of araban isolated from fruit of Lycium chinense Mill.  Shipin Kexue. 2003;  24 52-56
• 51 Kim S Y, Kim H P, Huh H, Kim C. Antihepatotoxic zeaxanthins from the fruit of Lycium chinense.  Arch Pharm Res. 1997;  20 529-532
• 52 Noculak-Palczewska A, Matkowski A, Gasiorowski K, Tabaka H, Oszmianski J, Lamer-Zarawska E. Chemical characterisation of methanolic-water extracts from the fruit of acclimated Lycium chinense Mill.  Herba Pol. 2004;  50 47-53
• 53 Kim S Y, Choi Y H, Huh H, Kim J, Kim Y C, Lee H S. New antihepatotoxic cerebroside from Lycium chinense fruits.  J Nat Prod. 1997;  60 274-276
• 54 Chin Y W, Lim S W, Kim S H, Shin D Y, Suh Y G, Kim Y B, Kim Y C, Kim J. Hepatoprotective pyrrole derivatives of Lycium chinense fruits.  Bioorg Med Chem Lett. 2003;  13 79-81
• 55 Itoh T, Tamura T, Matsumoto T. Triterpene alcohols in the seeds of Solanaceae.  Phytochemistry. 1977;  16 1723-1726
• 56 Itoh T, Ishi T, Tamura T, Matsumoto T. Four new and other 4α-methylsterols in the seeds of Solanaceae.  Phytochemistry. 1978;  17 971-977
• 57 Itoh T, Tamura T, Matsumoto T. 4-desmethylsterols in the seeds of Solanaceae.  Steroids. 1977;  30 425-433
• 58 Jung K, Chin Y W, Kim Y C, Kim J. Potentially hepatoprotective glycolipid constituents of Lycium chinense fruits.  Arch Pharm Res. 2005;  28 1381-1385
• 59 Sannai A, Fujimori T, Kato K. Neutral volatile components of “kukoshi” (Lycium chinense M.).  Agric Biol Chem. 1983;  47 2397-2399
• 60 Sannai A, Fujimori T, Kato K. Isolation of (−)-1,2-dehydro-α-cyperone and solavetivone from Lycium chinense.  Phytochemistry. 1982;  21 2986-2987
• 61 Lee G H, Shin Y, Oh M J. Aroma-active components of Lycii fructus (kukija).  J Food Sci. 2008;  73 C500-C505
• 62 Yahara S, Shigeyama C, Ura T, Wakamatsu K, Yasuhara T, Nohara T. Cyclic peptides, acyclic diterpene glycosides and other compounds from Lycium chinense Mill.  Chem Pharm Bull. 1993;  41 703-709
• 63 Yahara S, Shigeyama C, Nohara T. Structures of anti-ACE and -renin peptides from Lycii radicis cortex.  Tetrahedron Lett. 1989;  30 6041-6042
• 64 Morita H, Yoshida N, Takeya K, Itokawa H, Shirota O. Configurational and conformational analyses of a cyclic octapeptide, lyciumin A, from Lycium chinense Mill.  Tetrahedron. 1996;  52 2795-2802
• 65 Morota T, Sasaki H, Chin M, Sato T, Katayama N, Fukuyama K, Mitsuhashi H. Studies on the crude drug containing the angiotensin I-converting enzyme inhibitors (I). The active principles of Lycium chinense Miller.  Shoyakugaku Zasshi. 1987;  41 169-173 (CAN 108: 192630)
• 66 Noguchi M, Mochida K, Shingu T, Kozura M, Fujitani K. Über die Bestandteile der chinesischen Droge „Ti-ku'pi“. I. Isolierung und Konstitution von Lyciumamid, einem neuen Dipeptid.  Chem Pharm Bull. 1984;  32 3584-3587
• 67 Han S H, Lee H H, Lee I S, Moo Y H, Woo E R. A new phenolic amide from Lycium chinense Miller.  Arch Pharm Res. 2002;  25 433
• 68 Lee D G, Park Y, Kim M R, Jung H J, Seu Y B, Hahm K S, Woo E R. Antifungal effects of phenolic amides isolated from the root bark of Lycium chinense.  Biotechnol Lett. 2004;  26 1125-1130
• 69 Funayama S, Yoshida K, Konno C, Hikino H. Structure of kukoamine A, a hypotensive principle of Lycium chinense root barks.  Tetrahedron Lett. 1980;  21 1355-1356
• 70 Funayama S, Zhang G R, Nozoe S. Kukoamine B, a spermine alkaloid from Lycium chinense.  Phytochemistry. 1995;  38 1529-1531
• 71 Asano N, Kato A, Miyauchi M, Kizu H, Tomimori T, Matsui K, Nash R J, Molyneux R J. Specific α-galactosidase inhibitors, N-methylcalystegines. Structure/activity relationships of calystegines from Lycium chinense.  Eur J Biochem. 1997;  248 296-303
• 72 Chu Q, Fu L, Lin M, Ye J. Study on bioactive ingredients in Cortex lycii by capillary zone electrophoresis with amperometric detector.  Fenxi Huaxue. 2005;  33 1611-1614
• 73 Wei X, Liang J. Chemical studies on the root bark of Lycium chinense.  Zhongcaoyao. 2003;  34 580-581 (CAN 141: 346494)
• 74 Wei X, Liang J. Chemical study on the root bark of Lycium chinense Mill.  Zhongguo Yaoke Daxue Xueba. 2002;  33 271-273 (CAN 141: 137021)
• 75 Lee D G, Jung H J, Woo E R. Antimicrobial property of (+)-lyoniresinol-3α-O-β-D-glucopyranoside isolated from the root bark of Lycium chinense Miller against human pathogenic microorganisms.  Arch Pharm Res. 2005;  28 1031-1036
• 76 Li Y, Li P, Tu P, Chang H. Identification of chemical constituents of Lycium chinense.  Zhongcaoyao. 2004;  35 1100-1101
• 77 Noguchi M, Mochida K, Shingu T, Fujitani K, Kozuka M. Sugiol and 5α-stigmastane-3,6-dione from the Chinese drug “Ti-ku-p'i” (Lycii Radicis Cortex).  J Nat Prod. 1985;  48 342-343
• 78 Zhou X, Xu G, Wang Q. Studies on the chemical constituents in the roots of Lycium chinense mill.  Zhongguo Zhongyao Zazhi. 1996;  21 675-676 (CAN 126: 255338)
• 79 Mizobuchi K, Inoue Y, Kiuch T, Higashi J. Constituents of box thorn. II. Chemical components of the root bark of box thorn.  Shoyakugaku Zasshi. 1963;  17 16-18 (CAN 62: 16825)
• 80 Drost-Karbowska K, Hajdrych-Szaufer M, Kowalewski Z. Search for alkaloid-type bases in Lycium halimifolium.  Acta Pol Pharm. 1984;  41 127-129 (CAN 101: 167206)
• 81 Terauchi M, Kanamori H, Nobuso M, Yahara S, Yamasaki K. New acyclic diterpene glycosides, lyciumosides IV–IX from Lycium chinense Mill.  Nat Med. 1998;  52 167-171
• 82 Jassbi A R, Zamanizadehnajari S, Kessler D, Baldwin I T. A new acyclic diterpene glycoside from Nicotiana attenuata with a mild deterrent effect on feeding Manduca sexta larvae.  Z Naturforsch. 2006;  61 , [b]: 1138–1142
  
• 83 Haensel R, Huang J T, Rosenberg D. Zwei Withanolide aus Lycium chinese.  Arch Pharm. 1975;  308 653-654
• 84 Imai S, Murata T, Fujioka S, Goto M. Isolation of β-sitosterol β-D-glucoside from the leaves of Lycium chinense.  Yakugaku Zhassi. 1963;  83 1092 (CAN 60: 52965)
• 85 Zou Y. Flavones in leaves of Lycium chinense.  Fenxi Ceshi Xuebao. 2002;  21 76-78 (CAN 137: 75890)
• 86 Terauchi M, Kanamori H, Nobuse M, Yahara S, Nohara T. Detection and determination of antioxidative components in Lycium chinense.  Nat Med. 1997;  51 387-391
• 87 Aubert C, Kapetanidis I. New flavonoids from Lycium chinense.  Planta Med. 1989;  55 612
• 88 Haensel R, Huang J T. Lycium chinense, III. Isolierung von Scopoletin und Vanillinsäure.  Arch Pharm. 1977;  310 38-40
• 89 Noma M, Noguchi M. Occurence of nicotianamine in higher plants.  Phytochemistry. 1976;  15 1701-1702
• 90 Yoshimura Y, Take T, Otsuka H, Daigaku N, Niagata J. Taste substances in foods. XIV. Taste substances in the leaves of box thorn (Lycium chinense).  Kaseigaku Zasshi. 1969;  20 481-484 (CAN 72: 109981)
• 91 Kim S Y, Lee K H, Chang K S, Bock J Y, Jung M Y. Taste and flavor compounds in box thorn (Lycium chinense Miller) leaves.  Food Chem. 1997;  58 297-303
• 92 Sannai A, Fujimori T, Wegaki R, Akaki T. Isolation of 3-hydroxy-7,8-dehydro-β-ionone from Lycium chinense M.  Agric Biol Chem. 1984;  48 1629-1630
• 93 Christen P, Kapetanidis I. Flavonoids from Lycium halimifolium.  Planta Med. 1987;  53 571-572
• 94 Näf R, Velluz A, Thommen W. Isolation of a glucosidic precursor of damascenone from Lycium halimifolium Mil.  Tetrahedron Lett. 1990;  45 6521-6522
• 95 Zhao Q, Li C, Zhou D. Chemical constituents of Gouqi (Lycium barbarum) leaf.  Zhongcaoyao. 1987;  18 104 133 (CAN 107: 93549)
• 96 Qi Z, Li S, Wu J, Qu R, Yang Y, Zhang L, Yang X. Chemical constituents of Fructus lycii and Folium lycii. (I). Nutrients in Fructus lycii and Folium lycii.  Zhongyao Tongbao. 1986;  11 163 169-171 (CAN 105: 3596)
• 97 Harsh M L, Nag T N. Diosgenin and phytosterols from Lycium barbarum Linn.  Curr Sci. 1981;  50 235
• 98 Chang R C C, So K F. Use of anti-aging herbal medicine, Lycium barbarum, against aging-associated diseases. What do we know so far?.  Cell Mol Neurobiol. 2008;  28 643-652
• 99 Li X M, Li X L, Zhou A G. Evaluation of antioxidant activity of the polysaccharides extracted from Lycium barbarum fruits in vitro.  Eur Polymer J. 2007;  43 488-497
• 100 Li X L, Zhou A G. Evaluation of the antioxidant effects of polysaccharides extracted from Lycium barbarum.  Med Chem Res. 2007;  15 471-482
• 101 Ren B, Ma Y, Sheng Y, Gao B. Protective action of Lycium barbarum L. and betaine on lipid peroxidation of RBC membrane induced by hydrogen peroxide.  Zhongguo Zhongyao Zazhi. 1995;  20 303-304 (CAN 124: 21718)
• 102 Luo Q, Li Z, Huang X, Yan J, Zhang S, Cai Y. 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;  79 613-621
• 103 Ma L, Chen Q, Yang W, Xi S, Wan X, Tang X, Yu Y, Kang J. Effect of Lycium barbarum polysaccharide against atherosclerosis in rabbits.  Zhengzhou Daxue Xuebao, Yixueban. 2005;  40 328-330 (CAN 144: 324440)
• 104 Ming M, Guanhua L, Zhanhai Y, Guang C, Xuan Z. Effect of the Lycium barbarum polysaccharides administration on blood lipid metabolism and oxidative stress of mice fed high-fat diet in vivo.  Food Chem. 2009;  113 872-877
• 105 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;  126 365-371
• 106 Li X M. Protective effect of Lycium barbarum polysaccharides on streptozotocin-induced oxidative stress in rats.  Int J Biol Macromol. 2007;  40 461-465
• 107 Zhao R, Li Q, Xiao B. Effect of Lycium barbarum polysaccharide on the improvement of insulin resistance in NIDDM rats.  Yakugaku Zasshi. 2005;  125 981-988
• 108 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;  76 137-149
• 109 Du G, Liu L, Fang J. Experimental study of the enhancement of murine splenic lymphocyte proliferation by Lycium barbarum glycopeptide.  J Huazhong Univ Sci Technol. 2004;  24 518-520
• 110 Chen Z, Lu J, Srinivasan N, Tan B K H, Chan S H. Polysaccharide-protein complex from Lycium barbarum L. is a novel stimulus of dendritic cell immunogenicity.  J Immunol. 2009;  182 3503-3506
• 111 Gan L, Zhang S H, Liu Q, Xu H B. A polysaccharide-protein complex from Lycium barbarum upregulates cytokine expression in human peripheral blood mononuclear cells.  Eur J Pharmacol. 2003;  471 217-222
• 112 Gan L, Zhang S H, Yang X L, Xu H B. Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum.  Int J Immunopharmacol. 2004;  4 563-569
• 113 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 2115-2124
• 114 Chao J C J, Chiang S W, Wang C C, Tsai Y H, Wu M S. Hot water-extracted Lycium barbarum and Rehmannia glutinosa inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells.  World J Gastroenterol. 2006;  12 4478-4484
• 115 Liu X, Sun J, Li H, Zhang L, Qian B. Extraction and isolation of active component in fruit of Lycium barbarum for inhibiting PC3 cell proliferation in vitro.  Zhongguo Zhongyao Zazhi. 2000;  25 481-483 (CAN 134: 263473)
• 116 Li G, Sepkovic W, Bradlow H L, Telang N T, Wong G Y C. Lycium barbarum inhibits growth of estrogen receptor positive human breast cancer cells by favorably altering estradiol metabolism.  Nutr Cancer. 2009;  61 408-414
• 117 Gong H, Shen P, Jin L, Xing C, Tang F. Therapeutic effects of Lycium barbarum polysaccharide (LBP) on irradiation or chemotherapy-induced myelosuppressive mice.  Cancer Biother Radiopharm. 2005;  20 155-162
• 118 Yu M S, Leung S K Y, Lai S W, Che C M, Zee S Y, So K F, Yuen W H, Chang R C C. Neuroprotective effects of anti-aging oriental medicine Lycium barbarum against beta-amyloid peptide neurotoxicity.  Exp Gerontol. 2005;  40 716-727
• 119 Yu M S, Ho Y S, So K F, Yuen W H, Chang C C. Cytoprotective effects of Lycium barbarum against reducing stress on endoplasmic reticulum.  Int J Mol Med. 2006;  17 1157-1161
• 120 Yu M S, Lai Cora S W, Ho Y S, Zee S Y, So K F, Yuen W H, Chang R C C. Characterization of the effects of anti-aging medicine Fructus Lycii on beta amyloid peptide neurotoxicity.  Int J Mol Med. 2007;  20 261-268
• 121 Chan H C, Chang R C C, Ip A K C, Chiu K, Yuen W H, Zee S Y, So K F. Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma.  Exp Neurol. 2007;  203 269-273
• 122 Kim H P, Lee E J, Kim Y C, Kim J, Kim H K, Park J H, Kim S Y, Kim Y C. Zeaxanthin dipalmitate from Lycium chinense fruit reduces experimentally induced hepatic fibrosis in rats.  Biol Pharm Bull. 2002;  25 390-392
• 123 Kim S Y, Lee E J, Kim H P, Kim Y C, Moon A, Kim Y C. A novel cerebroside from Lycii fructus preserves the hepatic glutathione system in primary cultures of rat hepatocytes.  Biol Pharm Bull. 1999;  22 873-875
• 124 Kim S Y, Lee E J, Kim H P, Lee H S, Kim Y C. LCC, a cerebroside from Lycium chinense, protects primary cultured rat hepatocytes exposed to galactosamine.  Phytother Res. 2000;  14 448-451
• 125 Lin C C, Chuang S C, Lin J M, Yang J J. Evaluation of the anti-inflammatory hepatoprotective and antioxidant activities of Lycium chinense from Taiwan.  Phytomedicine. 1997;  4 213-220
• 126 Ha K T, Yoon S J, Choi D Y, Kim D W, Kim J K, Kim C H. Protective effect of Lycium chinense fruit on carbon tetrachloride-induced hepatotoxicity.  J Ethnopharmacol. 2005;  96 529-535
• 127 Lee S, Song K B. Isolation of an angiotensin converting enzyme inhibitory substance from Lycium chinense Miller.  J Food Sci Nutr. 2004;  9 95-97
• 128 Lin R D, Hou W C, Yen K Y, Lee M H. Inhibition of monoamine oxidase B (MAO-B) by Chinese herbal medicines.  Phytomedicine. 2003;  20 650-656
• 129 Li D Y, Yuan X L, Xia H F, Ma L, Guo Z Y, Shen Y Y, Rong Q Z. Preliminary clinical observations for effects of Ning Xia wolfberry extract on old peoples.  Chin Tradit Herb Drugs. 1989;  20 26-28
• 130 Li W, Dai S Z, Ma W, Gao L. Effects of oral administration of wolfberry on blood superoxide dismutase (SOD), haemoglobin (Hb) and lipid peroxide (LPO) levels in old people.  Chin Tradit Herb Drugs. 1991;  22 251 268
• 131 Amagase H, Nance D M. A randomized, double-blind, placebo-controlled, clinical study of the general effects of a standardized Lycium barbarum (Goji) juice, GoChi™.  J Altern Compl Med. 2008;  14 403-412
• 132 Amagase H, Sun B, Borek C. Lycium barbarum (goji) juice improves in vivo antioxidant biomarkers in serum of healthy adults.  Nutr Res. 2009;  29 19-25
• 133 Cao G W, Yang W G, Du P. Observation of the effects of LAK/IL-2 therapy combining with Lycium barbarum polysaccharides in the treatment of 75 cancer patients.  Zhonghua Zhong Liu Za Zhi (Chin J Oncol). 1994;  16 428-431
• 134 Gross P M, Zhang X, Zhang R. Wolfberry: nature's bounty of nutrition & health. Lake Dalla; Booksurge Publishing 2003
• 135 Brown L, Rimm E B, Seddon J M, Giovannucci E L, Chasan-Taber L, Spiegelman D, Willett W C, Hankinson S E. A prospective study of carotenoid intake and risk of cataract extraction in US men.  Am J Clin Nutr. 1999;  70 517-524
• 136 Seddon J M, Ajani U A, Sperduto R D, Hiller R, Blair N, Burton T C, Farber M D, Gragoudas E S, Haller J, Miller D T, Yanmuzi L A, Willett W. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration.  J Am Med Assoc. 1994;  272 1413-1420
• 137 Breithaupt D E, 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.  Brit J Nutr. 2004;  91 707-713
• 138 Schönfelder I, Schönfelder P. Der neue Kosmos Heilpflanzenführer. Stuttgart; Kosmos-Verlag 2001
• 139 Roth L, Daunderer M, Kormann K. Giftpflanzen – Pflanzengifte, 3. Auflage. Landsberg, München; Ecomed Verlagsgesellschaft 1988
• 140 Chang H M, But P P H, Yao S C, Wang L, Yeung S C S. Pharmacology and applications of Chinese Materia Medica, volume 2. New Jersey, London, Singapore, Hong Kong; World Scientific 2001
• 141 Yang H S, Chen C F. Subacute toxicity of 15 commonly used Chinese drugs (II).  J Food Drug Anal. 1997;  5 355-380
• 142 Tierra M. Westliche Heilkräuter in TCM und Ayurveda. München, Jena; Urban & Fischer Verlag 2001
• 143 Lam A Y, Elmer G W, Mohutsky M A. Possible interaction between warfarin and Lycium barbarum L.  Ann Pharmacother. 2001;  35 1199-1201
• 144 Leung H, Hung A, Hui A C F, Chan T Y K. Warfarin overdose due to the possible effects of Lycium barbarum L.  Food Chem Toxicol. 2008;  46 1860-1862
• 145 Mindell E, Handel R. Goji. The Himalayan health secret. Dallas; Momentum Media 2003
• 146 Food and Drug Administration .Letter of notice Ref. No. CL-06-HFS-810-214. May 8 2006. Available at. www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/CyberLetters/ucm056372.pdf Accessed August 7, 2009
• 147 Food and Drug Administration .Letter of notice Ref. No. CL-06-HFS-810-226. August 7 2006. Available at. www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/CyberLetters/ucm056356.pdf Accessed August 7, 2009
• 148 Potterat O, Hamburger M. Morinda citrifolia (Noni) fruit: phytochemistry, pharmacology, safety.  Planta Med. 2007;  73 191-199
• 149 European Commission .Commission decision of 5 June 2003 authorising the placing on the market of „noni juice“ (juice of the fruit of Morinda citrifolia L.) as a novel food ingredient under Regulation (EC) Nr. 258/97 of the European Parliament and of the Council. Official Journal of the European Union 2003: L 144/12, 12.6.2003. 
• 150 Food Standards Agency .Responses on Goji berries reviewed. 15 June 2007. Available at. www.food.gov.uk/multimedia/pdfs/gojiberriesrep.pdf Accessed August 7, 2009