Goji berries

Author: Stefano Piscitello
Date: 08/04/2014



Goji, goji berry or wolfberry is the fruit of Lycium barbarum and Lycium chinense, two very closely related species of boxthorn in the family Solanaceae (which also includes the potato, tomato, eggplant, deadly nightshade, chili pepper, and tobacco). The two species are native to Asia.
Wolfberry species are deciduous woody perennial plants, growing 1–3 m high. L. chinense is grown in the south of China and tends to be somewhat shorter, while L. barbarum is grown in the north, primarily in the Ningxia Hui Autonomous Region, and tends to be somewhat taller.
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.


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.
Recently, isolation and investigation of novel ingredients with biological activities and health benefit effects from natural resources have attracted a great deal of attention. The fruit of Lycium barbarum L., a well-known Chinese herbal medicine as well as valuable nourishing tonic, has been used historically as antipyretic, anti-inflammation and anti-senile agent for thousands of years. Modern pharmacological experiments have proved that polysaccharide is one of the major ingredients responsible for those biological activities in L. barbarum. It has been demonstrated that L. barbarum polysaccharides had various important biological activities, such as antioxidant, immunomodulation, antitumor, neuroprotection, radioprotection, anti-diabetes, hepatoprotection, anti-osteoporosis and antifatigue.
In the present study age-dependent changes in the antioxidant enzyme activity, immune function and lipid peroxidation product were investigated and effect of Lycium barbarum polysaccharides on age-induced oxidative stress in different organs of aged mice was checked. Lycium barbarum polysaccharides (200, 350 and 500 mg/kg b.w. in physiological saline) were orally administrated to aged mice over a period of 30 days. Aged mice receiving vitamin C served as positive control. Enzymatic and non-enzymatic antioxidants, lipid peroxides in serum and tested organs, and immune function were measured. Result showed that increased endogenous lipid peroxidation, and decreased antioxidant activities, as assessed by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (TAOC), and immune function were observed in aged mice and restored to normal levels in the polysaccharides-treated groups. Antioxidant activities of Lycium barbarum polysaccharides can be compable with normal antioxidant, vitamin C. Moreover, addition of vitamin C to the polysaccharides further increased the in vivo antioxidant activity of the latter. It is concluded that the Lycium barbarum polysaccharides can be used in compensating the decline in TAOC, immune function and the activities of antioxidant enzymes and thereby reduces the risks of lipid peroxidation accelerated by age-induced free radical.
Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice,2007


Macrophages, rather than T and B cells are principal immunostimulatory target cells of Lycium barbarum L. polysaccharide LBPF4-OL.
Lycium barbarum L. is a renowned Yin strengthening agent in traditional Chinese medicine. Lycium barbarum L. polysaccharide-protein complex is well-known for its immunoregulatory and antitumor effects. LBPF4-OL is the glycan part of Lycium barbarum L. polysaccharide-protein complex fraction 4 (LBPF4). LBPF4-OL's active contribution in LBPF4 is still blank. In the study, we enrich the polysaccharide part of Lycium barbarum L. polysaccharide-protein complex, and investigate its immunostimulatory effects on mouse spleen cells, T cells, B cells and macrophages.
Balb/C mice were used in vitro and in vivo studies. In vitro study, lymphocyte proliferations were analyzed with (3)H-TdR incorporation method. Miltenyi MicroBeads were used in the purification of lymphocytes. Activation of T and B cells was analyzed by flow cytometry. In order to obtain the peritoneal macrophages, mice were injected i.p. with 1mL of sodium thioglycollate 3 days prior to killing. Spleen cells were stimulated with LBPF4-OL and cytokine concentrations in the supernatants were determined by multiplex bead analysis. In in vivo study, mice were injected i.p. with 1 mL of normal saline or 100 μg/mL LBPF4-OL daily for 6 days. Peritoneal macrophage functions were analyzed by enzyme-linked immunosorbent assay and flow cytometry assay.
Spleen cells and lymphocyte proliferation assay indicated that LBPF4-OL markedly induced the spleen cell proliferation, but could not induce proliferation of purified T and B lymphocytes. Further research revealed that B cell proliferation took place in the presence of activated macrophages or LPS. Multiplex bead analysis showed that LBPF4-OL can obviously induce IL-6, IL-8, IL-10 and TNF-α production of the spleen cells in a concentration-dependent manner. Flow cytometric analysis showed that LBPF4-OL (i.p.) prompts CD86 and MHC-II molecules expression on macrophages. ELISA assay showed that LBPF4-OL can greatly strengthen macrophage releasing of TNF-α and IL-1β.
These results suggested that glycan LBPF4-OL plays an important role in the immunopharmacological activity of Lycium barbarum L. polysaccharide-protein complex, and primary mouse macrophages, rather than T and B cells, are the principal target cells of it.
Lycium barbarum polysaccharide LBPF4-OL may be a new Toll-like receptor 4/MD2-MAPK signaling pathway activator and inducer,2014

Lycium barbarum polysaccharide LBPF4-OL may be a new Toll-like receptor 4/MD2-MAPK signaling pathway activator and inducer.
Recognition of the utility of the traditional Chinese medicine Lycium barbarum L. has been gradually increasing in Europe and the Americas. Many immunoregulation and antitumor effects of L. barbarum polysaccharides (LBP) have been reported, but its molecular mechanism is not yet clear. In this study, we reported that the activity of the polysaccharide LBPF4-OL, which was purified from LBP, is closely associated with the TLR4-MAPK signaling pathway. We found that LBPF4-OL can significantly induce TNF-α and IL-1β production in peritoneal macrophages isolated from wild-type (C3H/HeN) but not TLR4-deficient mice (C3H/HeJ). We also determined that the proliferation of LBPF4-OL-stimulated lymphocytes from C3H/HeJ mice is significantly weaker than that of lymphocytes from C3H/HeN mice. Furthermore, through a bio-layer interferometry assay, we found that LPS but not LBPF4-OL can directly associate with the TLR4/MD2 molecular complex. Flow cytometry analysis indicated that LBPF4-OL markedly upregulates TLR4/MD2 expression in both peritoneal macrophages and Raw264.7 cells. As its mechanism of action, LBPF4-OL increases the phosphorylation of p38-MAPK and inhibits the phosphorylation of JNK and ERK1/2, as was observed through Western blot analysis. These data suggest that the L. barbarum polysaccharide LBPF4-OL is a new Toll-like receptor 4/MD2-MAPK signaling pathway activator and inducer.


Possible interaction between warfarin and Lycium barbarum L.

To describe a patient who was stabilized on warfarin and developed an elevated international normalized ratio (INR) after drinking a concentrated Chinese herbal tea. Additionally, to determine the effect of the tea on CYP2C9, the isoenzyme responsible for the metabolism of S-warfarin.

An elevated INR of 4.1 was observed in a 61-year-old Chinese woman, previously stabilized on anticoagulation therapy (INR 2-3). With no changes in her other medications or lifestyle, a review of her dietary habits revealed four days of drinking a concentrated Chinese herbal tea made from Lycium barbarum L. fruits (3-4 glasses daily) prior to her clinic visit Warfarin was withheld for one day and then resumed at a lower weekly dose. She discontinued the tea, while maintaining consistency with medications and dietary habits. A follow-up INR seven days later was 2.4, and seven subsequent INR values were in the 2.0-2.5 range.

L barbarum L. (family Solanaceae) is a commonly used Chinese herb considered to have a tonic effect on various organs. Any impact of an herbal product on the metabolism of S-warfarin, the enantiomer responsible for most of the anticoagulant activity, could alter the INR values. An herbal-drug interaction was suspected in this case. In vitro evaluation showed inhibition of S-warfarin metabolism by CYP2C9 by the tea of L. barbarum L.; however, the inhibition observed was weak, with a dissociation constant (Ki) value of 3.4 mg/mL, suggesting that the observed interaction may be caused by factors other than the CYP450 system.

There is a potential herbal-drug interaction between warfarin and L. barbarum L., based on an increased INRvalue noted with concurrent use. Thus, combination of L. barbarum L. and warfarin should be avoided. Vigilance is needed with other herbal combinations taken with drugs of narrow therapeutic indices.

Possible interaction between warfarin and Lycium barbarum L.,2001


Since the early 21st century, the dried fruit has been marketed in the West as a health food often accompanied by scientifically unsupported claims regarding its purported health benefits.
The level of vitamin C is comparable to many citrus fruits and strawberries as well as numerous other fruits and berries.
In February 2007, the Food Standards Agency (FSA) of the United Kingdom, an advisor for food safety to the European Food Safety Authority of the European Union (EU), published an inquiry to retailers and health food stores requesting evidence of significant use of wolfberries in Europe before 1997.Information from this period would document a safety history and evaluate how "novel" the berries are in the EU, affecting their authorization status for sale.
Proponents hoped this review would provide important safeguards for consumers by checking whether new foods are suitable for the whole population, including people with food allergies. Opponents on the other hand feared it would limit consumer choice and protect monopolistic interests rather than the public.Food safety in the EU relies importantly on a scientific basis for label information on foods like wolfberries that may be claimed to furnish health benefits.
In June 2007, the FSA announced its decision that wolfberries indeed had a history of use in Great Britain before 1997. Accordingly, wolfberries do not require registration as a novel food.
During 2006, the U.S. Food and Drug Administration (FDA) placed two goji juice distributors on notice with warning letters about marketing claims. These statements were in violation of the United States Food, Drug and Cosmetic Act [21 USC/321 (g)(1)] because they "establish the product as a drug intended for use in the cure, mitigation, treatment, or prevention of disease" when wolfberries or juice have had no such scientific evaluation. Additionally stated by the FDA, the goji juice was "not generally recognized as safe and effective for the referenced conditions" and therefore must be treated as a "new drug" under Section 21(p) of the Act. New drugs may not be legally marketed in the United States without prior approval of the FDA.

2014-04-08T17:09:05 - Stefano Piscitello
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