Xin YF. Zhou GL. Deng ZY. Chen YX. Wu YG. Xu PS. Xuan YX. Protective effect of Lycium barbarum on doxorubicin-induced cardiotoxicity. Phytotherapy Research. 21(11):1020-4, 2007 The objective of this work was to explore the hypothesis that Lycium barbarum (LB) may be protective against doxorubicin (DOX)-induced cardiotoxicity through antioxidant-mediated mechanisms. Male SD rats were treated with distilled water or a water extract of LB (25 mg/kg, p.o.) daily and saline or DOX (5 mg/kg, i.v.) weekly for 3 weeks. Mortality, general condition and body weight were observed during the experiment. DOX-induced cardiotoxicity was assessed by electrocardiograph, heart antioxidant activity, serum levels of creatine kinase (CK) and aspartate aminotransferase (AST) and histopathological change. The DOX group showed higher mortality (38%) and worse physical characterization. Moreover, DOX caused myocardial injury manifested by arrhythmias and conduction abnormalities in ECG (increased QT and ST intervals and ST elevation), a decrease of heart antioxidant activity, an increase of serum CK and AST, as well as myocardial lesions. Pretreatment with LB significantly prevented the loss of myofibrils and improved the heart function of the DOX-treated rats as evidenced from lower mortality (13%), normalization of antioxidative activity and serum AST and CK, as well as improving arrhythmias and conduction abnormalities. These results suggested that LB elicited a typical cardioprotective effect on DOX-related oxidative stress. Furthermore, in vitro cytotoxic study showed the antitumor activity of DOX was not compromised by LB. It is possible that LB could be used as a useful adjunct in combination with DOX chemotherapy.
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 Research. 1158:123-34, 2007 Lycium barbarum is an oriental medicinal herb that has long been used for its anti-aging and cell-protective properties. Previous studies have shown that aqueous extracts from L. barbarum exhibit neuroprotection via inhibiting pro-apoptotic signaling pathways. Other active components can also be accomplished by novel alkaline extraction method, which may give different profiles of water-soluble components. We hypothesize that another active component obtained by alkaline extraction method exerts different biological mechanisms to protect neurons. In this study, we aim to examine the neuroprotective effects from the alkaline extract of L. barbarum, namely LBB, to attenuate beta-amyloid (Abeta) peptide neurotoxicity. Primary cortical neurons were exposed to Abeta-peptides inducing apoptosis and neuronal cell death. Pretreatment of LBB significantly reduced the level of lactate dehydrogenase (LDH) release and the activity of caspase-3 triggered by Abeta. "Wash-out" procedures did not reduce its neuroprotective effects, suggesting that LBB may not bind directly to Abeta. We have further isolated three subfractions from LBB, namely LBB-0, LBB-I and LBB-II. LBB-I and LBB-II showed differential neuroprotective effects. Western blot analysis demonstrated that LBB-I and LBB-II markedly enhanced the phosphorylation of Akt. Taken together, our results suggested that the glycoconjugate isolated from novel alkaline extraction method can open up a new avenue for drug discovery in neurodegenerative diseases.
Chan HC. Chang RC. Koon-Ching Ip A. Chiu K. Yuen WH. Zee SY. So KF. Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma. Experimental Neurology. 203(1):269-73, 2007 Glaucoma is one of the major neurological disorders in eye leading to irreversible blindness in elderly. Increase in intraocular pressure (IOP) has been considered to be the major risk factor for the progressive loss of retinal ganglion cells (RGCs) in retina. While attenuation of IOP has been a major pharmaceutical target, reduction of IOP cannot prevent progressive loss of RGCs. In this regard, urgent need for alternative treatment has to be investigated. Anti-aging medicinal herb Lycium barbarum L. has been used for centuries in Eastern World to protect the eyes and maintain good health. Using an ocular hypertension (OH) model in rat by laser photocoagulation of episcleral and limbal veins, we attempted to investigate whether L. barbarum can promote RGCs survival against elevated IOP. Oral administration of L. barbarum in Sprague-Dawley rats (250-280 g) significantly reduced the loss of RGCs, although elevated IOP was not significantly altered. Rats fed with the 1 mg/kg extract could nearly totally escape from pressure-induced loss of RGCs. In conclusion, this is the first in vivo report showing the therapeutic function of L. barbarum against neurodegeneration in the retina of rat OH model. The results demonstrate that this extract may be a potential candidate for the development of neuroprotective drug against the loss of RGCs in glaucoma.
Li XM. Protective effect of Lycium barbarum polysaccharides on streptozotocin-induced oxidative stress in rats. International Journal of Biological Macromolecules. 40(5):461-5, 2007 Fruit from Lycium barbarum L. in the family Solanaceae is well-known in traditional Chinese herbal medicine. Lycium barbarum polysaccharides (LBP) have been identified as one of the active ingredients responsible for its biological activities. We isolated polysaccharides from dried Lycium barbarum fruits by boiling water extraction. In the study, 50 animals were divided into two groups: a nondiabetic control (n=10) and a diabetic group (n=40). Diabetes was induced by a single injection of streptozotocin (50mg/kg BW; Sigma, USA) freshly dissolved in a 0.1 mol/L citrate buffer (pH 4.5) into the intraperitonium. The normal control rats and the untreated diabetic control rats were only injected with the citrate buffer. Treated diabetic rats were administrated with LBP in drinking water through oral gavage for 30 days. At the end of experiment, oxidative indice in blood, liver and kidney of all groups were examined. The results show that administration of LBP can restore abnormal oxidative indice near normal levels. Therefore, we may assume that LBP is effective in the protection of liver and kidney tissue from the damage of STZ-induced diabetic rats and that the LBP may be of use as a antihyperglycemia agent.
Li XM. Ma YL. Liu XJ. Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice. Journal of Ethnopharmacology. 111(3):504-11, 2007 Oxidative damage of biomolecules increases with age and is postulated to be a major causal factor of various physiological function disorders. Consequently, the concept of anti-age by antioxidants has been developed. Lycium barbarum fruits have been used as a traditional Chinese herbal medicine and the data obtained in in vitro models have clearly established the antioxidant potency of the polysaccharides isolated from the fruits. In the present study, the 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.
Zhu J. Zhao LH. Zhao XP. Chen Z. Lycium barbarum polysaccharides regulate phenotypic and functional maturation of murine dendritic cells. Cell Biology International. 31(6):615-9, 2007 Lycium barbarum polysaccharides (LBPs) have been known to have a variety of immunomodulatory functions including activation of T cells, B cells and NK cells. Dendritic cells (DC) are potent antigen-presenting cells that play pivotal roles in the initiation of the primary immune response. However, little is known about the immunomodulatory effects of LBPs on murine bone marrow derived dendritic cells (BMDC). In the present study, the effects of LBPs on the phenotypic and functional maturation of murine BMDC were investigated in vitro. Compared to the BMDC that were only subjected to treatment with RPMI1640, the co-expression of I-A/I-E, CD11c and secretion of IL-12 p40 by BMDC stimulated with LBPs (100 microg/ml) were increased. In addition, the endocytosis of FITC-dextran by LBPs-treated BMDC (100 microg/ml) was impaired, whereas the activation of proliferation of allogenic lymphocytes by BMDC was enhanced. Our results strongly suggest that LBPs are capable of promoting both the phenotypic and functional maturation of murine BMDC in vitro.
Yu MS. Lai CS. Ho YS. Zee SY. So KF. Yuen WH. Chang RC. Characterization of the effects of anti-aging medicine Fructus lycii on beta-amyloid peptide neurotoxicity. International Journal of Molecular Medicine. 20(2):261-8, 2007 Alzheimer's disease (AD) is an age-related neurodegenerative disease. There are increasing lines of evidence showing that the molecular signaling pathways in aged cells are altered so that cells are susceptible to injury. We and other laboratories have demonstrated the significant involvement of double-stranded RNA-dependent protein kinase (PKR) in beta-amyloid (A beta) peptide neurotoxicity and in AD. Fructus lycii (the fruit of Lycium barbarum) has long been used in oriental medicine as an anti-aging agent. Our previous studies demonstrated that the aqueous extract isolated from L. barbarum exhibited significant protection on cultured neurons against harmful chemical toxins such as A beta and dithiothreitol. We also showed that the polysaccharide-containing extract (LBP) from L. barbarum exhibited neuroprotective effects in the retina against ocular hypertension in a laser-induced glaucoma animal model. In this study, we aimed to investigate whether LBP can elicit neuroprotection to neurons stressed by A beta peptides. Furthermore, we planned to isolate and identify the neuroprotective agent from LBP using chromatographic methods. Our results showed that pretreatment of LBP effectively protected neurons against A beta-induced apoptosis by reducing the activity of both caspase-3 and -2, but not caspase-8 and -9. A new arabinogalactan-protein (LBP-III) was isolated from LBP and attenuated A beta peptide-activated caspase-3-like activity. LBP-III markedly reduced the phosphorylation of PKR triggered by A beta peptide. Since the phosphorylation state of PKR increased with age, reduction of its phosphorylation triggered by A beta peptide may implicate that LBP-III from Fructus lycii is a potential neuroprotective agent in AD. As herbal medicine has received increasing attention for the treatment of AD, our study will open a window for the development of a neuroprotective agent for anti-aging from Chinese medicine.
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 - Journal of the Pharmaceutical Society of Japan. 126(5):365-71, 2006 The effects of polysaccharide extracted from Lycium barbarum (LBP) on blood glucose, oxidative stress and DNA damage in rats with non-insulin dependent diabetes mellitus (NIDDM) were studied. The results show that LBP treatment (10 mg/kg.d) for 4 weeks led to decreased levels of blood glucose, malondialdehyde (MDA) and nitric oxide (NO) in serum of fasting rats; and to increased serum level of superoxidedismutase (SOD). Furthermore, LBP could reduce cellular DNA damage in peripheral lymphocytes of NIDDM rats. The DNA damage was determined by using the single cell gel (comet) assay with alkaline electrophoresis and was quantified by measuring tail length and tail moment. These results suggest that LBP can control blood glucose and modulate the metabolism of glucose, leading to significant improvement of oxidative stress markers (SOD, MDA) in rats with NIDDM. And that, LBP decreases DNA damage possibly via a decrease in oxidative stress levels. In conclusion, LBP as a dietary supplement may prevent the development of complications or even tendency to carcinogenesis in NIDDM rats.
Yu MS. Ho YS. So KF. Yuen WH. Chang RC. Cytoprotective effects of Lycium barbarum against reducing stress on endoplasmic reticulum. International Journal of Molecular Medicine. 17(6):1157-61, 2006 Chinese medicinal herbs have been consumed for thousands of years for the purpose of healthy aging. Lycium barbarum is valued in Chinese culture for its benefits to anti-aging, vision, kidney and liver. Recent studies showed that extracts from L. barbarum possess biological activities including anti-aging, anti-tumor, immune-stimulatory and cytoprotection. Most of these studies emphasized that the protective function of L. barbarum is due to its anti-oxidative effects. We have previously demonstrated that extract from L. barbarum can protect neurons against beta-amyloid (Abeta) peptide-induced apoptosis. Since Abeta toxicity may be mediated via oxidative stress, it is still unclear whether the extract from L. barbarum is a simple anti-oxidant exhibiting cytoprotective effects. We hypothesized that extract from L. barbarum is not simply an anti-oxidant in order to function as a neuroprotective agent. The aim of this study is to investigate whether the extract from L. barbarum (LBG) protect neurons via mechanisms independent of anti-oxidative effects. Using a reducing agent, dithiothreitol (DTT), we found that LBG exhibits cytoprotective effects against reducing stress by lowering the DTT-induced LDH release and caspase-3 activity. DTT can trigger endoplasmic reticulum (ER) stress leading to PKR-like ER kinase (PERK) activation. We also showed that LBG attenuates DTT-induced PERK phosphorylation. The extract from L. barbarum is not simply an anti-oxidant; it can also exhibit cytoprotective effects against reducing stress by DTT.
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 Sciences. 79(7):613-21, 2006 Lycium barbarum, a famous Chinese medicinal herb, has a long history of use as a traditional remedy for male infertility. Polysaccharides are the most important functional constituent in L. barbarum fruits. We systematically investigated the effect of L. barbarum polysaccharides (LBP) on rat testis damage induced by a physical factor (43 degrees C heat exposure), on DNA damage of mouse testicular cells induced by a chemical factor (H2O2), and on sexual behavior and reproductive function of hemicastrated male rats. The results showed that LBP provided a protective effect against the testicular tissue damage induced by heat exposure. When compared with negative control, a suitable concentration of LBP significantly increased testis and epididymis weights, improved superoxide dismutase (SOD) activity, and raised sexual hormone levels in the damaged rat testes. LBP had a dose-dependent protective effect against DNA oxidative damage of mouse testicular cells induced by H2O2. LBP improved the copulatory performance and reproductive function of hemicastrated male rats, such as shortened penis erection latency and mount latency, regulated secretion of sexual hormones and increased hormone levels, raised accessory sexual organ weights, and improved sperm quantity and quality. The present findings support the folk reputation of L. barbarum fruits as an aphrodisiac and fertility-facilitating agent, and provide scientific evidence for a basis for the extensive use of L. barbarum fruits as a traditional remedy for male infertility in China.
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 Journal of Gastroenterology. 12(28):4478-84, 2006 AIM: To investigate the effect of hot water-extracted Lycium barbarum (LBE) and Rehmannia glutinosa (RGE) on cell proliferation and apoptosis in rat and/or human hepatocellular carcinoma (HCC) cells. METHODS: Rat (H-4-II-E) and human HCC (HA22T/VGH) cell lines were incubated with various concentrations (0-10 g/L) of hot water-extracted LBE and RGE. After 6-24 h incubation, cell proliferation (n = 6) was measured by a colorimetric method. The apoptotic cells (n = 6) were detected by flow cytometry. The expression of p53 protein (n = 3) was determined by SDS-PAGE and Western blotting. RESULTS: Crude LBE (2-5 g/L) and RGE (2-10 g/L) dose-dependently inhibited proliferation of H-4-II-E cells by 11% (P < 0.05) to 85% (P < 0.01) after 6-24 h treatment. Crude LBE at a dose of 5 g/L suppressed cell proliferation of H-4-II-E cells more effectively than crude RGE after 6-24 h incubation (P < 0.01). Crude LBE (2-10 g/L) and RGE (2-5 g/L) also dose-dependently inhibited proliferation of HA22T/VGH cells by 14%-43% (P < 0.01) after 24 h. Crude LBE at a dose of 10 g/L inhibited the proliferation of HA22T/VGH cells more effectively than crude RGE (56.8% +/- 1.6% vs 70.3% +/- 3.1% of control, P = 0.0003 < 0.01). The apoptotic cells significantly increased in H-4-II-E cells after 24 h treatment with higher doses of crude LBE (2-5 g/L) and RGE (5-10 g/L) (P < 0.01). The expression of p53 protein in H-4-II-E cells was 119% and 143% of the control group compared with the LBE-treated (2, 5 g/L) groups, and 110% and 132% of the control group compared with the RGE -treated (5, 10 g/L) groups after 24 h. CONCLUSION: Hot water-extracted crude LBE (2-5 g/L) and RGE (5-10 g/L) inhibit proliferation and stimulate p53-mediated apoptosis in HCC cells.
Yu MS. Leung SK. Lai SW. Che CM. Zee SY. So KF. Yuen WH. Chang RC. Neuroprotective effects of anti-aging oriental medicine Lycium barbarum against beta-amyloid peptide neurotoxicity. Experimental Gerontology. 40(8-9):716-27, 2005 As aged population dramatically increases in these decades, efforts should be made on the intervention for curing age-associated neurodegenerative diseases such as Alzheimer's disease (AD). Natural plant extracts of Lycium barbarum are well-known to exhibit anti-aging effects. We therefore hypothesized that they exhibit neuroprotective effects against toxins in aging-related neurodegenerative diseases. In this study, we aimed to investigate whether extracts from L. barbarum have neuroprotective effects against toxicity of fibrillar Abeta(1-42) and Abeta(25-35) fragments. Primary rat cortical neurons exposed to Abeta peptides resulted in apoptosis and necrosis. Pre-treatment with extract isolated from L. barbarum significantly reduced the release of lactate dehydrogenase (LDH). In addition, it attenuated Abeta peptide-activated caspases-3-like activity. The extract elicited a typical dose-dependent neuroprotective effect. Effective dosage of this extract was wider than that of a well-known western neuroprotective medicine lithium chloride (LiCl). We have further examined the underlying mechanisms of the neuroprotective effects. In agreement with other laboratories, Abeta peptides induce a rapid activation of c-Jun N-terminal kinase (JNK) by phosphorylation. Pre-treatment of aqueous extract markedly reduced the phosphorylation of JNK-1 (Thr183/Tyr185) and its substrates c-Jun-I (Ser 73) and c-Jun-II (Ser 63). Taken together, we have proved our hypothesis by showing neuroprotective effects of the extract from L. barbarum. Study on anti-aging herbal medicine like L. barbarum may open a new therapeutic window for the prevention of AD.
Jung K. Chin YW. Kim YC. Kim J. Potentially hepatoprotective glycolipid constituents of Lycium chinense fruits. Archives of Pharmacal Research. 28(12):1381-5, 2005 Further investigation of Lycium chinense fruits gave a mixture of (6'-O-palmitoyl)- and (6'-O-stearoyl)-beta-sitosterol-3-O-beta-D-glucopyranoside (1) and two glycolipids, 1-O-(9Z,12Z, 15Z-octadecatrienoyl)-2-O-(9Z, 12Z, 15Z-octadecatrienoyl)-3-O-beta-D-galactopyranosyl glycerol (2) and 1-O-(9Z, 12Z-octadecadienoyl)-2-O-(9Z, 12Z, 15Z-octadecatrienoyl)-3-O-beta-D-galactopyranosyl glycerol (3). These compounds were newly isolated as constituents of L. chinense.
Ha KT. Yoon SJ. Choi DY. Kim DW. Kim JK. Kim CH. Protective effect of Lycium chinense fruit on carbon tetrachloride-induced hepatotoxicity. Journal of Ethnopharmacology. 96(3):529-35, 2005 In the present study, we investigated the protective effect of Lycium chinense Miller (Solanaceae) fruit (LFE) against CCl(4)-induced hepatotoxicity and the mechanism underlying these protective effects in rats. The pretreatment of LFE has shown to possess a significant protective effect by lowering the serum aspartate and alanine aminotransferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation. In addition, pretreatment of LFE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CCl(4)-injected rats. The LFE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC(50) = 83.6 microg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. The expression level of cytochrome P450 2E1 (CYP2E1) mRNA and protein, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis, was significantly decreased in the liver of LFE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the LFE might be related to antioxidative activity and expressional regulation of CYP2E1.
Zhao H. Alexeev A. Chang E. Greenburg G. Bojanowski K. Lycium barbarum glycoconjugates: effect on human skin and cultured dermal fibroblasts. Phytomedicine. 12(1-2):131-7, 2005 Lycium barbarum L. (Solanaceae) glycoconjugates (LbGp) display an interesting array of anti-apoptotic and antioxidant properties, which may be beneficial for human skin. We therefore set out to determine the effects of LbGp in full-thickness human skin, and in dermal fibroblasts. It was found that LbGp decreased the level of MMP (matrix metalloproteinase)-1 significantly, but not that of MMP-3 or -13, in the whole human skin system, without compromising the viability of the skin. Consistently, LbGp inhibited skin expansion under mechanical stress, which in this model depends on the activity of MMP-1. We found that one of L. barbarum glycoconjugates, the LbGp5, promoted the survival of human fibroblasts cultured in suboptimal conditions. Furthermore, in the presence of LbGp5, these cultures also contained higher levels of the MMP-1 substrate--collagen type I. Together these results suggest that L. barbarum glycoconjugates in general, and LbGp5 in particular, may have important skin-protective properties.
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. British Journal of Nutrition. 93(1):123-30, 2005 Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.
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 Sciences. 76(18):2115-24, 2005 Lycium barbarum polysaccharide (LBP), extracted from Lycium barbarum that is a kind of traditional Chinese herb, is found to have anticancer activity. In this study, the effect of LBP on the proliferation rate, cell cycle distribution and apoptosis in the human hepatoma QGY7703 cell line were investigated. The effects of this compound were also tested on the concentration of calcium in cells. LBP treatment caused inhibition of QGY7703 cell growth with cycle arrest in S phase and apoptosis induction. The amount of RNA in cells and the concentration of intracellular Ca2+ were increased. Moreover, the distribution of calcium in cells was changed. Taken together, the study suggests that the induction of cell cycle arrest and the increase of intracellular calcium in apoptotic system may participate in the antiproliferative activity of LBP in QGY7703 cells.
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 Biotherapy & Radiopharmaceuticals. 20(2):155-62, 2005 AIM: The aim of this study was to investigate the effects of Lycium barbarum polysaccharide (LBP) on irradiation- or chemotherapy-induced myelosuppressive mice and cultured peripheral blood mononuclear cells (PBMCs). METHODS: In an in vivo experiment, mice were irradiated with a sublethal dose of 550 cGy X-ray or intraperitoneally (i.p.) injected with carboplatin (CB) 125 mg/kg to produce severe myelosuppression. Four to 6 hours after the irradiation or injection, mice were subcutaneously (s.c.) injected with LBP (50, 100, and 200 mg/kg) daily from day 0 to day 6. Blood samples were collected from the tail veins of mice at different time points, and peripheral white blood cells (WBC), red blood cells (RBC), and platelet (PLT) counts were monitored. In an in vitro experiment, human PBMCs were incubated with LBP at different concentrations in combination with phytohemagglutinin (PHA), and the production of granulocyte colony-stimulating factor (G-CSF) was tested. RESULTS: Compared to the control, 50 mg/kg LBP (LBP-L) significantly ameliorated the decrease of peripheral WBC of irradiated myelosuppressive mice on day 13, and 100 mg/kg LBP (LBP-M) did the same on days 17 and 21. All dosages of LBP significantly ameliorated the decrease of peripheral RBC of irradiated myelosuppressive mice on days 17 and 25. Two-hundred mg/kg LBP (LBP-H) and LBP-M significantly enhanced peripheral PLT counts of irradiated myelosuppressive mice on days 10, 13, 17, and 21, as did LBP-L on days 13 and 17. All dosages of LBP increased peripheral WBC counts of chemotherapy-induced myelosuppressive mice to some extent, but there was no statistic difference when compared to the control. LBP-H significantly ameliorated the decrease of peripheral RBC of chemotherapy-induced myelosuppressive mice on days 13, 15, 17, and 20, and LBP-M and LBP-L did the same on days 15 and 17. All dosages of LBP significantly enhanced peripheral PLT counts of chemotherapy-induced myelosuppressive mice on days 7 and 10, as did LBP-H on days 13, 15, and 17, and LBP-M on days 13 and 15. Also, LBP could obviously stimulate human PBMCs to produce G-CSF. CONCLUSIONS: LBP promoted the peripheral blood recovery of irradiation or chemotherapy-induced myelosuppressive mice, and the effects may be the result of the stimulation of PBMCs to produce G-CSF.
Zhao R. Li Q. Xiao B. Effect of Lycium barbarum polysaccharide on the improvement of insulin resistance in NIDDM rats. Yakugaku Zasshi - Journal of the Pharmaceutical Society of Japan. 125(12):981-8, 2005 Lycium barbarum is one of the traditional oriental medicines. It has been reported to reduce blood glucose levels. In this study, the effect of Lycium barbarum polysaccharide (LBP) on the improvement of insulin resistance and lipid profile was studied in rats, a model for non-insulin dependent diabetes mellitus (NIDDM). The rats were divided into three groups: control, NIDDM control, and NIDDM+LBP. Diabetes model groups were made by feeding high-fat diet and subjecting to i.p. streptozotocin (50 mg/kg). LBP treatment for 3 weeks resulted in a significant decrease in the concentration of plasma triglyceride and weight in NIDDM rats. Furthermore, LBP markedly decreased the plasma cholesterol levels and fasting plasma insulin levels, and the postprandial glucose level at 30 min during oral glucose tolerance test and significantly increased the Insulin Sensitive Index in NIDDM rats. In the present study, we have tested that LBP can alleviate insulin resistance and the effect of LBP is associated with increasing cell-surface level of glucose transporter 4 (GLUT4) in skeletal muscle of NIDDM rats. Under insulin stimulus, GLUT4 content in plasma membrane in NIDDM control rats was significantly lower than that of control (p<0.01), and GLUT4 content in the plasma membrane in NIDDM+LBP rats was higher than that of NIDDM control rats (p<0.01). In conclusion, LBP can ameliorate insulin resistance, and the mechanism may be involved in increasing cell-surface level of GLUT4, improving GLUT4 trafficking and intracellular insulin signaling.
Gan L. Hua Zhang S. Liang Yang X. Bi Xu H. Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum. International Immunopharmacology. 4(4):563-9, 2004 The modulation of a polysaccharide-protein complex from Lycium barbarum (LBP3p) on the immune system in S180-bearing mice was investigated. The mice inoculated with S180 cell suspension were treated p.o. with LBP3p (5, 10 and 20 mg/kg) for 10 days. The effects of LBP3p on transplantable tumors and macrophage phagocytosis, quantitative hemolysis of sheep red blood cells (QHS), lymphocyte proliferation, the activity of cytotoxic T lymphocyte (CTL), interleukin-2 (IL-2) gene expression and lipid peroxidation were studied. LBP3p could significantly inhibit the growth of transplantable sarcoma S180 and increase macrophage phagocytosis, the form of antibody secreted by spleen cells, spleen lymphocyte proliferation, CTL activity, IL-2 mRNA expression level and reduce the lipid peroxidation in S180-bearing mice. The effect is not dose-dependent in a linear fashion. A total of 10 mg/kg dose is more effective than 5 and 20 mg/kg doses. This suggests that LBP3p at 10 mg/kg has a highly significant effect on tumor weight and improves the immune system.
Luo Q. Cai Y. Yan J. Sun M. Corke H. Hypoglycemic and hypolipidemic effects and antioxidant activity of fruit extracts from Lycium barbarum. Life Sciences. 76(2):137-49, 2004 The hypoglycemic and hypolipidemic effects of Lycium barbarum fruit water decoction, crude polysaccharide extracts (crude LBP), and purified polysaccharide fractions (LBP-X) in alloxan-induced diabetic or hyperlipidemic rabbits were investigated through designed sequential trials and by measuring blood glucose and serum lipid parameters. Total antioxidant capacity was also assessed using trolox equivalent antioxidant capacity (TEAC) and oxygen radical absorbance capacity (ORAC) assay. It was found that the three Lycium barbarum fruit extracts/fractions could significantly reduce blood glucose levels and serum total cholesterol (TC) and triglyceride (TG) concentrations and at same time markedly increase high density lipoprotein cholesterol (HDL-c) levels after 10 days treatment in tested rabbits, indicating that there were substantial hypoglycemic and hypolipidemic effects. Hypoglycemic effect of LBP-X was more significant than those of water decoction and crude LBP, but its hypolipidemic effect seemed to be weaker. Total antioxidant capacity assay showed that all three Lycium barbarum extracts/fractions possessed antioxidant activity. However, water and methanolc fruit extracts and crude polysaccharide extracts exhibited stronger antioxidant activity than purified polysaccharide fractions because crude extracts were identified to be rich in antioxidants (e.g., carotenoids, riboflavin, ascorbic acid, thiamine, nicotinic acid). Lycium barbarum polysaccharides (glycocojugates), containing several monosaccharides and 17 amino acids, were major bioactive constituents of hypoglycemic effect. Both polysaccharides and vitamin antioxidants from Lycium barbarum fruits were possible active principles of hypolipidemic effect.
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. Journal of Experimental Therapeutics & Oncology. 4(3):181-7, 2004 AIM: To investigate the therapeutic effects of Lycium barbarum polysaccharide (LBP) on mitomycin C (MMC)-induced myelosuppressive mice. METHODS: Mice were intravenously injected with MMC 150 mg/kg for two consecutive days from day -1 to day 0 to produce severe myelosuppression, and then treated by s.c. injections of LBP (100 or 200 mg/kg/day) from days 0 to 6. Blood samples were collected from the tail veins of mice on days 7, 10, 12, 14, 17, 19, 21, 24 and 27, and peripheral white blood cells (WBC), red blood cells (RBC), hemoglobin (HGB) and platelet counts (PLT) etc. were monitored. RESULTS: LBP at 100 mg/kg (LBP-L) on day 14 and LBP at 200 mg/kg (LBP-H) on days 10, 14, 17, 19 and 21, significantly ameliorated the decrease of peripheral RBC, HGB and hematocrit (HCT) of myelosuppressive mice compared to the control. LBP-L on days 12 and days 14 and LBP-H on days 10, 12, 14, 17, 19 and 21, significantly enhanced peripheral PLT recovery of myelosuppressive mice compared to the control. LBP-H on days 12, 17, 19 and 21, significantly inhibited the increase of mean platelet volume (MPV) of myelosuppressive mice compared to the control. LBP showed no obviously effect on neutropenia induced in mice by MMC. CONCLUSION: LBP is effective on peripheral RBC and PLT recovery of MMC-induced myelosuppressive mice.
Wu SJ. Ng LT. Lin CC. Antioxidant activities of some common ingredients of traditional chinese medicine, Angelica sinensis, Lycium barbarum and Poria cocos. Phytotherapy Research. 18(12):1008-12, 2004 The antioxidant activities of three popular ingredients of traditional Chinese medicine, namely Angelica sinensis (AS), Lycium barbarum (LB) and Poria cocos (PC) were evaluated in this study. The results showed that aqueous extracts of these crude drugs exhibited antioxidant activities in a concentration-dependent manner. All extracts displayed an inhibitory effect on FeCl2-ascorbic acid induced lipid peroxidation in rat liver homogenate in vitro, with the order of activity LB > AS > PC. The tested extracts showed a superoxide anion scavenging activity ranging from 28.8% to 82.2% and anti-superoxide activity varying from 38.0% to 84.5%. Among the different extracts, LB extract exhibited the lowest IC50 values (0.77-2.55 microg/mL) in all model systems tested in this study. The present study concludes that LB extract possessed the strongest inhibition on malondialdehyde formation in rat liver homogenate, and superoxide anion scavenging and anti-superoxide formation activities. These results also suggest that LB extract is a good source of antioxidant agent in the daily dietary supplement.
Chin YW. Lim SW. Kim SH. Shin DY. Suh YG. Kim YB. Kim YC. Kim J. Hepatoprotective pyrrole derivatives of Lycium chinense fruits. Bioorganic & Medicinal Chemistry Letters. 13(1):79-81, 2003 As a part of our search for hepatoprotective compounds from Lycium chinense fruits, three new pyrrole derivatives (1-3) were isolated. These compounds and a related synthetic methylated compound (4) were evaluated for their biological activity and structure-activity relationship, and compounds 1 and 2 showed hepatoprotective effects comparable to silybin at the concentration of 0.1 microM (64.4 and 65.8%, respectively).
Gan L. Zhang SH. Liu Q. Xu HB. A polysaccharide-protein complex from Lycium barbarum upregulates cytokine expression in human peripheral blood mononuclear cells. European Journal of Pharmacology. 471(3):217-22, 2003 The production of cytokine is a key event in the initiation and regulation of an immune response. Many compounds are now used routinely to modulate cytokine production, and therefore the immune response, in a wide range of diseases, such as cancer. Interleukin-2 and tumor necrosis factor-alpha are two important cytokines in antitumor immunity. In this study, the effects of Lycium barbarum polysaccharide-protein complex (LBP(3p)) on the expression of interleukin-2 and tumor necrosis factor-alpha in human peripheral blood mononuclear cells were investigated by reverse transcription polymerase chain reaction (RT-PCR) and bioassay. Administration of LBP(3p) increased the expression of interleukin-2 and tumor necrosis factor-alpha at both mRNA and protein levels in a dose-dependent manner. The results suggest that LBP(3p) may induce immune responses and possess potential therapeutic efficacy in cancer.Deng HB. Cui DP. Jiang JM. Feng YC. Cai NS. Li DD. Inhibiting effects of Achyranthes bidentata polysaccharide and Lycium barbarum polysaccharide on nonenzyme glycation in D-galactose induced mouse aging model. Biomedical & Environmental Sciences. 16(3):267-75, 2003 OBJECTIVE: To investigate the inhibiting effects and mechanism of achyranthes bidentata polysaccharide (ABP) and lycium barbarum polysaccharide (LBP) on nonenzyme glycation in D-galactose induced mouse aging model. METHODS: Serum AGE levels were determined by AGE-ELISA, MTT method was used to determine lymphocyte proliferation, IL-2 activity was determined by a bioassay method. Spontaneous motor activity was used to detect mouse's neuromuscular movement, latency of step-through method was used to examine learning and memory abilities of mouse, colormetric assay was used to determine hydroxyproline concentration in mouse skin, pyrogallol autoxidation method was used to determine superoxide dismutase (SOD) activity of erythrocytes. RESULTS: Decreased levels of serum AGE, hydroxyproline concentration in mouse skin and spontaneous motor activity in D-galactose mouse aging model were detected after treated with ABP or LBP, while lymphocyte proliferation and IL-2 activity, learning and memory abilities, SOD activity of erythrocytes, were enhanced. CONCLUSIONS: ABP and LBP could inhibit nonenzyme glycation in D-galactose induced mouse aging model in vivo and ABP has a better inhibiting effect than LBP.
Kim HP. Lee EJ. Kim YC. Kim J. Kim HK. Park JH. Kim SY. Kim YC. Zeaxanthin dipalmitate from Lycium chinense fruit reduces experimentally induced hepatic fibrosis in rats. Biological & Pharmaceutical Bulletin. 25(3):390-2, 2002 We previously reported that zeaxanthin dipalmitate (ZD), a carotenoid from Lycium chinense fruit, reduces myofibroblast-like cell proliferation and collagen synthesis in vitro. To determine whether ZD might reduce the severity of hepatic fibrosis in an animal model, hepatic fibrosis was induced in rats by bile duct ligation/scission (BDL) for a period of 6 weeks. Treatment of BDL rats with ZD at a dose of 25 mg/kg body weight significantly reduced the activities of aspartate transaminase (p<0.05) and alkaline phosphatase (p<0.001) in serum. Furthermore, collagen deposition was significantly reduced as assessed by the Sirius Red binding assay in BDL rats administered ZD at the dose of 25 mg/kg body weight (p<0.01). In addition, the levels of thiobarbituric acid-reactive substances and 4-hydroxyproline were reduced when BDL rats received ZD at the dose of 25 mg/kg body weight. These results showed that ZD effectively inhibited hepatic fibrosis in BDL rats, at least in part via its antioxidative activity.
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. Journal of Ethnopharmacology. 82(2-3):169-75, 2002 Lycium barbarum L. (Solanaceae) is a Chinese medicinal plant whose fruits (Fructus Lycii) are used by Chinese physicians for treatment of infertility. However, the active ingredients and the mechanism of action underlying Lycium's fertility-facilitating effects remain unknown. Here we report that Fructus Lycii polysaccharides (FLPS) inhibit time- and hyperthermia-induced structural damage in murine seminiferous epithelium, in vitro. Moreover, we found that FLPS delayed apoptosis in this system, both at normothermic and hyperthermic culture conditions. Oxidative stress was reported to be a major cause of structural degradation and apoptosis in hyperthermic testes, and thus the protective effect of FLPS could implicate an antioxidant mechanism of action. To test this hypothesis we assayed the effect of FLPS on ultraviolet light-induced lipid peroxidation, and cytochrome c reduction by free radicals. We found that FLPS is a potent inhibitor of both of these reactions. Together, these results demonstrate the protective effect of FLPS on time- and hyperthermia-induced testicular degeneration in vitro, indicate the potential mechanism of action for this protective effect, and provide a scientific basis for the traditional use of this plant.
Kim SY. Lee EJ. Kim HP. Lee HS. Kim YC. LCC, a cerebroside from Lycium chinense, protects primary cultured rat hepatocytes exposed to galactosamine. Phytotherapy Research. 14(6):448-51, 2000 Primary cultures of rat hepatocytes exposed to galactosamine (GalN) were used as a screening system to assess whether a new cerebroside, LCC, isolated from the fruits of Lycium chinense, exhibits hepatoprotective activity. Cultured rat hepatocytes injured with GalN routinely release glutamic pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) into the culture medium. Treatment of these GalN-injured primary cultures with LCC markedly blocked the release of both GPT and SDH in a dose-dependent manner over concentrations of LCC ranging from 1 microM to 10 microM. To investigate the mechanism of action for the hepatoprotective activity of LCC, the extent of [(3)H]-uridine incorporation into RNA was measured in GalN-injured cultures of rat hepatocytes. [(3)H]-Uridine incorporation was significantly decreased in injured hepatocytes. LCC, however significantly restored the incorporation of [(3)H]-uridine into RNA in a dose-dependent manner over concentrations ranging from 1 microM to 10 microM. LCC also blocked the suppression of RNA synthesis caused by actinomycin D in a dose-dependent manner. These data suggest that LCC may have prominent hepatoprotective activity and that its therapeutic value should be investigated further.
