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Новые доказательства фармакологической активности и возможных молекулярных мишеней полисахаридов ягоды Годжи


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Antifatigue effects


Chronic fatigue syndrome (CFS) is a complicated disorder characterized by persistent fatigue that lasts for at least 6 months for adults and 3 months for children or adolescents, with at least four additional symptoms: impaired memory or concentration, sore throat, tender cervical or axillary lymph nodes, muscle pain, multi-joint pain, new headaches, unrefreshing sleep, or post-exertion malaise.5558 The fatigue is not due to exertion, not significantly relieved by rest, and is not caused by other medical conditions. The Centers for Disease Control report that more than 1 million Americans have CFS and approximately 80% of the cases are undiagnosed. Approximately 250,000 people in the UK are affected with the illness according to the National Health Service. Pharmacotherapy plays a minor role in CFS management, but herbal medicines may produce some benefits for CFS. The antifatigue effect of LBPs was tested with five different doses (5 mg/kg/day, 10 mg/kg/day, 20 mg/kg/day, 50 mg/kg/day, and 100 mg/kg/day) in mice.59 The results showed that LBPs induced remarkable adaptability to exercise load, enhanced resistance, and accelerated elimination of fatigue. LBPs could enhance the storage of muscle and liver glycogen, increase the activity of LDH before and after swimming, decrease the increase of blood urea nitrogen after strenuous exercise, and accelerate the clearance of blood urea nitrogen after exercise. The dosage of 10 mg/kg/day LBPs was the most effective among the five tested doses.59

Antiviral effects


Wang et al60 prepared four sulfated L. barbarum polysaccharides (sLBPs), sLBPS(0.7), sLBPS(1.1), sLBPS(1.5), and sLBPS(1.9), and compared their effects on the cellular infec-tivity of Newcastle disease viruses (NDVs) in chick embryo fibroblasts. Four sLBPSs at five concentrations, within the safety concentration scope, and NDVs were added into the cultivating system of chick embryo fibroblasts in three modes, pre- and post-adding polysaccharide, and simultaneous adding of polysaccharide and viruses after being mixed. The effects of sLBPSs on cellular infectivity of NDVs were assayed by MTT method taking the nonmodified LBPS as the control.60 The results showed that sLBPS(1.5), sLBPS(1.9), and sLBPS(1.1) in three sample-adding modes, sLBPS(0.7) in simultaneous adding after being mixed, significantly inhibited the infectivity of NDVs. The viral inhibitory rate of sLBPS(1.5) in pre-adding and simultaneous adding, and sLBPS(1.9) in post-adding, was the highest. Nonmodified LBPS did not present significant effect in any sample-adding mode.60 These results indicated that sulfated modification significantly enhanced the antiviral activity of LBPs, which was correlated with the degree of sulfation of LBPs. The mechanisms for the antiviral activity of LBPs are unknown.

Cardioprotective effects

Ischemic heart disease and I/R injury


Ischemic heart disease is the leading cause of death worldwide, causing 7,249,000 deaths in 2008, 12.7% of total global mortality.61 From 2006 to 2010, age-adjusted ischemic heart disease prevalence in the US declined overall from 6.7% to 6.0%.62 The myocardial protective effects of LBPs have been studied in rats and beagle dogs.6366

Lu and Zhao63 investigated the protective effects of LBPs on myocardial I/R damage in Wistar adult male rats. Dry Goji fruits were purchased from the herbs market in Xi’an city, Shaanxi, People’s Republic of China, and LBPs were extracted with methanol, acetone, ethanol, and boiling water. Rat hearts were rapidly excised from anesthetized rats and perfused retrogradely in Krebs–Henseleit solution at 15 mL/min at 37°C and aerated with 95% O2 plus 5% CO2 to maintain normal pH, pO2, and pCO2 levels. Surgical rats were treated with 150 mg/kg or 300 mg/kg body weight LBPs and subject to myocardial I/R injury. LBPs significantly decreased the myocardium LDH level and increased Na+/K+-ATPase and Ca2+-ATPase activities.63 In addition, LBPs dose-dependently decreased myocardium Bax-positive cell rate and myocardial cell apoptosis and increased Bcl-2-positive cell rate.63 These results suggest that LBPs protected rat heart from I/R injury via upregulation of heart Na+/K+-ATPase and inhibition of cardiomyocyte apop-tosis. In summary, the cardioprotective effect of LBPs against I/R injury is mainly due to the antioxidative, anti-inflammatory, and anti-apoptotic activities of LBPs (Figure 6).



Figure 6

Possible mechanisms for the cardioprotective effects of LBPs.



Notes: LBPs exert a remarkable cardioprotective effect in in vitro and in vivo models. LBPs increase the activity of Na+/K+-ATPase and Ca2+-ATPase, enhance the expression of GPx, SOD, and reduce the production of LDH, resulting in a marked reduction in oxidative stress. Also, LBPs increase the ratio of anti-apoptotic factor (Bcl-2) and decrease the pro-apoptotic factor (Bax), protecting the myocardial cells from apoptotic cell death.

Abbreviations: LBPs, Lycium barbarum polysaccharides; SOD, superoxide dismutase; GPx, glutathione peroxidase; LDH, lactate dehydrogenase.

Doxorubicin-induced cardiotoxicity


Doxorubicin (DOX) is a potent antitumor agent, but its dose-dependent cardiotoxicity limits its clinical use. DOX-induced cardiotoxicity involves the formation of free radicals and amplification of mitochondrial dysfunction. Due to relatively lower levels of CAT and the readily deactivated GPx in the cardiomyocytes, the heart is more susceptible to oxidative damage than other tissues. As an antioxidant, the cardioprotective effect of LBPs has been demonstrated in acute DOX-induced cardiotoxicity in rats66 and beagle dogs.65 Inhibition of oxidative stress is thought to be the main mechanism of the cardioprotective effects of LBPs. Xin et al66 suggested that LBPs might protect against DOX-induced cardiotoxicity through antioxidant-mediated mechanisms.

Xin et al65 conducted a mechanistic study in male Sprague–Dawley rats to explore the protective effect of LBPs on DOX-induced cardiotoxicity. Rats were administered orally with 200 mg/kg/day LBPs for 10 continuous days. About 10 mg/kg DOX was administered to rats via intravenous injection at day 7. At the end of the experiment, the rats were sacrificed with hearts promptly removed for biochemical and histological analysis. The results showed that pretreatment with 200 mg/kg LBPs for 10 days significantly reduced DOX-induced oxidative injury in cardiac tissue and significantly attenuated DOX-induced cardiac cytoplasmic vacuolization and myofibrillar disarrangement.65 LBP pretreatment decreased heart MDA level and increased heart SOD and GPx activities in DOX-treated rats. LBPs decreased the levels of serum CK and partially reversed DOX-induced bradycardia and prolonged QT interval as determined by electrocardiography.65 Furthermore, the cytotoxic study in vitro showed that 100 µg/mL LBPs protected against cytotoxicity of DOX in cardiac myoblasts H9c2. Incubation of human lung carcinoma A549 cells with 200 µg/mL LBPs did not alter the antiproliferative activity of DOX. These data indicated that LBPs elicit a potent protective effect on DOX-induced cardiomyocyte damages mainly via antioxidative and free radical-scavenging pathways.

Xin et al64 carried out a further study in beagle dogs to examine if LBPs alleviated DOX-induced cardiotoxicity. Intravenous administration of 15 mg/kg DOX significantly induced acute cardiotoxicity in beagle dogs characterized by conduction abnormalities including decreased heart rate, ST segment elevation, QT intervals prolongation, inverted T wave, arrhythmia, and myocardial ischemia and increased serum CK and aspartate aminotransferase (AST).64 Oral pretreatment with 20 mg/kg body weight LBPs daily for 7 days effectively alleviated both DOX-induced conduction abnormalities and increased serum CK and AST.64 All these results confirm and extend previous observations in rats concerning the protective effect of LBPs against DOX-induced cardiotoxicity.

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