Introduction:The increasing blood glucose level due to insulin resistance which occurs in diabetes mellitus (DM) may cause vascular damage. This study aims to prove the effect of the polysaccharide peptide (PsP)on improving vascular damage through an increase of circulating endothelial cells and circulating endothelial cells (CEC) ratio, decreased H2O2, triglyceride (TG), total cholesterol (TC) and insulin resistance in type 2 DM.

Methods:Our study is a true experimental study with randomized posttest control group design that used 35 Wistar rats divided into five groups: normal, control (+) and three groups of different variant PsP doses 50, 150 and 300 mg/kg BW (n=7).

Results:By using one-way ANOVA and post-hoc Duncan test, the results show a significant increase of endothelial progenitor cell (EPC) concentration (=0.000) and ratio EPC:CEC (0.000) by dose-dependent fashion and also reduced CEC concentration (=0.001), H2O2 (=0.03), TG (=0.001), TC (=0.01) and insulin resistance (=0.003).

Conclusion:In this study, PsP induced endothelial repairing process and reduced the risk factor with 300 mg/kg BW as optimum dose. However, further research on EPC and CEC detection markers is important. Further research on PsP and clinical trial for commercial uses is also needed.

The() mushroom is one of the most extensively studied functional foods, known for its numerous health benefits, including the inhibition of tumor cell growth. The present study assessed the anti-proliferative and pro-apoptotic activity of a novelpolysaccharide peptide (GL-PP) in human glioma U251 cells, which was purified from grass-cultured. GL-PP is a glycopeptide with an average molecular weight of 42,635 Da and a polysaccharide-to-peptide ratio of 88.70:11.30. The polysaccharides were composed of l-arabinose, d-mannose and d-glucose at a molar ratio of 1.329:0.372:2.953 and a total of 17 amino acids were detected. The results of the current study demonstrated that GL-PP significantly inhibited U251 cellular proliferation. The proportion of G/Gphase cells and sub-Gphase cells significantly increased as the concentration of GL-PP increased, as did the activity of caspase-3. These results indicate that GL-PP directly inhibited human glioma U251 proliferation by inducing cell cycle arrest and promoting apoptosis.

BACKGROUND:Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated. Further, GLP effect on microglial behavioural modulations in correlation with the inflammatory responses remains to be unravelled. The aim of this work was to quantitatively analyse the contributions of GLP on microglia.

METHODS:The BV2 microglia and primary mouse microglia were stimulated by lipopolysaccharides (LPS) and amyloid beta42 (Aβ42) oligomer, respectively. Investigation on the effect of GLP was carried by quantitative determination of the microglial pro- and anti-inflammatory cytokine expressions and behavioural modulations including migration, morphology and phagocytosis. Analysis of microglial morphology and phagocytosis modulations was confirmed in the zebrafish brain.

RESULTS:Quantitative results revealed that GLP down-regulates LPS- or Aβ-induced pro-inflammatory cytokines and promotes anti-inflammatory cytokine expressions in BV-2 and primary microglia. In addition, GLP attenuates inflammation-related microglial migration, morphological alterations and phagocytosis probabilities. We also showed that modulations of microglial behavioural responses were associated with MCP-1 and C1q expressions.

CONCLUSIONS:Overall, our study provides an insight into the GLP regulation of LPS- and Aβ-induced neuroinflammation and serves an implication that the neuroprotective function of GLP might be achieved through modulation of microglial inflammatory and behavioural responses.

Oxidative stress, inflammation, and foam cell formation in vascular smooth muscle cells (VSMCs) are considered to play crucial roles in the pathogenesis of atherosclerosis. Poria cocos polysaccharides (PCP) has been shown to possess anti-inflammatory, antitumor and anti-oxidative properties. In this study we explored the effects of PCP on ox-LDL-induced inflammation, oxidative stress and foam cell formation in VSMCs. PCP significantly attenuated ox-LDL-induced oxidative stress, as evidenced by the decreased reactive oxygen species (ROS) and MDA levels, and the increased SOD activity in VSMCs. PCP suppressed the induction effect of ox-LDL on inflammatory cytokines and inflammatory mediators. PCP also substantially inhibited VSMCs foam cell formation and intracellular lipids accumulation. Mechanistically, PCP suppressed ox-LDL-induced up-regulation of LOX-1, which is responsible for ox-LDL uptake. Western blotting suggested that PCP activated ERK1/2 signaling pathway, increased Nrf2 translocated from cytoplasm to nucleus and heme oxygenase-1 (HO-1) expression. Up-regulation of PCP on Nrf2/HO-1 signaling was reversed by pretreatment with ERK inhibitor PD98059, indicating the involvement of ERK in PCP activation of Nrf2/HO-1 signaling. In conclusion, these results demonstrated that PCP exerted its protection against oxidative stress and inflammation via the ERK/Nrf2/HO-1 signaling pathway and that PCP may be a promising candidate for the therapy of atherosclerosis.

Beta-amyloid (Abeta)-induced neurotoxicity is considered to be mediated through the formation of reactive oxygen species (ROS). In this study, the protective effects of Poria cocos water extract (PCW) against Abeta1-42-induced cell death were investigated using rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to the Abeta1-42 (20 microM) for 48h resulted in neuronal cell death, whereas pretreatment with PCW at the concentration range of 5-125 microg/ml reduced Abeta1-42-induced cell death. In addition, PC12 cells treated with Abeta1-42 exhibited increased accumulation of intracellular oxidative damages and underwent apoptotic death as determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL staining). However, PCW attenuated Abeta1-42-induced cytotoxicity, apoptotic features, and accumulation of intracellular oxidative damage. Moreover, PCW (5 to 125 microg/ml) decreased expression of apoptotic protein Bax and activity of caspase-3, but enhanced expression of anti-apoptotic protein Bcl-2. These results suggest that PCW may protect cells through suppressing the oxidative stress and the apoptosis induced by Abeta1-42, implying that PCW may be potential natural agents for Alzheimer's diseases.

ABSTRACT: BACKGROUND: Prostate cancer remains the most common malignancy among elderly men and the second leading cause of cancer death in the United States. Although several conventional therapies are currently available, they have a low efficacy and the more effective treatment modalities need to be established. Interferons (IFNs) are one of such options known as immunotherapy and demonstrated their antitumor effects on certain cancer types. Yet such antitumor activity should be improved or potentiated to have the satisfactory outcomes. In fact, combination therapy has been proposed as an alternative approach and is being underway in human and animal studies. Accordingly, we studied whether the combination of IFN-alpha and D-fraction (PDF), a bioactive mushroom extract, might potentiate anticancer activity of IFN-alpha in prostate cancer PC-3 cells in vitro. RESULTS: Potential effects of recombinant IFN-alpha2b (0-100,000 IU/ml), PDF (0-1,000 mug/ml), or their combinations were assessed on the growth of PC-3 cells at 72 h. Cell cycle analysis using a flow cytometer and Western blot analysis were performed to explore antiproliferative mechanism of these agents. The dose-dependent study showed that IFN-alpha2b up to 20,000 (20 K) IU/ml had no significant effects, but>60% growth reduction was attained60%) down-regulated in IFN/PDF-treated cells. CONCLUSION: The combination of IFN-alpha2b (10 K IU/ml) and PDF (250 mug/ml) is capable of inducing a ~65% reduction in PC-3 cell growth. This appears to be due to a synergistic potentiation of two agents, leading to a G1 cell cycle arrest. Thus, it is conceivable that PDF may potentiate IFN-alpha2b activity, improving immunotherapy for prostate cancer.

BACKGROUND:Although several therapeutic options are currently available for patients with various cancers, the outcomes are often disappointing and a more effective modality needs to be promptly established. We have been exploring an alternative approach using natural agents and two bioactive mushroom extracts isolated from Phellinus linteus (PL), namely PL-ES and PL-I-ES, were of our interest. As anticancer effects of similar extracts have been reported in several cancers, we investigated whether PL-ES and PL-I-ES might have such anticancer activities on a variety of human cancer cells in vitro.

METHODS:Ten different types of human cancer cell lines, including three metastatic prostate, bladder, kidney, lung, breast, stomach, liver, and brain cancer cells, were employed and tested with PL-ES or PL-I-ES. Cell growth/viability, exertion of oxidative stress, and induction of apoptosis were assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay, lipid peroxidation (LPO) assay, and specific enzymatic assay, respectively.

RESULTS:PL-ES (100µg/mL) exhibited potent anticancer activity, resulting in a significant (40-80%) growth reduction in all 10 cancer cells at 72 hours. PL-I-ES (100 µg/mL) was effective on only four cancer cells but its higher concentration at 250 µg/mL led to a significant (25-90%) growth reduction in seven cancer cells. LPO assays indicated that such a significant growth reduction by PL-ES (100 µg/mL) or PL-I-ES (100 or 250 µg/mL) could result from cell death due to a cytotoxic effect of oxidative stress (through free radicals). Moreover, enzymatic assays for caspase-3 (Csp-3) and caspase-9 (Csp-9), thepro-apoptotic regulators, showed that both enzymes were significantly activated by PL-ES or PL-I-ES, indicating that cell death due to oxidative stress was more likely associated with apoptosis.

CONCLUSIONS:The present study shows that both PL-ES and PL-I-ES indeed have anticancer effects on a variety of cancer cells, although PL-ES appears to be more potent than PL-I-ES. Such an anticancer effect is presumably attributed to oxidative stress, which will ultimately lead to apoptosis. Therefore, these two bioactive mushroom extracts may have clinical implications in a more effective therapeutic option for a variety of human malignancies.

ETHNOPHARMACOLOGICAL RELEVANCE: Inonotus obliquus (Chaga mushroom), one of the widely known medicinal mushrooms, has been used to treat various cancers in Russia and most of Baltic countries for many centuries. AIM OF THE STUDY: To examine the anti-proliferative effects of Inonotus obliquus extract on melanoma B16-F10 cells. Furthermore, to assess the anti-tumor effect of Inonotus obliquus extract in vivo in Balb/c mice. MATERIALS AND METHODS: The water extract of Inonotus obliquus was studied for anti-proliferative effects on the growth and morphology of B16-F10 melanoma cells and for anti-tumor effect using in vivo in Balb/c mice. RESULTS: Inonotus obliquus extract not only inhibited the growth of B16-F10 cells by causing cell cycle arrest at G(0)/G(1) phase and apoptosis, but also induced cell differentiation. These effects were associated with the down-regulation of pRb, p53 and p27 expression levels, and further showed that Inonotus obliquus extract resulted in a G(0)/G(1) cell cycle arrest with reduction of cyclin E/D1 and Cdk 2/4 expression levels. Furthermore, the anti-tumor effect of Inonotus obliquus extract was assessed in vivo in Balb/c mice. Intraperitoneal administration of Inonotus obliquus extract significantly inhibited the growth of tumor mass in B16-F10 cells implanted mice, resulting in a 3-fold (relative to the positive control, (*)p<0.05) inhibit at dose of 20mg/kg/day for 10 days. CONCLUSION: This study showed that the water extract of Inonotus obliquus mushroom exhibited a potential anticancer activity against B16-F10 melanoma cells in vitro and in vivo through the inhibition of proliferation and induction of differentiation and apoptosis of cancer cells.

Recent studies focused on the pharmacology and feasibility of herbal compounds as a potential strategy to target a variety of human diseases ranging from metabolic to brain disorders. Accordingly, bioactive ingredients which are found within a variety of herbal compounds are reported to produce both neuroprotective and psychotropic activities which may help to combat mental disorders such as depression, anxiety, sleep disturbances and cognitive alterations. In the present manuscript, we focus on three herbs which appear effective in mitigating anxiety or depression with favourable risk-benefit profiles, namely Scutellaria baicalensis (), Hericium erinaceus () and Rhodiola rosea (). These three traditional folk medicinal herbs target the main biochemical events that are implicated in mental disorders, mimicking, to some extent, the mechanisms of action of conventional antidepressants and mood stabilizers with a wide margin of tolerability. In detail, they rescue alterations in neurotransmitter and neuro-endocrine systems, stimulate neurogenesis and the synthesis of neurotrophic factors, and they counteract oxidative stress, mitochondrial dysfunction and inflammation. Albeit the encouraging results that emerge from both experimental and clinical evidence, further studies are needed to confirm and better understand the mental-health promoting, and specifically, the antidepressant effects of these herbs.

The postulated anticancer effect of D-fraction, the bioactive extract of maitake mushroom, on three types (CF33, CF21, and CL-1) of canine cancer cells was evaluated. The effect of D-fraction on several human cancer cells was also investigated. The effect of other beta-glucan products was likewise examined. D-fraction was highly effective on the canine cancer cells, either potently inhibiting cell growth or directly killing cells. Similar effects were also demonstrated in certain human cancer cells. However, other beta-glucan products relevant to D-fraction had no such effects on canine cancer cells. Therefore, D-fraction is a potent natural agent that could be useful in treating canine cancers as well as other veterinary cancers.

Ganoderma lucidum is an important medicinal mushroom species and there is continuous interest in its bioactive properties. This study evaluated whether it may additionally serve as a nutritional supplement for the trace elements: selenium (Se), copper (Cu), and zinc (Zn). Mushrooms were cultivated on substrates enriched with 0.1 to 0.8 mM of inorganic Se alone or in combination with Zn and/or Cu. Supplementation increased accumulation of the elements in fruiting bodies regardless of the applied cultivation model. G. lucidum demonstrated the ability to accumulate significant amounts of organic Se, maximally amounting to (i) over 44 mg/kg when the substrate was supplemented only with Se, (ii) over 20 mg/kg in the Se+Cu model, (iii) over 25 mg/kg in the Se+Zn model, and (iv) 15 mg/kg in the Se+Cu+Zn model. The accumulation of Cu and Zn steadily increased with their initial substrate concentrations. Maximum concentrations found after supplementation with 0.8 mM amounted to over 55 mg/kg (Se+Zn) and 52 mg/kg (Se+Cu+Zn) of Zn, and 29 mg/kg (Se+Cu) and over 31 mg/kg (Se+Cu+Zn) of Cu. The greater the supplemented concentration and number of supplemented elements, the lower the biomass of G. lucidum fruiting bodies. Nevertheless, it still remained high when the substrate was supplemented up to 0.4 mM with each element. These results highlight that G. lucidum can easily incorporate elements from the substrate and that, when biofortified, its dried fruiting bodies may serve as a nutritional source of these essential elements.

Mushroom (shiitake) extracts were dispersed with lecithin micelles to prepare superfine particles (0.05 to 0.2 microm in diameter) of beta-1,3-glucan (micellary mushroom extracts). When mice were fed with these micelles of beta-glucan (0.75 mg/day/mouse, smaller amounts of beta-glucan), the number of lymphocytes yielded by the small intestine increased by up to 40%. More interestingly, the ratio of CD8alphabeta(+)TCRalphabeta(+) cells/CD8alphaalpha(+)TCRalphabeta(+) cells increased prominently. In parallel with this deviation in the distribution of lymphocyte subsets, tumor cytotoxicity against P815 cells and cytokine productions were also augmented. In other words, phylogenetically developed lymphocytes (CD8alphabeta(+), TCRalphabeta(+)) were much more effectively activated by the oral administration of micellary beta-glucan. These results suggest that smaller amounts of micellary beta-glucan might be useful for the potentiation of intestinal immunity.

Neurological dysfunction and death are common events leading to acute and chronic neurodegenerative diseases. Neurodegenerative disorders such as Alzheimer's and Parkinson's disease account for a significant and increasing proportion of morbidity and mortality in the developed world. Ganoderma lucidum (G. lucidum, Lingzhi), one of highly nutritious and significantly effective medicinal herbs, has been used for clinical applications for thousands of years. Several researches have shown that it has a wide range of brain damage protection, such as amelioration of Alzheimer's disease, therapeutic effect on epilepsy, and the protective effect on neural cells in stroke injury. This chapter reviews the neuroprotective effects of G. lucidum and its extracts on brain injury diseases, including Alzheimer's disease, Parkinson's disease, stroke, epilepsy, and other neurodegenerative diseases, and the potential clinical applications.

As extracts from Ganoderma lucidum (G. lucidum, Lingzhi) have been reported to be an alternative adjuvant treatment for diabetes, numerous of work have been carried out on it. Among the many biologically active constituents of Ganoderma, polysaccharides, proteoglycans, proteins, and triterpenoids have been shown to have hypoglycemic effects. Based on our research and other references, this article discusses the antidiabetic effect of Ganoderma mediated by protecting pancreas islet; inhibiting protein tyrosine phosphatase 1B, a promising therapeutic target of diabetes; decreasing lymphocyte infiltration; and increasing the antibody detection of insulin in diabetic mice. This review summarizes researches about the hypoglycemic action effects of polysaccharides, proteoglycans, proteins, and triterpenoids from Ganoderma as a guide for future research on diabetes and its complications. In addition, clinical studies with diabetic indexes are reviewed.

The mechanisms of kidney diseases, such as acute kidney injury (AKI) and chronic kidney disease (CKD), have been intensively studied. Nonetheless, the morbidity and mortality of AKI and CKD increased in recent years. Recently, natural products have been increasingly recognized as an alternative source for treating renal diseases on account of the conventional experience and the multi-target characteristics. Ganoderma lucidum (G. lucidum, Lingzhi) has been used for centuries as nutraceuticals and alternative medicine to improve health and to treat numerous diseases. Benefiting from various biological activities, such as anti-oxidation, anti-inflammation, anti-tumor growth and metastasis, etc., G. lucidum has been proved to exhibit significant role in preventing and treating various kidney diseases. In this chapter, we review certain researches and provide comprehensive insights into the renoprotective effects of G. lucidum.

(HE) is a medicinal plant known to possess anticarcinogenic, antibiotic, and antioxidant activities. It has been shown to have a protective effect against ischemia-injury-induced neuronal cell death in rats. As an extending study, here we examined in pheochromocytoma 12 (PC12) cells, whether HE could exert a protective effect against oxidative stress and apoptosis induced by di(2-ethylhexyl)phthalate (DEHP), a plasticizer known to cause neurotoxicity. We demonstrated that pretreatment with HE significantly attenuated DEHP induced cell death. This protective effect may be attributed to its ability to reduce intracellular reactive oxygen species levels, preserving the activity of respiratory complexes and stabilizing the mitochondrial membrane potential. Additionally, HE pretreatment significantly modulated Nrf2 and Nrf2-dependent vitagenes expression, preventing the increase of pro-apoptotic and the decrease of anti-apoptotic markers. Collectively, our data provide evidence of new preventive nutritional strategy using HE against DEHP-induced apoptosis in PC12 cells.

 Bone marrow and intestinal damage limits the efficacy of radiotherapy for cancer and can result in death if the whole body is exposed to too high a dose, as might be the case in a nuclear accident or terrorist incident. Identification of an effective nontoxic biological radioprotector is therefore a matter of some urgency. In this study, we show that an orally administered hot-water extract from a Chinese herbal medicine, Cordyceps sinensis (CS), protects mice from bone marrow and intestinal injuries after total-body irradiation (TBI). CS increased the median time to death from 13 to 20 days after 8 Gy TBI and from 9 to 18 days after 10 Gy TBI. Although CS-treated mice receiving 10 Gy TBI survived intestinal injury, most died from bone marrow failure, as shown by severe marrow hypoplasia in mice dying between 18 and 24 days. At lower TBI doses of 5.5 and 6.5 Gy, CS protected against bone marrow death, an effect that was confirmed by the finding that white blood cell counts recovered more rapidly. In vitro, CS reduced the levels of free radical species (ROS) within cells, and this is one likely mechanism for the radioprotective effects of CS, although probably not the only one."

Cardiovascular diseases (CVDs) are disorders of the heart and blood vessels and include coronary heart diseases, cerebrovascular diseases, rheumatic heart diseases, and other conditions. CVDs are one of the most major causes of morbidity and mortality around the world, taking the lives of 17.9 million people every year. Several investigations have shown the influence of Ganoderma lucidum (G. lucidum, Lingzhi) on some metabolic markers, such as low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), blood pressure, and oxidative damage. G. lucidum potentially reduces the risk of suffering cardiovascular diseases. Some studies found that G. lucidum prevented from heart damage in a variety of disease models, such as streptozotocin (STZ)-induced diabetic, high-fat-diet-induced diabetic, isoprenaline (ISO)-induced myocardial hypertrophy, acute ethanol-induced heart toxicity, and transverse aortic constriction (TAC) models. This chapter summarizes putative preventive and therapeutic effects of G. lucidum on cardiovascular diseases and the potential clinical use of G. lucidum involved in these effects.

Cisplatin-induced nephrotoxicity is a serious adverse effect that limits the use of cisplatin in cancer patients. In the present study, we investigated the protective effect of lanostane triterpenoids (1-10) isolated from the ethanolic extract of Poria cocos Wolf against cisplatin-induced cell death in LLC-PK1 kidney tubular epithelial cells. Treatment of cisplatin induced significant cell death, which was suppressed by treatment with dehydroeburicoic acid monoacetate (1) and 3β-acetoxylanosta-7,9(11),24-trien-21-oic acid (9). Compound 1 exhibited the highest efficacy among the tested compounds and was thus subjected to further mechanistic studies. The increase in the percentage of apoptotic cells induced by cisplatin reduced by 4.3% after co-treatment of cells with compound 1 (50 and 100μM). Furthermore, phosphorylation of the mitogen-activated protein kinases JNK, ERK, and p38, and caspase-3, which characterize oxidative stress-mediated apoptosis, increased significantly after treatment with cisplatin, and decreased after treatment with compound 1. These resultsindicate that the renoprotective effects of compound 1 may be mediated by its anti-apoptotic activity.

ETHNOPHARMACOLOGICAL RELEVANCE:UVB is a high energy source that causes the major risk factor for sunburn and skin tumor. However, photochemical interactions lead to beneficial effects such as synthesis of vitamin D and corticosteroids. Therefore, a reasonable therapeutic regime is advocated to reduce UVB injuries but makes use of synthesizing sunlight metabolite. Many natural compounds improving plant cells resistant to oxidative stress by the harnessing of solar energy may be also used to protect human cells. Although many nature plants have shown photoprotective effects on skin, the mechanisms underlying of the effects are still ambiguous.

AIM OF THE STUDY:This study evaluates the protective effects of cultivated Cordyceps against UVB-induced damage in human keratinocytes and identifies the photoprotective mechanisms using a transcriptomic network approach.

MATERIALS AND METHODS:Cordyceps extract compositions were investigated by HPLC analysis. Cell survival, reactive oxygen species (ROS) generation, HOcontent, aquaporin 3 (AQP3) level and DNA damage were determined upon UVB irradiation in the presence of Cordyceps extract. In addition, next-generation sequencing was used to profile transcriptomic alteration of 20 mJ/cmUVB and non-UV. Finally, a network pharmacology method was applied to study Cordyceps extract-related natural compounds and their UVB-induced differentially change targets using the Cytoscape 3.7.1 software.

RESULTS:Adenosine and mannitol were the major contents in Cordyceps extract. Cordyceps caused a significant diminished in intracellular UVB-induced oxidative stress, including ROS production and intracellular HOcontent. Besides, AQP3 which mediated intracellular signal transmission and transported HOinto cells was significantly increased in the presence of Cordyceps extract against UVB irradiation. In addition, DNA repair effect of Cordyceps extract after UV irradiation was proven to be effective by comet assay. Moreover, KEGG analysis showed steroid hormone biosynthesis, ovarian steroidogenesis, fat digestion and absorption were enriched in top 3 between 20 mJ/cmUVB and non-UV. Gene ontology (Go) analysis showed that steroid metabolic process, sterol metabolic process, and cholesterol metabolic process were enriched in top3 biology process. By using network analysis, 125 potential bioactive ingredients in Cordyceps and 201 targets were identified. Finally, signal pathway analyses suggested that the protective effects of Cordyceps compounds against low dose UVB‑induced changes might target PPAR signaling pathway, cholesterol metabolism, and ovarian steroidogenesis.

CONCLUSION:Cordyceps extract may be an ideal product for external use of skin which could not only avoid UVB-induced adverse effects, but also could application of metabolite products by UVB such us steroid hormone and vitamin D3.