PMID: 

Biomolecules. 2019 08 19 ;9(8). Epub 2019 Aug 19. PMID: 31430968

Abstract Title: 

The Protective Effect of Hispidin against Hydrogen Peroxide-Induced Oxidative Stress in ARPE-19 Cells via Nrf2 Signaling Pathway.

Abstract: 

Hispidin, a polyphenol compound isolated from, has been reported to possess antioxidant activities. In this study, we aimed to investigate the mechanisms underlying the protective effect of hispidin against hydrogen peroxide (HO)-induced oxidative stress on Adult Retinal Pigment Epithelial cell line-19 (ARPE-19) cells. Hispidin was not cytotoxic to ARPE-19 cells at concentrations of less than 50μM. The levels of intracellular reactive oxygen species (ROS) were analyzed by dichlorofluorescin diacetate (DCFDA) staining. Hispidin significantly restored HO-induced cell death and reduced the levels of intracellular ROS. The expression levels of antioxidant enzymes, such as NAD(P)H:Quinine oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) were examined using real-time PCR and Western blotting. Our results showed that hispidin markedly enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1, NQO-1, GCLM, and GCLC in a dose-dependent manner. Furthermore, knockdown experiments revealed that transfection with Nrf2 siRNA successfully suppresses the hispidin activated Nrf2 signaling in ARPE-19 cells. Moreover, activation of the c-Jun N-terminal kinase (JNK) pathway is involved in mediating the protective effects of hispidin on the ARPE-19 cells. Thus, the present study demonstrated that hispidin provides protection against HO-induced damage in ARPE-19 cells via activation of Nrf2 signaling and up-regulation of its downstream targets, including Phase II enzymes, which might be associated with the activation of the JNK pathway.

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PMID: 

Biomed Rep. 2017 Dec ;7(6):567-572. Epub 2017 Oct 11. PMID: 29188061

Abstract Title: 

Effect ofglucan on the stimulation of cytokine production in sarcoma-180-bearing mice.

Abstract: 

(CV) contains high levels of bioactive compounds, including the glucan (1→6)-α-D-glucopyranosyl. However, there is a lack of data regarding the potential effect of this CV glucan (CVG) on the stimulation of cytokine production. The present study evaluated the effect of CVG on the stimulation of cytokine production in sarcoma-180-bearing mice. Mice were treated with three doses of CVG (40, 100 or 200 mg/kg body weight) for nine days, after which serum levels of cytokines, namely interleukin (IL)-2, -4, -6, -10, -17A and interferon (IFN)-α and -γ, were investigated by ELISA. CVG significantly promoted the secretion of IL-2, -4, -6, -10, -17A and IFN-α and -γ at the doses of 100 (P

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PMID: 

Phytother Res. 2018 Mar ;32(3):551-560. Epub 2017 Dec 15. PMID: 29243310

Abstract Title: 

Coriolus versicolor aqueous extract ameliorates insulin resistance with PI3K/Akt and p38 MAPK signaling pathways involved in diabetic skeletal muscle.

Abstract: 

Patients with type 2 diabetes mellitus (T2DM) are usually with poor immunity and easier to suffer from cancer and microbial infections. Herein, we report an efficient anti-diabetic medicinal mushroom, Coriolus versicolor (CV). This study aimed to investigate the anti-diabetic and anti-insulin-resistance effects of CV aqueous extract in myoblasts (L6 cells) and skeletal muscle of T2DM rat. Our results showed that CV extract treatment significantly reduced blood glucose levels of T2DM rats, whereas CV extract increased glucose consumption in insulin resistant L6 cells. Besides, the translocation and expression of glucose transporter 4 were enhanced by CV extract, which indicated that CV extract was effective in diabetic skeletal muscle. Moreover, CV extract treatments resulted in remarkable anti-insulin-resistance effects, which was reflected by the change of gene and protein expression levels in PI3K/Akt and p38 MAPK pathways. PI3K inhibitor, LY29004, and p38 MAPK inhibitor, SB203580 confirmed it further. In conclusion, our results demonstrated that the CV extract exhibited anti-diabetic and anti-insulin-resistance effects in diabetic skeletal muscle, and the effects were mediated by PI3K/Akt and p38 MAPK pathways. These findings are remarkable when considering the use of commercially available CV by diabetic patients who also suffer from cancer or microbial infections.

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PMID: 

Front Pharmacol. 2019 ;10:703. Epub 2019 Jul 3. PMID: 31333449

Abstract Title: 

andRelated Natural Products as an Adjunct Therapy for Cancers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract: 

Cancer incidence and mortality rates keep rising globally.andrelated natural products are commonly applied as a complementary therapeutic option for different stages and types of cancers. The aim of this study is to evaluate the efficacy and safety of the products for cancer therapy.Randomized controlled trials were identified by systematic search over seven databases from inceptions to May 10, 2019. Two independent reviewers extracted data and assessed the study quality. Meta-analyses were performed to pool hazard ratio (), risk ratio (), mean differences (), and 95%using random-effects models. The sources of heterogeneity were explored by subgroup analyses and sensitivity analyses. Publication bias was detected by Funnel plots, Begg's test, and Egger's test.Twenty-three trials involving 4,246 cancer patients were included in this work.andrelated natural products were significantly associated with lower risks of mortality (: 0.82; 95%: 0.72, 0.94) and higher total efficacy (: 1.30; 95%: 1.09, 1.55), but not associated with control rate (: 1.05; 95%: 0.96, 1.14) compared with control treatment. There was no significant difference betweenrelated natural products and control treatment in the effect on relapse-free survival (: 1.19; 95%: 0.91, 1.55). Compared with control treatment,andrelated natural products had a favorable effect on elevated levels of CD3 (: 9.03%; 95%: 2.10, 16.50) and CD4 (: 9.2%; 95%: 1.01, 17.39), but had no effect on the levels of CD8 (: -5.52%; 95%: -23.17, 12.13), CD4/CD8 (: 0.73; 95%:-0.45, 1.91), or NK(: 5.87%; 95%: -1.06, 12.8).In this meta-analysis, we found thatandrelated natural products might have potential benefits on the overall survival and quality of life in cancer patients.

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PMID: 

Phytother Res. 2019 Oct ;33(10):2737-2748. Epub 2019 Jul 23. PMID: 31338905

Abstract Title: 

Coriolus versicolor alleviates diabetic cardiomyopathy by inhibiting cardiac fibrosis and NLRP3 inflammasome activation.

Abstract: 

Coriolus versicolor (CV) is a traditional medicine and food mushroom. Our previous study demonstrated that CV extract exhibited anti-hyperglycemia and anti-insulin resistance effects. However, the effect of CV on cardiac function in diabetic cardiomyopathy (DCM) remains unclear. Therefore, we aimed to investigate the effect of CV on cardiac function in diabetes mellitus (DM) rats. We found that the cardiac dysfunction of DM rats was markedly improved by CV extract treatment. CV extract administration significantly attenuated cardiac fibrosis in DM rats, which was accompanied by suppressed transforming growth factor beta 1 (TGF-β1)/Smad signaling as indicated by decreased levels of TGF-β1, p-Smad2, and p-Smad3 and increased Smad7 expression. Moreover, CV extract treatment significantly alleviated cardiac inflammation as shown by decreased levels of NLRP3 receptor, cleaved caspase-1, IL-1β, and IL-18 in DM rats at leastpartly due to the inhibition of the NF-κB. In addition, high-glucose treatment induced cardiac fibrosis and increased cardiac inflammation in cardiac fibroblast cells, but these effects were ameliorated by CV extract treatment. Therefore, we conclude that the protective effect of CV on DCM is associated with the suppression of TGF-β1/Smad signaling and attenuation of NLRP3 inflammasome activation, suggesting that CV extract may be a potential therapeutic agent for DCM.

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PMID: 

Sci Rep. 2015 Oct 15 ;5:15015. Epub 2015 Oct 15. PMID: 26468932

Abstract Title: 

Different Brain Regions are Infected with Fungi in Alzheimer's Disease.

Abstract: 

The possibility that Alzheimer's disease (AD) has a microbial aetiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae. Fungal material can be detected both intra- and extracellularly using specific antibodies against several fungi. Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi. Fungal infection is also observed in blood vessels, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals.

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PMID: 

Sci Rep. 2017 07 17 ;7(1):5559. Epub 2017 Jul 17. PMID: 28717130

Abstract Title: 

Polymicrobial Infections In Brain Tissue From Alzheimer's Disease Patients.

Abstract: 

Several studies have advanced the idea that the etiology of Alzheimer's disease (AD) could be microbial in origin. In the present study, we tested the possibility that polymicrobial infections exist in tissue from the entorhinal cortex/hippocampus region of patients with AD using immunohistochemistry (confocal laser scanning microscopy) and highly sensitive (nested) PCR. We found no evidence for expression of early (ICP0) or late (ICP5) proteins of herpes simplex virus type 1 (HSV-1) in brain sections. A polyclonal antibody against Borrelia detected structures that appeared not related to spirochetes, but rather to fungi. These structures were not found with a monoclonal antibody. Also, Borrelia DNA was undetectable by nested PCR in the ten patients analyzed. By contrast, two independent Chlamydophila antibodies revealed several structures that resembled fungal cells and hyphae, and prokaryotic cells, but most probably were unrelated to Chlamydophila spp. Finally, several structures that could belong to fungi or prokaryotes were detected using peptidoglycan and Clostridium antibodies, and PCR analysis revealed the presence of several bacteria in frozen brain tissue from AD patients. Thus, our results show that polymicrobial infections consisting of fungi and bacteria can be revealed in brain tissue from AD patients.

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PMID: 

J Alzheimers Dis. 2017 ;58(1):55-67. PMID: 28387676

Abstract Title: 

Identification of Fungal Species in Brain Tissue from Alzheimer's Disease by Next-Generation Sequencing.

Abstract: 

The possibility that patients diagnosed with Alzheimer's disease (AD) have disseminated fungal infection has been recently advanced by the demonstration of fungal proteins and DNA in nervous tissue from AD patients. In the present study, next-generation sequencing (NGS) was used to identify fungal species present in the central nervous system (CNS) of AD patients. Initially, DNA was extracted from frozen tissue from four different CNS regions of one AD patient and the fungi in each region were identified by NGS. Notably, whereas a great variety of species were identified using the Illumina platform, Botrytis cinerea and Cryptococcus curvatus were common to all four CNS regions analyzed. Further analysis of entorhinal/cortex hippocampus samples from an additional eight AD patients revealed a variety of fungal species, although some were more prominent than others. Five genera were common to all nine patients: Alternaria, Botrytis, Candida, Cladosporium, and Malassezia. These observations could be used to guide targeted antifungal therapy for AD patients. Moreover, the differences found between the fungal species in each patient may constitute a basis to understand the evolution and severity of clinical symptoms in AD.

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PMID: 

Curr Pharm Des. 2017 ;23(19):2807-2834. PMID: 28103773

Abstract Title: 

Agaricus blazei Bioactive Compounds and their Effects on Human Health: Benefits and Controversies.

Abstract: 

BACKGROUND: The mushroom Agaricus blazei has evoked considerable scientific and practical interest in several fields, especially those linked to its medicinal properties. This review aims to summarize and evaluate the past decade findings related to nutritional and therapeutic uses of A. blazei, with especial emphasis on the most recent discoveries regarding its chemical composition and clinical investigations.METHODS: The specialized literature was searched for basic and clinical studies. The main isolated and identified compounds or fractions are described and confronted with their corresponding bioactivities.RESULTS: Basic research of high quality using ex vivo and in vivo conditions are quite abundant in the specialized literature, but ony 17 clinical studies and two case reports were found. A great number of active molecules have been identified, and they can be divided into three categories, (1) hydrophilic small molecules (e.g., phenolics), (2) lipophilic or partially lipophilic small molecules (e.g., agarol) (3) and macromolecules (e.g.,β-glucans). At least the following bioactivities can be considered as being supported by experimental evidence: antioxidant activity (in aging or disease), immunomodulation and cell signaling, anti-inflammatory activity, antiparasitic actions, antimicrobial activity, anticancer effects and tumor growth inhibiting effects, antimutagenic activity, hepatoprotection against chemical or viral infection and antidiabetic activity.CONCLUSION: The amount and quality of the evidence that has been accumulating during the last decade strongly speaks in favor of the health benefits of the ingestion of A.blazei or derived products. However, there are many uncertainties and limitations when attempts are made to extrapolate or to demonstrate their biological effects in the human organism in health or disease. Clearly, more clinical trials, using reliable statistical methods and standardized preparations are needed to establish the efficacy of A. blazei as a therapeutic agent.

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PMID: 

Basic Clin Pharmacol Toxicol. 2008 Jul ;103(1):48-54. Epub 2008 Jul 1. PMID: 18484961

Abstract Title: 

Licochalcone A inhibits the growth of colon carcinoma and attenuates cisplatin-induced toxicity without a loss of chemotherapeutic efficacy in mice.

Abstract: 

Although chemotherapy has an important function in the treatment of most solid tumours, its clinical applications are limited by severe side effects such as nephrotoxicity, hepatotoxicity, ototoxicity and neurotoxicity. Recently, a growing amount of attention has been focused on the investigation of the effects of chemopreventive agents on the inhibition of cancer cell growth and toxicity in combination with chemotherapeutics. The aim of this study was to determine whether licochalcone A (LCA) has the potential to serve as a beneficial supplement during cisplatin chemotherapy. We found that the administration of LCA alone significantly inhibited the size of the solid tumours in CT-26 cell-inoculated Balb/c mice, without any detectable induction of nephrotoxicity, hepatotoxicity and oxidative stress. LCA also suppressed cell proliferation by reducing DNA synthesis of CT-26 murine colon cancer cells in a dose-dependent manner. LCA did not affect the therapeutic efficacy of cisplatin. Furthermore, LCA inhibited the cisplatin-induced kidney damage characterized by increases in the serum creatinine and blood urea nitrogen, as well as the cisplatin-induced liver damage characterized by increases in the serum alanine aminotransferase and aspartate aminotransferase. The repeated oral administration of LCA prior to cisplatin treatment exerted a preventive effect on the cisplatin-mediated increases in the serum nitric oxide and the tissue lipid peroxidation levels, and recovered the depleted reduced glutathione levels in the tissues. These results suggest that supplementation with LCA may be beneficial in counteracting the side effects of cisplatin therapy in cancer patients.

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