PMID: 

Adv Exp Med Biol. 2019 ;1182:263-269. PMID: 31777023

Abstract Title: 

Anti-osteoporosis Effect of Ganoderma (Lingzhi) by Inhibition of Osteoclastogenesis.

Abstract: 

The anti-osteoporosis effect of Ganoderma lucidum (G. lucidum, Lingzhi) is closely associated with inhibition of osteoclastogenesis in the charge of osteoclasts. This article reviewed the anti-osteoporosis effect of Ganoderma and its active components, including a kind of triterpenoids, a polysaccharide and a protein named Ling Zhi-8 (LZ-8). Triterpenoids are a kind of active compounds as candidates for the treatment of osteoporosis. Among these, ganoderic acids are currently considered as the most important and potential components, and their structure-activity relationship highlights the essential group to hamper osteoclast differentiation. The data confirmed that the active compounds isolated from triterpenoids and meroterpenoids could suppress bone resorption of osteoclast via RANKL/RANK pathway and/or its downstream signaling transduction related to ERK, JNK and p38 MAPKs, contributing to inhibition of the level of c-Fos and NFATc1, two key target genes of osteoclast for osteoclastogenesis. However, the comprehensive mechanism remains to be elucidated in the future.

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PMID: 

J Food Biochem. 2020 Jan ;44(1):e13109. Epub 2019 Dec 3. PMID: 31793675

Abstract Title: 

Ganoderma polysaccharide and chitosan synergistically ameliorate lipid metabolic disorders and modulate gut microbiota composition in high fat diet-fed golden hamsters.

Abstract: 

High-fat diet (HFD) and sucrose intake can lead to hyperlipidemia, hypercholesterolemia, and nonalcoholic fatty liver disease (NAFLD) as well as disturbed gastrointestinal microbiota and dysfunctional intestinal barrier. In the present study, we showed that Ganoderma lucidum polysaccharide and chitosan (PC) significantly mitigated the hyperlipidemia in HFD-fed hamsters via lowering the contents of serum total triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and aspartate aminotransferase (AST). Furthermore, PC changed the composition of gastrointestinal microbiota and elevated the relative abundances of beneficial bacteria, such as Prevotella, Oscillibacter, and SCFA-producers. Interestingly, we also found that the abundances of Prevotella, Alloprevotella, Bifidobacterium, and Alistipes were negatively associated with serum lipid profiles. Collectively, the above-mentioned findings indicated that PC could improve lipid metabolic disorders, at least in part, by modulating gastrointestinal microbiota, suggesting thatPC could be used as a potential lipid-lowering ingredient in functional foods. PRACTICAL APPLICATIONS: PC could ameliorate lipid metabolism disorder, at least in part, by regulating specific gut microbiota, suggesting its potential as a novel lipid-lowering ingredient in functional foods. We believed that our findings could be of interest to the readers because they help others further understand the gut microbiota alterations that occurred after PC supplementation in the context of metabolic syndrome (MetS).

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PMID: 

Sci Rep. 2019 Dec 13 ;9(1):19059. Epub 2019 Dec 13. PMID: 31836806

Abstract Title: 

Discovery of Ganoderma lucidum triterpenoids as potential inhibitors against Dengue virus NS2B-NS3 protease.

Abstract: 

Dengue virus (DENV) infection causes serious health problems in humans for which no drug is currently available. Recently, DENV NS2B-NS3 protease has been proposed as a primary target for anti-dengue drug discovery due to its important role in new virus particle formation by conducting DENV polyprotein cleavage. Triterpenoids from the medicinal fungus Ganoderma lucidum have been suggested as pharmacologically bioactive compounds and tested as anti-viral agents against various viral pathogens including human immunodeficiency virus. However, no reports are available concerning the anti-viral activity of triterpenoids from Ganoderma lucidum against DENV. Therefore, we employed a virtual screening approach to predict the functional triterpenoids from Ganoderma lucidum as potential inhibitors of DENV NS2B-NS3 protease, followed by an in vitro assay. From in silico analysis of twenty-two triterpenoids of Ganoderma lucidum, four triterpenoids, viz. Ganodermanontriol (-6.291 kcal/mol), Lucidumol A (-5.993 kcal/mol), Ganoderic acid C2 (-5.948 kcal/mol) and Ganosporeric acid A (-5.983 kcal/mol) were predicted to be viral protease inhibitors by comparison to reference inhibitor 1,8-Dihydroxy-4,5-dinitroanthraquinone (-5.377 kcal/mol). These results were furtherstudied for binding affinity and stability using the molecular mechanics/generalized Born surface area method and Molecular Dynamics simulations, respectively. Also, in vitro viral infection inhibition suggested that Ganodermanontriol is a potent bioactive triterpenoid.

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PMID: 

Drug Des Devel Ther. 2018 ;12:4117-4127. Epub 2018 Dec 4. PMID: 30584276

Abstract Title: 

N-acetylcysteine amide provides neuroprotection via Nrf2-ARE pathway in a mouse model of traumatic brain injury.

Abstract: 

Background: Increasing evidence demonstrate N-acetylcysteine amide (NACA) provides neuroprotection and attenuated oxidative stress in rats following traumatic brain injury (TBI). The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signal pathway is activated after TBI and provides a protective effect against TBI. However, the function and mechanism of NACA in mice after TBI remain unknown. This study was to evaluate the neuroprotection of NACA and the potential action of the Nrf2-ARE pathway in a weight-drop mouse model of TBI.Materials and methods: Four groups of animals were randomly divided into sham, TBI, TBI+vehicle, and TBI+NACA (100 mg/kg, administered intraperitoneally). The protein levels of Nrf2, heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase-1 (NQO1), cleaved caspase-3 and the mRNA levels of HO-1 and NQO1 were detected. The neurobehavior, neuronal degeneration, apoptosis and oxidative stress were also assessed.Results: Treatment with NACA significantly improved neurologic status at days 1 and 3 following TBI. Moreover, NACA promoted Nrf2 activation a day after TBI. The protein and mRNA levels of HO-1 and NQO1 were upregulated by NACA. Meanwhile, NACA treatment significantly reduced the level of malondialdehyde (MDA) and enhanced the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx), which indicated NACA attenuated oxidative stress following TBI. NACA prominently reduced the protein level of cleaved caspase-3 and TUNEL-positive cells, indicating its antiapoptotic effect. Additionally, Fluoro-Jade C staining showed NACA alleviated neuronal degeneration a day after TBI.Conclusions: Our study reveals that NACA potentially provides neuroprotection via the activation of the Nrf2-ARE signaling pathway after TBI in mice.

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PMID: 

Integr Cancer Ther. 2019 Jan-Dec;18:1534735419890917. PMID: 31855073

Abstract Title: 

Exerts an Anticancer Effect on Human Osteosarcoma Cells via Suppressing the Wnt/β-Catenin Signaling Pathway.

Abstract: 

Current treatment of osteosarcoma is limited in part by side effects and low tolerability, problems generally avoided with traditional Chinese medicine., a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its molecular mechanisms in osteosarcoma cells.To investigate the effect ofon osteosarcoma cells and its mechanism.Osteosarcoma MG63 and U2-OS cells were treated with, followed by assays for cell proliferation (Cell Counting Kit-8), colony formation, and apoptosis (Alexa Fluor 647-Annexin V/propidium iodide, flow cytometry). Migration and invasion of cells were assessed by wound healing and Transwell invasion assays, and the effect ofon Wnt/β-catenin signal transduction was studied by real-time quantitative polymerase chain reaction, western blot, and dual-luciferase assay.inhibited the proliferation, migration, and invasion, and induced apoptosis of human osteosarcoma MG63 and U2-OS cells. Dual-luciferase assay showed thatsuppressed the transcriptional activity of T-cell factor/lymphocyte enhancer factor in the Wnt/β-catenin signaling pathway. Moreover,blocked Wnt/β-catenin signaling by inhibiting the Wnt co-receptor LRP5 and Wnt-related target genes, such as β-catenin, cyclin D1, C-Myc, MMP-2, and MMP-9. At the same time, when Wnt/β-catenin was inhibited, the expression of E-cadherin was upregulated.Our results suggest thatbroadly suppresses osteosarcoma cell growth by inhibiting Wnt/β-catenin signaling.

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PMID: 

Clin Exp Hepatol. 2018 Dec ;4(4):260-266. Epub 2018 Dec 3. PMID: 30603674

Abstract Title: 

N-acetylcysteine protects hepatocytes from hypoxia-related cell injury.

Abstract: 

Aim of the study: Hepatocyte transplantation has been discussed as an alternative to liver transplantation in selected cases of acute and chronic liver failure and metabolic diseases. Immediately after infusion of hepatocytes, hypoxia-related cell injury is inevitable. N-acetylcysteine (NAC) has been suggested to attenuate hypoxic damage. This study's objective was to evaluate NAC's protective effect in a model of hypoxia-related hepatocyte injury.Material and methods: HepG2 cells were used as a model for hepatocytes and were cultured under standardized hypoxia or normoxia for 24 hours with or without NAC. Growth kinetics were monitored using trypan blue staining. The activation of apoptotic pathways was measured using quantitative real-time PCR for Bcl-2/Bax and p53. The proportions of vital, apoptotic and necrotic cells were verified by fluorescence activated cell sorting using annexin V-labelling. The expression of hypoxia inducible factor 1 (HIF-1) was measured indirectly using its downstream target vascular endothelial growth factor A (VEGF-A).Results: After NAC, cell proliferation increased under both hypoxia and normoxia by 528% and 320% (

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PMID: 

J Exp Clin Cancer Res. 2019 Jan 3 ;38(1):2. Epub 2019 Jan 3. PMID: 30606241

Abstract Title: 

N-acetylcysteine decreases malignant characteristics of glioblastoma cells by inhibiting Notch2 signaling.

Abstract: 

BACKGROUND: Glioblastomas multiforme (GBM) is the most devastating primary intracranial malignancy lacking effective clinical treatments. Notch2 has been established to be a prognostic marker and probably involved in GBM malignant progression. N-acetylcysteine (NAC), a precursor of intracellular glutathione (GSH), has been widely implicated in prevention and therapy of several cancers. However, the role of NAC in GBM remains unclear and the property of NAC independent of its antioxidation is largely unknown.METHODS: The mRNA and protein levels of Notch family and other related factors were detected by RT-PCR and western blot, respectively. In addition, intracellular reactive oxygen species (ROS) was measured by flow cytometry-based DCFH-DA. Moreover, cell viability was assessed by CCK8 and cell cycle was analyzed by flow cytometry-based PI staining. The level of apoptosis was checked by flow cytometry-based Annexin V/PI. Cell migration and invasion were evaluated by wound healing and transwell invasion assays. At last, U87 Xenograft model was established to confirm whether NAC could restrain the growth of tumor.RESULTS: Our data showed that NAC could decrease the protein level of Notch2. Meanwhile, NAC had a decreasing effect on the mRNA and protein levels of its downstream targets Hes1 and Hey1. These effects caused by NAC were independent of cellular GSH and ROS levels. The mechanism of NAC-mediated Notch2 reduction was elucidated by promoting Notch2 degradation through Itch-dependent lysosome pathway. Furthermore, NAC could prevent proliferation, migration, and invasion and might induce apoptosis in GBM cells via targeting Notch2. Significantly, NAC could suppress the growth of tumor in vivo.CONCLUSIONS: NAC could facilitate Notch2 degradation through lysosomal pathway in an antioxidant-independent manner, thus attenuating Notch2 malignant signaling in GBM cells. The remarkable ability of NAC to inhibit cancer cell proliferation and tumor growth may implicate a novel application of NAC on GBM therapy.

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PMID: 

JBRA Assist Reprod. 2019 Apr 30 ;23(2):83-90. Epub 2019 Apr 30. PMID: 30633472

Abstract Title: 

Protective action of N-acetylcysteine on sperm quality in cyclophosphamide-induced testicular toxicity in male Wistar rats.

Abstract: 

BACKGROUND: Reductions in sperm quality due to free radical formation during cancer chemotherapy are well documented, hence the need for an adjunct antioxidant treatment during chemotherapy. This study was designed to investigate the effects of N-acetylcysteine on sperm quality following cyclophosphamide exposure in male Wistar rats.METHODS: wenty male Wistar rats weighing 150-170g were randomly assigned into 4 groups of five rats each, and were orally administered distilled water (Control), Cyclophosphamide (6mg/kg), N-acetylcysteine (100mg/kg) or Cyclophosphamide + N-acetylcysteine for 21 days. Sperm count, histone-protamine replacement, chromatin integrity, testicular histomorphometry and BAX Protein expression were assessed using standard procedures. The data was presented as mean± SEM and analyzed using students' t- test. A

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PMID: 

Reprod Toxicol. 2019 03 ;84:98-107. Epub 2019 Jan 8. PMID: 30633982

Abstract Title: 

N-acetylcysteine alleviates fluoride-induced testicular apoptosis by modulating IRE1α/JNK signaling and nuclear Nrf2 activation.

Abstract: 

We previously investigated excessive fluoride exposure elicited intracellular endoplasmic reticulum (ER) stress and led to Sertoli cells dysfunction in vitro. However, the mechanisms underlying fluoride-mediated male reproductive damage in vivo remain largely unknown. Considerable evidence has now revealed ER stress is closely linked with testicular oxidative damage. Hence, we aimed to explore whether ER stress signaling was involved in the testicular protective effects of antioxidant N-acetylcysteine (NAC) against testicular apoptosis induced by fluoride. Male SD rats were oral gavaged with sodium fluoride (NaF) for 7 weeks to induce fluorosis. The animals were pretreatment with or without NAC (150 mg/Bw•d). Our results demonstrated that sub-chronic NaF exposure triggered testicular apoptosis and sex hormonal disturbance in pituitary-testicular (PT) axis, promoted oxidative stress and the expression of ER stress mediators. Antioxidant NAC, however, prevented NaF-induced testicular apoptosis accompanied by activating Nrf2-mediated antioxidant potential. Simultaneously, NAC pretreatment downregulated XBP1 splicing, reduced JNK phosphorylation and further blocked cleavage of caspase-3, all these might contribute to the inhibition of testicular cell apoptosis. Collectively, the presentresults suggested that prolonged administration of NAC preserved testicular function and normalized sex hormonal disruption induced by NaF via the inhibition of Nrf2-associated oxidative damage and Ire1α-JNK-mediated apoptosis in rat testis.

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PMID: 

Clin Oral Investig. 2019 Oct ;23(10):3833-3842. Epub 2019 Jan 23. PMID: 30673864

Abstract Title: 

N-acetyl cysteine versus chlorhexidine mouthwashes in prevention and treatment of experimental gingivitis: a randomized, triple-blind, placebo-controlled clinical trial.

Abstract: 

OBJECTIVES: To compare the efficacy of N-acetyl cysteine (NAC) mouthwash with chlorhexidine (CHX) in prevention and treatment of experimental gingivitis MATERIALS AND METHODS: Sixty subjects were assigned randomly and blindly into one of three equal groups: NAC, CHX, or placebo group. The study was conducted in two stages: preventive and treatment substudies. Professional prophylaxis was performed ahead of starting the preventive substudy. Then, the subjects were instructed to stop oral hygiene practices and begin rinsing twice/day with 15 ml of the assigned mouthwash (1.25% NAC, 0.2% CHX, or inert base). Plaque index (PI), gingival index (GI), and papillary bleeding index (PBI) were measured at baseline, 7, 14, and 21 days. The treatment substudy started on day 21 in which the subjects in the placebo group (now with established experimental gingivitis) were assigned to NAC (n = 10) or CHX (n = 10); the abovementioned indices were measured at 28 and 35 days. Efficacy of these interventions was compared.RESULTS: All groups accumulated plaque and developed some degree of gingivitis: full-blown in the placebo group and remarkably mild in the CHX group. NAC had slight preventive properties at days 14 and 21. In the treatment substudy, CHX was associated with remarkable reduction in plaque and gingivitis while NAC resulted in insignificant reductions.CONCLUSIONS: 1.25% NAC is marginally effective in prevention and treatment of experimental gingivitis.CLINICAL RELEVANCE: When compared with the placebo, NAC showed promising preventive and treatment effects of gingivitis that deserve further development and studies.TRIAL REGISTRATION: ISRCTN31352091.

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