PMID: 

Eur J Pharmacol. 2019 Dec 1 ;864:172712. Epub 2019 Oct 2. PMID: 31586469

Abstract Title: 

Neohesperidin inhibits TGF-β1/Smad3 signaling and alleviates bleomycin-induced pulmonary fibrosis in mice.

Abstract: 

Idiopathic pulmonary fibrosis (IPF) is a fatal growing problem, with limited therapeutic options. Transforming growth factor beta 1 (TGF-β1) plays a critical role in many pathological processes that characterize pulmonary fibrosis. Effective and well-tolerated antifibrotic agents that interfere with TGF-β1 signaling would be an ideal treatment but no such treatments are available. In this study, we identified that the natural compound, neohesperidin, antagonizes TGF-β1/Smad3 signaling. We found that neohesperidin not only inhibited the TGF-β1-induced injury to alveolar epithelial cells but also decreased the TGF-β1-induced myofibroblast differentiation, extracellular matrix production, and fibroblast migration. Furthermore, we obtained in vivo evidence that neohesperidin treatment inhibited bleomycin-induced lung injuries and even attenuated established pulmonary fibrosis in mice. Our data suggest that neohesperidin can target the critical signaling pathway and profibrogenic responses in progressive pulmonary fibrosis and may have a potential use in treatment.

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PMID: 

Phytother Res. 2019 Aug ;33(8):2034-2043. Epub 2019 Jun 14. PMID: 31197891

Abstract Title: 

Neohesperidin suppresses IgE-mediated anaphylactic reactions and mast cell activation via Lyn-PLC-Capathway.

Abstract: 

Mast cells play an essential role in IgE-FcεR1-mediated allergic diseases. Citrus aurantium is a prolific source of flavonoids with various biological activities, including anti-inflammatory, antioxidant, and anti-tumor efficacies. Neohesperidin is a novel flavonoid isolated from the leaves of C. aurantium. In this study, the anti-allergicand anti-inflammatory potentials of neohesperidin were investigated along with its molecular mechanism. The anti-anaphylactic activity of neohesperidin was evaluated through hind paw extravasation study in mice. Calcium imaging was used to assess intracellular Camobilization. The levels of cytokines and chemokines were measured using enzyme immunoassay kits. Western blotting was used to explore the related molecular signaling pathways. Neohesperidin suppressed IgE-induced mast cell activations, including degranulation and secretion of cytokines and eicosanoids through inhibiting phosphorylation of Lyn kinase. Neohesperidin inhibited the release of histamine and other proinflammatory cytokines through a mast cell-dependent passive cutaneous anaphylaxis animal model. Histological studies demonstrated that neohesperidin substantially inhibited IgE-induced cellular infiltration and attenuated mast cell activation in skin tissue. In conclusion, our study revealed that neohesperidin could inhibit allergic responses in vivo and in vitro, and the molecule may be regarded as a novel agent for preventing mast cell-immediate and delayed allergic diseases.

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PMID: 

J Agric Food Chem. 2017 Oct 18 ;65(41):9061-9068. Epub 2017 Oct 9. PMID: 28942652

Abstract Title: 

Polyphenols from Blossoms of Citrus aurantium L. var. amara Engl. Show Significant Anti-Complement and Anti-Inflammatory Effects.

Abstract: 

Citrus aurantium L. var. amara Engl. (CAVA) was traditionally used as a digestant or expectorant in China. Crude polyphenols (CAVAP-W) extracted from blossoms of CAVA were mainly composed of eriocitrin/neoeriocitrin, eriocitrin/neoeriocitrin, rhoifolin, hesperidin, naringin, rutin, veronicastroside, neohesperidin, and hesperetin by LC-MS analysis. CAVAP-W showed significant anticomplement and anti-inflammatory effects. Due to the close relationship between anticomplement and anti-inflammatory activity, the anti-inflammatory effect was further investigated and the results showed that CAVAP-W significantly suppressed production of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and mRNA expression of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, IL-1β, and cyclooxygenase-2 (COX-2) in lipopolysaccharides-stimulated RAW264.7 cells. Furthermore, CAVAP-W inhibited mitogen-activated protein kinase (MAPK) phosphorylation and NF-κB activation through suppressing nuclear translocation of nuclear factor-kappa B (NF-κB) P65, degradation and phosphorylation of IκBα, phosphorylation of IκKα/ß, c-Jun N-terminal kinase (JNK), and P38, and activation of COX-2, thereby exerting the anti-inflammatory effects.

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PMID: 

Toxicol Lett. 2020 Jan 18. Epub 2020 Jan 18. PMID: 31962155

Abstract Title: 

N-acetyl cysteine protects against chlorine-induced tissue damage in an ex vivo model.

Abstract: 

High-level concentrations of chlorine (Cl) can cause life-threatening lung injuries and the objective in this study was to understand the pathogenesis of short-term sequelae of Cl-induced lung injury and to evaluate whether pre-treatment with the antioxidant N-acetyl cysteine (NAC) could counteract these injuries using Cl-exposed precision-cut lung slices (PCLS). The lungs of Sprague-Dawley rats were filled with agarose solution and cut into 250 µm-thick slices that were exposed to Cl(20-600 ppm) and incubated for 30 min. The tissue slices were pre-treated with NAC (5-25 mM) before exposure to Cl. Toxicological responses were analyzed after 5 h by measurement of LDH, WST-1 and inflammatory mediators (IL-1β, IL-6 and CINC-1) in medium or lung tissue homogenate. Exposure to Clinduced a concentration-dependent cytotoxicity (LDH/WST-1) and IL-1β release in medium. Similar cytokine response was detected in tissue homogenate. Contraction of larger airways was measured using electric-field-stimulation method, 200 ppm and control slices had similar contraction level (39 ± 5%) but in the 400 ppm Clgroup, the evoked contraction was smaller (7 ± 3%) possibly due to tissue damage. NAC-treatment improved cell viability and reduced tissue damage and the contraction was similar to control levels (50 ± 11%) in the NAC treated Cl-exposed slices. In conclusion, Clinduced a concentration-dependent lung tissue damage that was effectively prevented with pre-treatment with NAC. There is a great need to improve the medical treatment of acute lung injury and this PCLS method offers a way to identify and to test new concepts of treatment of Cl-induced lung injuries.

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PMID: 

Neurochem Int. 2020 Jan ;132:104605. Epub 2019 Nov 18. PMID: 31751620

Abstract Title: 

N-acetyl cysteine ameliorates depression-induced cognitive deficits by restoring the volumes of hippocampal subfields and associated neurochemical changes.

Abstract: 

Depression is highly comorbid with anxiety disorders and associated with profound cognitive impairment. Moreover, cognitive deficits associated with hippocampal dysfunction are central in depression and anxiety disorders. Furthermore, depression is accompanied by glutamatergic dysfunction which can further impair the functioning of the hippocampus. Recent studies have shown that N-acetyl cysteine (NAC), a glutamate modulator produces an antidepressant-like effect by normalization of the periterminal release of glutamate and/or antioxidant effects. However, the effects of repeated NAC treatment on depression-induced anxiety, cognitive deficits, and associated neurochemical and structural alterations are relatively unknown. Accordingly, we investigated whether chronic NAC treatment could reverse cognitive deficits, and associated hippocampal volume loss and monoaminergic alterations in the neonatal clomipramine (CLI) model of depression. We found that chronic NAC treatment produces antidepressive and antianhedonic-like effects. NAC treatment also reversed CLI-induced anxiety. Interestingly, repeated NAC treatment improved the performance of CLI rats in rewarded alternation task in T-maze. The antidepressive-like and procognitive effects of NAC was associated with normalization of volume loss in CA1, dentate gyrus (DG) and hilar subfields of the hippocampus. Furthermore, NAC restored CLI-induced decrease in levels of monoamines and normalized enhanced metabolism in the hippocampus. Taken together, chronic NAC treatment ameliorates depressive and anxiety-like behavior, spatial learning deficits, and reverses CLI-induced pathological alterations at structural and neurochemical levels in the hippocampus. Our findings might help in evolving NAC as a viable pharmacotherapy for reversal of cognitive deficits in depression and associated disorders.

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PMID: 

J Nutr Biochem. 2018 07 ;57:67-76. Epub 2018 Mar 16. PMID: 29677563

Abstract Title: 

Polysaccharide of Hericium erinaceus attenuates colitis in C57BL/6 mice via regulation of oxidative stress, inflammation-related signaling pathways and modulating the composition of the gut microbiota.

Abstract: 

Inflammatory bowel disease (IBD) is a disease caused by a dysregulated immune with unknown etiology. Hericium erinaceus (H. erinaceus) is a Chinese medicinal fungus, with the effect of prevention and treatment of gastrointestinal disorders. In this study, we have tested the anti-inflammatory effect of polysaccharide of H. erinaceus (HECP, Mw: 86.67 kDa) in the model of dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. Our data indicated that HECP could improve clinical symptoms and down-regulate key markers of oxidative stresses, including nitric oxide (NO), malondialdehyde (MDA), total superoxide dismutase (T-SOD), and myeloperoxidase (MPO). HECP also suppressed the secretion of interleukin (IL)-6, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and decreased the expression of related mRNA. Meanwhile, HECP blocked phosphorylation of nuclear factor-κB (NF-κB) p65, NF-κB inhibitor alpha (IκB-α), mitogen-activated protein kinases (MAPK) and Protein kinase B (Akt) in DSS-treated mice. Moreover, HECP reversed DSS-induced gut dysbiosis and maintained intestinal barrier integrity. In conclusion, HECP ameliorates DSS-induced intestinal injury in mice, which suggests that HECP can serve as a protective dietary nutrientagainst IBD.

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PMID: 

Neurol Res. 2019 Mar ;41(3):265-274. Epub 2018 Dec 20. PMID: 30570422

Abstract Title: 

Regenerative activity of Hericium erinaceus on axonal injury model using in vitro laser microdissection technique.

Abstract: 

OBJECTIVE: Peripheral nerve injury (PNI) is an important global health problem. Nerve Growth Factor (NGF) plays crucial role in the survival, growth, and maintenance of various neurons in the mammalian nervous system, human included. Hericium erinaceus (HE), an edible and medicinal mushroom, has been extensively studied for its neuroprotective properties. In this study, the neuroprotective and neurotogenic effects of HE and NGF were compared on mouse PNI model by using a laser microdissection technique.METHODS: Neuronal cultures were prepared from dorsal root ganglia (DRG) of 6-8 week aged mice, pretreated them with phosphate-buffered saline (PBS), NGF, HE, or the combination of NGF and HE. To model axonal injury in vitro, axons were cut (axotomy) with a microscope-controlled laser beam. Axotomized neurons were imaged under the microscope. Axotomized neurons' survival ratios were calculated using the propidium iodide (PI), which is a red-fluorescent nuclear dye. Their axon lengths were measured using the AxioVision 4.8 software.RESULTS: Although both HE and NGF have neuroprotective and regenerative effects on axotomized peripheral sensory neurons, HE exhibits a higher neuroprotective activity compared to the NGF. The combination of HE and NGF maximizes axonal regeneration ability of axotomized neurons.CONCLUSION: HE has capabilities of preventing the death of neurons and regenerating their axons in the experimental axonal injury model. Our findings provide experimental evidence that HE may serve as a neuroprotective and regenerative candidate for treating peripheral nerve injuries. Present study warrants further investigation of HE as a potential natural compound to remedy PNI.

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PMID: 

Biomed Res. 2019 ;40(4):125-131. PMID: 31413233

Abstract Title: 

Improvement of cognitive functions by oral intake of Hericium erinaceus.

Abstract: 

Hericium erinaceus has been recognized as medical mushroom since ancient time, but its scientific evidence for human health has been still uncertain. In this study, we tested a randomized, double-blind, placebo-controlled parallel-group comparative study to evaluate the improvement of the cognitive functions by taking supplements containing fruiting body of H. erinaceus for 12 weeks. We performed three kinds of tests: Mini Mental State Examination (MMSE), Benton visual retention test, and Standard verbal paired-associate learning test (S-PA). MMSE alone showed that oral intake of H. erinaceus significantly improved cognitive functions and prevented from the deterioration. We speculate that various chemical compounds, including hericenones, in the mushroom have multiple effects to the brain neural networks and improve cognitive functions. Oral intake of H.erinaceus is safe and convenient method for dementia prevention so far.

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PMID: 

Int J Biol Macromol. 2019 Nov 20. Epub 2019 Nov 20. PMID: 31759012

Abstract Title: 

A novel Hericium erinaceus polysaccharide: Structural characterization and prevention of HO-induced oxidative damage in GES-1 cells.

Abstract: 

In this paper, the structural characteristics and bioactivity of a novel polysaccharide from H. erinaceus (HEP) were investigated, wherein, physico-chemical characterization demonstrated that HEPwith an average molecular weight of 12.713 kDa was composed of mannose (5.13%), glucose (43.02%), and galactose (51.85%). The models in vitro for preventing oxidative damage of human gastric epithelium (GES-1) cells were established and used to investigate the preventive effects of HEPfrom oxidative damage. It was found that HEPcould significantly prevent GES-1 cells against HO-induced oxidative damage by promoting cell proliferation, inhibiting cell necrosis, reducing ROS levels, regulating mitochondrial membrane potential and maintaining mitochondrial membrane permeability. These results indicated HEPcan effectively prevent gastric cell damage in vitro and suggested the potential application of HEPas bioactive ingredient for healthy foods.

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PMID: 

Int J Biol Macromol. 2019 Nov 20. Epub 2019 Nov 20. PMID: 31759000

Abstract Title: 

Characterization of polysaccharides isolated from Hericium erinaceus and their protective effects on the DON-induced oxidative stress.

Abstract: 

In this study, the structure characteristic of the Hericium erinaceus polysaccharide (HEP) was investigated using Fourier transformed infrared spectrometry (FT-IR), gas chromatography-mass spectrometry (GC-MS), gel permeation chromatography (GPC), methylation and nuclear magnetic resonance (NMR). The results showed that HEP, with a molecular weight of 43 KDa, was mainly composed of glucose and rhamnose. The linkages of the sugar residues of HEP were → 6) β-d-Glcp-(1 → and → 2) -α-l-Rhap-(1 → residue at the end of the branches. The Fusarium toxin deoxynivalenol (DON)-induced cellular injury model for IPEC-J2 cells was established and used to investigate the protective effects of HEP against the oxidative stress. The results suggest that HEP could significantly protect IPEC-J2 cells from DON-induced oxidative stress, inhibit DON-induced apoptosis and reduce the production of reactive oxygen species (ROS). Overall, this study suggested that HEP could be explored as potential antioxidant agents for DON-induced intestinal mucosa injury.

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