Differentiation of bone marrow mesenchymal stem cells into Leydig-like cells with testicular extract liquid in vitro.

Differentiation of Leydig cells plays a key role in male reproductive function. Bone marrow mesenchymal stem cells (BMSCs) have emerged as a potential cell source for generating Leydig-like cells due to their multipotent differentiation capacity and accessibility. This study aimed to investigate the morphological and genetic expression changes of BMSCs during differentiation into Leydig-like cells. Testicular extract liquid, which simulates the microenvironment in vivo, induced the third passage BMSCs differentiated into Leydig-like cells. Changes in cell morphology were observed by microscopy, the formation of lipid droplets of androgen precursor was identified by Oil Red Staining, and the expression of testicular specific genes 3ß-HSD and SF-1 in testicular stromal cells was detected by RT-qPCR. BMSCs isolated from the bone marrow of Sprague-Dawley (SD) rats were cultured for 3 generations and identified as qualified BMSCs in terms of morphology and cell surface markers. After 14 days of induction with testicular tissue lysate, lipid droplets appeared in the cytoplasm of P3 BMSCs by Oil Red O staining. RT-qPCR detection was performed on BMSCs on the 3rd, 7th, 14th, and 21st day after induction. Relative expression levels of 3ß-HSD mRNA significantly increased after 14 days of induction, while the relative expression of SF-1 mRNA increased after 14 days of induction but was not significant. BMSCs can differentiate into testicular interstitial cells with reserve androgen precursor lipid droplets after induction by testicular tissue lysate. The differentiation ability of BMSCs provides the potential to reconstruct the testicular microenvironment and is expected to fundamentally improve testicular function and provide new treatment options for abnormal spermatogenesis diseases.

Ginsenoside Rg1 relieves rat intervertebral disc degeneration and inhibits IL-1ß-induced nucleus pulposus cell apoptosis and inflammation via NF-κB signaling pathway.

The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1ß-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1). The pathological change was observed by HE and safranin O-fast green staining. The expression of IL-1ß, IL-6, TNF-α, MMP3, aggrecan, and collagen II was detected. The expression of NF-κB p65 in IVD tissues was detected. Rat NP cells were induced by IL-1ß to simulate IVDD environment and divided into the control group, IL-1ß group, and 20, 50, and 100 µmol/L Rg1 groups. The cell proliferation activity, the apoptosis, and the expression of IL-6, TNF-α, MMP3, aggrecan, collagen II, and NF-κB pathway-related protein were detected. In IVDD rats, ginsenoside Rg1 improved the pathology of IVD tissues; suppressed the expression of IL-1ß, IL-6, TNF-α, aggrecan, and collagen II; and inhibited the expression of p-p65/p65 and nuclear translocation of p65, to alleviate the IVDD progression. In the IL-1ß-induced NP cells, ginsenoside Rg1 also improved the cell proliferation and inhibited the apoptosis and the expression of IL-6, TNF-α, aggrecan, collagen II, p-p65/p65, and IκK in a dose-dependent manner. Ginsenoside Rg1 alleviated IVDD in rats and inhibited apoptosis, inflammatory response, and ECM degradation in IL-1ß-induced NP cells. And Rg1 may exert its effect via inhibiting the activation of NF-κB signaling pathway.

Gentianella acuta improves TAC-induced cardiac remodelling by regulating the Notch and PI3K/Akt/FOXO1/3 pathways.

Cardiac remodelling mainly manifests as excessive myocardial hypertrophy and fibrosis, which are associated with heart failure. Gentianella acuta (G. acuta) is reportedly effective in cardiac protection; however, the mechanism by which it protects against cardiac remodelling is not fully understood. Here, we discuss the effects and mechanisms of G. acuta in transverse aortic constriction (TAC)-induced cardiac remodelling in rats. Cardiac function was analysed using echocardiography and electrocardiography. Haematoxylin and eosin, Masson's trichrome, and wheat germ agglutinin staining were used to observe pathophysiological changes. Additionally, real-time quantitative reverse transcription polymerase chain reaction and western blotting were used to measure protein levels and mRNA levels of genes related to myocardial hypertrophy and fibrosis. Immunofluorescence double staining was used to investigate the co-expression of endothelial and interstitial markers. Western blotting was used to estimate the expression and phosphorylation levels of the regulatory proteins involved in autophagy and endothelial-mesenchymal transition (EndMT). The results showed that G. acuta alleviated cardiac dysfunction and remodelling. The elevated levels of myocardial hypertrophy and fibrosis markers, induced by TAC, decreased significantly after G. acuta intervention. G. acuta decreased the expression of LC3 II and Beclin1, and increased p62 expression. G. acuta upregulated the expression of CD31 and vascular endothelial-cadherin, and prevented the expression of α-smooth muscle actin and vimentin. Furthermore, G. acuta inhibited the PI3K/Akt/FOXO1/3a pathway and activated the Notch signalling. These findings demonstrated that G. acuta has cardioprotective effects, such as alleviating myocardial fibrosis, inhibiting hypertrophy, reducing autophagy, and blocking EndMT by regulating the PI3K/Akt/FOXO1/3a and Notch signalling pathways.

Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome.

CONTEXT: The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear. OBJECTIVE: To assess the characteristics of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS. SETTING AND DESIGN: The intestinal flora of treatment-naïve PCOS patients and hormonally healthy controls was analyzed. Phenotype analysis, intestinal flora analysis, and global metabolomic profiling of caecal contents were performed on a letrozole-induced PCOS mouse model; similar analyses were conducted after 35 days of antibiotic treatment on the PCOS mouse model, and glucose tolerance testing was performed on the PCOS mouse model after a 35-day CDCA treatment. Mice receiving fecal microbiota transplants from PCOS patients or healthy controls were evaluated after 10 weeks. RESULTS: Bacteroides was significantly enriched in treatment-naïve PCOS patients. The enrichment in Bacteroides was reproduced in the PCOS mouse model. Gut microbiota removal ameliorated the PCOS phenotype and insulin resistance and increased relative FXR mRNA levels in the ileum and serum fibroblast growth factor 15 levels. PCOS stool-transplanted mice exhibited insulin resistance at 10 weeks but not PCOS. Treating the PCOS mouse model with CDCA improved glucose metabolism. CONCLUSIONS: Bacteroides is a key microbial biomarker in PCOS and shows diagnostic value. Gut dysbiosis can cause insulin resistance. FXR activation might play a beneficial rather than detrimental role in glucose metabolism in PCOS.

Superparamagnetic iron oxide nanoparticles conjugated with Aß oligomer-specific scFv antibody and class A scavenger receptor activator show therapeutic potentials for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. No disease-modifying strategy to prevent or delay AD progression currently exists. Aß oligomers (AßOs), rather than monomers or fibrils, are considered as the primary neurotoxic species. Therapeutic approaches that direct against AßOs and promote Aß clearance may have great value for AD treatment. RESULTS: We here reported a multifunctional superparamagnetic iron oxide nanoparticle conjugated with Aß oligomer-specific scFv antibody W20 and class A scavenger receptor activator XD4 (W20/XD4-SPIONs). Besides the diagnostic value, W20/XD4-SPIONs retained the anti-Aß properties of W20 and XD4 by inhibiting Aß aggregation, attenuating AßO-induced cytotoxicity and increasing microglial phagocytosis of Aß. When applied to APP/PS1 mice, W20/XD4-SPIONs significantly rescued cognitive deficits and alleviated neuropathology of AD mice. CONCLUSION: These results suggest that W20/XD4-SPIONs show therapeutic benefits for AD. In combination with the early diagnostic property, W20/XD4-SPIONs present as a promising agent for early-stage AD diagnosis and intervention.

miR-30a inhibits breast cancer progression through the Wnt/ß-catenin pathway.

BACKGROUND: miR-30a is a microRNA associated with the progression of malignant tumors such as gastric cancer, colon cancer, prostate cancer, and lung cancer, and can regulate the proliferation and migration of breast cancer (BC) cells in vitro. However, its expression, function, clinical significance and relationship with the Wnt/ß-catenin pathway in human BC were still unclear. METHODS: Immunohistochemistry, Western blotting and real-time quantitative PCR (RT-qPCR) were used to measure the expressions of miR-30a and ß-catenin in 114 pairs of human BC tumor tissues and adjacent normal tissues which were collected from March 2014 to October 2015. The effect of miR-30a on the expression of ß-catenin was studied in the MCF-7 cells in vitro. RESULTS: The expression levels of miR-30a in human BC tumor tissues were significantly lower than they were in the adjacent normal tissues (P < 0.001), and significantly higher in ß-catenin protein (P < 0.001), but there was no significant different in ß-catenin mRNA (P = 0.3816). The immunohistochemistry results showed that ß-catenin protein was only expressed on the cell membrane in paracancerous normal tissues, but ß-catenin protein was expressed on the cell membrane and cytoplasm in BC tumor cells. In addition, there was a significantly negative correlation (r = -0.816, P < 0.001) between the expression miR-30a and ß-catenin protein in BC tissues. The age of onset, PR expression, ER expression, and HER-2 expression of the BC patients were not related to miR-30a or ß-catenin protein expression (P > 0.05). Tumor diameter, histological grade, lymph node metastasis, TNM stage, and the prognosis of BC patients (P < 0.05) were significantly related to miR-30a or ß-catenin protein expression. In MCF-7 cells, miR-30a regulated the accumulation of ß-catenin protein by inhibiting the expression of BCL9 in BC cells. CONCLUSION: miR-30a was lowly expressed in breast cancer tissues and highly in ß-catenin protein, and miR-30a might block the Wnt/ß-catenin pathway by inhibiting the accumulation of ß-catenin, and then inhibiting breast cancer progression.

Inhibition of epithelial­mesenchymal transition in gastric cancer cells by miR­711­mediated downregulation of CD44 expression.

Gastric cancer is a common malignancy worldwide. The prognosis of early stage gastric cancer patients has significantly improved in recent years. However, in progressive stage gastric cancer patients, the prognosis remains relatively poor due to tumor metastases. In our previous study, we showed that the expression of miR­711 in gastric cancer tissues is low, and restoration of miR­711 inhibited the invasion and migration and the occurrence of epithelial­mesenchymal transition (EMT) in gastric cancer cells. Yet, the mechanisms involved in these processes remain unknown. In the present study, we demonstrated that miR­711­mediated downregulation of CD44 expression inhibited EMT of gastric cancer cells in vitro and in vivo by downregulating vimentin protein expression and upregulating E­cadherin protein expression through transfection, qRT­PCR and western blotting. Therefore, miR­711 may provide a promising target for EMT­related therapy for gastric cancer.

Naturally occurring autoantibodies against Aß oligomers exhibited more beneficial effects in the treatment of mouse model of Alzheimer's disease than intravenous immunoglobulin.

Alzheimer's disease (AD) is characterized by memory loss, intracellular neurofibrillary tangles, and extracellular plaque deposits composed of ß-amyloid (Aß). Previous reports showed that naturally occurring autoantibodies, such as intravenous immunoglobulin (IVIG), benefited patients with moderate-stage AD who carried an APOE-ε4 allele. However, the mechanism underlying the role of IVIG remains unclear. In this study, we identified naturally occurring autoantibodies against Aß oligomers (NAbs-Aßo), which were purified by Aß42 oligomer or Cibacron Blue affinity chromatography from IVIG and termed as Oli-NAbs and Blue-NAbs, respectively. Oli-NAbs and Blue-NAbs recognized Aß42 oligomers or both Aß40 and 42 oligomers, differently. Both antibodies inhibited Aß42 aggregation and attenuated Aß42-induced cytotoxicity. Compared with vehicles, Oli-NAbs, Blue-NAbs and IVIG significantly improved the memory and cognition, and reduced the soluble and oligomeric Aß levels in APPswe/PS1dE9 transgenic mice. Further investigation showed that Blue-NAbs at increased doses effectively decreased plaque burden and insoluble Aß levels, whereas Oli-NAbs significantly declined the microgliosis and astrogliosis, as well as the production of proinflammatory cytokines in vivo. Therefore, high levels of these antibodies against oligomeric Aß40 or Aß42 were required, correspondingly, to achieve the optimal effect. NAbs-Aßo could be condensed to a high concentration by affinity chromatography and its isolation from IVIG may not interfere with the normal function of conventional IVIG as its concentration is very low. Thus, the isolated NAbs-Aßo as an extra product of plasma required low cost and the enriched NAbs-Aßo may be more feasible than IVIG for the treatment of AD.

Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress.

Recent evidence showed that amylin deposition is not only found in the pancreas in type 2 diabetes mellitus (T2DM) patients, but also in other peripheral organs, such as kidneys, heart and brain. Circulating amylin oligomers that cross the blood-brain barrier and accumulate in the brain may be an important contributor to diabetic cerebral injury and neurodegeneration. Moreover, increasing epidemiological studies indicate that there is a significant association between T2DM and Alzheimer's disease (AD). Amylin and ß-amyloid (Aß) may share common pathophysiology and show strikingly similar neurotoxicity profiles in the brain. To explore the potential effects of rutin on AD, we here investigated the effect of rutin on amylin aggregation by thioflavin T dyeing, evaluated the effect of rutin on amylin-induced neurocytotoxicity by the MTT assay, and assessed oxidative stress, as well as the generation of nitric oxide (NO) and pro-inflammatory cytokines in neuronal cells. Our results showed that the flavonoid antioxidant rutin inhibited amylin-induced neurocytotoxicity, decreased the production of reactive oxygen species (ROS), NO, glutathione disulfide (GSSG), malondialdehyde (MDA) and pro-inflammatory cytokines TNF-α and IL-1ß, attenuated mitochondrial damage and increased the GSH/GSSG ratio. These protective effects of rutin may have resulted from its ability to inhibit amylin aggregation, enhance the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and reduce inducible nitric oxide synthase (iNOS) activity. These in vitro results indicate that rutin is a promising natural product for protecting neuronal cells from amylin-induced neurotoxicity and oxidative stress, and rutin administration could be a feasible therapeutic strategy for preventing AD development and protecting the aging brain or slowing neurodegenerative processes.

Diagnosis of malignancy of adult mediastinal tumors by conventional and transesophageal echocardiography.

BACKGROUND: Transesophageal echocardiography (TEE) is a well-established method for detecting and diagnosing heart tumors. In contrast, its role in assessing the presence, growth and evidence of malignant tumors originating from mediastinal sites remains unclear. The aim of this study was to compare the diagnostic impact of TEE and transthoracic echocardiography (TTE) for determining the localization, growth and malignancy of adult mediastinal tumors (MTs). METHODS: In a prospective and investigator-blinded study, we evaluated 144 consecutive patients with MT lesions to assess the diagnostic impact of TEE and TTE for detecting the presence of tumors spreading both inside and outside of the heart and for determining infiltration and invasion using pathological examination results as a reference. RESULTS: All tumor lesions were diagnosed and carefully evaluated by biopsy. Biopsy revealed malignant tumors in 79 patients and benign tumors in 65 patients. When compared to histological findings, TEE predicted malignancy from the presence of tumors spreading both inside and outside of the heart and from infiltration and invasion in 49/79 patients (62.0%). TTE predicted malignancy in only 8/79 patients (10.1%, P < 0.005). TEE visualized tumor lesions in 130 patients (90.3%) while the TTE visualized tumor lesions in 110 patients (76.4%) and was less effective at detecting MT lesions (P < 0.001). TTE and TEE could detect anterior MTs and adequately verified MTs (P > 0.05); TEE detected medium MTs better than TTE (P < 0.001). CONCLUSIONS: TEE is effective and superior to TTE for predicting the localization and growth of MTs as well as for accessing evidence of tumor malignancy. TTE and TEE were able to detect anterior MTs; TEE was able to detect medium MT better than TTE.

Decreasing oxidative stress and neuroinflammation with a multifunctional peptide rescues memory deficits in mice with Alzheimer disease.

Alzheimer disease (AD) is characterized by extracellular senile plaques, intracellular neurofibrillary tangles, and memory loss. Aggregated amyloid-ß (Aß), oxidative stress, and inflammation have pivotal roles in the pathogenesis of AD. Therefore, the inhibition of Aß-induced neurotoxicity, oxidative stress, and inflammation is a potential therapeutic strategy for the treatment of AD. In this study, a heptapeptide, isolated from a Ph.D.-C7C library by phage display, attenuated Aß42-induced cytotoxicity in SH-SY5Y neuroblastoma cells and reduced Aß42-induced oxidative stress by decreasing the production of reactive oxygen species and glutathione disulfide. As a result, glutathione level increased and superoxide dismutase and glutathione peroxidase activities were enhanced in vitro and in vivo. This peptide also suppressed the inflammatory response by decreasing the release of proinflammatory cytokines, such as tumor necrosis factor α and interleukin 1ß, in microglia and by reducing microgliosis and astrogliosis in AD transgenic mice. This peptide was intracerebroventricularly administered to APPswe/PS1dE9 transgenic mice. We found that this peptide significantly improved spatial memory and reduced the amyloid plaque burden and soluble and insoluble Aß levels. Our findings suggest that this multifunctional peptide has therapeutic potential for an Aß-targeted treatment of AD.

Activated scavenger receptor A promotes glial internalization of aß.

Beta-amyloid (Aß) aggregates have a pivotal role in pathological processing of Alzheimer's disease (AD). The clearance of Aß monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aß at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide XD4 activates the class A scavenger receptor (SR-A) on the glia by increasing the binding of Aß to SR-A, thereby promoting glial phagocytosis of Aß oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, XD4 enhances the internalization of Aß monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits Aß oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-α and IL-1ß, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.

Rutin improves spatial memory in Alzheimer's disease transgenic mice by reducing Aß oligomer level and attenuating oxidative stress and neuroinflammation.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular ß-amyloid (Aß) plaques and intracellular neurofibrillary tangles in the brain. Aß aggregation is closely associated with neurotoxicity, oxidative stress, and neuronal inflammation. The soluble Aß oligomers are believed to be the most neurotoxic form among all forms of Aß aggregates. We have previously reported a polyphenol compound rutin that could inhibit Aß aggregation and cytotoxicity, attenuate oxidative stress, and decrease the production of nitric oxide and proinflammatory cytokines in vitro. In the current study, we investigated the effect of rutin on APPswe/PS1dE9 transgenic mice. Results demonstrated that orally administered rutin significantly attenuated memory deficits in AD transgenic mice, decreased oligomeric Aß level, increased super oxide dismutase (SOD) activity and glutathione (GSH)/glutathione disulfide (GSSG) ratio, reduced GSSG and malondialdehyde (MDA) levels, downregulated microgliosis and astrocytosis, and decreased interleukin (IL)-1ß and IL-6 levels in the brain. These results indicated that rutin is a promising agent for AD treatment because of its antioxidant, anti-inflammatory, and reducing Aß oligomer activities.

Pan-amyloid oligomer specific scFv antibody attenuates memory deficits and brain amyloid burden in mice with Alzheimer's disease.

Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer's disease (AD), Parkinson disease (PD), Huntington's disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligomer-specific single-chain variable fragment (scFv) antibody, W20, isolated from a naïve human scFv library, can recognize oligomers assembled from α-synuclein, amylin, insulin, Aß40/42, prion peptide 106-126, and lysozyme, inhibit the aggregation of various amyloid, and attenuate amyloid oligomer-induced cytotoxicity In vitro. Furthermore, W20 recognized the amyloid oligomers in all types of plaques, Lewy bodies, and amylin deposits in the brain tissues of AD and PD patients and in the pancreas of type 2 diabetes patients. In the current study, we showed that W20 blocked the binding of Aß oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with Aß levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.

Surgical resection and amniotic membrane transplantation for treatment of refractory giant papillae in vernal keratoconjunctivitis.

PURPOSE: The aim of this study was to evaluate the outcome of surgical resection and amniotic membrane transplantation (AMT) for treatment of refractory symptomatic giant papillae in vernal keratoconjunctivitis (VKC). METHODS: This is a retrospective study of 13 eyes of 9 patients with refractory giant papillae associated with corneal shield ulcer and/or punctate epithelial erosions who underwent surgical resection of the papillae combined with AMT to cover the tarsal conjunctival defect. RESULTS: During 14.2 ± 4.2 months of postoperative follow-up, smooth tarsal conjunctival surface was achieved in all cases, with no recurrence of the giant papillae in any eye. Corneal shield ulcers and punctate epithelial erosions healed within 2 weeks after surgery and did not recur during the follow-up. Best-corrected visual acuity improved from 0.26 ± 0.21 logarithm of the minimum angle of resolution preoperatively to 0.02 ± 0.04 logarithm of the minimum angle of resolution postoperatively (P = 0.01). Three patients experienced recurrence of VKC symptoms, but without giant papillae, which could be well controlled by topical medications. CONCLUSIONS: Surgical resection combined with AMT is an effective procedure for treatment of refractory giant papillae in patients with VKC.

A peptide binding to the ß-site of APP improves spatial memory and attenuates Aß burden in Alzheimer's disease transgenic mice.

Amyloid precursor protein cleaving enzyme 1 (BACE1), an aspartyl protease, initiates processing of the amyloid precursor protein (APP) into ß-amyloid (Aß); the peptide likely contributes to development of Alzheimer's disease (AD). BACE1 is an attractive therapeutic target for AD treatment, but it exhibits other physiological activities and has many other substrates besides APP. Thus, inhibition of BACE1 function may cause adverse side effects. Here, we present a peptide, S1, isolated from a peptide library that selectively inhibits BACE1 hydrolytic activity by binding to the ß-proteolytic site on APP and Aß N-terminal. The S1 peptide significantly reduced Aß levels in vitro and in vivo and inhibited Aß cytotoxicity in SH-SY5Y cells. When applied to APPswe/PS1dE9 double transgenic mice by intracerebroventricular injection, S1 significantly improved the spatial memory as determined by the Morris Water Maze, and also attenuated their Aß burden. These results indicate that the dual-functional peptide S1 may have therapeutic potential for AD by both reducing Aß generation and inhibiting Aß cytotoxicity.

Rutin inhibits ß-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines.

Alzheimer's disease (AD) is a complex, multi-factorial neurodegenerative disease. The aggregation of soluble ß-amyloid (Aß) into fibrillar deposits is a pathological hallmark of AD. The Aß aggregate-induced neurotoxicity, inflammatory reactions, oxidative stress, and nitric oxide (NO) generation are strongly linked to the etiology of AD. Here, we show that the common dietary flavonoid, rutin, can dose-dependently inhibit Aß42 fibrillization and attenuate Aß42-induced cytotoxicity in SH-SY5Y neuroblastoma cells. Moreover, rutin decreases the formation of reactive oxygen species (ROS), NO, glutathione disulfide (GSSG), and malondialdehyde (MDA), reduces inducible nitric oxide synthase (iNOS) activity, attenuates mitochondrial damage, increases the glutathione (GSH)/GSSG ratio, enhances the activities of super oxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and modulates the production of proinflammatory cytokines by decreasing TNF-α and IL-1ß generation in microglia. Taken together, the actions of rutin on multiple pathogenic factors deserves further investigation for the prevention and treatment of AD.