Interactions between endophytic fungus Pestalotiopsis sp. DO14 and Dendrobium catenatum: Deciphering plant polysaccharide and flavonoid accumulation and underlying mechanisms by comparative transcriptome and metabolome analyses.

Dendrobium catenatum, which belongs to the Orchidaceae family, has been used as a traditional medicine and healthy food in China for over 2000 years, and is of enormous economic value. Polysaccharides and flavonoids are two major functional ingredients in D. catenatum stems that contribute to its health benefits. D. catenatum lives in close association with endophytic fungi, but the literature regarding the further relations between them, especially the fungal-induced accumulation of metabolites in the host plant, is sparse. Our previous study showed that Pestalotiopsis sp. DO14 isolated from D. catenatum improved the host plant growth and metabolite accumulation. This study was performed to investigate dynamic variations of the growth traits, key metabolites (polysaccharides and flavonoids), and expression of key genes of D. catenatum under conditions of the DO14 colonization. Colonization with DO14 promoted D. catenatum growth as indicated by increased leaf area, mid-stem thickness, and plant height. The content of polysaccharides, mannose, and sucrose increased even without DO14 entering the host cells or forming a mature symbiotic relationship concurrent with improved photosynthesis rate. Furthermore, DO14 induced upregulation of genes involved in sugar and flavonoid metabolism, especially phosphoenolpyruvate carboxykinase (PCKA), chalcone synthase (CHS) and UDP-glycose flavonoid glycosyltransferase (UFGT). These observations suggested that endophytic fungi induce the accumulation of polysaccharides and flavonoids by plants, increasing the efficiency of carbon assimilation and carbon turnover. The findings of this study provide insight into the mechanisms underlying Orchidaceae-endophyte interactions, and suggest potential novel applications of endophytic fungi in D. catenatum breeding to improved plant quality.

Angelica oil restores the intestinal barrier function by suppressing S100A8/A9 signalling in mice with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) progression is driven by the activation of immune cells that release pro-inflammatory mediators to disrupt intestinal epithelial barrier integrity. This study aimed to investigate the potential protective effects of Angelica oil (AO) on the intestinal epithelial barrier in mice with UC and the underlying mechanisms. METHODS: Improvement of the disease state and protective effect of AO on the intestinal epithelial barrier were observed in mice with dextran sulphate sodium salt (DSS)-induced UC. Protein microarrays were used to screen AO-affected cytokine pools and their recruited immune cells for accumulation in the tissues. Furthermore, quantitative proteomics was applied to search for AO-acting molecules and to verify in vitro the functions of key molecules between inflammation and the intestinal mucosal barrier. RESULTS: AO significantly alleviated intestinal inflammation, reduced intestinal permeability, and retained barrier function in mice with UC. Furthermore, cytokines inhibited by AO mainly promoted monocyte and neutrophil activation or chemotaxis. Moreover, proteomic screening revealed that S100A8/A9 was a key molecule significantly regulated by AO, and its mediated TLR4/NF-κB pathway was also inhibited. Finally, we verified that AO inhibited the activation of the S100A8/A9/TLR4 signalling pathway and enhanced the expression of tight junctions (TJs) proteins using a cellular model of intestinal barrier damage induced by S100A8/A9 or macrophage-derived medium. And the enhancement of TJs in intestinal epithelial cells and the inhibition of inflammatory signalling by AO were significantly attenuated due to the application of S100A8/A9 monoclonal antibody. CONCLUSION: These results demonstrated that AO improves intestinal mucosal barrier damage in the inflammatory environment of mice with UC by inhibiting the expression of S100A8/A9 and the activation of its downstream TLR4/NF-κB signalling pathway.

Retraction notice to "Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat" [J. Ethnopharmacol. 150 (2013) 371-381].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The authors have plagiarized/duplicated part of a paper that appeared in Neurosci Lett, 549 (2013) 63-68, (https://doi.org/10.1016/j.neulet.2013.06.002). Several images in the Journal of Ethnopharmacology paper; 3A, 3B, 4A, 4B correspond to figures; 2A, 2B, 3A and 3B respectively as published in Neuroscience Letters. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Isoliquiritigenin-mediated miR-23a-3p inhibition activates PGC-1α to alleviate alcoholic liver injury.

BACKGROUND: Alcoholic liver disease (ALD), one of the most prevalent forms of liver disease, has received wide attention worldwide. However, limited efficient and appropriate therapeutic agents were responded to ALD. Isoliquiritigenin (ISL), a flavonoid isolated from liquorice, possesses multiple pharmacological activities. PURPOSE: The current study investigated the hepatoprotective effect of ISL against ALD and further elucidate the involvement of miR-23a-3p/peroxisome proliferative activated receptor-γ coactivator 1 alpha (PGC-1α) in vivo and in vitro experiments. STUDY DESIGN AND METHODS: In the study, H&E and Oil Red O staining were employed to detect liver histopathological changes and the accumulation of lipid droplets. Quantitative real-time PCR, bioinformatics, luciferase assay, immunofluorescence staining, reactive oxygen species (ROS), Western blot, and siRNA were used to further explore the mechanism of ISL protection. RESULTS: ISL significantly reduced the liver-to-body weight ratios and biochemical index. The staining results showed that ISL remarkedly ameliorated the histopathological changes in the liver. Furthermore, ISL promoted fatty acid metabolism via induction in the expression of PGC-1α-target genes PPARα, CPT1α, and ACADs, and inhibited the ROS, TNF-α, IL-1ß, and IL-6 expression. Bioinformatics and Luciferase assay analysis confirmed that miR-23a-3p might bind to PGC-1α mRNA in ALD. Significantly, the expression of miR-23a-3p was increased in the ALD, which was significantly decreased by ISL. In addition, the miR-23a-3p inhibitor also promoted lipid metabolism in ALD via PGC-1α activation. CONCLUSIONS: We first demonstrated that ISL could alleviate ALD, and further verified that ISL exerted protective effects through modulating miR-23a-3p/PGC-1α-mediated lipid metabolism in vivo and in vitro.

[Effects of germplasm and host tree trunk on endophytic fungal communities in epiphytic Dendrobium catenatum].

In order to investigate the effects of germplasm and host tree trunk on endophytic fungal communities in epiphytic Dendrobium catenatum, a total of 3 835 isolates were recovered from roots, stems and leaves of four D. catenatum germplasms attached to one kind of host tree trunk and one germplasm attached to four kinds of epiphyte-host tree trunks. A total of 152 taxa were identified and classified based on the fungal cultural characteristics and phylogenetic analyses of ITS sequences. The taxa were assigned to 60 genera, 35 families, 21 orders and 5 classes of 2 phyla. The results indicated that D. catenatum cultivated in stereo cultivation harbor variety of fungi. The dominant fungal groups were different between Lin'an and Yiwu. Moreover, several groups showed geographical specificity, such as Arthrinium, Coniochaeta, Fusarium, Neofusicoccum and Zopfiella only dominating in Panshan of Lin'an, while Alternaria, Bjerkandera, Cercophora, Nigrospora and Trichoderma only dominating in Shangxi of Yiwu. There was no significant difference in diversity or species richness of endophytic fungi neither among germplasm nor host tree trunk. However, the richness and diversity indices exhibited a strong dependence on tissue type (P<0.05). The germplasm and host tree trunk impact the distribution patterns of endophytic fungi less than tissue type. Nevertheless, the relative frequencies of the dominant fungal groups were different among germplasms or host tree trunk types. Furthermore, there were some fungal species specific to certain germplasm or host tree trunk. This might be due to the distinctions in growth traits and chemical compositions of D. catenatum owning to the differences in D. catenatumgenetic background and microenvironment of host tree. Most of fungal taxa exhibit tissue specificity or preference. These results provide the basis for the study on the relationship between endophytic fungi and D. catenatum in stereo cultivation mode.

Ginseng improves cognitive deficit via the RAGE/NF-κB pathway in advanced glycation end product-induced rats.

BACKGROUND: Ginseng, the root of Panax ginseng (PG), is used widely as a herbal medicine to prevent and treat various diseases. Panax ginseng has pharmacological effects on neurodegenerative diseases such as Alzheimer's disease (AD). The present study evaluated the neuroprotective effects of PG and its possible neuroprotective mechanisms in advanced glycation end product (AGE)-induced AD in a rat model. METHODS: Advanced glycation end products were injected bilaterally into the CA3 region of the rats' brains. The Morris water maze test and step-down type passive avoidance test were performed to evaluate their memory and cognitive abilities. The oxidation indexes in the hippocampus were detected. Immunohistochemistry was conducted to visualize the receptors for advanced glycation end products (RAGEs) and nuclear factor-kappa-light-chain-enhancer of activated B cell (NF-κB). RESULTS: Behavioral results showed that PG (1 g/kg, 0.5 g/kg, and 0.25 g/kg) significantly shortened the escape latency, remarkably increased the number of crossing times, significantly decreased the number of errors, and prolonged the latency in rats with AGE-induced AD. Panax ginseng also significantly reduced the malondialdehyde level, increased the glutathione content, and increased superoxide dismutase activity in the hippocampus. Panax ginseng significantly decreased the expression of RAGE and NF-κB. The blockade of anti-RAGE antibody could significantly reduce AGE-induced impairments and regulate these expressions. CONCLUSION: Our results demonstrated that PG significantly inhibits AGE-induced memory impairment and attenuates Alzheimer-like pathophysiological changes. These neuroprotective effects of PG may be associated with the RAGE/NF-κB pathway. Our results provided the experimental basis for applying PG in preventing and treating AD.

Antidepressant-like effect of essential oil of Perilla frutescens in a chronic, unpredictable, mild stress-induced depression model mice.

Perilla frutescens (Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens (EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress (CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF (3, 6, and 9 mg·kg(-1)) and a positive control drug fluoxetine (20 mg·kg(-1)) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3(rd) week. Open-field test, sucrose consumption test, tail suspension test (TST), and forced swimming test (FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in mouse hippocampus were determined by HPLC-ECD. Serum interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α levels were evaluated by enzyme-linked immunosorbent assay (ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1ß, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1ß, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of serotonergic responses and anti-inflammatory effects.

Qifu-Yin attenuates AGEs-induced Alzheimer-like pathophysiological changes through the RAGE/NF-κB pathway.

Qifu-Yin (QFY), a widely used formula of traditional Chinese medicine (TCM) derived from "Jingyue Quanshu", is one of the most commonly used TCM prescriptions for the clinical treatment of Alzheimer disease. The role of advanced glycation end products (AGEs) and its receptor RAGE have attracted increasing attention as the pivotal role of Aß has been questioned. The present study was designed to test the neuroprotective effects of QFY, and the possible mechanism in AGE-induced Alzheimer model rats. After injection of AGE in the CA3 area of the hippocampus, QFY (8.6, 4.3, and 2.15 g·kg(-1)), and a positive control drug donepezil (2 mg·kg(-1)) were administrated through gastric intubation to rats once daily for thirty consecutive days. Another positive control group was the AGE + anti-RAGE group, which was simultaneously injected with anti-RAGE antibody before AGE treatment. The control group, sham-operated group, as well as the AGE + anti-RAGE group received saline at the same dosage. The Morris water maze test and the step-down passive avoidance test were conducted to evaluate the cognitive function of the rats. The expression of RAGE and NF-κB were assayed by immunohistochemical staining. The levels of Aß, TNF-α, and IL-1ß in the hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that QFY could significantly attenuate the memory impairment induced by AGE, decrease the expressions of RAGE and NF-κB, and reduce the levels of Aß, TNF-α, and IL-1ß in the hippocampus in a dose-dependent manner. Also, the blockage of RAGE could significantly reduce the impairments caused by AGEs. In conclusion, QFY could attenuate AGEs-induced, Alzheimer-like pathophysiological changes. These neuroprotective effects might be related to the RAGE/NF-κB pathway and its anti-inflammatory activity.

Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang decoction (LWDHD) is a well-known prescription of traditional Chinese medicine (TCM) and consists of six crude drugs including Rehmannia glutinosa Libosch. (family: Scrophulariaceae), Cornus officinalis Sieb. (family: Cornaceae), Dioscorea oppositifolia L. (family: Dioscoreaceae), Paoenia ostii (family: Paeoniaceae), Alisma orientale (G. Samuelsson) Juz (family: Alismataceae) and Poria cocos (Schw.) Wolf (family: Polyporaceae). It has been used for the treatment of "Kidney-Yin" deficiency syndrome in clinic in China for a long time. Recent studies found that LWDHD had a potential benefit for the treatment of diabetic complications. The aim of the present study is to investigate the neuroprotective effect of LWDHD on memory and cognition deficits in streptozotocin (STZ)-induced diabetic encephalopathy (DE) rats. MATERIALS AND METHODS: Adult male Sprague Dawley (SD) rats were fed with high-glucose-fat diet for 50 days and then received an intraperitoneal injection of STZ (40 mg/kg) to induce DE model. Morris water maze test was used to evaluate the memory and cognition capability of DE rats. Choline acetyltransferase (ChAT), acetylcholinesterase (AChE), Na(+)-K(+)-ATP enzyme, iNOS and GSH kits were used to determine their activities or content in hippocampus. TUNEL staining, immunohistochemistry and Congo red staining were conducted to evaluate the apoptosis, caspase-3 protein expression, insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) expressions, as well as Aß deposition. RESULTS: The treatment with LWDHD (1 and 2g/kg, p.o., once daily, 30 days) could significantly reduce the escape latency time and path length, and obviously enhance the spent time in the target quadrant and platform crossings in Morris water maze test compared with model group (P<0.05, P<0.01). LWDHD could also significantly decrease the level of fasting blood glucose, increase Na(+)-K(+)-ATP enzyme and ChAT activities, enhance remarkedly GSH level while decrease significantly AChE and iNOS activities in hippocampus (P<0.05, P<0.01). Furthermore, TUNEL staining, Congo red staining and immunohistochemistry showed that LWDHD significantly improved the expressions of IGF-1 and BDNF, attenuated the neural apoptosis, overexpression of caspase-3 and Aß deposition in the hippocampus and cerebral cortex of STZ-induced DE rats (P<0.01). CONCLUSION: Our findings suggested that LWDHD had a neuroprotective effect on DE rats. LWDHD may be of benefit in the treatment of DE.

Hypoglycemic and antioxidant activities of paeonol and its beneficial effect on diabetic encephalopathy in streptozotocin-induced diabetic rats.

Diabetic encephalopathy (DE) is one of the severe complications in patients with diabetes mellitus. Paeonol, an active compound isolated from the root bark of Paeonia suffruticosa, has significant antidiabetic activity in vivo. However, its underlying beneficial effects on DE were unclear. In the present study, the protective activity of paeonol on DE was evaluated in streptozotocin (STZ)-induced diabetic rats. Paeonol at 50 and 100 mg/kg significantly increased body weight and decreased blood glucose levels, glycosylated serum proteins, and serum advanced glycation end products (AGEs) levels. Immunohistochemistry assays and Western blot analysis revealed a significant decrease in expressions on receptor for advanced glycation end products (RAGE) and nuclear factor kappa B (NF-κB) in hippocampus and cerebral cortical neurons after paeonol treatment. Furthermore, paeonol significantly increased glutathione content and remarkedly decreased induced nitric oxide synthase activity in hippocampus tissue. Our findings indicated that paeonol could improve the pathological damage of DE in STZ-induced diabetic rats. It might be associated with the modulating AGEs/RAGE/NF-κB pathway. This study suggested that paeonol might be a promising candidate for the prevention and treatment of DE.