Context: Quercetin (QCT) has been known as a potential therapeutic strategy for gastrointestinal diseases because it contributes to the stabilization of mast cells, the prevention of histamine release and modulation of CaCC chloride channel.Objective: We investigated the laxative effect and action mechanism of QCT in Lop-induced constipation model.Materials and methods: Constipation of SD rats was induced by subcutaneous injection of loperamide (Lop) (4 mg/kg weight) in 0.5% Tween 20 twice a day for three days. After 24 h, the constipation group was further treated with 1× PBS (Lop + Vehicle treated group), 10 mg/kg of QCT (Lop + LQCT treated group), 20 mg/kg of QCT (Lop + MQCT treated group) or 40 mg/kg QCT (Lop + HQCT treated group) at once. At 24 h after QCT treatment, the constipation phenotypes were measured and the transverse colon was collected from SD rats.Results: The gastrointestinal motility, the number of stools and histological structures were significantly recovered in Lop + QCT treated group compared with the Lop + Vehicle treated group. Also, above activity of epithelial cells and smooth muscle cells were regulated by the mRNA expression of the muscarinic acetylcholine receptors M2 and M3 (mAChR M2 and M3) and some mediators of their downstream signalling pathway. Finally, laxative effects of QCT on mAChR signalling pathway were significantly inhibited by the treatment of mAChR antagonist in primary smooth muscle of rat intestine cells (pRISMCs).Conclusions: This study provides the first strong evidence that QCT can be considered an important candidate for improving chronic constipation induced by Lop treatment in animal models.

Background Although constipation has been researched in various neurological disorders, including Parkinson’s disease (PD) and spinal cord injury (SCI), the pathological mechanism of this symptom has not been investigated in Alzheimer’s disease (AD) associated with loss of nerve cells in the brain. This study was undertaken to gain scientific evidences for a molecular correlation between constipation and AD. Methods To understand the etiology, we measured alterations in various constipation parameters, muscarinic acetylcholine receptors (mAChRs) and endoplasmic reticulum (ER) stress response, in 11-month-old Tg2576 transgenic (Tg) mice showing AD-like phenotypes. Results A high accumulation of amyloid beta (Aβ) peptides, a key marker of AD pathology, were detected in the cortex and hippocampus of Tg mice. Furthermore, significant alterations were observed in various constipation parameters including stool weight, histological structure, cytological structure and mucin secretion in Tg2576 mice. Moreover, M2 and M3 expression and the downstream signaling pathways of mAChRs were decreased in the Tg group, as compared with non-Tg (NT) group. Furthermore, activation of ER stress proteins and alteration of ER structure were also detected in the same group. Conclusions The results of the present study provide strong novel evidence that the neuropathological constipation detected in Tg2576 mice is linked to dysregulation of the mAChR signaling pathways and ER stress response.

The therapeutic effects of mulberry ( Morus alba ) leaves on lipid metabolism, including lipogenesis, lipolysis and hyperlipidemia are widely known, although their fermented products are yet to be applied. To investigate the therapeutic effects of a novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) on lipid metabolism, the lipid profile of serum, lipid accumulation, lipolytic activity and lipogenesis regulation were measured in high fat diet (HFD)-induced obese C57BL/6 mice treated with EMfC for 12 weeks. Briefly, the concentrations of low-density lipoprotein, triglyceride, total cholesterol and glucose significantly decreased in the serum of the HFD+EMfC treated group when compared with the HFD+Vehicle treated group, while the levels of high-density lipoprotein increased in the HFD+EMfC group. The amount of abdominal fat and the size of adipocytes were significantly lower in the HFD+EMfC treated group when compared with the HFD+Vehicle treated group. The weight and number of lipid droplets of liver tissue exhibited a similar decrease. Furthermore, the mRNA levels of peroxisome proliferator-activated receptor-γ for adipogenesis as well as adipocyte protein 2 and Fas cell surface death receptor for lipogenesis reduced following EMfC treatment for 12 weeks. Phosphorylation of perilipin and hormone-sensitive lipase, and in the adipose triglyceride lipase expression showed a significant increase in the HFD+EMfC treated group. These results indicated that EMfC may prevent fat accumulation in the HFD-induced obese C57BL/6 mice through the inhibition of lipogenesis and by stimulating lipolysis. Thus, the results provide evidence for the potential use of EMfC as an anti-obesity complex in the treatment of obesity.

Introduction: Roots of Asparagus cochinchinensis, which have pharmacologically active ingredients, have received great attention because they show good therapeutic effects for various inflammatory diseases without specific toxicity. This study investigated the anti-asthmatic effects of a butanol extract of Asparagus cochinchinensis roots that had been fermented with Weissella cibaria (BAW) and its possible underlying cholinergic regulation. Methods: Alterations of the anti-asthmatic markers and the molecular response factors were measured in an ovalbumin (OVA)-induced asthma model after treatment with BAW. Results: Treatment with BAW decreased the intracellular reactive oxygen species (ROS) production in lipopolysaccharides (LPS) activated RAW264.7 cells. The results of the animal experiments revealed lower infiltration of inflammatory cells and bronchial thickness, and a significant reduction in the number of macrophages and eosinophils, concentration of OVA-specific IgE, and expression of Th2 cytokines in the OVA + BAW treated group. In addition, a significant recovery of goblet cell hyperplasia, MMP-9 expression, and the VEGF signaling pathway was observed upon airway remodeling in the OVA + BAW treated group. Furthermore, these responses of BAW were linked to recovery of acetylcholine esterase (AChE) activity and muscarinic acetylcholine receptor (mAChR) M3 downstream signaling pathway in epithelial cells, smooth muscle cells, and afferent sensory nerves of OVA + BAW-treated mice. Conclusion: Overall, these findings are the first to provide evidence that the therapeutic effects of BAW can prevent airway inflammation and remodeling through the recovery of cholinergic regulation in structural cells and inflammatory cells of the chronic asthma model.

Background A novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) is reported to exert anti-obesity activity, although their molecular mechanism during hepatic steatosis has not verified. Methods To investigate the role of inflammation and autophagy during the anti-hepatic steatosis effects of EMfC, we measured alterations in the key parameters for inflammatory response and autophagy pathway in liver tissues of the high fat diet (HFD) treated C57BL/6N mice after exposure to EMfC for 12 weeks. Results Significant anti-hepatic steatosis effects, including decreased number of lipid droplets and expression of Klf2 mRNA, were detected in the liver of the HFD + EMfC treated group. The levels of mast cell infiltration, expression of two inflammatory mediators (iNOS and COX-2), and the MAPK signaling pathway were remarkably decreased in the liver of HFD + EMfC treated group as compared to the HFD + Vehicle treated group. Furthermore, a similar inhibitory effect was measured for the expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and NF-κB. The expression level of members in the AKT/mTOR signaling pathway (a central regulator in autophagy) was recovered after treatment with EMfC, and autophagy-related proteins (Beclin and LC3-II) were remarkably decreased in the HFD + EMfC treated group compared to the HFD + Vehicle treated group. Moreover, the HFD + EMfC treated group showed decreased transcript levels of autophagy-regulated genes including Atg4b, Atg5, Atg7 and Atg12. Conclusions Taken together, findings of the present study provide novel evidences that the anti-hepatic steatosis of EMfC is tightly linked to the regulation of the inflammatory response and autophagy pathway in the liver tissue of HFD-induced obesity mice.