morroniside and Disease-Models--Animal

We have previously reported that morroniside promoted motor activity after spinal cord injury (SCI) in rats. However, the mechanism by which morroniside induces recovery of injured spinal cord (SC) remains unknown. In the current study, RNA sequencing (RNA-seq) was employed to evaluate changes of gene expressions at the transcriptional level of the injured spinal cords in morroniside-administrated rats. Principal component analysis, analysis of enriched Gene Ontology (GO), enrichment analyses Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and other bioinformatics analyses were executed to distinguish differentially expressed genes (DEGs). The results of RNA-seq confirmed the anti-inflammatory and anti-apoptotic effects of morroniside on injured SC tissues, and provided the basis for additional research of the mechanisms involving the protective effects of morroniside on SCI.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Female; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Gene Regulatory Networks; Glycosides; Principal Component Analysis; Random Allocation; Rats; Sequence Analysis, RNA; Spinal Cord Injuries

Bone remodeling is a continuous process of bone synthesis and destruction that is regulated by osteoblasts and osteoclasts. Here, we investigated the anti-osteoporotic effects of morroniside in mouse preosteoblast MC3T3-E1 cells and mouse primary cultured osteoblasts and osteoclasts in vitro and ovariectomy (OVX)-induced mouse osteoporosis in vivo. Morroniside treatment enhanced alkaline phosphatase activity and positively stained cells via upregulation of osteoblastogenesis-associated genes in MC3T3-E1 cell lines and primary cultured osteoblasts. However, morroniside inhibited tartrate-resistant acid phosphatase activity and TRAP-stained multinucleated positive cells via downregulation of osteoclast-mediated genes in primary cultured monocytes. In the osteoporotic animal model, ovariectomized (OVX) mice were administered morroniside (2 or 10 mg/kg/day) for 12 weeks. Morroniside prevented OVX-induced bone mineral density (BMD) loss and reduced bone structural compartment loss in the micro-CT images. Taken together, morroniside promoted increased osteoblast differentiation and decreased osteoclast differentiation in cells, and consequently inhibited OVX-induced osteoporotic pathogenesis in mice. This study suggests that morroniside may be a potent therapeutic single compound for the prevention of osteoporosis.

Topics: Animals; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Cell Differentiation; Cell Line; Cell Survival; Cornus; Disease Models, Animal; Female; Glycosides; Mice; Mice, Inbred ICR; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; Phytotherapy; Plant Extracts

Osteoarthritis (OA) is a common degenerative disease that results in joint inflammation as well as pain and stiffness. A previous study has reported that

Topics: Animals; Cartilage, Articular; Chondrocytes; Cornus; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Gene Expression Regulation; Glycosides; Humans; Inflammation; Interleukin-1beta; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; Menisci, Tibial; Mice; Osteoarthritis; Plant Extracts; Primary Cell Culture; RAW 264.7 Cells; Signal Transduction

Angiogenesis is critical for re-establishing blood supply to the ischemic myocardium after acute myocardial infarction (AMI). This study aimed to investigate the effects of morroniside on angiogenesis after AMI and explored associated proangiogenic mechanisms. A rat model of AMI was established by ligation of the left anterior descending coronary artery followed by administration of three doses of morroniside. Immunofluorescence staining was performed to identify newly generated endothelial cells and arterioles. The protein expression levels associated with angiogenesis were examined by western blots. Echocardiography was used to examine cardiac function. Our data revealed that morroniside promoted angiogenesis and improved cardiac function in rats with AMI. The proangiogenic effect of morroniside might be mediated by the VEGFA/VEGF receptor 2 signaling pathway.

Topics: Administration, Oral; Animals; Coronary Vessels; Disease Models, Animal; Glycosides; Humans; Male; Myocardial Infarction; Myocardium; Neovascularization, Physiologic; Rats; Signal Transduction; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

Morroniside and loganin are iridoid glycosides extracted from Cornus officinalis, a plant species widely used in traditional Chinese medicine. However, the anti-inflammatory effects of morroniside and loganin in colitis are barely understood. The aim of the present study was to explore the effects of morroniside and loganin on the dextran sodium sulfate (DSS)-induced murine model of colitis and an LPS-induced colorectal cancer (CRC) cell inflammation model, and to clarify the underlying mechanisms. We found that morroniside and loganin were able to ameliorate clinical features, including disease activity index (DAI), histological inflammation score and periodic acid-Schiff staining (PAS). In the mouse model, morroniside and loganin treatment increased expression of tight junction proteins (TJs) and decreased pro-inflammatory cytokine production. Moreover, our findings showed that the expression of p-STAT3 and p-p65 were suppressed compared to the disease group. In in vitro experiments, treatment with morroniside and loganin had no obvious effects on proliferative activity in HCT116 cells and HIEC-6 cells. Expression of pro-inflammatory cytokines was inhibited by morroniside and loganin treatment in comparison with the LPS-treated group. Taken together, morroniside and loganin have beneficial effects on colitis in vivo and are anti-inflammatory in vitro. Possible mechanisms of the anti-inflammatory response may include blockade of the STAT3/NF-κB pathway.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Colitis; Colitis, Ulcerative; Cornus; Dextran Sulfate; Disease Models, Animal; Glycosides; Humans; Iridoid Glycosides; Iridoids; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; NF-kappa B; Phosphorylation; Signal Transduction; STAT3 Transcription Factor

Alzheimer's disease (AD), also defined as a tauopathology, is a common neurodegenerative disease. Hyper-phosphorylation, cleavage or truncation, and aggregation of tau contribute to AD. Thus, targeting the post-translational modifications on tau may be a therapeutic strategy to treat AD. This study understood how cornel iridoid glycoside (CIG) affects tau post-translational modifications and synaptic abnormalities. The 10-month old P301S tau transgenic mice were given CIG at 100 and 200 mg/kg every day orally for 1 month. Hyperphosphorylated and truncated tau, synapse-associated proteins and glutamatergic receptors were all detected using Western blotting. The interactions between Morroniside (MOR) or Loganin (LOG) and tau were detected using Autodock and Surface Plasmon Resonance (SPR). The effects of CIG on the aggregation of tau were investigated using a cell-free system. CIG attenuated tau hyperphosphorylation at Thr205, Ser212, Ser262, Thr231 and Ser235 (AT180), but had no effect on tau truncation in the brains of 10-month old P301S mice. Binding free energies and interactions revealed that MOR and LOG bound with tau. We also found that CIG upregulated synapse-associated proteins such as PSD-95, syntaxin1A and synaptotagmin. In addition, CIG restored N-methyl-D-aspartic acid receptor and glutamate receptor levels. CIG improves post-translational modification of tau as well as synaptic abnormalities. The data presented here reveal that CIG may be used in the treatment of AD.

Topics: Administration, Oral; Animals; Brain; Cell-Free System; Disease Models, Animal; Female; Glycosides; Humans; Iridoids; Male; Mice; Mice, Transgenic; Models, Molecular; Molecular Docking Simulation; Mutation; Phenotype; Protein Binding; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; tau Proteins; Tauopathies; Treatment Outcome

Preservation of cerebral microvascular functional integrity is crucial for protecting and repairing the brain after stroke. Our previous study demonstrated that morroniside promoted angiogenesis 7days after stroke. The current study aimed to further evaluate the long-term effects of morroniside on angiogenesis and to examine whether angiogenesis induced by morroniside could improve blood flow velocity. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO), and morroniside was then administered once per day at a dose of 270mg/kg. New vessel formation and the expression of ephrinB2/VEGFR2 signaling pathway components were examined 14days after MCAO to examine angiogenesis and the associated mechanisms. The dynamics of regional cerebral blood flow (rCBF) and the number of vessels of the leptomeningeal anastomoses were analyzed to characterize microvascular circulation 3days after MCAO. We demonstrated that morroniside promoted angiogenesis by regulating the ephrinB2/VEGFR2 signaling pathway 14days post-ischemia. By 3days post-ischemia, morroniside improved rCBF and increased the number of vessels of the leptomeningeal anastomoses. Moreover, morroniside decreased the infarct volume and improved neurological function 14days after MCAO. Our findings suggest that morroniside promoted long-term angiogenesis, thereby improving microvascular circulation and neurological function. It suggested that the angiogenic mechanism of morroniside might be mediated by the ephrinB2/VEGFR2 signaling pathway.

Topics: Angiogenesis Inducing Agents; Animals; Brain; Brain Ischemia; Cerebrovascular Circulation; Disease Models, Animal; Ephrin-B2; Glycosides; Male; Microvessels; Neovascularization, Physiologic; Random Allocation; Rats, Sprague-Dawley; Reperfusion Injury; Stroke; Vascular Endothelial Growth Factor Receptor-2

Despite extensive studies on the multifaceted roles of morroniside, the main active constituent of iridoid glycoside from Corni Fructus, the effect of morroniside on osteoarthritis (OA) chondrocytes remains poorly understood. Here, we investigated the influence of morroniside on cultured human OA chondrocytes and a rat experimental model of OA. The results showed that morroniside enhanced the cell viability and the levels of proliferating cell nuclear antigen expression (PCNA), type II collagen and aggrecan in human OA chondrocytes, indicating that morroniside promoted chondrocyte survival and matrix synthesis. Furthermore, different doses of morroniside activated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) in human OA chondrocytes, and in turn, triggered AKT/S6 and ERK/P70S6K/S6 pathway, respectively. The PI3K/AKT inhibitor LY294002 or the MEK/ERK inhibitor U0126 attenuated the effect of morroniside on human OA chondrocytes, indicating that the activation of AKT and ERK contributed to the regulation of morroniside in human OA chondrocytes. In addition, the intra-articular injection of morroniside elevated the level of proteoglycans in cartilage matrix and the thickness of articular cartilage in a rat experimental model of OA, with the increase of AKT and ERK activation. As a consequence, morroniside has chondroprotective effect on OA chondrocytes, and may have the therapeutic potential for OA treatment.

Topics: Aged; Animals; Arthroplasty, Replacement, Knee; Cartilage; Cell Survival; Chondrocytes; Disease Models, Animal; Enzyme Activation; Extracellular Matrix; Extracellular Signal-Regulated MAP Kinases; Female; Glycosides; Humans; Male; Middle Aged; Models, Biological; Osteoarthritis; Phosphorylation; Protective Agents; Proto-Oncogene Proteins c-akt