ABSTRACT
Background: Traditional Chinese medicine (TCM) has certain advantages in treating diabetes via TCM syndromes differentiation, and health-related behaviors can regulate TCM syndromes. This study aimed to identify the clusters of TCM syndromes in type 2 diabetes mellitus (T2DM) patients and to explore the association between health-related behaviors and those TCM syndromes clusters. Methods: This was a cross-sectional study of 1761 T2DM patients from the Ningxia Province. The TCM syndromes (11 TCM syndromes in total) scale was used to collect the syndrome information. Health-related behaviors, including smoking, alcohol use, tea drinking, the intensity of physical activity, sleep quality, and sleep duration, were collected via a face-to-face interview questionnaire. Latent profile analysis was employed to identify clusters of 11 TCM syndromes. Multinomial logistic regression was employed to examine the relationships between health-related behaviors and clusters of TCM syndromes. Results: TCM syndromes in T2DM patients were classified into three profiles using latent profile analysis: light, moderate, and heavy. Participants with poor health-related behaviors were more likely to have heavy 1.49 (95% CI: 1.12, 1.99) or moderate 1.75 (95% CI: 1.10, 2.79) profiles than those with good health-related habits. Smokers, tea drinkers, and those with poor sleep quality were more likely to have a moderate profile and heavy profile than a light profile. Compared with heavy physical activity, moderate activity 0.24 (95% CI: 0.07, 0.88) was negatively associated with a heavy profile. Conclusion: Results showed that most participants had light or moderate levels of TCM syndromes, and those with poor health-related behaviors were more likely to have heavy or moderate profiles. In the context of precision medicine, these results have important implications for understanding the prevention and treatment of diabetes via changing lifestyles and behaviors to regulate TCM syndromes.
ABSTRACT
Lycium barbarum polysaccharide (LBP) is the main active component of Fructus Lycii, exhibiting various biological activities. This study aims to explore the protective effects of LBP on human corneal epithelial cells (HCEC) and a rat corneal injury model. Potential target points for LBP improving corneal injury repair were screened from public databases, and functional and pathway enrichment analyses of core targets were conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Rat corneal alkali burns and HCEC oxidative stress injury models were established, and the results were validated through slit lamp examination, HE staining, TUNEL assay, immunofluorescence, CCK-8 assay, flow cytometry, scratch assay, and qRT-PCR methods. In the context of database retrieval, identification of 10 LBP monosaccharide components and 50 corneal injury repair-related targets was achieved. KEGG pathway analysis suggested that LBP might regulate the IL-17 and TNF signaling pathways through targets such as JUN, CASP3, and MMP9, thereby improving corneal damage. In vivo and in vitro experimental results indicated that LBP could reduce the increase of inflammation index scores (p < 0.05), inflammatory cell density (p < 0.01), TUNEL-positive cells (p < 0.01), corneal opacity scores (p < 0.01), and expression of corneal stromal fibrosis-related proteins α-SMA, FN, and COL (p < 0.01) caused by chemical damage to rat corneas. LBP inhibited oxidative stress-induced decreases in cell viability (p < 0.001) and migration healing ability (p < 0.01) in HCECs, reducing apoptosis rates (p < 0.001), ROS levels (p < 0.001), and the expression of inflammatory factors TNF-α and IL-6 (p < 0.01). qRT-PCR results demonstrated that LBP intervention decreased the mRNA levels of JUN, CASP3, and MMP9 in H2O2-induced alkaline-burned corneas and HCECs (p < 0.01).The integrated results from network pharmacology and validation experiments suggest that the inhibitory effects of LBP on apoptosis, inflammation, and fibrosis after corneal injury may be achieved through the suppression of the TNF and IL-17 signaling pathways mediated by JUN, CASP3, and MMP9.
Subject(s)
Corneal Injuries , Drugs, Chinese Herbal , Interleukin-17 , Humans , Animals , Rats , Caspase 3 , Matrix Metalloproteinase 9 , Hydrogen Peroxide , Cornea , Corneal Injuries/drug therapy , Fibrosis , Inflammation/drug therapyABSTRACT
Phenylalanine ammonia-lyase is one of the most widely studied enzymes in the plant kingdom. It is a crucial pathway from primary metabolism to significant secondary phenylpropanoid metabolism in plants, and plays an essential role in plant growth, development, and stress defense. Although PAL has been studied in many actual plants, only one report has been reported on potato, one of the five primary staple foods in the world. In this study, 14 StPAL genes were identified in potato for the first time using a genome-wide bioinformatics analysis, and the expression patterns of these genes were further investigated using qRT-PCR. The results showed that the expressions of StPAL1, StPAL6, StPAL8, StPAL12, and StPAL13 were significantly up-regulated under drought and high temperature stress, indicating that they may be involved in the stress defense of potato against high temperature and drought. The expressions of StPAL1, StPAL2, and StPAL6 were significantly up-regulated after MeJa hormone treatment, indicating that these genes are involved in potato chemical defense mechanisms. These three stresses significantly inhibited the expression of StPAL7, StPAL10, and StPAL11, again proving that PAL is a multifunctional gene family, which may give plants resistance to multiple and different stresses. In the future, people may improve critical agronomic traits of crops by introducing other PAL genes. This study aims to deepen the understanding of the versatility of the PAL gene family and provide a valuable reference for further genetic improvement of the potato.
Subject(s)
Phenylalanine Ammonia-Lyase , Solanum tuberosum , Gene Expression Profiling , Gene Expression Regulation, Plant , Humans , Phenylalanine Ammonia-Lyase/genetics , Phenylalanine Ammonia-Lyase/metabolism , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Plants/metabolism , Solanum tuberosum/metabolismABSTRACT
As a traditional Chinese medicine formula, Mi-Jian-Chang-Pu decoction (MJCPD) has been successfully used in patients with language dysfunction and hemiplegia after ischemic stroke (IS). Given the excellent protective effects of MJCPD against nerve damage caused by IS in clinical settings, the present investigation mainly focused on its underlying mechanism on ischemia-reperfusion (IR) injury. Firstly, by applying the MCAO-induced cerebral IR injury rats, the efficacy of MJCPD on IS was estimated using the neurological deficit score, TTC, HE, and IHC staining, and neurochemical measurements. Secondly, an UHPLC-QTOF-MS/MS-based nontargeted metabolomics was developed to elucidate the characteristic metabolites. MJCPD groups showed significant improvements in the neurological score, infarction volume, and histomorphology, and the changes of GSH, GSSG, GSH-PX, GSSG/GSH, LDH, L-LA, IL-6, TNF-α, and VEGF-c were also reversed to normal levels after the intervention compared to the MCAO model group. Metabolomics profiling identified 21 different metabolites in the model group vs. the sham group, 10 of which were significantly recovered after treatment of MJCPD, and those 10 metabolites were all related to the oxidative stress process including glucose, fatty acid, amino acid, glutamine, and phospholipid metabolisms. Therefore, MJCPD might protect against IS by inhibiting oxidative stress during IR.
Subject(s)
Brain Ischemia , Ischemic Stroke , Reperfusion Injury , Animals , Brain Ischemia/drug therapy , Glutathione Disulfide , Humans , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Tandem Mass SpectrometryABSTRACT
Jujube (Ziziphus jujuba Mill.) fruit (JF) is widely consumed as food in Asian countries due to its potential effects for human health. As a traditional Chinese medicine, JF is often used to treat anorexia, fatigue and loose stools caused by spleen deficiency syndromes in China, but the mechanism underlying this effect has not been thoroughly elucidated. In this study, a rat model of spleen deficiency syndromes was adopted to investigate the therapeutic effect of JF extract and its possible mechanism by metabolomics analyses of plasma and urine as well as the intestinal flora analysis. The results showed that the changes in plasma and urine metabolites caused by spleen deficiency were reversed after administration of JF, and these changed endogenous metabolites were mainly involved in retinol metabolism, pentose and glucuronate interconversions, nicotinate and niacinamide metabolism pathways. The 16S rDNA sequencing results showed that JF could regulate intestinal flora imbalance caused by spleen deficiency. The covariance analysis of intestinal flora structure and metabolome indicated that Aerococcus may be a candidate strain for predicting and treating the metabolic pathways of spleen deficiency and related disorders. In summary, it can be revealed that spleen deficiency, which alters metabolic profiles and the intestinal flora, could be alleviated effectively by JF extract.
Subject(s)
Gastrointestinal Microbiome , Ziziphus , Animals , Fruit/chemistry , Fruit/metabolism , Metabolomics , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Spleen , Syndrome , Ziziphus/chemistry , Ziziphus/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: To explore the effective components, potential targets and neuroprotective related mechanisms of Mijianchangpu decoction (MJCPD), a well-known TCM used by the Chinese Hui minorities to treat stroke, on the prevention and treatment of ischemic stroke (IS) by using experimental models combined with network pharmacology. MATERIALS AND METHODS: The neuroprotective efficacy of MJCPD was estimated by applying the middle cerebral artery occlusion (MCAO) induced cerebral ischemia rats, and the neurological deficits score, TTC and HE staining as well as behavioral evaluation tests were employed to evaluate the beneficial effects. Meanwhile, the bioactive components of MJCPD responsible for the neuroprotective effects were identified by detecting the constituents in the brain of the MCAO rats with UHPLC-QTOF-MS/MS techniques, and these compounds were then underwent for network pharmacology analysis. Firstly, the targets of the bioactive compounds of MJCPD were predicted using Pharmmapper database, and simultaneously, the targets of IS disease were obtained from disease databases including DisGenet, OMIM, and GeneCards. Secondly, the protein-protein interaction (PPI) network between the targets and diseases were established to give the possible therapeutic targets for IS. Thirdly, the go function and KEGG pathway enrichment analysis were carried out and the compound-target-pathway network was constructed by Cytoscape software. Finally, the effective compounds, core targets and possible pathways were obtained by analyzing the connectivity of the network. More importantly, the core targets were verified by western blot experiments to validate the reliability of this study. RESULTS: MJCPD exhibited significant neuroprotective effect on IS, and 16 bioactive components of MJCPD were identified in the brain of the MCAO rats. 59 and 1982 targets related with IS disease were explored from Pharmapper and disease databases, respectively, and 32 intersecting targets were obtained as hypothetical therapeutic targets. Based on the results of the compound-target-pathway and PPI network with the degree was greater than the median, 8 effective compounds (suberic acid, epishyobunone, crocetin monomethyl ester, sfaranal, (Z)-6-octadccenoic acid, nerolidol and gurjunene) and 5 hub targets (SRC, MAPK8, MAPK14, EGFR and MAPK1) as well as 12 pathways were predicted. Western blot results showed that EGFR, p38, ERK and SRC proteins were expressed significantly different after MJCPD treatment as compared with the model group. CONCLUSION: The present study employed network pharmacology, pharmacodynamics and molecular biology techniques to predict and validate the core potential targets and signaling pathways as well as the bioactive components of MJCPD responsible for the treatment of IS. All of which are very helpful to clarify the neuroprotective mechanism of MJCPD, and obviously, the active compounds and targets in this study can also provide clues for the treatment of IS.
Subject(s)
Brain Ischemia , Drugs, Chinese Herbal , Network Pharmacology , Phytotherapy , Stroke , Animals , Male , Brain Ischemia/drug therapy , Drugs, Chinese Herbal/pharmacology , Gene Expression Regulation/drug effects , Infarction, Middle Cerebral Artery , Nimodipine , Rats, Sprague-Dawley , Specific Pathogen-Free Organisms , Stroke/drug therapy , Stroke/pathologyABSTRACT
Hui Medicine ZhaLi NuSi Prescription (ZLNS) is described in "Hui Hui Prescription," and it has been used to treat cerebral infarction in Hui Region, China. In this study, a rapid and reliable ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) method was established and applied to simultaneously determine geniposidic acid, oxypaeoniflorin, hydroxysafflor yellow A, caffeic acid, magnoflorine, paeoniflorin, ferulic acid, ß-ecdysterone, icariin, rhein, and baohuoside I in rat plasma. The pharmacokinetic parameters of these components and the influence of essential oils (EOs) on them were investigated in normal rats. The results showed that the pharmacokinetic parameters (AUC0 - t , AUC0 - ∞ , t1/2 , tmax , cmax ) of the aforementioned compounds were significantly changed after co-administering with ZLNS EO. The AUC values of oxypaeoniflorin, paeoniflorin, ferulic acid, and baohuoside I with EOs were decreased significantly. This is the first report for the comparative pharmacokinetic study of ZLNS bioactive components in normal rats, which may provide the basis for drug interaction study in vivo and insight into their clinical applications.
Subject(s)
Drugs, Chinese Herbal , Oils, Volatile , Animals , Chromatography, High Pressure Liquid/methods , Coumaric Acids/blood , Coumaric Acids/chemistry , Coumaric Acids/pharmacokinetics , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Glucosides/blood , Glucosides/chemistry , Glucosides/pharmacokinetics , Herb-Drug Interactions , Limit of Detection , Linear Models , Male , Monoterpenes/blood , Monoterpenes/chemistry , Monoterpenes/pharmacokinetics , Oils, Volatile/administration & dosage , Oils, Volatile/analysis , Oils, Volatile/pharmacokinetics , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Tandem Mass Spectrometry/methodsABSTRACT
Kava (Piper methysticum Forst) is a popular and favorable edible medicinal herb which was traditionally used to prepare a nonfermented beverage with relaxant beneficial for both social and recreational purposes. Numerous studies conducted on kava have confirmed the presence of kavalactones and flavokawains, two major groups of bioactive ingredients, in this miraculous natural plant. Expectedly, both kavalactone and flavokawain components exhibited potent antianxiety and anticancer activities, and their structure-activity relationships were also revealed. However, dozens of clinical data revealed the hepatotoxicity effect which is indirectly or directly associated with kava consumption, and most of the evidence currently seems to point the compounds of flavokawains in kava were responsible. Therefore, our aim is to conduct a systematic review of kavalactones and flavokawains in kava including their biological activities, structure-activity relationships, and toxicities, and as a result of our systematic investigations, suggestions on kava and its compounds are supplied for future research.
ABSTRACT
BACKGROUND AND OBJECTIVES: Primary Intestinal Lymphangiectasia (PIL) is a rare congenital and digestive disease, which could present through a broad spectrum of clinical manifestations, diagnostic and treatment management. The aim of this study was to introduce the diagnosis and nutrition treatment of children with PIL through the twelve years of experience. METHODS AND STUDY DESIGN: The patients diagnosed with PIL admitted to the Department of Gastroenterology and Nutrition in Xinhua Hospital from June 2006 to September 2017 were included in the study. RESULTS: Ten patients were found to have PIL, and 5 of them were male. The mean age was 66 months at the time of diagnosis and 11 months at onset. The main clinical manifestations were diarrhea, edemas and abdominal distention. Marked dilatation of the intestinal lymphatic vessels was the characteristic of the endoscopic. All the patients presented with hypoproteinemia and hypoimmunoglobulinia. Six of them were treated with parenteral nutrition, and 9 of them were treated with a low-long-chain triglycerides (LCT), high-protein diet supplemented with medium-chain triglycerides (MCT). The clinical symptoms of the patients have improved after the MCT diet therapy. CONCLUSIONS: PIL should be considered first when there are clinical manifestations of chronic diarrhea, edema and abdominal distention, and biochemical results indicated the hypoproteinemia and hypoimmunoglobulinia, and the general treatment is invalid. Gastroscopy and E-colonoscopy with biopsies are the preferred method of diagnosis. Diet intervention (MCT diet) is the cornerstone and longtime medical treatment, which can improve the nutritional status and promote the survival quality of patients with PIL.
Subject(s)
Lymphangiectasis, Intestinal , Child , Child, Preschool , Diarrhea/diagnosis , Diarrhea/therapy , Diet , Humans , Lymphangiectasis, Intestinal/diagnosis , Lymphangiectasis, Intestinal/therapy , Male , Nutritional Status , TriglyceridesABSTRACT
Color in nature mediates numerous among and within species interactions,1 and anthropogenic impacts have long had major influences on the color evolution of wild animals.2 An under-explored area is commercial harvesting, which in animals can exert a strong selection pressure on various traits, sometimes greater even than natural selection or other human activities.3,4 Natural populations of plants that are used by humans have likely also suffered strong pressure from harvesting, yet the potential for evolutionary change induced by humans has received surprisingly little attention.5 Here, we show that the leaf coloration of a herb used in traditional Chinese medicine (Fritillaria delavayi) varies among populations, with leaves matching their local backgrounds most closely. The degree of background matching correlates with estimates of harvest pressure, with plants being more cryptic in heavily collected populations. In a human search experiment, the time it took participants to find plants was greatly influenced by target concealment. These results point to humans as driving the evolution of camouflage in populations of this species through commercial harvesting, changing the phenotype of wild plants in an unexpected and dramatic way.
Subject(s)
Biological Mimicry/physiology , Fritillaria/physiology , Plants, Medicinal/physiology , Color , Medicine, Chinese Traditional , Phytotherapy , Pigmentation/physiology , Plant Leaves/physiologyABSTRACT
Amyloid ß (Aß) induced microglial activation and attendant neuroinflammation play pivotal roles in Alzheimer's disease (AD) pathogenesis. Matrine is a natural anti-inflammation compound from the Chinese herbal medicine Sophora flavescens Ait. (Kushen). This study aimed to investigate the effects of matrine on memory deficit and neuroinflammation in an oligomeric Aß (oAß)-induced AD mice model. Whether microglial activation and NADPH oxidase were involved in these effects were further studied. Different doses of matrine (10, 20, or 40 mg/kg) were intragastrically administered once a day after intracerebroventricular oAß injection (2.5 µg/µl, 4 µl). 15 days after the oAß injection, behavioral experiments including novel object recognition (NOR) test and Morris water maze (MWM) test were performed. 21 days after the oAß injection, concentration of ROS, TNF-α, IL-1ß and IL-6 as well as expression of NADPH oxidase subunits gp91phox and p47phox in mice hippocampal tissues were assessed, and microglial activation were evaluated by Iba-1 immunohistochemical staining. Results of NOR test and MWM test revealed that oAß injection could remarkably impair learning and memory function in AD mice, and matrine administration could significantly ameliorate the impairment. ROS, TNF-α, IL-1ß and IL-6 levels increased after oAß injection, while matrine could significantly reduce the concentrations of these inflammatory factors. OAß induced protein expression of NADPH oxidase subunits gp91phox and p47phox were also significantly reduced by matrine. Iba-1 immunohistochemistry results showed less activated microglia in matrine-treated mice brain. These results indicate that matrine could ameliorate learning and memory impairment and neuroinflammation induced by oAß injection. These effects were found to be mediated through inhibition of microglial activation and NADPH oxidase expression in hippocampal tissue. The results suggest that matrine may be a valuable natural compound with therapeutic potential against AD.
Subject(s)
Alkaloids/pharmacology , Alzheimer Disease/drug therapy , Anti-Inflammatory Agents/pharmacology , Cognitive Dysfunction/drug therapy , Quinolizines/pharmacology , Alkaloids/administration & dosage , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/metabolism , Animals , Anti-Inflammatory Agents/administration & dosage , Cognitive Dysfunction/physiopathology , Disease Models, Animal , Dose-Response Relationship, Drug , Hippocampus/pathology , Inflammation/drug therapy , Inflammation/pathology , Male , Maze Learning/drug effects , Memory Disorders/drug therapy , Memory Disorders/pathology , Mice , Mice, Inbred C57BL , Quinolizines/administration & dosage , MatrinesABSTRACT
Ca2+-activated Cl- channels (CaCCs) wildly exist in many tissues which play an important role in ion transport and excitation conduction, especially fluid secretion and smooth muscle contraction in epithelial tissues. TMEM16A as a classic CaCC expresses in the intestine, and has become a potential target of intestinal physiological and pathological researches and therapeutic drug screening. In this study, we identified trans-δ-viniferin (TVN), a resveratrol dimmer, could inhibit TMEM16A activity in TMEM16A expressed FRT cells with IC50 of 19.7⯵M, it also prevented Ca2+-activated Cl- current in HT-29 cells with IC50 of 4.65⯵M and in colonic mucosa. In the mechanism studies, TVN showed no significant inhibition on CFTR and basal Na+/K+-ATPase in both intestinal epithelial cells and colonic tissues, except for inhibition of calcium concentration and Ca2+-activated K+ channel to some degree. In anti-diarrheal studies, TVN could effectively prevent diarrhea caused by rotavirus infection and reduce the pellet number in IBS-D mice. These physiological effects are at least partially attributed to the inhibitory effect of TVN on CaCC-mediated intestinal fluid secretion and the reduction of smooth muscle contraction force by inhibiting TMEM16A. Collectively, the present study identified a new pharmacological target of TVN which provided the theoretical basis for the application of TVN in the treatment of rotavirus-infected diarrhea and IBS-D.
Subject(s)
Benzofurans/pharmacology , Chloride Channels/antagonists & inhibitors , Diarrhea/drug therapy , Epithelial Cells/drug effects , Resorcinols/pharmacology , Stilbenes/pharmacology , Animals , Calcium/analysis , Diarrhea/virology , Gastrointestinal Motility/drug effects , HT29 Cells , Humans , Inflammatory Bowel Diseases/drug therapy , Intestinal Mucosa/cytology , Mice , Mice, Inbred C57BL , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Rats , RotavirusABSTRACT
Testicular dysfunction is one of the serious secondary complications in diabetes. Lycium barbarum polysaccharide (LBP) has long been considered to possess a wide range of beneficial properties including antiaging, anticancer and reproductive-enhancing. Abnormal autophagy was reported to play a significant role in accelerating diabetic reproductive injury. However, the autophagy regulation mechanism of LBP on diabetic testicular dysfunction is incompletely understood. We investigate the protective effects of LBP on diabetic testicular dysfunction and its underlying mechanism with different approaches. Protective effects of LBP (40 mg/kg) on testicular functions were assessed through the use of sperm parameters, testosterone levels and hematoxylin and eosin staining. Antioxidant capacity and serum malondialdehyde levels were determined using assay kits. Immune intensity of Beclin-1 and LC3I in testes was detected by immunofluorescence staining. Western blot analysis was used to detect expressions of p-PI3K, Akt, p-Akt, Beclin-1, LC3I and LC3II proteins. Q-PCR was used to evaluate Beclin-1 and LC3I mRNA expressions in testis. Administration of LBP (40 mg/kg) considerably recovered testicular function, obviously improved testicular histopathologic structure and significantly increased antioxidant enzyme activities. Immunofluorescence staining showed that immune intensity of Beclin-1 and LC3I significantly decreased in the LBP 40 mg/kg group. The results of Q-PCR and western blot analysis showed that LBP 40 mg/kg significantly downregulated Beclin-1 and LC3I protein expressions upregulated p-PI3K and p-Akt protein expressions and decreased Beclin-1 and LC3I mRNA expressions compared with diabetic mice. In conclusion, inhibition of PI3K/Akt pathway-mediated testicular excessive autophagy may be a target for protective effects of LBP on diabetic testicular dysfunction.
Subject(s)
Autophagy , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/physiopathology , Drugs, Chinese Herbal/therapeutic use , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Testis/pathology , Testis/physiopathology , Animals , Autophagosomes/drug effects , Autophagosomes/metabolism , Autophagosomes/ultrastructure , Autophagy/drug effects , Autophagy/genetics , Autophagy-Related Proteins/genetics , Autophagy-Related Proteins/metabolism , Beclin-1/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/genetics , Drugs, Chinese Herbal/pharmacology , Male , Mice, Inbred ICR , Microtubule-Associated Proteins/metabolism , Oxidative Stress/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction/drug effects , Spermatozoa/drug effects , Spermatozoa/metabolism , Testis/drug effects , Testosterone/bloodABSTRACT
Tamarix ramosissima is a traditional Chinese herbal medicine used for rheumatoid arthritis (RA) treatment in Northwest China. Chemical investigation of EtOH/H2O extracts of T. ramosissima led to the discovery of a new flavonol, ramosissimin (1), together with the known flavonoids compounds quercetin (2), quercetin-3'4'-dimethylether (3) and kaempferol (4). By means of high resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D and 2D-NMR experiments, and after comparison with literature data, the structures of the compounds were determined. The effect of compound 1 on the viability of RA fibroblast-like synoviocytes (RA-FLS) was evaluated by MTT assay. Apoptosis-inducing effect of compound 1 in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and activated caspase-3/7 level assessment using luminescent assay. The results revealed that ramosissimin displayed remarkable proliferation inhibitory effect in RA-FLS. Furthermore, compound 1 could significantly induce cellular apoptosis of RA-FLS and increase activated caspase-3/7 levels. It is suggested that ramosissimin may inhibit the proliferation of RA-FLS by inducing apoptosis.
Subject(s)
Antirheumatic Agents/pharmacology , Apoptosis/drug effects , Fibroblasts/drug effects , Flavonols/pharmacology , Synovial Membrane/drug effects , Tamaricaceae/chemistry , Caspases/metabolism , Cell Proliferation/drug effects , Cells, Cultured , Flavonols/chemistry , Humans , In Situ Nick-End Labeling , Magnetic Resonance Spectroscopy , Plant Extracts/pharmacology , Plant Leaves/chemistry , Synovial Membrane/cytologyABSTRACT
Pulmonary hypertension (PH) is fatal disease which closely involves Rho A/ Rho kinsase (ROCK) pathway. Aloperine is a main active alkaloid extracted from Sophora alopecuroides, which is a traditional Chinese herbal medicine that has been used widely. However, the effects of this alkaloid on pulmonary hypertension and its mechanisms remain unclear. Therefore, this study is designed to investigate whether aloperine has protective effects on PH induced by monocrotaline, whether these effects may be related to regulation of RhoA/ROCK pathway in rats. Pulmonary hypertension was induced by monocrotaline (60mg/kg), and subsequently oral administration of aloperine (25, 50, 100mg/kg/day) for 21 days. At the end of the experiment, rats were underwent hemodynamic and morphologic assessments. At same time, the expression of Rho A, ROCK1, ROCK2, as well as activities of ROCK in the lung of rat has been detected. Afterwards, the expression of p27kip1, Bax, Bcl-2, which was the downstream proliferation and apoptosis factors of ROCK, were tested. The result indicted that aloperine treatment showed significantly improvement in hemodynamic and pathomorphologic data. Moreover, the reduction in expression of Rho A, ROCK1, ROCK2, and suppression in activities of ROCK were found in rat lungs after aloperine treatment. Furthermore, aloperine also alleviated the MCT-induced changes of p27kip1, Bax and Bcl-2. In summary, this study indicates that aloperine have protective effects on monocrotaline-induced PH. And these effects may be partially related to RhoA/ROCK pathway. Thus, aloperine could be considered a possible therapeutic strategy for PH.
Subject(s)
Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/drug therapy , Piperidines/therapeutic use , Protective Agents/therapeutic use , rho-Associated Kinases/metabolism , rhoA GTP-Binding Protein/metabolism , Animals , Cardiomegaly/complications , Cardiomegaly/drug therapy , Cardiomegaly/physiopathology , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Electrocardiography , Hemodynamics/drug effects , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/physiopathology , Lung/drug effects , Lung/pathology , Lung/physiopathology , Male , Monocrotaline , Piperidines/pharmacology , Proliferating Cell Nuclear Antigen/metabolism , Protective Agents/pharmacology , Pulmonary Artery/drug effects , Pulmonary Artery/pathology , Pulmonary Artery/physiopathology , Quinolizidines , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Vascular Remodeling/drug effects , bcl-2-Associated X Protein/metabolism , rho-Associated Kinases/genetics , rhoA GTP-Binding Protein/geneticsABSTRACT
Diabetes-associated male sexual dysfunction and fertility impairments are both common clinical complications with limited therapeutic options; hence it seriously affects the quality of life of the patients, in particular, the patients of reproductive age. Lycium barbarum polysaccharide (LBP) has long being believed to maintain and to promote reproductive functions in the traditional medical practice in China. The current study was to investigate if LBP may contribute to recovery of male sexual dysfunction and fertility impairments in diabetic individuals. The effects of LBP on sexual behaviors and histological changes of testis were studied in the type-1 diabetes male mice induced by intra-peritoneal (i.p.) injection of streptozotocin (STZ). After oral administration of LBP (10, 20 or 40 mg/kg), sildenafil citrate (SC, 5 mg/kg) or saline for 62 consecutive days, the typical abnormal changes in the sperm parameters, in relative weight of reproductive organs and in morphology of testis were observed in diabetic mice. LBP treatment of the diabetic mice considerably reversed those changes and Johnsen's testicular score, serum testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) level were also increased to different degrees. Moreover, our data have also shown that a marked improvement in sexual behavior and fertility level after administration of LBP (40 mg/kg) compared to the diabetic group. These results suggested that LBP can exert functional recovery of male sexual dysfunction and fertility damages induced by diabetes in male mice, which is likely to be mediated through regulating the hypothalamus- pituitary-gonadal axis endocrine activity.
Subject(s)
Diabetes Mellitus, Experimental/complications , Drugs, Chinese Herbal/therapeutic use , Hypothalamo-Hypophyseal System/drug effects , Infertility, Male/drug therapy , Protective Agents/therapeutic use , Sexual Behavior, Animal/drug effects , Sexual Dysfunction, Physiological/drug therapy , Animals , Diabetes Mellitus, Experimental/blood , Drugs, Chinese Herbal/pharmacology , Follicle Stimulating Hormone/blood , Infertility, Male/blood , Infertility, Male/etiology , Luteinizing Hormone/blood , Male , Mice , Phosphodiesterase 5 Inhibitors/pharmacology , Phosphodiesterase 5 Inhibitors/therapeutic use , Protective Agents/pharmacology , Sexual Dysfunction, Physiological/blood , Sexual Dysfunction, Physiological/etiology , Sildenafil Citrate/pharmacology , Sildenafil Citrate/therapeutic use , Testis/drug effects , Testosterone/bloodABSTRACT
KEY MESSAGE: Sex allocation in Cyananthus delavayi. Gynodioecy, where females and hermaphrodites coexist in the same natural population, is particularly suitable for predicting the ecological pressures that drive the stability of gender polymorphism. Since females have a disadvantage in that they only contribute to the next generation via ovules, they should gain an advantage via other means, of which resource allocation is an important component. Thus, to study their sex allocation is very helpful to understand how the dimorphic sexual system is maintained in natural systems. We studied the sex allocation patterns and reproductive output of the gynodioecious Cyananthus delavayi in three populations with different soil qualities (organic matter, N, P and K). The hermaphroditic flowers and pistils were much larger than those of female individuals. Although both gender morphs invested similar biomass in the pistils, females allocated more of their resource pool to the seed production, while hermaphrodites allocated more to pollinator advertisement. The pollen production of hermaphrodites did not differ between populations, suggesting that pollen production by hermaphrodites was not limited by soil nutrients. Fruit set of females, but not hermaphrodites, decreased with declining soil quality, whereas seeds per fruit of both females and hermaphrodites were highest in poor soils. Overall, this study shows that females achieve greater reproductive success by allocating more of their resource pool to enhancing seed production, which should favor their presence in gynodioecious populations. The hermaphrodites achieve reproductive success from both pollen and seed production, and unnecessarily reduce their allocation to pollen production. Soil quality should explain, at least partially, the sexual allocation patterns. Furthermore, some of our findings contradict previous hypotheses, thus adding a new example to the body of research on plant sex allocation and the development of future theories.
Subject(s)
Campanulaceae/physiology , Soil/chemistry , Biomass , Flowers/physiology , Pollen/physiology , Reproduction , Sex Determination ProcessesABSTRACT
Lycium barbarum polysaccharides (LBP) have been reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer. However, the anti-inflammation mechanism of LBP on primary cultured rat hippocampal neurons injured by oxygen-glucose deprivation/reperfusion (OGD/RP) is incompletely understood. We investigate the neuroprotective effects of LBP on neonatal rat primary cultured hippocampal neurons injured by OGD/RP with different approaches: MTT assay was used to detect cell viability, lactate dehydrogenase leakage was used to detect neuronal damage, formation of reactive oxygen species was determined by using fluorescent probe DCFH-DA. Hoechst 33,342 staining and TUNEL staining were used to determine the cell apoptosis. JC-1 was used to evaluate loss of mitochondrial membrane potential (MMP). The fluorescence intensity of [Ca2+]i in hippocampal neurons was determined by laser scanning confocal microscopy. The expression of various apoptotic markers such as TLR4, IκB, IL-6 and NF-κB were investigated by RT-PCR and western blot analysis. Results from each approach demonstrated that LBP increased the cell abilities and decreased the cell morphologic impairment. Furthermore, LBP increased MMP but inhibited [Ca2+]i elevation and significantly suppressed overexpression of NF-κB, IL-6 TLR4 and increased IκB expression.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Hippocampus/cytology , Neurons/metabolism , Animals , Apoptosis/drug effects , Calcium/metabolism , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cell Survival/drug effects , Cells, Cultured , Female , Glucose/deficiency , Interleukin-6/metabolism , L-Lactate Dehydrogenase/metabolism , Male , Membrane Potential, Mitochondrial/drug effects , NF-kappa B/metabolism , Neurons/drug effects , Oxygen , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Reperfusion , Toll-Like Receptor 4/metabolismABSTRACT
Increasing evidence demonstrates inflammation contributes to neuronal death following cerebral ischemia. Lycium barbarum polysaccharide (LBP) has been reported to prevent scopolamine-induced cognitive and memory deficits. We recently indicated that LBP exerts neuroprotective effect against focal cerebral ischemic injury in mice via attenuating the mitochondrial apoptosis pathway. The aim of this study was to investigate the neuroprotective effects of LBP against the behavioral dysfunction induced by focal cerebral ischemia injury in mice. Following 7 successive days of pretreatment with LBP (10, 20 and 40 mg/kg) and nimodipine (4 mg/kg) by intragastric gavage, mice were subjected to middle cerebral artery occlusion (MCAO). Following reperfusion, cerebral blood flows, the total power of the spontaneous EEG, and morphological changes were estimated. Learning and memory ability, and motor coordination were determined by Morris water maze task, rotarod and grip test. Western blot analysis, Real-Time fluorogenic PCR assays, and immunofluorescence staining were used to examine the expression of proinflammatory mediators and activation of microglia. The present study showed that LBP pretreatment significantly enhanced regional cortical blood flow and the total power of the spontaneous EEG, improved memory and motor coordination impairments, and inhibited over-activation of microglia and astrocytes after MCAO. Further study demonstrated LBP suppressed MCAO-induced activations of P65 NF-κB and P38 MAPK, and prevented up-regulations of proinflammatory mediators in hippocampus. Our data suggest that LBP can exert functional recovery of memory and motor coordination deficits and neuroprotective effect against cerebral ischemic injury in mice.
Subject(s)
Brain Ischemia/drug therapy , Drugs, Chinese Herbal/pharmacology , Infarction, Middle Cerebral Artery/drug therapy , Memory/drug effects , Neuroprotective Agents/pharmacology , Animals , Apoptosis/drug effects , Astrocytes/drug effects , Astrocytes/metabolism , Brain Injuries/drug therapy , Brain Injuries/metabolism , Brain Ischemia/metabolism , Cell Death/drug effects , Hippocampus/drug effects , Hippocampus/metabolism , Infarction, Middle Cerebral Artery/metabolism , Male , Mice , Microglia/drug effects , Microglia/metabolism , Neurons/metabolismABSTRACT
Chinese Herbal Medicine (CHM) plays a significant role in breast cancer treatment. We conduct the study to ascertain the relative molecular targets of effective Chinese herbs in treating stage IV breast cancer.Survival benefit of CHM was verified by Kaplan-Meier method and Cox regression analysis. A bivariate correlation analysis was used to find and establish the effect of herbs in complex CHM formulas. A network pharmacological approach was adopted to explore the potential mechanisms of CHM.Patients in the CHM group had a median survival time of 55 months, which was longer than the 23 months of patients in the non-CHM group. Cox regression analysis indicated that CHM was an independent protective factor. Correlation analysis showed that 10 herbs were strongly correlated with favorable survival outcomes (P<0.01). Bioinformatics analyses suggested that the 10 herbs might achieve anti-breast cancer activity primarily through inhibiting HSP90, ERα and TOP-II related pathways.