The bio-active components of the Mongolian medicine Horcha-6 and therapeutic mechanism in the rat migraine model

Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.

Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in a Chinese community-based population of euthyroid people aged 40 years and older

This study investigated whether high-normal thyrotropin（TSH） levels are associated with metabolic syndrome in euthyroid Chinese people≥40 years old.Clinical and metabolic factors were assessed in 2,356 subjects（40-77 years old） with TSH levels in the normal range（0.35-5.00 mU/L）.Using 2.50 mU/L as the cut-off point of TSH level within the normal range,we divided subjects into the high-TSH（2.50-5.00 mU/L;n= 1,064） and low-TSH（0.35-2.50mU/L;n= 1,292） group.The results showed that the mean levels of body mass index（BMI）,total cholesterol（TC）,low density lipoprotein cholesterol（LDL-C）,and fasting plasma glucose（FPG） were higher in the high-TSH group and TSH levels were significantly positively con-elated with BMI,LDL-C,TC,and FPG.The prevalence of central obesity,hypertriglyceridemia,low high density lipoprotein cholesterol（HDL-C）,and high FPG（〉5.60 mmol/L） was significantly higher in females and subjects with high-TSH levels.Metabolic syndrome was also more prevalent in the high-TSH group.People over the age of 40 years with high-normal TSH levels had a 1.2-fold increased risk of metabolic syndrome,compared with those with low-normal TSII levels,after adjusting for age and gender.In conclusion,high normal TSH is a risk factor for metabolic syndrome in people ≥40 years old.

Expression Analysis of Genes Related to Auxin Metabolism at Different Growth Stages of Pak Choi

Pak choi is a low-temperature vernalized plant that readily undergoes premature bolting during spring, but little is known about the governing molecular regulation of vernalization. In order to enhance our understanding of mechanism about premature bolting, we discussed the relationship between auxin(indole-3-acetic acid, IAA) and flowering of pak choi. During vernalization, hormone metabolism is an important regulatory pathway, and IAA plays a specific role. IAA metabolism has been studied in Arabidopsis thaliana and other plants, but not in pak choi. In this paper, the IAA content in pak choi shoot apices during vernalization and different growth stages was compared. The IAA content decreased significantly after low-temperature treatment(4 °C) and then increased rapidly during vegetative growth. During floral bud initiation,the IAA content decreased rapidly and was the lowest. Expressions of genes encoding key IAA metabolic enzymes were analyzed, and a major synthetase-encoding gene was downregulated, while a key degrading enzyme-encoding gene was upregulated during each comparison period,resulting in decreased IAA content. Expressions of four genes(Bra034975, Bra030246, Bra012239 and Bra040296) were consistent with changes in the IAA content. The functions of differentially expressed genes(DEGs) were analyzed, and 15 DEGs were found to be related to IAA metabolism.The findings illuminated the molecular mechanism regulating IAA content during vernalization in pak choi.

Meta Analysis of the Efficacy of Nonpharmaceutical Chinese Medicine Therapy in the Treatment of Obese Polycystic Ovary Syndrome

Objective:To systematically evaluate the effects of acupuncture,auricular point sticking,acupoint catgut embedding,cupping and other non-pharmaceutical Chinese medicine therapies on sex hormone as well as glucose and lipid metabolism in patients with obese polycystic ovary syndrome.Method:The databases such as China National Knowledge Infrastructure were searched by computer to collect the literature on the treatment of obese polycystic by non-pharmaceutical Chinese medicine therapy combined with western medicine or lifestyle change,and the literature quality of the included literature was evaluated,and finally the data were analyzed.A total of 15 randomized controlled trial(RCT)literature were included in this study,with a total of 1263 patients.Results:Non-pharmaceutical Chinese medicine therapy combined with metformin or lifestyle can reduce body mass index,insulin resistance index,fasting plasma insulin,fasting blood glucose,luteinizing hormone,ratio of luteinizing hormone to follicle stimulating hormone,testosterone,but it has no obvious advantage over follicle stimulating hormone(FSH).Conclusion:Compared with simple application of metformin or lifestyle change,traditional Chinese medicine non drug therapy combined with metformin or lifestyle change can better improve sex hormone and blood glucose metabolism in obese PCOS patients.

Studies on the Free Radicals and Thyroid Hormone Metabolism in Cattle with Iodine and Selenium Deficicncy

In order to interpret pathologic mechanism of free radicals and thyroid hormone metabolism in cattle iodine and selenium deficiency, 20 heads of yellow cattle were selected from NiuJia town, Wu Chang City, Heilongjiang Province, China, and were randomly devided into 4 groups with 5 for each. ① supplemented with 0.7 mg·kg -1 iodine(potassium iodine), ② supplemented with 0.2 mg·kg -1 selenium (sodium selenite), ③ supplemented with 0.7 mg·kg -1 iodine(potassium Iodine) plus 0.2 mg·kg -1 selenium (sodium selenite) per day for 30 days, respectively. ④control group. The whole blood glutathione peroxidase (GSH-px) and catalase (CAT) activities, free radicals (FR) concentration, erythrocyte superoxide dismutase (SOD) activity and molonaldehyde (MDA) concentration, the serum triiodothyronine (T 3)、thyroxine (T 4) and thyrotropin (TSH) were determined on the day of supplementation day-0 and day-30, respectively. It was showed that average iodine concentration in drinking water and diet were 3.82 μg·L -1 and 0.285mg·kg -1 , respectively, Diet selenium was 0.0498mg·kg -1 , Serum protein bound iodine(PBI) was 7.02 μg·100 mL, Blood selenium was 0.14 mg·L -1 , the schoolchildren′s goiter was 21.8%. It indicated that iodine and selenium were deficient in the investigated area. Whole blood GSH-px and CAT activities and serum T 3 concentration were significantly higher (P< 0.01 ), FR concentration and serum TSH were significantly lower(P<0.01) in the first three groups than that of the control, T 4 content in the first group was higher(P<0.05), T 4 was also higher (P>0.05) in the second group. and lower in the third group. The SOD and MDA in erythrocyte were not changed during the experimental period, The results also showed that GSH-px and CAT activities were increased, and FR decreased oberviously in the third group more than the other two groups, In addition, Thyroid hormone metabolism was more coincided with the physiologic status in the third group. the iodine and the selenium played an important role in the pathologic process of free radical metabolic disorder. selenium not only had the function of antioxidation by derectly scavenging free radicals, but also affected through GSH-px and CAT activities. iodine deficiency results in the Goiter, selenium deficiency aggravated iodine deficiency, Iodine and the selenium were dependent and restrained each other in the course of free radicals and thyroid hormone metabolism with a synergistic state.

Metabolic actions of FGF21:molecular mechanisms and therapeutic implications

Fibroblast growth factor 21(FGF21)is an atypical member of the FGF family that functions as an endocrine factor.In obese animals,elevation of plasma FGF21 levels by either pharmacological or genetic approaches reduces body weight,decreases hyperglycemia and hyperlipidemia,alleviates fatty liver and increases insulin sensitivity.FGF21 exerts its pleiotropic metabolic effects through its actions on multiple targets,including adipose tissue,liver,brain and pancreas.The expression of FGF21 is under the control of both peroxisome proliferator-activated receptor gamma(PPARγ)and peroxisome proliferator.-activated receptor alpha(PPARα).A growing body of evidence suggests that the metabolic benefits of these two nuclear receptors are mediated in part by induction of FGF21.In humans,plasma levels of FGF21 are elevated in obese subjects and patients with type 2 diabetes,but are reduced in patients with autoimmune diabetes.This review summarizes recent advances in understanding the physiological roles of FGF21 and the molecular pathways underlying its actions,and also discusses the future prospective of developing FGF21 or its agonists as therapeutic agents for obesity-related medical complications.

Metabolic syndrome and androgen deprivation therapy in metabolic complications of prostate cancer patients

Background Incidence of prostate cancer in Chinese males grows significantly in the past decades. Androgen deprivation therapy has been generally employed in the treatment of locally advanced and metastatic prostate cancer for many years, yet only little data was known about the metabolic syndrome in patients receiving hormonal therapy. This study described the prevalence and the changing trends of hormone-related metabolic complications, and analyzed their correlation with different therapies. Methods In 125 patients treated with castration or maximal androgen blockage for at least 12 months, metabolic indicators were analyzed. Results Totally, 13.5% patients in castration group and 30.1% patients in maximal androgen blockage group were diagnosed metabolic syndrome 12 months after the beginning of treatments （X2=4.739, P=0.029）. In castration group, increased triglyceride and decreased high-density lipoprotein-cholesterol were significant at the month 12, increased fasting plasma glucose and blood pressure were significant at the month 4. In maximal androgen blockage group, increased triglyceride and decreased high-density lipoprotein-cholesterol were significant at the month 4, increased fasting plasma glucose and blood pressure were significant at the month 8. Total testosterone and free testosterone in maximal androgen blockage group were significantly lower than castration group at all visits, which were proved to show positive or negative correlations with metabolic indications. Severity of metabolic complications in maximal androgen blockage group was generally more serious than people received castration, with significantly statistical difference or not. Trends of high-density lipoprotein-cholesterol and fasting plasma glucose were significant different between two kinds of therapy （P=0.005, P=-0.019, respectively）.

Hibernation with rhythmicity:the circadian clock and hormonal adaptations of the hibernating Asiatic toads(Bufo gargarizans)

Hibernation is one of the fundamental strategies in response to cold environmental temperatures.During hibernation,the endocrine and circadian systems ensure minimal expenditure of energy for survival.The circadian rhythms of key hormones,melatonin(MT),corticosterone(CORT),triiodothyronine(T3),and thyroxine(T4),and the underlying molecular regulatory mechanisms of hibernation have been well determined in mammals but not in ectotherms.Here,a terrestrial hibernating species,Asiatic toad(Bufo gargarizans),was employed to investigate the plasma CORT,MT,T3,and T4;and the retina,brain,and liver mRNA expression of the core clock genes,including circadian locomotor output cycles kaput(Clock),brain and muscle ARNT-like 1(Bmal1),cryptochrome(Cry)1 and 2,and period(Per)1 and 2,at 7-time points over a 24-h period under acute cold(1 day at 4℃),and hibernation(45 days at 4℃).Our results showed that the circadian rhythms of the core clock genes were rather unaffected by acute cold exposure in the retina,unlike the brain and liver.In contrast,during hibernation,the liver clock genes displayed significant circadian oscillations,while those in the retina and brain stopped ticking.Furthermore,plasma CORT expressed circadian oscillations in both groups,and T3 in acute cold exposure group,whereas T4 and MT did not.Our results reveal that the plasma CORT and the liver sustain rhythmicity when the brain was not,indicating that the liver clock along with the adrenal clock synergistically maintains the metabolic requirements to ensure basic survival in hibernating Asiatic toads.

Jasmonic Acid Oxidase 2 Hydroxylates Jasmonic Acid and Represses Basal Defense and Resistance Responses against Botrytis cinerea Infection

Jasmonates （JAs） orchestrate immune responses upon wound/herbivore injury or infection by necrotro- phic pathogens. Elucidation of catabolic routes has revealed new complexity in jasmonate metabolism. Two integrated pathways attenuate signaling by turning over the active hormone jasmonoyl-isoleucine （JA-Ile） through w-oxidation or deconjugation, and define an indirect route forming the derivative 12OH-JA. Here, we provide evidence for a second 12OH-JA formation pathway by direct jasmonic acid （JA） oxidation. Three jasmonic acid oxidases （JAOs） of the 2-oxoglutarate dioxygenase family catalyze spe- cific oxidation of JA to 12OH-JA, and their genes are induced by wounding or infection by the fungus Botrytis cinerea. JA02 exhibits the highest basal expression, and its deficiency in jao2 mutants strongly enhanced antifungal resistance. The resistance phenotype resulted from constitutive expression of antimi- crobial markers rather than from their higher induction in infected jao2 plants and could be reversed by ectopic expression of any of the three JAOs injao2. Elevated defense injao2 was dependent on the activity of JASMONATE RESPONSE 1 （JAR1） and CORONATINE-INSENSITIVE 1 （COI1） but was not correlated with erihanced JA-Ile accumulation. Instead, jao2 mutant lines displayed altered accumulation of several JA species in healthy and challenged plants, suggesting elevated metabolic flux through JA-Ile. Collectively, these data identify the missing enzymes hydroxylating JA and uncover an important metabolic diversion mechanism for repressing basal JA defense responses.