Arginine promotes seed energy metabolism,increasing wheat seed germination at low temperature

Low temperatures during germination inhibit seed growth,lead to small and weak seedlings,and significantly reduce the wheat yield.Alleviating the adverse effects of low temperature on wheat seed germination is highly important for achieving high and stable wheat yields.In this study,Tongmai 6(insensitive)and Zhengmai 113(sensitive),which have different low-temperature sensitivities during germination were treated with low temperature during germination.The transcriptome,metabolome and physiological data revealed that low temperature decreased the germination rate,downregulated the expression of a large number of genes involved in regulating glycometabolism,and inhibited carbon,nitrogen(especially amino acids)and energy metabolism in the seeds.Arginine content increased at low temperature,and its increase in the low-temperature-tolerant variety was significantly greater than that in the sensitive variety.Arginine priming experiment showed that treatment with an appropriate concentration of arginine improved the seed germination rate.The conversion of starch to soluble sugar significantly increased under exogenous arginine conditions,the content of key metabolites in energy metabolism increased,and the utilization of ATP in the seeds increased.Taken together,arginine priming increased seed germination at low temperature by relieving inhibition of seed carbon and nitrogen metabolism and improving seed energy metabolism.

Effects of Wuwei Xiaodu Decoction on Uterine Energy Metabolism and Serum Inflammatory Factors in Rats with Acute Pelvic Inflammatory Disease

[Objectives]To observe the effects of Wuwei Xiaodu Decoction on uterine energy metabolism and serum inflammatory factors in the acute pelvic inflammatory disease(APID)model.[Methods]75 Wistar rats(females)were randomly divided into control group,model group and Wuwei Xiaodu Decoction low,medium and high dose groups(n=15).Except for the control group,the rat APID model was established by right uterine inoculation.On the fifth day after inoculation,the low,medium and high dose groups of Wuwei Xiaodu Decoction were administered at 4,8 and 16 g/kg,and the control group and model group received normal saline.Rats were killed 12 h after nondose administration,blood was collected from the abdominal aorta and measured by ELISA for serum interleukin-6(interleukin-6,IL-6),IL-8,and C-reactive proteins(CRP);the right uterus of rats was tested for high-energy phosphate adenosine phosphate(AMP),adenosine diphosphate(ADP),adenosine triphosphate(ATP)and total adenine nucleotides(TAN)level to evaluate the uterine energy metabolism.[Results]AMP,ADP,ATP and TAN were significantly higher in the Wuwei Xiaodu Decoction of low,medium and high dose than the model group,while the serum IL-6,IL-8 and CRP were significantly lower than the model group,and the difference between the low,medium and high doses(P<0.05).[Conclusions]The Wuwei Xiaodu Decoction can dose-dependent promote uterine energy metabolism and inhibit inflammatory response in APID model rats.

Protective Role of Wumen Jianzhong Qiangxin Granules in Rats with Post-myocardial Infarction Heart Failure and Effect on Myocardial Energy Metabolism

[Objectives]The paper was to determine the effect of Wumen Jianzhong Qiangxin granules(WJQG)on myocardial energy metabolism in a chronic heart failure rat model after myocardial infarction(MI).[Methods]Totally 40 normal male SD rats were randomly divided into sham operation group,model group,trimetazidine group and WJQG group(n=10).The model of MI was established by ligation of the left anterior descending branch except sham operation group.The rats in trimetazidine and WJQG groups were gavaged with 60 mg/kg and 16 g/kg emodin daily,respectively.After administration for 4 weeks,the changes in heart rate(HR),R-R interval(RRI),systolic arterial pressure(SAP),diastolic arterial pressure(DAP),mean arterial pressure(MAP),pulse pressure(PP),left ventricular end-diastolic pressure(LVEDP),rates of maximum positive left ventricular pressure development(+dp/dtmax)and rates of maximum negative left ventricular pressure development(-dp/dtmax)were analyzed.Morphology of myocardial tissues was observed by HE staining,the levels of myocardial tissue adenosine triphosphate(ATP)and glucose transporter type 4(GLUT-4)were determined using scientific research kit,and the expressions of mitochondrial creatine kinase(mit-CK),creatine kinase MM isoenzyme(CK-MM)and adenine nucleotide translocator(ANT)in myocardial tissues were determined by Western blotting.[Results](i)Compared with sham group,LVEDP obviously increased,while+dp/dtmax and-dp/dtmax significantly decreased in model group,with extremely significant difference in statistics(P<0.01).Compared with model group,LVEDP decreased,while+dp/dtmax and-dp/dtmax increased in trimetazidine group and WJQG group,with significant difference in statistics(P<0.05 orP<0.01).(ii)The cardiomyocytes ultrastructure of rats in sham group was normal,while in model group,extensive focus of MI can be seen under optic microscope.In the infarction focus,we can see outline of the necrotic tissue,infiltration of inflammatory cells,few fibroblasts,as well as the slow growth of granulation tissue.Focus of MI in both trimetazidine group and WJQG group were located in a certain part.In the infarction focus,we can see living myocardial cells distributing as islands and islets,more fibroblasts than in model group,as well as active hyperplasia of granulation tissue.(iii)Compared with sham group,the levels of myocardial tissues ATP and GLUT-4 in left ventricular myocardial cells in model group went down,with extremely significant difference(P<0.01).Compared with model group,the levels of myocardial tissues ATP and GLUT-4 in left ventricular myocardial cells in both trimetazidine group and WJQG group went up,with extremely significant difference(P<0.05).(iv)Compared with sham group,the expression level of CK-MM,mit-CK and ANT in left ventricular myocardial cells in model group went down,with extremely significant difference(P<0.01 orP<0.001).Compared with model group,the expression levels of CK-MM,mit-CK and ANT in left ventricular myocardial cells in both trimetazidine group and WJQG group went up,with extremely significant difference in statistics(P<0.05 orP<0.01 orP<0.001).[Conclusions]WJQG can effectively increase the levels of myocardial tissues ATP and GLUT-4,as well as the expression levels of CK-MM,mit-CK and ANT of rats with heart failure after MI,and thus enhance the full exchange between ATP and ADP on the inner membrane of mitochondria conducted by ANT.The prescription also helps to ensure myocardial energy supply and remodel the process of myocardial energy metabolism,and finally protects the cardiac function of rats.

Effects of Astragalus membranaceus on Energy Metabolism and Expression of CNTF Protein in Skeletal Muscle of Exercise-induced Fatigue Rats

[Objectives]This study was conducted to investigate the effects of Astragalus membranaceus in different groups on energy metabolism and CNTF protein expression in skeletal muscle of exercise-induced fatigue rats.[Methods]Thirty-five clean male SD rats were randomly divided into a normal group,and low-,meddle-and high-dose groups of A.membranaceus aqueous solution,with 7 rats in each group.The low-dose,medium-dose and high-dose groups were given by gavage at 0.65,1.3 and 2.6 g/kg,respectively,while the normal group and the model group were given normal food and water.The weight of rats was observed.The contents of serum urea,lactate,muscle glycogen,liver glycogen and CNTF expression were detected.[Results]After modeling,compared with the normal group,the serum lactate and urea contents of rats in the model group significantly increased(P<0.01),while the muscle glycogen content(P<0.01)and liver glycogen content(P<0.05)of the skeletal muscle significantly decreased.Compared with the model group,the low-,meddle-and high-dose groups of A.membranaceus significantly reduced the levels of lactate and urea in serum(P<0.01),while the levels of muscle glycogen and liver glycogen in the skeletal muscle significantly increased(P<0.01,P<0.05).[Conclusions]This study provides a good research foundation for the treatment of exercise-induced fatigue using traditional Chinese herb A.membranaceus in modern clinical practice.

Discussion on reprogramming of tumor energy metabolism and intervention of traditional Chinese medicine based on the theory of“collateral Q i stagnation”

The theory of stagnation of collateral Qi(Chinese medicine refers to the most fundamental and subtle substances thatconstitute the human body and maintain life activities,and also has the meaning of physiological functions)originates from the theory of collateral disease,which refers to the deficiency of Qi in the body’s collaterals,the loss of Qi and blood,and the failure of stagnation of collateral Qi,which leads to the loss of Qi,blood and body fluid,and the formation of pathological products such as deficiency,depression,phlegm,blood stasis in the local area,and ultimately damage the pathological process of collaterals.Based on the in-depth study of the pathogenesis of collateral Qi stagnation and the previous study of meridian channels,we believe that the key pathogenesis of the formation,evolution and spread of malignant tumors is“collateral Qi deficiency stagnation,collateral Qi stagnation and collateral Qi decay”.As an important energy resonance channel of the body,meridians play a key role in the process of material transformation and energy metabolism.It is believed that the small focus caused by the pathogenesis of stagnation is the cause of malignant transformation of tumor,the reprogramming of energy metabolism induced by the lesion of collateral Qi is the basis of the progress of tumor pathogenesis,and the formation of tumor microenvironment regulated by the tumor toxin vena is the root of alienation of tumor development.Guided by this theory,focusing on the correlation between collateral Qi and tumor energy metabolism,using Professor Hua Baojin's treatment method of“Regulating Qi and detoxifying”to prescribe drugs can adjust collateral Qi function,achieve the relative balance of internal environment,and then inhibit the progress of tumor.Based on the above understanding,this study tries to enlighten new diagnosis and treatment ideas under the guidance of“stagnation of collateral Qi”in traditional Chinese medicine,in order to provide some theoretical support for the intervention of traditional Chinese medicine in the process of tumor development.

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

AIM To investigate the effects of heme oxygenase-1(HO-1)-modified bone marrow mesenchymal stem cells(BMMSCs)on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation(RLT)in a rat model.METHODS BMMSCs were isolated and cultured in vitro using an adherent method,and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs.A rat acute rejection model following 50%RLT was established using a two-cuff technique.Recipients were divided into three groups based on the treatment received:normal saline(NS),BMMSCs and HO-1/BMMSCs.Liver function was examined at six time points.The levels of endothelin-1(ET-1),endothelial nitric-oxide synthase(e NOS),inducible nitric-oxide synthase(i NOS),nitric oxide(NO),and hyaluronic acid(HA)were detected using an enzyme-linked immunosorbent assay.The portal vein pressure(PVP)was detected by Power Lab ML880.The expressions of ET-1,i NOS,e NOS,and von Willebrand factor(v WF)protein in the transplanted liver were detected using immunohistochemistry and Western blotting.ATPase in the transplanted liver was detected by chemical colorimetry,and the ultrastructural changes were observed under a transmission electron microscope.RESULTS HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver,and improve the liver function of rats following 50%RLT,with statistically significant differences compared with those of the NS group and BMMSCs group(P<0.05).In term of the microcirculation of hepatic sinusoids:The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group(P<0.01);HO-1/BMMSCs could inhibit the expressions of ET-1 and i NOS,increase the expressions of e NOS and inhibit amounts of NO production,and maintain the equilibrium of ET-1/NO(P<0.05);and HO-1/BMMSCs increased the expression of v WF in hepatic sinusoidal endothelial cells(SECs),and promoted the degradation of HA,compared with those of the NS group and BMMSCs group(P<0.05).In term of the energy metabolism of the transplanted liver,HO-1/BMMSCs repaired the damaged mitochondria,and improved the activity of mitochondrial aspartate aminotransferase(ASTm)and ATPase,compared with the other two groups(P<0.05).CONCLUSION HO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly,and recover the energy metabolism of damaged hepatocytes in rats following RLT,thus protecting the transplanted liver.

Wnt gene expression in adult porcine longissimus dorsi and its association with muscle fiber type,energy metabolism,and meat quality

This study investigated the expression profiles of Writ genes in adult porcine Iongissimus dorsi （LD） from different porcine genotypes and their associations with meat quality. The results showed that Wnt5a gene expression level was the highest in Jinhua （JHP） pigs, followed by Zhongbai （ZBP）, DurocxZhongbai （DZB）, and Duroc×Yorkshire×Landrace （DYL） pigs, with significant differences between ZBP, DZB, and DYL （P〈0.05）. This genotypic order was reversed for Wnt7a, Wnt10b, and Wnt11 expression, with JHP and DYL having the lowest and highest expressive levels, respectively. Wnt5a expression was negatively correlated with pH,5 min and ApH （P〈0.01）, some glycolytic markers （P〈0.05）, and positively correlated with meat color （a＊）, shear force （SF） value （P〈0.05）, myosion heavy chain （MyHC） I mRNA proportion （P〈0.01）, turnover ratio of creatine phosphate （CP）, and creatine kinase （CK） activity （P〈0.05）. Opposite correlations were observed for Writ2, Wnt7a, Wnt10b, and Wnt11. These results revealed that Wnt5a, Wnt7a, Wnt10b, and Wnt11 gene expressions in adult porcine muscle contributed to differences between porcine genotypes and affected pork quality. Wnt5a gene expression could be beneficial for the formation of high quality pork by regulating muscle fiber types and postmortem energy metabolism.

Effects of L-Tetrahydropalmatine on Energy Metabolism,Endothelin-1 and NO during Acute Cerebral Ischemia-reperfusion of Rats

To investigate the effects of L-tetrahydropalmatine (L-THP) on ener-gy metabolism, endothelin-1 (ET-1 ) and NO during acute cerebral ischemia-reperfusion of rats, 24 Wistar rats were randomly divided into four groups, with 6rats in each group: sham-operation group, simple ischemia group, ischemia-reperfusion group and treatment group (L-THP group). Cerebral ATP, lactate,ET-1 and NO levels were measured in all groups. Our results showed that treat-ment with L-THP could increase cerebral ATP levels, but decrease cerebral lac-tate, ET-1 and NO concentrations during ischemia-reperfusion in the treatmentgroup. It is concluded that L-THP could improve cerebral energy metabolism and protect the injured brain tissue, the mechanism of which might be related to suppression of overproduction of ET-1 and NO.

Application of methyl jasmonate postharvest maintains the quality of Nanguo pears by regulating mitochondrial energy metabolism

The present study was conducted to investigate the effects of methyl jasmonate(Me JA)dipping treatment on mitochondrial energy metabolism and quality parameters of Nanguo pears during room temperature storage.The results showed that Me JA treatment suppressed the respiration rate and weight loss,and maintained the flesh firmness of Nanguo pears.Me JA also effectively maintained the content of ascorbic acid and titratable acidity in the fruit.Furthermore,the activities of H^(+)-ATPase,Ca^(2+)-ATPase,succinate dehydrogenase(SDH)and cytochrome C oxidase(CCO)of the Me JA-treated fruit were significantly higher than those of the untreated fruit.The contents of adenosine triphosphate(ATP)and adenosine diphosphate(ADP)and the energy charge were also enhanced by Me JA treatment.These results suggest that postharvest Me JA treatment could maintain the quality of Nanguo pears,in part by modulating mitochondrial energy metabolism during room temperature storage.

Metformin improves boar sperm quality via 5′-AMPactivated protein kinase-mediated energy metabolism in vitro

Sperm are specialized cells that require adenosine triphosphate(ATP) to support their function.Maintaining sperm energy homeostasis in vitro is vitally important to improve the efficacy of boar sperm preservation. Metformin can activate 5′-AMPactivated protein kinase(AMPK) to improve metabolic flexibility and maintain energy homeostasis. Thus, the aim of the present study was to investigate whether metformin can improve boar sperm quality through AMPK mediation of energy metabolism. Sperm motility parameters, membrane integrity,acrosomeintegrity,mitochondrial membrane potential(ΔΨm), ATP content, glucose uptake,and lactate efflux were analyzed.Localization and expression levels of AMPK and phospho-Thr172-AMPK(p-AMPK) were also detected by immunofluorescence and western blotting. We found that metformin treatment significantly increased sperm motility parameters, ΔΨm, and ATP content during storage at 17 ℃. Moreover, results showed that AMPK was localized at the acrosomal region, connecting piece, and midpiece of sperm and p-AMPK was distributed at the post-acrosomal region, connecting piece, and midpiece. When sperm were incubated with metformin for 4 h at 37 ℃, sperm motility parameters, ΔΨm, ATP content,p-AMPK, glucose uptake, and lactate efflux all significantly increased, whereas the addition of Compound C treatment, an inhibitor of AMPK,counteracted these positive effects. Together, our results suggest that metformin promotes AMPK activation, which contributes to the maintenance of energy hemostasis and mitochondrial activity,thereby maintaining boar sperm functionality and improving the efficacy of semen preservation.

Effect of Yuxingeng Fluid (愈心梗液) on Myocardial Energy Metabolism in Wistar Rats with Acute Myocardial Infarction

Objective: To examine the effect of Yuxingeng fluid (愈心梗液, YXGF) on myocardial energy metabolism in Wistar rats with acute myocardial infarction (AMI) by observing the ultrastructure of mitochondria and the enzyme activities of rat myocardial adenosine triphosphate (ATP), succinate dehydrogenase (SDH), acid phosphatase (ACP), alkaline phosphatase (ALP) and the content of glycogen. Methods; AMI models were established by ligature of left anterior descending coronary artery and then the rats with AMI were randomly divided into 7 groups: namely, blank group, model group, sham-operated group, captopil group, high-dose YXGF group, middle-dose YXGF group and low-dose YXGF group. From the next day after modeling, the rats were given YXGF through gastrogavage which lasted for 4 weeks. And then, the ultra-structure of mitochondria was observed by electronic microscope and the enzyme activities of ATP, SDH, ACP, ALP and the content of glycogen were determined. Results: Compared with model group, the other three groups of high-dose YXGF, middle-dose YXGF, low-dose YXGF and captopril group could protect the ultrastructure of mitochondria and significantly increase enzyme activities of ATP, SDH, ACP, ALP and the content of glycogen (P<0.01). Conclusion: YXGF can protect mitochondria and increase myocardial enzyme activities and the content of glycogen, which may be one of the mechanisms intervening in the pathological course of the early ventricular remodeling in rats with AMI.

Bone Remodeling and Energy Metabolism:New Perspectives

Bone mineral, adipose tissue and energy metabolism are interconnected by a complex and multilevel series of networks. Calcium and phosphorus are utilized for insulin secretion and synthesis of high energy compounds. Adipose tissue store lipids and cholecalciferol, which, in turn, can influence calcium balance and energy expenditure. Hormones long-thought to solely modulate energy and mineral homeostasis may influence adipocytic function. Osteoblasts are a target of insulin action in bone. Moreover, endocrine mediators, such as osteocalcin, are synthesized in the skeleton but regulate carbohydrate disposal and insulin secretion. Finally, osteoblasts and adipocytes originate from the same mesenchymal progenitor. The mutual crosstalk between osteoblasts and adipocytes within the bone marrow microenvironment plays a crucial role in bone remodeling. In the present review we provide an overview of the reciprocal control between bone and energy metabolism and its clinical implications.

Effect of food restriction on the energy metabolism of the Chinese bulbul（Pycnonotus sinensis）

Food resources play an important role in the regulation of animals’ physiology and behavior. We investigated the effect of short-term food restriction on metabolic thermogenesis of Chinese bulbuls（Pycnonotus sinensis） by measuring changes in body mass, body fat, basic metabolic rate（BMR）, and organ mass of wild-caught Chinese bulbuls from Wenzhou, China. Short-term food restriction induced a significant decrease in body mass and body fat but body mass returned to normal levels soon after food was no longer restricted. Food restriction caused a significant reduction in BMR after 7 days（P〈0.05）, which returned to normal levels after food restriction ceased. Log total BMR was positively correlated with log body mass（r2=0.126, P〈0.05）. The dry masses of livers and the digestive tract were higher in birds that had been subject to temporary food restriction than in control birds and those subject to continual food restriction（P〈0.001 and P〈0.05, respectively）. There was also significant differences in the dry mass of the lungs（P〈0.05）, heart（P〈0.01）, and spleen（P〈0.05） in birds subject to short-term food restriction compared to control birds and those subject to continual food restriction. BMR was positively correlated with body and organ（heart, kidney and stomach） mass. These results suggest that the Chinese bulbul adjusts to restricted food availability by utilizing its energy reserves, lowering its BMR and changing the weight of various internal organs so as to balance total energy requirements. These may all be survival strategies that allow birds to cope with unpredictable variation in food abundance.

Effects of microwave radiation on brain energy metabolism and related mechanisms

With the rapid development of electronic technologies, anxiety regarding the potential health hazards induced by microwave radiation(MW) has been growing in recent years. The brain is one of the most sensitive target organs for microwave radiation, where mitochondrial injury occurs earlier and more severely than in other organs. Energy metabolism disorders do play an important role during the process of microwave radiation-induced brain damage. In this paper, we will review the biological effects of microwave radiation, the features of brain energy supply and consumption and the effects of microwave radiation on mitochondrial energy metabolism and potential related mechanisms.

Natural Products and Derivatives Targeting at Cancer Energy Metabolism:A Potential Treatment Strategy

In the 1920s,Dr Otto Warburg first suggested the significant difference in energy metabolism between malignant cancer cells and adjacent normal cells.Tumor cells mainly adopt the glycolysis as energy source to maintain tumor cell growth and biosynthesis under aerobic conditions.Investigation on energy metabolism pathway in cancer cells has aroused the interest of cancer researchers all around the world.In recent years,plentiful studics suggest that targeting the peculiar cancer energy metabolic pathways,including glycolysis,mitochondrial respiration,amino acid metabolism,and fatty acid oxidation may be an effective strategy to starve cancer cells by blocking essential nutrients.Natural products (NPs)are considered as the “treasure trove of small molecules drugs” and have played an extremely remarkable role in the discovery and development of anticancer drugs.And numerous NPs have been reported to act on cancer energy metabolism targets.Herein,a comprehensive overview about cancer energy metabolism targets and their natural-occurring inhibitors is prepared.

Dried Rehmannia root protects against glutamate-induced cytotoxity to PC12 cells through energy metabolism-related pathways

Rehmannia has been shown to be clinically effective in treating neurodegenerative diseases; however, the neuroprotective mechanisms remain unclear. In this study, we established a model of neurodegenerative disease using PC12 cytotoxic injury induced by glutamate. The cells were treated with 20 mM glutamate in the absence or presence of water extracts of dried Rehmannia root of varying concentrations（70%, 50% and 30%）. The different concentrations of Rehmannia water extract significantly increased the activity of glutamate-injured cells, reduced the release of lactate dehydrogenase, inhibited apoptosis, increased the concentrations of NADH, NAD and ATP in cells, ameliorated mitochondrial membrane potential, and reduced the levels of light chain 3. Taken together, our findings demonstrate that Rehmannia water extracts exert a cytoprotective effect against glutamate-induced PC12 cell injury via energy metabolism-related pathways.

Energy metabolism and survival of liver grafts from non-heart-beating donor rats with warm ischemia injury

BACKGROUND: The shortage of donor livers is a critical limiting factor for the use of liver transplantation in treatment of end-stage liver diseases. Organs from non- heart-beating donors seem to be an effective option to alleviate this problem. Warm ischemia injury, however, directly influences the grafts' activity and functional recovery after operation. We investigated the energy metabolism and post-transplant survival of liver grafts after different warm ischemia times (WITs) in rats and determined the maximum limit for liver grafts with warm ischemia. METHODS: Rats were randomized into 7 groups with WITs of 0 (control), 10, 15, 20, 30, 45 or 60 minutes. The indices of energy metabolism were measured by reversed- phase high performance liquid chromatograpy and all liver graft specimens were subjected to ultrastructural observation. After orthotopic liver transplantation (OLT), the recovery of energy metabolism in liver grafts after 24 and 48 hours and the survival of the rats were assessed. RESULTS: The levels of adenosine triphosphate (ATP) and energy charge (EC) decreased gradually after different WITs in a time-dependent manner, and this was especially significant within 30 minutes. The levels of ATP and EC in liver grafts with 30 minutes of warm ischemia largely recovered 24 hours after OLT, with 45 minutes of warm ischemia partially recovered 48 hours after OLT, and with 60 minutes of warm ischemia, hardly recovered even 48 hours after OLT. The survival time after OLT did not significantly change with up to 30 minutes of WIT, while long-term survival was reduced with 45 and 60 minutes of WIT.CONCLUSIONS: The levels of ATP and EC after OLT may be important criteria for evaluating the quality of a liver graft. The WIT of a liver graft is closely related to the recovery of hepatic energy metabolism and the graft survival.

Glycolysis in energy metabolism during seizures

Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter Y-aminobutyric acid, and changes in the intra- and extracellular environment.

Anti-arthritis effect of berberine associated with regulating energy metabolism of macrophage through AMPK/HIF-1α pathway

OBJECTIVE To investigate berberine(BBR)attenuates arthritis in adjuvant-induced arthritic(AA)rats associated with regulating the energy metabolism and correcting the polarization of macrophages through activation of AMP-activated protein kinase(AMPK)and inhibition of hypoxia inducible factor 1α(HIF-1α).METHODS AA rats were treated with BBR(40,80,or 160 mg·kg-1)from days 15 to 29 after immunization.The histopathology of ankle joint was examined through hematoxylin-eosin(HE)staining.The concentrations of tumour necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,IL-2,IL-17A,interferon-gamma(IFN-γ),monocyte chemotactic protein 1(MCP-1),IL-4,IL-10,transforming growth factor-β1(TGF-β1),ATP,and lactic acid were measured by using ELISA kits.The percentage of M1 and M2 macro⁃phage cells in joint tissues were evaluated by immune-fluorescence.The expressions of p-AMPK and HIF-1αin joint of AA rats were determined according to immunohistochemistry analysis.The migration of macrophage was detected by Transwell assays.The expression of inducible nitric oxide synthase(iNOS),Arginase-1(Arg1),p-AMPK,AMPK and HIF-1αwere examined by Western blotting.The labeled macrophages were observed with laser confocal microscopy.RESULTS BBR relieved signs and symptoms of AA rats and reversed pathological changes.BBR treatment group exhibited decreases in pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-2,IL-17A,IFN-γ,and MCP-1)coupled with increases anti-inflammatory cytokines(IL-4,IL-10,TGF-β1)in the serum.The number of M1 macrophage was reduced,while the number of M2 macrophage was increased in BBR group joint tissues.Moreover,BBR showed marked up-regu⁃lation the expression of p-AMPK and down-regulation the expression of HIF-1αin joint of AA rats.Next in vitro study,we found BBR up-regulated the expression of p-AMPK,Arg1(M2 marker)and down-regulated the expression of HIF-1α,iNOS(M1 marker)induced by LPS in peritoneal macrophages from normal SD rat.Furthermore,BBR treatment inhibited the migration of macrophages stimulated by LPS.The level of ATP was elevated and lactic acid was reduced in LPSinduced macrophages after treated by BBR.However,Compound C significantly attenuated the effects of BBR on acti⁃vated macrophages.CONCLUSION BBR alleviates inflammation by regulating energy metabolism and correcting the polarization of macrophage through AMPK-HIF-1αpathway.BBR might have great therapeutic value for RA.

Effect of Tiaoxin Recipe(调心方)on Spatial Memory and Energy Metabolism of Oxidation Injured Alzheimer's Disease Rats

Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in treating AD. Methods: Eighty-eight SD rats were randomly divided into five groups (normal group, operative group, "AD" model group,TXR group and Aricept group). An oxygen free radical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate, DHF-FeCl3-ADP) was used to create oxidation injured rat models mimic to AD; spatial learning and memory impairment (Morris water maze method), the activity of Succinate-oxidase, NADH-oxidase, CytC-oxidase (Clark oxygen electrode method) and the expression of cytochrome oxidase (CO) II mRNA (in situ hybridization method) were observed. Results: Compared with the normal group, the spatial memory, activity of CytC-oxidase and COII mRNA expression of oxidation injured "AD" rats were obviously decreased; TXR, however, could improve these functions in "AD" rat models obviously. Conclusion: The mechanism of the action of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mitochondrial energy metabolism.