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ObjectiveTo investigate the effect of Gegen Qinliantang on glucose and lipid metabolism in the rat model of catch-up growth （CUG） induced by a high-fat diet and the underlying mechanism. MethodA total of 60 SD rats were randomized into a normal control group （n=18） and a modeling group （n=42）. The rat model of CUG was established with a restricted diet followed by a high-fat diet， and the changes of general status and body weight were observed. The levels of fasting blood glucose （FBG）， fasting insulin （FINS）， triglyceride （TG）， and total cholesterol （TC） were measured in 6 rats in each group at the end of the 4th and 8th week， respectively. The homeostasis model assessment of insulin resistance index （HOMA-IR） was calculated， and the insulin sensitivity and body composition changes of CUG rats were evaluated. The successfully modeled rats were assigned into 6 groups： normal control， model， high-， medium-， and low-dose Gegen Qinliantang （2.5， 5， 10 g·kg-1）， and pioglitazone （3.125 mg·kg-1）. The rats were administrated with corresponding drugs by gavage for 6 weeks， and the normal control group and model group were administrated with the same amount of normal saline. During the experiment period， the changes of body weight were recorded， and the FBG， FINS， HOMA-IR， TG， and TC were determined at the end of the experiment. Hematoxylin-eosin （HE） staining was employed to observe the pathological changes of skeletal muscle in rats. The levels of reactive oxygen species （ROS） and malondialdehyde （MDA） in the skeletal muscle were measured strictly according to the manuals of the reagent kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was performed to measure the mRNA levels of silencing information regulator 1 （SIRT1）， peroxisome proliferator-activated receptor-gamma coactivator1α （PGC1α）， and nuclear respiratory factor 1 （Nrf1） in the skeletal muscle. Western blot and immunohistochemistry were employed to assess the expression of SIRT1， PGC1α， and Nrf1 in the skeletal muscle. ResultCompared with the normal control group， the model group presented elevated levels of FBG， FINS， TG， and TC （P<0.05， P<0.01）， increased HOMA-IR （P<0.01）， increased diameter of muscle fibers and adipocytes between muscle cells in the skeletal muscle， rising levels of ROS and MDA in the skeletal muscle （P<0.01）， and down-regulated mRNA and protein levels of SIRT1， PGC1α， and Nrf1 （P<0.05， P<0.01）. Compared with the model group， Gegen Qinliantang （especially the medium and high doses） and pioglitazone decreased the body weight， FINS， HOMA-IR， and TG （P<0.05， P<0.01） and reduced interstitial components such as intermuscular fat in the skeletal muscles and the diameter of muscle fibers. Furthermore， the drugs lowerd the levels of ROS and MDA （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of SIRT1， PGC1α， and Nrf1 （P<0.05， P<0.01） in the skeletal muscle. ConclusionGegen Qinliantang can ameliorate the glucose and lipid metabolism disorders and insulin resistance in CUG rats by regulating the SIRT1/PGC1α/Nrf1 signaling pathway.
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ObjectiveTo explore the effect of precocious puberty on glucose metabolism and lipid metabolism in female rats. MethodsSixty two-day-old female rats were randomly divided into 2 groups. When aged 5 days， the precocious puberty group and normal group were given a single subcutaneous injection of danazol and solvent soybean oil respectively. The vaginal opening of rats was monitored from their 21 days of age. After 12 hours of fasting， all successful modeling rats were randomly executed within 3 days after vaginal opening， when aged 7 and 12 weeks. Then we measured the rats’ body weight and length， determined the concentrations of glucose， insulin， blood lipids， estradiol， leptin and adiponectin with enzyme-linked immunosorbent assay and observed the pathological changes of perirenal fat， uterus and ovary. ResultsFor body weight and length， rats in the precocious puberty group were smaller than those in the normal group within 3 days after vaginal opening， but which did not affect their subsequent growth and development， and there was no significant difference between the two groups at 7 and 12 weeks of age. Within 3 days after vaginal opening， insulin levels had significant difference between the two groups （P = 0.001）， the precocious group showed hyperinsulinemia and increased number of perirenal adipocytes. At three execution times， no significant difference was noted in estradiol， leptin and adiponectin levels between the two groups. The same was true in the ratios of ovary or uterus to body weight between the two groups. ConclusionsPrecocious puberty makes earlier onset of pubertal development and allows body maladaptation to the sudden changes of the internal environment. However， the changes due to precocious puberty are temporary and reversible， and they may become normal in adulthood.
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Aim To express and purify recombinant hCGH-CTP fusion protein in high-density suspension culture of Chinese hamster ovary cells (CHO-S), and to verify the lipid accumulation effect of rhCGH-CTP on 3T3-L1 mature adipocytes. Methods The recombinant protein expression vector (pcDNA3. 1-rhCGH-CTP) was constructed, achieved by fusing the human glycoprotein hormone beta 5/alpha 2 cDNA with CTP Linker. The expression plasmid was transiently transfected into the suspended CHO-S to express rhCGH-CTP protein and then purified, and the protein biological activity was verified. Intervention with 3T3-L1 mature adipocyte cells for 24 h was performed to detect the changes of intracellular triglyceride (TG) level. Results Western blot results showed that rhCGH-CTP protein was successfully expressed in CHO-S cells, and the yield was up to 715. 4 mg • L~ . The secreted protein was purified by AKTA pure system with higher purity that was up to 90% as identified by SDS-PAGE. In addition, the intracellular cAMP content of mature adipocytes with high expression of TSHR gene significantly increased after intervention with different concentrations of rhCGH-CTP protein by ELISA kit, indicating that rhCGH-CTP protein had biological activity. Oil red 0 staining showed that compared with the control group, the lipid content of mature adipocytes in the intervention groups with different concentrations of rhCGH-CTP protein significantly decreased (P < 0. 05) . Conclusions The rhCGH-CTP protein has been successfully expressed and purified with biological activity, and effectively reduce TG. This research provides an important theoretical basis for further revealing the physiological role of CGH protein and its potential application in clinical practice.
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Age-related macular degeneration(ARMD)is a neurodegenerative disease associated with oxidative stress. It is characterized by progressive death of photoreceptors and retinal pigment epithelium(RPE), and is one of the leading causes of irreversible loss of central vision in patients over the age of 65 years old. MicroRNA(miRNA)is a class of regulatory short-chain non-coding RNA that can bind and inhibit multiple gene targets in the same biological pathway. This unique property makes microRNA an ideal target for exploring the pathogenesis, diagnosis and treatment of non-exudative ARMD. Previous studies have found that the pathogenesis of non-exudative ARMD involves age, genetics, environment, oxidative stress, lipid metabolism, autophagy and immunity. However, the exact mechanisms have not been fully clarified. As biomarkers of non-exudative ARMD, miRNA play a role in oxidative stress and lipid metabolism. This article summarizes the role of various miRNA in targeting Nrf2 and HIF-1α to inhibit hypoxia-related angiogenesis signaling, thereby affecting oxidative stress. Additionally, miRNA regulate lipid uptake and the expression of ABCA1 in RPE and macrophages, thereby influencing lipid metabolism. This deepens the understanding of the role of miRNA in oxidative stress and lipid metabolism in non-exudative ARMD, and provides directions for further improving the understanding of the pathogenesis and prevention of non-exudative ARMD.
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ObjectiveBased on network pharmacology and transcriptomics， the mechanism of Zishen Qinggan prescription （ZSQGF） in improving glucose and lipid metabolism in type 2 diabetes （T2DM） model rats was explored. MethodBased on network pharmacology analysis of the differential genes between ZSQGF and T2DM， gene ontology（GO）analysis and Kyoto encyclopedia of genes and genomes（KEGG） analysis were conducted， and molecular docking analysis was used to verify the binding between components and targets. A T2DM rat model was established by high-fat feeding and injection of streptozotocin （STZ）. The rats were randomly divided into the control group， model group， metformin （Met， 72 mg·kg-1） group， and ZSQGF high-， medium-， and low-dose groups （ZSQGF-H， ZSQGF-M， and ZSQGF-L， with 4.8， 2.4， and 1.2 g·kg-1 raw drug in the solution）. The living status of rats was monitored and the levels of total cholesterol （TC）， total triglycerides （TG）， high density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in rat serum were detected. The liver tissues were subjected to Hematoxylin eosin（HE） staining and oil red O staining. The differential genes were analyzed through transcriptomics， GO and KEGG analysis， and the protein-protein interaction（PPI） network was obtained to screen key targets. With network pharmacology and transcriptomics analysis results， the protein pathways were identified. The expression levels of nuclear factor-κB （NF-κB）， matrix metalloproteinase（MMP）-1 and MMP-9 proteins in liver tissues were detected by Western blot. The mRNA expression of B-cell lymphoma-2（Bcl-2） modifying factor（BMF）， nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4）， and fatty acid synthase（FASN） was detected by real-time polymerase chain reaction（Real-time PCR）. The expression of MMP-1 and MMP-9 in the liver was detected by immunofluorescence staining. ResultTranscriptomics and network pharmacology analysis suggested that ZSQGF may protect the liver through the glucose and lipid metabolism pathway and the inflammation pathway. Experiments showed that after 8 weeks of administration， the body weight， blood sugar， serum indicators， and pathological staining results of rats were improved. Western blot results indicated a decrease in the relative expression levels of NF-κB， MMP-1 and MMP-9 proteins in the liver. Real-time PCR results showed a decrease in the transcriptional expression of BMF， NOX4， and FASN in the ZSQGF-H group， while immunofluorescence staining results present decreased expression of MMP-1 and MMP-9 in the ZSQGF groups. ConclusionZSQGF can improve the glucose and lipid metabolism by inhibiting the expression of FASN， reducing lipid synthesis， and regulating the NF-κB signaling pathway.
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ObjectiveTo explore the effect and mechanism of Qizhu prescription on liver lipid anabolism and oxidative stress in mice with non-alcoholic steatohepatitis （NASH） based on adenylate activated protein kinase （AMPK） signaling pathway. MethodA total of 60 male C57BL/6J mice were randomly divided into a normal group （n = 10） and a modeling group （n = 50）. The modeling group was fed by high-fat and high-cholesterol diet for 16 weeks to establish the NASH mice model and was randomly divided into model group， low-， medium， and high-dose groups of Qizhu prescription， and Yishanfu group， with 10 mice in each group. Qizhu prescription was administered intragastrically once a day at a dose of 4.75， 9.50， and 19.00 g·kg-1 in each group and 228 mg·kg-1 in Yishanfu group. The normal group and model group were given equal volumes of pure water for eight weeks. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total cholesterol （TC）， triglyceride （TG）， and glucose （GLU） levels were detected. The pathological changes of liver tissue were observed by hematoxylin-eosin （HE） and oil red O staining. Serum levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， free fatty acids （FFA）， reduced glutathione （GSH）， malondialdehyde （MDA）， catalase （CAT）， and superoxide dismutase （SOD） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of acetyl-CoA carboxylase （ACC）， carnitine palmitoyl transferase 1A（CPT1A）， and mitochondrial uncoupling protein 2 （UCP2） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Protein expression levels of AMPK， p-AMPK， ACC， CPT1A， and UCP2 in liver tissue were detected by Western blot. ResultCompared with the normal group， the liver steatosis of the model group was obvious， with multiple inflammatory clusters and large amounts of intracellular lipid deposition. The activity of serum AST， ALT， as well as levels of IL-6， IL-1β， TNF-α， FFA， and MDA were significantly increased， the activity of CAT and SOD was significantly decreased， and the mRNA and protein expressions of ACC were significantly increased. The mRNA and protein expressions of CPT1 and UCP2 were significantly decreased， and the protein expression of p-AMPK was significantly decreased （P<0.01）. Compared with the model group， the degree of liver steatosis in the Qizhu prescription and Yishanfu groups was reduced， the activity of AST and ALT， as well as the levels of IL-6， IL-1β， TNF-α， FFA， and MDA was significantly decreased， and the activity of CAT and SOD was significantly increased （P<0.01）. The mRNA and protein expressions of ACC in liver tissue of mice in medium- and high-dose groups of Qizhu prescription were significantly decreased， while the mRNA and protein expressions of CPT1A and UCP2， as well as p-AMPK protein were significantly increased （P<0.01）. ConclusionQizhu prescription can improve liver lipid metabolism， reduce oxidative stress， and promote liver cell repair in NASH mice by activating the AMPK signaling pathway.
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Hyperlipidemia is characterized by elevated levels of blood lipids. The clinical manifestations are mainly atherosclerosis caused by the deposition of lipids in the vascular endothelium. The link between abnormal lipid metabolism and sudden hearing loss remains unclear. This article presents a case study of sudden hearing loss accompanied by familial hyperlipidemia. Pure tone audiometry indicated intermediate frequency hearing loss in one ear. Laboratory tests showed abnormal lipid metabolism, and genetic examination identified a heterozygous mutation in theAPOA5 gene. Diagnosis: Sudden hearing loss; hypercholesterolemia. The patient responded well to pharmacological treatment. This paper aims to analyze and discuss thepotential connection between abnormal lipid metabolism and sudden hearing loss.
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Humanos , Audiometría de Tonos Puros , Sordera/complicaciones , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Súbita/diagnóstico , Hiperlipidemias/complicaciones , LípidosRESUMEN
Background Exposure to diisononyl phthalate (DINP), an endocrine disruptor associated with metabolic diseases and widely used in plastic products, has been linked to the development of several adverse health outcomes in the liver, including non-alcoholic fatty liver disease (NAFLD). Objective To investigate the effects and the possible molecular mechanisms of DINP exposure on lipid metabolism in human hepatocellular carcinoma cells (HepG2 cells). Methods First, HepG2 cells were treated with DINP at three time spots (24, 48, and 72 h) and eleven doses (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mmol·L−1). Cell viability were detected using cell counting kit 8 (CCK8). Intracellular lipid deposition was determined by oil red O staining and lipid content detection, and triglyceride (TG) and cholesterol (TC) were further detected. Finally, the mRNA expression levels were detected by fluorescence quantitative PCR, including fatty acid synthesis related genes [acetyl-CoA carboxylase alpha (Accα), fatty acid synthase (Fasn), malonyl-CoA decarboxylase (Mlycd), and sterol regulatory element binding protein 1 (Srebp1)] and β-oxidation related genes [peroxisome proliferator activated receptor alpha (Pparα), AMP-activated protein kinase (Ampk), carnitine palmitoyltransferase 1A (Cpt-1a), transcription factor A, mitochondrial (Tfam), nuclear respiratory factor 1 (Nrf1), and peroxisome proliferator-activated receptor gamma and coactivator 1 alpha (Pgc1-α)]. Results Compared with the control group (0 mmol·L−1), the no observed adverse effect levels (NOAEL) of HepG2 cell viability were 0.3, 0.1, and 0.1 mmol·L−1 after 24, 48, and 72 h exposure to DINP, respectively, and the corresponding lowest observed adverse effect levels (LOAEL) were 1, 0.3, and 0.3 mmol·L−1, respectively (P<0.05). After exposure to 30 mmol·L−1 and 100 mmol·L−1 DINP for 24 h, the intracellular lipid content, lipid deposition, TG, and TC levels were increased significantly compared with the control group (P<0.01). Compared with the control group, the mRNA expression levels of genes related to fatty acid synthesis, such as Mlycd, Srebp1, Fasn, and Accα, were down-regulated after the 100 mmol·L−1 DINP exposure for 24 h, while the mRNA expression level of Mlycd was up-regulated in the 30 mmol·L−1 group. The β-oxidation related genes such as Ampk, Pparα, and Tfam were up-regulated significantly after the 100 mmol·L−1 DINP exposure, while Cpt-1a mRNA expression level was down-regulated (P<0.05). Conclusion Exposure to DINP at 30 mmol·L−1 and 100 mmol·L−1 can interfere with fatty acid synthesis and β-oxidation in lipid metabolism of HepG2 cells, resulting in lipid deposition.
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Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.
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Primary biliary cholangitis （PBC） is an autoimmune liver disease characterized by progressive and non-purulent inflammation of small- and medium-sized bile ducts in the liver. Recent studies have shown that abnormal lipid metabolism is relatively common in patients with PBC， and 76% of PBC patients have dyslipidemia. The effects and harms of dyslipidemia have attracted much attention. Lipid metabolism disorders play an important role in the progression of PBC. This article mainly reviews the research advances in the manifestation， role， diagnosis， and treatment of lipid metabolism disorders in PBC， so as to provide new ideas for the treatment of PBC.
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Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.
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ObjectiveTo observe and compare the intervention effect of modified Cangfu Daotantang on glucose and lipid metabolism in simple obese children with phlegm dampness and stagnation. MethodA total of 60 children with simple obesity were randomly divided into two groups according to the simple randomization method of the random number table. The odd number was included in the test group， and the even number was included in the basic treatment group， with 30 cases in each group. On the basis of signing the informed consent notice， the treatment group was given modified Cangfu Daotantang combined with basic treatment， while the control group was only given basic treatment. After three months of treatment， the body mass index （BMI）， glucose and lipid metabolism level ［total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， fasting plasma glucose （FPG）， fasting insulin （FINS）， and homeostasis model assessment-insulin resistance （HOMA-IR）］， the change in the total score of traditional Chinese medicine （TCM） syndromes， and the effective rate of treatment were observed and compared. ResultAfter treatment， the BMI of the observation group and the control group decreased significantly （P<0.01）. Compared with the control group， the BMI level in the observation group decreased significantly （P<0.05）. After treatment， the levels of TC， TG， and LDL-C in the observation group and the control group decreased significantly （P<0.01）. Compared with the control group， the levels of TC， TG， and LDL-C in the observation group decreased significantly （P<0.05）. In addition， the level of TC in the observation group improved significantly compared with that in the control group （P<0.01）. The levels of FPG， FINS， and HOMA-IR in the observation group and the control group were significantly lower than those before treatment （P<0.05）. After treatment， compared with the control group， the levels of FPG， FINS， and HOMA-IR in the observation group were significantly reduced （P<0.05）. The level of FPG in the observation group was significantly improved compared with that in the control group （P<0.01）. After treatment， the total score of TCM syndromes in the two groups decreased significantly （P<0.01）. Compared with the control group， the total score of TCM syndromes in the observation group was lower （P<0.01）. After treatment， the total effective rate of treatment was 86.67% （26/30） in the observation group and 73.33% （22/30） in the control group. By rank sum test， the total effective rate of the observation group was better than that of the control group （Z=-2.100， P<0.05）. ConclusionModified Cangfu Daotantang combined with basic treatment can effectively reduce the BMI of obese children and improve their glucose and lipid metabolism. It has good clinical effects and high clinical application value， which is worth further in-depth research and promotion.
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ObjectiveTo investigate the different effects of Yunvjian with or without Achyranthis Bidentatae Radix on glucose and lipid metabolism and inflammatory response in diabetic rats with the syndrome of Yin deficiency and internal heat. MethodThe rat model of diabetes due to Yin deficiency and internal heat was established by feeding with a high-sugar and high-fat diet and injection of thyroxine and streptozotocin. The successfully modeled rats were randomized into model control， Yunvjian without Achyranthis Bidentatae Radix （11.8 g·kg-1）， Yunvjian with Achyranthis Bidentatae Radix （12.8 g·kg-1）， and Achyranthis Bidentatae Radix （1.0 g·kg-1） groups （n=10）， and another 10 rats were taken as the normal control group. Each group was administrated with corresponding drugs or saline by gavage for 28 days. The fasting blood glucose （FBG）， fasting insulin （FINS）， total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in rats were measured. Enzyme-linked immunosorbent assay was employed to determine the levels of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， triiodothyronine （T3）， thyroxine （T4）， interleukin （IL）-1β， IL-6， tumor necrosis factor （TNF）-α， and C-reactive protein （CRP） in the serum. The histopathological changes of the liver were observed. The expression of lipoxygenase-2 （COX-2） was detected by immunofluorescence. The mRNA levels of nuclear transcription factors-κB （NF-κB）， monocyte chemotactic protein-1 （MCP-1）， and intercellular adhesion molecule-1 （ICAM-1） were determined by real-time polymerase chain reaction （Real-time PCR）.Western blot was employed to determine the protein levels of NF-κB in hibitory protein（IκB） kinase β （IKKβ）， IκBα， and phosphorylated IκBα （p-IκBα） in the liver and the protein levels of NF-κB in the cytoplasm and nucleus. ResultCompared with the normal group， the model group showed elevated levels of FBG， FINS， insulin resistance index， TC， TG， LDL-C， cAMP， T3， T4， IL-1β， IL-6， TNF-α， and CRP， up-regulated mRNA levels of NF-κB， MCP-1， and ICAM-1， and up-regulated protein levels of COX-2， p-IκBα， and nuclear NF-κB （P<0.01）. Compared with the model group， Yunvjian without Achyranthis Bidentatae Radix lowered the levels of FBG， FINS， insulin resistance index， TC， TG， LDL-C， cAMP， T3， T4， IL-1β， IL-6， TNF-α， and CRP， down-regulated the mRNA levels of NF-κB， MCP-1， and ICAM-1， and down-regulated the protein levels of COX-2， p-IκBα and nuclear NF-κB （P<0.05， P<0.01）. Compared with the Yunvjian without Achyranthis Bidentatae Radix， Yunvjian with Achyranthis Bidentatae Radix showed lowered levels of FBG， FINS， insulin resistance index， and inflammatory cytokines， down-regulated mRNA levels of NF-κB， MCP-1， and ICAM-1， and down-regulated protein levels of p-IκBα and nuclear NF-κB （P<0.05， P<0.01）. ConclusionAchyranthis Bidentatae Radix can enhance the performance of Yunvjian in reducing blood glucose and inhibiting inflammation in diabetic rats with the syndrome of yin deficiency and internal heat by down-regulating the IKK/IκB/NF-κB signaling pathway.
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OBJECTIVE To explore the mechanism of Yishen tongluo formula （YSTLF） in improving abnormal lipid metabolism based on the sterol regulatory element binding proteins （SREBPs） pathway. METHODS Using C57BLKS/J （db/db） mice as model and C57BLKS/J （db/m） mice as normal control， the mechanism of 1， 2.5 and 5 g/kg YSTLF improving abnormal lipid metabolism of db/db mice was investigated by determining the liver coefficient， the contents of serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL） and high-density lipoprotein （HDL）， observing steatosis and lipid accumulation in liver tissue of mice， detecting the protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription levels of Srebp- 1c， Srebp-2 and their downstream lipid metabolism-related target genes （Fasn， Acc1， Scd5， Fads1， Hmgcr， Dhcr24， Insig-1， Fdps） in liver tissue of mice. Using low-fat cultured human liver cancer cell HepG2 as an in vitro cell model for abnormal lipid metabolism， and 25-HC （SREBPs inhibitor， 10 μmol/L） as the control， the effects of 125， 250 and 500 μg/mL YSTLF on protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription of SREBP-1c， SREBP-2 and their downstream lipid metabolism-related target genes were investigated to verify the mechanism in vitro. RESULTS 1， 2.5， 5 g/kg YSTLF significantly reduced the levels of TC， TG and LDL， the percentage of lipid droplet-positive region in liver tissue and liver coefficient， significantly down-regulated protein expressions of Pre-SREBP-1， n-SREBP-1， Pre-SREBP-2 and n-SREBP-2， and mRNA transcription of Srebp-1c， Srebp-2 and their downstream target genes in liver tissue， while significantly increased HDL level， with statistical significance （P＜0.05 or P＜0.01）. In the cell experiment in vitro， the expressions of the above-mentioned proteins and genes in the cells treated with YSTLF at 125， 250 and 500 μg/mL for 24 hours were consistent with those in the animal experiment； there was no significant difference in the expressions of the above-mentioned proteins and genes between inhibitor control group and 250， 500 μg/mL YSTLF groups （P＞0.05）. CONCLUSIONS YSTLF can regulate the expression of transcription factor SREBPs， so as to inhibit the high expression of fatty acid and cholesterol synthesis-related genes， promote the degradation of TC and TG， improve the abnormality of lipid metabolism and inhibit lipid accumulation， thus playing the role of lipid-lowering.
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OBJECTIVE To investigate the improvement effects and possible mechanism of Phyllanthus emblica water extracts on lipid metabolism disorder and insulin resistance （IR） in diabetic model rats. METHODS IR model of male SD rats was established and randomly divided into model group， positive control group， P. emblica water extracts high-dose， medium-dose and low-dose groups， and another blank group was set up， with 10 rats in each group. P. emblica water extracts high-dose， medium- dose and low-dose groups were given P. emblica water extract diluent at the doses of 800， 400 and 200 mg/kg respectively； positive control group was given pioglitazone solution 2.7 mg/kg； blank group and model group were given the same volume of normal saline， by intragastrical administration， once a day， for consecutive 4 weeks. The general state of rats was observed， and the body mass and the levels of serum lipid metabolism indexes [triacylglycerol （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] were measured； fasting insulin of serum （FINS）， insulin resistance index （IRI） and insulin sensitivity index （ISI） were measured and calculated by enzyme-linked immunosorbent assay （ELISA）. The pathological morphology of liver tissue was observed by hematoxylin-eosin staining； the expression of glycogen in the liver was observed by periodic acid-Schiff staining， and the staining area was calculated； the protein expressions of peroxisome proliferator-activated receptor γ （PPARγ）， nuclear factor κB（NF-κB） and AMP-activated protein kinase （AMPK） were detected by Western blot. RESULTS Compared with blank group， the rats in the model group had obvious symptoms of polydipsia， polyphagia and polyuria， and the serum levels of TC， TG， LDL-C， FINS and IRI were significantly increased （P＜0.05）， while ISI was significantly reduced （P＜ 0.05）； the structure of hepatic lobule was obviously disordered， the liver cells were deformed and enlarged， and there were many lipid deposits and fat vacuoles； PAS staining area of glycogen was significantly reduced（P＜0.05）； the protein expression levels of PPARγ and p-AMPK were significantly decreased （P＜0.05）， while the protein expression level of NF-κB was significantly increased （P＜0.05）. Compared with model group， the mental state of rats， liver histopathological morphology and glycogen expression were improved significantly in P. emblica water extracts high-dose and medium-dose groups； the levels of the above indicators were significantly reversed（P＜0.05）. CONCLUSIONS P. emblica water extracts may improve glucose and lipid metabolism disorders， liver function and IR in IR model rats， and regulate IR by activating the PPARγ/AMPK/NF-κB signaling pathway.
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With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.
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Humanos , Glucosa , Metabolismo de los Lípidos , Simulación del Acoplamiento Molecular , Medicamentos Herbarios Chinos/farmacología , Ginsenósidos , Proteínas , Saponinas , ARN MensajeroRESUMEN
Atherosclerosis(AS) is the key pathological basis of coronary heart disease(CHD), and lipid infiltration is a classical theory to explain the pathological mechanism of AS. The theory highlights that the occurrence and development of AS are closely related to abnormal lipid metabolism, with the essence of the pathological reaction caused by the invasion of lipids into arterial intima from plasma. Phlegm and blood stasis are physiologically homologous and subject to pathological co-existence. Phlegm-blood stasis correlation is the basic theory to explain the pathogenesis characteristics of CHD and has important guiding significance for revealing the mecha-nism of lipid infiltration of CHD. Phlegm is the pathological product of abnormal metabolism of Qi, blood, and body fluid, and a gene-ral summary of a series of abnormally expressed lipid substances. Among them, turbid phlegm invades the heart vessels, gradually accumulates, and condenses to achieve the qualitative change from "invisible pathogen" to "tangible pathogen", which corresponds to the mechanism of lipid migration and deposition in the intima of blood vessels, and is the starting factor of the disease. Blood stasis is the continuous development of phlegm, and it is a result of pathological states such as decreased blood fluidity, increased blood coagulation, and abnormal rheology. The fact that blood stasis caused by phlegm accords with the pathological process of "lipid abnormality-circulatory disturbance" and is the central link of the disease. Phlegm and blood stasis aggravate each other and lead to indissoluble cementation. The phlegm-blood stasis combination serves as common pathogen to trigger the disease, which is the inevitable outcome of the disease. Based on the phlegm-blood stasis correlation theory, the simultaneous treatment of phlegm and blood stasis is established. It is found that this therapy can simultaneously regulate blood lipid, reduce blood viscosity, and improve blood circulation, which can fundamentally cut off the biological material basis of the reciprocal transformation between phlegm and blood stasis, thus exerting a significant curative effect.
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Humanos , Medicina Tradicional China , Enfermedad Coronaria , Moco , Aterosclerosis , LípidosRESUMEN
According to the traditional Chinese medicine(TCM) theory, coronary heart disease(CHD) is mainly caused by heart vessel obstruction due to Qi stagnation, blood stasis, and phlegm turbidity. Chest impediment with combined phlegm and stasis is a common syndrome of CHD, with the manifestations of chest tightness, chest pain, and asthma. Lymphatic system is one of the important immune systems in the human body and has a close relationship with the Qi and blood movement in TCM. The dysfunction of the lymphatic system may lead to metabolism disorders, the generation of dampness pathogen which turns into sticky and difficult-to-dissolve phlegm turbidity. Moreover, it can affect blood circulation and coagulation, causing slow blood flow, increased blood viscosity, and microcirculation disorders. Alterations in lymphatic hydrodynamics may affect the interaction between blood circulation and the lymphatic system. A variety of small molecule drugs and TCM can treat cardiovascular diseases by targeting the lymphatic system. This review discusses the role of the lymphatic system in CHD based on the theory of combined phlegm and stasis, involving the influences of mechanical factors on lymphatic function and the effects and pharmacological mechanisms of TCM and chemicals that target lymphocyte function and lymphatic circulation. By expounding the development process of combined phlegm and stasis in CHD from the lymphatic system, this paper aims to provide new ideas for deciphering pharmacological mechanisms of TCM for resolving phlegm and stasis.
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Humanos , Enfermedad Coronaria , Medicina Tradicional China , Moco , Sistema Linfático , CorazónRESUMEN
The global incidence rate of nonalcoholic steatohepatitis (NASH) continues to rise. The pathogenesis of NASH is complex, and there is no effective clinical treatment. Previous study has shown that DEAD box protein 5 (DDX5) can significantly alleviate the NASH process in mice. This study screened the natural product library of the research group and found that the active compound hypercalin B (HB) in Hypericum beanii N. Robson, a traditional Chinese medicine, can upregulate the expression of DDX5 protein in a dose-dependent manner. In this study, an in vitro model of NASH stimulated by palmitic acid (PA) and an animal model of NASH induced by the methionine- and choline-deficient diet (MCD) were constructed. Different concentrations of HB were used to investigate the effect and mechanism of HB in alleviating NASH progression. All animal experiments in this paper were approved by the Ethics Committee of China Pharmaceutical University (NO: 2021-02-003). In vitro model results showed that HB significantly reduced the intracellular lipid deposition induced by free fatty acid (FFA). Animal experiments showed that HB improved liver injury by significantly reducing lipid accumulation in the liver of NASH mice, and reducing serum aspartate transaminase (AST) and alanine transaminase (ALT) levels. Moreover, HB could inhibit liver inflammation by reducing the mRNA levels of liver pro-inflammatory cytokines including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNFα). Further research showed that HB could reduce the phosphorylation level of the mechanical target of rapamycin (mTOR) and reduce the expression of sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN), thereby improving lipid metabolism and alleviating NASH progression, and the effects of HB against NASH were dependent on DDX5. In conclusion, HB can improve lipid metabolism and inhibit inflammatory activation by suppressing mTORC1 pathway via upregulating DDX5 protein, and showed promising anti-NASH activity in vitro and in vivo.
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Gouty arthritis is a type of metabolic rheumatic disease caused by autoimmune abnormalities. Currently, the use of Western medicine in the clinical treatment of gouty arthritis has been associated with a high risk of adverse reactions. Therefore, there is a growing interest in exploring therapeutic drugs from traditional Chinese medicine as a potential alternative. According to the theory of traditional Chinese medicine, gouty arthritis has been classified as damp-heat arthralgia syndrome. Shirebi granules has been found to have good clinical efficacy in treating gouty arthritis. However, its underlying pharmacological mechanisms remain unclear. To address this problem, the study first established the interaction network of candidate targets for Shirebi granules, which is used to treat damp-heat syndrome of gouty arthritis. Then, the key candidate targets of Shirebi granules for treating gouty arthritis with damp-heat syndrome were screened by calculating the topological features of the network nodes. Then, the functional mining of the key candidate targets revealed that the candidate targets of Shirebi granules may intervene in the biological process of inflammatory response and lipid metabolism through the crosstalk of Wnt/β-catenin signaling. To verify the effectiveness of Shirebi granules in treating gouty arthritis with damp-heat syndrome, a rat model was established. The results demonstrated that the granules significantly improved the severity of arthritis in rats with this condition, reduced joint inflammation, gait score, swelling index, increased mechanical pain threshold (P < 0.05), and reduced the content of serum inflammatory factors IL-1β, IL-6, and TNF-α in gouty arthritis rats with damp-heat syndrome (P < 0.01) gouty. It was also found that Shirebi granules effectively alleviated the symptoms of dampness heat syndrome such as local joint fever and dry mouth by reducing the temperature of the joints in acute gouty arthritis with damp-heat syndrome (AD) rats, increasing the threshold of heat pain, increasing water intake (P < 0.01), and inhibiting abnormal changes in the content of fatty acid oxidation related enzymes (P < 0.01). Western blot analysis showed that Shirebi granules increased the protein expression levels of Wnt and β-catenin (P < 0.01) while decreasing the protein expression of p65, p-p65 and PPARγ (P < 0.01) in rats with gouty arthritis and damp-heat syndrome. The results showed that Shirebi granules may reverse the "inflammation-immune" imbalance and lipid metabolism disorder by regulating the crosstalk of Wnt/β-catenin signaling, and play a role in alleviating the severity of the disease. This study provides a methodological reference for elucidating the pharmacological mechanisms of traditional Chinese medicine formulas. It also presents research ideas for the appropriate clinical use of Chinese patent medicines and the development of new clinical drugs for gouty arthritis therapy. The animal welfare and experiment procedures of this study were performed in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences (grant No. ERCCACMS11-2302-08).