ABSTRACT
This study investigated the mechanism of Zexie Decoction(ZXD) in promoting white adipose tissue browning/brown adipose tissue activation based on the GLP-1R/cAMP/PKA/CREB pathway. A hyperlipidemia model was induced by a western diet(WD) in mice, and the mice were divided into a control group, a model group(WD), and low-, medium-, and high-dose ZXD groups. An adipogenesis model was induced in 3T3-L1 cells in vitro, and with forskolin(FSK) used as a positive control, low-, medium-, and high-dose ZXD groups were set up. Immunohistochemistry and immunofluorescence results showed that compared with the WD group, ZXD promoted the expression of UCP1 in white and brown adipose tissues, and also upregulated UCP1, CPT1β, PPARα, and other genes in the cells. Western blot analysis showed a dose-dependent increase in the protein expression of PGC-1α, UCP1, and PPARα with ZXD treatment, indicating that ZXD could promote the white adipose tissue browning/brown adipose tissue activation. Hematoxylin-eosin(HE) staining results showed that after ZXD treatment, white and brown adipocytes were significantly reduced in size, and the mRNA expression of ATGL, HSL, MGL, and PLIN1 was significantly upregulated as compared with the results in the WD group. Oil red O staining and biochemical assays indicated that ZXD improved lipid accumulation and promoted lipolysis. Immunohistochemistry and immunofluorescence staining for p-CREB revealed that ZXD reversed the decreased expression of p-CREB caused by WD. In vitro intervention with ZXD increased the protein expression of CREB, p-CREB, and p-PKA substrate, and increased the mRNA level of CREB. ELISA detected an increase in intracellular cAMP concentration with ZXD treatment. Molecular docking analysis showed that multiple active components in Alismatis Rhizoma and Atractylodis Macrocephalae Rhizoma could form stable hydrogen bond interactions with GLP-1R. In conclusion, ZXD promotes white adipose tissue browning/brown adipose tissue activation both in vivo and in vitro, and its mechanism of action may be related to the GLP-1R/cAMP/PKA/CREB pathway.
Subject(s)
Mice , Animals , Adipose Tissue, Brown , Molecular Docking Simulation , PPAR alpha/metabolism , Adipose Tissue, White , RNA, Messenger/metabolismABSTRACT
Three sesquiterpenoids were isolated and purified from the 95% ethanol extract of Atractylodis Macrocephalae Rhizoma by column chromatography on silica gel, Sephadex LH-20, ODS, and high-performance liquid chromatography(HPLC). Their chemical structures were identified on the basis of spectroscopic analysis and physiochemical properties as(7Z)-8β,13-diacetoxy-eudesma-4(15),7(11)-diene(1), 7-oxo-7,8-secoeudesma-4(15),11-dien-8-oic acid(2), and guai-10(14)-en-11-ol(3). Compounds 1 and 2 are new compounds and compound 3 was obtained from Compositae family for the first time. Compounds 1, 2, and 3 showed weak inhibitory activities against sterol regulatory element-binding proteins(SREBPs).
Subject(s)
Atractylodes/chemistry , Drugs, Chinese Herbal/chemistry , Rhizome/chemistry , Sesquiterpenes, Eudesmane/pharmacology , Sterol Regulatory Element Binding Proteins/antagonists & inhibitorsABSTRACT
The present study investigated the pharmaceutical effect and underlying mechanism of Zexie Decoction(ZXD) on nonalcoholic fatty liver disease(NAFLD) in vitro and in vivo via the LKB1/AMPK/PGC-1α pathway based on palmitic acid(PA)-induced lipid accumulation model and high-fat diet(HFD)-induced NAFLD model in mice. As revealed by the MTT assay, ZXD had no effect on HepG2 activity, but dose-dependently down-regulated alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver cell medium induced by PA, and decreased the plasma levels of ALT and AST, and total cholesterol(TC) and triglyceride(TG) levels in the liver. Nile red staining showed PA-induced intracellular lipid accumulation, significantly increased lipid accumulation of hepatocytes induced by PA, suggesting that the lipid accumulation model in vitro was properly induced. ZXD could effectively improve the lipid accumulation of hepatocytes induced by PA. Oil red O staining also demonstrated that ZXD improved the lipid accumulation in the liver of HFD mice. JC-1 staining for mitochondrial membrane potential indicated that ZXD effectively reversed the decrease in mitochondrial membrane potential caused by hepatocyte injury induced by PA, activated PGC-1α, and up-regulated the expression of its target genes, such as ACADS, CPT-1α, CPT-1β, UCP-1, ACSL-1, and NRF-1. In addition, as revealed by the Western blot and immunohistochemistry, ZXD up-regulated the protein expression levels of LKB1, p-AMPK, p-ACC, and PGC-1α in vivo and in vitro. In conclusion, ZXD can improve NAFLD and its mechanism may be related to the regulation of the LKB1/AMPK/PGC-1α pathway.
Subject(s)
Animals , Mice , AMP-Activated Protein Kinases/metabolism , Alanine Transaminase/metabolism , Diet, High-Fat , Liver/metabolism , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaABSTRACT
The mammalian target of rapamycin (mTOR)-sterol regulatory element-binding proteins (SREBPs) signaling promotes lipogenesis. However, mTOR inhibitors also displayed a significant side effect of hyperlipidemia. Thus, it is essential to develop mTOR-specific inhibitors to inhibit lipogenesis. Here, we screened the endogenous inhibitors of mTOR, and identified that FKBP38 as a vital regulator of lipid metabolism. FKBP38 decreased the lipid content
ABSTRACT
BACKGROUND: Posterior pedicle screw fixation is a common method for treatment of thoracolumbar compression fractures. The fixation method contains long-segment fixation, short-segment fixation and vertebral fixation. Clinical effects of vertebral fixation and inter-vertebral short-segment fixation for treating thoracolumbar fractures remain unclear. OBJECTIVE: To compare the stability of posterior vertebral fixation and inter-vertebral pedicle screw fixation for treating thoracolumbar compression fractures. METHODS: Clinical data of 46 patients with thoracolumbar compression fractures were retrospectively analyzed. According to the fixation methods, they were divided into the vertebral fixation group (n=21) and inter-vertebral fixation group (n=25). The operation time, intraoperative bleeding, intraoperative blood transfusion, the time of lying in bed, vertebral Cobb angle, anterior vertebral height and visual analog scores were evaluated for a long time. RESULTS AND CONCLUSION: (1) During repair, in both groups, operation time, intraoperative bleeding and intraoperative blood transfusion were better in the inter-vertebral fixation group than in the vertebral fixation group (P < 0.05-0.01). The time of lying in bed was better in the vertebral fixation group than in inter-vertebral fixation group (P < 0.01). (2) No significant difference in Cobb angle and anterior vertebral height was detected before and after treatment and during repair in both groups, but final fol ow-up and fol ow-up loss were better in the vertebral fixation group than in inter-vertebral fixation group (P < 0.05-0.01). (3) No significant difference in visual analog scores was detected before and after treatment in both groups. Visual analog scores were better in the vertebral fixation group than in the inter-vertebral fixation group (P <0.01). (4) These results suggested that the two fixation methods obtained satisfactory repair effects in long-term fol ow-up. The dominance in maintaining the height and curvature of the spine was more obvious in the vertebral fixation group than in the inter-vertebral fixation group. The vertebral fixation can be more effective to reconstruct the spinal physiological sequence and restore its stability. After repair, low back pain can also be effectively control ed.
ABSTRACT
As a culinary and medicinal herb, rosemary is widely used. The present work aimed to investigate the effects of rosemary extracts on metabolic diseases and the underlying mechanisms of action. Liver cells stably expressing SREBP reporter were used to evaluate the inhibitory effects of different fractions of rosemary extracts on SREBP activity. The obese mice induced by Western-type diet were orally administered with rosemary extracts or vehicle for 7 weeks, the plasma and tissue lipids were analyzed. SREBPs and their target genes were measured by quantitative RT-PCR. We demonstrated that the petroleum ether sub-fraction of rosemary extracts (PER) exhibited the best activity in regulating lipid metabolism by inhibiting SREBPs, while water and n-BuOH sub-fraction showed the SREBPs agonist-effect. After PER treatment, there was a significant reduction of total SREBPs in liver cells. PER not only decreased SREBPs nuclear abundance, but also inhibited their activity, resulting in decreased expression of SREBP-1c and SREBP-2 target genes in vitro and in vivo. Inhibiting SREBPs by PER decreased the total triglycerides and cholesterol contents of the liver cells. In the mice fed with Western-type diet, PER treatment decreased TG, TC, ALT, glucose, and insulin in blood, and improved glucose tolerance and insulin sensitivity. Furthermore, PER treatment also decreased lipid contents in liver, brown adipose tissue, and white adipose tissue. Our results from the present study suggested that petroleum ether fraction of rosemary extracts exhibited the best potential of improving lipid metabolism by inhibiting SREBPs activity.
Subject(s)
Animals , Humans , Male , Mice , Alkanes , Chemistry , Cholesterol , Metabolism , Hepatocytes , Metabolism , Hyperlipidemias , Drug Therapy , Genetics , Metabolism , Insulin , Metabolism , Insulin Resistance , Liver , Metabolism , Mice, Inbred C57BL , Petroleum , Plant Extracts , Chemistry , Rosmarinus , Chemistry , Sterol Regulatory Element Binding Protein 1 , Genetics , Metabolism , Sterol Regulatory Element Binding Protein 2 , Genetics , MetabolismABSTRACT
Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized (OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet β cells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion (GSIS), which was abolished by estrogen receptor (ER) antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.
Subject(s)
Animals , Female , Humans , Mice , Rats , Drugs, Chinese Herbal , Glucose , Metabolism , Insulin , Metabolism , Insulin Secretion , Insulin-Secreting Cells , Metabolism , Menopause , Metabolism , Metabolic Syndrome , Drug Therapy , Metabolism , Rats, Sprague-DawleyABSTRACT
To refine and analyze the characteristics and laws of acupoint selection in treatment of hyperlipidemia with acupuncture and moxibustion. By retrieving the main databases of Chinese and English version, the clinical research literature is included on the definite acupoints for hyperlipidemia treated with acupuncture and moxibustion, and the characteristics and laws are analyzed on the acupoint selection for hyperlipidemia treated with acupuncture and moxibustion. It is found out that the special points have been mainly used in treatment of hyperlipidemia. The first five top acupoints of high frequency use include Fenglong (ST 40), Zusanli (ST 36), Sanyinjiao (SP 6), Neiguan (PC 6) and Tianshu (ST 25). Totally 10 meridians are involved in acupoint prescriptions. The meridians of higher frequency use include the Stomach Meridian, the Spleen Meridian, the Conception Vessel, the Bladder Meridian and the Pericardium Meridian. The specific points are mainly from the Stomach Meridian, the Spleen Meridian, the Conception Vessel, the Bladder Meridian and the Pericardium Meridian in the treatment of hyperlipidemia. The acupoint prescription of acupuncture and moxibustion for hyperlipidemia is characterized as determining the treating principle based on the spleen theory, selecting the acupoints along the running courses of the spleen and stomach meridians, combining the nearby acupoints with the distal ones, selecting the acupoints for adjusting the deficiency and excess of zangfu and syndrome differentiation, collaborating the acupoints located in the front and on the back, as well as supplementing the acupoints based on symptoms.
Subject(s)
Humans , Acupuncture Points , Acupuncture Therapy , Hyperlipidemias , Therapeutics , MoxibustionABSTRACT
AIM@#To profile the chemical constituents in Jinqi Jiangtang tablets.@*METHOD@#Based on the chromatographic retention behavior, fragmentation patterns of chemical components, and published literatures, a high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-Q-TOF/MS) method was established to characterize and identify components in Jinqi Jiangtang tablets.@*RESULTS@#A total of 52 chemical compounds, including eight iridoid glycosides, seven phenolic acids, twelve alkaloids, six flavonoids, and nineteen saponins, were identified in Jinqi Jiangtang tablets.@*CONCLUSION@#The established method could serve as a powerful tool for structural characterization and quality control of this Chinese herbal preparation.
Subject(s)
Alkaloids , Astragalus Plant , Chromatography, High Pressure Liquid , Coptis , Drugs, Chinese Herbal , Chemistry , Flavonoids , Iridoid Glycosides , Lonicera , Phenols , Saponins , Spectrometry, Mass, Electrospray Ionization , Tandem Mass SpectrometryABSTRACT
<p><b>OBJECTIVE</b>To explore the feasibility of electroacupuncture compound anesthesia in radiofrequency ablation for hypertrophic inferior turbinate.</p><p><b>METHODS</b>The patients confirmed to the enrolled criteria were randomly divided into an observation group (n = 31) and a control group (n = 30). The observation group was treated with electroacupuncture at Sibai (ST 2), Xiaguan (ST 7), Hegu (LI 4) and Zhigou (TE 6) on the left side and routine local anesthesia on the right side. The control group was treated with routine local anesthesia on the both side. The feelings of pain, circulatory index and operation effect were observed and compared.</p><p><b>RESULTS</b>During radiofrequency ablation, the pain grade of two measurements on the left side and the 2nd measurement on the right in the observation group were all lower than those in the control group (all P<0.05). In the observation group, the pain grades on the left side were lower than that on the right side (P<0.05), and the systolic blood pressure and the heart rate were lower than that in the control group when undergoing the 2nd radiofrequency ablation on the right side and on the left side, respectively (both P<0.05). There was no significant difference in operation effect between the two groups.</p><p><b>CONCLUSION</b>Electroacupuncture compound anesthesia can meet the analgesia requirement of radiofrequency ablation for treatment of hypertrophic inferior turbinate, and would be helpful to prevent cyclic fluctuation during the operation at the same time.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Acupuncture Analgesia , Anesthesia , Catheter Ablation , Electroacupuncture , Treatment Outcome , Turbinates , General SurgeryABSTRACT
Focused on nanobiology and nanomedicine, this article elucidates its main research targets and contents, discusses the important of researches in this field, introduces the tasks and objectives of the corresponding researches in the national long- and mid-term science and technology development planning, and also describes the present research status in China.