Research progress of ferroptosis and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disorder of the gastrointestinal tract, imposing significant burdens on both society and individuals. As a new type of regulated cell death (RCD), ferroptosis is different from classic RCDs such as apoptosis and necrosis in cell morphology, biochemistry and genetics. The main molecular mechanisms of ferroptosis include dysregulation of iron metabolism, impaired antioxidant capacity, mitochondrial dysfunction, accumulation of lipid-associated super-oxides, and membrane disruption. In recent years, increasing evidence has shown that ferroptosis is involved in the pathophysiology of inflammatory bowel disease. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This article reviews the mechanism of ferroptosis in the occurrence and development of inflammatory bowel disease, in order to provide new ideas for the pathophysiological research of inflammatory bowel disease. Additionally, we discuss potential strategies for the prevention and treatment of inflammatory bowel disease by targeting ferroptosis.

Chitinase-Like Protein PpCTL1 Contributes to Maintaining Fruit Firmness by Affecting Cellulose Biosynthesis during Peach Development.

The firmness of the flesh fruit is a very important feature in the eating process. Peach fruit is very hard during development, but its firmness slightly decreases in the later stages of development. While there has been extensive research on changes in cell wall polysaccharides during fruit ripening, little is known about the changes that occur during growth and development. In this study, we investigated the modifications in cell wall components throughout the development and ripening of peach fruit, as well as its impact on firmness. Our findings revealed a significant positive correlation between fruit firmness and cellulose content at development stage. However, the correlation was lost during the softening process, suggesting that cellulose might be responsible for the fruit firmness during development. Members of the chitinase-like protein (CTL) group are of interest because of their possible role in plant cell wall biosynthesis. Here, two CTL homologous genes, PpCTL1 and PpCTL2, were identified in peach. Spatial and temporal expression patterns of PpCTLs revealed that PpCTL1 exhibited high expression abundance in the fruit and followed a similar trend to cellulose during fruit growth. Furthermore, silencing PpCTL1 expression resulted in reduced cellulose content at 5 DAI (days after injection), this change that would have a negative effect on fruit firmness. Our results indicate that PpCTL1 plays an important role in cellulose biosynthesis and the maintenance of peach firmness during development.

Garlic-derived exosomes carrying miR-396e shapes macrophage metabolic reprograming to mitigate the inflammatory response in obese adipose tissue.

Low-grade chronic inflammation originating from the adipose tissue and imbalance of lipid metabolism in the liver are the main drivers of the development of obesity and its related metabolic disorders. In this work, we found that garlic-derived exosomes (GDE) supplementation improved insulin resistance, altered the levels of inflammatory cytokines in serum and epididymal white adipose tissue (eWAT) by decreasing the accumulation of macrophages in HFD-fed mice. Meanwhile, we also observed that GDE regulated the expression of 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), one of the critical glycolytic enzymes, to shape the metabolic reprograming of macrophage induced by lipopolysaccharide (LPS) and mitigate the inflammatory response in adipocytes via macrophage-adipocyte cross-talk. Data from small RNA sequencing, bioinformatical analysis and the gene over-expression revealed that miR-396e, one of the most abundant miRNAs of GDE, played a critical role in promoting the metabolic reprogramming of macrophage by directly targeting PFKFB3. The findings of this study not only provide an in-depth understanding of GDE protecting against inflammation in obesity but supply evidence to study the molecular mechanisms associated with the interspecies communication.

Nasal Sinus Mucoceles Manifesting Ocular Symptoms.

INTRODUCTION: To describe the ocular symptoms in a series of patients with nasal sinus mucoceles of different locations. METHODS: The authors analyzed the diagnosis and treatment of patients with sinus mucoceles and ocular symptoms who presented to the hospital from February 2010 to April 2020. A total of 61 patients were included in the study. The locations of the mucoceles were the frontal sinus (8 patients), ethmoid sinus (25 patients), and sphenoid sinus (28 patients). The authors selected 1 typical mucocele case from each of the sinuses, including the frontal, ethmoid, and sphenoid sinuses, and analyzed the history, diagnosis, and treatment of mucoceles in each location. RESULTS: The main clinical manifestations were ophthalmic symptoms, such as exophthalmos or displacement, eye pain, blindness or decreased vision, blepharoptosis, and diplopia; no obvious nasal symptoms were noted. Most patients with these symptoms went to an ophthalmologist first. All lesions in this study were found through imaging examinations. Most symptoms improved after surgical interventions. Only 2 of the 61 patients had no improvement in vision because of the long period of vision loss. CONCLUSIONS: Although sinus mucoceles are located in the sinuses, ocular symptoms are more prevalent than nasal symptoms. The earlier the imaging examinations are performed; the sooner lesions are detected, and the patients can be treated.

[Association of liver damage with coronary artery lesion and no response to intravenous immunoglobulin in the acute stage of Kawasaki disease]. / å·å´Žç— æ€¥æ€§æœŸè‚æŸå®³ä¸Žå† çŠ¶åŠ¨è„‰æŸä¼¤å’Œå ç–«çƒè›‹ç™½æ— ååº”çš„å ³ç³».

OBJECTIVES: To summarize the clinical features of liver damage in children in the acute stage of Kawasaki disease (KD), and to investigate the clinical value of liver damage in predicting coronary artery lesion and no response to intravenous immunoglobulin (IVIG) in children with KD. METHODS: The medical data were collected from 925 children who were diagnosed with KD for the first time in Beijing Children's Hospital from January 1, 2016 to December 31, 2017. According to the presence or absence of abnormal alanine aminotransferase (ALT) level on admission, the children were divided into a liver damage group (n=284) and a non-liver damage group (n=641). A logistic regression analysis was used to investigate the clinical value of the indicators including liver damage in predicting coronary artery lesion and no response to IVIG in children with KD. RESULTS: Compared with the non-liver damage group, the liver damage group had a significantly earlier admission time and significantly higher serum levels of inflammatory indicators (P<0.05). The liver damage group had a significantly higher incidence rate of coronary artery lesion on admission than the non-liver damage group (P=0.034). After initial IVIG therapy, the liver damage group had a significantly higher proportion of children with no response to IVIG than the non-liver damage group (P<0.001). In children with KD, coronary artery lesion was associated with the reduction in the hemoglobin level and the increases in platelet count, C-reactive protein, and ALT (P<0.05), and no response to IVIG was associated with limb changes, the reduction in the hemoglobin level, the increases in platelet count, C-reactive protein, and ALT, and coronary artery lesion (P<0.05). CONCLUSIONS: Compared with those without liver damage, the children in the early stage of KD with liver damage tend to develop clinical symptoms early and have higher levels of inflammatory indicators, and they are more likely to have coronary artery lesion and show no response to IVIG treatment.

Blueberry-derived exosomes-like nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress.

Accumulating evidence indicates that mitochondrial dysfunction and oxidative stress play a pivotal role in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). In this study, we found that blueberry-derived exosomes-like nanoparticles (BELNs) could ameliorate oxidative stress in rotenone-induced HepG2 cells and high-fat diet (HFD)-fed C57BL/6 mice. Preincubation with BELNs decreased the level of reactive oxygen species (ROS), increased the mitochondrial membrane potential, and prevented cell apoptosis by inducing the expression of Bcl-2 and heme oxygenase-1 (HO-1) and decreasing the content of Bax in rotenone-treated HepG2 cells. We also found that preincubation with BELNs accelerated the translocation of Nrf2, an important transcription factor of antioxidative proteins, from the cytoplasm to the nucleus in rotenone-treated HepG2 cells. Moreover, administration of BELNs improved insulin resistance, ameliorated the dysfunction of hepatocytes, and regulated the expression of detoxifying/antioxidant genes by affecting the distribution of Nrf2 in the cytoplasm and nucleus of hepatocytes of HFD-fed mice. Furthermore, BELNs supplementation prevented the formation of vacuoles and attenuated the accumulation of lipid droplets by inhibiting the expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1), the two key transcription factors for de novo lipogenesis in the liver of HFD-fed mice. These findings suggested that BELNs can be used for the treatment of NAFLD because of their antioxidative activity.

Genome-wide identification, classification, and expression analysis of the JmjC domain-containing histone demethylase gene family in birch.

BACKGROUND: Histone methylation occurs primarily on lysine residues and requires a set of enzymes capable of reading, writing, and erasing to control its establishment and deletion, which is essential for maintaining chromatin structure and gene expression. Histone methylation and demethylation are contributed to plant growth and development, and are involved in adapting to environmental stresses. The JmjC domain-containing proteins are extensively studied for their function in histone lysine demethylation in plants, and play a critical role in sustaining histone methylation homeostasis. RESULTS: In this study, a total of 21 JmjC domain-containing histone demethylase proteins (JHDMs) in birch were identified and classified into five subfamilies based on structural characteristics and phylogenetic relationships among Arabidopsis, rice, maize, and birch. Although the BpJMJ genes displayed significant schematic variation, their distribution on the chromosomes is relatively uniform. Additionally, the BpJMJ genes in birch have never experienced a tandem-duplication event proved by WGD analysis and were remaining underwent purifying selection (Ka/Ks < < 1). A typical JmjC domain was found in all BpJMJ genes, some of which have other essential domains for their functions. In the promoter regions of BpJMJ genes, cis-acting elements associated with hormone and abiotic stress responses were overrepresented. Under abiotic stresses, the transcriptome profile reveals two contrasting expression patterns within 21 BpJMJ genes. Furthermore, it was established that most BpJMJ genes had higher expression in young tissues under normal conditions, with BpJMJ06/16 having the highest expression in germinating seeds and participating in the regulation of BpGA3ox1/2 gene expression. Eventually, BpJMJ genes were found to directly interact with genes involved in the "intracellular membrane" in respond to cold stress. CONCLUSIONS: The present study will provide a foundation for future experiments on histone demethylases in birch and a theoretical basis for epigenetic research on growth and development in response to abiotic stresses.

Genome-wide identification and expression analysis of the AT-hook Motif Nuclear Localized gene family in soybean.

BACKGROUND: Soybean is an important legume crop and has significant agricultural and economic value. Previous research has shown that the AT-Hook Motif Nuclear Localized (AHL) gene family is highly conserved in land plants, playing crucial roles in plant growth and development. To date, however, the AHL gene family has not been studied in soybean. RESULTS: To investigate the roles played by the AHL gene family in soybean, genome-wide identification, expression patterns and gene structures were performed to analyze. We identified a total of 63 AT-hook motif genes, which were characterized by the presence of the AT-hook motif and PPC domain in soybean. The AT-hook motif genes were distributed on 18 chromosomes and formed two distinct clades (A and B), as shown by phylogenetic analysis. All the AHL proteins were further classified into three types (I, II and III) based on the AT-hook motif. Type-I was belonged to Clade-A, while Type-II and Type-III were belonged to Clade-B. Our results also showed that the main type of duplication in the soybean AHL gene family was segmented duplication event. To discern whether the AHL gene family was involved in stress response in soybean, we performed cis-acting elements analysis and found that AHL genes were associated with light responsiveness, anaerobic induction, MYB and gibberellin-responsiveness elements. This suggest that AHL genes may participate in plant development and mediate stress response. Moreover, a co-expression network analysis showed that the AHL genes were also involved in energy transduction, and the associated with the gibberellin pathway and nuclear entry signal pathways in soybean. Transcription analysis revealed that AHL genes in Jack and Williams82 have a common expression pattern and are mostly expressed in roots, showing greater sensitivity under drought and submergence stress. Hence, the AHL gene family mainly reacts on mediating stress responses in the roots and provide comprehensive information for further understanding of the AT-hook motif gene family-mediated stress response in soybean. CONCLUSION: Sixty-three AT-hook motif genes were identified in the soybean genome. These genes formed into two distinct phylogenetic clades and belonged to three different types. Cis-acting elements and co-expression network analyses suggested that AHL genes participated in significant biological processes. This work provides important theoretical basis for the understanding of AHLs biological functions in soybean.

Comparison of clinical outcome between endoscopic and postauricular incision microscopic type-1 tympanoplasty.

BACKGROUND: Microscopic type-1 tympanoplasty (T1T) is a classical method for the treatment of chronic otitis media. However, it has its limitations. The development of otoendoscopy provided a new method for T1T. OBJECTIVE: To investigate the difference between endoscopic T1T and microscopic T1T. MATERIAL AND METHODS: Seventy-four patients who underwent T1T were evaluated retrospectively. About 52 cases underwent endoscopic T1T, and 22 cases accepted microscopic T1T. Parameters including operative duration, incision size, graft site, duration of postoperative hospitalization, visual analog scale (VAS) score, complications, hearing improvement, and expenses were compared. RESULTS: Operative duration of endoscopic T1T (47.0 ± 8.2 min) was shorter than microscopic T1T (58.0 ± 9.3 min) (p < .05). The VAS score under endoscopic T1T (1.5 ± 0.2) was lower than microscopic T1T (5.6 ± 0.4) (p < .05). There was no complication during endoscopic T1T, but damage to the chorda tympani nerve (one case) was noted for microscopic T1T. There was no difference in hearing improvement between endoscopic (15.0 ± 1.5 dB) and microscopic T1T (16.0 ± 1.1 dB). Duration of postoperative hospitalization and expenses were lower for endoscopic T1T. CONCLUSIONS AND SIGNIFICANCE: Endoscopic T1T is a minimally invasive surgery with similar graft success rate, comparable hearing improvement, fast recovery, low cost, and high patient satisfaction compared to microscopic T1T.

Mief1 augments thyroid cell dysfunction and apoptosis through inhibiting AMPK-PTEN signaling pathway.

Objective: Inflammation-mediated thyroid cell dysfunction and apoptosis increases the like-hood of hypothyroidism.Aim: Our aim in the present study is to explore the role of mitochondrial elongation factor 1 (Mief1) in thyroid cell dysfunction induced by TNFα.Materials and methods: Different doses of TNFα were used to incubate with thyroid cells in vitro. The survival rate, apoptotic index and proliferation capacity of thyroid cells were measured. Cellular energy metabolism and endoplasmic reticulum function related to protein synthesis were detected.Results: In response to TNFα treatment, the levels of Mief1 were increased, coinciding with a drop in the viability of thyroid cells in vitro. Loss of Mief1 attenuates TNFα-induced cell death through reducing the ratio of cell apoptosis. Further, we found that Mief1 deletion reversed cell energy metabolism and this effect was attributable to mitochondrial protection. Mief1 knockdown sustained mitochondrial membrane potential and reduced mitochondrial ROS overproduction. In addition, Mief1 knockdown also reduced endoplasmic reticulum stress, as evidenced by decreased levels of Chop and Caspase-12. Finally, our data verified that TNFα treatment inhibited the activity of AMPK-PTEN pathway whereas Mief1 deletion reversed the activity of AMPK and thus promoted the upregulation of PTEN. However, inhibition of AMPK-PTEN pathways could abolish the beneficial effects exerted by Mief1 deletion on thyroid cells damage and dysfunction.Conclusions: Altogether, our data indicate that immune abnormality-mediated thyroid cell dysfunction and death are alleviated by Mief1 deletion possible driven through reversing the activity of AMPK-PTEN pathways.

Unfolded protein response is involved in geniposide-regulating glucose-stimulated insulin secretion in INS-1 cells.

The growing evidence shows that in the early stage of type 2 diabetes mellitus (T2DM) development, when challenged by hyperglycemia and/or insulin resistance, pancreatic islets would produce more insulin to maintain the balance of blood sugar, but at the same time, endoplasmic reticulum (ER) stress will be initiated for the reason of over-compensation, which might be a crucial caused factor of dysfunction and death of pancreatic beta cell. In this study, we showed that high glucose induced a remarkably unfolded protein response (UPR) with the phosphorylation of PERK/eIF2α and IRE1α in INS-1 cells, but geniposide prevented the role of high glucose on the phosphorylation of PERK/eIF2α and IRE1α, respectively. Although inhibition of Txnip expression by siRNA had no significant effect on geniposide-regulating UPR, PERK and IRE1α were associated with geniposide-regulating Txnip degradation and glucose-stimulated insulin secretion (GSIS) in high glucose-cultured INS-1 cells. All these data suggest that geniposide might be an important regulator of ER stress and GSIS, and a promising compound for the treatment of T2DM. SIGNIFICANCE OF THE STUDY: Mounting evidence indicates that endoplasmic reticulum (ER) stress plays an essential role to maintain the normal cellular functions and dysfunction. In this study, we revealed that geniposide might be an important regulator of ER stress and glucose-stimulated insulin secretion in pancreatic beta cells.

Glutathione S-transferase gene polymorphisms and risk of nasal or colorectal polyposis.

We observed inconsistent conclusions regarding the genetic role of glutathione S-transferase gene polymorphisms, including glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase pi (GSTP1) Ile105Val polymorphisms, in the susceptibility to nasal or colorectal polyposis (NP or CP). Thus, we aimed to perform a meta-analysis to comprehensively evaluate this association by applying Stata/SE software. After the heterogeneity assumption, Mantel-Haenszel statistics were used to obtain the odds ratio (OR), 95% confidence interval (95% CI) and P-value of the association test (PA ). We obtained a total of 235 articles by searching online databases. After screening, ten eligible case-control studies were finally enrolled in our meta-analysis. For the meta-analysis of the GSTT1 gene under present versus null, we observed a decreased risk of NP [OR = 0.65; PA =0.018], but not CP. In addition, we did not detect any evident association between the GSTM1 present/null polymorphism and NP or CP risk. For the meta-analysis of the GSTP1 Ile105Val polymorphism, compared with controls, an increased risk of NP cases was detected under the models of Val versus Ile (OR = 1.36; PA =0.027), Ile/Val versus Ile/Ile (OR = 1.70; PA =0.011) and Ile/Val+Val/Val versus Ile/Ile (OR = 1.65; PA =0.010). In conclusion, the null genotype of the GSTT1 polymorphism may be linked to an increased susceptibility to NP, whereas the Ile/Val genotype of the GSTP1 Ile105Val polymorphism may be associated with a decreased risk of NP.

Geniposide Increases Unfolded Protein Response-Mediating HRD1 Expression to Accelerate APP Degradation in Primary Cortical Neurons.

Altered proteostasis induced by amyloid peptide aggregation and hyperphosphorylation of tau protein, is a prominent feature of Alzheimer's disease, which highlights the occurrence of endoplasmic reticulum stress and triggers the activation of the unfolded protein response (UPR), a signaling pathway that enforces adaptive programs to sustain proteostasis. In this study, we investigated the role of geniposide in the activation of UPR induced by high glucose in primary cortical neurons. We found that high glucose induced a significant activation of UPR, and geniposide enhanced the effect of high glucose on the phosphorylation of IRE1α, the most conserved UPR signaling branch. We observed that geniposide induced the expression of HRD1, an ubiquitin-ligase E3 in a time dependent manner, and amplified the expression of HRD1 induced by high glucose in primary cortical neurons. Suppression of IRE1α activity with STF-083010, an inhibitor of IRE1 phosphorylation, prevented the roles of geniposide on the expression of HRD1 and APP degradation in high glucose-treated cortical neurons. In addition, the results from RNA interfere on HRD1 revealed that HRD1 was involved in geniposide regulating APP degradation in cortical neurons. These data suggest that geniposide might be benefit to re-establish proteostasis by enhancing the UPR to decrease the load of APP in neurons challenged by high glucose.

Geniposide protects pancreatic ß cells from high glucose-mediated injury by activation of AMP-activated protein kinase.

Our previous works indicated that geniposide could regulate glucose-stimulated insulin secretion (GSIS), and improved chronic high glucose-induced dysfunctions in pancreatic ß cells, but the molecular mechanisms remain largely unknown. In the present study, we investigated the role of 5'-AMP-activated protein kinase (AMPK) in high glucose induced cell injury and explored the associated molecular mechanisms in rat INS-1 pancreatic ß cells. Data suggested that geniposide obviously prevented the cell damage induced by high (25 mM) glucose in INS-1 cells, which increased the protein levels of cell apoptosis-associated enzymes, including heme oxygenase-1 (HO-1), and Bcl-2, but apparently attenuated the protein level of Bax, an apoptotic protein. In addition, Compound C, an AMPK inhibitor, remarkably inhibited the effects of geniposide on the protein levels of HO-1, Bcl-2, and Bax, but AICAR, an AMPK activator, potentiated the role of geniposide on the protein levels of HO-1, Bcl-2, and Bax. More importantly, geniposide directly prevented the cleavage of caspase-3 induced by high glucose, and this effect was also evidently prohibited by the pre-incubation of compound C in high glucose-treated INS-1 cells. Furthermore, using the method of RNA interfere, we further proved that treatment with AMPK siRNA attenuated the effects of geniposide on the apoptosis-associated proteins and cell viability. All these data suggest that AMPK plays a crucial role on geniposide antagonizing high glucose-induced pancreatic ß cells injury.

Geniposide attenuates the level of Aß1-42 via enhancing leptin signaling in cellular and APP/PS1 transgenic mice.

An large body of evidence indicates that leptin has protective role against Alzheimer's disease, where it reduces ß-amyloid (Aß) production in both cell culture and animal models. Our previous studies revealed that geniposide could attenuate the production of Aß1-42 and antagonize the neurotoxicity of Aß1-42 in neurons. However, the mechanism that underlies these effects remains to be clarified. To investigate whether leptin signaling is involved in regulating the production of Aß1-42 by geniposide, we treated primary neurons with leptin antagonist (LA), and determined the influence of LA on the activities of leptin signaling molecules and the expressions of secretases associated with the production of Aß1-42. The finding showed that, accompanied with the inhibition on the level of Aß1-42 in primary neurons and APP/PS1 transgenic mice, geniposide induced the phosphorylation of JAK2 and STAT3, regulated the expression level of α- and ß-secretase, and all of these could be prevented by the pre-incubation with LA. The results of this study suggest that geniposide may regulate the production of Aß1-42 via leptin signaling.

5'-AMP-activated protein kinase plays an essential role in geniposide-regulated glucose-stimulated insulin secretion in rat pancreatic INS-1 ß cells.

Our previous work showed that geniposide affected glucose-stimulated insulin secretion (GSIS) via regulating glucose uptake and metabolism in pancreatic ß cells; however, the molecular mechanisms remain largely unknown. Substantial evidence suggests that activation of 5'-AMP-activated protein kinase (AMPK) plays a central role in GSIS. Here, we aim to determine the role of AMPK on geniposide-regulated GSIS in rat pancreatic INS-1 cells. The results demonstrated that 6-[4-(2-piperidin-1-yletoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-α] pyrimidine (Compound C; an AMPK inhibitor) significantly attenuated the effects of geniposide on glucose uptake, energy metabolism, and insulin secretion in INS-1 cells. We also observed that geniposide induced phosphorylation of acetyl-CoA carboxylase (ACC), a marker of AMPK activity, in a time-dependent manner in INS-1 cells; however, in the presence of Compound C, the influence of geniposide on ACC phosphorylation was obviously inhibited. Furthermore, the knockdown of AMPK protein with AMPK siRNA treatment decreased the effects of geniposide on glucose uptake, adenosine triphosphate production, and GSIS. All these data indicate that AMPK plays an essential role in geniposide-regulated GSIS in pancreatic ß cells.

The flower of Edgeworthia gardneri (wall.) Meisn. suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: The flower of Edgeworthia gardneri (Wall.) Meisn., locally named "Lvluohua, ", has been widely used as Tibetan folk medicine for the treatment of metabolic diseases for a long time. AIM OF THIS STUDY: To evaluate the anti-adipogenesis effect of ethyl acetate extract of the flower of E. gardneri (EEG extract) in 3T3-L1 adipocytes. MATERIALS AND METHODS: Obesity-related parameters such as lipid accumulation and TG content were determined by Oil red O staining and enzymatic kit, respectively. Western blotting was used to determine the expressions of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein-α (C/EBPα), phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). Moreover, main constituents of EEG extract were analyzed by high performance liquid chromatography (HPLC). RESULTS: EEG extract decreased the lipid and triglyceride (TG) accumulations during the differentiation process and down-regulated the adipogenesis-related transcriptional factors PPARγ and C/EBPα. EEG extract treatment increased AMPK and ACC phosphorylation. In addition, pretreatment with AMPK inhibitor, weakened the inhibitory effects of EEG extract on the expressions of PPARγand C/EBPα. HPLC analysis indicated that tiliroside was the main constituent in EEG extract. CONCLUSIONS: These results suggest that EEG extract may exert anti-adipogenic effects through modulation of the AMPK signaling pathway.

In vitro Screening and Evaluation of 37 Traditional Chinese Medicines for Their Potential to Activate Peroxisome Proliferator-Activated Receptors-γ.

BACKGROUND: Peroxisome proliferator-activated receptors (PPAR)-γ is widely used as an attractive target for the treatment of type 2 diabetes mellitus. Thiazolidinediones, the agonists of PPARγ, has been popularly utilized as insulin sensitizers in the therapy of type 2 diabetes whereas numerous severe side-effects may also occur concomitantly. OBJECTIVE: The PPARγ activation activity of different polar extracts, including petroleum ether, ethyl acetate, n-butanol, residual of ethanol, the precipitate part of water and the supernatant of water extracts, from 37 traditional Chinese medicines were systematically evaluated. MATERIALS AND METHODS: HeLa cells were transiently co-transfected with the re-constructed plasmids of GAL4-PPARγ-ligand binding domain and pGL4.35. The activation of PPARγ by different polarity extracts were evaluated based on the PPARγ transactivation assay and rosiglitazone was used as positive control. RESULTS: Seven medicines (root bark of Lycium barbarum, Anoectochilus sroxburghii, the rhizome of Phragmites australis, Pterocephalus hookeri, Polygonatum sibiricum, fruit of Gleditsia sinensis, and Epimedium brevicornu) were able to significantly activate PPARγ. CONCLUSION: As seven medicines were able to activate PPARγ, the anti-diabetic activity of them is likely to be mediated by this nuclear receptor. SUMMARY: Lots of the tested medicinal products had activation effects on activating PPARγEthyl acetate extracts of root bark of L.barbarum, rhizome of P.saustralis and fruit of G.siasinensis showed good PPARγ activation effect similar or higher than that of positive control, 0.5 µg/mL rosiglitazonePetroleum ether extracts of A.roxburghii, P. hookeri, P. sibiricum, E.brevicornu also can significantly activate PPARγ, the effects of them were higher than t0.5 µg/mL rosiglitazoneSchisandra chinensis (Turcz.) Baill., the fruit Cornus officinalis Siebold and Zucc., Alisma plantago-aquatica L. and the root of Trichosanthes Kirilowii Maxim., traditional anti-diabetic mediciness in China, had no effects on the activation of PPARγ. Abbreviations used: PPARγ: Peroxisome Proliferator-activated Receptors-γ, TCMs: Traditional Chinese medicines, TZDs: Thiazolidinediones, LBD: Ligand binding domain, DMSO: Dimethyl sulfoxide, FBS: Fetal bovine serum, DMEM: Dulbecco's modified Eagle's medium.