The anti-angiogenic herbal composition Ob-X from Morus alba,Melissa officinalis,and Artemisia capillaris regulates obesity in genetically obese ob/ob mice

Context: The growth and development of adipose tissue leading to obesity is suggested to depend on angiogenesis. Our previous study showed that Melissa officinalis L. (Labiatae), Morus alba L. (Moraceae), and Artemisia capillaris Thunb. (Compositae) are involved in the regulation of angiogenesis. We hypothesized that Ob-X, a mixture of three herbs, M. alba, M. officinalis, and A. capillaris, can regulate obesity.

Objective: To investigate the inhibitory effect of Ob-X on obesity in genetically obese ob/ob mice.

Materials and methods: The effect of Ob-X on angiogenesis was measured using a mouse Matrigel plug assay. The effects of Ob-X on obesity were investigated in ob/ob mice.

Results: Ob-X inhibited angiogenesis in a dose-dependent manner, as evidenced by decreased blood vessel density in a mouse matrigel plug assay. Administration of Ob-X to ob/ob mice for 5 weeks produced a significant reduction in body weight gain by 27% compared with control (12.1?±?3.01 vs. 16.6?±?2.24?g, respectively). Ob-X also significantly decreased visceral adipose tissue mass by 15% (0.87?±?0.12 vs. 1.02?±?0.15?g, respectively). The size of adipocytes in visceral adipose tissue was reduced by 46% in Ob-X-treated mice. Ob-X treatment inhibited hepatic lipid accumulation and significantly decreased circulating glucose levels compared with controls (197?±?56.5 vs. 365?±?115?mg/dL, respectively).

Discussion and conclusion: These results suggest that Ob-X, which has an anti-angiogenic activity, reduces body weight gain and visceral adipose tissue mass in genetically obese mice, providing evidence that obesity can be prevented by angiogenesis inhibitors.     

Korean red ginseng (Panax ginseng) prevents obesity by inhibiting angiogenesis in high fat diet-induced obese C57BL/6J mice

Adipose tissue growth and development are thought to be associated with angiogenesis and extracellular matrix remodeling. Because ginseng has been shown to inhibit angiogenesis and matrix metalloproteinase (MMP) activity, we hypothesized that adipose tissue growth and obesity can be regulated by Korean ginseng (Panax ginseng C.A. Meyer). Wild-type C57BL/6J mice were fed for 8 weeks with a low fat diet, a high fat diet (HFD), or HFD supplemented with 0.5% or 5% Korean red ginseng extract. We measured body weight, adipose tissue mass, food intake, MMP activity, and the expression of genes involved in angiogenesis and MMPs. Administering ginseng to HFD-induced obese mice produced reductions in body weight and adipose tissue mass compared with untreated counterparts. Ginseng treatment decreased blood vessel density and MMP activity in adipose tissues. Ginseng also reduced mRNA levels of angiogenic factors (e.g., VEGF-A and FGF-2) and MMPs (e.g., MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (e.g., TSP-1, TIMP-1, and TIMP-2) in adipose tissues. These results demonstrate that ginseng effectively reduces adipose tissue mass and prevents obesity in diet-induced obese mice and that this process may be mediated in part through the anti-angiogenic actions of ginseng.     

The herbal composition GGEx18 from Laminaria japonica,Rheum palmatum,and Ephedra sinica inhibits visceral obesity and insulin resistance by upregulating visceral adipose genes involved in fatty acid oxidation

Abstract

Context: The herbal composition Gyeongshingangjeehwan 18 (GGEx18) extracted from Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae) is traditionally used as an anti-obesity drug by local clinics in Korea.

Objective: This study investigates the effects of GGEx18 on visceral obesity and insulin resistance and determines the molecular mechanisms involved in this process.

Materials and methods: After C57BL/6J mice were fed a high-fat diet supplemented with GGEx18 (125, 250, and 500?mg/kg) for 8 weeks and 3T3-L1 adipocytes were treated with GGEx18 (0.1, 1, and 10?μg/ml); variables and determinants of visceral obesity and insulin resistance were measured using in vivo and in vitro approaches.

Results: Administration of GGEx18 to obese mice decreased visceral adipose tissue weight with an ED₅₀ value of 232?mg/kg. 3T3-L1 adipocytes treated with GGEx18 showed a reduction in lipid accumulation with an ED₅₀ value of 0.7?µg/ml. GGEx18 significantly increased the expression of fatty acid oxidation genes, including adiponectin, AMPKs, PPARα and its target enzymes, and CPT-1, in both mesenteric adipose tissues and 3T3-L1 cells. However, GGEx18 treatment decreased the mRNA levels of adipocyte marker genes such as PPARγ, aP2, TNFα, and leptin. GGEx18 normalized hyperglycemia and hyperinsulinemia in obese mice. Blood glucose levels of GGEx18-treated mice were significantly reduced during oral glucose tolerance tests compared with obese controls.

Discussion and conclusion: These results suggest that GGEx18 may treat visceral obesity and visceral obesity-related insulin resistance by upregulating the visceral adipose expression of fatty acid oxidative genes.     

Exposure to bioaccumulative organochlorine compounds alters adipogenesis, fatty acid uptake, and adipokine production in NIH3T3-L1 cells

Exposure to the organochlorine compounds p,p′-dichlorodiphenyldichloroethylene (DDE) and oxychlordane have been associated with an increased prevalence of diabetes. Although the exact etiology of diabetes, especially type 2 diabetes, is not known, it is thought that adipose dysfunction plays a vital role in the progression of this disease. Thus, the present study examined whether exposure to these bioaccumulative compounds promotes adipocyte dysfunction including alterations in adipogenesis, fatty acid storage, and adipokine production within the adipocyte. We employed the NIH3T3-L1 cell line as a model for adipogenesis and mature adipocyte function. Exposure to DDE or oxychlordane prior to and throughout differentiation did not affect adipogenesis. In mature NIH3T3-L1 adipocytes, exposure to oxychlordane, DDE, or dieldrin had no effect on insulin-stimulated fatty acid uptake but did increase basal fatty acid uptake over a 24 h period. There was no observed effect of exposure to these compounds on lipolysis. Exposure to DDE significantly increased the release of leptin, resistin, and adiponectin from mature adipocytes with corresponding increases in expression of resistin and adiponectin. Taken together, the current data suggest that exposure to these compounds, especially DDE, may promote some aspects of adipocyte dysfunction that are commonly associated with obesity and type 2 diabetes.     

Expression of multiple Transient Receptor Potential channel genes in murine 3T3-L1 cell lines and adipose tissue

BackgroundCalcium and its signaling have a role in adipogenesis. Transient Receptor Potential (TRP) channels are non-selective cation channels with a high permeability to calcium.MethodsIn the present study the expression of multiple TRP channels on mouse 3T3-L1 preadipocyte and adipocyte cells, white (WAT) and brown (BAT) adipose tissues was investigated using real time PCR (RT-PCR).ResultsTRPV1, TRPV3, TRPM8, TRPC4, TRPC6 were differentially expressed in preadipocytes and adipocytes suggesting their significance in adipogenesis. Genes for multiple TRP channels were also expressed in murineWAT and BAT, out of which TRPV4, TRPV6 and TRPC6 showed differential expression.ConclusionPresent study demonstrates the expression of TRP channels in mouse cell lines and adipose tissues.     

Alterations in serum MMP and TIMP concentrations following chronic heroin abuse

Abstract

Context: Although opiate abuse is known to affect matrix metalloproteinases (MMPs), data on these enzymes and their tissue inhibitors in heroin addicts are scarce.

Objective: In the present study, we determined serum concentrations of MMP-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in heroin users, and compared them with healthy individuals. We evaluated whether 21?d of abstinence are adequate to reverse the effect of opiates and we compared seropositive with seronegative, for anti-HCV antibodies, heroin users.

Materials and methods: Twenty-six heroin-dependent male volunteers and an equal number of healthy individuals participated in this study. ELISA was used to assess the serum levels of MMP-2, MMP-9, TIMP-1 and TIMP-2. Heroin users were assessed both upon admission and upon completion of a 21-d detoxification program.

Results: Serum TIMP-1 concentrations were significantly lower and the ratios MMP-2/TIMP-1, MMP-9/TIMP-1 and MMP-2/TIMP-2 were significantly higher in heroin users compared to healthy individuals. Heroin users who were seropositive had lower MMP concentrations, as well as lower MMP/TIMP ratios, compared to those who were seronegative.

Discussion: Our results showed that in heroin-addicted individuals, and especially those who are positive for anti-HCV antibodies, the balance between MMPs and TIMPs in serum is disrupted and this disruption cannot be restored within 21?d of abstinence.

Conclusion: Chronic heroin abuse disrupts the balance between MMPs and TIMPs in serum and this effect is not reversible within 21?d of abstinence.     

Role and mechanism of ORM in adipose tissue fibrosis and insulin resistance in obese mice

OBJECTIVE During the development of obesity, adipose tissue fibrosis occurs as a hallmark of adipose tissue dysfunction, leading to metabolic dysfunction such as insulin resistance. We previously reported adipokine orosomucoid(ORM) could be a negative feedback signal in energy homeostasis, and its level was significantly elevated in response to obese state. Here we aimed to explore the role of ORM in adipose tissue fibrosis and insulin resistance during obesity, and its possible mechanism. METHODS MRI was used to assess the distribution of fat and the fat or lean mass in ORM1 knockout mice. HE staining, masson staining, qPCR, and Western blotting were used to assess the fibrosis status of mice. And we used glucose tolerance test(GTT) and insulin tolerance test(ITT) to evaluate the regulation of blood glucose and insulin sensitivity in mice. Leptin receptor-deficient db/db mice and high fat diet-induced obese mice were used as obese models. 3 T3-L1 cells were used in vitro. RESULTS ORM1-deficient mice exhibited an obese phenotype with adipose tissue fibrosis and insulin resistance. The m RNA and protein levels of the fibrogenic genes encoding Col1a1, Col3a1, Col6a3 and ECM regulators MMP-2, MMP-13, MMP-14 TIMP-1,TIMP-2, and TIMP-3 in ORM1-deficient mice were significantly increased. GTT and ITT showed abnormal glucose tolerance and insulin resistance in ORM1-deficient mice.Moreover, exogenous administration of ORM attenuated excessive expression of type Ⅵ collagen, MMP-13 and TIMP-1 induced by adipose fibrosis in obese db/db(lep Rdeficient) mice. GTT and ITT showed ORM treatment improved insulin resistance in db/db mice. Moreover,ORM synergized with insulin to activate Akt in adipose tissue of db/db mice. Further studies found that ORM could bind to C-C chemikine receptor 5(CCR5) and ORM improves insulin resistance in high fat diet-induced obese mice, which could be blocked by maraviroc, an antagonist against CCR5. In addition, the effect of ORM in synergy with insulin to activate Akt in adipose tissue of db/db mice was also abolished by maraviroc. We also found that ORM stimulated AMPK activity and inhibits the TGF-β_1 expression in adipose tissue of db/db mice,thereby attenuating adipose tissue fibrosis. In vitro, ORM treatment also alleviated abnormal expression of fibrogetic genes in 3 T3-L1 fibroblasts induced by TGF-β_1. Of note,the inhibitory effects of ORM on fibrosis were abolished by dorsomorphin, a selective inhibitor of AMPK. CONCLUSION ORM alleviates adipose tissue fibrosis and insulin resistance through CCR5. ORM is expected to be a novel target for the treatment of obesity and its related diseases.     

Anti-obesity effect of sulfated glucosamine by AMPK signal pathway in 3T3-L1 adipocytes

In this study, we investigated the effect of sulfated glucosamine (SGlc) on adipogenesis of 3T3-L1 adipocytes during differentiation of preadipocytes into adipocytes by measuring lipid accumulation and adipogenesis related factors. Treatment with SGlc reduced the triglyceride content in Oil-Red O staining and enhanced glycerol secretion in adipocytes in a dose-dependent manner. In addition, SGlc induced the down-regulation of adipogenesis related factors and adipocyte specific gene promoters. Moreover, treatment of 3T3-L1 adipocytes with SGlc activated the phosphorylated adenosine monophosphate-activated protein kinase (AMPK) α and β along with their substrate, acetyl-CoA carboxylase (ACC). These results suggest that inhibitory effect of SGlc on adipocyte differentiation might be mediated through the up-regulation of AMPK pathway.     

17β-Estradiol inhibition of PPARγ-induced adipogenesis and adipocyte-specific gene expression

Aim:

To investigate the molecular interaction of peroxisome proliferator-activated receptor γ (PPARγ) with 17β-estradiol (E) in the regulation of adipogenesis.

Methods:

Female ovariectomized (OVX) mice and differentiated 3T3-L1 adipocytes were treated with combinations of the PPARγ agonist troglitazone or E, and the variables and determinants of adipogenesis were measured using in vivo and in vitro approaches.

Results:

Troglitazone (250 mg·kg⁻¹·d⁻¹ for 13 weeks) decreased the size of adipocytes without the change in white adipose tissue (WAT) mass and increased the expression of adipocyte-specific genes, such as PPARγ, adipocyte fatty acid binding protein, and lipoprotein lipase, compared with OVX control mice. E (0.05 mg/pellet, sc implanted) significantly reduced WAT mass, adipocyte size, and adipose marker gene expression. When mice were concomitantly treated with troglitazone and E, E blunted the effects of troglitazone on WAT mass, adipocyte size, and adipose PPARγ target gene expression. Consistent with the in vivo data, E (10 μmol/L) treatment inhibited lipid accumulation and the expression of adipocyte-specific genes caused by troglitazone (10 μmol/L) in 3T3-L1 cells. E (10 μmol/L) also decreased troglitazone-induced PPARγ reporter activity through both estrogen receptor (ER) α and ERβ. Mechanistic studies indicated that E (0.1 μmol/L) decreased the DNA binding of PPARγ induced by troglitazone (1 μmol/L) and inhibited the recruitment of the PPARγ coactivator CREB-binding protein.

Conclusion:

These results suggest that in vivo and in vitro treatment of E interferes with the actions of PPARγ on adipogenesis by down-regulating adipogenesis-related genes, which are mediated through the inhibition of PPARγ coactivator recruitment. In addition, it is likely that the activities of PPARγ activators may be enhanced in estrogen-deficient states.     

Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

Aim:

Wogonin (5,7-dihydroxy-8-methoxyflavone), a major bioactive compound of the flavonoid family, is commonly extracted from the traditional Chinese medicine Scutellaria baicalensis and possesses antioxidant and anti-inflammatory activities and is assumed to have anti-diabetes function. Indeed, a current study has shown that it can possibly treat metabolic disorders such as those found in db/db mice. However, the underlying molecular mechanism remains largely unclear. The aim of this study was to investigate the impact of wogonin on osteopontin (OPN) expression in adipose tissue from type 1 diabetic mice and in 3T3-L1 adipocytes.

Methods:

Type 1 diabetes was induced by streptozotocin (STZ) injection. 3T3-L1 preadipocytes were converted to 3T3-L1 adipocytes through treatment with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IBMX). Western blot analysis and RT-PCR were performed to detect protein expression and mRNA levels, respectively.

Results:

Wogonin treatment suppressed the increase in serum OPN levels and reduced OPN expression in adipose tissue from STZ-induced type 1 diabetic mice. Administration of wogonin enhanced PPARα expression and activity. Silencing of PPARα diminished the inhibitory effects of wogonin on OPN expression in 3T3-L1 adipocytes. Furthermore, the levels of c-Fos and phosphorylated c-Jun were reduced in wogonin-treated adipose tissue and 3T3-L1 adipocytes. In addition, wogonin treatment dramatically mitigated p38 MAPK phosphorylation. Pharmacological inhibition of p38 MAPK by its specific inhibitor SB203580 increased PPARα activity and decreased OPN expression.

Conclusion:

Our results suggest that wogonin downregulated OPN expression in adipocytes through the inhibition of p38 MAPK and the sequential activation of the PPARα pathway. Given the adverse effects of high OPN levels on metabolism, our results provide evidence for the potential administration of wogonin as a treatment for diabetes.     

祛瘀化痰、散结消癥中药复方对细胞外基质降解调控系统及TGF-β_1 mRNA的影响

目的:研究祛瘀化痰、散结消癥中药复方对肾小球硬化中细胞外基质(ECM)降解调控系统及转化生长因子(TGF)-β1 mRNA的影响。方法:采用脂多糖刺激体外培养的大鼠肾小球系膜细胞,复制细胞增殖模型,用给药动物血清干预后,酶联免疫吸附法检测细胞上清液中基质金属蛋白酶(MMP-9)、基质金属蛋白酶抑制物(TIMP-1)的表达,计算MMP-9与TIMP-1比值,荧光定量PCR法检测细胞TGF-β1 mRNA表达。结果:各祛瘀化痰、散结消癥中药复方均能不同程度地抑制TIMP-1、上调MMP-9的表达,提高MMP-9与TIMP-1的比值,并下调细胞中TGF-β1 mRNA表达,其中以川芎+鳖甲+海藻组作用最明显。结论:祛瘀化痰、散结消癥中药复方能增强ECM降解,下调肾小球系膜细胞中TGF-β1 mRNA表达。     

Ablation of steroid receptor coactivator-3 in mice impairs adipogenesis and enhances energy expenditure

Obesity is a medical condition in which excess body fat has accumulated to an extent and may have an adverse effect on health, leading to reduced life expectancy, impaired energy homeostasis and increased health problems. The p160 steroid receptor coactivator (SRC) gene family members have been suggested to be involved in energy homeostasis, but the impact of SRC-3 ablation on white and brown adipose tissue needs to be elucidated. In the current study, we collected in vivo data and carried out morphological studies on the effect of SRC-3 deficiency on white adipose tissue (WAT) and brown adipose tissue (BAT). Primary cells were cultured to investigate the differentiation ability of both adipocytes. Western blot was applied to detect the expression of master genes governing adipogenesis and thermogenesis. We observed that SRC-3−/− mice were lean, with reduced WAT and decreased serum leptin levels, mainly due to the smaller white adipocyte size caused by impaired adipogenesis, presented by decreased peroxisome proliferator activated receptor γ (PPARγ) expression. In the BAT, the lipid droplets decreased significantly in SRC-3−/− mice as demonstrated by histological analysis and electron microscopic observation, which could be explained by enhanced thermogenesis. The expression of thermogenic marker gene PPARγ coactivator 1α and uncoupling protein-1 increased in BAT of SRC-3−/− mice, which proved our observations. Collectively, these results demonstrate that SRC-3 plays a key role in adipogenesis and energy expenditure.     

Status of research on matrix metalloproteinases (MMPs) in India

Introduction: MMPs are extracellular matrix (ECM)-degrading enzymes that play a crucial role in embryogenesis, tissue remodeling, inflammation and angiogenesis. MMP-2 and -9 (also called type 2 and type 4 collagenase, or gelatinase A and B) are the key molecules that control invasion, tumor growth and metastasis. Tissue inhibitor of matrix metalloproteinase (TIMP) -2 and -1 are specific inhibitors of MMP-2 and MMP-9 respectively, and play a crucial role in regulation of MMP-2 and -9 activation, during pathophysiological processes. MMPs can specifically degrade native gelatin, collagens, fibronectin, ectactin and elastin. MMP-2 and -9 are overexpressed in almost all types of cancers, and so act as important therapeutic targets.

Areas covered: The status of MMP research in India from 1998 to 2010. In this review, the authors cover the role of matrix metalloproteinase inhibitors in cancer therapy.

Expert opinion: As compared with other parts of the world, Indian scientists have not generated a significant number of specific MMP inhibitors for the treatment of cancer, or other diseases. MMPs and membrane type (MT)-MMPs are potentially important therapeutic targets in many diseases, including cancers, therefore, designing specific inhibitors from natural products or through synthetic routes, is crucial.     

Effects of Polygonatum sibiricum rhizome ethanol extract in high-fat diet-fed mice

Abstract

Context: The rhizome of Polygonatum sibiricum Redoute (Liliaceae) has long been used to treat diabetes-associated complications. However, the pharmacological mechanism of P. sibiricum on metabolic disorders is not clear.

Objective: This study investigates the effect of an ethanol extract of P. sibiricum rhizomes (designated ID1216) on obesity conditions including weight loss in high-fat (HF) diet-fed mice and explores the potential underlying mechanisms.

Methods: To identify the metabolic impact of the P. sibiricum rhizome extract, HF diet-fed mice were administered ID1216 orally at doses of 250 and 1000?mg/kg/d for 10?weeks, and various factors related to metabolic syndrome were analyzed. We also examined the effects of ID1216 on the expression of genes involved in adipogenesis and lipolysis in 3T3-L1 cells, as well as genes associated with energy homeostasis in C2C12 myocytes.

Results: ID1216 administration led to significant decreases in body weight gain (37.5%), lipid accumulation in adipose tissues (52.8%), and the levels of plasma triglycerides (26.4%) and free fatty acids (28.1%) at a dose of 250?mg/kg/d, compared with the vehicle-treated group, as well as improved insulin resistance. In addition, ID1216 was found to regulate the expression of genes related to adipogenesis and fatty acid oxidation in 3T3-L1 cells and enhance the expression of genes that modulate energy homeostasis in C2C12 myocytes.

Conclusions: ID1216 may be a promising therapeutic agent for improving obesity conditions through the sirtuin-1 and peroxisome proliferator-activated receptor γ coactivator-1α pathway.     

Very low density lipoprotein receptor promotes adipocyte differentiation and mediates the proadipogenic effect of peroxisome proliferator-activated receptor gamma agonists

Very low density lipoprotein receptor (VLDLR) is a member of the low density receptor family, expressed mostly in adipose tissue, heart, and skeletal muscles. VLDLR binds apolipoprotein-E-triglyceride-rich lipoproteins and plays a key role in lipid metabolism. In adipocytes, VLDLR expression increases with differentiation but it is not known whether it plays a role in the adipogenesis. Here we report that VLDLR expression in 3T3-L1 adipocytes is upregulated by PPARγ agonist 15-deoxy-delta^12,14-prostaglandin J₂ (15d-PGJ₂) in dose- and time-dependant manners. Knockdown of peroxisome proliferator-activated receptor-γ (PPARγ) with siRNA abolished pioglitazone- and 15d-PGJ₂-induced VLDLR expression and simultaneously reduced VLDL uptake in adipocytes. In addition, PPARγ-agonist treatment of control mouse adipocytes (vldlr^+/+) enhanced adipogenesis and VLDL uptake concurrently with the induction of VLDLR expression. However, vldlr deficiency (vldlr^−/−) significantly blunted the proadipogenic effects of PPARγ agonists. Sequence analysis revealed the presence of a putative PPARγ responsive sequence (PPRE) within the vldlr promoter, which is responsive to natural (15d-PGJ₂) and synthetic (pioglitazone) PPARγ agonists. Reporter gene assays using serial deletion of the 5′-flanking region showed that this putative PPRE site induced promoter transactivation, while a site-targeted mutation abolished transactivation. Moreover, electrophoresis mobility shift assay (EMSA) and chromatic immunoprecipitation (ChIP) assays showed the specific binding of PPARγ to the PPRE sequence.Together, these results support a crucial function for VLDLR in adipocyte differentiation and mediation of the proadipogenic effect of PPARγ.     

Subchronic treatment of rats with oxytocin results in improved adipocyte differentiation and increased gene expression of factors involved in adipogenesis

BACKGROUND AND PURPOSE

Treatment with thiazolidinediones, insulin-sensitizing drugs, enhances adipogenesis, which may result in unwanted increase in adiposity. Based on the suggested metabolic effects of oxytocin, the aims of the present study were to: (i) determine whether chronic treatment with oxytocin exerts positive effects on white adipose tissue growth without increasing adiposity; (ii) investigate possible mechanisms of action of oxytocin by measuring the level of gene expression of adipogenic factors; and (iii) test the hypothesis that oxytocin''s effect on adipose tissue involves specific activation of eukaryotic elongation factor 2 (eEF2).

EXPERIMENTAL APPROACH

Adult rats were subcutaneously treated with oxytocin (3.6 µg·100 g⁻¹ body weight day⁻¹) via osmotic minipumps for 2 weeks. Adipocytes from epididymal adipose tissue were isolated and their size evaluated by light microscopy. Gene expression of adipogenic and angiogenic factors was determined by real-time PCR and dephosphorylation of eEF2 by immunoblotting.

KEY RESULTS

Oxytocin treatment decreased the diameter of adipocytes and increased the epididymal adipose tissue protein content without changing the adipose tissue mass. Increases in fatty acid binding protein, peroxisome proliferator-activated receptor γ, insulin-sensitive glucose transporter 4, leptin and CD31 mRNA levels were noted in the epididymal and/or retroperitoneal fat tissue of oxytocin-treated rats. Oxytocin enhanced the dephosphorylation of eEF2 in the epididymal adipose tissue.

CONCLUSIONS AND IMPLICATIONS

The present results demonstrate that subchronic treatment with oxytocin induces adipogenic and angiogenic effects and that the eEF2 signalling pathway is involved in these effects of oxytocin on adipose tissue in vivo. These findings are likely to motivate further research and indicate new approaches for modulating adipose tissue morphology and metabolism.     

In vitro inhibition of angiogenesis by heat and low pH stable hydroalcoholic extract of Peganum harmala seeds via inhibition of cell proliferation and suppression of VEGF secretion

Abstract

Context: Progression of cancer cells is completely dependent on its angiogenesis. Inhibition of tumor angiogenesis has shed new light on cancer treatment. As a result, anti-angiogenesis therapy represents one of the most significant advances in clinical oncology. Peganum harmala L. (Zygophyllaceae) is a native plant from the eastern Iranian region, which is used as a traditional folk medicine. Although some biological properties of this plant are determined, its effect on angiogenesis is still unclear.

Objective: We investigated the anti-angiogenic effects of heat and low pH stable hydroalcoholic extract of P. harmala seeds on endothelial cells (ECs) proliferation and VEGF secretion.

Materials and methods: Dried Peganum seeds were purchased from Kermanshah Traditional Bazar in 2011. Hydroalcoholic extract of dried seeds (0, 10, 20, 40, 60, 80, 100, 120, and 150?μg/ml) was used for in vitro evaluation of its cytotoxicity, anti-proliferative, and anti-angiogenic effects on ECs. In vitro effect of the extract on VEGF secretion was assayed using ELISA.

Results: Treatment with hydroalcoholic extract at seven different concentrations resulted in significant decrease of ECs proliferation and angiogenesis with an ID₅₀ of ～85?μg/ml. VEGF secretion was (inhibited) decreased by the extracts at concentrations higher than 10?μg/ml.

Discussion and conclusion: Herbal plant extracts still attract attention owing to their fewer side effects comparing to synthetic drug agents. Current study indicated that hydroalcoholic extract of P. harmala seeds contains a potent anti-angiogenic component, which exerts its inhibitory effect mainly through down-regulation of essential mediators such as VEGF.