Metformin decreases angiogenesis via NF-κB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1

Tan, Bee K.; Adya, Raghu; Chen, Jing; Syed, Farhatullah; Heutling, Dennis; Mitchell, Daniel A.; Lehnert, Hendrik; Randeva, Harpal S.

doi:10.1093/cvr/cvp131

Cited by 107 publications

(98 citation statements)

References 19 publications

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“…Bee venom inhibits the DNA-binding activity of NF-κB by inhibiting IκB phosphorylation (14). Thus, our findings are in agreement with those of others showing that the anti-inflammatory activity of honey bee venom is mediated through suppression of the NF-κB signaling pathway (27,28). So, increased levels of CRP can be adjusted by treating rats with honey bee venom for 14 days.…”

Section: Discussionsupporting

confidence: 93%

Bee venom treatment reduced C-reactive protein and improved follicle quality in a rat model of estradiol valerate-induced polycystic ovarian syndrome

Karimzadeh¹,

Nabiuni²,

Sheikholeslami³

et al. 2012

J. Venom. Anim. Toxins incl. Trop. Dis

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Polycystic ovarian syndrome (PCOS) is a low grade inflammatory disease characterized by hyperandrogenemia and chronic anovulation. C-reactive protein (CRP), released by adipocytes, plays a key role in PCOS. Apis mellifera honeybee venom (HBV) contains a variety of biologically active components with various pharmaceutical properties. This study was designed to assess the possibility of HBV application as an anti-inflammatory therapeutic agent. To induce PCOS, 1 mg/100 g body weight estradiol valerate (EV) was subcutaneously (SC) injected into eight-week-old rats. After 60 days, 0.5 mg/kg HBV was administered SC for 14 consecutive days, and the results of PCOS treatment were investigated. Rats were then anesthetized with chloroform, and their ovaries and livers were surgically removed to determine histomorphometrical changes. Testosterone and 17-β-estradiol were detected by chemiluminescence immunoassay. In order to detect serum CRP, ELISA kit was used in three groups of EV-induced PCOS, HBV-treated PCOS and control animals. Thickness of the theca layer, number of cysts and the level of serum CRP significantly decreased in HBV group in comparison with PCOS group. Moreover, corpus luteum, as a sign of ovulation, was observed in HBV-treated ovaries which were absent in PCOS group. Our results suggest that the beneficial effect of HBV may be mediated through its inhibitory effect on serum CRP levels.

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Section: Discussionsupporting

confidence: 93%

Bee venom treatment reduced C-reactive protein and improved follicle quality in a rat model of estradiol valerate-induced polycystic ovarian syndrome

Karimzadeh¹,

Nabiuni²,

Sheikholeslami³

et al. 2012

J. Venom. Anim. Toxins incl. Trop. Dis

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show abstract

“…Three previous studies in overweight/obese women with PCOS reported a decline in circulating PAI-1 levels after treatment with metformin for 6 months, [20][21][22] but two others did not show a significant change after treatment for 1.5 to 24 months. 23,24 In normal weight women with PCOS, we observed a significant reduction in plasma PAI-1 antigen levels after treatment with metformin for 6 months.…”

Section: Discussionmentioning

confidence: 83%

“…6 Interestingly, in the three studies that reported a decline in PAI-1 levels after treatment with metformin there was no change in BMI, whereas markers of IR improved. [20][21][22] In contrast, IR did not change despite a reduction in BMI in a study that did not detect a change in PAI-1 levels after treatment with metformin. 23 Therefore, the improvement of IR appears to contribute more Table 1.…”

Section: Discussionmentioning

confidence: 90%

Disparate effects of pharmacotherapy on plasma plasminogen activator inhibitor-1 levels in women with the polycystic ovary syndrome

Koiou¹,

Τζιόμαλος²,

Katsikis³

et al. 2013

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ObJEctIVE: Polycystic ovary syndrome (PcOs) is characterized by obesity and insulin resistance (Ir), which result in elevated plasminogen activator inhibitor-1 (PAI-1) levels. We aimed to assess the changes in PAI-1 levels in PcOs during treatment with metformin and during weight loss. DEsIGN: twenty-three normal weight women with PcOs were given metformin 850 mg bid for 6 months. Fifty overweight/obese women with PcOs were prescribed an energy-restricted diet, were instructed to exercise and were randomized to orlistat 120 mg tid or sibutramine 10 mg qd for 6 months. rEsULts: In normal weight women, treatment with metformin reduced the body mass index (bMI) and circulating androgens, improved markers of Ir and lowered PAI-1 levels. In overweight/obese women, sibutramine and orlistat yielded comparable reductions in bMI and markers of Ir. In contrast, the effects on the free androgen index (FAI) differed (p=0.027): sibutramine reduced the FAI (p=0.005), whereas orlistat had no effect. the effects of sibutramine and orlistat on PAI-1 levels also differed (p=0.042): sibutramine reduced PAI-1 levels (p<0.001), whereas orlistat had no effect. cONcLUsIONs: Metformin and sibutramine, but not orlistat, reduce PAI-1 levels in PcOs. the reduction in circulating androgens during metformin and sibutramine treatment might be implicated in this decline.

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“…Varma et al, (2008) reported a small but positive correlation between gene expression of TSP-1 in adipose tissue and BMI with no effect of prior metformin administration. However, Tan et al, (2009) found that 6-months treatment with metformin of women with PCOS elevated the low circulating levels of TSP-1. The available evidence does not support the claim that TSP-1 is an adipokine released by fat cells that has any causal relationship to obesity and insulin resistance.…”

Section: Thrombospondin-1 [Tsp1]mentioning

confidence: 93%

Effect of Obesity on Circulating Adipokines and Their Expression in Omental Adipose Tissue of Female Bariatric Surgery Patients

Fain¹

2012

Advanced Bariatric and Metabolic Surgery

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Metformin decreases angiogenesis via NF-κB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1

Abstract: TSP-1 levels are lower in PCOS women. Metformin treatment increases serum TSP-1 in these women. Our findings provide novel insights into the relationship between obesity, IR, and angiogenesis.

Cited by 107 publications

References 19 publications

Bee venom treatment reduced C-reactive protein and improved follicle quality in a rat model of estradiol valerate-induced polycystic ovarian syndrome

Bee venom treatment reduced C-reactive protein and improved follicle quality in a rat model of estradiol valerate-induced polycystic ovarian syndrome

Disparate effects of pharmacotherapy on plasma plasminogen activator inhibitor-1 levels in women with the polycystic ovary syndrome

Effect of Obesity on Circulating Adipokines and Their Expression in Omental Adipose Tissue of Female Bariatric Surgery Patients

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