Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes

Abstract

Objective: Evodiamine (evo) has been shown to exert anti-inflammatory, antinociceptive and anticancer effects. In this study, we investigated the effects of evo alone and in combination with rosiglitazone (rosi) on in vitro adipocyte differentiation and in vivo obesity related to diabetes. Methods: Adipocyte differentiation was investigated in vitro using 3T3-L1 and C3H10T1/2 cells. To determine the degree of differentiation, Oil Red O staining and reverse transcription-PCR were carried out. Four groups of db/db mice were treated intraperitoneally once per day with vehicle, evo, rosi and evo þ rosi. The mice were killed after 14 days and the blood, liver and adipose tissue were analyzed. Results: The presence of evo or evo combined with rosi during adipogenic induction has been shown to inhibit adipocyte differentiation to a significant degree, particularly at the commitment and early induction stages. The evo and evo þ rosi groups of db/db mice evidenced significant reductions in body weight gain. The ratio of epididymal white adipocyte tissue weight to body weight of the evo group was also significantly reduced. It is important to note that in the evo þ rosi treatment, blood glucose levels were reduced to a degree similar to that of the rosi group, and plasma insulin levels were reduced significantly better than that of rosi group. Furthermore, hepatic lesions associated with fat and glycogen deposition were morphologically improved in the evo and evo þ rosi groups. Conclusion:The results of this study showed that evo exerts an inhibitory effect on in vitro adipocyte differentiation and in vivo obesity, and also an improvement effect on insulin resistance. These desirable effects of evo were noted even in the presence of rosi. These results indicate that evo improves the undesirable effects of rosi, including adipogenesis, body weight gain and hepatotoxicity, while preserving its desirable blood-glucose-lowering effect.

Scaffold Diversity Inspired by the Natural Product Evodiamine: Discovery of Highly Potent and Multitargeting Antitumor Agents

“…1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 positive) m/z calcd for C 19 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 …”

Evodiamine activates AMPK and promotes adiponectin multimerization in 3T3-L1 adipocytes

“…Evodiamine treatment also increases the HMW/total ratio of adiponectin in the culture medium (data not shown). Evodiamine has been demonstrated to have blood-glucose-lowering and anti-obesity effects [25]. Activation of AMPK by evodiamine was also found to inhibit the differentiation of 3T3-L1 preadipocytes (unpublished results), similar to BBR and emodin [10,11].…”

Amelioration of insulin resistance in rat cells by Astragalus polysaccharides and associated mechanisms

“…Decreases in PPAR-γ transcriptional activity increase inflammatory cytokine secretion and decrease levels of adiponectin, resulting in a decrease in insulin sensitivity (15). mRNA expression and adiponectin secretion in humans, obese (ob/ob) mice and cultured 3T3-L1 cells increase following treatment with PPAR-γ agonists (16–19). PPAR belongs to the hormone nuclear receptor superfamily and is composed of three subtypes encoded by three different genes: PPAR-α, -δ and -γ. PPAR-γ is one of the most adipose tissue-specific nuclear transcription factors with important functions in the proliferation and differentiation of fat cells.…”