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Journal of Integrative Medicine ›› 2020, Vol. 18 ›› Issue (3): 253-264.doi: 10.1016/j.joim.2020.02.001

• Original Experimental Research • Previous Articles     Next Articles

Caulerpa okamurae extract attenuates inflammatory interaction, regulates glucose metabolism and increases insulin sensitivity in 3T3-L1 adipocytes and RAW 264.7 macrophages

Bikash Manandhara, Hyun Jung Kimb, Dong Young Rhyua   

  1. a. Department of Oriental Medicine Resources and Institute of Korean Herbal Medicine Industry, Mokpo National University, Jeonnam 58554, South Korea
    b. College of Pharmacy, Mokpo National University, Jeonnam 58554, South Korea
  • Received:2019-04-02 Accepted:2019-12-23 Online:2020-05-08 Published:2020-02-26
  • About author:Dong Young Rhyu


To examine whether Caulerpa okamurae ethanolic extract (COE) could inhibit obesity-mediated inflammation, improve glucose metabolism and increases insulin sensitivity, using in vitro cell models of RAW 264.7 macrophages and 3T3-L1 adipocytes. 


We cocultured 3T3-L1 adipocytes in direct contact with lipopolysaccharide-stimulated RAW 264.7 macrophages and induced insulin resistance in 3T3-L1 adipocytes with tumor necrosis factor-α (TNF-α) in the presence or absence of 250 μg/mL of COE. We investigated various markers of inflammation, glucose regulation and insulin sensitivity in these models using Griess reagent to measure nitric oxide (NO) production, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose to measure glucose uptake, Western blot analysis to quantify protein expression and reverse transcriptase-polymerase chain reaction to evaluate mRNA expression.


We found that COE (250 μg/mL) significantly inhibited the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages by downregulating NO production, nitric oxide synthase 2 expression and nuclear translocation of nuclear factor-κB. COE also showed similar anti-inflammatory activity in coculture, along with decreased TNF-α, interleukin-6 and monocyte chemoattractant protein mRNA expression. In addition, COE also improved glucose uptake in coculture by upregulating glucose transporter-4 (GLUT-4) and adiponectin and reducing serine phosphorylation of insulin receptor substrate-1 (IRS1). In the TNF-α-induced insulin resistance model of 3T3-L1 adipocytes, COE significantly improved both basal and insulin-stimulated glucose uptake, accompanied by phosphorylation of IRS1 at tyrosine 632, phospho-5' adenosine monophosphate-activated protein kinase α and glycogen synthase kinase-3β (Ser9) as well as upregulation of GLUT-4.


Together, these findings suggest that COE has potential to treat or prevent obesity-induced metabolic disorders.

Key words: Caulerpa okamurae, , RAW 264.7 macrophages, 3T3-L1 adipocytes, Coculture, Metabolic disorder

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