OBJECTIVE: To examine whether Caulerpa okamurae ethanolic extract (COE) could inhibit obesity-mediated inflammation, improve glucose metabolism and increase insulin sensitivity, using in vitro cell models of RAW 264.7 macrophages and 3T3-L1 adipocytes. METHODS: 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. RESULTS: 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. CONCLUSION Together, these findings suggest that COE has potential to treat or prevent obesity-induced metabolic disorders.

Aegle marmelos Linn. (Rutaceae), commonly known as "bael" in Nepal and India, is a valuable medicinal plant and is considered sacred by the Hindus. It is used to cure several diseases in the Indian traditional medicine system of Ayurveda and has had similar uses among many ethnic communities residing in Indian subcontinent for over 5000 years. Its leaves, bark, stem, fruits and seeds have been used for various medicinal purposes. Bael fruits are especially effective in the treatment of chronic diarrhea, dysentery and peptic ulcers, while they are also useful as a laxative and cure for respiratory infections. Scientific studies have validated many of the ethnomedicinal uses of A. marmelos, which include antibacterial, antiviral, antidiarrheal, gastroprotective, anti-ulcerative colitis, hepatoprotective, antidiabetic, cardioprotective and radioprotective effects. Recently, this plant has also received attention as an anticancer agent for the treatment of various types of cancers. Thus, this review focuses on scientific evidence verifying the important pharmacological activity such as antioxidant, antidiabetic, antimicrobial, hepatoprotective, cardioprotective and anticancer activity of A. marmelos.
Aegle ; chemistry ; Animals ; Anti-Infective Agents ; chemistry ; pharmacology ; Antioxidants ; chemistry ; pharmacology ; Humans ; Phytochemicals ; chemistry ; pharmacology ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry