Preventive Effect of Geniposide on Metabolic Disease Status in Spontaneously Obese Type 2 Diabetic Mice and Free Fatty Acid-Treated HepG2 Cells

Abstract

Obesity, diabetes, hyperlipidemia and hypertension, which are caused by hypernutrition and lack of exercise, are often found in the same person. These symptoms used to be called "the deadly quartet," "Syndrome X" or "insulin resistance syndrome," but these names have recently been collectively replaced with "metabolic syndrome (MS)," since the presence of visceral fat accumulation-type obesity has been recognized as the major disease base. It should be noted that progression of MS increases the risk of future onset of ischemic cardiac diseases and cerebrovascular diseases, and the importance of "prevention" and "early therapy" of MS is emphasized.Gardeniae fructus, the fruit of Gardenia jasminoides ELLIS, is widely used in Asian countries as a natural colorant, and it is also used as a Japanese and Chinese traditional medicine since it has a homeostatic effect, an antiphlogistic effect, an analgesic effect, an antipyretic effect, a hepatoprotective effect and a hypolipidaemic effect.1,2) Geniposide, an iridoid glycoside contained in Gardeniae fructus, is reported to have a hepatoprotective effect, an antioxidant effect, a hypoglycemic effect, a vascular endothelial cell adhesion-suppressing effect, an anti-lipopolysaccharide (LPS) effect, a neuroprotective effect, and an anti-inflammatory effect. [3][4][5][6][7][8][9] In addition, genipin, which is the aglycone portion of geniposide and is formed as a metabolite, is also reported to have an anti-inflammatory effect, a bile secretion-enhancing effect, and an anti-thrombotic effect. [10][11][12] Geniposide is promising as a seed compound for developing therapeutic medicines for metabolic diseases. However, no publication has reported the effect of geniposide on various metabolic disease symptoms based on visceral fat accumulation. TSOD mice are model animals showing spontaneously multifactorial genetic Type 2 diabetes based on visceral fat accumulation. [13][14][15][16][17][18] Since the cause of onset and the symptoms are very similar to those of human MS, this model is regarded as promising for the study of MS. In the present study, we investigated the effect of geniposide on various metabolic disease symptoms based on visceral fat accumulation using TSOD mice. In addition, a fatty liver model was prepared by adding a free fatty acid to human liver cancer cells (HepG2 cells), 19) and the direct effect of genipin on the liver was investigated. MATERIALS AND METHODSReagents Geniposide and genipin (Fig. 1) were supplied by Tsumura and Co. (Ibaraki, Japan). Palmitic acid powder was purchased from Sigma-Aldrich (MO, U.S.A.). The other reagents used were of the highest grade available.Animal Experiments Experimental Animals: Male TSOD mice and corresponding control animals (TSNO mice) were purchased from the Institute for Animal Reproduction (Ibaraki) at the age of 3 weeks. They were acclimated under controlled circumstances (temperature: 23Ϯ1°C, humidity: 55Ϯ5%, lighting hours: 12 h) for one week. During the acclimation period, the animals were given ordinary powder ...

Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function

“…Geniposide is one of the active ingredients in traditional Chinese medicine used to fight obesity [35] . For instance, geniposide has been used for the amelioration of spontaneously obese type 2 diabetic mice and has been shown to suppress body weight and visceral fat accumulation [36] . Inflammatory cytokine release and neutrophil infiltration play an important role in colitis; MPO can indirectly reflect the vitality of neutrophil infiltration [37] .…”

Genipin Reverses HFD-Induced Liver Damage and Inhibits UCP2-Mediated Pyroptosis in Mice

“…Collectively, these data show that GNP has therapeutic benefits in patients with liver disease. Interestingly, another study showed that inhibition of UCP2 with GNP exacerbated palmitate-induced hepatic steatosis, which is controversial with previous study demonstrating decreased triacylglycerol concentrations [46], may be attributed to the low concentration (5 μM) and the compensatory effect of upregulated UCP2 expression.…”

Effects of Single Administered Bofutsushosan-Composed Crude Drugs on Diabetic Serum Parameters in Streptozotocin-Induced Diabetic Mice

“…This reducing effect might depend on geniposide, the main compound of Gardeniae Fructus. Geniposide had the effect on lowering the quantity of visceral fat and showed an alleviating effect on abnormal glucose/lipid metabolism [24]. The lowering effect of Gardeniae Fructus on serum triglyceride was parallel with its anti-hyperglycemic action.…”