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The accumulation of visceral adipose tissue usually results from an energy imbalance involving the combination of excessive calorie consumption with insufficient energy expenditure. Increased visceral adiposity can induce insulin resistance and lead to type 2 diabetes mellitus, dyslipidemia, hypertension, and cardiovascular disease.1) "Metabolic syndrome" is the combination of multiple cardiovascular risk factors, including visceral obesity, dyslipidemia, glucose intolerance, and hypertension in one individual.2,3) Obesity resulting from an accumulation of visceral adiposity is a primary cause of metabolic syndrome.Propolis is a sticky, resinous substance collected by honey bees (Apis mellifera) from the sap, leaves, and buds of plants, and then mixed with secreted beeswax. The chemical constituents of propolis are mainly flavonoids, phenolic compounds, caffeoylquinic acids, cinnamic acid derivatives, diterpenoic acid, lignan, coumarin acid and other compounds. 4,5) Propolis has been used as a folk medicine in many countries from ancient times especially in Brazil and Eastern Europe. It has been characterized variously as an anti-bacterial, 6,7) anti-viral, 8) anti-inflammatory, 9-11) anti-oxidant, 12) and anti-carcinogenesis agent. 13,14) Obesity is caused by various environmental and genetic factors.15) One of the main environmental factors causing obesity is the intake of a high-fat diet, now common in many populations. A diet-induced obesity animal model has been developed to investigate human obesity, replicating the effects of human obesity more accurately than genetic obesity models.16) Mice that are fed a high-fat diet, develop obesity, hyperglycemia, and hyperlipidemia, and differ from those fed a normal diet in the expression levels of specific genes transcripts.17) Recent studies have reported that propolis prevented and mitigated diabetes and hypertension, [18][19][20][21][22] but it remains unclear whether propolis similarly prevents and mitigates the accumulation of visceral adipose tissues and hyperlipidemia. In this study we examined the effect of propolis on visceral fat and hyperlipidemia induced in a high-fat dietinduced obesity mouse model, and analyzed hepatic gene expression involved in lipid metabolism. MATERIALS AND METHODS Preparation of Propolis ExtractPropolis used in this study was obtained from Apiai, Sao Paulo in Brazil. Propolis (1 kg) was treated with 50% ethanol (3 l) at room temperature for 24 h, and filtered. This extract included 10.8% of solid contents of propolis. Total flavonoids content in the extract was determined as amounts of quercetin by using the aluminum nitrate method as described previously.23) In addition, the extract was subjected to reversed-phase column chromatography using following conditions: column, Shim Pack CLC-ODS (6 mm i.d.ϫ150 mm, Shimadzu, Japan); column temperature, 50°C; gradient system, A solvent (30% MeOH, 70% H 2 O and 1% AcOH) and B solvent (75% MeOH, 25% H 2 O and 1% AcOH), 0-20 min 100% A isocratic, 20-55 min 100% B isocratic, 55-75 min 100% ...

We have previously shown that royal jelly (RJ) promoted collagen production by skin fibroblasts in the presence of ascorbic acid-2-O-alpha-glucoside (AA-2G). In this study, we purified the honeybee RJ-derived collagen production-promoting factor (HBRJ-CPF) from an alkali-solubilized fraction of RJ by C18 reverse-phase column chromatography. The elution profile by the C18 column chromatography and the molecular mass of the purified HBRJ-CPF material coincided with those of 10-hydroxy-2-decenoic acid (10H2DA). We then examined the collagen productionpromoting activities of several commercially available fatty acids contained in RJ. We found that 10H2DA and 10-hydroxydecanoic acid increased the collagen production in a dose-dependent manner. Furthermore, 10H2DA induced the fibroblast cell line, NHDF, to produce transforming growth factor-1 (TGF-1) which is an important factor for collagen production. As expected, the collagen production-promoting activity of 10H2DA was neutralized by the anti-TGF-1 antibody. These result suggest that HBRJ-CPF identified as 10H2DA promoted the collagen production of AA-2G-treated fibroblasts by inducing TGF-1 production.

In experiments using the renal carcinogen ferric nitrilotriacetate (Fe-NTA) in male ddY mice, primary pulmonary cancers were also induced in bronchiolar and alveolar tissues. 4-Hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), products of oxidative processes, increased in bronchiolar and alveolar cells after administration of Fe-NTA. These substances disappeared after oral administration of propolis or artepillin C, as shown histochemically, and correlated with an anticancer prophylactic effect of propolis and artepillin C. From our investigation, lipid peroxidation seems to play an important role in pulmonary carcinogenesis. Malignant progression from adenoma of bronchiolar or alveolar origin to malignant tumors has been proposed to involve a stepwise transformation. In our study, adenomas developed into adenocarcinomas and large cell carcinomas after treatment with Fe-NTA. In contrast, after oral administration of propolis or artepillin C, adenomas did not progress to carcinomas. Instead of developing into large cell cancers, as induced by Fe-NTA in control mice, adenomas showed remarkable proliferation of macrophages and local anti-oxidant activity after treatment with either propolis or artepillin C. Propolis and artepillin C therefore appear to inhibit lipid peroxidation and the development of pulmonary cancers.