Efficacy of Kaempferia parviflora in a mouse model of obesity-induced dermatopathy.

Obesity results from excessive energy intake and physical inactivity, and predisposes one to various diseases. One of these reasons is that enlargement of adipocytes raises the lipid metabolic abnormalities that affect various organs. The skin is one such organ, and it has been reported that subcutaneous adipocyte cells secrete various factors and these factors are involved in reduction of dermal collagen fibers and fragility of the skin in obesity. The present study explored the efficacy of Kaempferia parviflora (KP) in preventing obesity-induced dermatopathy. We used Tsumura Suzuki obese diabetes (TSOD) mice as an obesity model. TSOD mice were fed a standard diet (MF) mixed with either an ethanol extract from KP (KPE), polymethoxyflavonoid-rich extract from KP (PMF), or polymethoxyflavonoid-poor extract from KP (X). We then evaluated the effect of these three KP fractions on aging-like skin damage induced by UVB irradiation. KPE and PMF caused a significant decrease of mouse body weight, and suppressed the increase in the thickness of the subcutaneous fat layer. In addition, KPE shifted the frequency of subcutaneous adipocyte sizes towards smaller cells possibly via its polypharmacological actions. Scanning electron microscopy revealed that the stereostructure of the collagenous fibers in the dermis was better retained in the KPE and PMF groups, in that order. These results offer the first evidence that KPE can attenuate obesity-induced dermatopathy more effectively than PMF, suggesting that KPE (or KP) might be a candidate supplement for preventing obesity-related skin disorders.

Gallic Acid, the Active Ingredient of Terminalia bellirica, Enhances Adipocyte Differentiation and Adiponectin Secretion.

Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10-30 µM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARγ), although it does not alter the expression of the upstream genes PPARγ and CCAAT enhancer binding protein alpha. In the PPARγ ligand assay, the binding of gallic acid to PPARγ was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome.

Effects of ethyl acetate extract of Kaempferia parviflora on brown adipose tissue.

We have previously reported the effects of Kaempferia parviflora (KP), including anti-obesity, preventing various metabolic diseases, and regulating differentiation of white adipose cells. In this study we used Tsumura, Suzuki, Obese Diabetes (TSOD) mice--an animal model of spontaneous obese type II diabetes--and primary brown preadipocytes to examine the effects of the ethyl acetate extract of KP (KPE) on brown adipose tissue, which is one of the energy expenditure organs. TSOD mice were fed with MF mixed with either KPE 0.3 or 1% for 8 weeks. Computed tomography images showed that whitening of brown adipocytes was suppressed in the interscapular tissue of the KPE group. We also examined mRNA expression of uncoupling protein 1 (UCP-1) and ß3-adrenalin receptor (ß3AR) in brown adipose tissue. As a result, mRNA expression of UCP-1 significantly increased in the KPE 1% treatment group, indicating that KPE activated brown adipose tissue. We then evaluated the direct effects of KPE on brown adipocytes using primary brown preadipocytes isolated from interscapular brown adipocytes in ICR mice. Triacylglycerol (TG) accumulation in primary brown preadipocytes was increased by KPE in a dose-dependent manner. Each mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), UCP-1, and ß3AR exhibited an upward trend compared with the control group. Moreover, some polymethoxyflavonoids (PMFs), the main compound in KP, also increased TG accumulation. This study therefore showed that KPE enhanced the thermogenesis effect of brown adipocytes as well as promoted the differentiation of brown adipocyte cells.

Preventive effect of Terminalia bellirica on obesity and metabolic disorders in spontaneously obese type 2 diabetic model mice.

Visceral obesity induces insulin resistance and is recognized as an important risk factor for metabolic syndrome (MS). Therefore, inhibition of lipid absorption from the intestine is regarded as an effective way of preventing MS. Terminalia bellirica is extensively used in Ayurvedic medicine in India and neighboring countries, and the fruit of this plant has been reported to have hypoglycemic and hypolipidemic effects. In this study, we investigated the preventive effect of a hot water extract of T. bellirica fruit (TB) on obesity and various metabolic disorders, and explored its molecular mechanisms and active ingredients. TB treatment had a preventive effect on obesity, insulin resistance, and hyperlipidemia in spontaneously obese type 2 diabetic TSOD mice. To clarify the molecular mechanisms of TB in preventing obesity, we investigated the inhibitory effect on lipid absorption. TB suppressed absorption of triacylglycerol in an olive oil loading test (in vivo) and showed a strong inhibitory effect on pancreatic lipase activity (in vitro). Furthermore, a search for the active ingredients in TB revealed that gallic acid is the component primarily responsible for the inhibition of pancreatic lipase activity. Thus, our findings indicate that TB could be useful in preventing MS. The mechanisms probably involve suppression of the absorption of meal-derived lipids mediated by gallic acid.