A nutritional perspective on UCP1-dependent thermogenesis.

Kaempferia parviflora (KP), a health-promoting herb, has been traditionally used for treating a variety of diseases. Pharmacological studies have claimed the various benefits from KP and its main effective methoxyflavones, including cellular metabolism-regulating activity, anticancer activity, vascular relaxation and cardioprotective activity, sexual enhancing activity, neuroprotective activity, antiallergic, anti-inflammatory, and antioxidative activity, antiosteoarthritis activity, antimicroorganism activity, and transdermal permeable activity. These might be associated with increased mitochondrial functions and activated cGMP-NO signaling pathway. However, the underlying molecular mechanisms of KP and its methoxyflavones are still under investigation. The clinical applications of KP and its methoxyflavones may be limited due to their low bioavailability. But promising strategies are on the way. This review will comprehensively discuss the biological activities of KP and its methoxyflavones.

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Kaempferia parviflora and Its Methoxyflavones: Chemistry and Biological Activities.

Background: Plants belonging to the genus Kaempferia (family: Zingiberaceae) are distributed in Asia, especially in the southeast region, and Thailand. They have been widely used in traditional med ...

Recent Advances in Kaempferia Phytochemistry and Biological Activity: A Comprehensive Review

Extracts of Salacia reticulata Wight (Hypocrataceae) roots, stems, and leaves have been used in Asia for hundreds of years for the folkloric treatment of diabetes and other health problems. Constituents that have been identified as exhibiting anti‐diabetic effects include salacinol, kotalanol, ponkorinol, salaprinol, and their corresponding de‐0‐sulfonated compounds. Mangiferin, kotalagenin 16‐acetate and various proanthocyanidin oligomers have also been isolated. Studies indicate that Salacia extracts modulate multiple targets that influence carbohydrate and lipid metabolism including α‐glucosidase, aldose reductase, pancreatic lipase, peroxisomal proliferator‐activated receptor‐α, glucose transporter‐4 mediated glucose uptake, and angiotensin II type 1 receptor. Furthermore, Salacia extracts exhibit free radical scavenging, antioxidant and hepatoprotectant activities. In human studies, Salacia extracts have been shown to decrease plasma glucose and insulin levels, decrease HbA1c, and modulate serum lipid levels with no adverse effects being reported. Similar results have been demonstrated in rat and mouse models as well as in vitro systems. Safety of S. reticulata and other Salacia species as S. oblonga and S. chinensis in rats and mice indicate that extracts are exceedingly safe. No clinical studies have examined the effects of Salacia extracts on human weight loss, although weight loss and decreases in weight gain have been demonstrated in animal models. Because of the large number of pharmacologically active compounds, it is difficult to establish standards for extracts. © 2015 The Authors. Phytotheraphy Research published by John Wiley & Sons Ltd.

Anti-diabetic and Anti-hyperlipidemic Effects and Safety of Salacia reticulata and Related Species

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.

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

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 β3-adrenalin receptor (β3AR) 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 β3AR 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.

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

Salacia reticulata Wight (S. reticulata) is a herbal medicine used for treatment of early diabetes in Ayurvedic medicine. In previous reports, the extract of S. reticulata showed preventive effects on obesity and various metabolic disorders and a suppressive effect on differentiation in premature adipocytes. The aim of this research was to elucidate the therapeutic efficacy of the extract of S. reticulata on obesity and various metabolic disorders in 12-week-old TSOD mice with obesity and metabolic disorders and in mature 3T3-L1 adipocytes. In TSOD mice, S. reticulata therapy produced a reduction in body weight and mesenteric fat accumulation, an improvement in abnormal glucose metabolism, and an increase in adiponectin level in plasma. In addition, the mRNA expressions of hormone-sensitive lipase (HSL) and adiponectin were increased in mesenteric fat. In in vitro experiments, S. reticulata therapy produced suppression of intracellular triacylglycerol accumulation and enhancement of glycerol release into the medium in mature 3T3-L1 cells. The mRNA expressions of lipogenesis factor (peroxisome proliferator-activated receptor γ, lipoprotein lipase, CD36, and fatty acid binding protein 4) were down-regulated, while the expressions of lipolysis factor (adipose tissue triacylglycerol lipase and HSL) and adiponectin were up-regulated. Moreover, the extract of S. reticulata enhanced the expression of total AMP-activated protein kinase α (AMPKα) and phosphorylated AMPKα in mature adipocytes. These findings demonstrate that the extract of S. reticulata has therapeutic effects on obesity and metabolic disorders by enhancing lipogenesis genes and suppressing lipolysis genes through the activation of AMPKα in adipocytes.

Salacia reticulata has therapeutic effects on obesity

Knee osteoarthritis (OA) is becoming more prevalent worldwide due to increases in the numbers of elderly and obese patients. Currently, pharmaceutical medicines used for the treatment of OA are for symptomatic therapy and therefore new therapeutic agents are needed. Kaempferia parviflora (KP) is a plant growing naturally in Southeast Asia and has various pharmacological effects including an anti-inflammatory effect, but no effect on OA has yet been reported. We therefore conducted a search for the effects KP and the active components of KP extract (KPE) exert on OA as well as its mechanism of action. Results from a study of KPE using the monoiodoacetic acid rat OA model revealed that KPE reduced the pain threshold and severity of osteoarthritic cartilage lesions. The mechanism of action and active components were then investigated using IL-1β-treated human knee-derived chondrocytes. KPE, as well as 5,7-dimethoxyflavone and 5,7,4'-trimethoxyflavone, which are key constituents of KPE and highly absorbable into the body, reduced the expression of matrix metalloproteinases (MMPs), which are the main extracellular matrix enzymes that degrade collagen within cartilage. As mentioned above, KPE acted to suppress OA and 5,7-dimethoxyflavone and 5,7,4'-trimethoxyflavone were shown to be involved as part of KPE's mechanism that inhibits MMPs.

Effect of Kaempferia parviflora extract on knee osteoarthritis

5,7-Dimethoxyflavone (5,7-DMF), one of the major components of Kaempferia parviflora, has anti-obesity, anti-inflammatory, and antineoplastic effects. On the other hand, in vitro studies have reported that it directly inhibits the drug metabolizing enzyme family cytochrome P450 (CYP) 3As. In this study, its safety was evaluated from a pharmacokinetic point of view, based on daily ingestion of 5,7-DMF. Midazolam, a substrate of CYP3As, was orally administered to mice treated with 5,7-DMF for 10 days, and its pharmacokinetic properties were investigated. In the group administered 5,7-DMF, the area under the curve (AUC) of midazolam increased by 130% and its biological half-life was extended by approximately 100 min compared to the control group. Compared to the control group, 5,7-DMF markedly decreased the expression of CYP3A11 and CYP3A25 in the liver. These results suggest that continued ingestion of 5,7-DMF decreases the expression of CYP3As in the liver, consequently increasing the blood concentrations of drugs metabolized by CYP3As.

Effect of the active ingredient of Kaempferia parviflora, 5,7-dimethoxyflavone, on the pharmacokinetics of midazolam

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Hiroko Kobayashi

Papers

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

Salacia reticulata has therapeutic effects on obesity

Effect of Kaempferia parviflora extract on knee osteoarthritis

Effect of the active ingredient of Kaempferia parviflora, 5,7-dimethoxyflavone, on the pharmacokinetics of midazolam

Pharmacokinetics of 6-shogaol, a pungent ingredient of Zingiberis Rhizoma, and the anti-inflammatory activity of its metabolite, 6-paradol