Cymbopogon citratus is a widely distributed perennial herb belonging to the Poaceae family and has been extensively consumed for its medicinal, cosmetic, and nutritional effects for centuries. A large number of reports have been published describing the pharmacological, biological, and therapeutic actions of this herb. In this review, we summarized the literatures on related studies (up to January, 2014) that highlighted the pharmacologic and biological effects of the major phytochemicals isolated from C. citratus extracts and its essential oil. The components of the essential oils found in C. citratus have a similar pharmacokinetic properties, including absorption, distribution, metabolism, and excretion. They are quickly absorbed following oral, pulmonary, and dermal administration. Based on the published reports, it can also be inferred that, after absorption from the small intestine, some phytochemicals in C. citratus can undergo oxidation, glucuronidation, sulfation, and/or O-methylation. Excretion is through urine, feces and/or expired volatiles. The biotransformation reactions of C. citratus bioactive constituents are essential for its relatively safe consumption and therapeutic applications. The data available so far warrant further studies evaluating C. citratus pharmacokinetics. Reliable pharmacokinetic data in humans would be critical for a better understanding of the the systemic handling of C. citratus.
Animals ; Anti-Infective Agents ; pharmacokinetics ; pharmacology ; therapeutic use ; Anti-Inflammatory Agents ; pharmacokinetics ; pharmacology ; therapeutic use ; Anti-Obesity Agents ; pharmacokinetics ; pharmacology ; therapeutic use ; Antineoplastic Agents ; pharmacokinetics ; pharmacology ; therapeutic use ; Antioxidants ; pharmacokinetics ; pharmacology ; therapeutic use ; Central Nervous System Agents ; pharmacokinetics ; pharmacology ; therapeutic use ; Cymbopogon ; Ethnopharmacology ; Hematologic Agents ; pharmacokinetics ; pharmacology ; therapeutic use ; Humans ; Hypoglycemic Agents ; pharmacokinetics ; pharmacology ; therapeutic use ; Male ; Mice ; Oils, Volatile ; pharmacokinetics ; pharmacology ; therapeutic use ; Plant Extracts ; pharmacokinetics ; pharmacology ; therapeutic use ; Plant Oils ; pharmacokinetics ; pharmacology ; therapeutic use ; Rats, Inbred F344 ; Urological Agents ; pharmacokinetics ; pharmacology ; therapeutic use

OBJECTIVETo investigate the effects of Chang-Chul-Eui-Ee-In-Tang ([see text], CCEET), modififi ed CCEET (MCCEET), and Semen Coicis (SC, a major component of CCEET) on energy and glucose homeostasis. The possible mechanism of action of CCEET was also determined.

METHODSA total of 100 Sprague Dawley female rats were randomly assigned to 5 groups, with 20 in each group. Rats in 4 groups were fed with a high fat diet supplementation (2 g/kg body weight), and water extracts of CCEET, MCCEET, SC, and cellulose (negative control), respectively. The last group was fed with a low-fat diet as a positive control.

RESULTSCCEET and MCCEET decreased body weight and body fat (mesenteric and retroperitoneal fat) more than SC. This decrease was due to decreased energy intake and increased energy expenditure and fat oxidation. The improvement in energy homeostasis was associated with the enhancement of the hypothalamic leptin signalling pathway involving potentiating the phosphorylation of the signal transducer and activator of transcription-3, as well as attenuating the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK). Both CCEET and MCCEET improved glucose tolerance without changing serum insulin levels during an oral glucose tolerance test but MCCEET had a better effect than CCEET.

CONCLUSIONSBoth CCEET and MCCEET safely exerted anti-obesity effects by enhancing energy balance in female rats with diet-induced obesity; MCCEET showed a better effect on glucose homeostasis.

Adenylate Kinase ; metabolism ; Adipose Tissue ; drug effects ; Animals ; Anti-Obesity Agents ; adverse effects ; pharmacology ; therapeutic use ; Blood Glucose ; metabolism ; Body Weight ; drug effects ; Calorimetry ; Diet ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Energy Metabolism ; drug effects ; Female ; Glucose Tolerance Test ; Homeostasis ; drug effects ; Hypothalamus ; drug effects ; enzymology ; Leptin ; metabolism ; Motor Activity ; drug effects ; Obesity ; blood ; drug therapy ; pathology ; physiopathology ; Phosphorylation ; drug effects ; Rats ; Rats, Sprague-Dawley ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects

Higher levels of body fat are associated with an increased risk for development numerous adverse health conditions. FTY720 is an immune modulator and a synthetic analogue of sphingosine 1-phosphate (S1P), activated S1P receptors and is effective in experimental models of transplantation and autoimmunity. Whereas immune modulation by FTY720 has been extensively studied, other actions of FTY720 are not well understood. Here we describe a novel role of FTY720 in the prevention of obesity, involving the regulation of adipogenesis and lipolysis in vivo and in vitro. Male C57B/6J mice were fed a standard diet or a high fat diet (HFD) without or with FTY720 (0.04 mg/kg, twice a week) for 6 weeks. The HFD induced an accumulation of large adipocytes, down-regulation of phosphorylated AMP-activated protein kinase alpha (p-AMPKalpha) and Akt (p-Akt); down-regulation of hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL) and perilipin mRNA as well as up-regulation of phosphorylated HSL (p-HSL, Ser563) and glycogen synthase kinase 3 alpha/beta (p-GSK3alpha/beta). All these effects were blunted by FTY720 treatment, which inhibited adipogenesis and promoted lipolysis. Also, FTY720 significantly decreased lipid accumulation in maturing preadipocytes. FTY720 down-regulated the transcriptional levels of the PPARgamma, C/EBPalpha and adiponectin, which are markers of adipogenic differentiation. FTY720 significantly increased the release of glycerol and the expression of the HSL, ATGL and perilipin, which are regulators of lipolysis. These results show that FTY720 prevented obesity by modulating adipogenesis and lipolysis, and suggest that FTY720 is used for the treatment of obesity.
3T3-L1 Cells ; AMP-Activated Protein Kinases/metabolism ; Adipocytes/*drug effects/physiology ; Adipogenesis/drug effects ; Animals ; Anti-Obesity Agents/*pharmacology/therapeutic use ; Antigens, Differentiation/genetics/metabolism ; Carrier Proteins/genetics/metabolism ; Cell Size ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Enzyme Activation ; Gene Expression Regulation, Enzymologic/drug effects ; Glycogen Synthase Kinase 3/genetics/metabolism ; Lipase/genetics/metabolism ; Lipolysis/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/etiology/metabolism/*prevention & control ; Phosphoproteins/genetics/metabolism ; Phosphorylation ; Propylene Glycols/*pharmacology/therapeutic use ; Protein Processing, Post-Translational ; Proto-Oncogene Proteins c-akt/metabolism ; Sphingosine/*analogs & derivatives/pharmacology/therapeutic use ; Sterol Esterase/metabolism

Lysimachia foenum-graecum has been used as an oriental medicine with anti-inflammatory effect. The anti-obesity effect of L. foenum-graecum extract (LFE) was first discovered in our screening of natural product extract library against adipogenesis. To characterize its anti-obesity effects and to evaluate its potential as an anti-obesity drug, we performed various obesity-related experiments in vitro and in vivo. In adipogenesis assay, LFE blocked the differentiation of 3T3-L1 preadipocyte in a dose-dependent manner with an IC50 of 2.5 microg/ml. In addition, LFE suppressed the expression of lipogenic genes, while increasing the expression of lipolytic genes in vitro at 10 microg/ml and in vivo at 100 mg/kg/day. The anti-adipogenic and anti-lipogenic effect of LFE seems to be mediated by the inhibition of PPARgamma and C/EBPalpha expression as shown in in vitro and in vivo, and the suppression of PPARgamma activity in vitro. Moreover, LFE stimulated fatty acid oxidation in an AMPK-dependent manner. In high-fat diet (HFD)-induced obese mice (n = 8/group), oral administration of LFE at 30, 100, and 300 mg/kg/day decreased total body weight gain significantly in all doses tested. No difference in food intake was observed between vehicle- and LFE-treated HFD mice. The weight of white adipose tissues including abdominal subcutaneous, epididymal, and perirenal adipose tissue was reduced markedly in LFE-treated HFD mice in a dose-dependent manner. Treatment of LFE also greatly improved serum levels of obesity-related biomarkers such as glucose, triglycerides, and adipocytokines leptin, adiponectin, and resistin. All together, these results showed anti-obesity effects of LFE on adipogenesis and lipid metabolism in vitro and in vivo and raised a possibility of developing LFE as anti-obesity therapeutics.
3T3-L1 Cells ; Adipogenesis/*drug effects ; Adipose Tissue/drug effects/metabolism ; Adipose Tissue, White ; Animals ; Anti-Obesity Agents/administration & dosage/pharmacology/*therapeutic use ; Body Weight/drug effects ; CCAAT-Enhancer-Binding Protein-alpha/genetics ; Cell Differentiation/drug effects ; Eating/drug effects ; Fatty Acids/metabolism ; Gene Expression/drug effects ; Lipid Metabolism/*drug effects ; Lipids ; Lipogenesis/drug effects ; Mice ; Mice, Inbred C57BL ; Obesity/prevention & control ; PPAR gamma/antagonists & inhibitors/genetics ; Plant Extracts/*pharmacology ; Plants, Medicinal ; Primulaceae/*chemistry