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Effect of Lonicera japonica flower on body weight gain and glucose tolerance in rodents
Abstract
Inhibitory activities of herbal extracts against digesting enzymes, including alpha-glucosidase and alpha-amylase, were assayed to evaluate their potential as an anti-obesity measure. The ethylacetate fraction of the methanol extract of Lonicera japonica Thunb flower inhibited porcine pancreatic alpha-amylase activity in a dose-dependent manner, with an IC50 of 0.2 mg/mL. The ethylacetate fraction of the herb extract also significantly inhibited both intestinal sucrase and isomaltase activities at a concentration of 0.5 mg/mL, although it did not show a typical dose-response pattern in isomaltase inhibition. Sprague Dawley rats fed the powder of L japonica flower experienced a significant suppression of body weight gain and body fat increase. Furthermore, the herb extract improved the glucose tolerance in genetically diabetic mice (db/db). In conclusion, the flower of L japonica has potential as anti-obesity and anti-diabetes measures.
... Yangkyuksanhwa-tang, prescribed to patients with diabetes in Korea, consists of nine herbal medicines: LJT, RGL, Forsythiae Fructus, Gardeniae Fructus, Menthae Herba, Anemarrhena Rhizome, Gypsum Fibrosum, Schizonepetae Herba, and Ledebouriellae Radix [14]. Methanol extract of Lonicera japonica flower has been investigated for having suppression effect of body weight gain and body fat increase [15]. Aqueous extract of RGL has been closely studied for stimulating the expression of proinsulin gene in T2DM rats [16]. ...
Lonicera japonica
Thunb. (LJT) and
Rehmannia glutinosa
Libosch. (RGL) have been used traditionally as a herbal medicine in Korean medicine. Using LC/Q-TOF was performed to profile the two herbal medicines and the mixture of LJR and RGL (JAL2, ratio 1 : 1). We performed oral glucose tolerance test (OGTT) and plasma GLP-1 and insulin secretion by multiplex assays to investigate antidiabetic effects of LJT, RGL, and JAL2 in
db/db
mice, the mice model of type 2 diabetes mellitus (T2DM). Also, the antiobesity-related factors such as plasma peptide YY (PYY), triglyceride, total cholesterol, HDL, LDL, and weight of liver, epididymal, and retroperitoneal fat tissue were investigated. Through the multiplex assay, it was found that JAL2 treatment more efficiently attenuated high levels of blood glucose by stimulating GLP-1 secretion and reduced LDL concentration and weight of liver and retroperitoneal fat tissue compared to LJT or RGL treated separately. These results suggest that the JAL2 has antidiabetes and antiobesity effects in T2DM mice model.
... Lonicera japonica is often combined with other Chinese medicinal herbs for maximum effect (Bensky and Gamble 1993), such as in the popular herbal product Quilinggao (Wong and Chan 2003). Recent studies have confirmed the effectiveness of some traditional uses of L. japonica (for example, Chang and Hsu 1992;Lee et al. 2001;Houghton et al. 1993;Kwak et al. 2003;Kwon et al. 2004), and given its medicinal activity there have been numerous recent attempts to isolate its active ingredients for pharmacological purposes (for example, Tang and Eisenbrand 1992;Peng et al. 2005). ...
Japanese honeysuckle (Lonicera japonica Thunb.) is a twining semi-evergreen vine native to Japan, Korea and eastern China. Over the past 150 yr it has been introduced as an ornamental and become established in temperate and tropical regions worldwide. It was first discovered in Canada in 1976 in southwestern Ontario woodlands and has since been found growing without cultivation in 15 localities. While L. japonica does not occur very frequently in southern Ontario, climate change models suggest that it may become more abundant in this region. Its predominance elsewhere derives from morphological and physiological characteristics that allow it to be particularly successful in the edge habitats of fragmented landscapes. Through extensive vegetative propagation and competitive ability it occupies space which may otherwise host a diverse native flora. The plant has many uses in Asian medicine and is a popular ornamental, but has been prohibited in some regions due to its displacement of other species. A combination of cutting and foliar application of glyphosate has proven to be an effective control method in some circumstances. Planting of L. japonica should be discouraged and horticulturalists should consider alternative attractive vines. The spread of L. japonica should be monitored in Ontario and control of newly established populations should be considered to avoid costly large scale control in the future.
... The food intake, body weight, and feed efficiency values of the S. chinensis Baill group did not significantly differ from the control group (Table 3). Chronic feeding of Lonicera japonica flowers with α-glucosidase inhibitory activity to rats significantly decreased body weight gain, suggesting that α-glucosidase inhibitors may exert an anti-obesity effect (Kwon et al., 2004). In our study, however, S. chinensis Baill did not show any significant influence on body weight of rats fed 30% fat diet. ...
Saururus chinensis Baill was reported to inhibit alpha-glucosidase in vitro and flatten postprandial increase in blood glucose in streptozotocin (STZ)-induced diabetic rats. We studied the effect of chronic consumption of S. chinensis Baill on blood glucose and lipid profile in STZ-induced diabetic male rats fed high fat diet. Male rats weighing 100-120 g were fed 30% fat diet with and without 10% freeze-dried leaves of S. chinensis Baill for 7 weeks after 1 week of adaptation. The rats were rendered diabetic by intravenous injection of STZ (60 mg/kg) after 6-week feeding of the assigned diets. At 1 week after the injection, the rats were sacrificed after an overnight fast. Plasma glucose (380.2 +/- 14.4 mg/dL), total cholesterol (93.9 +/- 7.9 mg/dL) and triglyceride levels (123.6 +/- 7.5 mg/dL) of the S. chinensis Baill group were significantly lower than those of the control group (418.1 +/- 12.0 mg/dL, 119.9 +/- 9.4 mg/dL, 152.0 +/- 10.3 mg/dL, respectively, p<0.05). Chronic consumption of S. chinesis Baill significantly decreased maltase activity of the small intestinal mucosa (120.1 +/- 8.7 U/g protein) compared with the control group (96.8 +/- 7.0 U/g protein, p<0.05). These results suggest that S. chinensis Baill have hypoglycemic and hypolipidemic effects by inhibiting alpha-glucosidase activity in the animal model of diabetes mellitus.
Twenty-one naturally occurring flavonoids were tested for inhibitory activities against alpha-glucosidase (EC 3.2.1.20) and alpha-amylase (EC 3.2.1.1). Luteolin, amentoflavone, luteolin 7-O-glucoside, and daidzein were the strongest inhibitors among the compounds tested. Luteolin inhibited alpha-glucosidase by 36% at the concentration of 0.5 mg/ml and was stronger than acarbose, the most widely prescribed drug, in inhibitory potency, suggesting that it has the possibility to effectively suppress postprandial hyperglycemia in patients with non-insulin dependent diabetes mellitus. Luteolin also inhibited alpha-amylase effectively although it was less potent than acarbose. The clinical value of luteolin needs to be further evaluated.
Oleylethanolamide (OEA) is a naturally occurring lipid that regulates satiety and body weight. Although structurally related to the endogenous cannabinoid anandamide, OEA does not bind to cannabinoid receptors and its molecular targets have not been defined. Here we show that OEA binds with high affinity to the peroxisome-proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor that regulates several aspects of lipid metabolism. Administration of OEA produces satiety and reduces body weight gain in wild-type mice, but not in mice deficient in PPAR-alpha. Two distinct PPAR-alpha agonists have similar effects that are also contingent on PPAR-alpha expression, whereas potent and selective agonists for PPAR-gamma and PPAR-beta/delta are ineffective. In the small intestine of wild-type but not PPAR-alpha-null mice, OEA regulates the expression of several PPAR-alpha target genes: it initiates the transcription of proteins involved in lipid metabolism and represses inducible nitric oxide synthase, an enzyme that may contribute to feeding stimulation. Our results, which show that OEA induces satiety by activating PPAR-alpha, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders.
Effects of the polyphenolic compounds isolated from Lonicera japonica Thunb on platelet aggregation, platelet thromboxane biosynthesis and hydrogen peroxide-induced endothelial cell injury were studied. With regard to the inhibitory effect on human platelet aggregation, methyl caffeate, 3,4-di-O-caffeoylquinic acid and methyl 3,4-di-O-caffeoylquinate had a strong effect. They significantly inhibited the second wave of platelet aggregation induced by ADP. Concerning thromboxane biosynthesis triggered by calcium ionophore A23187 in platelets, methyl caffeate and methyl 3,4-di-O-caffeoylquinate had the most potent inhibitory effect. Methyl 3,4-di-O-caffeoylquinate directly inhibited the conversion of arachidonic acid to thromboxane by platelet microsomes, while methyl caffeate did not have any significant effect on thromboxane biosynthesis in platelet microsomes. In the prevention of hydrogen peroxide-induced endothelial cell injury in culture, protocatechuic acid, methyl caffeate, methyl chlorogenic acid and luteolin were significantly effective. The inhibitory effect on platelet activation and the cytoprotective effect on hydrogen peroxide-induced cell injury may explain the possible role of polyphenolic compounds isolated from Lonicera japonica Thunb in maintaining vascular homeostasis.
The effect of prolonged treatment with acarbose, an inhibitor of alpha-glycosidase, has been studied in mice made obese and hyperinsulinaemic by goldthioglucose. After the onset of obesity, one month after goldthioglucose administration, mice were then treated, with or without a 10% sucrose supplement, for four months with acarbose, added to the diet at 50 mg/100 g food. When mice received a standard diet, acarbose had no effect on body weight, blood glucose or insulin levels. In contrast, in the control obese mice receiving a 10% sucrose-enriched diet, it decreased the body weight gain, and prevented the rise in glycaemia and insulinaemia. Basal (non insulin-stimulated) glucose uptake, which is decreased in isolated soleus muscle from untreated obese mice, returned to normal values under acarbose treatment. However, muscle insulin resistance was not improved in acarbose-treated obese mice at maximal and submaximal effective concentrations, despite a higher insulin binding in muscles of acarbose-treated obese than in control obese animals. Furthermore, insulin receptor autophosphorylation and tyrosine kinase activity were altered similarly in treated and untreated obese mice compared to lean mice.
Obesity is an increasingly prevalent and important health problem. Although treatment is available, the long-term maintenance
of medically significant weight loss (5 to 10 percent of initial body weight) is rare. Since 1995 there has been an explosion
of research focused on the regulation of energy balance and fat mass. Characterization of obesity-associated gene products
has revealed new biochemical pathways and molecular targets for pharmacological intervention that will likely lead to new
treatments. Ideally, these treatments will be viewed as adjuncts to behavioral and lifestyle changes aimed at maintenance
of weight loss and improved health.
It is widely accepted that the most challenging goal in the management of patients with diabetes mellitus is to achieve blood glucose levels as close to normal as possible. In general, normalising postprandial blood glucose levels is more difficult than normalising fasting hyperglycaemia. In addition, some epidemiological studies suggest that postprandial hyperglycaemia (PPHG) or hyperinsulinaemia are independent risk factors for the development of macro-vascular complications of diabetes mellitus.
Recently, several drugs with differing pharmacodynamic profiles have been developed which target PPHG. These include insulin lispro, amylin analogues, α-glucosidase inhibitors and meglitinide analogues. Insulin lispro has a more rapid onset of action and shorter duration of efficacy compared with regular human insulin. In clinical trials, the use of insulin lispro was associated with improved control of PPHG and a reduced incidence of hypoglycaemic episodes.
Repaglinide, a meglitinide analogue, is a short-acting insulinotropic agent which, when given before meals, stimulates endogenous insulin secretions and lowers postprandial hyperglycaemic excursions. Both insulin lispro and repaglinide are associated with postprandial hyperinsulinaemia. In contrast, amylin analogues reduce PPHG by slowing gastric emptying and delivery of nutrients to the absorbing surface of the gut. α-Glucosidase inhibitors such as acarbose, miglitol and voglibose also reduce PPHG primarily by interfering with the carbohydrate-digesting enzymes and delaying glucose absorption.
With the availability of agents which preferentially reduce postprandial blood glucose excursions, it is now possible to achieve glycaemic goals in a larger proportion of individuals with diabetes mellitus.
Researchers studying type 2 diabetes are optimistic that they are closing in on the elusive causes of the world's most prevalent metabolic disorder--although no one is willing to bet the bank on it. Using both biochemical and genetic approaches, diabetes researchers have identified multiple intracellular signaling pathways that appear to lie at the heart of this condition, which affects some 250 million people worldwide and is the leading cause of blindness, kidney failure, and amputation among adults. And in the process, they have thrown out much of the dogma of the past 10 years.
Five caffeoylquinic acids and esters (1-5), including a new compound, 3,5-dicaffeoylquinic acid butyl ester (5), were isolated from the flowers and buds of Lonicera japonica and their structures were determined by NMR spectral analysis.
Peroxisome proliferator-activated (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor family. PPARs function as regulators of lipid and lipoprotein metabolism and glucose homeostasis and influence cellular proliferation, differentiation and apoptosis. PPARalpha is highly expressed in tissues such as liver, muscle, kidney and heart, where it stimulates the beta-oxidative degradation of fatty acids. PPARgamma is predominantly expressed in intestine and adipose tissue. PPARgamma triggers adipocyte differentiation and promotes lipid storage. The hypolipidemic fibrates and the antidiabetic glitazones are synthetic ligands for PPARalpha and PPARgamma, respectively. Furthermore, fatty acids and eicosanoids are natural PPAR ligands: PPARalpha is activated by leukotriene B4, whereas prostaglandin J2 is a PPARgamma ligand. These observations suggested a potential role for PPARs not only in metabolic but also in inflammation control. The first evidence for a role of PPARalpha in inflammation control came from the demonstration that PPARalpha deficient mice display a prolonged response to inflammatory stimuli. It was suggested that PPARalpha deficiency results in a reduced beta-oxidative degradation of these inflammatory fatty acid derivatives. More recently, PPAR activators were shown to inhibit the activation of inflammatory response genes (such as IL-2, IL-6, IL-8, TNFalpha and metalloproteases) by negatively interfering with the NF- kappaB, STAT and AP-1 signalling pathways. PPAR activators exert these anti-inflammatory activities in different immunological and vascular wall cell types such as monocyte/macrophages, endothelial, epithelial and smooth muscle cells in which PPARs are expressed. These recent findings indicate a modulatory role for PPARs in the control of the inflammatory response with potential therapeutic applications in inflammation-related diseases, such as atherosclerosis and inflammatory bowel disease.
Two secoiridoid glycosides, loniceracetalides A and B, were isolated in very small amounts, together with 10 known iridoid glycosides, from the flower buds of Lonicera japonica. The structures of loniceracetalides A and B were determined by spectroscopic analysis.
Lonicera japonica (Caprifoliaceae) has long been used for treatment of infectious diseases. In the present study, the anti-inflammatory effects of L. japonica water extract (AELJ) were investigated in proteinase-activated receptor 2 (PAR2)-mediated mouse paw edema.
Paw edema was induced by injection of trypsin or trans-cinnamoyl-LIGRLO-NH(2) (tc-NH(2)) into hindpaw of mice. AELJ (10, 50, 100, and 200 mg/kg) was orally administered 1 h before induction of inflammation.
At doses of 50, 100 and 200 mg/kg, the AELJ showed significant inhibition of both change in paw thickness and vascular permeability. The AELJ (100 mg/kg) also significantly inhibited PAR2 agonists-induced myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-alpha expression in paw tissue.
The present study demonstrated that AELJ has an anti-inflammatory action for PAR2-mediated paw edema.