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Acute effects of Fraxinus excelsior L. seed extract on postprandial glycemia and insulin secretion on healthy volunteers
Abstract
Fraxinus excelsior L. (Family: Oleaceae) seeds are consumed as a food, condiment, and folk medicine. The seeds are traditionally used as a potent hypoglycemic agent, but no clinical evidence exists in as to this regard. We assessed the clinical efficacy and safety of the seed extract (FraxiPure, Naturex), containing 6.8% of nuzhenide and 5.8% of GI3 (w/w), on plasma glucose and insulin levels against glucose (50 g) induced postprandial glycemia.
Preselected dose (1.0 g) was used in a double blind, randomized, crossover, placebo (wheat bran) controlled study on 16 healthy volunteers. Each treatment was given immediately after a fasting blood glucose sample (0 min). Postprandial plasma glucose levels were estimated at 0, 15, 30, 45, 60, 90 and 120 min; and postprandial plasma insulin at 0, 30, 60, 90 and 120 min.
The extract lowered the incremental postprandial plasma glucose concentration as compared to placebo at 45 min (P = 0.06) and 120 min (P = 0.07). It statistically (P = 0.02) reduced the glycemic area under the blood glucose curve. The seed, also, induced a significant (P = 0.002) secretion of insulin at 90 min after glucose administration. However, the insulinemic area under the blood insulin curve was not different than the placebo. No adverse events were reported.
Our findings confirm the hypoglycemic action of Fraxinus excelsior L. seed extract. These promising results, thus, encourage conducting long-term clinical studies to further evaluate the efficacy and safety of Fraxinus excelsior L. seed extract in healthy and diabetic volunteers and also to explore the possible mechanism(s) of action.
... Ash (Fraxinus excelsior L.), belonging to the Oleaceae family, locally known as "l'ssanel'ousfour". It is known worldwide as an antioxidant [5] , antiinflammatory, antirheumatic [6] , analgesic and antipyretic plant [5] . It has been reported that seed extract of F. excelsior possessed hypoglycaemic activity [5] . ...
... Ash (Fraxinus excelsior L.), belonging to the Oleaceae family, locally known as "l'ssanel'ousfour". It is known worldwide as an antioxidant [5] , antiinflammatory, antirheumatic [6] , analgesic and antipyretic plant [5] . It has been reported that seed extract of F. excelsior possessed hypoglycaemic activity [5] . ...
... It is known worldwide as an antioxidant [5] , antiinflammatory, antirheumatic [6] , analgesic and antipyretic plant [5] . It has been reported that seed extract of F. excelsior possessed hypoglycaemic activity [5] . In the present study, the antioxidant capacity of many extracts of F. excelsior was investigated using DPPH and β-carotene/linoleic acid tests and compared those with the results obtained using an electrochemical method. ...
This study involved investigation of the antioxidant and antibacterial activities of Algerian Fraxinus excelsior extracts. Antioxidant activity was evaluated using spectrophotometric and electrochemical techniques. Phytochemical screening revealed the presence of alkaloids, tannins, polyphenols, flavonoids, sterols/triterpenes, and coumarins. The total polyphenol contents in the extracts were in the order of ethyl acetate>methanol>butanol>chloroform>aqueous>petroleum ether, while flavonoid contents were in the order of, ethyl acetate>chloroform>methanol>butanol>aqueous>petroleum ether. In the 2,2'-diphenyl-1-picrylhydrazyl test, ethyl acetate extract exhibited maximum activity followed by chloroform extract, methanol extract, butanol extract, aqueous extract and petroleum ether extract. β-Carotene-linoleate and metal chelation tests showed closely the same order, ethyl acetate, chloroform, methanol, butanol, aqueous and petroleum ether extracts. Antioxidant activity measured using cyclic voltammetry method demonstrated activity in the order of ethyl acetate, chloroform, methanol, butanol and aqueous while petroleum ether extract did not show any activity. Results also demonstrated that some extracts possessed antibacterial activity. In conclusion, Fraxinus excelsior extracts contain active compounds, which have antioxidant and antibacterial effects and could be useful in the treatment of pathologies where these activities are needed.
... Ash (Fraxinus excelsior L.), belonging to the Oleaceae family, locally known as "l'ssanel'ousfour". It is known worldwide as an antioxidant [5] , antiinflammatory, antirheumatic [6] , analgesic and antipyretic plant [5] . It has been reported that seed extract of F. excelsior possessed hypoglycaemic activity [5] . ...
... Ash (Fraxinus excelsior L.), belonging to the Oleaceae family, locally known as "l'ssanel'ousfour". It is known worldwide as an antioxidant [5] , antiinflammatory, antirheumatic [6] , analgesic and antipyretic plant [5] . It has been reported that seed extract of F. excelsior possessed hypoglycaemic activity [5] . ...
... It is known worldwide as an antioxidant [5] , antiinflammatory, antirheumatic [6] , analgesic and antipyretic plant [5] . It has been reported that seed extract of F. excelsior possessed hypoglycaemic activity [5] . In the present study, the antioxidant capacity of many extracts of F. excelsior was investigated using DPPH and β-carotene/linoleic acid tests and compared those with the results obtained using an electrochemical method. ...
This study involved investigation of the antioxidant and antibacterial activities of Algerian Fraxinus
excelsior extracts. Antioxidant activity was evaluated using spectrophotometric and electrochemical
techniques. Phytochemical screening revealed the presence of alkaloids, tannins, polyphenols, flavonoids,
sterols/triterpenes, and coumarins. The total polyphenol contents in the extracts were in the order of ethyl
acetate>methanol>butanol>chloroform>aqueous>petroleum ether, while flavonoid contents were in the
order of, ethyl acetate>chloroform>methanol>butanol>aqueous>petroleum ether. In the 2,2’-diphenyl-
1-picrylhydrazyl test, ethyl acetate extract exhibited maximum activity followed by chloroform extract,
methanol extract, butanol extract, aqueous extract and petroleum ether extract. β-Carotene-linoleate and
metal chelation tests showed closely the same order, ethyl acetate, chloroform, methanol, butanol, aqueous
and petroleum ether extracts. Antioxidant activity measured using cyclic voltammetry method demonstrated
activity in the order of ethyl acetate, chloroform, methanol, butanol and aqueous while petroleum ether
extract did not show any activity. Results also demonstrated that some extracts possessed antibacterial
activity. In conclusion, Fraxinus excelsior extracts contain active compounds, which have antioxidant and
antibacterial effects and could be useful in the treatment of pathologies where these activities are needed.
... These beneficial effects were observed with doses ranging between 100 and 200 mg per kg of body weight per day, corresponding to a Human Equivalent Dose (HED = animal dose in mg/kgˆ(animal weight in kg/human weight in kg) 0.33 ) of~1.0 g/day for a 60 kg person. Notably, the acute administration of 1 g of the Fraxinus extract first evidenced the reduction of glycemia in healthy humans [6] and the daily administration of 1 g of the Fraxinus extract for three weeks in elderly overweight/obese subjects resulted in a significantly lower incremental glucose area under the curve, lower 2 h blood glucose levels and modified levels of fructosamine and adiponectin:leptin ratio [7]. This Fraxinus extract, prepared using a patented extraction protocol [8], was reported to contain a standardized amount (~10%) of the secoiridoid glycoside nuzhenide (CAS registry number 60037-39-0) plus the dimeric secoiridoid glycoside GL3 (glycosylated esters of tyrosol and elenolic acid; CAS registry number 39011-92-2) ( Figure 1). ...
... These two compounds were shown to activate peroxisome proliferator-activated receptor alpha (PPARα) and to inhibit adipocyte differentiation in cultured adipocytes providing a potential molecular mechanism underlying the metabolic regulatory activity of the Fraxinus extract [9]. These secoiridoids have thus been proposed as the main bioactive constituents of the extract potentially responsible for its beneficial effects [4,6,9] but the biological effects of these compounds within the organism depend largely on their metabolism and uptake from the gastrointestinal tract. ...
... These beneficial effects were observed with doses ranging between 100 and 200 mg per kg of body weight per day, corresponding to a Human Equivalent Dose (HED = animal dose in mg/kg × (animal weight in kg/human weight in kg) 0.33 ) of ~1.0 g/day for a 60 kg person. Notably, the acute administration of 1 g of the Fraxinus extract first evidenced the reduction of glycemia in healthy humans [6] and the daily administration of 1 g of the Fraxinus extract for three weeks in elderly overweight/obese subjects resulted in a significantly lower incremental glucose area under the curve, lower 2 h blood glucose levels and modified levels of fructosamine and adiponectin:leptin ratio [7]. This Fraxinus extract, prepared using a patented extraction protocol [8], was reported to contain a standardized amount (~10%) of the secoiridoid glycoside nuzhenide (CAS registry number 60037-39-0) plus the dimeric secoiridoid glycoside GL3 (glycosylated esters of tyrosol and elenolic acid; CAS registry number 39011-92-2) ( Figure 1). ...
The bark, seeds, fruits and leaves of the genus Fraxinus (Oleaceae) which contain a wide range of phytochemicals, mostly secoiridoid glucosides, have been widely used in folk medicine against a number of ailments, yet little is known about the metabolism and uptake of the major Fraxinus components. The aim of this work was to advance in the knowledge on the bioavailability of the secoiridoids present in a Fraxinus angustifolia Vahl seed/fruit extract using both targeted and untargeted metabolomic analyses. Plasma and urine samples from nine healthy volunteers were taken at specific time intervals following the intake of the extract and analyzed by UPLC-ESI-QTOF. Predicted metabolites such as tyrosol and ligstroside-aglycone glucuronides and sulfates were detected at low intensity. These compounds reached peak plasma levels 2 h after the intake and exhibited high variability among the participants. The ligstroside-aglycone conjugates may be considered as potential biomarkers of the Fraxinus secoiridoids intake. Using the untargeted approach we additionally detected phenolic conjugates identified as ferulic acid and caffeic acid sulfates, as well as hydroxybenzyl and hydroxyphenylacetaldehyde sulfate derivatives which support further metabolism of the secoiridoids by phase I and (or) microbial enzymes. Overall, the results of this study suggest low uptake of intact secoiridoids from a Fraxinus angustifolia Vahl extract in healthy human volunteers and metabolic conversion by esterases, glycosidases, and phase II sulfo- and glucuronosyl transferases to form smaller conjugated derivatives.
... Acute and long-term clinical models have been standardized by the workers for these natural health products for glycemic control in type 2 diabetes [101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118]. Such a standardization process will allow health professionals and consumers to determine which of the majority of medicinal plants, herbs and dietary supplements are effective for hyperglycaemia. ...
... After the end of study, they were asked to fill a posttest questionnaire. The entire time spent in the clinic was approximately 2.5 h [114]. ...
... A whey protein supplement decreases post-prandial glycemia (113) (Figure 3). C. Study 3: Acute effects of Fraxinus excelsior L. seed extract on postprandial glycemia and insulin secretion on healthy volunteers (114) (Figure 3). D. Study 4: Korean red ginseng (KRG; Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety (106) (Figure 4). ...
Background: Recent epidemiological studies predict that the worldwide incidence of type 2 diabetes, atherosclerosis, and cardiovascular diseases are increasing at an alarming rate. Currently, limited cures are available to prevent or cure diabetes and related postprandial glycemia, atherosclerosis and cardiovascular diseases. Insufficiency of current therapies for the treatment of type 2 diabetes and atherosclerosis, combined with both the lack of patient trust in conventional medical treatment and inability of the economy to absorb the cost of synthetic pharmaceuticals, have created a growing public interest in the use of Complementary and Alternative Medicines (CAM). Especially dietary and herbal remedies have become more popular because of their therapeutic effectiveness, relatively lesser or no side effects and low cost. Methods: Our publications, internet search of research articles from Pub Med and University of Toronto library, as well as discussions with nutritional scientists and basic researchers. Results: Unfortunately, the vast majority of herbal remedies lack quality control, standardization, and clinical scrutiny for treatment of ailments. Thus patients continue self-medicating with herbal products with little or no evidence of their safety and efficacy. WHO study groups strongly emphasize the optimal and rational uses of traditional medicines. Regulatory agencies like Food Trade Commission, Food & Drug Administration of USA, and Health Canada are deeply concerned about the effectiveness and safety of natural health products and alternative therapies. The increasingly high demand of CAM, in the absence of evidence-based safety and efficacy, adequate regulatory standards, patient disclosures to physicians and physician education, have prompted a unified call from the medical and scientific community for randomized controlled clinical trials of herbal medicines, dietary supplements and functional foods, in order to understand their therapeutic potential and to provide a valid basis for legitimate health promotion claims. Several researchers have developed and standardized scientific models (randomized, double blind, crossover, placebo-controlled clinical trials) for faster and cost-effective clinical validation of medicinal herbs and functional foods for their application in the management of type 2 diabetes using 2-hour oral glucose tolerance test. This scientific approach has been strongly recommended in this communication. The management and prevention of atherosclerosis, diabetes-linked cardiovascular diseases, and metabolic syndrome should be done by following healthy life styles, dietary interventions, nutraceutical therapies, and alternative medicines as discussed in this review. Conclusion: The reviewed information may not only provide the rationale of proposing the scientific models for clinical testing of CAM therapies, but would also be beneficial in managing type 2 diabetes and atherosclerosis effectively.
... Glucevia ® , a natural extract from the seeds/ fruits of Fraxinus excelsior L. standardized in the secoiridoid glucosides nuzhenide and Gl3 (US 8293292), belongs to the class of herbal insulin sensitizer. Indeed, the effects of a single dose of Glucevia ® have been evaluated on postprandial glycaemia and insulin secretion in nondiabetic healthy individuals and exhibited a significant reduction in the mean area under the plasma time-concentration curve (AUC) for glucose levels without significantly altering insulin secretion [4]. This natural insulin sensitizer property has been checked in a randomized, crossover, double-blind and placebo-controlled 7-week nutritional intervention in non-diabetic overweight/obese healthy subjects [5]. ...
... The standard chow (PanLab, Barcelona) had the following composition: 14.3% protein, 4.0% fat, 48.0% carbohydrate, 4.1% crude fiber, 18.0% neutral detergent fiber and 4.7% ash; energy density, 2.9 kcal/g). The dose correspond to an initial 170 mg of extract per kg body weight per day, approximately 13,7 mg per kg body weight HED, similar to the dose used during the clinical trials conducted [4,5]. Dietary intervention lasted for 28 weeks. ...
... Ibarra et al. [7] reported that mice fed a high-fat diet and administered Glucevia ® also decreased significantly fasting insulin levels at the end of the 16-week study compared to mice fed a high-fat diet alone. Furthermore, the extract was found to maintain a similar insulin area under the curve, concomitant with a better glucose tolerance after an OGTT in acute clinical trial on healthy subjects [4]. In the current study, the HOMA-IR parameter was significantly lower in the treated animals, implying reduced insulin-resistance. ...
Background: Non-alcoholic fatty liver is recognized as one of harmful consequences of the metabolic syndrome
and hepatocytes steatosis is well connected with loss of insulin sensitivity, impaired glucose tolerance and can
lead to impaired fasting glucose and type2 diabetes mellitus. Fraxinus excelsior L. seed extract has been used
as traditional folk medicine by Mediterranean population and Glucevia®, a natural extract of Fraxinus excelsior L. derived from seeds/fruits of the plant and standardized to 10% Nuzhenide and GI3, has been previously reported to regulate glucose homeostasis in healthy overweight people.
Methods: The effect of seven-month administration of Glucevia® on liver parameters was investigated in
a diabetic mouse strain (BKS ++Lepr db (db/db)). The severity of fatty change and grading of hepatic steatosis
were determined by estimating the fat hepatocytes contain in animals fed with a control diet or with a control diet supplemented with 0.07 % (w/w) of the extract.
Results: Glucevia® was shown to significantly reduce fatty liver in diabetics mice (-54%; p<0.05). A concomitant
improvement in alkaline phosphatase (ALP) levels and in aspartate aminotransferase/alanine aminotransferase
(AST/ALT) ratio were observed between groups (p<0.05). A significant decrease in insulin plasma level (-22%;
p<0.05) was measured in Glucevia® group leading to an improvement of HOMA-IR between groups (p<0.001) while no significant change of fasting blood glucose was observed between group.
Conclusion: The results observed supports the potential hepatoprotective function of Glucevia®, which seems to prevent fatty liver formation in type 2 diabetes mice model
... More recent studies on a patented seed extract of F. excelsior, marketed as FraxiPure™, have confirmed the ability of this seed extract to reduce glycemia both in vivo and in an acute clinical study (Visen et al., 2009;Ibarra et al., 2011). Mice fed a highfat diet supplemented with FraxiPure™ displayed significant reductions in fasting blood glucose and fasting plasma insulin levels at study end compared to the high-fat diet control (Ibarra et al., 2011). ...
... The effects of FraxiPure™ on postprandial glycemia and insulin secretion were evaluated in healthy human volunteers in an acute randomized, double-blind, placebo-controlled, crossover study (Visen et al., 2009). Participants (with a mean blood fasting glucose level of 4.4 ± 0.09 mmol/L and a mean BMI of 26 ± 2.2 kg/m 2 ) consumed 1000 mg of FraxiPure™ after overnight fasting and were immediately challenged using the oral glucose tolerance test. ...
... The seeds of F. excelsior L. were collected from rural communities in Morocco and deposited into the herbarium (voucher specimen J02/02/A7; Reference #RB3524) at Naturex Maroc, Technopole Nouasser BP 42, Casablanca 20240, Morocco. Harvesting, collection and analysis of the seeds were performed as described by Visen et al. (2009). ...
... More recent studies on a patented seed extract of F. excelsior, marketed as FraxiPure™, have confirmed the ability of this seed extract to reduce glycemia both in vivo and in an acute clinical study (Visen et al., 2009;Ibarra et al., 2011). Mice fed a highfat diet supplemented with FraxiPure™ displayed significant reductions in fasting blood glucose and fasting plasma insulin levels at study end compared to the high-fat diet control (Ibarra et al., 2011). ...
... The effects of FraxiPure™ on postprandial glycemia and insulin secretion were evaluated in healthy human volunteers in an acute randomized, double-blind, placebo-controlled, crossover study (Visen et al., 2009). Participants (with a mean blood fasting glucose level of 4.4 ± 0.09 mmol/L and a mean BMI of 26 ± 2.2 kg/m 2 ) consumed 1000 mg of FraxiPure™ after overnight fasting and were immediately challenged using the oral glucose tolerance test. ...
... The seeds of F. excelsior L. were collected from rural communities in Morocco and deposited into the herbarium (voucher specimen J02/02/A7; Reference #RB3524) at Naturex Maroc, Technopole Nouasser BP 42, Casablanca 20240, Morocco. Harvesting, collection and analysis of the seeds were performed as described by Visen et al. (2009). ...
... The acute intake of a patented seed extract of Fraxinus excelsior has confirmed the ability of this seed extract in producing an acute significant decrease in the mean plasma time-concentration area under curve (AUC) for glucose levels in healthy subjects aged 18-55 years compared to a placebo group (Visen et al. 2009). These hypoglycemic properties should be considered since impaired glucose tolerance (IGT) and impaired fasting glycaemia (IFG) are risk categories for the future onset of diabetes and cardiovascular disease (WHO 2006). ...
... Considering glucose area under the curve as the main variable and the results on a previous acute intake study (Visen et al. 2009), while assuming a difference between treatments of 34 ± 30 min*mmol/l, with a 95% confidence interval (˛ = 0.05) and an 80% statistical power, a sample of 15 volunteers was calculated as needed. Taking into account an expected dropout rate around 25% and the crossover design, sample size needed for the present study was established in 20 participants. ...
... The Fraxinus excelsior L. seeds are consumed as a food, condiment or folk medicine and also traditionally used as a potent hypoglycemic agent, but controlled trials are necessary to validate this preliminary evidence. In this sense, a previous investigation assessed the acute effects of Fraxinus excelsior L. seed extract on postprandial glycemia and insulin secretion on healthy volunteers aged 18-55 years (Visen et al. 2009), but clinical studies to demonstrate a longer-term efficacy have not been reported. To our knowledge, this study is a pioneer in evaluating the effects of Fraxinus excelsior L. within a nutritional intervention in elderly people (50-80 years). ...
... A patented extract from the seeds of this tree (FraxiPure Ò ) (FXE) has been studied for its glucose-homeostasis properties (He et al., 2012). Visen et al. (2009) suggested that acute consumption of FXE may produce a slight reduction in glucose levels in healthy individuals without significantly altering insulin secretion. A subchronic study in a high-fat diet animal model confirmed it to regulate glycaemia and fasting plasma insulin levels (Ibarra et al., 2011). ...
... The materials were: (i) apple juice prepared from 66 g/L (70 Brix) apple concentrate (Concentrados Villaviciosa S.A., La Almunia, Spain), (ii) FraxiPure Ò (FXE) a standardized extract of F. excelsior seeds/fruits (Naturex S.A., Glucevia Ò , Avignon, France), obtained according to Visen et al. (2009), (iii) nuzhenideand and GI-3 secoiridoids (purified standards), (iv) sweetener (Productos Aditivos S.A., Polisucra, Barcelona, Spain), (v) apple flavour (Dohler España Natural Beverage Ingredients S.L., Applessence, Las Rozas, Spain) and (vi) citric acid, ascorbic acid, and potassium sorbate (Agrovin, Alcazar de San Juan, Spain). ...
... The nutritional facts of the FXE beverages are shown in Table 1. Consumption of 2 servings of the 250 mL bottles of this beverage would provide 1 g daily of FXE which has been reported to be effective for maintaining glucose homeostasis (Visen et al., 2009). The apple juice was supplemented to 0.021 g/100 mL nuzhenide and GI3, (expressed as their contents' sum) as its active compounds for glycaemic homeostasis (Bai et al., 2010). ...
To be successful, an innovative functional food must be perceived by the consumer to present a clear concept and significant health benefit. The main purpose of this study was to evaluate the perception of diabetic and non-diabetic populations to a newly developed beverage containing a Fraxinus excelsior seed extract with previously demonstrated effects on glucose homeostasis in an apple juice. Both the diabetic and non-diabetic populations accepted the health benefits of the functional beverage and no differences were found between their perceptions. No difference was found between perception of both population and specific product information provides a better functional benefits understanding. The consumers made a strong connection between F excelsior seed extract and diabetes in agreement with provided information. Sensory evaluation of the developed functional beverage compared with the apple juice matrix showed that perceived bitterness affected product acceptance and should be corrected.
... The effects of FXE on postprandial glycaemia and insulin secretion have been evaluated in healthy human volunteers in a randomized, double-blind, placebo-controlled, crossover study. 11 The results showed that acute administration of FXE (1000 mg) and glucose (50 g) to 16 non-diabetic, healthy volunteers could signicantly reduce the mean area under the plasma time-concentration curve for glucose levels compared to placebo (P ¼ 0.02). No signicant difference was noted in the mean insulin AUC values between the extract and placebo groups, suggesting that acute consumption of FXE may produce a slight reduction in glucose levels in non-diabetic, healthy individuals without signicantly altering insulin secretion. ...
... Research to date on FXE has indicated that it can play a role in controlling glucose homeostasis in normal and diabetic animals 8 and healthy humans. 11 Nevertheless, FXE may also have an effect on the global metabolic state and could, based on previous research, also provide cardiovascular health benets. The purpose of this study is to elucidate the effect of FXE on metabolic parameters and vascular reactivity in various animal models which are representative of the diseased cardiovascular state. ...
... The range of doses was chosen according to the dose of 100 mg per kg body weight per day (FXE100) which is equivalent, according to Reagan-Shaw et al., 16 to the dose used in humans during the clinical trial conducted by Visen et al. 11 In addition, a lower (20 mg per kg body weight per day, FXE20) and a higher (400 mg per kg body weight per day, FXE400) dose were also chronically administered in Zucker rats. According to the results obtained with the acute treatment, the dose of 20 mg per kg body weight per day was not tested in SHR rats. ...
Nuzhenide and GI3, the principal secoiridoids of an extract obtained from the seeds of Fraxinus excelsior L. (FXE), are believed to be the active compounds responsible for the previously reported hypoglycemic effects of this extract. In this study, the effects of FXE were studied in two animal models which are representative of metabolic disorders: spontaneously hypertensive rats (SHR) and obese Zucker rats. SHR were acutely treated (oral gavage) with different doses of FXE. In addition, SHR and Zucker rats were chronically fed (20 or 5 weeks, respectively) with standard chow supplemented with FXE. Acute treatment with FXE (200 mg per kg body weight) decreased systolic blood pressure as in the case with captopril (50 mg per kg body weight). Chronic treatment with FXE at 100 mg per kg body weight per day, a dose equivalent to that showing hypoglycemic activity in humans, resulted in a significant decrease in glycemia (-16.3%), triglyceridemia (-33.4%) and body weight (-8.1%) in Zucker rats as well as a significant decrease in SBP in SHR (-6.7%), with a concomitant improvement in endothelial function in both strains. The broad-ranging effects of FXE may be due to a unique compositional profile that could be useful to prevent the metabolic syndrome, characterized by obesity, insulin resistance, glucose intolerance, hypertriglyceridemia and elevated blood pressure.
... Scientific evaluation of F. excelsior has revealed several biological activities including anti-oxidative (Meyer et al., 1995; Middleton et al., 2005; Schempp et al., 2000 ), anti-inflammatory (Ghazaly et al., 1992; von Kruedener et al., 1996), analgesic (Okpanyi et al., 1989), antipyretic, both individually (Okpanyi et al., 1989) and as part of a combined plant drug (Strehl et al., 1995), hypoglycemic (Eddouks and Maghrani, 2004; Maghrani et al., 2004 ), and hypotensive effects (Eddouks et al., 2005). More recent studies on a patented seed extract of F. excelsior, marketed as FraxiPure™, have confirmed the ability of this seed extract to reduce glycemia both in vivo and in an acute clinical study (Visen et al., 2009; Ibarra et al., 2011 ). Mice fed a highfat diet supplemented with FraxiPure™ displayed significant ...
... The results suggested that the extract itself was without adverse effects on the liver and that FraxiPure™ may possess hepatoprotective properties. The effects of FraxiPure™ on postprandial glycemia and insulin secretion were evaluated in healthy human volunteers in an acute randomized, double-blind, placebo-controlled, crossover study (Visen et al., 2009). Participants (with a mean blood fasting glucose level of 4.4 ± 0.09 mmol/L and a mean BMI of 26 ± 2.2 kg/m 2 ) consumed 1000 mg of FraxiPure™ after overnight fasting and were immediately challenged using the oral glucose tolerance test. ...
... The seeds of F. excelsior L. were collected from rural communities in Morocco and deposited into the herbarium (voucher specimen J02/02/A7; Reference #RB3524) at Naturex Maroc, Technopole Nouasser BP 42, Casablanca 20240, Morocco . Harvesting, collection and analysis of the seeds were performed as described by Visen et al. (2009). ...
... In a previous study, we developed a well-standardized extract of F. excelsior seeds (FraxiPure TM , Naturex Inc.) (Visen et al. 2009), in which a glucose screen (50 g) was used to assess the effects of FraxiPure TM on plasma glucose and insulin levels. The intervention was double-blinded, randomized, crossover design that tested FraxiPure TM (1.0 g) versus matching placebo (1.0 g of wheat bran) in 16 healthy volunteers. ...
... The intervention was double-blinded, randomized, crossover design that tested FraxiPure TM (1.0 g) versus matching placebo (1.0 g of wheat bran) in 16 healthy volunteers. FraxiPure TM significantly reduced the glycemic area under the curve (Visen et al. 2009). ...
... F. excelsior seed extract F. excelsior seeds were collected from rural communities in Morocco and deposited into the herbarium (voucher specimen # J02/02/A7; Reference # RB3524) at Naturex Maroc, Technopole Nouasser BP 42, Casablanca 20240, Morocco. Extracts of the sample were generated through an established industrial process at Naturex France (FraxiPure TM , Reference: EA149251, Naturex SA, Site d'Agroparc BP 1218, 84911 Avignon Cedex 9, France) (Visen et al. 2009). ...
The aim of this study was to determine whether a Fraxinus excelsior L. seed extract, FraxiPure™ (0.5% in the diet), limits weight gain and hyperglycemia in mice. In a previous report, we identified several secoiridoids in FraxiPure™, some of which activated peroxisome proliferator-activated receptor alpha (PPARα) in vitro and inhibited the differentiation of 3T3-L1 preadipocyte cells. In a separate study, FraxiPure™ reduced glycemia in healthy volunteers, following an oral glucose tolerance test. These findings suggest that FraxiPure™ has antiobesity and antihyperglycemia effects.
FraxiPure™ was tested in mice that were fed a high-fat diet over 16 weeks and compared with low-fat and high-fat diet controls. Weight gain, omental and retroperitoneal fat, fasting blood glucose, and fasting blood insulin were measured.
FraxiPure™ reduced gains in body weight by 32.30% (p < 0.05), omental fat by 17.92%, and retroperitoneal fat by 17.78%. FraxiPure™ also lowered fasting blood glucose levels by 76.52% (p < 0.001) and plasma insulin levels by 53.43% (p < 0.05) after 16 weeks. Moreover, FraxiPure™ lowered liver weight gains by 63.62% (p < 0.05) and the incidence of fatty livers by 66.67%.
Our novel results demonstrate the antiobesity effects of chronic administration of an F. excelsior seed extract and confirm its ability to regulate glycemia and insulinemia. In addition, this extract, which is rich in secoiridoid glucosides, protects against obesity-related liver steatosis.
... In this study, three plant extracts derived from Fraxinus excelsior L. (FEAE), Zingiber zerumbet (ZZAE), and Isatis tinctoria L. (ITAE) were used to fabricate sustainable corrosion inhibitors, and their inhibition performance and interfacial behavior were evaluated. A brief description of each of these natural products is provided in the Supplementary Information ( Figure S1) [21][22][23][24][25][26][27]. Due to their unique characteristics, such as strong affinity, good solubility and high adsorption capability, the synthesized extracts are considered as the promising eco-friendly corrosion inhibitors that have a significant effect on the physical and chemical processes of electrochemical corrosion behaviors by promoting the formation of a protective layer on the metal surface. ...
... Table 1. Chemical structure of the major constituents found in the studied plant extracts [21][22][23]27]. ...
In the present work, we present the superior corrosion inhibition properties of three plant-based products, Fraxinus excelsior (FEAE), Zingiber zerumbet (ZZAE), and Isatis tinctoria (ITAE), that efficiently inhibit the corrosion of mild steel in phosphoric acid. The anti-corrosion and adsorption characteristics were assessed using a combination of experimental and computational approaches. Weight loss, potentiodynamic polarization, and electrochemical impedance spectroscopy methods were used to evaluate the inhibitive performance of the inhibitors on the metal surface. Then, both DFT/DFTB calculations and molecular dynamic simulations were further adopted to investigate the interaction between organic inhibitor molecules and the metal surface. The protective layers assembled using the active constituents, such as carbonyl and hydroxyl groups, of the three plant-based products offer high electrochemical stability at high temperatures and robust protection against aggressive acidic solutions. All electrochemical measurements showed that the inhibition performance of extracts increased by increasing their concentration and improved in the following order: FEAE > ZZAE > ITAE. Further, these extracts worked as mixed-type inhibitors to block the anodic and cathodic active sites on the mild steel surface. Multi-level computational approaches revealed that FEAE is the most adsorbed inhibitor owing to its ability to provide electron lone pairs for electrophilic reactions. The experimental and theoretical results showed good agreement. These results indicate the possibility of replacing conventional compounds with natural substituted organic products in the fabrication of hybrid materials with effective anti-corrosion performance.
... A Fraxinus excelsior L. seed extract (FESE) was obtained via a patented process [10]. The analytical study of FESE revealed that it was rich in nuzhenide and GI3, two phenolic compounds belonging to the secoiridoid type [11]. FESE lowered the incremental postprandial plasma glucose concentration in nondiabetic volunteers [11] and limited weight gain and hyperglycemia in high-fat induced obese mice [12]. ...
... The analytical study of FESE revealed that it was rich in nuzhenide and GI3, two phenolic compounds belonging to the secoiridoid type [11]. FESE lowered the incremental postprandial plasma glucose concentration in nondiabetic volunteers [11] and limited weight gain and hyperglycemia in high-fat induced obese mice [12]. Recently, we have demonstrated the short-term antihypertensive effect of this extract in spontaneously hypertensive rats (SHR), a model for essential hypertension in humans. ...
The effect of long-term intake of different doses (20, 40, and 60 mg/kg/day) of a Fraxinus excelsior L. seed extract (FESE) on spontaneously hypertensive rats (SHR) was evaluated. Water was used as control and captopril (50 mg/kg/day) was used as positive control. Systolic blood pressure, body weight, and food and liquid intake were registered weekly in SHR. The antioxidant and vascular relaxing properties of FESE were also studied in these animals. The development of hypertension was attenuated in the groups treated with captopril or FESE. The antihypertensive effect was more accentuated in the captopril group than in the FESE groups, and it was paradoxically more accentuated in the groups treated with 20 mg/kg/day or 40 mg/kg/day of FESE than in the group treated with the highest dose of this extract. Body weight gain and food intake increased in the FESE groups. After removing the corresponding antihypertensive treatment, the arterial blood pressure and the body weight of the FESE treated animals returned to control values. In addition, FESE increased plasma antioxidant capacity and decreased plasma and liver malondialdehyde levels. Moreover, acetylcholine relaxation improved in the aorta rings from the FESE treated rats.
... Los extractos de estas semillas se sabe que tienen propiedades antioxidantes [67][68][69] , antiinflamatorias 70,71 , antireumáticas 71,72 , analgésicas 73 y antipiréticas 74 . Los extractos acuosos de estas semillas se sabe además que son muy potentes para disminuir los niveles plasmáticos de glucosa, pero no modifican los niveles de insulina 66,[75][76][77] . El efecto hipoglucemiante de las semillas de fresno se ha sugerido que podría relacionarse con su capacidad para inhibir la reabsorción tubular renal de la glucosa 66 , y también que podría relacionarse con una inhibición de la diferenciación de los adipocitos y una activación de los receptores activados por proliferadores de peroxisomas tipo α (PPARα) 78 . ...
... Durante los últimos años, se han aislado iridoides muy diferentes en las semillas del fresno común. La caracterización de muestras de un extracto de fresno denominado FraxiPure TM , indicó que la nuzenida y el G13, cuyas estructuras aparecen en la figura 4, eran probablemente los secoiridoides mayoritarios en esta planta 77 . Estos iridoides se volvieron a aislar recientemente en las semillas de Fraxinus excelsior L., y se aislaron además dos nuevos glucósidos secoiridoides en estas semillas, denominados excelsido A y excelsido B. Mediante resonancia magnética nuclear (RMN) y espec-trometría de masas (MS) se identificaron las siguientes estructuras para el excelsido A y excelsido B: "(2S, 4S, 3E) -metil 3-etiliden-4-dihidro-2H-pirano-5-carboxilato" y "(2S, 4S, 3E) -metil 3-etiliden -4-[2-[2-(4-hidroxifenil) etil] oxi -2-oxoetil] -2-[(6-O-β-D-glucopiranosil-β-Dglucopiranosil) oxi] -3,4-dihidro -2H-piran -5-carboxilato". ...
Food components can have biological activity and healthy properties. Some of them, produced by plants, are named phytochemicals. The diversity of phytochemicals is amazing and this term refers in fact to a wide variety of compounds. Some of them, biosynthesized from isoprene, are named terpenes, and an important group of biciclic monoterpenes, derived from geraniol, are named iridoids. Iridoids can have open structures (secoiridoids) or closed structures (really iridoids) and they appear usua lly as heteroside compounds, in particular as glycosides. They have beneficial effects on liver and bi - liary function. Moreover, they have also demonstrated anti-inflammatory, antibacterial, anti-carcinogenic and antiviral activity, and they can be used as antidote in mushroom intoxications, in particular, those caused by Amanita type. Iridoids are present in particular in plants such as olive, harpagophytum, the valerian plant, the gentian plant and the ash tree. All these plants have been reported to be used as traditional medicine in many cultures. Nowadays, their leaves, tubercles, roots, seeds, and extracts are also considered important for pharmacology, and some of their active compounds have been identified. This review refers to the origin and biosynthetic pathways of iridoids. It des - cribes the characteristics and properties of the plants mentioned above, and it also mentions the principal iridoids isolated from them.
... A Fraxinus excelsior L. seed extract (FESE) was obtained via a patented process [10]. The analytical study of FESE revealed that it was rich in nuzhenide and GI3, two phenolic compounds belonging to the secoiridoid type [11]. FESE lowered the incremental postprandial plasma glucose concentration in nondiabetic volunteers [11] and limited weight gain and hyperglycemia in high-fat induced obese mice [12]. ...
... The analytical study of FESE revealed that it was rich in nuzhenide and GI3, two phenolic compounds belonging to the secoiridoid type [11]. FESE lowered the incremental postprandial plasma glucose concentration in nondiabetic volunteers [11] and limited weight gain and hyperglycemia in high-fat induced obese mice [12]. Recently, we have demonstrated the short-term antihypertensive effect of this extract in spontaneously hypertensive rats (SHR), a model for essential hypertension in humans. ...
The effect of long-term intake of different doses (20, 40, and 60 mg/kg/day) of a Fraxinus excelsior L. seed extract (FESE) on spontaneously hypertensive rats (SHR) was evaluated. Water was used as control and captopril (50 mg/kg/day) was used as positive control. Systolic blood pressure, body weight, and food and liquid intake were registered weekly in SHR. The antioxidant and vascular relaxing properties of FESE were also studied in these animals. The development of hypertension was attenuated in the groups treated with captopril or FESE. The antihypertensive effect was more accentuated in the captopril group than in the FESE groups, and it was paradoxically more accentuated in the groups treated with 20 mg/kg/day or 40 mg/kg/day of FESE than in the group treated with the highest dose of this extract. Body weight gain and food intake increased in the FESE groups. After removing the corresponding antihypertensive treatment, the arterial blood pressure and the body weight of the FESE treated animals returned to control values. In addition, FESE increased plasma antioxidant capacity and decreased plasma and liver malondialdehyde levels. Moreover, acetylcholine relaxation improved in the aorta rings from the FESE treated rats.
... ± 0.69 mg/100 g FW), as shown in Figure 2. Fraxinus excelsior L. (FE) has been widely used in traditional medicine due to several claimed beneficial health effects including antioxidant, antiinflammatory, anti-rheumatic and anti-pyretic activities [17]. Several findings from in vivo studies showed that the FE extract has hypoglycemic and anti-hyperlipidemic activities, providing anti-diabetic and anti-obesity effects [18,19]. -QP is particularly rich in ellagic acid (231.56 ± 0.65 mg/100 g FW), catechins (especially epicatechin, 199.92 ± 0.46 mg/100 g FW) and quercitrin (188.45 ± 0.79 mg/100 g FW). ...
Bud derivatives (BDs) represent a category of botanicals obtained by macerating the meristematic tissues (buds or young sprouts) of plants; widely used since ancient times in complementary medicine, they remain poorly investigated to date. In this study, a contribution is made toward the identification of the correct “a posteriori” attribution of the botanical species in commercial BDs, which is very important for ensuring the quality and safety of these natural products. Excitation–emission matrix (EEM) fluorescence spectroscopy proved to be a rapid, non-destructive and low-cost analytical instrument for providing a preliminary qualitative characterization of the BDs, allowing for the identification of specific spectral regions related to flavonol compounds and cinnamic and benzoic acids, in agreement with the targeted chromatographic analysis (HPLC-DAD), which completely defined a phytochemical profile for each BD considered. This information will be implemented in the first web application for the recognition of vegetable buds, named GEMMAPP, which was designed by the Authors and is proposed as a tool and future scientific data repository for providing information about the main, typical BDs of the France–Italy Alcotra territory.
... Fraxinus excelsior l. (family Oleaceae) is found in europe, North africa and asia. immature fruits are traditionally used as a condiment in some countries and as an herbal medicine [23,24]. it has been reported to have anticancer, antioxidative, anti-inflammatory and analgesic effects [25][26][27]. ...
Background: Traditional Persian medicine has introduced effective remedies in opioid dependence care. One of the most widely used remedies is an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. (HF). This study investigated the effects of HF to attenuate the withdrawal signs and rewarding effects in morphine-dependent rats.
Methods: Forty-nine male Wistar rats were randomly divided into seven groups. The control and vehicle groups received normal saline and sodium carboxymethyl cellulose, respectively. The morphine group received morphine for one week. The single and daily dose of HF groups received morphine similar to the morphine group, and HF (1.4 and 2.8 g/kg) once a day in the daily dose group and only on the last day of the experiment in the single dose of HF group. Finally, the withdrawal signs as well biochemical tests were evaluated. The behavioral parameters were assessed by conditioned place preference, elevated plus-maze and Y-maze tests. The antioxidant activity of HF was evaluated by measurement of serum contents of malondialdehyde, stable nitric oxide metabolites and total antioxidant capacity. Moreover, the protein expression of c-fos was assessed by western blotting.
Results: Daily treatment with HF significantly reduced the score of conditioned place preference behavioral test, all of the withdrawal signs, total antioxidant capacity, and the c-fos protein level.
Conclusions: The results indicated that HF might be a promising complementary treatment in reducing morphine-induced physical and psychological dependence probably through modulation of c-fos protein expression.
... The seeds have been used traditionally as food or condiment and administered mainly for their hypoglycemic action in the treatment of metabolic disorders [23]; investigations on the As early as 600 in Italy, F. ornus was cultivated for the extraction of manna in the south-central peninsula and in the islands of Sardinia and Sicily. And it is precisely in Sicily that this cultivation will continue to spread and be preserved up to the present day with alternating events that have also caused fear of its disappearance, averted thanks to local entrepreneurship that has meant that the manna of the ash trees found alternative uses to industry pharmaceutical company freed from the need to resort to drugs extracted from ash trees to obtain health products required by the market, the manna will enter on the one hand in sought after and expensive herbal products ( Figure 6), on the other in the confectionery industry ( Figure 7) and then again a nutraceutical, and recent in the gastronomic inventions of re ined chefs [13]. ...
“Manna” is the product obtained from the solidification of the elaborate sap that comes out of the incisions made during the summer season on the stem and on the main branches of some species of the genus Fraxinus (Oleaceae). The cultivation of manna ash trees dates back to ancient times in Sicily and elsewhere ash trees – known as sacred trees, a symbol of abundance and therefore auspicious – was increasingly widespread until the middle of the last century. Subsequently, however, the crop underwent a progressive decline, remaining relegated to restricted areas of Sicily, in particular in the Madonie district (Palermo, Italy). In this brief review, the essential characteristics of the manna and the ash trees from which it is extracted are summarized. The aspects of the current productivity of manna in the Sicilian territory and the implications of a potential recovery and increase of an ancient craft, ash tree cultivation, are also reported in a perspective of sustainable development and green economy for the Mediterranean area and beyond. Finally, the authors remember what has been done to ensure the conservation not only of the active cultivation of manna ash but also of all the relative agro-biodiversity. The conservation of the living germplasm of the ancient cultivars recovered in the Madonie area (Palermo, Sicily) represents one of the most qualifying results.
... The FE species have been used as food and stuffing as well as in traditional medicine due to a number of claimed beneficial biological activities including anti-oxidative, anti-inflammatory, anti-pyretic and anti-rheumatic properties (Eddouks, Maghrani, Zeggwagh, Haloui, & Michel, 2005;Meyer, Schneider, & Elstner, 1995). Some findings suggest that its extract has anti-hyperglycemic, anti-hypoglycemic, anti-diabetic and anti-obesity effects Ibarra et al., 2011;Visen et al., 2009). ...
In this study, common ash (Fraxinus excelsior L.) seed oil compositions were determined for the first time. Effect of the moisture content and microwave pretreatment of the seeds on the oil yield and its composition were also investigated. The optimum level of moisture content to obtain the maximum oil (18.18%) yield was 1% with 3 min pre-treatment. The main triacylglycerol composition of the oil was linoleic–linoleic–oleic, followed by oleic-oleic-linoleic and linoleic–linoleic-linoleic. The main fatty acid of the oil was linoleic acid (C18:2), followed by oleic acid (C18:1) and palmitic acid (C16:0). The main phytosterol of the oil was β-sitosterol, followed by Δ⁵-avenasterol and campesterol. The main tocopherol of the oil was α-tocopherol, followed by β and γ-tocopherols. The main essential oil of the oil was bicyclogermacrene, followed by delta-cadinene. These results suggest that this oil is a good source of valuable nutritional compounds and that microwave pretreatment is a promising and environmentally friendly method to extract it as a new vegetable oil source.
... The aqueous extract of Momordica charantia and Eugenia jambolana for 15 days substantially prevented hyperglycemia and hyperinsulinemia induced by a diet high in fructose in 10 Type 2 diabetic patients (Waheed et al., 2007). Administration of two capsules (500 mg) of the aqueous extract of Fraxinus excelsior with 7 days break in 16 (50 g) glucose-induced postprandial hyperglycemic persons, showed a decrease in postprandial glucose levels and a significant increase in insulin secretion (Visen et al., 2009). This indicates that further clinical investigation of the traditionally used antidiabetic plants is imperative in order to provide a sound base for the development of antidiabetic agents. ...
... The aqueous extract of Momordica charantia and Eugenia jambolana for 15 days substantially prevented hyperglycemia and hyperinsulinemia induced by a diet high in fructose in 10 Type 2 diabetic patients (Waheed et al., 2007). Administration of two capsules (500 mg) of the aqueous extract of Fraxinus excelsior with 7 days break in 16 (50 g) glucose-induced postprandial hyperglycemic persons, showed a decrease in postprandial glucose levels and a significant increase in insulin secretion (Visen et al., 2009). This indicates that further clinical investigation of the traditionally used antidiabetic plants is imperative in order to provide a sound base for the development of antidiabetic agents. ...
Diabetes is the most devastating and serious metabolic disease. The available natural remedies are considered valuable source of therapeutic agents. A scientific validation of the reported antidiabetic plants on the basis of their traditional use may pave the way for the development of novel and effective antidiabetic drugs. Such approaches are the necessity of the day because the available medicines are insufficient to manage all consequences of diabetes, and the economic problems and shortage of current therapies in most developing countries. This review comprises information of 184 antidiabetic medicinal plants of Pakistan with respect to traditional knowledge. The manuscript also includes the in-vitro or in-vivo potential, toxicity, mode of action, and perspective for future research. This effort may serve as leading point for formulation of novel herbal mixtures, development of antidiabetic drugs or precursors.
... In previous clinical studies, the acute intake of patented F excelsior seed extract has already been found to be effective in reducing the mean plasma timeconcentration area under curve (AUC) for glucose levels immediately after eating in healthy subjects aged 18 to 55 years. 3 This development is noteworthy, because impaired glucose tolerance and impaired fasting glycemia are risk factors for the onset of diabetes and cardiovascular disease. 4,5,6 The aim of the Glucevia study was to investigate the effectiveness of the product on postprandial glycemia and the metabolic disturbances associated with high levels of blood glucose with a focus on nondiabetic, overweight, or obese subjects aged between 50 and 80 years. ...
... Its leaves are also used as fodder [15]. Use of the extract of F. excelsior seeds in diabetic volunteers had significantly reduced the postprandial rise in glycemia while enhanced the insulin secretion [21]. Treatment of obese mice with extracts of F. excelsior seeds limited the gain in weight and hyperglycemia [22]. ...
Background
Leaves and root bark of Fraxinus xanthoxyloides Wall. (Oleaceae) are used locally for the treatment of jaundice, malaria and pneumonia. Decoction of stem, twigs and bark is used in pain, internal injuries, rheumatism and in bone fracture. In this investigation we have evaluated the methanol extract of leaves for its hepatoprotective potential against CCl4 induced hepatic injuries in rat.
Methods
Powder of F. xanthoxyloides leaves was extracted with methanol (FXM) and subjected for the determination of polyphenolics through HPLC-DAD analysis. Sprague–Dawley (Rattus novergicus) male rats were divided into eight groups (six rats in each). Group I: non-treated control; Group II: vehicle treated (DMSO plus olive oil) while Group III- VI treated with 1 ml/kg body weight (bw) of CCl4 (30 % in olive oil) for 30 days (15 dosages) to induce the hepatic injuries. Group IV: treated with silymarin (100 mg/kg bw); Group V and VI with FXM (200, 400 mg/kg bw) on alternate days with CCl4 treatment. Group VII and VIII was administered with FXM (200, 400 mg/kg bw) alone (15 dosages). After 30 days the serum was evaluated for liver function enzymes and biochemical markers, liver samples for antioxidant enzymes, biochemical markers, comet assay and for histopathology.
Results
HPLC-DAD analysis of FXM revealed the existence of rutin and caffeic acid. In CCl4 treated rats the level of alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin was significantly increased while the albumin concentration in serum was decreased as compared to control group. The level of hepatic antioxidant enzymes, catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione reductase (GSR) was significantly decreased against the control group. Further, significant decrease in GSH while increase in lipid peroxides (TBARS), H2O2, DNA damages and comet length was induced with CCl4 in hepatic tissues of rat. In contrast, co-administration of FXM and silymarin restored the biochemical and histopathological status of the liver.
Conclusion
Results of present investigation revealed that F. xanthoxyloides leaves possibly protect the liver against CCl4 induced injuries like silymarin by its antioxidant constituents.
... The parts of the plants have been reported to be effective in the treatment of various diseases. The barks of Fraxinus excelsior have long been used as antibacterial (Middleton et al. 2005), seed extract has been used as a potent hypoglycemic agent (Visen et al. 2009). The alcoholic extract of bark has been reported to possess an anti-inflammatory property (Ghazaly et al. 1992). ...
... The parts of the plants have been reported to be effective in the treatment of various diseases. The barks of Fraxinus excelsior have long been used as antibacterial (Middleton et al. 2005), seed extract has been used as a potent hypoglycemic agent (Visen et al. 2009). The alcoholic extract of bark has been reported to possess an anti-inflammatory property (Ghazaly et al. 1992). ...
The biosynthesis of nanoparticles has been proposed as a cost effective and environmentally benevolent alternative to chemical and physical methods. In the present study, microwave assisted synthesis of silver
nanoparticles (AgNPs) has been demonstrated using leaf extract of Fraxinus excelsior reducing aqueous AgNO solution. The synthesized nanoparticles have been characterized on the basis of fourier transform
infrared spectroscopy (FTIR), UV–Vis spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive Xray (EDX) analysis. The presence of a characteristic surface plasmon resonance (SPR) absorption band at 425 nm in UV–Vis reveals the reduction of silver metal ions into silver nanoparticles. FTIR analysis was carried out to probe the possible functional group involved in the synthesis of AgNPs. Further leaf extracts and AgNPs were evaluated for antiradical scavenging activity
by 1,1diphenyl2picrylhydrazyl (DPPH) assay.
... It was also demonstrated that oleuropein-rich extract reduced the secretion of the proinflammatory cytokine such as TNF, IFN-γ, IL-2, IL-6, IL-1β and IL-17A, whereas it increased the levels of the antiinflammatory cytokine IL-10 and enhanced the expression of insulin receptor substrate-1 (IRS-1) mRNA expression in streptozotocin-induced diabetic mice (Liu, Jung, Park, & Kim, 2014;Park et al., 2013). Evidence for the hypoglycaemic activity of oleuropeinrich extract was also confirmed in humans (Visen et al., 2009). In their double blind, randomized, crossover, placebo controlled study, authors pinpointed that oleuropein-rich extract from F. excelsior induced a regular decrease of postprandial glycaemia which may be due to increased insulin secretion and improved insulin resistance suggesting a direct action of oleuropein on the pancreatic islet cells (Visen et al., 2009). ...
An emerging body of evidence indicates that oleuropein, a biophenol usually found in olive leaves, extra-virgin olive oil and in some species of the Oleaceae family has potent biological and pharmacological properties. Its main pharmacological activities such as anticancer, cardioprotective, neuroprotective, gastroprotective, hepato-protective, anti-diabetes, anti-obesity and radioprotective, among others, are in large part attributed to its putative antioxidant and anti-inflammatory effects. This mini-review collects and discusses the scattered data available in the literature concerning oleuropein and/or oleuropein-rich extracts and highlights its chemistry, biosynthesis, biological activities and its possible mechanisms of action.
... All the plants were searched in combination with the keywords "diabetes mellitus" and "polyphenols". [87] Camellia sinensis [88,89] Flavan-3-ols and tannins catechins (proanthocyanidins), epicatechins, gallotannins, ellagitannins Fraxinus excelsior [90][91][92] Chalcones davidigenin, 2',4'-dihydroxy-4-methoxydihydrochalcone Urticadioica [93][94][95][96] Stilbens resveratrol, moracins C, D, N Morus alba [49,50,[97][98][99] Phenolic acid derivatives Caffeic, ferulicchlorogenic acids, cynarin, p-coumaric s, vanillicgallic acid, p-hydroxybenzoic acids Cynarascolymus [66] Curcuminoids curcumin, demethoxycurcumin, Bisdemethoxycurcumin Curcuma longa [73][74][75] Alkaloids and saponins Conophylline, piperine, pipernonaline, Phaseolus vulgaris [69-72, 100, 101] alleviates insulin resistance by improving insulin signaling via protein kinase C (PKC) activity inhibition and glucose uptake enhancement in insulin-resistant cells [80] quercetin Hippophaërhamnoides (sea buckthorn) stimulates glucose metabolism by enhancing hepatic glucokinase activity increases insulin release from beta cells by rising intracytosolic calcium concentration [44,45] resveratrol red wine and grape seed extracts restores insulin receptor substrate 1-mediated PI 3kinase/Akt/Foxo1 signaling and peripheral insulin sensitivity decreases lipid peroxidation and increases antioxidant enzyme levels in different brain areas of diabetic rats [13] [ 14] quercetin and resveratrol red wine and grape seed extracts optimizes glucose tolerance in rats, hepatic glucokinase, hexokinase activities and the lipid profile inhibits intestinal alpha-glucosidase increases paraoxonase 1 (PON1) activity in control and diabetic rats [12] [10] [11] phenolic acids (ferulic acid) cereals neutralizes free radicals, stops the production of oxidative radical compounds and increases beta-cell mass [77] Chlorogenic acid Coffeaarabica (Coffee) slows carbohydrate catabolism, delays glucose absorption in the intestine, reduces the mobilization of glucose by the liver, increases the uptake of glucose by the peripheral tissues decreases fasting blood glucose and stimulates glucose transport in skeletal muscle through the translocation of transporter type 4 (GLUT -4) ...
In recent years, there is growing evidence that polyphenols-rich natural products, like nutraceuticals and food supplements, may offer unique treatment modalities for various aspects of type 2 diabetes mellitus (T2DM), due to their biological properties. Therefore, research is now focused on potential efficacy of different types of polyphenols, including phenolic acids, flavonoids, stilbenes, lignans and anthocyans. Animal and human studies showed that polyphenols modulate carbohydrate and lipid metabolism, decrease glycemia, atherogenic dyslipidemia and insulin resistance, improve adipose tissue metabolism, and modulate oxidative stress and inflammatory processes. It is relevant to understand the proper dose and duration of supplementation with polyphenols-rich extracts in order to guide effective therapeutic interventions in diabetic patients.
... Inhibition of adipocyte differentiation and peroxisome proliferator-mediated receptor-α or (PPARα)-mediated mechanisms might be relevant pathways for the antidiabetic activity of the Fraxinus excelsior extract. Majorana hortensis, a native of Cyprus and Turkey, has alpha-glucosidase inhibition activity, which indicates that inclusion of herbs from Lamiaceae family could potentially help manage hyperglycemia linked to type 2 diabetes [38][39][40][41][42] . ...
Diabetes mellitus is a lifestyle disorder that is rapidly becoming a major threat to populations all over the globe. Over the past 30 years, the status of diabetes has changed from being considered as a mild lifestyle disorder of the elderly to one of the major causes of morbidity and mortality, affecting people of all ages. India is slated to be the diabetic capital of the world, with 50.8 million diabetics. There seems to be a renewed interest in herbal medicines across the world today and plants are a powerhouse of sources for antidiabetic principles. Hence, a review on the antidiabetic plants has been done and the plants with antidiabetic principles isolated have been tabulated. Electronic searches were conducted in numerous databases and relevant journals. Sources also included various books and newspaper articles. Hand searches were also carried out in additional journals and secondary references. Researchers in the field of Ayurveda, Siddha, Unani and Homeopathy were consulted for access to ongoing research and various references. Molecular docking studies were performed on three selected plants to authenticate their affinity and therapeutic efficacy.
... Few human studies have explored vegetables as a potential source of phytochemicals which could effect PPG. A Flaxinius species extract was found to have an acute effect postprandial glucose levels in healthy male volunteers (Visen et al., 2009). Another particularly phytochemical rich plant source found to effect PPG in healthy volunteers was seaweed (Goni et al., 2000). ...
Abstract Nutritional management of blood glucose levels is a strategic target in the prevention and management of type 2 diabetes mellitus (T2DM). To implement such an approach it is essential to understand the effect of food on glycaemic regulation and on the underlying metabolic derangements. This comprehensive review summarises the results from human dietary interventions exploring the impact of dietary components on blood glucose levels. Included are the major macronutrients; carbohydrate, protein and fat, micronutrient vitamins and minerals, non-nutrient phytochemicals and additional foods including low-calorie sweeteners, vinegar and alcohol. Based on the evidence presented in this review, it is clear that dietary components have significant and clinically relevant effects on blood glucose modulation. An integrated approach that includes reducing excess body weight, increased physical activity along with a dietary regime to regulate blood glucose levels will not only be advantages in T2DM management, but will benefit the health of the population and limit the increasing worldwide incidence of T2DM.
Background
Syringa microphylla Diels is a plant in the family Syringa Linn. For hundreds of years, its flowers and leaves have been used as a folk medicine for the treatment of cough, inflammation, colds, sore throat, acute hepatitis, chronic hepatitis, early liver cirrhosis, fatty liver, and oesophageal cancer.
Purpose
For the first time, we have comprehensively reviewed information on Syringa microphylla Diels that is not included in the Pharmacopoeia, clarified the pharmacological mechanisms of Syringa microphylla Diels and its active ingredients from a molecular biology perspective, compiled in vivo and in vitro animal experimental data and clinical data, and summarized the toxicology and pharmacokinetics of Syringa microphylla Diels. The progress in toxicology research is expected to provide a theoretical basis for the development of new drugs from Syringa microphylla Diels, a natural source of compounds that are potentially beneficial to human health.
Methods
The PubMed, Google Scholar, China National Knowledge Infrastructure, Web of Science, SciFinder Scholar and Thomson Reuters databases were utilized to conduct a comprehensive search of published literature as of July 2021 to find original literature related to Syringa microphylla Diels and its active ingredients.
Results
To date, 72 compounds have been isolated and identified from Syringa microphylla Diels, and oleuropein, verbascoside, isoacteoside, echinacoside, forsythoside B, and eleutheroside B are the main active components. These compounds have antioxidant, antibacterial, anti-inflammatory, and neuroprotective effects, and their safety and effectiveness have been demonstrated in long-term traditional applications. Molecular pharmacology experiments have indicated that the active ingredients of Syringa microphylla Diels exert their pharmacological effects in various ways, primarily by reducing oxidative stress damage via Nrf2/ARE pathway regulation, regulating inflammatory factors and inducing apoptosis through the MAPK and NF-κB pathways.
Conclusion
This comprehensive review of Syringa microphylla Diels provides new insights into the correlations among molecular mechanisms, the importance of toxicology and pharmacokinetics, and potential ways to address the limitations of current research. As Syringa microphylla Diels is a natural low-toxicity botanical medicine, it is worthy of development and utilization and is an excellent choice for treating various diseases.
In many Asian and European countries, medicinal plants have been used for a long time for the treatment of different ailments and diseases. In 400 bc, Greek physician Hippocrates, known as the Father of Medicine, said ‘Food should be medicine and medicine should be food’ and elaborated on several dietary plants that could be prospective sources of medicine. Iridoids, an important class of secondary plant metabolites, have been found in several dietary folk medicinal plants of angiosperm plant families.
Fraxinus angustifolia subsp. angustifolia is a plant with an age-old use for the production of manna. However, it is also a valuable source of fixed oil rich-seeds. In the present study we examined the chemical and biological properties of this oil in order to support a possible application in foodstuffs, nutraceuticals and cosmetics. Fatty acid composition, volatile and phenolic substances were evaluated. Oleic and linoleic acid represented 45.5% and 50.0%, respectively, of the total fatty acid composition. Among polar phenolic substances identified (secoiridoids, phenylethanoid glycosides, phenolic acids and alcohols, flavonoids, coumarins) isoverbascoside is for the first time reported in this species. Volatiles were mainly characterized by sesquiterpenes. The oil showed good antioxidant activity, in terms of ABTS radical scavenging activity, with an IC 50 value of 28.2 μg/mL. The antiproliferative activity was also investigated: amelanotic melanoma (C32) and lung carcinoma (A549) cells were the most sensitive with IC 50 values comparable to that of the positive control vinblastine. These findings shed light on the potential use of F. angustifolia subsp. angustifolia fixed oil in nutraceutics and cosmetics.
Osteoarthritis (arthritis) is biomechanical, biochemical and cellular phenomenon, and is not known as a degenerative disease. Arthritis is one of the common chronic diseases and the most important reason of physical disability in the world. According to its side effect such as peptic ulcers, gastrointestinal bleeding, liver toxicity and renal complications dueofprescribing current treatment contain corticosteroid and non-steroidal, we decided to evaluate possible effect of anti-inflammatory Esential oil of Fraxinus excelsior (EOFE) on biomarkers involved in disease. EOFE were prepared of genetic resources center. Bovine articular cartilage derived from the metacarpophalangeal joints of 14–18-month-old animals (without any sign of inflammation and bleeding) sent to laboratory in sterile bags at 4ºC. Cells were cultured in appropriate condition and counted by hemocytometer, viability assessed by trypan blue. After LPS treatment, cytokine levels were assayed. Cells cultures again and were kept in 37C, 90% humidity in CO2 incubator and after RNA extraction, RT-PCR and PCR done. Also by Real-time PCR, gene expression was evaluated. E.E.F.E level cause down regulation of COX-2, IL-1β, TNF-α in LPS-stimulated cells.
Natural products have always been exploited to promote health and served as a valuable source for the discovery of new drugs. In this review, the great potential of natural compounds and medicinal plants for the treatment or prevention of cardiovascular and metabolic disorders, global health problems with rising prevalence, is addressed. Special emphasis is laid on natural products for which efficacy and safety have already been proven and which are in clinical trials, as well as on plants used in traditional medicine. Potential benefits from certain dietary habits and dietary constituents, as well as common molecular targets of natural products, are also briefly discussed. A glimpse at the history of statins and biguanides, two prominent representatives of natural products (or their derivatives) in the fight against metabolic disease, is also included. The present review aims to serve as an "opening" of this special issue of Molecules, presenting key historical developments, recent advances, and future perspectives outlining the potential of natural products for prevention or therapy of cardiovascular and metabolic disease.
Seeds are commonly used foods, and several seeds are rich in nutraceuticals. Examples include the seeds of the members of the Apiaceae family, that are used as spices. Seeds are also rich in omega-3-fatty acids, tocotrienols and phytosterols. In addition, there are several unutilized seed species that are rich in nutraceuticals. Consumption of these seeds regularly has been considered to be a health beneficial practice. This chapter provides a comprehensive account of several types of seeds, and their potential influences on health.
Osmanthus fragrans is a traditional economic and ornamental plant in China. Iridoid glycosides are one of the main active ingredients of this plant. The ethanol extract of O. fragrans’ seeds was analyzed by an HPLC method. The HPLC profile allowed the isolation of nuzhenide and GI-3 from O. fragrans’ seeds for the first time. A C18 column was used with a mixture of methanol and water as the mobile phase using a gradient elution technique. Nuzhenide and GI-3 as the major components were used successfully as chemical markers to determine the optimal time of O. fragrans’ seeds for collection. Experimental results show nuzhenide and GI-3 reached the highest level in the last ten days of April, with contents of 6.04 mg (g of dw)−1 and 13.24 mg (g of dw)−1, higher than that of olive seeds. The study showed that O. fragrans’ seeds can serve as a source of iridoid glycosides.
At an excavation of the late medieval St Margaretha Convent in Leiden (The Netherlands), archaeobotanical results could be
compared with historical data. Both wood and macroremains were analysed to reconstruct the local vegetation and seek evidence
of the cultivation of plants. The historical sources available for this estate are a charter prepared in 1572, which listed
all trees present just after the abandonment of the convent, and an illustration from 1574 of the convent and its grounds.
The charter mentions Salix and Alnus as the most numerous trees present, followed by several other taxa. The archaeological evidence from the wood remains, mostly
construction timber with a dominance of Quercus, shows the use of indigenous taxa and some non-indigenous material, which was partly re-used. It is possible that some of
the Coniferae were very early home-grown specimens. The trees represented in the macroremains were most probably growing in
the immediate vicinity. They specify some of the taxa found as wood or mentioned in the historical text. The identified cultivated
plants could all have been grown locally. The vegetation is in general represented by ruderal taxa and plants growing in wet
conditions, which form an assemblage typical of an abandoned rural area.
Alnus glutinosa, Fraxinus excelsior and Papaver rhoeas have long been used in folkloric medicine for the treatment of various ailments. As part of our continuing screening of plant extracts for biological activities, the extracts of A. glutinosa, F. excelsior and P. rhoeas have been screened for their antioxidant and antibacterial activities, as well as their general toxicity towards brine shrimps. Among the extracts, the methanol (MeOH) extract of F.excelsior displayed the highest level of antioxidant activity (RC50=1.35x10-2 mg/mL) and the dichloromethane (DCM) extract of P. rhoeas was the most toxic extract towards brine shrimps (LD50=2.4x10-2 mg/mL). The n-hexane and DCM extracts of F. excelsior and the MeOHextract of A. glutinosa were active (MIC values were within 1.25x10-1 and 1.00 mg/mL)against all 8 bacterial species tested, including methicillin-resistant Staphylococcus aureus (MRSA).
Despite a lack of medical evidence to support its therapeutic efficacy, the use of herbal medicine has increased considerably. Ginseng, one of the most widely used herbs, is hypothesized to play a role in carbohydrate metabolism and diabetes mellitus. We therefore undertook a preliminary short-term clinical study to assess whether American ginseng (Panax quinquefolius L) affects postprandial glycemia in humans.
On 4 separate occasions, 10 nondiabetic subjects (mean [+/-SD] age, 34+/-7 years; mean [+/-SD] body mass index [BMI], 25.6 +/- 3 kg/m2) and 9 subjects with type 2 diabetes mellitus (mean [+/-SD] age, 62 +/- 7 years; mean [+/-SD] BMI, 29 +/- 5 kg/m2; mean [+/-SD] glycosylated hemoglobin A1c, 0.08+/-0.005) were randomized to receive 3-g ginseng or placebo capsules, either 40 minutes before or together with a 25-g oral glucose challenge. The placebo capsules contained com flour, in which the quantity of carbohydrate and appearance matched the ginseng capsules. A capillary blood sample was taken fasting and then at 15, 30, 45, 60, 90, and 120 (only for subjects with type 2 diabetes mellitus ) minutes after the glucose challenge.
In nondiabetic subjects, no differences were found in postprandial glycemia between placebo and ginseng when administered together with the glucose challenge. When ginseng was taken 40 minutes before the glucose challenge, significant reductions were observed (P<.05). In subjects with type 2 diabetes mellitus, the same was true whether capsules were taken before or together with the glucose challenge (P<.05). Reductions in area under the glycemic curve were 18%+/-31% for nondiabetic subjects and 19+/-22% and 22+/-17% for subjects with type 2 diabetes mellitus administered before or together with the glucose challenge, respectively.
American ginseng attenuated postprandial glycemia in both study groups. For nondiabetic subjects, to prevent unintended hypoglycemia it may be important that the American ginseng be taken with the meal.
Cohort studies indicate that cereal fiber reduces the risk of diabetes and coronary heart disease (CHD). Therefore, we assessed the effect of wheat bran on glycemic control and CHD risk factors in type 2 diabetes.
A total of 23 subjects with type 2 diabetes (16 men and 7 postmenopausal women) completed two 3-month phases of a randomized crossover study. In the test phase, bread and breakfast cereals were provided as products high in cereal fiber (19 g/day additional cereal fiber). In the control phase, supplements were low in fiber (4 g/day additional cereal fiber).
Between the test and control treatments, no differences were seen in body weight, fasting blood glucose, HbA(1c), serum lipids, apolipoproteins, blood pressure, serum uric acid, clotting factors, homocysteine, C-reactive protein, magnesium, calcium, iron, or ferritin. LDL oxidation in the test phase was higher than that seen in the control phase (12.1 +/- 5.4%, P < 0.034). Of the subjects originally recruited, more dropped out of the study for health and food preference reasons from the control phase (16 subjects) than the test phase (11 subjects).
High-fiber cereal foods did not improve conventional markers of glycemic control or risk factors for CHD in type 2 diabetes over 3 months. Possibly longer studies are required to demonstrate the benefits of cereal fiber. Alternatively, cereal fiber in the diet may be a marker for another component of whole grains that imparts health advantages or a healthy lifestyle.
To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes.
We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale.
A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported.
There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.
Five iridoid glycosides, including the two new compounds scropolioside-D(2) (1) and harpagoside-B (2), were isolated from the aerial parts of Scrophularia deserti DEL (Scrophulariaceae). Their structures were elucidated on the basis of spectral data to be 6-O-[2",4"-di-O-acetyl-3"-O-trans-cinnamoyl)-alpha-L-rhamnopyranosyl]-8 alpha-hydroxymethyl-1 alpha,5 beta,6 alpha,7 alpha,9 beta-pentahydro-7(8)-epoxy-2-oxaind-3-ene-1-O-beta-D-glucopyranoside-6'-O-acetate (1) and 5-O-beta-hydroxy-8-O-beta-trans-cinnamoyl-8 alpha-methyl-1,6,7,9-tetrahydro-2-oxaind-3-ene-1-O-beta-D-glucopyranoside (2), respectively. In addition, three more iridoid glycosides, scropolioside-D (3), koelzioside (4), and 8-O-acetyl-harpagide (5), were also isolated and characterized from this source. The biological activity and the structure activity relationship of the compounds were also studied, and scropolioside-D (3) and harpagoside-B (2) were found to possess significant antidiabetic and antiinflammatory activity, respectively.
We have repeatedly reported that a batch of American ginseng with a specific ginsenoside (glycosidal saponin) profile decreases acute postprandial glycemia. We investigated whether Asian ginseng is able to replicate this glycemia-lowering efficacy in two separate acute dose escalation studies.
Each study was conducted in a separate sample of 11 healthy subjects (gender: 8M:3F and 6M:5F, age: 29 +/- 2y and 27 +/- 3y, BMI: 28.5 +/- 2.1 kg/m(2) and 26.9 +/- 1.4 kg/m(2)) using a randomized, single-blind, placebo-controlled, multiple-crossover design. Treatments consisted of 0 (placebo), 1, 2, and 3 g of Asian ginseng for the first study and 0 (placebo), 3, 6, and 9 g Asian ginseng for the second study administered 40 minutes before a 75g-OGTT protocol with blood drawn at -40, 0, 15, 30, 45, 60, 90, and 120 minutes. Ginsenosides were analyzed by HPLC-UV.
Neither the main effect of pooled-treatment, nor dose, nor either factors interaction with time was significant for incremental plasma glucose and insulin. But the diagnostically and therapeutically relevant two-hour plasma glucose (2h-PG) value was significantly higher for pooled Asian ginseng treatment than placebo (5.46 +/- 0.31 versus 4.99 +/- 0.30 mmol/L, p = 0.050). Ginsenoside analyses showed that the Asian ginseng contained up to 96% lower and sevenfold higher quantities of various ginsenosides and their ratios than our previous efficacious batch of American ginseng.
Asian ginseng showed both null and opposing effects on indices of acute postprandial plasma glucose and insulin. This is in contrast to our findings with American ginseng. One explanation may be the marked ginsenoside differences. Practitioners and consumers should be aware of ginseng's variable effects.
It is unclear whether other ginseng sources can replicate the glycemic-lowering efficacy observed previously with American ginseng and whether ginsenosides are mediators. We assessed the effect of eight popular ginseng types on postprandial plasma glucose (PG) and insulin (PI) indices, linking effects to ginsenoside profiles.
Using a double-blind, randomized, multiple-crossover design, 12 healthy participants (gender: 6M:6F, age: 34 +/- 3 y, BMI: 25.8 +/- 1.2 kg/m(2)) received 10 3g treatments: American, American-wild, Asian, Asian-red, Vietnamese-wild, Siberian, Japanese-rhizome, and Sanchi ginsengs and two placebos. Each treatment was given 40-minutes before a 75g-oral-glucose-tolerance-test (75g-OGTT) with blood drawn at -40, 0, 15, 30, 45, 60, 90, 120-minutes. HPLC-UV analysis quantified seven principal ginsenosides.
Two-factor analysis showed the main effects of ginseng-type and time were significant for PG and PI, with an interaction for PG (p < 0.05). Subsequent one-factor analysis showed an effect of ginseng-type on 90-min-PG and 90-min-PI (p < 0.05). This was reflected in effects on peak-PG, area under the curve (AUC)-PG and AUC-PI (p < 0.05). But the effect on 90-min-PI and AUC-PI were significant (p < 0.05) only in overweight participants (BMI > 25 kg/m(2), n = 6). Planned comparisons with placebo showed a tendency for American ginseng and Vietnamese ginseng to lower 90-min-PG (p < 0.06), while Asian ginseng raised peak-PG and AUC-PG, American-wild ginseng raised 120-min-PG, and Siberian ginseng raised 90-min-PG, 120-min-PG, and AUC-PG (p < 0.05). Stepwise-multiple-regression assessed the protopanaxadiol:protopanaxatriol (PPD:PPT)-ginsenoside ratio as the sole predictor (p < 0.05) for 90-min-PG (beta = -0.43, r(2) = 0.072), AUC-PG (beta = -0.25, r(2) = 0.06), 90-min-PI (beta = -0.26, r(2) = 0.065), AUC-PI (beta = -0.20, r(2) = 0.04).
Ginseng has variable glycemic effects, in which the PPD:PPT-ginsenoside ratio might be involved. But the low variance explained suggests the involvement of other unmeasured ginsenoside or non-ginsenoside components.
To determine the effect of different doses of Salacia oblonga extract, an herbal alpha-glucosidase inhibitor, on postprandial glycemic, insulinemic, and breath hydrogen responses in healthy adults.
Double-masked, randomized crossover design.
Subjects, after fasting for 12 hours, consumed four test meals consisting of 480 mL of study beverage (14 g fat, 82 g carbohydrate, and 20 g protein) with 0, 500, 700, or 1,000 mg of S oblonga extract on four separate occasions. Capillary finger-prick plasma glucose and venous serum insulin concentrations were measured at baseline and for 2 hours postprandially. Breath hydrogen excretion was measured at baseline and hourly for 8 hours postprandially.
Thirty-nine healthy, nondiabetic adults (body mass index=23.7+/-0.4, age=25.7+/-0.9 years.
Repeated-measures analysis of variance was applied to the raw data or data that had been transformed (log, rank) when necessary due to nonnormality. The Tukey-Kramer post hoc test was used for pairwise comparisons.
Compared with the control, the 1,000-mg S oblonga extract dose reduced the plasma glucose and serum insulin incremental areas under the curve (0 to 120 minutes postprandial) by 23% ( P =.32) and 29% ( P =.01), respectively. The other doses of S oblonga extract did not impact glycemia or insulinemia. Breath hydrogen excretion increased linearly as the dose of S oblonga extract was advanced.
The presence of S oblonga extract tended to lower postprandial glycemia and significantly reduced the postprandial insulin response. The increase in breath hydrogen excretion suggests a mechanism similar to prescription alpha-glucosidase inhibitors. Future studies of S oblonga extract in patients with diabetes are needed.
We tested whether the dominant intestinal sugar transporter GLUT2 was inhibited by intestinal luminal compounds that are inefficiently absorbed and naturally present in foods. Because of their abundance in fruits and vegetables, flavonoids were selected as model compounds. Robust inhibition of glucose and fructose transport by GLUT2 expressed in Xenopus laevis oocytes was produced by the flavonols myricetin, fisetin, the widely consumed flavonoid quercetin, and its glucoside precursor isoquercitrin [corrected]. IC50s for quercetin, myricetin, and isoquercitirin [corrected]were approximately 200- to 1000-fold less than glucose or fructose concentrations, and noncompetitive inhibition was observed. The two other major intestinal sugar transporters, GLUT5 and SGLT1, were unaffected by flavonoids. Sugar transport by GLUT2 overexpressed in pituitary cells and naturally present in Caco-2E intestinal cells was similarly inhibited by quercetin. GLUT2 was detected on the apical side of Caco-2E cells, indicating that GLUT2 was in the correct orientation to be inhibited by luminal compounds. Quercetin itself was not transported by the three major intestinal glucose transporters. Because the flavonoid quercetin, a food component with an excellent pharmacology safety profile, might act as a potent luminal inhibitor of sugar absorption independent of its own transport, flavonols show promise as new pharmacologic agents in the obesity epidemic.
There is controversy as to whether intestinal absorption of glycosylated flavonoids, and particularly quercetin glycosides, involves their uptake in intact form via the human sodium-coupled glucose transporter hSGLT1. We here describe studies using Xenopus oocytes that express hSGLT1 and the two-electrode voltage clamp technique to determine the transport characteristics of a variety of flavonoids carrying glucose residues at different positions as well as of their aglycones (altogether 27 compounds). Neither quercetin, luteolin, apigenin, naringenin, pelarginidin, daidzein, or genistein, nor any of their glycosylated derivatives generated significant transport currents. However, the inward current evoked by 1 mM of the hSGLT1 substrate alpha-methyl-D-glucopyranoside was potently reduced by the simultaneous application of not only various flavonoid glycosides but also by some aglycones. The inhibitory potency remained unchanged when the attached glucose was replaced by galactose, suggesting that these residues may bind to SGLT1. Kinetic analysis by Dixon plots revealed inhibition of competitive type with high affinities, particularly when the glucose was attached to the position 4' of the aromatic ring of the flavonoids. The affinities became lower when the glucose was attached to a different position. Unexpectedly, the aglycone form of luteolin also inhibited the transport competitively with high affinity. These data show that hSGLT1 does not transport any of the flavonoids and seems therefore not involved in their intestinal absorption. However, not only glycosylated but also a few nonglycosylated flavonoids show a structure-dependent capability for effective inhibition of SGLT1.
In our previous study, Corni Fructus (Cornus officinalis SIEB. et ZUCC.), a component crude drug of the Chinese prescription Hachimi-jio-gan, was reported to reduce glucotoxicities, up-regulate renal function, and consequently ameliorate glycation-associated renal damage as well as Hachimi-jio-gan. Based upon these facts, we prepared Corni Fructus fractions and evaluated which fraction contained the effective components against diabetes, using one iridoid glycoside and three polyphenol fractions, which were expected to possess stronger activities than Corni Fructus, administered orally at a dose of 20 mg/kg body weight/d for 10 d, respectively. As a result, iridoid glycosides and low molecular weight polyphenol fractions could reduce the pathogenesis of diabetic renal damage, each having different mechanisms, i.e., iridoid glycosides successfully decreased the hyperglycemic state and affected renal advanced glycation end-product (AGE) accumulation, such as N(epsilon)-(carboxyethyl)lysine and N(epsilon)-(carboxymethyl)lysine, while low molecular weight polyphenol fractions could reduce renal lipid peroxidation, the receptor for AGE, and inducible nitric oxide synthase. Overall, these data suggest that iridoid glycosides and low molecular weight polyphenols purified from Corni Fructus improve metabolic parameters associated with the development of diabetic renal damage. The main active components of these fractions are discussed.
Unlabelled:
Herbal antirheumatics are successfully used in painful inflammatory or degenerative rheumatic diseases. One of these herbal medicines is Phytodolor (STW 1), a fixed combination of extracts from aspen leaves and bark (Populus tremula), common ash bark (Fraxinus excelsior), and golden rod herb (Solidago virgaurea). Its effects as well as those of its components have been verified in experimental and human pharmacological investigations. The mode of action of STW 1 includes antiinflammatory, antioedematous, antioxidative and analgesic properties, and it is considered to be broader than that of synthetic antirheumatics. Open clinical studies and randomised, placebo- or verum-controlled double-blind trials, performed in different subtypes of rheumatic diseases, confirm the pharmacological evidence of efficacy, such as by reducing the intake of non-steroidal antiinflammatory drugs (NSAIDs). STW 1 has a high drug safety.
Conclusion:
Phytodolor (STW 1) is a reasonable alternative to NSAIDs and to cyclooxygenase(COX)-2-inhibitors such as rofecoxib.
Fraxinus exelsior; Oleaceae; coumarins; fraxidin 8-0-beta-D-ghtcoside; mandshurin; iridoid
glucoside; 10-hydroxyligstroside.
A new secoiridoid named excelsioside has been isolated from the leaves of Fraxinus excelsior along with several known secoirioids and verbascoside. The compounds were identified by NMR, and the structure of excelsioside was finally assigned on the basis of a long-range selective proton decoupling (LSPD) 13C NMR experiment.
Diabetes mellitus is a debilitating and often life-threatening disease with increasing incidence in rural populations throughout the world. A scientific investigation of traditional herbal remedies for diabetes may provide valuable leads for the development of alternative drugs and therapeutic strategies. Alternatives are clearly needed because of the inability of current therapies to control all of the pathological aspects of diabetes, and the high cost and poor availability of current therapies for many rural populations, particularly in developing countries. This review provides information on more than 1200 species of plants reported to have been used to treat diabetes and/or investigated for antidiabetic activity, with a detailed review of representative plants and some of great diversity of plant constituents with hypoglycemic activity, their mechanisms of action, methods for the bioassay of hypoglycemic agents, potential toxicity problems, and promising directions for future research on antidiabetic plants. The objective of this work is to provide a starting point for programs leading to the development of indigenous botanical resources as inexpensive sources for standardized crude or purified antidiabetic drugs, and for the discovery of lead compounds for novel hypoglycemic drug development.
Metabolites, previously designated Gl 3, Gl 5, and Gl 6, from embryos of the American ash (Fraxinus americana) were examined by spectral methods, degradation achieved by methanolysis and conversion to acetates. Gl 6 is identified as nüzhenide. Acetylation of Gl 3 and Gl 5 gives 1H NMR determined undecaacetate and octaacetate, respectively, thus providing evidence for the number of free hydroxyl groups and furnishing material suitable for molecular weight determinations by vapor-phase osmometry. Evidence for the identity and sequence of the various units was obtained, among other methods, through methanolysis, Gl 3 giving nüzhenide and oleoside 7-methyl ester and Gl 5 giving ligstroside and oleoside 7-methyl ester. Gl 3 contains one unit of 2-(4-hydroxyphenyl)ethanol (Tyo), three units of glucose [all as 1-β-D-glucopyranosides (β-D-Glc)], and two of oleoside aglucon (β-Olo) in the sequence: β-D-Glcl-1β-Olo7-6β-D-Glcl-1Tyo6-7β-Olol-1β-D-Glc. Gl 5 contains the same components as Gl 3 but one less glucose unit in the sequence β-D-Glcl-1β-Olo7-1Tyo6-7β-Olol-1β-D-Glc. 13C NMR proves to be an especially valuable tool in determining the sequence of units in the intact metabolites.
The hypoglycemic activity of olive leaf was studied. Maximum hypoglycemic activity was obtained from samples collected in the winter months, especially in February. One of the compounds responsible for this activity was oleuropeoside, which showed activity at a dose of 16 mg/kg. This compound also demonstrated antidiabetic activity in animals with alloxan-induced diabetes. The hypoglycemic activity of this compound may result from two mechanisms: (a) potentiation of glucose-induced insulin release, and (b) increased peripheral uptake of glucose.
Aqueous/alcoholic extracts of Populus tremula, Solidago virgaurea and Fraxinus excelsior (components of Phytodolor N) were tested individually and in 3 different combinations for anti-inflammatory activity using carrageenan induced edema and/or adjuvant induced arthritis of the rat paw. The tested combinations as well as the individual extracts significantly reduced the paw edema to varying degrees and also dose dependently inhibited the arthritic paw volume. The anti-inflammatory activity of the combinations was respectively comparable to the tested doses of diclofenac.
There is controversy regarding the clinical utility of classifying foods according to their glycemic responses by using the glycemic index (GI). Part of the controversy is due to methodologic variables that can markedly affect the interpretation of glycemic responses and the GI values obtained. Recent studies support the clinical utility of the GI. Within limits determined by the expected GI difference and by the day-to-day variation of glycemic responses, the GI predicts the ranking of the glycemic potential of different meals in individual subjects. In long-term trials, low-GI diets result in modest improvements in overall blood glucose control in patients with insulin-dependent and non-insulin-dependent diabetes. Of perhaps greater therapeutic importance is the ability of low-GI diets to reduce insulin secretion and lower blood lipid concentrations in patients with hypertriglyceridemia.
Antiinflammatory, Analgesic and Antipyretic Effects of Various Plant Extracts and a Combination Thereof in Animal Models. The three main components comprising the efficacy of non-steroidal antiinflammatory drugs could be demonstrated for STW 1 in different animal models. The phytotherapeutic preparation, containing three individual plant extracts (Populus tremula, Solidago virgaurea, Fraxinus excelsior) produced dose-dependent antiinflammatory, analgesic and antipyretic effects which were similar to those of the reference substances salicyl alcohol and indometacin. As each of the individual extracts displayed considerable efficacy, it may be assumed that each of them contributes to the overall effects of the combination STW 1.
The effects of phenolic compounds on Na+-dependent D-glucose transport were investigated in brush border membrane vesicles isolated from rat small intestine. Screening experiments were conducted with different classes of phenolic compounds in both their native and oxidized forms. Pretreatment of vesicles with tannic acid (1 mg/ml) completely abolished the characteristic overshoot of active glucose accumulation. With chlorogenic acid (1mM), 80% of the glucose transport capacity was lost. Reductions of 30-40% were observed in vesicles treated with catechin, ferulic or caffeic acids. Treatment with gallic acid (1 mM) had little effect. Phenolic oxidation state did not exacerbate the degree of glucose transport inhibition, with the exception of catechol (1 mM), which gave maximal inhibition (86%) in its oxidized form. Gradient-independent glucose uptake was not altered, nor did phenolic treatment increase nonspecific binding of glucose to the membrane vesicles. Possible mechanisms of D-glucose transport inhibition were examined in chlorogenic acid-and tannic acid-treated vesicles. Factors such as alterations in vesicle permeability, size and leakage of transported glucose out of the vesicles were ruled out. Measurements of D-glucose uptake under conditions of Na+ equilibrium suggest that tannic and chlorogenic acids reduce glucose uptake by favoring the dissipation of the Na+ electrochemical gradient, which provides the driving force for active glucose accumulation.
Aqueous-ethanolic extracts from Fraxinus excelsior, Populus tremula and Solidago virgaurea inhibit biochemical model reactions representing inflammatory situations to various extents. These model reactions include xanthine oxidase, diaphorase in the presence of the autoxidizable quinone juglone, lipoxygenase and photodynamic reactions driven by riboflavin or rose bengal. The tested extracts are the components of the phytomedicine Phytodolor N (abbreviated as PD) which possesses antipyretic, analgesic, antiinflammatory and antirheumatic activity. Since several reactive oxygen species produced by the mentioned model systems are also involved in inflammatory processes, the beneficial activities of the complete drug may at least in part be due to the reported antioxidative functions of the individual components.
Aqueous-ethanolic extracts of Fraxinus excelsior, Populus, tremula and Solidago virgaurea in a combination of 1: 3: 1 (v/v/v) are the components of the plant drug Phytodolor N (abbreviated as PD), which exhibits antipyretic, analgesic and antirheumatic activity. Similar to a broad variety of synthetic non-steroidal anti-inflammatories the mentioned plant extracts inhibit dihydrofolate reductase. The following concentrations as percentage in the test volumes represent the individual I50-values: F. excelsior = 0.26% (v/v); P. tremula = 0.46% (v/v) and S. virgaurea = 0.6% (v/v). The combined extracts in PD exhibit an I50 at 0.3% (v/v). Testing the activity of the water-soluble compounds of corresponding dry extracts, the activity of F. excelsior with an apparent I50-value of 0.008% (w/v) by far dominates the inhibitory overall effect of the combination (I50 = 0.014%, w/v).
Anti-inflammatory properties of Populus tremula are mainly deduced from its components, the well investigated salicylates. Solidago extracts have spasmolytic, antihypertensive and diuretic effects. Fraxinus excelsior itself has hardly been investigated, but its coumarin components proved to have a variety of pharmacological properties, i.e. inhibition of T-cell activation and of the arachidonic acid cascade. Phytodolor N (abbreviated as PD) is a combination of the above mentioned plants. Various in vitro and especially in vivo studies proved its anti-inflammatory and antirheumatic properties, often comparable to non-steroidal anti-inflammatories, but with little or no side effects.
Extracts from Populus tremula, Solidago virgaurea and Fraxinus excelsior are used as anti-inflammatory drugs. The effects of these extracts on myeloperoxidase (MPO), an enzyme liberated by activated granulocytes and known to produce the destructive agent hypochloric acid, were investigated. Populus and Fraxinus inhibited this enzyme, Solidago was without effect. These results were obtained concordantly with four different MPO-assays (H2O2/MPO; X/XOD/MPO; activated PMN; and elastase/alpha 1-PI-MPO). Fractionation of Populus and Fraxinus extracts showed that this inhibition is due to several different compounds. Well known or wide spread substances as e.g. rutin, salicylic acid, chlorogenic acid etc. had no or only little effect on the enzyme.
Biochemische Modellreaktionen zur Darstellung von Entzündungsprozessen /Aktivität von Extrakten aus Fraxinus excelsior und Populus tremula
Atmosphärischer Sauerstoff ist sehr reaktionsträge und muß für eine Reaktion mit anderen Molekülen erst aktiviert werden. Dabei entstehen reaktive Sauerstoff-Spezies (ROS), an die sich alle aeroben Zellen anpassen mußten. Solche ROS sind verantwortlich für zahlreiche pathologische Prozesse, wie z. B. für Entzündungen. Abhängig von der Andauer und der Stärke dieser Aktivierungsreaktionen treten Symptome auf, die auf Abweichungen von Metabolismen im homöostatischen Gleichgewicht hinweisen. In diesen pathologischen Situationen reichen die intrinsischen Schutzsysteme nicht mehr aus und es kommt zu den bekannten Krankheitsbildern. Antioxidantien, zu denen Radikalfänger und Modulatoren angeregter Zustände zählen, umfassen große Klassen von Naturstoffen, wie die der Phenole. Zahlreiche Komponenten der Nahrung - aber auch Heilmittel - wirken auf diese Weise. Phytodolor® enthält Extrakte aus Fraxinus excelsior, Populus tremula und Solidago virgaurea. In einer Reihe von Arbeiten wurden biochemischen Modellreaktionen vorgestellt und gezeigt, dass (und wie) diese Extrakte als Antioxidantien wirken. Diese Arbeiten werden nachfolgend zusammengefaßt. Darüber hinaus werden neue Reaktionen vorgestellt, mit denen dokumentiert wird, daß auch die für entzündliche Prozesse charakteristische Tyrosin-Nitrierung durch diese Extrakte unterbunden wird.
Epidemiological studies have shown that the incidence of heart disease and certain cancers is lower in the Mediterranean region. This has been attributed to the high consumption of olive oil in the Mediterranean diet, which contains polyphenolic compounds with antioxidant activity. Although many in vitro studies have been performed to elucidate mechanisms by which these compounds may act, there are virtually no data relating to their fate after ingestion. Therefore, we decided to investigate the intestinal absorption of one of the major olive oil polyphenolics, oleuropein. To do this, a novel in situ intestinal perfusion technique was developed, and the absorption of oleuropein was studied under both iso-osmotic and hypotonic luminal conditions. Oleuropein was absorbed, with an apparent permeability coefficient (P:(app)) of 1.47 +/- 0.13 x 10(-6) cm/s (+/-SE) observed under iso-osmotic conditions. The mechanism of absorption is unclear but may involve transcellular transport (SGLT1) or paracellular movement. Under hypotonic conditions, the permeability of oleuropein was significantly greater (5.92 +/- 0.49 x 10(-6) cm/s, P: < 0.001). This increase is thought to be due to an increase in paracellular movement facilitated by the opening of paracellular junctions in response to hypotonicity. Overall, we determined that the olive oil polyphenolic oleuropein can be absorbed, albeit poorly, from isolated perfused rat intestine. Therefore, it is possible that it or its metabolites may confer a positive health benefit after the consumption of olive oil, most likely via an antioxidant mechanism.
Despite significant achievements in treatment modalities and preventive measures, the prevalence of diabetes has risen exponentially in the last decade. Because of these limitations there is a continued need for new and more effective therapies. An increasing number of people are using dietary and herbal supplements, even though there is a general lack of evidence for their safety and efficacy. Consequently, science based medical and government regulators are calling for more randomized clinical studies to provide evidence of efficacy and safety. Our research group has selected two such promising and functionally complementary therapies for further investigation as potentially emerging alternative therapies for type 2 diabetes: Konjac-mannan (KJM) and American ginseng (AG). We have generated a mounting body of evidence to support the claim that rheologically-selected, highly-viscous KJM, and AG with a specific composition may be useful in improving diabetes control, reducing associated risk factors such as hyperlipidemia and hypertension, and ameliorating insulin resistance. KJM has a demonstrated ability to modulate the rate of absorption of nutrients from the small bowel, whereas AG has post-absorptive effects. Consequently, it appears that KJM and AG are acting through different, yet complementary, mechanisms: KJM by increasing insulin sensitivity and AG likely by enhancing insulin secretion. Before the therapeutic potential of KJM and AG as novel prandial agents for treatment of diabetes can be fully realized, further controlled trials with larger sample sizes and of longer duration are required. A determination of the active ingredients in AG, and the rheology-biology relationship of KJM are also warranted.
For the first time a biossay-directed study of triterpenoids isolated from the leaves of Olea europaea from Greece, from wild African olive and from a cultivar of O. europaea grown in Cape Town was reported. The experiment was undertaken since our preliminary analyses showed that the African wild olive leave is rich in triterpenoids and contain only traces of the glycoside oleuropein, which is typical for the European olive leaves. The isolate of the African wild olive leaves (AO) used in the experiments was found to contain 0.27% 1:1 mixture of oleanolic acid and ursolic acid, named oleuafricein. The isolate of Greek olive leaves (GO) was found to contain 0.71% oleanolic acid, and the Cape Town cultivar (CT) contained 2.47% oleanolic acid. No ursolic acid was found in either GO or CT. The antihypertensive, diuretic, antiatherosclerotic, antioxidant and hypoglycemic effects of authentic oleanolic and ursolic acid and the three isolates (GO, AO and CT) were studied on Dahl salt-sensitive (DSS), insulin-resistant rat genetic model of hypertension. All three isolates, in a dose 60 mg/kg b.w. for 6 weeks treatment, prevented the development of severe hypertension and atherosclerosis and improved the insulin resistance of the experimental animals. GO, OA and CT isolates could provide an effective and cheap treatment of this particular, most common type of salt-sensitive hypertension in the African population.
N'-beta-phenethylformamidiny-liminourea (DBI), a synthetic substance, administered parenterally or orally, causes hypoglycemia in guinea-pigs, rats, rabbits, cats and Rhesus monkeys. It can also reduce blood sugar in alloxan-diabetic rats, rabbits and monkeys and maintain them at a normal level. DBI does not cause significant changes in glycogen content of liver or muscle. Further work will be necessary to elucidate its mechanism of action and assess its possible clinical usefulness.
The hypoglycaemic effect of the aqueous extracts of Fraxinus excelsior (FE) seed and Silybum marianum (SM) aerial part was investigated in normal and streptozotocin (STZ) diabetic rats. After a single dose or 15 daily doses, oral administration of the aqueous extracts (20 mg/kg) produced a significant decrease of blood glucose levels in both normal and STZ diabetic rats (P < 0.001). From the first week, the body weight was increased in normal rats (P < 0.05) and decreased in STZ rats (P < 0.01) after FE administration. In addition, no changes were observed in basal plasma insulin concentrations after both FE and SM treatments in either normal and STZ diabetic rats indicating that these plants exert their pharmacological activity without affecting insulin secretion. We conclude that the aqueous extracts of FE and SM exhibit potent hypoglycaemic and anti-hyperglycaemic activities in normal and STZ rats, respectively, without affecting basal plasma insulin concentrations.
The purpose of this study was to determine the underlying mechanism of the hypoglycaemic activity of the aqueous extract perfusion of Fraxinus excelsior L. (FE) in normal and streptozotocin-induced diabetic rats. The aqueous extract was administered intravenously and the blood glucose changes were determined within four hours after starting the treatment. Plasma insulin concentrations and glycosuria were determined. The aqueous extract at a dose of 10 mg/kg/h produced a significant decrease in blood glucose levels in normal rats (P < 0.001) and even more in diabetic rats (P < 0.001). This hypoglycaemic effect might be due to an extra-pancreatic action of the aqueous extract of FE, since the basal plasma insulin concentrations were unchanged after FE treatment. A potent increase of glycosuria was observed both in normal and diabetic rats (P < 0.001). We conclude that aqueous extract perfusion of FE caused a potent inhibition of renal glucose reabsorption. This renal effect might be at least one mechanism explaining the observed hypoglycaemic activity of this plant in normal and diabetic rats.
The effect of different classes of dietary polyphenols on intestinal glucose uptake was investigated using polarised Caco-2 intestinal cells. Glucose uptake into cells under sodium-dependent conditions was inhibited by flavonoid glycosides and non-glycosylated polyphenols whereas aglycones and phenolic acids were without effect. Under sodium-free conditions, aglycones and non-glycosylated polyphenols inhibited glucose uptake whereas glycosides and phenolic acids were ineffective. These data suggest that aglycones inhibit facilitated glucose uptake whereas glycosides inhibit the active transport of glucose. The non-glycosylated dietary polyphenols appear to exert their effects via steric hindrance, and (-)-epigallochatechingallate, (-)-epichatechingallate and (-)-epigallochatechin are effective against both transporters.
The hypotensive effect of an aqueous extract of Fraxinus excelsior L. was investigated in both normotensive (WKY) and spontaneously hypertensive rats (SHR). Daily oral administration of Fraxinus excelsior (20 mg/kg) aqueous extract for 3 weeks produced a significant decrease in systolic blood pressure (SBP) with variation coefficient (Delta%) of 13.5% in SHR (p<0.01) and 9% in WKY rats (p<0.05). The aqueous extract of Fraxinus excelsior significantly enhanced the urination in both SHR (p<0.05 compared to control) and WKY (p<0.05 compared to control). Irbesartan (Avapro), an angiotensin II antagonist, was used as reference drug. Furthermore, oral administration of aqueous Fraxinus excelsior extract at a dose of 20 mg/kg produced a significant increase in urinary excretion of sodium (p<0.01 compared to control), potassium (p<0.001 compared to control) and chlorides (p<0.01) in SHR rats. In normal rats, the aqueous Fraxinus excelsior extract administration induced a significant increase of the urinary elimination of sodium (p<0.05 compared to control), chlorides (p<0.01 compared to control) and potassium (p<0.01 versus control). While there were no significant changes in heart rate (HR) after Fraxinus excelsior treatment in both SHR and WKY rats, glomerular filtration rate (GFR) showed a significant increase in SH rats (p<0.001) after Fraxinus excelsior treatment. These results suggest that oral administration of aqueous extract of Fraxinus excelsior exhibited hypotensive and diuretic actions.
Patients with diabetes mellitus are likely to develop certain complication such as retinopathy, nephropathy and neuropathy as a result of oxidative stress and overwhelming free radicals. Treatment of diabetic patients with antioxidant may be of advantage in attenuating these complications. Oleuropein, the active constituent of olive leaf (Olea europaea), has been endowed with many beneficial and health promoting properties mostly linked to its antioxidant activity. This study aimed to evaluate the significance of supplementation of oleuropein in reducing oxidative stress and hyperglycemia in alloxan-induced diabetic rabbits. After induction of diabetes, a significant rise in plasma and erythrocyte malondialdehyde (MDA) and blood glucose as well as alteration in enzymatic and non-enzymatic antioxidants was observed in all diabetic animals. During 16 weeks of treatment of diabetic rabbits with 20 mg/kg body weight of oleuropein the levels of MDA along with blood glucose and most of the enzymatic and non-enzymatic antioxidants were significantly restored to establish values that were not different from normal control rabbits. Untreated diabetic rabbits on the other hand demonstrated persistent alterations in the oxidative stress marker MDA, blood glucose and the antioxidant parameters. These results demonstrate that oleuropein may be of advantage in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggest that administration of oleuropein may be helpful in the prevention of diabetic complications associated with oxidative stress.
Fractionation of a ginseng source to produce differences in the ginsenoside profile might influence its effect on postprandial glycemia. To explore this possibility and identify an efficacious ginseng for a longterm study, we conducted a preparation-finding study of different Korean red ginseng (KRG) root fractions followed by a dose-finding study of the most efficacious fraction.
A double-blind, randomized, within-subject design was used in both studies. In the preparation-finding study, 7 healthy subjects (sex: 3m:4f, age: 32 +/- 4 y, BMI: 24 +/- 2 kg/m2) received 6 g placebo and KRG-rootlets, -body, and -H2O extract 40 min before a 50 g-OGTT with finger-prick blood samples at -40-, 0-, 15-, 30-, 45-, 60-, 90-, 120-min. In the dose-finding study, 12 healthy subjects (sex: 9M,3F, age: 29 +/- 3 y, BMI: 22.5 +/- 1 kg/m2) received 0 g (placebo), 2 g, 4 g, and 6 g of the most efficacious root fraction following the same protocol. Ginsenosides were analyzed using HPLC-UV.
In the preparation-finding study, a wide variation in the ginsenoside profiles was achieved across the 3 KRG fractions. This variation coincided with differential effects. The main effects of KRG-rootlets (p = 0.050) and time (p < 0.001) and their interaction (p < 0.1) were significant. This was reflected in a 29% reduction in area under the curve (AUC) by KRG-rootlets compared with placebo (p = 0.052). Conversely, neither KRG-H2O extract nor KRG-body affected glycemia. Stepwise-multiple regression models identified Rg1 as the sole predictor of mean- and AUC postprandial blood glucose. In the dose-finding study, KRG-rootlets were tested as the most efficacious fraction. A significant effect of KRG-rootlets treatment (mean of 3 doses) but not dose was found. The mean of 3 doses decreased AUC by 17% compared with placebo (p = 0.057).
Together the studies indicate 2 g KRG-rootlets is sufficient to achieve reproducible reductions in postprandial glycemia. But the longterm sustainability of KRG selected using this approach remains to be tested.
We have conducted a detailed investigation into the absorption, metabolism and microflora-dependent transformation of hydroxytyrosol (HT), tyrosol (TYR) and their conjugated forms, such as oleuropein (OL). Conjugated forms underwent rapid hydrolysis under gastric conditions, resulting in significant increases in the amount of free HT and TYR entering the small intestine. Both HT and TYR transferred across human Caco-2 cell monolayers and rat segments of jejunum and ileum and were subject to classic phase I/II biotransformation. The major metabolites identified were an O-methylated derivative of HT, glucuronides of HT and TYR and a novel glutathionylated conjugate of HT. In contrast, there was no absorption of OL in either model. However, OL was rapidly degraded by the colonic microflora resulting in the formation of HT. Our study provides additional information regarding the breakdown of complex olive oil polyphenols in the GI tract, in particular the stomach and the large intestine.
Uncoupling protein 2 (UCP2) negatively regulates insulin secretion. UCP2 deficiency (by means of gene knockout) improves obesity- and high glucose-induced beta cell dysfunction and consequently improves type 2 diabetes in mice. In the present study, we have discovered that the small molecule, genipin, rapidly inhibits UCP2-mediated proton leak. In isolated mitochondria, genipin inhibits UCP2-mediated proton leak. In pancreatic islet cells, genipin increases mitochondrial membrane potential, increases ATP levels, closes K(ATP) channels, and stimulates insulin secretion. These actions of genipin occur in a UCP2-dependent manner. Importantly, acute addition of genipin to isolated islets reverses high glucose- and obesity-induced beta cell dysfunction. Thus, genipin and/or chemically modified variants of genipin are useful research tools for studying biological processes thought to be controlled by UCP2. In addition, these agents represent lead compounds that comprise a starting point for the development of therapies aimed at treating beta cell dysfunction.
To address the paucity of randomized clinical studies assessing ginseng on long-term outcomes in type 2 diabetes, we assessed the clinical antidiabetic efficacy and safety of 12 weeks of supplementation with a Korean red ginseng (KRG) preparation, dose, and mode of administration, selected from an acute, clinical, screening model.
Nineteen participants with well-controlled type 2 diabetes (sex: 11 M:8 F, age: 64+/-2 years, BMI: 28.9+/-1.4 kg/m(2), HbA(1c): 6.5%) completed the study. Using a double-blind, randomized, crossover design, each participant received the selected KRG preparation (rootlets) and placebo at the selected dose (2 g/meal=6 g/day) and mode of administration (preprandial oral agent [-40 min]) for 12 weeks as an adjunct to their usual anti-diabetic therapy (diet and/or medications). Outcomes included measures of efficacy (HbA1c and fasting- and 75-g oral glucose tolerance test [OGTT]-plasma glucose [PG], plasma insulin [PI], and insulin sensitivity index [ISI] indices); safety (liver, kidney, haemostatic, and blood-pressure function); and compliance (returned capsules, diet-records, and body-weight). There was no change in the primary endpoint, HbA(1c). The participants, however, remained well-controlled (HbA1c=6.5%) throughout. The selected KRG treatment also decreased 75 g-OGTT-PG indices by 8-11% and fasting-PI and 75 g-OGTT-PI indices by 33-38% and increased fasting-ISI (homeostasis model assessment [HOMA]) and 75 g-OGTT-ISI by 33%, compared with placebo (P<0.05). Safety and compliance outcomes remained unchanged.
Although clinical efficacy, as assessed by HbA1c, was not demonstrated, 12 weeks of supplementation with the selected KRG treatment maintained good glycemic control and improved PG and PI regulation safely beyond usual therapy in people with well-controlled type 2 diabetes. Further investigation with similarly selected KRG treatments may yield clinical efficacy.