Background and purpose: Galegine and guanidine, originally isolated from Galega officinalis, led to the development of the biguanides. The weight-reducing effects of galegine have not previously been studied and the present investigation was undertaken to determine its mechanism(s) of action. Experimental approach: Body weight and food intake were examined in mice. Glucose uptake and acetyl-CoA carboxylase activity were studied in 3T3-L1 adipocytes and L6 myotubes and AMP activated protein kinase (AMPK) activity was examined in cell lines. The gene expression of some enzymes involved in fat metabolism was examined in 3T3-L1 adipocytes. Key results: Galegine administered in the diet reduced body weight in mice. Pair-feeding indicated that at least part of this effect was independent of reduced food intake. In 3T3-L1 adipocytes and L6 myotubes, galegine (50 mM-3 mM) stimulated glucose uptake. Galegine (1-300 mM) also reduced isoprenaline-mediated lipolysis in 3T3-L1 adipocytes and inhibited acetylCoA carboxylase activity in 3T3-L1 adipocytes and L6 myotubes. Galegine (500 mM) down-regulated genes concerned with fatty acid synthesis, including fatty acid synthase and its upstream regulator SREBP. Galegine (10 mM and above) produced a concentration-dependent activation of AMP activated protein kinase (AMPK) in H4IIE rat hepatoma, HEK293 human kidney cells, 3T3-L1 adipocytes and L6 myotubes. Conclusions and implications: Activation of AMPK can explain many of the effects of galegine, including enhanced glucose uptake and inhibition of acetyl-CoA carboxylase. Inhibition of acetyl-CoA carboxylase both inhibits fatty acid synthesis and stimulates fatty acid oxidation, and this may to contribute to the in vivo effect of galegine on body weight.

Background: Dendrophthoe pentandra (L.) Miq. is a mistletoe species used in traditional medicine. Juice of leaves is used in wound healing, skin infection and cancer; whereas the whole plant is used to treat hypertension and cough. D. pentandra leaf extract has attracted interest due to its pharmacological properties including antioxidant, cytotoxicity and anti-inflammatory effects. In this study, we have investigated the hepatopotective, antihyperglycemic and antidiabetic potential of D. pentandra leaf extracts in rats. Methods: D. pentandra leaf methanolic extract (DPLME) at a fixed dose of 400 mg/kg body weight was evaluated for its effects on fasting glucose levels of rats. DPLME at the same dose was also used to determine the antidiabetic potential in alloxan-induced diabetic rats and the hepatopotective effects on Paracetamol (PCM) intoxicated rats. Results: Oral administration of DPLME exhibited a significantly notable oral glucose tolerance in rats. Single doses of the DPLME displayed very significant antidiabetic activity which was comparable to the activity of the standard antihyperglycemic agent Metformin (MET). DPLME also offered significant hepatoprotection to PCM-intoxicated rats at levels commensurable to the standard hepatoprotective drug Silymarin (SIL).

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Galega officinalis (galega, Goat's Rue, French Lilac) is well known for its hypoglycaemic action and has been used as part of a plant mixture in the treatment of diabetes mellitus. During pharmacological investigations of an ethanolic extract of a powdered mixture of equal proportions of G. officinalis, Cressa cretica, Mangifera indica and Syzygium jambolanum, a weight reducing effect of galega was discovered. In this study we have investigated the novel weight reducing effect of galega in mice. Galega herb (10% w/w in the diet) caused a significant reduction in body weight in both normal and genetically obese (ob/ob) animals treated for 28 days when compared with respective controls (P < 0.01). In normal mice, the weight loss was reversible and initially associated with a transient reduction in food intake but was then maintained even in the presence of increased eating above the control level. Pair-fed normal mice receiving galega for seven days also showed significant weight loss (P < 0.01, compared with the control) in the presence of increasing food intake. In sharp contrast, weight loss in galega-treated ob/ob mice was accompanied by a persistent reduction in food intake over the 28-day treatment period. Post-mortem examinations of all galega-treated mice revealed a striking absence of body fat. Serum glucose was significantly reduced in both strains of mice receiving galega for 28 days (P < 0.01), whereas serum insulin was significantly reduced only in obese mice (P < 0.01). In summary, together with its established hypoglycaemic effects, galega has a novel weight reducing action that, in normal mice, is largely independent of a reduction in food intake. The mechanism of the weight reducing action of galega is unclear but involves loss of body fat.

BackgroundSevere acute malnutrition (SAM) is associated with high levels of gamma Proteobacteria chronic gut inflammation and poor gut health. In this study, we aimed to assess the effects of probiotic and/or prebiotic supplementation on gut inflammation and fecal pH in young infants with SAM.MethodsThis study was a single-blind RCT where infants aged between 2 and 6 months were randomized to receive either: probiotic (B. infantis EVC001), synbiotic (prebiotic, Lacto-N-neotetraose [LNnT] plus probiotic [B. infantis EVC001]), or placebo (Lactose) for 28 days followed by 28 days of post-supplementation follow up. Stool samples were collected at baseline and at day 10, day 28 and day 56. Fecal myeloperoxidase (MPO), as an indicator of gut inflammation and fecal pH were measured and the change in the levels of these biochemical parameters between the sample collection time points were calculated and denoted as ∆MPO and ∆pH. Kruskal-Wallis test was done to assess the effect of the supplementations on ∆MPO and ∆pH. Multivariate quantile regression analysis was performed to analyze the association of the supplements with ∆MPO and ∆pH.ResultsIn comparison to the placebo group at day 10, a significant decrease in ∆MPO was found for the probiotic group (β-coefficient: -18.44; 95% CI: -31.62 µg/ml, -52.47 µg/ml; p = 0.007) and for the synbiotic group (β-coefficient: -17.24; 95% CI: -30.94 µg/ml, -35.36 µg/ml; p = 0.015). This reduction in ∆MPO in comparison to the placebo group was sustained only in the synbiotic group at other time points. Decrease in ∆pH was observed only in the synbiotic group at day 10 and day 28, but not at day 56 in comparison to the placebo group.ConclusionOur findings demonstrate that the use of this synbiotic supplementation may result in sustained effects in reduction of gut inflammation in young infants with SAM. However, further studies are required to fully evaluate the role of this synbiotic intervention for sustained reduction in fecal pH in this study population.Trial registrationThe trial is registered at ClinicalTrials.gov (NCT0366657). Registered on 12 September, 2018 (https://clinicaltrials.gov/ct2/show/NCT03666572)