Antidiabetic Property of Symplocos cochinchinensis Is Mediated by Inhibition of Alpha Glucosidase and Enhanced Insulin Sensitivity

The study is designed to find out the biochemical basis of antidiabetic property of Symplocos cochinchinensis (SC), the main ingredient of ‘Nisakathakadi’ an Ayurvedic decoction for diabetes. Since diabetes is a multifactorial disease, ethanolic extract of the bark (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90% ethanol) were evaluated by in vitro methods against multiple targets relevant to diabetes such as the alpha glucosidase inhibition, glucose uptake, adipogenic potential, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPP-IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition (IC₅₀ value-82.07±2.10 µg/mL), insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F (3.5 fold increase) and reduced triglyceride accumulation (22% decrease) in 3T3L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells (59.57% decrease) with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence and quantity of bioactives (beta-sitosterol, phloretin 2′glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. We conclude that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with moderate antiglycation and antioxidant activity.     

Effect of Gymnema montanum Leaves on Serum and Tissue Lipids in Alloxan Diabetic Rats

The effect of Gymnema montanum leaves on alloxaninduced hyperlipidemia was studied in male Wistar rats. Ethanolic extract of G. montanum leaves was administered orally and different doses of the extract on blood glucose, serum and tissue lipids, hexokinase, glucose-6-phosphatase, thiobarbituric acid–reactive substances (TBARS), hydroperoxides, and glutathione in alloxan-induced diabetic rats were studied. G. montanum leaf extract (GLEt) at doses of 50, 100, 200 mg/kg body weight for 3 weeks suppressed the elevated blood glucose and lipid levels in diabetic rats. GLEt at 200 mg/kg body weight was found to be comparable to glibenclamide, a reference drug. These data indicate that G. montanum represents an effective antihyperglycemic and antihyperlipidemic adjunct for the treatment of diabetes and a potential source of discovery of new orally active agent for future therapy.     

Effect of <Emphasis Type="Italic">Gymnema montanum</Emphasis> leaves on red blood cell resistance to oxidative stress in experimental diabetes

The aim of the present study was to evaluate the protective effect of Gymnema montanum on red blood cell (RBC) membrane in diabetic rats during lipid peroxidation. Ethanol extract of G. montanum leaves (GLEt) was administered orally to alloxan-induced diabetic rats for 3 weeks, and the effects on blood glucose, insulin, lipid peroxidation markers, thiobarbituric acid reactive substances, hydroperoxides in plasma and antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase activities in erythrocytes were studied. Administration of GLEt to diabetic animals at doses of 50, 100, and 200 mg/kg body weight lowered elevated blood glucose levels by 24, 35, and 66%, respectively, relative to untreated diabetic rats. In comparison, treatment with the known antidiabetic drug, glibenclamide (600 μg/kg body weight) decreased blood glucose concentrations by 51%. Plasma insulin concentrations were increased in the diabetic rat by 73% with GLEt (200 mg/kg body weight) and 45% with glibenclamide (600 μg/kg body weight). Although a significant decrease in the lipid peroxidation markers was observed in plasma on treatment with GLEt and glibenclamide, the RBC antioxidant levels were increased significantly in diabetic rats. Furthermore, erythrocytes from the GLEt-treated animals were found to be more resistant to H₂O₂-induced peroxidation than that of untreated diabetic animals. The chemical characterization of the polyphenolics of the extract showed the presence of gallic acid (5.29% w/w), resveratrol (2.2% w/w), and quercetin (16.6% w/w). The results of this study suggest that G. montanum may be useful for the control, management, and prevention of oxidative stress associated with diabetes.     

Identification of Novel Human Dipeptidyl Peptidase-IV Inhibitors of Natural Origin (Part II): In Silico Prediction in Antidiabetic Extracts

Background

Natural extracts play an important role in traditional medicines for the treatment of diabetes mellitus and are also an essential resource for new drug discovery. Dipeptidyl peptidase IV (DPP-IV) inhibitors are potential candidates for the treatment of type 2 diabetes mellitus, and the effectiveness of certain antidiabetic extracts of natural origin could be, at least partially, explained by the inhibition of DPP-IV.

Methodology/Principal Findings

Using an initial set of 29,779 natural products that are annotated with their natural source and an experimentally validated virtual screening procedure previously developed in our lab (Guasch et al.; 2012) [1], we have predicted 12 potential DPP-IV inhibitors from 12 different plant extracts that are known to have antidiabetic activity. Seven of these molecules are identical or similar to molecules with described antidiabetic activity (although their role as DPP-IV inhibitors has not been suggested as an explanation for their bioactivity). Therefore, it is plausible that these 12 molecules could be responsible, at least in part, for the antidiabetic activity of these extracts through their inhibitory effect on DPP-IV. In addition, we also identified as potential DPP-IV inhibitors 6 molecules from 6 different plants with no described antidiabetic activity but that share the same genus as plants with known antidiabetic properties. Moreover, none of the 18 molecules that we predicted as DPP-IV inhibitors exhibits chemical similarity with a group of 2,342 known DPP-IV inhibitors.

Conclusions/Significance

Our study identified 18 potential DPP-IV inhibitors in 18 different plant extracts (12 of these plants have known antidiabetic properties, whereas, for the remaining 6, antidiabetic activity has been reported for other plant species from the same genus). Moreover, none of the 18 molecules exhibits chemical similarity with a large group of known DPP-IV inhibitors.     

Antidiabetic properties of aqueous and methanol extracts from the trunk bark of Ceiba pentandra in type 2 diabetic rat

The type 2 diabetes is one of the major global health issues that affects millions of people. This study evaluated the antidiabetic activity of aqueous extracts (AECP) and methanol extracts (MECP) from Ceiba pentandra trunk bark on an experimental model of type 2 diabetes (T2D). This model was induced in rats by the combination of a high-fat diet (HFD) and a single dose of streptozotocin (40 mg/kg, intraperitoneal) at the seventh day of experimentation. Diabetes was confirmed on day 10 by fasting blood glucose more than or equal to 200 mg/dL. Diabetic animals still under HFD were treated orally and twice daily, with MECP and AECP (75 and 150 mg/kg) or metformin (40 mg/kg) for 14 days. During the experiment, blood glucose and animal weights were determined. Oral glucose tolerance test was performed on day 15, followed by animals sacrifice for blood, liver, and pancreas collection. Total cholesterol and triglyceride levels were evaluated in plasma, whereas malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, and catalase were quantified in tissue homogenates. AECP and MECP significantly reduced the hyperglycemia by up to 62% and significantly improved the oral glucose tolerance test. The impaired levels of cholesterol and triglycerides registered in diabetic control were significantly reversed by both extracts at all the doses used. Alterations in diabetic pancreas weight, GSH, and MDA were also significantly reversed by plant extracts. AECP and MECP possess type 2 antidiabetic effects that could result from their ability to improve the peripheral use of glucose, lipid metabolism or from their capacity to reduce oxidative stress. These finding provide a new avenue for better control and management of early or advanced T2D.     

Antidiabetic,Antihyperlipidemic and Antioxidant Activities of a Novel Proteoglycan from Ganoderma Lucidum Fruiting Bodies on db/db Mice and the Possible Mechanism

Previously, we screened a proteoglycan for anti-hyperglycemic, named FYGL, from Ganoderma Lucidum. For further research of the antidiabetic mechanisms of FYGL in vivo, the glucose homeostasis, activities of insulin-sensitive enzymes, glucose transporter expression and pancreatic function were analyzed using db/db mice as diabetic models in the present work. FYGL not only lead to a reduction in glycated hemoglobin level, but also an increase in insulin and C-peptide level, whereas a decrease in glucagons level and showed a potential for the remediation of pancreatic islets. FYGL also increased the glucokinase activities, and simultaneously lowered the phosphoenol pyruvate carboxykinase activities, accompanied by a reduction in the expression of hepatic glucose transporter protein 2, while the expression of adipose and skeletal glucose transporter protein 4 was increased. Moreover, the antioxidant enzyme activities were also increased by FYGL treatment. Thus, FYGL was an effective antidiabetic agent by enhancing insulin secretion and decreasing hepatic glucose output along with increase of adipose and skeletal muscle glucose disposal in the late stage of diabetes. Furthermore, FYGL is beneficial against oxidative stress, thereby being helpful in preventing the diabetic complications.     

Antidiabetic potential of gallic acid from Emblica officinalis: Improved glucose transporters and insulin sensitivity through PPAR-γ and Akt signaling

BackgroundNature has gifted a variety of vital phytochemicals having potential therapeutic application against various ailments. Emblica officinalis (E. officinalis), an ancient plant, has long been used as a remedy for diabetes and cardiovascular complications, and presence of abundant amount of gallic acid could be accountable for its medicinal potential.PurposeThe study was aimed to determine the in-vivo and in-vitro anti-diabetic potential of gallic acid and fruit juice of E. officinalis. Molecular mechanism of gallic acid as well as fruit juice of E. officinalis for anti-diabetic potential has also been revealed.Experimental study designAnti-diabetic potential of E. officinalis and gallic acid was evaluated in 3T3-L1 preadipocytes and various animal models like db/db mice and fructose administered rats. PPAR-γ expression and glucose translocation were observed using western blot and PCR techniques.ResultsTreatment of E. officinalis fruit juice and gallic acid facilitated their glucose homeostasis; improved insulin sensitivity; reduced obesity; abridged elevated blood pressure and declined cholesterol level, and also induced adipogenesis in 3T3-L1 adipocytes. Mechanistically, treatment increased expression of PPAR-γ through activation of C/EBPs and simultaneously increased Glut4 translocation in 3T3-L1 adipocytes. Moreover, gallic acid treatment increased insulin sensitivity through activation of Akt rather than AMPK signaling pathway while fruit juice of E. officinalis showed dual activation, Akt and AMPK as well.ConclusionThese findings reveal the role of gallic acid in E. officinalis mediated antidiabetic potential, and delineate the upregulation of pAkt, PPAR-γ and Glut4 in gallic acid mediated antidiabetic activity, thus providing potential therapy for diabetes and related disorders.     

A novel Steroid from Elephantopus scaber L. an Ethnomedicinal plant with antidiabetic activity

Acetone extract of Elephantopus scaber, an ethnomedicnal plant, reduced the blood glucose levels in streptozotocin-induced diabetic rats significantly. Acute toxicity studies revealed the non-toxic nature of the crude extract. Fractionation of the acetone extract yielded a new steroid, 28Nor-22(R)Witha 2,6,23-trienolide. Biological testing of the compound demonstrated a significant antidiabetic activity by reducing the elevated blood glucose levels and restoring the insulin levels in streptozotocin-induced diabetic rats. This compound can be a useful candidate to treat diabetes.     

Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation, insulin resistance, and body weight in developing obese Zucker rats

Super CitriMax (HCA-SX) is a novel calcium/potassium salt of (−)-hydroxycitric acid extracted from the dried fruit rind of the plant Garcinia cambogia, and commonly consumed as weight loss dietary supplement. In the present study, we investigated the effect of HCA-SX on inflammation, oxidative stress and insulin resistance in developing obese Zucker rats, an animal model of type II diabetes associated with inflammation and oxidative stress. Male Zucker rats (5-week old) were supplemented with vehicle (control) and HCA-SX in drinking water for 7 weeks. Oxidative stress markers, including malondialdehyde (MDA), protein carbonyl (DNPH), and protein tyrosine nitration (tyr-NO₂) were measured in the liver and kidney tissues using biochemical and immunoblotting techniques. Compared to controls, the levels of MDA, DNPH and tyr-NO₂ were lower in the liver and kidney of HCA-SX-treated animals. Furthermore, the levels of C-reactive protein and interleukin-6, markers of inflammation measured by ELISA, were lower in the plasma of HCA-SX-supplemented animals compared to controls, as were levels of fasting plasma insulin, glucose, and triglycerides. Interestingly, insulin resistance did not develop in HCA-SX-supplemented rats. Food-intake and body weight gain was also lower in rats supplemented with HCA-SX compared to their control counterparts. These results suggest that HCA-SX supplementation in obese Zucker rats reduces food-intake, body weight gain, and also attenuates the increases in inflammation, oxidative stress, and insulin resistance observed in untreated animals. Therefore, HCA-SX may be used as an intervention to overcome obesity-related complications, including inflammation, oxidative stress, and insulin resistance.     

Antioxidative effects of extracts from Trifolium species on blood platelets exposed to oxidative stress

Clovers (Trifolium) may possess a significant therapeutic potential, but the effects of compounds from these plants on blood platelets and haemostasis have been poorly recognized. The present study was designed to evaluate the antioxidative action of extracts from three species of clovers: Trifolium pratense, Trifolium pallidum and Trifolium scabrum in the protection of human blood platelets in vitro. Platelet suspensions were pre-incubated with crude extract and phenolic fraction of T. pratense or phenolic fractions of T. scabrum and T. pallidum, at the final concentrations of 0.5–50 μg/ml. Then, for the induction of oxidative stress, 100 μM peroxynitrite was added. The antioxidative activity of plant extracts was assessed by measurements of the level of 3-nitrotyrosine, thiol groups and lipid peroxidation products (hydroperoxides and thiobarbituric acid-reactive substances). Despite the significant differences in the composition of the investigated extracts, we observed antioxidative effects of all used mixtures. The presence of Trifolium extracts considerably reduced the peroxynitrite-mediated modifications of proteins and diminished peroxidation of lipids in platelets. Our results indicate on a strong antioxidative activity of the tested extracts-statistically significant effects were found even for the lowest concentrations (0.5 μg/ml) of all extracts. This action may be useful in the protection of blood components, very susceptible to oxidative modifications. The obtained results suggest that the examined clovers are a promising source of compounds, valuable for the protection against oxidative stress-induced damage to blood platelets.     

Metabolic and molecular action of <Emphasis Type="Italic">Trigonella foenum-graecum</Emphasis> (fenugreek) and trace metals in experimental diabetic tissues

Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycaemia resulting in defective insulin secretion, resistance to insulin action or both. The use of biguanides, sulphonylurea and other drugs are valuable in the treatment of diabetes mellitus; their use, however, is restricted by their limited action, pharmaco-kinetic properties, secondary failure rates and side effects. Trigonella foenum-graecum, commonly known as fenugreek, is a plant that has been extensively used as a source of antidiabetic compounds from its seeds and leaf extracts. Preliminary human trials and animal experiments suggest possible hypoglycaemic and anti-hyperlipedemic properties of fenugreek seed powder taken orally. Our results show that the action of fenugreek in lowering blood glucose levels is almost comparable to the effect of insulin. Combination with trace metal showed that vanadium had additive effects and manganese had additive effects with insulin on in vitro system in control and diabetic animals of young and old ages using adipose tissue. The Trigonella and vanadium effects were studied in a number of tissues including liver, kidney, brain peripheral nerve, heart, red blood cells and skeletal muscle. Addition of Trigonella to vanadium significantly removed the toxicity of vanadium when used to reduce blood glucose levels. Administration of the various combinations of the antidiabetic compounds to diabetic animals was found to reverse most of the diabetic effects studied at physiological, biochemical, histochemical and molecular levels. Results of the key enzymes of metabolic pathways have been summarized together with glucose transporter, Glut-4 and insulin levels. Our findings illustrate and elucidate the antidiabetic/insulin mimetic effects of Trigonella, manganese and vanadium.     

Comparative study of genotoxicity and antimutagenicity of methanolic extracts from Teucrium chamaedrys and Teucrium montanum in human lymphocytes using micronucleus assay

Since Teucrium chamaedrys and Teucrium montanum are the most popular plants used in the treatment of many diseases, we evaluated genotoxic potential of their methanolic extracts on cultured human peripheral blood lymphocytes (PBLs) using cytokinesis-block micronucleus (MN) assay. Cultures were treated with four concentrations of both plants (125, 250, 500 and 1,000 μg/ml), both separately and in combination with mitomycin C (MMC). The results revealed that extract of T. chamaedrys administered at the tested concentrations did not significantly affect the mean MN frequency in comparison to untreated cells. Methanolic extract of T. montanum increased the mean MN frequency in PBL at the tested concentrations, but significantly only at the concentration of 1,000 μg/ml. In all tested concentrations, the extract of T. chamaedrys significantly reduced the MMC-induced MN frequency, in a dose dependent manner (r = − 0.687, p < 0.01). The extract of T. montanum decreased the MMC-induced MN frequency at the tested concentrations, but statistically only at 125 μg/ml. Both extracts administered alone did not significantly affect the nuclear division index (NDI) at the tested concentrations. In the combined treatments with MMC, the extract obtained from T. chamaedrys in the concentrations of 500 and 1,000 μg/ml significantly decreased NDI values in comparison to MMC-treated cells alone, while the extract of T. montanum significantly decreased NDI at all tested concentrations. Both extracts nonsignificantly decreased NDI at all tested concentrations in comparison to untreated cells. Our results suggest the important function of T. chamaedrys extract in cancer therapy, this methanolic extract may prevent genotoxic effects of chemotherapy in PBLs.     

In vivo and in vitro application of black soybean peptides in the amelioration of endoplasmic reticulum stress and improvement of insulin resistance

AimsHepatic endoplasmic reticulum (ER) stress plays a key role in the development of obesity-induced insulin resistance. This study evaluated the effects of peptides from black soybean (BSP) on ER stress and insulin signaling in vitro and in vivo.Main methodsUsing C2C12 myotubes or HepG2 cells, we evaluated the effects of BSP on the expression of proteins involved in insulin signaling and in the ER stress response in insulin-sensitive or insulin-resistant cells. BSP was given orally to db/db mice for 5 weeks to investigate its antidiabetic effects in vivo and the underlying mechanisms.Key findingsBSP increased GLUT4 translocation and glucose transport in myotubes and stimulated Akt-mediated glycogen synthase kinase-3β (GSK-3β) and Foxo1 phosphorylation in HepG2 cells. BSP significantly restored the suppression of insulin-mediated Akt phosphorylation in insulin-resistant cells. BSP significantly inhibited the activation of ER stress-responsive proteins by thapsigargin. BSP also significantly reduced blood glucose and improved glucose tolerance in db/db mice. The serum lipid profile (triglyceride and high-density lipoprotein concentrations) improved concomitantly with the BSP-induced downregulation of hepatic fatty acid synthase expression in db/db mice. Consistent with the results observed in HepG2 cells, BSP downregulated the elevated hepatic ER stress response in diabetic mice concomitantly with an increased expression of phospho-Foxo1.SignificanceA peptide mixture, BSP, showed beneficial effects through multiple mechanisms involving the suppression of hepatic ER stress and restoration of insulin resistance, suggesting that it has potential as an antidiabetic agent.     

Novel Approach to Identify Potential Bioactive Plant Metabolites: Pharmacological and Metabolomics Analyses of Ethanol and Hot Water Extracts of Several Canadian Medicinal Plants of the Cree of Eeyou Istchee

We evaluated and compared the antidiabetic potential and molecular mechanisms of 17 Cree plants’ ethanol extracts (EE) and hot water extracts (HWE) on glucose homeostasis in vitro and used metabolomics to seek links with the content of specific phytochemicals. Several EE of medical plants stimulated muscle glucose uptake and inhibited hepatic G6Pase activity. Some HWE partially or completely lost these antidiabetic activities in comparison to EE. Only R. groenlandicum retained similar potential between EE and HWE in both assays. In C2C12 muscle cells, EE of R. groenlandicum, A. incana and S. purpurea stimulated glucose uptake by activating AMP-activated protein kinase (AMPK) pathway and increasing glucose transporter type 4 (GLUT4) expression. In comparison to EE, HWE of R. groenlandicum exhibited similar activities; HWE of A. incana completely lost its effect on all parameters; interestingly, HWE of S. purpurea activated insulin pathway instead of AMPK pathway to increase glucose uptake. In the liver, for a subset of 5 plants, HWE and EE activated AMPK pathway whereas the EE and HWE of S. purpurea and K. angustifolia also activated insulin pathways. Quercetin-3-O-galactoside and quercetin 3-O-α-L-arabinopyranoside, were successfully identified by discriminant analysis as biomarkers of HWE plant extracts that stimulate glucose uptake in vitro. More importantly, the latter compound was not identified by previous bioassay-guided fractionation.     

Molecular Structure-Based Screening of the Constituents of Calotropis procera Identifies Potential Inhibitors of Diabetes Mellitus Target Alpha Glucosidase

Diabetes mellitus is a disorder characterized by higher levels of blood glucose due to impaired insulin mechanisms. Alpha glucosidase is a critical drug target implicated in the mechanisms of diabetes mellitus and its inhibition controls hyperglycemia. Since the existing standard synthetic drugs have therapeutic limitations, it is imperative to identify new potent inhibitors of natural product origin which may slow carbohydrate digestion and absorption via alpha glucosidase. Since plant extracts from Calotropis procera have been extensively used in the treatment of diabetes mellitus, the present study used molecular docking and dynamics simulation techniques to screen its constituents against the receptor alpha glucosidase. Taraxasterol, syriogenin, isorhamnetin-3-O-robinobioside and calotoxin were identified as potential novel lead compounds with plausible binding energies of −40.2, −35.1, −34.3 and −34.3 kJ/mol against alpha glucosidase, respectively. The residues Trp⁴⁸¹, Asp⁵¹⁸, Leu⁶⁷⁷, Leu⁶⁷⁸ and Leu⁶⁸⁰ were identified as critical for binding and the compounds were predicted as alpha glucosidase inhibitors. Structurally similar compounds with Tanimoto coefficients greater than 0.7 were reported experimentally to be inhibitors of alpha glucosidase or antidiabetic. The structures of the molecules may serve as templates for the design of novel inhibitors and warrant in vitro assaying to corroborate their antidiabetic potential.     

Composition and antioxidant activity of aqueous and ethanolic Pelargonium radula extracts

Pelargonium radula (Cav.) L'Hér is a plant with hypoglycaemic properties originating from South Africa. Since oxidative stress plays a major role in the development of diabetic complications, the aim of this study was to evaluate if P. radula, besides its glucose-lowering properties, can have additional beneficial effects on diabetes. For preparation of extracts fresh or dried leaves were extracted at 20 °C with either ethanol or water. Since P. radula is commercially cultivated for its essential oil, the residues obtained after steam distillation of essential oil from dry or fresh leaves were also included in the investigation. Content of phenols (total phenols, flavonoids and tannins) was determined in the extracts. Antioxidant activity was established as radical scavenging and chelating activity, reducing power and activity in β-carotene-linoleic acid assay. To establish possible intracellular effects of the extracts, lactate dehydrogenase (LDH) leakage was determined in Hep G2 cells with glucose induced oxidative stress. All the extracts were found to possess antioxidant activities and were able to reduce LDH leakage from Hep G2 cells. In addition to having excellent extraction yields the residues obtained after steam distillation of essential oil showed the most pronounced antioxidant activity in our study. The results of the present study suggest that P. radula leaf might be useful as complementary therapy in diabetes.     

Peroxisome proliferator-activated receptor gamma is essential for stress adaptation by maintaining lipid homeostasis in female fish

Reduction of lipid synthesis often causes free fatty acid (FFA) overload, resulting consequential oxidative stress and health damage. Environmental stresses also induce cellular oxidative stress in organisms. The functional peroxisome proliferator-activated receptor gamma (pparg) gene is essential for lipid synthesis and homeostatic lipid maintenance. However, the relationship between the pparg-mediated lipid synthesis and environmental stress adaptation awaits full elucidation. Here, we generated a pparg-knockout zebrafish model. The conversion of free fatty acids into triglycerides in the female pparg mutants was hampered by reduced esterification efficiency, thus induced lipotoxicity, as evidenced by high oxidative stress and damaged health in these mutants, which led to reduced resistance to cold, heat and ammonia nitrogen stresses. Activating pparg in the wild-type female fish via dietary supplementation with rosiglitazone (a pparg agonist), or reducing oxidative stress in the female pparg mutants via dietary supplementation with N-acetylcysteine (an antioxidant), or promoting mitochondrial fatty acid β-oxidation in the female pparg mutants via dietary supplementation with l-carnitine, resulted in significantly reduced cellular injury, and improved environmental stress resistance. Collectively, our findings reveal that the regulative function of pparg in FFA esterification is important in stress resistance in female fish, and highlight the tight correlation existing between lipotoxicity and environmental adaptation.     

Modulation of flavonoid and tannin production of Carpobrotus rossii by environmental conditions

Dietary supplementation with plant-derived polyphenolic compounds such as the flavonoids epigallocatechin-3-gallate (EGCG), quercetin and resveratrol can result in a beneficial effect on degenerative disease processes through both radical scavenging and activation of cellular ion channels. Preliminary investigations have shown that extracts from the halophyte species Carpobrotus rossii have high in vitro antioxidant and in vivo low-density-lipoprotein-lowering activities. In this study, we have investigated the environmental conditions responsible for inducing flavonoid production in C. rossii in an attempt to maximise production of these compounds. Both field surveys and controlled glasshouse experiments were conducted. Flavonoid production appears to be related to conditions known to cause oxidative stress in plants such as exposure to excessive light, reduced water availability, and low soil potassium levels. Flavonoid production was minimal under salinity levels optimal for C. rossi growth (around 50 mM NaCl) and increased dramatically at sub- and supra-optimal salinities. Flavonoids were clearly concentrated in metabolically active palisade mesophyll tissue rather than the spongy parenchyma. Non-optimal (outside 50–100 mM range) NaCl levels significantly increased flavonoid concentration on a per leaf basis. However, the reduction in biomass production at sub and supra optimal salinities diminished absolute flavonoid production per plant. As a result, saline conditions favouring optimal plant growth appear to be most suitable for maximising production of flavonoids in C. rossii.