1H NMR-based metabolic study reveals the improvements of bitter melon (Momordica charantia) on energy metabolism in diet-induced obese mouse

Context: Obesity can be ameliorated by some natural products such as polyphenol, flavones and saponin. As a typical medicinal plant, Momordica charantia L. (Cucurbitaceae) (bitter melon, BM) contains these natural chemicals and reduces diet-induced obesity in mice.

Objective: This study evaluates the metabolic effects of dietary BM supplement, investigates a global metabolic profile and determines associated perturbations in metabolic pathways.

Materials and methods: Male C57BL/6 mice were fed with low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with 5% BM based on 37.6?g/kg body weight in average for 12 weeks, respectively. Then energy metabolism was quantified using PhenoMaster/LabMaster. The spectroscopy of urine was acquired by nuclear magnetic resonance and latent biomarkers were identified. Pattern recognition analysis was used to discriminate associated metabolic profiles.

Results: Dietary BM supplement reduced body weight gain (?0.15-fold, p?<?0.01) and blood glucose levels (?0.19-fold, p?<?0.01) in HFD-fed mice. Meanwhile, the levels of energy metabolism were enhanced (0.08–0.11-fold, p?<?0.01). According to pattern recognition analysis, dietary BM supplement changed metabolic profiles in HFD-fed mice and the modified profiles were similar to those in LFD-fed mice. Finally, the mapping of metabolic pathways showed that dietary BM supplement primarily affected glucose metabolism-associated pathways.

Discussion and conclusion: The results indicated that BM improves weight loss in diet-induced obesity and elevate energy expenditure in HFD-fed mice. The pattern recognition with metabolic study may be used as a noninvasive detection method to assess the effects of dietary BM supplement on mouse energy metabolism.     

Hypolipidemic and antioxidant effects of ethanol extract of Cassia fistula fruit in hyperlipidemic mice

Context: The plant Cassia fistula L. (Caesalpiniaceae) fruit was widely used by traditional practitioners to treat cardiovascular diseases (CVDs) in India. Hyperlipidemia is a lipid metabolism disorder and the major risk factor for the development of CVDs. Although most of the current hypolipidemic drugs are expensive and have potential side effects, the research focusing on natural alternative medicines is relevant.

Objective: To investigate the hypolipidemic and antioxidant effects of ethanol extract of C. fistula fruit (CFE) in high-fat diet (HFD) induced hyperlipidemia in mice.

Materials and methods: Oral administration of CFE at 100, 300 and 500?mg/kg body weight on HFD induced hyperlipidemia mice for 30 days. The standard drug atorvastatin (20?mg/kg) was used to compare the efficacy of CFE. Hypolipidemic effect was evidenced by the measurement of serum lipid profile and further confirmed by Oil Red O staining of adipose tissue. The hepatic and cardiac melondialdehyde (MDA) level and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase were determined.

Results: Treatment with CFE at different doses has significantly restored the levels of serum lipid, MDA and enzymes activities in the liver and heart of hyperlipidemia mice. Oil Red O staining of visceral adipose tissue has shown marked reduction of lipid accumulation in adipocytes; whereas, administration of CFE at 500?mg/kg showed remarkable (p?<?0.001) hypolipidemic and antioxidant effects in HFD fed mice.

Conclusion: C. fistula fruit demonstrated hypolipidemic and antioxidant properties in vivo and the results corroborate the use of this plant in traditional medicine for cardiac ailments.     

Effects of the hydroalcoholic extract of Rosa damascena on learning and memory in male rats consuming a high-fat diet

Context: High-fat diet (HFD) can cause deficits in learning and memory through oxidative stress and increase Alzheimer disease risk. Rosa damascena Mill. (Rosaceae) extract possesses potent antioxidant properties.

Objective: This study investigated the effects of the hydroalcoholic extracts of petals of R. damascena on learning and memory in male rats consuming an HFD.

Materials and methods: Forty male Wistar rats (200–250?g) were randomly assigned to four groups: control, R. damascena extract, HFD and HFD?+?extract. The extract (1?g/kg bw daily) was administered by oral gavage for 1?month. Animals were allowed free access to high-fat chow for 3?months. The Morris water maze and the passive avoidance learning tests were used to assess learning and memory.

Results: In the passive avoidance learning test, the step-through latencies in the retention test (STLr) of the extract (147.4?±?23.3) and HFD (150.3?±?25.2) groups were significantly lower than those of the control group (270.4?±?10.5) (respectively, p?p?p?p?Discussion and conclusion: Our results indicate that, while HFD or R. damascena extract alone leads to memory deficits, R. damascena extract exerted a positive effect on HFD-induced memory deficits. We hypothesize that the observed effects of R. damascena extract are likely due to its strong antioxidant properties.     

Evaluation of the cytotoxic potential of a new pentacyclic triterpene from Rhododendron arboreum stem bark

Context: Traditionally, Rhododendron arboreum Sm. (Ericaceae) is a very important medicinal plant having oxytocic, estrogenic, anti-inflammatory, analgesic and hepatoprotective activities; it also inhibits the prostaglandin synthetase.

Objectives: This study determines the cytotoxic potential of 15-oxoursolic acid isolated from R. arboreum against selected human cancer cell lines.

Materials and methods: Extraction from stem bark (5?kg) of R. arboreum was performed with methanol, which was successively partitioned into hexane, dichloromethane and ethyl acetate fractions, respectively. The new antitumor agent [15-oxoursolic acid (1)] was isolated from ethyl acetate fraction through column chromatography. Structure elucidation of new compound was performed through extensive spectroscopy i.e., IR, MS and 1D and 2D NMR. Cytotoxicity of isolated compound was determined at doses 5–100?μM for a period of 72?h on specified human cancer cell lines [renal cell carcinoma (A498), non-small cell lung (NCI-H226), squamous cell carcinoma (H157) and human ovarian carcinoma (MDR-2780AD)].

Results: Structure of isolated compound was characterized as 15-oxoursolic acid on the basis of various extensive spectroscopic techniques. 15-Oxoursolic acid revealed considerable anticancer activity with IC₅₀ values of 2.3?±?0.1?μM, 4.9?±?0.2?μM, 9.2?±?0.2?μM and 10.3?±?0.1?μM against MDR 2780AD, Hep G2, H157 and NCI-H226, respectively, while in the case of A498, the activity was good (IC₅₀ 32.8?±?1.2?μM).

Conclusions: This study highlighted the potential of 15-oxoursolic acid to be further explored as a new lead compound for cancer chemotherapy.     

Houttuynia cordata alleviates high-fat diet-induced non-alcoholic fatty liver in experimental rats

Abstract

Context: Houttuynia cordata Thunb. (Saururaceae) is used traditionally in Asian countries to treat various disease symptoms.

Objective: To study the effect of H. cordata ethyl acetate (HC-EA) extract on high-fat diet (HFD)-induced hepatic steatosis.

Materials and methods: HFD fed rats were orally dosed with HC-EA (100, 200, or 300?mg/kg) once daily for 8?weeks and the lipid profiles and protein expressions in hepatocytes were evaluated.

Results: HFD rats showed an increase (p?<?0.05) in the plasma lipid levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), free fatty acids (FFAs), and reduced the high-density lipoprotein (HDL) levels. Treatment with HC-EA extract (300?mg/kg) restored the changes in plasma lipid levels of TC, TG, LDL, FFA, and HDL in HFD-fed rats by 34.8, 31.1, 51.4, 32.4, and 56.3%, respectively, compared with control rats (p?<?0.01). HC-EA treatment also decreased the hepatic lipid accumulation (p?<?0.001 at 300?mg/kg) and improved hepatic histological lesions. HC-EA extract enhanced AMPK phosphorylation and its primary downstream targeting enzyme, acetyl-CoA carboxylase (ACC), up-regulated the gene expression of carnitine palmitoyl transferase-1 (CPT-1), and down-regulated sterol regulatory element binding protein 1, fatty acid synthase, and glutamate pyruvate transaminase protein levels in the livers of HFD-fed rats. Further, the increased expression of hepatic cytochrome P450 (CYP) composition such as CYP2E1 and CYP4A was also suppressed.

Discussion and conclusion: Data suggest that HC-EA extract might act by regulating the AMPK-dependent pathway and related mediators and might be used in treating obesity-related liver diseases.     

Crataegus Aronia protects and reverses vascular inflammation in a high fat diet rat model by an antioxidant mechanism and modulating serum levels of oxidized low-density lipoprotein

Context: Crataegus aronia (Willd.) Bosc (Rosaceae) (syn. Azarolus L) is traditionally used to treat cardiovascular disorders.

Objectives: To investigate C. aronia protection against a high-fat diet (HFD)-induced vascular inflammation in rats.

Materials and methods: Wistar Male rats (180–220?g) were divided (n?=?10/group) as control fed a standard diet (STD), STD + C. aronia (200?mg/kg, orally), HFD, HFD + C. aronia and HFD post-treated with C. aronia. Simvastatin (20?mg/kg) was co- or post-administered as a positive control drug. HFD was given for 8?weeks, and all other treatments were administered for 4?weeks.

Results: Most significantly, co-administration of C. aronia to HFD-fed rats reduced the thickness of aorta tunica media (90?±?5 vs. 160?±?11.3?µm) and adventitia (54.3?±?3.8 vs. 93.6?±?9.4?µm). It also lowered protein levels of TNF-α (0.51?±?0.15 and 0.15?±?0.16 vs. 0.1?±?0.09%) and IL-6 (0.52?±?0.19 vs. 1.0?±?0.2%) in their aorta or serum (5.9?±?0.91 vs. 12.98?±?1.3?ng/mL and 78.1?±?6.7 vs. 439?±?78?pg/mL, respectively). It also lowered all serum lipids and increased aorta levels of GSH levels (70.4?±?4.0 vs. 40.7?µM) and activity of SOD (5.7?±?0.7 vs. 2.9?±?0.6?U/mg) and decreased serum levels of ox-LDL-c (566.7?±?46 vs. 1817?±?147?ng/mL). Such effects were more profound than all other treatments.

Conclusions: C. aronia inhibits the HFD-induced vascular inflammation and its use in clinical trials is recommended.     

A novel animal model of metabolic syndrome with non-alcoholic fatty liver disease and skin inflammation

Abstract

Context: Metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) are the emerging co-morbidities of skin inflammation. Occurrence of skin inflammation such as psoriasis is substantially higher in NAFLD patients than normal. Currently, there are no animal models to study the interaction between these co-morbidities.

Objective: The present study seeks to develop a simple mouse model of NAFLD-enhanced skin inflammation and to study the effect of NAFLD on different parameters of skin inflammation.

Materials and method: Metabolic syndrome and NAFLD were induced in C57BL/6 mice by feeding high-fat diet (HFD, 60% kcal) and high fructose liquid (HFL, 40% kcal) in drinking water. Skin inflammation was induced by repeated application of oxazolone (1% sensitization and repeated 0.5% challenge) in both normal and NAFLD mice and various parameters of skin inflammation and NAFLD were measured.

Results: HFD and HFL diet induced obesity, hyperglycemia, hyperinsulinemia, and histological features of NAFLD in mice. Oxazolone challenge significantly increased ear thickness, ear weight, MPO activity, NF-κB activity, and histological features of skin inflammation in NAFLD mice as compared with normal mice. Overall, induction of oxazolone-induced skin inflammation was more prominent in NAFLD mice than normal mice. Hence, HFD and HFL diet followed by topical oxazolone application develops metabolic syndrome, NAFLD, and enhanced skin inflammation in mice.

Discussion and conclusion: This simple model can be utilized to evaluate a therapeutic strategy for the treatment of metabolic syndrome and NAFLD with skin inflammation and also to understand the nexus between these co-morbidities.     

Effects of linalool on inflammation,matrix accumulation and podocyte loss in kidney of streptozotocin-induced diabetic rats

Abstract

Context: This study aimed to evaluate the renoprotective action of linalool (LIN) on streptozotocin (STZ)-induced diabetic rats.

Objective: The pathological changes in diabetic nephropathy (DN) include oxidative stress, renal injury, matrix accumulation and podocyte abnormalities. We investigated the renoprotective actions of LIN, a monoterpene alcohol, present in herbal essential oils in STZ-induced diabetic rats with renal injury.

Materials and methods: STZ-diabetic rats were administered LIN (25?mg/kg) for 45 days, after which the activities of key enzymes of glucose metabolism, collagen content, oxidative damage and expression of glucose transporter-1 (GLUT-1), transforming growth factor-β₁ (TGF-β₁), nuclear factor-κBp65 (NF-κB p65) and nephrin were analyzed.

Results: Diabetic rats displayed altered glucose metabolism, collagen accumulation and increased TGF-β₁ and NF-κB expression in kidney. LIN treatment restored glucose-metabolizing enzymes, collagen content and GLUT-1 expression and also prevented nephrin loss. LIN also rescued kidney from oxidative stress and inflammation by decreasing the expression of TGF-β₁ and NF-κB. Ultrastructural changes such as basement membrane thickening, reduction in podocyte number and loss of filtration barrier integrity in diabetic rats were mitigated by LIN.

Discussion and conclusion: The results of this study suggest that LIN can attenuate nephropathic changes induced in kidney of diabetic rats. These findings highlight the utility of LIN as a potential drug to treat renal damage in diabetic subjects.     

Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice

Context: Silymarin is the main flavonoid extracted from milk thistle, which has been used to treat liver diseases.

Objective: The in vivo effect of silymarin on HFD-induced insulin resistance and fatty liver in mice was studied.

Materials and methods: Male C57BL/6 mice were fed with high-fat diet (HFD) to induce obesity and insulin resistance and treated with 30, 60?mg/kg silymarin for 18 days. Food intake, body weight and the content/histology of epididymal fat and liver tissue were examined; the content of lipids, AST, ALT and inflammatory cytokines in serum were estimated.

Results: Administration of silymarin caused bodyweight loss in diet induced obesity (DIO) mice (HFD group: 47.7?g, 60?mg/kg group: 43.0?g) while the food intake remain unchanged. Silymarin (60?mg/kg) significantly reduced the epididymal fat mass (from 1.75?g to 1.12?g). Elevated plasma lipids (TC 6.1?mM, TG 1.3?mM, LDL 1.2?mM) in DIO mice were all suppressed by silymarin (TC 4.5?mM, TG 0.89?mM, LDL 0.9?mM), as well as insulin (5.1?ng/ml in HFD group to 2.0?ng/ml (60?mg/kg silymarin). Examination of cytokine levels (TNF-α, IL-1β and IL-6) in each group proved that silymarin treatment significantly decreased inflammation in DIO mice. Finally, silymarin effectively protected liver from HFD-induced injury as evidenced by decreasing histological damage and reducing ALT and AST levels, as follows: ALT; 47.4?U/L in HFD group to 28.4?U/L (60?mg/kg silymarin); AST; 150.1?U/L in HFD group to 88.1?U/L (60?mg/kg silymarin) in serum.

Discussion and conclusion: Our results suggested that silymarin-induced alleviation of inflammatory response could be a mechanism responsible for its benefits against liver damage and insulin resistance.     

New approaches to the treatment of nephropathy in diabetes

Introduction: In individuals with diabetes, the presence and severity of kidney disease adversely affects their well-being, significantly contributes to burden of morbidity and increases their risk of a premature death. The efficiency of current management strategies for the treatment of diabetic nephropathy, even in optimal combination, is partial, at best. There remains an unmet need for additional renoprotective interventions in patients with diabetes.

Areas covered: This review presents a comprehensive summary of some of the ‘new contenders’ for the treatment of diabetic nephropathy that have been tested or are being tested in randomised clinical trials in patients with diabetes with a predefined renal endpoint, but are not currently indicated for renoprotective therapy. Many of these drugs have been in clinical use for other indications, or initially developed for other purposes.

Expert opinion: Although substantial progress has been made towards understanding the pathogenesis of diabetic nephropathy, at present there are no new drugs that provide the solutions we want for our patients. Even when used in combination with standard medical care, current data indicate that renal complications are at best only modestly reduced, at the expense of additional pill burden and exposure to off-target effects. Given the ever-growing burden of diabetic kidney disease, there is a substantial opportunity for better and more targeted (‘smarter’) therapeutic interventions in this context.     

Monoterpene phenolic compound thymol prevents high fat diet induced obesity in murine model

Context: Obesity has become a worldwide health problem. Most of the synthetic anti-obesity drugs have failed to manage the obesity due to either ineffectiveness or adverse effect. The research of prominent chemical constituents from herbal for the management of obesity has greatly increased.

Objective: The main objective of the present study was intended to examine the effects of thymol in high-fat diet (HFD)-induced obesity in murine model.

Methods: Male Wistar rats were fed HFD for 6 weeks to induce obesity. Thymol (14?mg/kg) administered orally twice a day to HFD-fed rats for 4 weeks. Alteration in body weight gain, visceral fat-pads weight and serum biochemical markers were assessed.

Results: At the end of study, rats fed with HFD exhibited significantly (p?p?Discussion and conclusions: Thymol prevents HFD-induced obesity in murine model through several mechanisms including attenuation of visceral fat accumulation, lipid lowering action, improvement of insulin and leptin sensitivity and enhanced antioxidant potential.     

Effects of Grifola frondosa non-polar bioactive components on high-fat diet fed and streptozotocin-induced hyperglycemic mice

Abstract

Context: Consumption of medicinal mushrooms for disease prevention and maintaining health has a very long history in Asia. Grifola frondosa (Fr) S.F. Gray (GF) (Meripilaceae) is a medicinal fungus popularly used for enhancing immune systems, lowering blood glucose, and improving spleen, stomach, and nerve functions.

Objective: This study examines the hypoglycemic effects of GF in vitro and in vivo, and analyzes the chemical profiles of its bioactive components.

Materials and methods: In vitro hypoglycemic effects of GF was evaluated enzymatically using α-amylase and α-glucosidase inhibition assays, whereas in vivo study was conducted on high-fat diet fed and streptozotocin (HFD?+?STZ)-induced hyperglycemic mice. GC-MS was used to determine the chemical profiles of bioactive components.

Results: The non-polar fraction of GF exhibited a stronger anti-α-glucosidase activity (IC₅₀: 0.0332?mg/ml) than acarbose, but its anti-α-amylase activity (IC₅₀: 0.671?mg/ml) was weaker. Oral administration of GF at 600?mg/kg (GF600) significantly lowered the blood glucose, HbA1c, average blood glucose, and serum total cholesterol levels in hyperglycemic mice. Although GF was found to contain mainly oleic acid and linoleic acid, their levels in the fungus were low, suggesting that the effects of GF on HFD?+?STZ-induced hyperglycemic mice could be due to factors other than these fatty acids.

Conclusion: These results conclude that GF possesses anti-α-glucosidase activity, and hypoglycemic effect in HFD?+?STZ-induced hyperglycemic mice.     

Lipid metabolism and body composition in Gclm(-/-) mice

In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate–cysteine ligase modifier subunit gene (Gclm(−/−)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(−/−) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(−/−) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(−/−) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(−/−) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(−/−) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(−/−) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(−/−) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis.     

Antihyperlipidemic activity of Ichnocarpus frutescens in triton WR-1339-induced and high-fat diet animals

Context: Ichnocarpus frutescens (L.) R.Br. (Apocynaceae) is used to treat diabetes and hyperlipidemia in folk medicine.

Objective: The crude methanol extract and fractions of I. frutescens were investigated for antihyperlipidemic effect.

Materials and methods: Fresh leaves of I. frutescens were extracted with methanol and fractionated with hexane, benzene, ethyl acetate, acetone, and methanol. The active acetone fraction was subfractionated, which resulted in active fraction 3. The antihyperlipidemic effects of the methanol extract and fractions of I. frutescens were studied in triton WR-1339-induced and high-fat diet (HFD) obese animals. Further, lipid absorption and excretion were studied.

Results and discussion: The methanol extract significantly reduced total cholesterol (TC) by 29.63% and triglyceride (Tg) by 51.10% at 400?mg/kg in triton WR-1339-induced animals and significantly reduced TC (27.81%) and Tg (37.03%) at 400?mg/kg in HFD animals. Fraction 3 showed significant reduction in TC (25.03%) and Tg (58.05%) at 200?mg/kg. Feeding of HFD consisting 3% of fraction 3 increased feces weight and Tg level in mice. Fraction 3, showed significant decrease in plasma Tg level at the second hour, after oral administration of the lipid emulsion to rats.

Conclusion: The observed properties apparently validate the folk medicinal use of this plant in amelioration of hyperlipidemia.     

Effects of Piper nigrum extracts: Restorative perspectives of high-fat diet-induced changes on lipid profile,body composition,and hormones in Sprague–Dawley rats

Abstract

Context: Piper nigrum Linn (Piperaceae) (PnL) is used in traditional medicine to treat gastric ailments, dyslipidemia, diabetes, and hypertension.

Objective: The present study explores the possible protective effects of P. nigrum extracts on high-fat diet-induced obesity in rats.

Materials and methods: High-fat diet-induced obese rats were treated orally with 200?mg/kg bw of different extracts (hexane, ethylacetate, ethanol, and aqueous extracts) of PnL for 42?d. The effects of PnL extracts on body composition, insulin resistance, biochemical parameters, leptin, adiponectin, lipid profile, liver marker enzymes, and antioxidants were studied.

Results and discussion: The HFD control group rats showed a substantial raise in body weight (472.8?±?9.3?g), fat% (20.8?±?0.6%), and fat-free mass (165.9?±?2.4?g) when compared with normal control rats whose body weight, fat%, and fat-free mass were 314.3?±?4.4?g, 6.4?±?1.4%, and 133.8?±?2.2?g, respectively. Oral administration of ethyl acetate or aqueous extracts of PnL markedly reduced the body weight, fat%, and fat-free mass of HFD-fed rats. In contrast to the normal control group, a profound increase in plasma glucose, insulin resistance, lipid profile, leptin, thiobarbituric acid reactive substance (TBARS), and the activities of lipase and liver marker enzymes, and a decrease in adiponectin and antioxidant enzymes were noted in HFD control rats. Administration of PnL extracts to HFD-induced obese rats significantly (p?<?0.05) restored the above profiles.

Conclusion: PnL extracts significantly reduced the body weight, fat%, and ameliorated HFD-induced hyperlipidemia and its constituents.     

Flavonoid-enriched extract from Hippophae rhamnoides seed reduces high fat diet induced obesity,hypertriglyceridemia, and hepatic triglyceride accumulation in C57BL/6 mice

Context: Flavonoid-enriched extract from Hippophae rhamnoides L. (Elaeagnaceae) seed (FSH) has shown beneficial effects in anti-hypertension and lowering cholesterol level. However, evidence for its efficacy in treating obesity is limited.

Objective: We sought to determine if FSH can reduce body weight and regulate lipid metabolism disorder in high fat diet (HFD)-induced obese mouse model, and to investigate potential molecular targets involved.

Materials and methods: C57BL/6 mice were fed with HFD for 8 weeks to induce obesity. The modeled mice were divided into four groups and treated with vehicle, rosiglitazone (2?mg/kg), low (100?mg/kg) and high (300?mg/kg) dose of FSH, respectively. Normal control was also used. The treatments were administered orally for 9 weeks. We measured the effect of FSH on regulating body weight, various liver and serum parameters, and molecular targets that are key to lipid metabolism.

Results: FSH administration at 100 and 300?mg/kg significantly reduced body weight gain by 33.06 and 43.51%, respectively. Additionally, triglyceride concentration in serum and liver were decreased by 15.67 and 49.56%, individually, after FSH (300?mg/kg) treatment. Upon FSH (100 and 300?mg/kg) treatment, PPARα mRNA expression was upregulated in liver (1.24- and 1.42-fold) and in adipose tissue (1.66- and 1.72-fold). Furthermore, FSH downregulated PPARγ protein level both in liver and adipose tissue. Moreover, FSH inhibited macrophage infiltration into adipose tissues, and downregulated TNFα mRNA expression in adipose tissue (38.01–47.70%).

Conclusion: This effect was mediated via regulation of PPARγ and PPARα gene expression, and suppression of adipose tissue inflammation.     

Salvianolic acid B attenuates tubulointerstitial fibrosis by inhibiting EZH2 to regulate the PTEN/Akt pathway

ContextSalvianolic acid B (SAB) can alleviate renal fibrosis and improve the renal function.ObjectiveTo investigate the effect of SAB on renal tubulointerstitial fibrosis and explore its underlying mechanisms.Materials and methodsMale C57 mice were subjected to unilateral ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) for renal fibrosis indication. Vehicle or SAB (10 mg/kg/d, i.p.) were given consecutively for 2 weeks in UUO mice while 4 weeks in AAN mice. The serum creatinine (Scr) and blood urine nitrogen (BUN) were measured. Masson’s trichrome staining and the fibrotic markers (FN and α-SMA) were used to evaluate renal fibrosis. NRK-49F cells exposed to 2.5 ng/mL TGF-β were treated with SAB in the presence or absence of 20 μM 3-DZNep, an inhibitor of EZH2. The protein expression of EZH2, H3k27me3 and PTEN/Akt signaling pathway in renal tissue and NRK-49F cells were measured by Western blots.ResultsSAB significantly improved the levels of Scr by 24.3% and BUN by 35.7% in AAN mice. SAB reduced renal interstitial collagen deposition by 34.7% in UUO mice and 72.8% in AAN mice. Both in vivo and in vitro studies demonstrated that SAB suppressed the expression of FN and α-SMA, increased PTEN and decreased the phosphorylation of Akt, which were correlated with the down-regulation of EZH2 and H3k27me3. The inhibition of EZH2 attenuated the anti-fibrotic effects of SAB in NRK-49Fs.ConclusionSAB might have therapeutic potential on renal fibrosis of CKD through inhibiting EZH2, which encourages further clinical trials.     

Cardioprotective potential of a lanosteryl triterpene from Protorhus longifolia

Context: The current rapid increase in the incidence of cardiovascular events indicates a need for the discovery of more effective cardioprotective agents.

Objective: This study evaluated the cardioprotective potential of a lanosteryl triterpene from Protorhus longifolia (Benrh.) Engl. stem bark.

Materials and methods: Spectroscopic data analysis was used to confirm the structure of methyl-3β-hydroxylanosta-9, 24-dien-21-oate (RA-3). The cardioprotective effect of RA-3 in isoproterenol-induced myocardial injury in hyperlipidemic rats was investigated. Rats were divided into the normal diet (ND) fed and high fat diet (HFD) fed groups. The HFD rats were further subdivided into three groups. The experimental group was orally administered with RA-3 (100?mg/kg) for 15 days. The rats were then injected with isoproterenol (85?mg/kg) to induce myocardial injury. At the end of the experiment, hearts and blood tissues were collected and used for histology and biochemical assays, respectively.

Results: RA-3 exhibited a cardioprotective effect as it minimized myocardial injury in HFD rats. Few lesions of acute hyaline degeneration and reduced fat deposition were observed in the heart tissue of the triterpene pretreated rats. Lactate dehydrogenase (LDH) activity was decreased in the blood of the RA-3 pretreated rats (44.1?mU/mL) compared to the untreated group (64.8?mU/mL). Increased glutathione (GSH) content and catalase (CAT) activity along with lower levels of malondialdehyde (MDA) in the triterpene pretreated animals (120.8?nmol/μL) than in the non-treated HFD fed rats (143.6?nmol/μL) were also observed.

Discussion and conclusion: The cardioprotective effect exhibited by RA-3 indicates its potential use in the management of cardiovascular diseases (CVD) and related health problems.     

Which antihypertensive drugs are the most nephroprotective and why?

Importance of the field: Hypertension is a major independent risk factor for kidney disease and for faster renal function loss. Choice of antihypertensive strategies with highest nephroprotective effect is crucial to prevent or reverse progression to end stage renal disease (ESRD).

Areas covered in this review: The present review focuses on the role of hypertension in the progression of chronic kidney disease (CKD), the renoprotective effects of different antihypertensive therapies, and the blood pressure levels that should be targeted in different patient populations. To this end, the PubMed (1975 – 2010) database was searched for English-language articles, using the following keywords: hypertension, kidney disease, ACE-inhibitor, angiotensin receptor blocker, aldosterone antagonist, renin inhibitor, proteinuria.

What the reader will gain: A comprehensive review of data on the association between hypertension and progression of chronic nephropathies and on the antihypertensive treatments with highest nephroprotective effects.

Take home message: Blood pressure should be targeted to 140/90 mmHg or less in patients with hypertension but no renal injury and 130/80 mmHg or less in those with CKD. Amongst different antihypertensive drugs, renin angiotensin aldosterone system (RAAS) inhibitors have an incremental nephroprotective effect in proteinuric patients. Maximal RAAS inhibition should be aimed to optimize renoprotection in hypertensive patients with CKD and proteinuria.     

Hydroxysafflor yellow A suppresses liver fibrosis induced by carbon tetrachloride with high-fat diet by regulating PPAR-γ/p38 MAPK signaling

Context: One approach to protect against liver fibrosis is the use of herb-derived natural compounds, such as hydroxysafflor yellow A (HSYA). The antifibrosis effect of HYSA against liver fibrosis has been investigated; however, its mechanisms have not yet been entirely revealed.

Objectives: To study the protective effects of HSYA on liver fibrosis induced by carbon tetrachloride (CCl₄) and a high-fat diet (HFD), and to determine the mechanism of action of HSYA.

Materials and methods: CCl₄ and HFD were used to mimic liver fibrosis in rats, and serum biochemical indicators were determined. The antifibrosis effects of HSYA were evaluated and its mechanisms were investigated by histopathological analysis, immunohistochemical staining, enzyme-linked immunosorbent assays, real-time-PCR, and western blotting.

Results: HSYA reduced CCl₄- and HFD-mediated liver fibrosis and ameliorated serum biochemical indicator, downregulated the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) (0.31?±?0.03 protein, 0.59?±?0.02 mRNA) and transformin growth factor-β1 (TGF-β1) (0.81?±?0.02 protein, 0.58?±?0.04 mRNA), and upregulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) (1.57?±?0.13 protein, 2.48?±?0.19 mRNA) and matrix metallopeptidases-2 (MMP-2) (2.31?±?0.16 protein, 2.79?±?0.22 mRNA) (p?Discussion and conclusion: These data demonstrate a novel role for HSYA in inhibiting CCl₄- and HFD-mediated liver fibrosis, and reveal that PPAR-γ and p38 MAPK signaling play pivotal roles in the prevention of liver fibrosis induced by CCl₄ and HFD.