Chiung-Huei Peng

Mulberry Water Extracts Possess an Anti-obesity Effect and Ability To Inhibit Hepatic Lipogenesis and Promote Lipolysis

Obesity plays a critical role in dyslipidemia and related disorders. Mulberry water extracts (MWEs) contain polyphenols, including gallic acid, chlorogenic acid, rutin, and anthocyanins. In this study, using 6-week-old male hamsters, we investigated the anti-obese effect of MWEs. After 12 weeks of treatment, MWEs lowered high-fat diet (HFD)-induced body weight and visceral fat, accompanied with hypolipidemic effects by reducing serum triacylglycerol, cholesterol, free fatty acid, and the low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio (n=8 for each group). MWEs decreased hepatic lipids, thus protected livers from impairment. The hepatic peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1 were elevated, while fatty acid synthase and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase were reduced by MWEs, indicating that MWEs regulated lipogenesis and lipolysis, which exerted the anti-obese and hypolipidemic effects. Noticeably, MWEs showed both efficacy and safety in vivo. In concluson, MWEs can be used to reduce body weight, serum, and liver lipids.

Supercritical fluid extracts of rosemary leaves exhibit potent anti-inflammation and anti-tumor effects

Supercritical fluid SF-CO2 treatment of Rosemarinus officinalis L. fresh leaves under optimum conditions (80 °C at 5,000 psi) yielded 5.3% of extract supercritical fluid extraction (SFE)-80, in which five major active principles were identified by liquid chromatography/mass spectrometry (LC/MS), viz., rosmarinic acid, carnosol, 12-methoxycarnosic acid, carnosic acid, and methyl carnosate. Total phenolic content was 155.8 mg/ gallic acid equivalent (GAE)/g in SFE-80, which showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging of 81.86% at 0.01 mg/ml. When treated in RAW 264.7, apparent dose-dependent NO inhibition occurred at dosages of 1.56 to 6.25 μg/ml, and more drastically at 12.5 and 25 μg/ml. At 0.5 to 5.0 μg/ml, SFE-80 exhibited dose-dependent viability suppression and significant tumor necrosis factor alpha (TNF-α) production in Hep 3B, whereas no effect was found in Chang liver cells. Furthermore, no effect was observed in RAW 264.7 at dosages of 3.13 to 25 μg/ml, indicating that SFE-80 exhibited a noncytotoxic character. Conclusively, rosemary can be considered an herbal anti-inflammatory and anti-tumor agent.

Hibiscus sabdariffa Polyphenolic Extract Inhibits Hyperglycemia, Hyperlipidemia, and Glycation-Oxidative Stress while Improving Insulin Resistance

H. sabdariffa polyphenolic extract (HPE) was demonstrated to inhibit high glucose-stimulated cellular changes. In this study, we analyzed the composition of HPE and used a type 2 diabetic rat model to test its protective effect. At least 18 phenolic compounds were found in HPE. Treatment with HPE reduced hyperglycemia and hyperinsulinemia, especially at the dose of 200 mg/kg. HPE decreased serum triacylglycerol, cholesterol, and the ratio of low density lipoprotein/high density lipoprotein (LDL/HDL). Diabetes promoted plasma advanced glycation end product (AGE) formation and lipid peroxidation, while HPE significantly reduced these elevations. Immunohistological observation revealed that HPE inhibited the expression of connective tissue growth factor (CTGF) and receptor of AGE (RAGE), which was increased in type 2 diabetic aortic regions. Furthermore, HPE recovered the weight loss found in type 2 diabetic rats. In conclusion, we demonstrated the anti-insulin resistance properties of HPE and its effect on hypoglycemia, hypolipidemia, and antioxidation. HPE has the potential to be an adjuvant for diabetic therapy.

The Hypolipidemic Effect of Hibiscus sabdariffa Polyphenols via Inhibiting Lipogenesis and Promoting Hepatic Lipid Clearance

Hibiscus sabdariffa extract (HSE) was shown to lower the plasma lipid level and reduce the liver damage. In the present study, we investigated if Hibiscus sabdariffa polyphenols (HPE) exerted a hypolipidemic effect and its putative mechanism on liver. HPE exhibited more potency to decrease plasma cholesterol and LDL cholesterol than the crude extract HSE, and increased HDL cholesterol dose-dependently. It decreased the lipid content of hepatocyte through the activation of AMPK and reduction of SREBP-1, thus inhibiting the expression of fatty acid synthase and HMG-CoA reductase. LDLR and LDL binding of HepG2 cells were enhanced when treated with HPE. In conclusion, HPE is worthy of being further investigated and could be developed as an adjunctive for hepatic lipid control and hypolipidemic therapy.

Insulin secretagogue bioactivity of finger citron fruit (Citrus medica L. var. Sarcodactylis Hort, Rutaceae).

Finger citron [Citrus medica L. var. Sarcodactylis Hort, Rutaceae] (FC) fruits, widely cultivated in Japan, the southern provinces of China and Taiwan, are commonly used as functional vegetables and preserved as sweetmeats. Previously we identified the major compounds in essential oils (% in EO) of FC fruits to be d-limonene (51.24), gamma-terpenene (33.71), alpha-pinene (3.40), and beta-pinene (2.88). Documented evidence on its insulin secretion characteristics is still lacking. In parallel to compositional analysis, we performed in vivo the safety, hypoglycemic, and antidiabetic tests in Sprague-Dawley-SPF rats and Wistar DIO rats respectively. By kinetic analysis on the hypoglycemic patterns of the intraperitoneal glucose tolerance (IPGTT) and the insulin-glucose tolerance tests (IGTT), its insulin secretagogue effect was confirmed. In conclusion, FC fruits that concomitantly possess insulin secretagogue and slimming effects would be very beneficial to type 2 diabetes mellitus patients.

Mulberry Leaf Polyphenols Possess Antiatherogenesis Effect via Inhibiting LDL Oxidation and Foam Cell Formation

Oxidized low-density lipoprotein (ox-LDL) and its uptake by machrophage are the hallmark in atherogenesis. In the present study, we aimed to investigate the antiatherogenic effect of mulberry leaf extracts (MLE) and the polyphenolic extracts (MLPE), which contained polyphenols including quercetin (11.70%), naringenin (9.01%) and gallocatechin gallate (10.02%). Both MLE and MLPE inhibited the oxidation and lipid peroxidation of LDL, while MLPE was shown to be more potent. As 1.0 mg/mL MLE reduced 30% of ox-LDL-generated ROS, 0.5 mg/mL MLPE decreased 46% of the ROS and was shown to be more potent on elevating SOD-1 and GPx in macrophages. At the same dose of 0.5 mg/mL, MLPE exhibited 1.5-fold potency than MLE in decreasing the formation of foam cells. Both MLE and MLPE reduced the expression of PPARγ, CD36 and SR-A, implicating the molecular regulation on ox-LDL uptake. These results suggested that MLPE potentially could be developed as an antiatherogenic agent and deserve further investigation.

Astaxanthine Secured Apoptotic Death of PC12 Cells Induced by β-Amyloid Peptide 25–35: Its Molecular Action Targets

Astaxanthine (ASTx) is a novel carotenoid nutraceutical occurring in many crustaceans and red yeasts. It has potent antioxidant, photoprotective, hepatodetoxicant, and anti-inflammatory activities. Documented effect of ASTx on treatment of neurodegenerative disease is still lacking. We used the beta-amyloid peptide (Abeta) 25-35-treated PC12 model to investigate the neuron-protective effect of ASTx. The parameters examined included cell viability, caspase activation, and various apoptotic biomarkers that play their critical roles in the transduction pathways independently or synergistically. Results indicated that Abeta25-35 at 30 microM suppressed cell viability by 55%, whereas ASTx was totally nontoxic below a dose of 5.00 microM. ASTx at 0.1 microM protected PC12 cells from damaging effects of Abeta25-35 in several ways: (1) by securing the cell viability; (2) by partially down-regulating the activation of caspase 3; (3) by inhibiting the expression of Bax; (4) by completely eliminating the elevation of interleukin-1beta and tumor necrosis factor-alpha; (5) by inhibiting the nuclear translocation of nuclear factor kappaB; (6) by completely suppressing the phosphorylation of p38 mitogen-activated protein kinase; (7) by completely abolishing the calcium ion influx to effectively maintain calcium homeostasis; and (8) by suppressing the majority (about 75%) of reactive oxygen species production. Conclusively, ASTx may have merit to be used as a very potential neuron protectant and an anti-early-stage Alzheimers disease adjuvant therapy.

Hibiscus sabdariffa inhibits vascular smooth muscle cell proliferation and migration induced by high glucose--a mechanism involves connective tissue growth factor signals.

Recently, the herbal extract of Hibiscus sabdariffa was shown to have multiple bioactive effects, including anti-atherosclerosis. On the basis of this, we aimed to examine whether the polyphenolic isolate of H. sabdariffa (HPI) could protect high-glucose-treated vascular smooth muscle cell (VSMC) and its putative transduction signals. Results showed that HPI dose- and time-dependently reduced the high-glucose-stimulated cell proliferation and migration. HPI suppressed the proliferating cell nuclear antigen (PCNA) level and matrix metalloproteinase (MMP)-2 activation. In addition, the expressions of connective tissue growth factor (CTGF) and receptor of advanced glycation end product (RAGE) enhanced by high glucose were prominently suppressed by HPI. The proliferation signal mediated by high glucose was demonstrated via CTGF/RAGE, while MMP-2 was regulated by CTGF but not RAGE. Conclusively, the results suggest that HPI potentially can be a promising adjuvant herbal therapy for diabetic patients.

Epigallocatechin gallate attenuates amyloid β-induced inflammation and neurotoxicity in EOC 13.31 microglia.

Microglia are the primary immune cells that contribute to neuroinflammation by releasing various proinflammatory cytokines and neurotoxins in the brain. Microglia-mediated neuroinflammation is one of the key characteristics of Alzheimers disease (AD). Therefore, inhibitory reagents that prevent microglial activation may be used as potential therapeutic agents for treating AD. Recently, many studies have been performed to determine the bioactivities of green tea polyphenol epigallocatechin-3-gallate (EGCG), an efficient antioxidant that prevents neuroinflammation. However, limited information is available on the effects of EGCG on microglia-mediated neuroinflammation. In this study, we investigated the inhibitory effects of EGCG on amyloid β (Aβ)-induced microglial activation and neurotoxicity. Our results indicated that EGCG significantly suppressed the expression of tumor necrosis factor α (TNFα), interleukin-1β, interleukin-6, and inducible nitric oxide synthase (iNOS) in Aβ-stimulated EOC 13.31 microglia. EGCG also restored the levels of intracellular antioxidants nuclear erythroid-2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), thus inhibiting reactive oxygen species-induced nuclear factor-κB (NF-κB) activation after Aβ treatment. Furthermore, EGCG effectively protected neuro-2a neuronal cells from Aβ-mediated, microglia-induced cytotoxicity by inhibiting mitogen-activated protein kinase-dependent, Aβ-induced release of TNFα. Taken together, our findings suggested that EGCG suppressed Aβ-induced neuroinflammatory response of microglia and protected against indirect neurotoxicity. These results suggest that EGCG is a possible therapeutic agent for preventing Aβ-induced inflammatory neurodegeneration.

Hibiscus sabdariffa extract inhibits obesity and fat accumulation, and improves liver steatosis in humans

Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our previous report suggested that Hibiscus sabdariffa extracts (HSE) had a metabolic-regulating and liver-protecting potential. In this study, we performed a clinical trial to further confirm the effect of HSE. Subjects with a BMI ≧ 27 and aged 18-65, were randomly divided into control (n = 17) and HSE-treated (n = 19) groups, respectively, for 12 weeks. Our data showed that consumption of HSE reduced body weight, BMI, body fat and the waist-to-hip ratio. Serum free fatty acid (FFA) was lowered by HSE. Anatomic changes revealed that HSE improved the illness of liver steatosis. Ingestion of HSE was well tolerated and there was no adverse effect during the trial. No alteration was found for serum α-amylase and lipase. The clinical effect should mainly be attributed to the polyphenols of HSE, since composition analysis showed that branched chain-amino acids, which is associated with obesity, is not obviously high. In conclusion, consumption of HSE reduced obesity, abdominal fat, serum FFA and improved liver steatosis. HSE could act as an adjuvant for preventing obesity and non-alcoholic fatty liver.