Yi-Sun Yang

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.

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.

DPP‐4 Inhibitor Linagliptin Attenuates Aβ‐induced Cytotoxicity through Activation of AMPK in Neuronal Cells

It is now clear that insulin signaling has important roles in regulation of neuronal functions in the brain. Dysregulation of brain insulin signaling has been linked to neurodegenerative disease, particularly Alzheimers disease (AD). In this regard, there is evidence that improvement of neuronal insulin signaling has neuroprotective activity against amyloid β (Aβ)‐induced neurotoxicity for patients with AD. Linagliptin is an inhibitor of dipeptidylpeptidase‐4 (DPP‐4), which improves impaired insulin secretion and insulin downstream signaling in the in peripheral tissues. However, whether the protective effects of linagliptin involved in Aβ‐mediated neurotoxicity have not yet been investigated.

Acquired hypophosphatemia osteomalacia associated with Fanconi's syndrome in Sjögren's syndrome

Sjögren’s syndrome is an autoimmune disorder involving exocrine glands that occurs alone or in association with various autoimmune and connective tissue diseases. The severity of Sjögren’s syndrome ranges from isolated sicca syndrome to severe complications such as vasculitis, lung and renal involvement. Overt or latent renal tubular acidosis caused by autoimmune tubulointerstitial nephritis, is a common extraglandular manifestation in Sjögren’s syndrome. Osteomalacia is a rare complication of renal tubular acidosis, and it was reported to be associated with distal renal tubular acidosis in Sjögren’s syndrome. We report a 60-year-old woman who presented with multiple bone deformity and general muscle weakness. Osteomalacia was secondary to Fanconi’s syndrome, and the Fanconi’s syndrome was a result of renal involvement in Sjögren’s syndrome. Fanconi’s syndrome is a rare kidney manifestation in Sjögren’s syndrome. It may be latent and may precede the subjective sicca symptoms. These findings suggest that evidence for Sjögren’s syndrome should be sought in adult patients with unexplained osteomalacia and renal tubular acidosis, even in the absence of subjective sicca syndrome. Conversely, in patients with Sjögren’s syndrome, early investigation and treatment of renal tubular dysfunction may prevent future complications, such as osteomalacia.

Polyphenols of Hibiscus sabdariffa Improved Diabetic Nephropathy via Attenuating Renal Epithelial Mesenchymal Transition

We previously reported that Hibiscus sabdariffa polyphenol extracts (HPE) are beneficial for diabetic nephropathy. Since an epithelial to mesenchymal transition (EMT) is critical in renal fibrosis, the present study aimed to investigate whether HPE could prevent EMT of tubular cells. Treatment of HPE reduced angiotensin II receptors (AT)-1 and transforming growth factor β1 (TGF-β1) evoked by high glucose and recovered the increased vimentin and decreased E-cadherin. HPE decreased fibronectin, thus avoiding EMT and accompanying fibrosis. AT-1 was upstream to TGF-β1, while there were recruitment signals between AT-1 and TGF-β1. Scan electron microscopy (SEM) and immunohistochemistry (IHC) revealed that the interacting filaments of tubular cells disappeared when treated with high glucose, and type IV collagen of tubulointerstitial decreased in diabetic kidneys. Treatment of HPE recovered morphological changes of cell junction and basement membrane. We suggest that HPE has the potential to be an adjuvant for diabetic nephropathy by regulating AT-1/TGF-β1 and EMT.

Adherence to self-care behavior and glycemic effects using structured education

The purpose of the present study was to examine glycemic control in suboptimally controlled type 2 diabetes provided by a structured education group using the Diabetes Conversation Map™ (CM™) vs usual care in a university‐based hospital primary care clinic.

Hibiscus sabdariffa Polyphenols Alleviate Insulin Resistance and Renal Epithelial to Mesenchymal Transition: A Novel Action Mechanism Mediated by Type 4 Dipeptidyl Peptidase

The epithelial to mesenchymal transition (EMT) is important in renal fibrosis. Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 (S307)) is a hallmark of insulin resistance. We report that polyphenol extracts of Hibiscus sabdariffa (HPE) ameliorate diabetic nephropathy and EMT. Recently it has been observed that type 4 dipeptidyl peptidase (DPP-4) inhibitor linagliptin is effective for treating type 2 diabetes and albuminuria. We investigated if DPP-4 and insulin resistance are involved in renal EMT and explored the role of HPE. In high glucose-stimulated tubular cells, HPE, like linagliptin, inhibited DPP-4 activation, thereby regulating vimentin (EMT marker) and IRS-1 (S307). IRS-1 knockdown revealed its essential role in mediating downstream EMT. In type 2 diabetic rats, pIRS-1 (S307) abundantly surrounds the tubular region, with increased vimentin in kidney. Both the expressions were reduced by HPE. In conclusion, HPE exerts effects similar to those of linagliptin, which improves insulin resistance and EMT, and could be an adjuvant to prevent diabetic nephropathy.

Antrodia cinnamomea Prevents Obesity, Dyslipidemia, and the Derived Fatty Liver via Regulating AMPK and SREBP Signaling

Antrodia cinnamomea (AC), a protogenic fungus that only grows on the heartwood of endemic Cinnamomum kanehirae Hayata in Taiwan, is used to treat a variety of illness including liver disease. However, little is known about the benefit of AC against obesity and the related hepatic disorder. Using high-fat-diet (HFD) feed mice, we aimed to investigate whether the extract of AC (ACE) could reduce excessive weight, body fat, and serum lipids and prevent the development of non-alcoholic fatty liver (NAFLD). C57BL/6 mice were divided into five groups fed with different diets: control, HFD, and HFD with 0.5%, 1%, or 2% of ACE, respectively. After 10 weeks the animals were sacrificed, with serum and liver collected. HFD-induced elevation of body weight gain, body fat deposition, and serum free fatty acid (FFA), triacylglycerol (TGs), total cholesterol, and ratio of LDL cholesterol (LDL-C)/HDL cholesterol (HDL-C), were significantly restored by ACE. ACE reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hepatic lipid deposits increased by HFD. ACE increased p-AMP activated protein kinase (pAMPK) but decreased Sterol regulatory element binding protein (SREBP), fatty acid synthase (FAS), 1-acylglycerol-3-phosphate acyltransferase (AGPAT), and 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase. The chemical analysis reveals ACE is full of triterpenes, the most abundant of which is Antcin K, followed by sulphurenic acid, eburicoic acid, antcin C, dehydrosulphurenic acid, antcin B, and propanoic acid. In conclusion, ACE should be used to prevent obesity and derived fatty liver. The applicability of ACE on NAFLD deserves further investigation.

Iodinated Contrast Media Increased the Risk of Thyroid Dysfunction: A 6-Year Retrospective Cohort Study

CONTEXT The risks of thyroid dysfunction after iodinated contrast media (ICM) exposure are largely unknown, especially in Asian populations. OBJECTIVE The objective was to determine whether ICM exposure in patients with normal thyroid would increase the risk of thyroid dysfunction, including hyperthyroidism or hypothyroidism. DESIGN This was a retrospective cohort study including a random selection of 1 million people in 2005. SETTING General population of Taiwan was studied. PATIENTS Patients with ICM exposure were identified as cases, whereas patients without any ICM exposure were selected as controls. INTERVENTION Interventions included ICM exposure or nonexposure in normal thyroid function patients. MAIN OUTCOME The primary endpoint was the composite risk of thyroid dysfunction associated with ICM exposure. RESULTS A total of 19 642 cases and 78 568 matched controls were recruited in this study. The mean ages of ICM exposure and nonexposure were 53.9 and 53.6 years, respectively, and mean follow-up durations were 4.1 and 5.6 years, respectively. After adjustment, patients with ICM exposure had a significantly higher risk of thyroid dysfunction (hazard ratio, 1.46; 95% confidence interval [CI], 1.29-1.66). In the subgroup analysis, the adjusted hazard ratios of hyperthyroidism and hypothyroidism compared with controls were 1.22 (95% CI, 1.04-1.44) and 2.00 (95% CI, 1.65-2.44), respectively. CONCLUSIONS ICM exposure was associated with higher risk of thyroid dysfunction, including hyperthyroidism and hypothyroidism.

Diabetes-related avoidable hospitalizations in Taiwan.

BACKGROUND An avoidable hospitalization (AH) is a condition that could have been prevented through effective treatment in outpatient care. Diabetes is often referred to as an ambulatory care-sensitive condition, and its associated hospitalizations are often referred to as avoidable hospitalizations. There are limited data on avoidable hospitalizations for individuals with diabetes in Taiwan. METHOD We used the National Health Interview Survey (NHIS) dataset to obtain diabetes-related avoidable hospitalizations for subjects aged above 12 years. We included data from 20,826 subjects who had completed the interview between 2004 and 2005. Data were collected from a total of 15,574 people, who had agreed to link their health information to the Taiwan National Health Insurance Research Database, including basic demographic variables, inpatient or outpatient medical events, admission date, discharge date, and diagnosis. The 1005 individuals who self-reported having diabetes or had at least 1 hospitalization or 2 physician service claims for diabetes mellitus with an ICD-9 diagnosis of 250 were included in the analysis. We divided those with diagnosis of diabetes into two groups: never hospitalized and hospitalized. The never hospitalized group served as the control group. We further identified hospitalized subjects with long-term complications due to diabetes (PQI-3) that included ICD-CM codes 250.4-250.9. RESULTS The mean ages of patients with diabetes-related long-term complications in the hospitalized and never hospitalized groups were 65 years and 58 years, respectively (p-value<0.01). More than half (52%) of the patients with diabetes-related long-term complications had a body mass index (BMI) lower than 24. The hospitalized group also had lower educational status compared with that of patients in the never hospitalized group (equal to or lower than elementary school, 63% vs. 50%; junior high school, 23% vs. 14%; equal or higher than senior high school, 14% vs. 36%). Furthermore, hospitalized patients tended to have lower household monthly income, were unmarried, and did not have private medical insurance. There were no significance differences in ethnic composition between the groups. Interestingly, patients with frequent retinal examination, and those with lower body mass index had higher frequency of avoidable hospitalization (p<0.01). CONCLUSION We found that the following factors were associated with a higher frequency of avoidable hospitalization among patients with type 2 diabetes: elderly, male, lower body mass index, lower household income, non-exercise, higher disease comorbidity, and frequent retinal examination.