Cod (Gadus) skin collagen peptide powder reduces inflammation, restores mucosal barrier function, and inhibits fibrosis in dextran sodium sulfate-induced colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Cod (Gadus), a kind of herb from the Chinese herb. Traditionally, it has used to treat trauma, reduce swelling and relieve pain in order to exert its anti-inflammatory activity. Recent reports based on its hydrolyzed or enzymatic extracts have shown its anti-inflammatory, mucosal barrier protecting properties. However, its mechanism of improvement in ulcerative colitis is not clear. AIM OF THE STUDY: This study aimed to explore the preventive and protective effect of cod skin collagen peptide powder (CP) on mice with UC and to explore the underlying mechanism. MATERIALS AND METHODS: Mice with dextran sodium sulfate (DSS)-induced UC were treated with CP by gavage, and the anti-inflammatory effects of CP were assessed using general physical, pro-inflammatory cytokine, histopathological, immunohistochemical, macrophage flow cytometry, and inflammatory signaling pathway assays. RESULTS: CP ameliorates inflammation by upregulating mitogen-activated protein kinase phosphatase-1 (MKP-1) and thereby decreasing the phosphorylation levels of P38 and JNK. It also polarizes macrophages in the colon towards the M2 phenotype, which helps to reduce tissue damage and promotes colon repair. At the same time, CP also inhibits the development of fibrosis, one of the complications of UC, by upregulating ZO-1, Occludin, and downregulating α-SMA, Vimentin, Snail, and Slug. CONCLUSION: In this study, we found CP reduced inflammation in mice with UC by inducing MKP-1 expression, which caused dephosphorylation of mitogen-activated protein kinase (MAPK). CP also restored mucosal barrier function and inhibited the development of fibrosis complicating UC in these mice. Taken together, these results suggested that CP improved the pathological manifestations of UC in mice, suggesting that it can play a biological role as a nutritional supplement for preventing and treating UC.

Association between coffee intake and the risk of oral cavity cancer: a meta-analysis of observational studies.

The association between coffee intake and the risk of oral cavity cancer has been inconsistent in previous studies. Therefore, we conducted a meta-analysis to summarize the evidence regarding the strength of association between coffee intake and oral cavity cancer. PubMed, Embase, and Cochrane Library were searched to select studies on the relationship between coffee intake and oral cavity cancer conducted up to September 2018. Case-control or cohort studies and those that have reported about the effect estimates with 95% confidence intervals (CIs) of oral cavity cancer according to the different categories of coffee intake were included. The odds ratio (OR) and its corresponding 95% CI were calculated using the random-effects model. Fourteen case-control and five cohort studies that recruited 6456 patients with oral cavity cancer were included in the final quantitative meta-analysis. High versus low coffee intake was associated with a reduced risk of oral cavity cancer (OR: 0.68; 95% CI: 0.56-0.82; P < 0.001) in case-control studies (OR: 0.70; 95% CI: 0.55-0.90; P = 0.006) and cohort studies (OR: 0.65; 95% CI: 0.48-0.87; P = 0.004). Moreover, intermediate coffee intake was significantly associated with a reduced risk of oral cavity cancer (OR: 0.85; 95% CI: 0.77-0.94; P = 0.002), and such associations were mainly observed in case-control studies (OR: 0.86; 95% CI: 0.76-0.98; P = 0.021) but not in cohort studies (OR: 0.83; 95% CI: 0.67-1.02; P = 0.071). High or intermediate coffee intake might have protective effects against oral cavity cancer. However, the underlying mechanisms must be further evaluated in large-scale prospective cohort studies.

Effects of Acupuncture on Neurological Disease in Clinical- and Animal-Based Research.

Neurological disease, including Alzheimer's disease (AD), Parkinson's disease (PD), which were caused by abnormalities in the nervous system involves the accumulation of false proteins, neurotransmitter abnormalities, neuronal apoptosis, etc. As an alternative supplementary medicine (ASM), acupuncture plays an important role in the treatment of neurological diseases. In this review article, we summarized the current evidence for the treatment efficacy of acupuncture in AD and PD from the perspective of clinical trials and animal model. Acupuncture can inhibit the accumulation of toxic proteins in neurological diseases, modulate energy supply based on glucose metabolism, depress neuronal apoptosis, etc., and exert a wide range of neuroprotective effects.

[Determination of seven indicative ingredients in oral liquids of Chinese medicine by liquid chromatography-electrospray ionization-ion mobility spectrometry].

A two-dimensional separation and analysis method, based on liquid chromatography-electrospray ionization-ion mobility spectrometry (LC-ESI-IMS), is developed for the determination of seven indicative ingredients (danshensu, glycyrrhizic acid, gastrodin, chlorogenic acid, puerarin, baicalin, and rutin) in oral liquids of Chinese medicine. The sample was first separated on an ACQUITY UPLC BEH C18 column (50 mm×1 mm, 1.7 µm). The post-column effluent was directed to an adjustable flow splitter with a split ratio of 50:1. The low-flow and high-flow outlets were connected to an ion mobility spectrometer and a triple quadrupole mass spectrometer, respectively. The experimental conditions for LC, spray voltage, drift tube temperature, gas pre-heating temperature, and drift gas velocity were systematically optimized. The limits of detection (LODs) and quantitation (LOQs) for the seven analytes were 2-10 µg/mL and 5-25 µg/mL, respectively. The proposed method was applied for the analysis of real oral liquids of Chinese medicine samples. By coupling LC and IMS, two-dimensional separation could be achieved based on hydrophobicity difference and ionic mobility disparity, thus providing more comprehensive measurement information than LC or IMS used alone.

Panax notoginseng saponins alleviate skeletal muscle insulin resistance by regulating the IRS1-PI3K-AKT signaling pathway and GLUT4 expression.

Panax notoginseng saponins (PNS) are a commonly used traditional medicine to treat diabetes in China. Recent studies have confirmed their anti-diabetic effects, but the underlying mechanisms have remained unclear. The present study was designed to explore whether PNS decrease hyperglycemia by improving insulin sensitivity in skeletal muscle and to elucidate the molecular mechanisms. The anti-diabetic effects of PNS were analyzed in a skeletal myoblast cell line, C2C12, and in high fat diet-induced diabetic KKAy mice. C2C12 cells were treated with PNS (50, 100, and 200 µg·L-1 ) and examined for glucose uptake, cell viability and expression of components of the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. KKAy mice were intraperitoneally injected with PNS (200 mg·kg-1 ) for 6 weeks. Body weight, blood glucose, serum insulin, serum lipid, glucose and insulin tolerance were measured to evaluate the anti-diabetic effects of PNS. Pathological changes, apoptosis and the PI3K-AKT signaling pathway were analyzed in KKAy skeletal muscle. PNS significantly increased insulin-induced glucose uptake, but did not affect the cell viability of C2C12 cells. In addition, PNS reduced blood glucose and serum insulin levels and improved glucose tolerance and insulin tolerance of KKAy mice. Pathological changes and apoptosis of skeletal muscle were relieved by PNS treatment. Moreover, PNS treatment enhanced expression of mRNA encoding IRS1 and GLUT4, as well as the protein expression of phosphorylated (p) -insulin receptor substrate 1 (IRS1), p-PI3K, p-AKT and glucose transporter type 4 (GLUT4) in C2C12 and KKAy mouse muscle. Collectively, these data indicate that PNS reduces hyperglycemia and insulin resistance through up-regulating GLUT4 expression and the IRS1-PI3K-AKT signaling pathway. Furthermore, PNS alleviated diabetes skeletal muscle pathological damage. Thus, our data suggest that PNS may be promising anti-diabetic compounds.

Protective effects of Jiayan Kangtai granules on autoimmune thyroiditis in a rat model by modulating Th17/Treg cell balance.

OBJECTIVE: To investigate the protective effects of Jiayan Kangtai (JYKT) granules, consisting of 9 Chinese herbs, in a rat model of autoimmune thyroiditis (AIT), and the possible underlying mechanism. METHODS: Female Lewis rats (6-8 weeks) were randomly apportioned to 5 groups of 10, including a normal control. AIT was induced in the untreated AIT-model group, and rats treated subsequently with daily low, medium, or high dose JYKT granules. After 12 weeks, plasma levels of thyroid autoantibodies and morphological changes in the thyroid were detected by enzyme-linked immunosorbent assay and histological examination, respectively. The presence of interleukin (IL)-6, IL23p19, and IL-2 in thyroid tissue was assessed by immunohistochemical staining. The percentages of T helper (Th)17 cells and regulatory T cells (Tregs) in the peripheral blood were analyzed by flow cytometry. Relevant levels of cytokines and proteins were examined via bead-based multiplex flow cytometry and ELISA, respectively. Expressions of genes and proteins regulated by Th17 cells and Tregs were shown by real-time PCR and Western blot. RESULTS: Compared to the control, AIT-model rats had higher plasma concentrations of thyroid autoantibodies. The high-dose JYKT rats showed significantly lower levels of thyroid autoantibodies compared with the AIT model group. Rats in the AIT-JYKT groups also had fewer thyroid lesions and less lymphocytic infiltration, a lower percentage of Th17 cells, and a higher percentage of Tregs, compared with the AIT-model. Rats given high-dose JYKT had a significantly lower Th17/Treg ratio compared with the AIT model. Differences in plasma cytokine concentrations and relevant gene and protein expressions in the spleens of JYKT-treated rats and the AIT group suggested an association between JYKT treatment and lower Th17 cell percentage and higher Treg activity. CONCLUSION: JYKT treatment appeared to be protective against AIT in rats, possibly via the regulation of the Th17 cell/Treg imbalance in AIT.

Cyclocarya paliurus (Batal.) Ijinskaja Aqueous Extract (CPAE) Ameliorates Obesity by Improving Insulin Signaling in the Hypothalamus of a Metabolic Syndrome Rat Model.

BACKGROUND: Antiobesity drugs may not be optimal for treating obesity. However novel antiobesity agents, especially those derived from natural products, may be suitable. Therefore, we investigated the effects and mechanisms of Cyclocarya paliurus (CP) aqueous extract (CPAE) on obesity. METHODS: SHR.Cg-Leprcp/NDmcr (SHR/cp) rats were used as a model of obesity and metabolic syndrome. Experimental animals were allocated into two groups-control and CPAE (0.5 g/kg)-for a 7-week treatment period. Examinations were performed, including general physiological characteristics, obesity-related biochemical parameters, and insulin-signaling pathway-related proteins in the hypothalamus. RESULTS: Treatment with CPAE reduced food intake, body weight, organ weight, fat mass, and body mass index (BMI) in SHR/cp rats. Meanwhile, CPAE also decreased the levels of fasting serum glucose, fasting serum insulin, HOMA-IR, serum free fatty acids, serum malondialdehyde, serum superoxide dismutase, and serum total-glutathione. The levels of phosphorylation of target proteins-including InsR, IRS1, PI3Kp85, Akt, and FoXO1 as well as protein expression of POMC-were significantly upregulated in the hypothalamus, but NPY expression remarkably decreased. CONCLUSIONS: CPAE has antiobesity, antihypoglycemic, antihypolipidemic, and antioxidant properties. The mechanism responsible for the antiobesity effect of CPAE may be related to suppression of energy intake via regulation of insulin-signaling pathway in the hypothalamus.

Qiwei granules alleviates podocyte lesion in kidney of diabetic KK-Ay mice.

BACKGROUND: Chinese medicine comprised of all natural herbs is widespread used in the treatment of diabetic nephropathy (DN). Podocyte contributes to the integrity of glomerular filtration barrier whose injury plays an important role in the initiation and progression of DN. Our study aimed to investigate the effect of Qiwei granules on podocyte lesion in diabetic KK-A(y) mice kidney and its underlying mechanism. METHODS: Twelve-week-old male KK-A(y) mice were randomly divided in vehicle group and Qiwei granules group, while C57BL/6J mice were used as normal control. The mice were gavage with 1.37 g/kg/day Qiwei granules or water for 10 weeks. We measured water, food intake and body weight (BW) and fasting blood glucose (FBG) every 2 weeks, and urine protein every 4 weeks. At the end of the experiment, all surviving mice were sacrificed. The kidney weight and serum renal parameters were measured, and the renal morphology was observed. To search the underlying mechanism, we examined the podocyte positive marker, slit diaphragm protein expression and some involved cell signal pathway. RESULTS: Qiwei granules treatment significantly improved the metabolic parameters, alleviated the urinary protein, and protected renal function in KK-A(y) mice. In addition, the glomerular injuries and podocyte lesions were mitigated with Qiwei granules treatment. Furthermore, Qiwei granules increased expression of nephrin, CD2AP, and integrin alpha3beta1 in the podocytes of KK-A(y) mice. Qiwei granules improved the phosphoration of Akt and inhibited cleaved caspase-3 protein expression. CONCLUSION: These finding suggest that Qiwei granules protects the podocyte from the development of DN via improving slit diaphragm (SD) molecules expression and likely activating Akt signaling pathway in KK-A(y) mice.

Tang-Nai-Kang alleviates pre-diabetes and metabolic disorders and induces a gene expression switch toward fatty acid oxidation in SHR.Cg-Leprcp/NDmcr rats.

Increased energy intake and reduced physical activity can lead to obesity, diabetes and metabolic syndrome. Transcriptional modulation of metabolic networks has become a focus of current drug discovery research into the prevention and treatment of metabolic disorders associated with energy surplus and obesity. Tang-Nai-Kang (TNK), a mixture of five herbal plant extracts, has been shown to improve abnormal glucose metabolism in patients with pre-diabetes. Here, we report the metabolic phenotype of SHR.Cg-Leprcp/NDmcr (SHR/cp) rats treated with TNK. Pre-diabetic SHR/cp rats were randomly divided into control, TNK low-dose (1.67 g/kg) and TNK high-dose (3.24 g/kg) groups. After high-dose treatment for 2 weeks, the serum triglycerides and free fatty acids in SHR/cp rats were markedly reduced compared to controls. After 3 weeks of administration, the high dose of TNK significantly reduced the body weight and fat mass of SHR/cp rats without affecting food consumption. Serum fasting glucose and insulin levels in the TNK-treated groups decreased after 6 weeks of treatment. Furthermore, TNK-treated rats exhibited obvious improvements in glucose intolerance and insulin resistance. The improved glucose metabolism may be caused by the substantial reduction in serum lipids and body weight observed in SHR/cp rats starting at 3 weeks of TNK treatment. The mRNA expression of NAD+-dependent deacetylase sirtuin 1 (SIRT1) and genes related to fatty acid oxidation was markedly up-regulated in the muscle, liver and adipose tissue after TNK treatment. Furthermore, TNK promoted the deacetylation of two well-established SIRT1 targets, PPARγ coactivator 1α (PGC1α) and forkhead transcription factor 1 (FOXO1), and induced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in different tissues. These observations suggested that TNK may be an alternative treatment for pre-diabetes and metabolic syndrome by inducing a gene expression switch toward fat oxidation through the activation of SIRT1 and AMPK signaling.

Isoquercitrin activates the AMP-activated protein kinase (AMPK) signal pathway in rat H4IIE cells.

BACKGROUND: Isoquercitrin, a flavonoid compound that is widely distributed in medicinal and dietary plants, possesses many biological activities, including inhibition of adipocyte differentiation. In this study, we investigated the effect of isoquercitrin on lipid accumulation and its molecular mechanisms in rat hepatoma H4IIE cells. METHODS: To investigate the effect of isoquercitrin on lipid accumulation, H4IIE cells were induced by FFA and the total lipid levels were detected by Oil Red O staining. Furthermore, The protein levels of AMPK and acetyl-CoA carboxylase (ACC), the gene expressions of transcriptional factor, lipogenic genes, and adiponectin receptor 1 (AdipoR1) were analyzed by Western blotting and quantitative real-time PCR. To further confirm the pathway of isoquercitrin-mediated hepatic lipid metabolism, H4IIE cells were treated with an AMPK inhibitor and AdipoR1 siRNA. RESULTS: Isoquercitrin significantly enhances AMPK phosphorylation, downregulates sterol regulatory element binding protein transcription factor 1 (SREBP-1) and fatty acid synthase (FAS) gene expressions. Pretreatment with AMPK inhibitor, significantly decreased the AMPK phosphorylation and increased FAS expression stimulated by isoquercitrin. Isoquercitrin might also upregulate the expression of AdipoR1 dose-dependently via AMPK in the presence of an AMPK inhibitor and AdipoR1 siRNA. CONCLUSIONS: Isoquercitrin appears to regulate AMPK activation, thereby enhancing AdipoR1 expression, suppressing SREBP-1 and FAS expressions, and resulting in the regulation of lipid accumulation. These results suggest that isoquercitrin is a novel dietary compound that can be potentially be used to prevent lipid metabolic disorder and nonalcoholic fatty liver disease.

Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle.

BACKGROUND: Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome. METHODS: Male rats at 7 weeks of age were administered with vehicle water or treated by gavage with 2 g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured. RESULTS: Compared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120 min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42 days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles. CONCLUSIONS: These data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.

Antihyperglycemic and antihyperlipidemic action of cinnamaldehyde in C57BLKS/J db/db mice.

OBJECTIVE: To investigate the effects of cinnamaldehyde (CA), an active and major compound in cinnamon, on glucose metabolism and insulin resistance in C57BLKS/J db/db mice. METHODS: Sixteen male C57BLKS db/db mice were randomly divided into control and CA treatment groups. CA was given (20 mg x kg(-1) x day(-1), p. o.) for 4 weeks. Pure water was given to control and db/+ mice. Subsequently, the levels of fasting blood glucose (FBG), fasting serum insulin, triglyeride, cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and free fatty acids (FFA), as well as the mRNA content of adiponectin and tumor necrosis factor (TNF)-alpha in adipose tissue, glucose transporter type 4 (GLUT-4) in skeletal muscle, and protein expressions of Akt, phospho-Akt (Thr308), AMPKalpha, phospho-AMPKalpha (Thr172) in skeletal muscle were measured. RESULTS: 1) CA decreased serum levels of FBG and insulin as well as body weight in db/db mice; 2) CA increased serum HDL-C levels; 3) CA significantly decreased the mRNA expression of TNF-alpha in adipose tissue and upregulated mRNA expression of GLUT-4 in skeletal muscle; 4) protein expression of p-Akt was increased in CA-treated mice, but Akt, AMPKalpha and p-AMPKalpha showed no change. CONCLUSION: CA has antihyperglycemic and antihyperlipidemic actions in db/db mice and could be useful in the treatment of type-2 diabetes.

Antidiabetic effects of Tangnaikang on obese Zucker rats and the mechanism.

OBJECTIVE: To observe the effects of Tangnaikang (TNK), a compound traditional Chinese herbal medicine, on glucose metabolism and insulin resistance in obese Zucker rats. METHODS: Twelve male obese Zucker rats, 6 weeks old, were randomly divided into control group and TNK group (3.24 g/kg) after being fed for 2 weeks. All rats received high-fat diet and 4-week treatment. Body weight and blood glucose were tested every week. Oral glucose tolerance test (OGTT) was performed and fasting insulin level was tested on days 0, 14 and 28. Triglyceride, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acids (FFA) were tested on day 28. Glucose infusion rate (GIR) was tested by hyperinsulinemic-euglycemic clamp from day 29. The protein expressions of protein kinase B (Akt), phospho-Akt (p-Akt) (Thr308) and glucose transporter protein 4 (GLUT4) in skeletal muscle and GLUT4 in adipose tissue were measured after hyperinsulinemic-euglycemic clamp test. RESULTS: Compared with the control group, the fed blood glucose level and glucose level of OGTT at 120 min had a significant decline in TNK group on day 28, and TNK caused no alteration of the fasting serum insulin, and the GIR increased significantly in hyperinsulinemic-euglycemic clamp study. Furthermore, TNK increased Akt and p-Akt (Thr308) protein expressions in skeletal muscle and decreased the protein expression of GLUT4 in white adipose tissue. Body weight, and triglyceride, cholesterol, LDL-C and FFA contents were slightly decreased in the TNK group, but there were no statistically significant effects. CONCLUSION: TNK increases the protein expressions of Akt and p-Akt (Thr308) of the signal transduction pathway to influence the translocation of GLUT4 in skeletal muscle and improves glucose metabolism by reducing insulin resistance.