Huangkui capsule attenuates diabetic kidney disease through the induction of mitophagy mediated by STING1/PINK1 signaling in tubular cells.

BACKGROUND: Mitochondria is critic to tubulopathy, especially in diabetic kidney disease (DKD). Huangkui capsule (HKC; a new ethanol extract from the dried corolla of Abelmoschus manihot) has significant clinical effect on DKD. Previous studies have shown that HKC protects kidney by regulating mitochondrial function, but its mechanism is still unclear. The latest research found that the stimulator of interferon genes (STING1) signal pathway is closely related to mitophagy. However, whether HKC induces mitophagy through targeting STING1/PTEN-Induced putative kinase (PINK1) in renal tubular remains elusive. OBJECTIVE: This study aims to clarify the therapeutic effect of HKC on renal tubular mitophagy in DKD and its potential mechanism in vivo and in vitro. METHODS: Forty male C57BL/6 mice were randomly divided into 5 groups: CON group, DKD group, HKC-L (1.0 g/kg/day, by gavage), HKC-H (2.0 g/kg/day), and LST group. Diabetes model was induced by high-fat diet (HFD) combined with intraperitoneal injection of Streptozotocin (STZ). LST (losartan) is used as a positive control drug. Then, the glomeruli, renal tubular lesions, mitochondrial morphology and function of renal tubular cells and mitophagy levels were detected in mice. In addition, a high glucose injury model was established using HK2 human renal tubular cells. Pretreate HK2 cells with HKC or LST and detect mitochondrial function, mitophagy level, and autophagic flux. In addition, small interfering RNAs (siRNAs) of STING1 and PINK1 and overexpressing pcDNA3.1 plasmids were transfected into HK-2 cells to validate the mitophagy mechanism regulated by STING1/PINK1 signaling. RESULTS: The ratio of urinary albumin to creatinine (ACR), fasting blood glucose, body weight in the early DKD mice model was increased, with damage to the glomerulus and renal tubules, mitochondrial structure and dysfunction in the renal tubules, and inhibition of STING1/PINK1 mediated mitophagy. Although the fasting blood glucose, body weight and serum creatinine levels were hardly ameliated, high dose HKC (2.0 g/kg/day) treatment significantly reduced ACR in the DKD mice to some extent, improved renal tubular injury, accurately upregulated STING1/PINK1 signaling mediated mitophagy levels, improved autophagic flux, and restored healthy mitochondrial pools. In vitro, an increase in mitochondrial fragments, fusion to fission, ROS and apoptosis, and a decrease in respiratory function, mtDNA, and membrane potential were observed in HK2 cells exposed to high glucose. HKC treatment significantly protected mitochondrial dynamics and function, which is consistent with in vivo results. Further research has shown that HKC can increase the level of mitophagy mediated by STING1/PINK1 in HK2 cells. CONCLUSIONS: Our results suggest that HKC ameliorates renal tubulopathy in DKD and induces mitophagy partly through the up-regulation of the STING1/PINK1 pathway. These findings may provide an innovative therapeutic basis for DKD treatment.

Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation.

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.

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Analyzing the pattern of altitudinal variation in the leaf traits and their networks of a particular tree species of similar age and its influencing factors could contribute to understanding the impacts of environmental factors on leaf traits and excluding the interference of genetic factors. We investigated the stomatal, structural, chemical, and vein traits of Daphniphyllum macropodum leaves in middle-aged forests, following the altitudinal gradient (1100, 1500, and 1900 m) on Mao'er Mountain. The objectives of this study were to reveal patterns in leaf trait and leaf trait networks variation, the life strategy of the tree species, and the major environmental factors affecting the altitudinal variations. The results showed that leaf area, specific leaf area, leaf thickness, leaf dry matter content, chlorophyll content, nitrogen content, phosphorus content, C:N, C:P, vein density, and vein diameter varied significantly across altitudes. Mean annual temperature and total radiation explained 42.1% and 16.2% of leaf-trait variation, respectively. They served as key environmental factors driving the altitudinal variation in leaf traits. Mean annual temperature exhibited the greatest influence on leaf area (R2=0.73), and total radiation exerted the most prominent effect on leaf thickness (R2=0.72). Both relationships were significantly positive. D. macropodum exhibited low leaf nitrogen and phosphorus at the low altitude of 1100 m, and the overall and local trait networks were loose, adopting a conservative resource strategy. At the medium altitude of 1500 m, leaf nutrient contents were relatively high. The overall network of leaf traits was tightly connected and local network was loose. By enhancing the dependency among leaf traits, and improving phosphorus utilization efficiency, D. macropodum could cope with competition in deciduous forests and adopt resource acquisition strategies. Further, at the highest altitude of 1900 m, D. macropodum had relatively large leaf thickness, chlorophyll content, and leaf dry matter content, but relatively small leaf area. The local network connections were tight while the overall network looseness, indicating a resource conserving strategy. The trade-off relationship between C:P and leaf phosphorus content was closely related to phosphorus use efficiency, and its variation was an important indicator for identifying life strategies of D. macropodum in different altitudes.

High doses of butyrate induce a reversible body temperature drop through transient proton leak in mitochondria of brain neurons.

AIMS: Sodium butyrate (SB) is a major product of gut microbiota with signaling activity in the human body. It has become a dietary supplement in the treatment of intestinal disorders. However, the toxic effect of overdosed SB and treatment strategy remain unknown. The two issues are addressed in current study. MATERIALS AND METHODS: SB (0.3-2.5 g/kg) was administrated through a single peritoneal injection in mice. The core body temperature and mitochondrial function in the brown adipose tissue and brain were monitored. Pharmacodynamics, targeted metabolomics, electron microscope, oxygen consumption rate and gene knockdown were employed to dissect the mechanism for the toxic effect. KEY FINDINGS: The temperature was reduced by SB (1.2-2.5 g/kg) in a dose-dependent manner in mice for 2-4 h. In the brain, the effect was associated with SB elevation and neurotransmitter reduction. Metabolites changes were seen in the glycolysis, TCA cycle and pentose phosphate pathways. Adenine nucleotide translocase (ANT) was activated by butyrate for proton transportation leading to a transient potential collapse through proton leak. The SB activity was attenuated by ANT inhibition from gene knockdown or pharmacological blocker. ROS was elevated by SB for the increased ANT activity in proton leak in Neuro-2a. SIGNIFICANCE: Excessive SB generated an immediate and reversible toxic effect for inhibition of body temperature through transient mitochondrial dysfunction in the brain. The mechanism was quick activation of ANT proteins for potential collapse in mitochondria. ROS may be a factor in the ANT activation by SB.

Molecularly imprinted ratiometric fluorescent probe for visual and fluorescent determination of aristolochic acid I based on a Schiff-base fluorescent compound.

A molecularly imprinted ratiometric fluorescent probe (MIRF probe) was synthesized for the determination of aristolochic acid I (AAI) based on the Schiff-base fluorescent compound N,N'-bis(o-carboxybenzylidene)-p-4,4'-diaminobiphenyl (BDDB). The BDDB was immobilized in the silica nanoparticle (BDDB@SiO2) as an internal standard material. The blue-emitting BDDB@SiO2 and the yellow-emitting carbon quantum dots (y-CDs) were wrapped in the molecularly imprinted polymer (MIP) to provide a reliable reference signal at 440 nm and a fluorescent response signal at 530 nm at the excitation wavelength of 365 nm, respectively. In the preparation of the MIP of the MIRF probe, 4-vinylbenzoic acid as the functional monomer and AAI as the template molecule were used. An imprinting factor of 2.25 was obtained. Under the optimum conditions, the fluorescent response signal at 530 nm was quenched gradually by AAI in the range 1.0 to 120.0 µmol/L, while the reference signal at 440 nm remained unchanged. The limit of detection was 0.45 µmol/L, and the fluorescent color of the MIRF probe changed gradually from yellow to green to blue, which illustrated that the developed probe had a specific AAI recognition ability, a good anti-interference ability, and a sensitively visual determination ability. The probe was successfully applied to the AAI determination in traditional Chinese medicine (TCM) Asarum. The results showed that it had satisfactory recoveries (95.5-107.3%) and low relative standard deviations (2.0%). Furthermore, this method has a potential for the onsite naked eye determination of AAI in TCM samples.Graphical abstract.

A multicenter consensus: A role of furin in the endothelial tropism in obese patients with COVID-19 infection.

Furin, a cleavage enzyme, is increasingly recognized in the pathogenesis of metabolic syndrome. Its cleavage action is an essential activation step for the endothelial pathogenicity of several viruses including SARS-CoV-2. This Furin-mediated endothelial tropism seems to underlie the multi-organ system involvement of COVID-19; which is a feature that was not recognized in the older versions of coronaviridae. Obese and diabetic patients, males, and the elderly, have increased serum levels of Furin, with its increased cellular activity; this might explain why these subgroups are at an increased risk of COVID-19 related complications and deaths. In contrast, smoking decreases cellular levels of Furin, this finding may be at the origin of the decreased severity of COVID-19 in smokers. Chinese herbal derived luteolin is suggested to be putative Furin inhibitor, with previous success against Dengue Fever. Additionally, Furin intracellular levels are largely dependent on concentration of intracellular ions, notably sodium, potassium, and magnesium. Consequently, the use of ion channel inhibitors, such as Calcium Channel blockers or Potassium Channel blockers, can prevent cellular transfection early in the course of the illness. Nicotine patches and Colchicine have also been suggested as potential therapies due to Furin mediated inhibition of COVID-19.

Sennoside A restores colonic barrier function through protecting colon enterocytes from ROS-induced mitochondrial damage in diet-induced obese mice.

The intestinal barrier dysfunction is closely implicated in low-grade chronic inflammation for insulin resistance in diet-induced obesity (DIO). It is generally believed that degradation of colon enterocytes contributes to intestinal barrier dysfunction in the pathological process of obesity. Sennoside A (SA) is reported to improve metabolic disorders, but the effect and mechanism of SA on colonic barrier function of DIO remains unknown. In this study, SA was found to restore colonic barrier function by protecting the continuity and integrity of colon enterocytes in DIO mice. An increase in mRNA expression of tight junction proteins Occludin, Claudin-2 and ZO-1 provides another mechanism of restoring colonic barrier function in SA-treated group. In the research of mechanism, mitophagy was inhibited by SA via a protection of mitochondrial structure and function in colon. A reduction was found in production of reactive oxygen species (ROS) in the colon, and the benefical effect was attributed to an inhibition of activity in complex I and III with a reduction of protein expression and an increase of Mn-SOD activity. The results indicate that SA can restores colonic barrier function through protecting colon enterocytes from ROS-induced mitochondrial damage in DIO mice.

Regulation of microbiota-GLP1 axis by sennoside A in diet-induced obese mice.

Sennoside A (SA) is a bioactive component of Chinese herbal medicines with an activity of irritant laxative, which is often used in the treatment of constipation and obesity. However, its activity remains unknown in the regulation of insulin sensitivity. In this study, the impact of SA on insulin sensitivity was tested in high fat diet (HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR (homeostatic model assessment for insulin resistance) and glucose tolerance test (GTT). SA restored plasma level of glucagon-like peptide 1 (GLP1) by 90% and mRNA expression of Glp1 by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids (SCFAs), and mucosal structure in the colon. A mitochondrial stress was observed in the enterocytes of HFD mice with ATP elevation, structural damage, and complex dysfunction. The mitochondrial response was induced in enterocytes by the dietary fat as the same responses were induced by palmitic acid in the cell culture. The mitochondrial response was inhibited in HFD mice by SA treatment. These data suggest that SA may restore the function of microbiota-GLP1 axis to improve glucose metabolism in the obese mice.

Anti-diabetic Effect of Punica granatum Flower Polyphenols Extract in Type 2 Diabetic Rats: Activation of Akt/GSK-3ß and Inhibition of IRE1α-XBP1 Pathways.

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes with more than hundreds of millions of patients worldwide. However, the medicines for treatment of T2DM are very limited. In China, Punica granatum L. flower (PGF) has been used as an anti-diabetic herb in the herbal medicine. The activity involves in improvement of insulin sensitivity. However, the underlying mechanism of action is elusive. The current study was designed to address this issue by investigating the effect of polyphenols extract of PGF in diabetic rats. A rat model was orally administrated with PGF polyphenols extract at doses of 50 and 100 mg/kg for 4 weeks. Insulin sensitivity was improved as indicated by oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and homeostasis model assessment of insulin resistance (HOMA-IR). At the molecular level, insulin signaling activity was improved with an elevation in insulin-stimulated phosphorylation of insulin receptor substrate (IRS-1), Akt and GSK-3ß. Endoplasmic reticulum (ER) stress signals including phosphorylation of inositol-requiring kinase1 (IRE1) and activation of X box binding protein (XBP-1) splicing were decreased by the PGF treatment. Expressions of IRE1α, XBPs, and CHOP were all decreased by PGF. Blood lipid profile, liver glycogen content and antioxidant status were improved by PGF in the rats. The observations suggest that PGF is able to lower glucose levels in T2DM rats by improving the insulin resistance. The mechanism is likely related to the activation of Akt-GSK3ß signaling pathway and inhibition of ER stress.

Polyphenol-enriched extract of Rosa rugosa Thunb regulates lipid metabolism in diabetic rats by activation of AMPK pathway.

This study was designed to investigate the mechanism of polyphenol-enriched extract of Rosa rugosa Thunb (RPE) in the control of dyslipidemia in diabetic rats. RPE was tested at three dosages (37.5 mg/kg, 75 mg/kg and 150 mg/kg) in the rat dyslipidemia model established with high fat diet feeding in combination with STZ injection (30 mg/kg). The RPE effect was evaluated after 4 weeks of treatment. In the RPE-treated rats, hepatic total cholesterol (TC) and triglyceride (TG) were significantly reduced, lipoprotein lipase (LPL) and liver lipase (HL) were significantly increased. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were decreased in the serum. Those effects of RPE were observed primarily at the mediate and high dosages. Expression of FGF21 was increased in the liver tissue and hepatic cell line 1c1c7 by RPE. The signals of p-AMPK, p-ACC, ACC, p-SIRT, and PGC-1α were significantly induced in the liver by RPE. The results suggest that RPE may improve hepatic steatosis and liver function by induction of AMPK signaling activity in the control of dyslipidemia.

Vitamin D limits inflammation-linked microRNA expression in adipocytes in vitro and in vivo: A new mechanism for the regulation of inflammation by vitamin D.

Inflammation of adipose tissue is believed to be a contributing factor to many chronic diseases associated with obesity. Vitamin D (VD) is now known to limit this metabolic inflammation by decreasing inflammatory marker expression and leukocyte infiltration in adipose tissue. In this study, we investigated the impact of VD on microRNA (miR) expression in inflammatory conditions in human and mouse adipocytes, using high-throughput methodology (miRNA PCR arrays). Firstly, we identified three miRs (miR-146a, miR-150, and miR-155) positively regulated by TNFα in human adipocytes. Interestingly, the expression of these miRs was strongly prevented by 1,25(OH)2D preincubation. These results were partly confirmed in 3T3-L1 adipocytes (for miR-146a and miR-150). The ability of VD to control the expression of these miRs was confirmed in diet-induced obese mice: the levels of the three miRs were increased following high fat (HF) diet in epididymal white adipose tissue and reduced in HF diet fed mice supplemented with VD. The involvement of NF-κB signaling in the induction of these miRs was confirmed in vitro and in vivo using aP2-p65 transgenic mice. Finally, the ability of VD to deactivate NF-κB signaling, via p65 and IκB phosphorylation inhibition in murine adipocyte, was observed and could constitute a driving molecular mechanism. This study demonstrated for the first time that VD modulates the expression of miRs in adipocytes in vitro and in adipose tissue in vivo through its impact on NF-κB signaling pathway, which could represent a new mechanism of regulation of inflammation by VD.

Phytotoxic cis-clerodane diterpenoids from the Chinese liverwort Scapania stephanii.

Five cis-clerodane diterpenoids, stephanialides A-E, along with seven known cis-clerodanes, scaparvins A-C, parvitexins B and C, 3-chloro-4-hydroxy-parvitexin A, and scapanialide B, were isolated from the Chinese liverwort Scapania stephanii. Their structures were established unequivocally on the basis of spectroscopic data. The absolute configuration of stephanialide A was determined by analysis of CD data using the octant rule. Phytotoxic activity evaluation showed that this type of diterpenoids can significantly inhibit root elongation of the seeds of Arabidopsis thaliana, Lepidium sativum and Brassica pekinensis.

Variations in the contents of gingerols and chromatographic fingerprints of ginger root extracts prepared by different preparation methods.

In the present study, an HPLC-DAD method was optimized for the quantitative determination of 6-gingerol, 6-shogaol, 8-gingerol, and 10-gingerol in ginger extracts. A chromatographic fingerprinting method was also established to differentiate and evaluate the ginger extracts for bioactivity. Twenty-one extracts were prepared by methods differing in ginger type (fresh versus dried), solvent, and extraction methods. The ANOVA analysis showed the methods' influence on the mean extraction yields of gingerols increased in the order of: high pressure-high temperature (HP)>blender (BD)>low pressure (LP). The optimal solvent to extract gingerols was found to be 95% ethanol. The type of ginger used had significant effects on the content of gingerols, but its overall influence depended on the solvent used. In order to maximize the extraction efficiency of gingerols, a combination of dry ginger, 95% ethanol, and the HP extraction method should be employed. The chromatographic fingerprints were obtained to differentiate the unknown components from all ginger extracts. The similarity of the chromatographic fingerprints was used to evaluate the differences among all extracts. It can be concluded that the chromatographic fingerprints are able to ensure the stability of each extract and have some correlation with the observed bioactivity.

GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents.

Exaggerated GLP-1 and PYY secretion is thought to be a major mechanism in the reduced food intake and body weight after Roux-en-Y gastric bypass surgery. Here, we use complementary pharmacological and genetic loss-of-function approaches to test the role of increased signaling by these gut hormones in high-fat diet-induced obese rodents. Chronic brain infusion of a supramaximal dose of the selective GLP-1 receptor antagonist exendin-9-39 into the lateral cerebral ventricle significantly increased food intake and body weight in both RYGB and sham-operated rats, suggesting that, while contributing to the physiological control of food intake and body weight, central GLP-1 receptor signaling tone is not the critical mechanism uniquely responsible for the body weight-lowering effects of RYGB. Central infusion of the selective Y2R-antagonist BIIE0246 had no effect in either group, suggesting that it is not critical for the effects of RYGB on body weight under the conditions tested. In a recently established mouse model of RYGB that closely mimics surgery and weight loss dynamics in humans, obese GLP-1R-deficient mice lost the same amount of body weight and fat mass and maintained similarly lower body weight compared with wild-type mice. Together, the results surprisingly provide no support for important individual roles of either gut hormone in the specific mechanisms by which RYGB rats settle at a lower body weight. It is likely that the beneficial effects of bariatric surgeries are expressed through complex mechanisms that require combination approaches for their identification.

Resistant starch from high amylose maize (HAM-RS2) and dietary butyrate reduce abdominal fat by a different apparent mechanism.

OBJECTIVE: Obesity is a health concern. Resistant starch (RS) type 2 from high-amylose maize (HAM-RS2) and dietary sodium butyrate (SB) reduce abdominal fat in rodents. RS treatment is associated with increased gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), but it is not known if SB increases these hormones. DESIGN AND METHODS: This was investigated in a 2 × 2 rat study with HAM-RS2 (0 or 28% weight) and dietary sodium butyrate (0 and 3.2%) resulting in isocaloric treatments: energy control (EC), sodium butyrate (SB), HAM-RS2 (RS), and the combination (SBRS). RESULTS: RS and SB reduced abdominal fat and the combination reduced abdominal fat compared to SB and RS. RS was associated with increased fermentation in the cecum. Serum PYY and GLP-1 total were increased with RS treatment. RS treatment was associated with increased cecal butyrate produced from fermentation of RS, but there was no cecal increase for dietary SB. CONCLUSIONS: SB after its absorption into the blood appears to not affect production of PYY and GLP-1, while butyrate from fermentation in the cecum promotes increased PYY and GLP-1. Future studies with lower doses of RS and SB are warranted and the combination may be beneficial for human health.

Secondary metabolites from the Chinese liverwort Cephaloziella kiaeri.

Sixteen new clerodane diterpenoids, cephaloziellins A-P (1-16), and two known analogues (17 and 18) were isolated from an EtOH extract of the Chinese liverwort Cephaloziella kiaeri. The structures of the new compounds were elucidated from extensive spectroscopic data (IR, UV, HRESIMS, 1D NMR, and 2D NMR), and the structures of 5, 9, and 15 were confirmed by single-crystal X-ray diffraction analyses. The absolute configurations of all new compounds were established by comparing experimental and calculated electronic circular dichroism spectra.

Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis.

Berberine (BBR) is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French). It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK) and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS) was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1), sterol regulatory element-binding protein 1c (SREBP1) and carbohydrate responsive element-binding protein (ChREBP) were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP) level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.

Shilianhua extract inhibits GSK-3beta and promotes glucose metabolism.

The extract of plant Shilianhua (SLH; Sinocrassula indica Berge) is a component in a commercial product for control of blood glucose. However, it remains to be investigated whether the SLH extract enhances insulin sensitivity in a model of type 2 diabetes. To address this question, the SLH crude extract was fractionated into four parts on the basis of polarity, and bioactivities of each part were tested in cells. One of the fractions, F100, exhibited a strong activity in the stimulation of glucose consumption in vitro. Glucose consumption was induced significantly by F100 in 3T3-L1 adipocytes, L6 myotubes, and H4IIE hepatocytes in the absence of insulin. F100 also increased insulin-stimulated glucose consumption in L6 myotubes and H4IIE hepatocytes. It increased insulin-independent glucose uptake in 3T3-L1 adipocytes and insulin-dependent glucose uptake in L6 cells. The glucose transporter-1 (GLUT1) protein was induced in 3T3-L1 cells, and the GLUT4 protein was induced in L6 cells by F100. Mechanism study indicated that F100 induced GSK-3beta phosphorylation, which was comparable with that induced by insulin. Additionally, the transcriptional activity of NF-kappaB was inhibited by F100. In RAW 264.7 macrophages, mRNA expression of NF-kappaB target genes (TNFalpha and MCP-1) was suppressed by F100. In KK.Cg-A(y)/+ mice, F100 decreased fasting insulin and blood glucose and improved insulin tolerance significantly. We conclude that the F100 may be a bioactive component in the SLH plant. It promotes glucose metabolism in vitro and in vivo. Inhibition of GSK-3beta and NF-kappaB may be the potential mechanism.

Soy protein intake has sex-specific effects on the risk of metabolic syndrome in middle-aged and elderly Chinese.

Soy protein intake has been postulated to improve lipid profiles, glucose homeostasis, and blood pressure. However, data linking soy protein intake and metabolic syndrome (MetS) are limited. We evaluated the association between soy protein intake and the risk of MetS and its components among middle-aged and elderly Chinese. A cross-sectional study was conducted among 2811 Chinese men and women aged 50-70 y, who were free of diagnosed cardiovascular diseases and cancers. Dietary data, including soy protein intake, was collected using a 74-item FFQ. MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. We used multivariate logistical regression models to quantify these associations. The median level of soy protein intake was 7.82 g/d (7.64 g/d in men and 8.02 g/d in women). Overall, the association of soy protein intake and the risk of MetS differed between men and women (P for interaction = 0.008). In men, the adjusted odds ratio comparing the extreme quartiles was 1.64 (95% CI: 0.95-2.81; P-trend = 0.077), whereas for women, it was 0.66 (95% CI: 0.42-1.03; P-trend = 0.138). Soy protein intake was positively associated with hyperglycemia (P-trend = 0.005) in men, whereas it was inversely associated with elevated blood pressure (P-trend = 0.049). It was not associated with any component in women. In conclusion, habitual soy protein intake may have sex-dependent effects on risk of MetS in middle-aged and elderly Chinese.