Phenolic acids from Chicory roots ameliorate dextran sulfate sodium-induced colitis in mice by targeting TRP signaling pathways and the gut microbiota.

BACKGROUND: Inflammatory bowel disease (IBD) is a type of immune-mediated condition associated with intestinal homeostasis. Our preliminary studies disclosed that Cichorium intybus L., a traditional medicinal plant, also known as Chicory in Western countries, contained substantial phenolic acids displaying significant anti-inflammatory activities. We recognized the potential of harnessing Chicory for the treatment of IBD, prompting a need for in-depth investigation into the underlying mechanisms. METHODS: On the third day, mice were given 100, 200 mg/kg of total phenolic acids (PA) from Chicory and 200 mg/kg of sulfasalazine (SASP) via gavage, while dextran sodium sulfate (DSS) concentration was 2.5 % for one week. The study measured and evaluated various health markers including body weight, disease activity index (DAI), colon length, spleen index, histological score, serum concentrations of myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD), lipid oxidation (MDA), and inflammatory factors. We evaluated the TRP family and the NLRP3 inflammatory signaling pathways by Western blot, while 16S rDNA sequencing was used to track the effects of PA on gut microbes. RESULTS: It was shown that PA ameliorated the weight loss trend, attenuated inflammatory damage, regulated oxidative stress levels, and repaired the intestinal barrier in DSS mice. Analyses of Western blots demonstrated that PA suppressed what was expressed of transient receptor potential family TRPV4, TRPA1, and the expression of NLRP3 inflammatory signaling pathway, NLRP3 and GSDMD. In addition, PA exerted therapeutic effects on IBD by regulating gut microbiota richness and diversity. Meanwhile, the result of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis showed that gut microbiota was mainly related to Membrane Transport, Replication and Repair, Carbohydrate Metabolism and Amino Acid Metabolism. CONCLUSION: PA derived from Chicory may have therapeutic effects on IBD by regulating the TRPV4/NLRP3 signaling pathway and gut microbiome. This study provides new insights into the effects of phenolic acids from Chicory on TRP ion channels and gut microbiota, revealing previously unexplored modes of action.

Blueberry and Blackberry Anthocyanins Ameliorate Metabolic Syndrome by Modulating Gut Microbiota and Short-Chain Fatty Acids Metabolism in High-Fat Diet-Fed C57BL/6J Mice.

In this study, blueberry (Vaccinium ssp.) anthocyanins (VA) and blackberry (Rubus L.) anthocyanins (RA) were used to investigate the effects on metabolic syndrome (MetS) and the potential mechanisms. Importantly, all of the data presented in this study were obtained from experiments conducted on mice. As a result, VA and RA reduced body weight gain and fat accumulation while improving liver damage, inflammation, glucose, and lipid metabolism induced by a high-fat diet. Moreover, VA and RA regulated the gut microbiota composition, decreasing the pro-obesity and proinflammation bacteria taxa, such as the phylum Actinobacterium and the genera Allobaculum and Bifidobacterium, and increasing those negatively associated with obesity and inflammation, such as the phylum Bacteroidetes and the genera Prevotella and Oscillospira. Additionally, the supplementation with VA and RA reversed the elevated levels of valeric, caproic, and isovaleric acids observed in the high-fat diet (HFD) group, bringing them closer to the levels observed in the Chow group. This reversal indicated that alterations in the composition and abundance of gut microbiota may contribute to the restoration of short-chain fatty acids (SCFAs) levels. Additionally, PICRUSt2 exhibited that cyanamino acid metabolism and betalain biosynthesis might be the major metabolic pathways in the HVA group compared with the HFD group, while in the HRA group, it was the phosphotransferase system. These findings suggest that VA and RA can ameliorate MetS by modulating the gut microbiota and production of SCFAs.

Luteolin Alleviates Oxidative Stress in Chronic Obstructive Pulmonary Disease Induced by Cigarette Smoke via Modulation of the TRPV1 and CYP2A13/NRF2 Signaling Pathways.

The current study aims to investigate the therapeutic potential of luteolin (Lut), a naturally occurring flavonoid found in various medicinal plants, for treating chronic obstructive pulmonary disease (COPD) through both in vitro and in vivo studies. The results demonstrated that Lut increased body weight, reduced lung tissue swelling and lung damage indices, mitigated systemic oxidative stress levels, and decreased alveolar fusion in cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced COPD mice. Additionally, Lut was observed to downregulate the expression of the TRPV1 and CYP2A13 proteins while upregulating SIRT6 and NRF2 protein expression in CS + LPS-induced COPD mice and cigarette smoke extract (CSE)-treated A549 cells. The concentrations of total reactive oxygen species (ROS) and mitochondrial ROS in A549 cells induced by CSE significantly increased. Moreover, CSE caused a notable elevation of intracellular Ca2+ levels in A549 cells. Importantly, Lut exhibited inhibitory effects on the inward flow of Ca2+ and attenuated the overproduction of mitochondrial and intracellular ROS in A549 cells treated with CSE. In conclusion, Lut demonstrated a protective role in alleviating oxidative stress and inflammation in CS + LPS-induced COPD mice and CSE-treated A549 cells by regulating TRPV1/SIRT6 and CYP2A13/NRF2 signaling pathways.

Chicoric Acid Attenuated Renal Tubular Injury in HFD-Induced Chronic Kidney Disease Mice through the Promotion of Mitophagy via the Nrf2/PINK/Parkin Pathway.

As the main factor in the pathogenesis of chronic kidney disease (CKD), the excessive apoptosis of renal tubular epithelial cells (RTECs) and its underlying mechanism of action are worth further investigation. Chicoric acid (CA), a major active constituent of the Uyghur folk medicine chicory, was recorded to possess a renal protective effect. The precise effect of CA on renal tubular injury in obesity-related CKD remains unknown. In the current study, CA was proven to ameliorate metabolic disorders including overweight, hyperglycemia, hyperlipidemia, and hyperuricemia in high fat diet (HFD)-fed mice. Furthermore, the reverse effect of CA on renal histological changes and functional damage was confirmed. In vitro, the alleviation of lipid accumulation and cell apoptosis was observed in palmitic acid (PA)-exposed HK2 cells. Treatment with CA reduced mitochondrial damage and oxidative stress in the renal tubule of HFD-fed mice and PA-treated HK2 cells. Finally, CA was observed to activate the Nrf2 pathway; increase PINK and Parkin expression; and regulate LC3, SQSTM1, Mfn2, and FIS1 expression; therefore, it would improve mitochondrial dynamics and mitophagy to alleviate mitochondrial damage in RTECs of obesity-related CKD. These results may provide fresh insights into the promotion of mitophagy in the prevention and alleviation of obesity-related CKD.

Simultaneous Determination of Five Coumarins in Peucedanum Decursivum Radix by UPLC.

OBJECTIVE: To establish an ultra-high performance liquid chromatography (UPLC) method for simultaneous determination of umbelliferonel, nodakenin, psoralen, xanthotoxin and bergapten contents in Peucedanum decursivum Radix. METHODS: The analysis was achieved on a Symmetry®C18 column (4.6 mm × 250 mm, 5 µm), with acetonitrile and water as the mobile phase in gradient elution mode. The column temperature was maintained at 30°C, with flow rate 1.0 mL·min-1. The injection volume of sample was 10 µL. The ultraviolet detection wavelength was set at the maximum absorption wavelength 325 nm for umbelliferonel and nodakenin, 259 nm for psoralen, xanthotoxin and bergapten, respectively. RESULTS: The five kinds of coumarins in Peucedanum decursivum Radix were separated well and the linear relation was obtained (R2 ≥ 0.9998). The average recoveries were 101.31, 105.27, 90.85, 106.42 and 90.19%, respectively, with Relative standard deviation (RSD) 3.07, 3.17, 1.62, 2.53 and 4.54%, respectively. CONCLUSIONS: The established method was accurate and feasible, which could be used as the basis of quality control of Peucedanum decursivum Radix.

Phenolic profiles, antioxidant activity and inhibition of digestive enzymes of water caltrop pericarps.

BACKGROUND: Water caltrop (Trapa natans L.) is widely cultivated as a popular vegetable or fruit in Asian countries. In China, water caltrop pericarp is also used as a functional food to treat metabolic syndrome. However, the profiling of bioactive substances and their pharmacological activities in different water caltrop varieties remains to be investigated. In the present study, three varieties of water caltrop pericarps collected from 13 origins in China were analyzed for their phenolic substances. To investigate the pharmacological activities, samples were tested for their free radical scavenging capacity and inhibitory potency against α-glucosidase and pancreatic lipase. RESULTS: In total, 46 phenolic compounds were identified in the ethanol extract of water caltrop pericarp using a liquid chromatography-quadrupole time of flight-tandem mass spectrometry method, most of which were hydrolyzable tannins. Two cultivated varieties samples exhibited a relatively higher phenolic content and stronger antioxidant and inhibitory activities against α-glucosidase and pancreatic lipase compared to those from the wild variety. Correlation analysis between phenolic contents and biological activities suggested that phenolic compounds exhibited potential free radical scavenging capacity, α-glucosidase and pancreatic lipase inhibitory activities. CONCLUSION: It is concluded that the phenolic compounds of water caltrop pericarp are promising sources of natural antioxidants, α-glucosidase and pancreatic lipase inhibitors. © 2021 Society of Chemical Industry.

Total Sesquiterpene Glycosides from Loquat Leaves Ameliorate HFD-Induced Insulin Resistance by Modulating IRS-1/GLUT4, TRPV1, and SIRT6/Nrf2 Signaling Pathways.

Loquat (Eriobotrya japonica Lindl.), a subtropical fruit tree native to Asia, is not only known to be nutritive but also beneficial for the treatment of diabetes in the south of China. To expand its development, this study was undertaken concerning the potential therapeutic role of total sesquiterpene glycosides (TSGs) from loquat leaves in insulin resistance (IR), the major causative factor of type 2 diabetes mellitus (T2DM). Male C57BL/6 mice were fed on high-fat diet (HFD) to induce IR and then were given TSG by oral administration at 25 and 100 mg/kg/day, respectively. TSG notably improved metabolic parameters including body weight, serum glucose, and insulin levels and prevented hepatic injury. Moreover, inflammatory response and oxidative stress were found to be remarkably alleviated in IR mice with TSG supplement. Further research in liver of IR mice demonstrated that TSG repaired the signalings of insulin receptor substrate-1 (IRS-1)/glucose transporter member 4 (GLUT4) and AMP-activated protein kinase (AMPK), which improved glucose and lipid metabolism and prevented lipid accumulation in liver. It was also observed that TSG suppressed the expression of transient receptor potential vanilloid 1 (TRPV1), whereas the signaling pathway of sirtuin-6 (SIRT6)/nuclear factor erythroid 2-related factor 2 (Nrf2) was significantly promoted. Based on the results, the current study demonstrated that TSG from loquat leaves potentially ameliorated IR in vivo by enhancing IRS-1/GLUT4 signaling and AMPK activation and modulating TRPV1 and SIRT6/Nrf2 signaling pathways.

Flavonoids isolated from loquat (Eriobotrya japonica) leaves inhibit oxidative stress and inflammation induced by cigarette smoke in COPD mice: the role of TRPV1 signaling pathways.

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease with few successful treatments, and is strongly associated with cigarette smoking (CS). Since the novel coronavirus has spread worldwide seriously, there is growing concern that patients who have chronic respiratory conditions like COPD can easily be infected and are more prone to having severe illness and even mortality because of lung dysfunction. Loquat leaves have long been used as an important material for both pharmaceutical and functional applications in the treatment of lung disease in Asia, especially in China and Japan. Total flavonoids (TF), the main active components derived from loquat leaves, showed remarkable anti-inflammatory and antioxidant activities. However, their protective activity against CS-induced COPD airway inflammation and oxidative stress and its underlying mechanism still remain not well-understood. The present study uses a CS-induced mouse model to estimate the morphological changes in lung tissue. The results demonstrated that TF suppressed the histological changes in the lungs of CS-challenged mice, as evidenced by reduced generation of pro-inflammatory cytokines including interleukin 6 (IL-6), IL-1ß, tumor necrosis factor α (TNF-α), nitric oxide (NO), and inducible nitric oxide synthase (iNOS) and diminished the protein expression of transient receptor potential vanilloid 1 (TRPV1). Moreover, TF also inhibited phosphorylation of IKK, IκB and NFκB and increased p-Akt. Interestingly, TF could inhibit CS-induced oxidative stress in the lungs of COPD mice. TF treatment significantly inhibited the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD). In addition, TF markedly downregulated TRPV1 and cytochrome P450 2E1 (CYP2E1) and upregulated the expression of SOD-2, while the p-JNK level was observed to be inhibited in COPD mice. Taken together, our findings showed that the protective effect and putative mechanism of the action of TF resulted in the inhibition of inflammation and oxidative stress through the regulation of TRPV1 and the related signal pathway in lung tissues. It suggested that TF derived from loquat leaves could be considered to be an alternative or a new functional material and used for the treatment of CS-induced COPD.

The Essential Oil from Acori Tatarinowii Rhizome (the Dried Rhizome of Acorus tatarinowii Schott) Prevents Hydrogen Peroxide-Induced Cell Injury in PC12 Cells: A Signaling Triggered by CREB/PGC-1α Activation.

Acori Tatarinowii Rhizome (ATR, the dried rhizome of Acorus tatarinowii Schott), a well-recognized traditional Chinese herbal medicine, is prescribed to treat neurological disorders. The essential oil is considered as the active fraction of ATR, and the neuroprotection of ATR essential oil (ATEO) is proven, including the protection against oxidative stress. However, the cellular mechanism of ATEO against oxidative stress has not been fully illustrated. In this study, to investigate the cellular mechanism of ATEO, the cytoprotective effect of ATEO against H2O2-induced injury was revealed in PC12 cells. ATEO treatment increased the viability of cells affected by H2O2-mediated injury, inhibited reactive oxygen species (ROS) accumulation, and induced the expression of several antioxidant proteins (SODs, GPx, and UCPs). The cytoprotective effect of ATEO was related to upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression, which was counteracted by PGC-1α specific knockdown. Using inhibitor of protein kinase A (PKA), we found that cAMP-response element binding protein (CREB) activation was involved in ATEO-induced PGC-1α expression. Taken together, we suggest that ATEO effectively prevents H2O2-induced cell injury possibly through the activation of CREB/PGC-1α signaling in PC12 cells. The results provide a molecular insight into the effect of ATEO on cytoprotection against oxidative stress.

Polyphenol-rich Trapa quadrispinosa pericarp extract ameliorates high-fat diet induced non-alcoholic fatty liver disease by regulating lipid metabolism and insulin resistance in mice.

In China, Trapa quadrispinosa (also called water caltrop) has long been used as a function food and folk medicine to treat diabetes mellitus for years. In the present study, the extract of T. quadrispinosa pericarp (TQPE) which mainly contains hydrolysable tannins was prepared to investigate the potential therapeutic action in non-alcoholic fatty liver disease (NAFLD) mice induced by high fat-diet (HFD). After the administration of TQPE (15, 30 mg/kg/day) for 8 weeks, the increased weight of body and liver were significantly suppressed. TQPE also ameliorated liver lipid deposition and reduced lipids parameters of blood in mice. Moreover, TQPE attenuated oxidative stress and showed a hepatoprotective effect in mice. TQPE was also found to decrease the value of homeostatic model assessment for insulin resistance. In addition, TQPE administration increased the phosphorylation of AMP-activated protein kinase (AMPK) and Acetyl-CoA carboxylase (ACC) and inhibited sterol regulatory element-binding protein (SREBP) in the liver tissue. Meanwhile, TQPE elevated insulin receptor substrate-1 (IRs-1) and protein kinase B (Akt) phosphorylation. These results reflected that, as a nature product, TQPE is a potential agent for suppressing the process of NAFLD via regulation of the AMPK/SREBP/ACC and IRs-1/Akt pathways.

Trapa natans pericarp extract ameliorates hyperglycemia and hyperlipidemia in type 2 diabetic mice

Abstract The pericarp of Trapa natans L., an annual aquatic floating herb belonging to Lythraceae family, is used as a folk medicine in China. In this study, extracts of Trapa natans pericarp were tested both in vitro and in vivo through a high-fat diet with a single medium dosage streptozotocin injection induced type 2 diabetic mice. Different solvent extracts of Trapa natans pericarp showed α-amylase and α-glucosidase inhibitory activity. After four weeks administration, the ethyl acetate extract of Trapa natans pericarp (50 and 100 mg/kg b.w.) reduced fasting blood glucose level, ameliorated oral glucose tolerance and insulin resistance, improved serum lipids alterations in type 2 diabetic mice as well. Additionally, ethyl acetate extract significantly elevated the insulin receptor substrate 1 and Akt serine/threonine kinase phosphorylation compared to diabetic group. HPLC-MS and HPLC-DAD analysis showed that the ethyl acetate extract was rich in hydrolysable tannins. Results support the notion that Trapa natans pericarp extract has a potential hypoglycemic activity.

Hepatoprotective Effect of Seed Coat ofEuryale ferox Extract in Non-alcoholic Fatty Liver Disease Induced by High-fat Diet in Mice by Increasing IRs-1 and Inhibiting CYP2E1.

Non-alcoholic fatty liver disease (NAFLD), a common chronic liver disease characterized by hepatic steatosis, affects 30-40% of the population in the world. The seed of Euryale ferox salisb. possesses several pharmacological actions, including metabolic syndrome. However, the seed coat of E. ferox was usually discarded as waste, which contains comparatively abundant polyphenols, and its biological activity has been rarely investigated. In this work, we evaluate the hepatoprotective effect of E. ferox seed coat extract (EFSCE), in NAFLD mice induced by high-fat diet (HFD). The HPLC-MS analysis indicated that the main components of EFSCE were polyphenols. And then, mice were treated with HFD for 4 weeks to induce NAFLD. The result showed that the body weight, weight of adipose tissue, the ratio of liver to body weight in NAFLD mice increased compared with control group. In addition, blood lipids parameters including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) also increased in NAFLD mouse model. It was showed that, after treated with EFSCE (15 and 30 mg/kg/day) for 4 weeks, the body weight, lipids deposition in the liver and blood lipids in HFD-induced NAFLD mice markedly reduced. Compared with NAFLD mice, EFSCE administration could also prevent malondialdehyde (MDA) overproduction and strengthen Superoxide Dismutase (SOD) activity to counteract oxidative stress. Moreover, EFSCE was also found effective in reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in HFD-induced NAFLD model, which indicated liver injury in NAFLD. Therefore, EFSCE (rich in polyphenols) is indicated as bioactive nature product for HFD-induced NAFLD treatment, by eliminating lipid accumulation and oxidative stress via regulation of IRs-1 and CYP2E1.

Antitussive and expectorant properties of growing and fallen leaves of loquat (Eriobotrya japonica)

ABSTRACT Folium Eriobotryae, the dried leaves of loquat (Eriobotrya japonica, (Thunb.) Lindl., Rosaceae), is a traditional Chinese medicine used to treat cough with phlegm in China. Fallen and growing loquat leaves were tested for their effect on coughing and expectoration in mice. HPLC-ELSD and HPLC-MS analyses of aqueous and ethanol extracts of fallen or growing leaves were used to identify the chemical components responsible for this effect. Both the aqueous and ethanol extracts of growing and fallen leaves of loquat contained antitussive and expectorant activities. Moreover, an aqueous extract of growing loquat leaves with a higher flavonoid content displayed a stronger expectorant activity while the ethanol extract of fallen loquat leaves that contained a higher content of triterpenoid acids induced a stronger antitussive activity.

A novel sesquiterpene glycoside from Loquat leaf alleviates oleic acid-induced steatosis and oxidative stress in HepG2 cells.

Loquat (Eriobotrya japonica) leaf has displayed beneficial effect on metabolic syndrome. In our previously study, total sesquiterpene glycosides (TSG) isolated from Loquat leaf exhibited therapeutic effect on Non-alcoholic fatty liver disease (NAFLD) in vivo, but the accurate active compound remains unknown. Sesquiterpene glycoside 1 (SG1) is a novel compound, which is exclusively isolated from Loquat leaf, but its biological activity has been rarely reported. The present study was designed to evaluate the pharmacological effect of SG1, the main component of TSG, in oleic acid (OA)-induced HepG2 cell model of NAFLD with its related mechanisms of action. In this study, both SG1 and TSG were found to significantly reduce the lipid deposition in the cell model. They could also decrease total cholesterol (TC), triglyceride (TG) and intracellular free fatty acid (FFA) contents. Compared with OA-treated cells, the superoxide dismutase (SOD) level increased, and the malondialdehyde (MDA) and 4-hydroxynonenal levels respectively decreased after the administration of SG1 or TSG. The high dose of SG1 (140 µg/mL) displayed a similar therapeutic effect as TSG at 200 µg/mL. Both SG1 and TSG were found to suppress the expression of cytochrome P450 2E1 (CYP2E1) and the phosphorylation of c-jun terminal kinase (JNK) and its downstream target c-Jun in OA-treated cell. These results demonstrate again that TSG are probably the main responsible chemical profiles of Loquat leaf for the treatment of NAFLD, for which it can effectively improve OA-induced steatosis and reduce oxidative stress, probably by downregulating of CYP2E1 expression and JNK/c-Jun phosphorylation, while SG1 may be the principle compound.

Wuling San protects kidney dysfunction by inhibiting renal TLR4/MyD88 signaling and NLRP3 inflammasome activation in high fructose-induced hyperuricemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Wuling San, a famous prescription in Chinese medicine, is composed of Polyporus, Poria, Alismatis rhizoma, Cinnamomi cortex and Atractylodis macrocephalae rhizoma, and promotes kidney function and diuresis. The main purpose of this study was to investigate its renal protective effect in high fructose-induced hyperuricemic mice. MATERIALS AND METHODS: ICR mice were fed with 30% fructose in drinking water for 6 weeks to induce hyperuricemia and renal dysfunction. Then mice were orally administrated for other 6 weeks with Wuling San (987, 1316, 1755 and 2340mg/kg), allopurinol (5mg/kg) and water daily, respectively. Serum and urine levels of uric acid, creatinine and blood urea nitrogen (BUN) were measured. Hematoxylin and eosin staining was used to assess renal histological changes. Renal interleukin (IL)-1ß concentrations were measured using ELISA kit. Renal protein levels of organic ion transporters, as well as toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling and pyrin domain containing 3 (NLRP3) inflammasome were determined by Western blot assay. RESULTS: Wuling San significantly decreased serum uric acid, creatinine and BUN levels, increased fractional excretion of uric acid (FEUA) in fructose-fed mice. It restored fructose-induced dysregulation of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), ATP-binding cassette subfamily G member 2 (ABCG2) and organic anion transporter 1 (OAT1), as well as organic cation transporter 1 (OCT1) and OCT2 in mice. Wuling San obviously alleviated infiltration of inflammation cells in kidney glomerulus of fructose-fed mice. Moreover, Wuling San suppressed the activation of TLR4/ MyD88 signaling to inhibit nuclear factor κB (NF-κB) signaling and mitogen-activated protein kinases (MAPKs) activation in fructose-fed mice. Additionally, Wuling San decreased NLRP3 inflammasome activation and IL-1ß secretion in the kidney of fructose-fed mice. CONCLUSION: Wuling San exerts renal protective effect by modulating renal organic ion transporters in fructose-induced hyperuricemic mice. The molecular mechanism of its action may be associated with the suppression of TLR4/MyD88 signaling and NLRP3 inflammasome activation to reduce IL-1ß production in high fructose-induced hyperuricemic mice.

Wuling san ameliorates urate under-excretion and renal dysfunction in hyperuricemic mice.

AIM: The present study was undertaken to characterize the effects of Wuling San on urate excretion and renal function, and explore its possible mechanisms of action in hyperuricemic mice. METHODS: Mice were administered with 250 mg·kg(-1) potassium oxonate by gavage once daily (10 animals/group) for seven consecutive days to develop a hyperuricemia model. Different doses of Wuling powder were orally initiated on the day 1 h after oxonate was given, separately. Allopurinol was used as a positive control. Serum and urine levels of uric acid and creatinine, and fractional excretion of uric acid (FEUA) were measured in hyperuricemic mice treated with Wuling San and allopurinol. Simultaneously, renal mRNA and protein levels of urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1), as well as organic cation/carnitine transporters mOCT1, mOCT2 and mOCTN2, were assayed by semi-quantitative RT-PCR and Western blot methods, respectively. RESULTS AND CONCLUSION: Compared to the hyperuricemia control group, Wuling San significantly reduced serum uric acid and creatinine levels, increased 24 h urate and creatinine excretion, and FEUA in hyperuricemic mice, exhibiting its ability to enhance urate excretion and improve kidney function. Wuling San was found to down-regulate mRNA and protein levels of mURAT1 and mGLUT9, as well as up-regulate mOAT1 in the kidney of hyperuricemic mice. Moreover, Wuling San up-regulated renal mRNA and protein levels of mOCT1, mOCT2 and mOCTN2, leading to kidney protection in this model.

Quercetin and allopurinol reduce liver thioredoxin-interacting protein to alleviate inflammation and lipid accumulation in diabetic rats.

BACKGROUND AND PURPOSE: Thioredoxin-interacting protein (TXNIP), a regulator of cellular oxidative stress, has been associated with activation of NOD-like receptor 3 (NLRP3) inflammasome, inflammation and lipid metabolism, suggesting it has a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in diabetes. In this study we investigated whether TXNIP is involved in type 1 diabetes-associated NAFLD and whether antioxidants, quercetin and allopurinol, alleviate NAFLD by targeting TXNIP. EXPERIMENTAL APPROACH: Diabetes was induced in male Sprague-Dawley rats by a single i.p. injection of 55 mg · kg⁻¹ streptozotocin. Quercetin and allopurinol were given p.o. to diabetic rats for 7 weeks. Hepatic function, oxidative stress, inflammation and lipid levels were determined. Rat BRL-3A and human HepG2 cells were exposed to high glucose (30 mM) in the presence and absence of antioxidants, TXNIP siRNA transfection or caspase-1 inhibitor, Ac-YVAD-CMK. KEY RESULTS: Quercetin and allopurinol significantly inhibited the TXNIP overexpression, activation of NLRP3 inflammasome, down-regulation of PPARα and up-regulation of sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, fatty acid synthase and liver X receptor α, as well as elevation of ROS and IL-1ß in diabetic rat liver. These effects were confirmed in hepatocytes in vitro and it was further shown that TXNIP down-regulation contributed to the suppression of NLRP3 inflammasome activation, inflammation and changes in PPARα and SREBPs. CONCLUSIONS AND IMPLICATIONS: Inhibition of hepatic TXNIP by quercetin and allopurinol contributes to the reduction in liver inflammation and lipid accumulation under hyperglycaemic conditions. The targeting of hepatic TXNIP by quercetin and allopurinol may have therapeutic implications for prevention of type 1 diabetes-associated NAFLD.

Protection of curcumin against fructose-induced hyperuricaemia and renal endothelial dysfunction involves NO-mediated JAK-STAT signalling in rats.

Increasing evidence has demonstrated that excess fructose consumption as a risk factor for metabolic syndrome causes hyperuricaemia and renal injury. Curcumin, a natural plant phenolic food additive, lowered serum urate, creatinine and blood urea nitrogen levels, and increased urinary urate and nitrate/nitrites levels, as well as renal nitric oxide (NO) production in fructose-fed rats. Moreover, curcumin regulated urate transport-related proteins and inhibited activation of the JAK2-STAT3 cascade and overexpression of SOCS3 and TGF-ß1 in the kidneys of fructose-fed rats. These results suggested that the anti-hyperuricaemic and renal protective actions of curcumin might be the result of renal NO-mediated JAK2-STAT3 signalling and TGF-ß1 normality, which ameliorated renal endothelial dysfunction to improve renal urate transporter system in this model. The present study may provide the evidence for the potential use of a functional food ingredient curcumin because of its action against hyperuricaemia and renal injury induced by high fructose intake.