Accumulated LPS induced by colitis altered the activities of vitamin D-metabolizing hydroxylases and decreased the generation of 25-hydroxyvitamin D.

It is generally accepted that low vitamin D (VD) levels are associated with a high prevalence factor for Inflammatory bowel disease (IBD). IBD patients have observed higher levels of lipopolysaccharide (LPS), ALT, and AST than healthy people. Gut-derived LPS causes inflammatory injury in the liver and kidney. The VD-metabolizing mechanism is involved in the liver and kidney, which means IBD might impact VD metabolism. However, whether IBD affects VD metabolism has not been studied. In vitro LPS resulted in decreased CYP2R1 in liver cells as well as decreased CYP27B1 and increased CYP24A1 in kidney cells, revealing that LPS changed the activities of several hydroxylases. Mice with acute colitis had an increased LPS in serum and liver with mild hepatic injuries, while mice with chronic colitis had a significant elevation of LPS in serum, liver, and kidney with hepatorenal injuries. Thus, the liver hydroxylase for VD metabolism would be the first to be affected in IBD. Consequently, serum 25-hydroxyvitamin D declined dramatically with a significant elevation of 24,25-dihydroxyvitamin D and 1,24,25-trihydroxyvitamin D. Unchanged serum levels of 1,25-dihydroxyvitamin D might be the result of other factors in vivo. In acute colitis, a small dosage (4 IU/day) of cholecalciferol could protect the colon, decrease the serum level of LPS, and finally increase serum 25-hydroxyvitamin D. However, this improvement of cholecalciferol was fading in chronic colitis. These results suggested that VD supplementations for preventing and curing IBD in the clinic should consider hepatorenal hydroxylases and be employed as soon as possible for a better outcome.

Esculin inhibits hepatic stellate cell activation and CCl4-induced liver fibrosis by activating the Nrf2/GPX4 signaling pathway.

BACKGROUND: Liver fibrosis (LF) is a pathological process of the liver that threatens human health. Currently, effective treatments are still lacking. Esculin, a prominent constituent found in the Fraxinus rhynchophylla. (bark), Aesculus hippocastanum. (bark), and Cichorium intybus. (herb), has been shown to possess significant anti-inflammatory, antioxidant, and antibacterial properties. However, to date, there have been no studies investigating its potential efficacy in the treatment of LF. OBJECTIVE: The study aims to investigate the therapeutic effect of esculin on LF and elucidate its potential molecular mechanism. METHODS: Carbon tetrachloride (CCl4) was injected intraperitoneally to induce LF in mice, and transforming growth factor ß1 (TGF-ß1) was injected to induce LX-2 cells to investigate the improvement effect of esculin on LF. Kit, histopathological staining, immunohistochemistry (IHC), immunofluorescence (IF), polymerase chain reaction (PCR), and western blot (WB) were used to detect the expression of fiber markers and nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway in liver tissue and LX-2 cells. Finally, molecular docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) were used to verify the targeting between Nrf2 and esculin. RESULTS: Esculin significantly inhibited CCl4-induced hepatic fibrosis and inflammation in mice. This was evidenced by the improvement of liver function indexes, fibrosis indicators, and histopathology. Additionally, esculin treatment prominently reduced the levels of pro-inflammatory factors, oxidative stress, and liver Fe2+ in CCl4-induced mice. In vitro studies also showed that esculin treatment significantly inhibited TGF-ß1-induced LX-2 cell activation and decreased alpha-smooth muscle actin (α-SMA) and collagen I expression. Mechanism experiments proved that esculin can activate the Nrf2/GPX4 signaling pathway and inhibit liver ferroptosis. However, when LX-2 cells were treated with the Nrf2 inhibitor (ML385), the therapeutic effect of esculin significantly decreased. CONCLUSION: This study is the first to demonstrate that esculin is a potential natural active ingredient in the treatment of LF, which can inhibit the activation of hepatic stellate cells (HSC) and improve LF. Its therapeutic effect is related to the activation of the Nrf2/GPX4 signaling pathway.

Monotropein inhibits colitis associated cancer through VDR/JAK1/STAT1 regulation of macrophage polarization.

Colorectal cancer (CRC) is a growing concern due to its high morbidity and mortality, and the search for effective and less toxic active substances against inflammatory bowel diseases has been a hot topic in the research and development of drugs against CRC. It is reported that monotropein isolated from the roots of Morinda officinalis, can improve Dextran Sodium Sulfate (DSS)-induced ulcerative colitis in mice, but its therapeutic effects and mechanisms for CRC treatment are still to be investigated. In the present study, we first used molecular docking, BLI, CESTA, and DARTS methods to detest whether monotropein targets VDR proteins. In addition, we used tumor cell conditioned co-culture and four models of macrophage polarisation to investigate the regulation of four macrophage polarisations by monotropein using RT-PCR, IF and western blot. Furthermore, we further validated the target of action of monotropein for the treatment of Azoxymethane (AOM)/DSS induced colitis associated cancer (CAC) using knockout animals. Meanwhile, we further explored the mechanism of action of monotropein in regulating polarisation by detecting JAK/STAT1-related genes and proteins. Molecular docking and biofilm interference techniques showed that monotropein bound to the VDR, and additional results from CESTA and DARTS suggested that VDR proteins are targets of monotropein. Furthermore, in tumor cell conditioned co-cultures or LPS + IFN-γ induced RAW264.7 cells, VDR translocation to the nucleus was reduced, JAK1/STAT1 signaling pathway proteins were up-regulated, and macrophages were polarised towards the M1-type after monotropein intervention. Animal models in which normal VDR or myeloid VDR was knocked out confirmed that JAK1 levels in intestinal tissues were increased after monotropein intervention, macrophages were polarised towards the M1 type, and CAC paracarcinomas were ameliorated. Taken together, the present study concluded that monotropein inhibited colitis-associated cancers through macrophage polarisation regulated by VDR/JAK1/STAT1.

Asperuloside alleviates lipid accumulation and inflammation in HFD-induced NAFLD via AMPK signaling pathway and NLRP3 inflammasome.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome of hepatic parenchymal cell steatosis caused by excessive lipid deposition, which is the chronic liver disease with the highest incidence in China. Asperuloside (ASP), a kind of iridoid compound, possesses natural pharmacological effects of anti-tumor, anti-inflammatory, antioxidant and anti-obesity. However, whether ASP can improve NAFLD remains unclear. PURPOSE: We aimed to investigate the effect of ASP on NAFLD mice induced by high-fat diet (HFD), and explore its mechanism in vivo and in vitro. METHODS: Pharmacodynamics of ASP was studied by HFD induction in NAFLD mice. HepG2 cells were induced by palmitic acid (PA) as cell model to investigate the effect of ASP on lipid deposition and inflammatory infiltration. Expression of Adenosine monophosphate - activated protein kinase (AMPK) signaling pathway and NOD-like receptor pyrin containing 3 (NLRP3) inflammasome were detected by Western blot and RT-PCR. Cytokines IL-1ß and TNF-α were detected by ELISA. RESULTS: ASP alleviated liver injury and inflammatory damage in mice with NAFLD. In addition, ASP improved lipid deposition as well as inflammatory response in HFD-induced NAFLD mice and PA-stimulated HepG2 cells. ASP ameliorated lipid deposition and inflammatory response by regulating the p-AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome. CONCLUSION: Our results suggest that ASP improve lipid deposition and inflammatory infiltration in NAFLD mice via regulating the AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome, which may be an effective candidate for the treatment of NAFLD.

Vitexin Regulates Angiogenesis and Osteogenesis in Ovariectomy-Induced Osteoporosis of Rats via the VDR/PI3K/AKT/eNOS Signaling Pathway.

It is extremely important to promote angiogenesis-dependent osteogenesis and ameliorate bone loss for the prevention and treatment of osteoporosis (OP) development. Vitexin, as one of the major active components in pigeonpea leave, promoted the proliferation of osteoblast and HUVECs in hypoxia. The present study aimed to investigate the effect of vitexin on alleviating osteoporosis in ovariectomized (OVX) rats and further explore its underlying mechanisms. Herein, the OVX rat model was established and treated with vitexin (10 mg kg-1) for 3 months. After being sacrificed, we performed hematoxylin-eosin (H&E) staining and micro-computed tomography (micro-CT) to assess bone mass, which found that trabecular bone was damaged in the OVX rat model. Vitexin could repair bone injury and promote osteoblast biochemical indicators and angiogenesis indicators. Furthermore, EAhy926 cells were used to further explore the effect of vitexin on improving hypoxia-induced endothelial injury in vitro. Vitexin had a protective effect on hypoxia-treated EAhy926 cells and up-regulated vitamin D receptor (VDR) signaling and promoted phosphorylation of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), and endothelial NO synthase (eNOS), which enhanced endothelial cell migration and tube formation. VDR small-interfering RNA (siRNA) transfection significantly decreased both VDR and p-eNOS proteins, and VDR siRNA transfection + vitexin could not further increase VDR and downstream proteins. Overall, this study presented that vitexin regulates angiogenesis and osteogenesis in ovariectomy-induced osteoporosis of rats via the VDR/eNOS signaling pathway.

Gingerenone A Alleviates Ferroptosis in Secondary Liver Injury in Colitis Mice via Activating Nrf2-Gpx4 Signaling Pathway.

Patients with ulcerative colitis (UC) have been found to be frequently associated with secondary liver injury (SLI). In this study, we investigated the protective effect of GA on dextran sodium sulfate (DSS)-induced SLI in mice and its mechanism. The SLI was established by adding 4% DSS in the drinking water of mice, and the effects of GA (5, 20 mg/kg, p.o., once a day for 7 days) in hepatic tissues were analyzed. HepG2 cells were induced by lipopolysaccharide (LPS) to detect the effect of GA on ferroptosis and the underlying mechanism. Pathological damage was determined by H&E. Liver parameters (AST and ALT), antioxidant enzyme activities (MDA and SOD), and the level of Fe2+ in the liver were detected by kits. Cytokine levels (TNF-α, IL-1ß, and IL-6) and Gpx4 activity in the liver were detected by ELISA. Finally, the activation of nuclear factor erythroid 2-like 2 (Nrf2) was detected to explore the mechanism. The results indicated that GA significantly attenuated DSS-induced hepatic pathological damage, liver parameters, and cytokine levels and increased the antioxidant enzyme activities. Moreover, GA attenuated ferroptosis in DSS-induced liver injury and upregulated Gpx4 expression in DSS-induced mice. Mechanistic experiments revealed that GA activated Nrf2 in mice. Taken together, this study demonstrates that GA can alleviate ferroptosis in SLI in DSS-induced colitis mice, and its protective effects are associated with activating the Nrf2-Gpx4 signaling pathway.

Vitexin Protects against Dextran Sodium Sulfate-Induced Colitis in Mice and Its Potential Mechanisms.

Vitexin, one of the major active components in hawthorn, has been shown to possess multiple pharmacological activities. Here, we sought to investigate the effect of vitexin on an ameliorating dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mouse model and further explored its potential mechanism. The results indicated that vitexin administration could significantly alleviate the signs of colitis via suppressing body weight loss, reducing disease activity index (DAI) score, and mitigating colonic damage. Also, vitexin treatment in colitis mice markedly inhibited the production of pro-inflammation cytokines (such as IL-1ß, IL-6, and TNF-α). Meanwhile, vitexin also could markedly down-regulate the phosphorylation levels of p65, IκB, and STAT1. Moreover, vitexin also dose-dependently increased the expressions of muc-2, ZO-1, and occludin proteins in colonic tissues of colitis mice. Further studies revealed that vitexin dramatically modulated the disturbed intestinal flora in colitis mice. Vitexin is beneficial for regulating abundances of some certain bacteria, such as Bacteroides, Helicobacter, Alistipes, Lachnospiraceae_NK4A136_group, and Lachnospiraceae_UCG-006. Interestingly, the correlation analysis indicated that key microbes were strongly correlated with colitis features, such as pro-inflammatory cytokines and gut barrier. Collectively, these results demonstrated that vitexin treatment alleviated inflammation, intestinal barrier dysfunction, and intestinal flora dysbiosis in colitis mice. Vitexin is expected to be a promising compound for UC treatment.

Asperuloside inhibited epithelial-mesenchymal transition in colitis associated cancer via activation of vitamin D receptor.

BACKGROUND: Asperuloside is a natural compound extracted from various herbs with several bioactivities. Its effects on anti-inflammation and anti-tumor indicated that asperuloside might prevent colorectal cancer developing from inflammatory bowel diseases (IBD). But there were few reports about the efficacy and mechanism of asperuloside on improving colorectal cancer. It has been reported that vitamin D receptor (VDR) could regulate the expression of SMAD3. In previous study, asperuloside could significantly improve the expression of VDR and reduced Smad3 mRNA in IEC-6 cell. PURPOSE: The present study was aimed to investigate the potential mechanism of asperuloside on inhibiting epithelial-mesenchymal transition (EMT) in colitis associated cancer. STUDY DESIGN: First, in LPS-injured IEC-6 cell, asperuloside inhibited phosphorylated p65 (p-p65) level, improved VDR expression and reduced Smad3 mRNA. Second, we wonder the relationship between VDR signaling and nucleus factor-kappaB (NF-κB) signaling during asperuloside on reducing Smad3 mRNA. And then, the effect of asperuloside on inhibiting EMT development through VDR/Smad3 was investigated. Finally, we testified the effect of asperuloside on protecting against colitis associated cancer (CAC) by inhibiting EMT development through VDR/Smad3. METHODS: Pyrrolidinedithiocarbamate ammonium (PDTC) was used for established NF-κB-inhibited IEC-6 cell. This cell was applied for investigating the relationship between NF-κB and VDR of asperuloside on inhibiting Smad3. VDR-inhibited cell was established by small interfering RNA (siRNA) of VDR and was employed to investigate the role of VDR for asperuloside on decreasing Smad3. Transforming growth factor ß1 (TGFß1) was used for inducing EMT/fibrosis in IEC-6 cell. TGFß1-stimulated cell was used for testifying the effect of asperuloside on inhibiting EMT development. AOM/DSS-induced CAC was established to investigate the effect of asperuloside on suppressing cancer development. RESULTS: Asperuloside inhibited the level of p-p65 which was up-regulated by LPS. Asperuloside could up-regulate VDR signaling and reduce Smad3 mRNA in NF-κB-knockdown IEC-6 cells. Asperuloside failed to reduce Smad3 mRNA due to VDR knockdown, which implied that asperuloside might down-regulate Smad3 mRNA dependently on activation of VDR signaling and independently on inhibiting NF-κB signaling. Asperuloside exhibited significant prevention of EMT development in TGFß1-induced IEC-6 cell (EMT cell) and mice CAC. Asperuloside reduced the transform of epithelial phenotype into motile mesenchymal phenotype in EMT cell along with decreasing levels of EMT markers by inhibiting Smad3 mRNA via activation of VDR. In mice with CAC, expression of VDR in colon was improved by asperuloside. Symptoms of colitis, tumor number and tumor size were significantly inhibited by asperuloside. Suppressed EMT development was determined by reduced α-SMA expression and decreased mRNAs of several EMT markers. CONCLUSION: Asperuloside might prevent CAC through inhibiting EMT development via regulation of VDR/Smad3 pathway.

Combined Administration of Vitamin D3 and Geniposide Is Less Effective than Single Use of Vitamin D3 or Geniposide in the Treatment of Ulcerative Colitis.

With the increasing incidence of ulcerative colitis (UC) in China, Chinese medicinal herbs or relatively active compounds are widely applied in treating UC. These medicines may be combined with other therapeutic agents such as vitamin D3. Nevertheless, the efficacy of these combinations for UC is unclear. Geniposide is an active component in many Chinese herbal medicines. It could ameliorate dextran sulfate sodium (DSS)-induced colitis in mice. This study was designed to determine the efficacy and mechanism of the single use and combination of geniposide and vitamin D3 on a mouse model of acute colitis. Data showed that a single administration of geniposide (2 mg/kg) or vitamin D3 (4 IU/day) could significantly improve the symptoms of UC and relieve colon damage. Geniposide and vitamin D could significantly decrease the levels of TNF-α and IL-6 in serum and colon, and increase the level of IL-10 in the colon. However, the combined treatment of geniposide (2 mg/kg) and vitamin D3 (4 IU/day) exerted less beneficial effects on UC in mice, indicating by less improvement of UC symptoms, colon damage, and inflammatory infiltration. The combination only downregulated the level of TNF-α in serum and IL-6 in the colon. Our data further demonstrated that geniposide could inhibit the activation of p38 MAPK and then restrict the vitamin D receptor signaling stimulated by vitamin D3. These results implied that the combination of geniposide and vitamin D3 might not be an ideal combined treatment for acute colitis, and the combination of vitamin D supplementary and geniposide (or herbal medicines rich in geniposide) need more evaluation before being applied to treat UC in clinic.

Phloridzin Ameliorates Lipid Deposition in High-Fat-Diet-Fed Mice with Nonalcoholic Fatty Liver Disease via Inhibiting the mTORC1/SREBP-1c Pathway.

We aimed to investigate whether phloridzin could alleviate nonalcoholic fatty liver disease (NAFLD) in mice, which was induced by feeding a high-fat diet (HFD). We initially analyzed the effect of phloridzin on alleviating HFD-induced NAFLD in C57BL/6J mice and oleic acid (OA)-stimulated human normal liver L-02 cells (L02). Then, we investigated the mechanism of phloridzin on the mTORC1/sterol-regulatory element-binding protein-1c (SREBP-1c) signaling pathway by siRNA analysis, qRT-PCR, flow cytometry, and western blot analysis in vivo and in vitro. The results revealed that phloridzin significantly inhibited the increase in body weight, alleviated abnormal lipid metabolism, and decreased lipid biosynthesis and insulin resistance. Moreover, phloridzin augmented the number of CD8+CD122+PD-1+ Tregs and CD4+FoxP3+ Tregs in HFD-fed C57BL/6J mice and HFD-fed aP2-SREBF1c mice and downregulated the mTORC1/SREBP-1c signaling pathway-related protein expressions in vivo and in vitro. Furthermore, phloridzin reduced the expression of SREBP-1c in SREBP-1c-RNAi-lentivirus-transfected L02 cells and reversed the SREBP-1c expression in HFD-fed aP2-SREBF1c transgenic mice. Phloridzin ameliorates lipid accumulation and insulin resistance via inhibiting the mTORC1/SREBP-1c pathways. These results indicated that phloridzin may actively ameliorate NAFLD.

Asperuloside suppressing oxidative stress and inflammation in DSS-induced chronic colitis and RAW 264.7 macrophages via Nrf2/HO-1 and NF-κB pathways.

BACKGROUND: Inflammatory bowel diseases (IBDs), which mainly include Crohn's disease (CD) and ulcerative colitis (UC), are chronic idiopathic inflammatory disease of the gastrointestinal tract for which effective pharmacological treatments are lacking or options are very limited. PURPOSE: Here, we aim to investigate the therapeutic effects of an iridoid glycoside, asperuloside (ASP) on mice experimental chronic colitis induced by dextran sulfate sodium (DSS) and further explore underlying mechanisms in vitro and in vivo. METHODS: LPS-treated RAW 264.7 cells showed inflammation and were assessed for various physiological, morphological and biochemical parameters in the absence or presence of ASP. Chronic colitis was induced by 2% DSS in mice, which were used as an animal model to explore the pharmacodynamics of ASP. We detected p65 and Nrf2 pathway proteins via Western blot and RT-PCR analysis, assessed the cytokines TNF-α and IL-6 via ELISA, tested p65 and Nrf2 nuclear translocation via fluorescence. In addition, the docking affinity of ASP and p65 or Nrf2 proteins in the MOE 2015 software. RESULTS: We found that ASP attenuated weight loss, disease activity index (DAI) and colonic pathological damage in colitis mice and restored the expressions of inflammatory cytokines in the colon. In addition, ASP restored antioxidant capacity in DSS-induced chronic colitis mice and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, ASP suppressed oxidative stress through increasing Nrf2, HO-1 and NQO-1 proteins expressions, and down-regulated nuclear levels of p65 to inhibit DSS-induced colonic oxidative stress and inflammation. Validation of the molecular docking results also indicated that ASP interacts with Nrf2 or p65 proteins. In summary, ASP improved DSS-induced chronic colitis by alleviating inflammation and oxidative stress, activating Nrf2/HO-1 signaling and limiting NF-κB signaling pathway, which may be an effective candidate for the treatment of IBD.

Vitexin prevents colitis-associated carcinogenesis in mice through regulating macrophage polarization.

BACKGROUND: Patients with inflammatory bowel disease are at increased risks of developing ulcerative colitis-associated colorectal cancer (CAC). Vitexin can suppress the proliferation of colorectal carcinoma cells in vitro orin vivo. However, different from colorectal carcinoma, CAC is more consistent with the transformation from inflammation to cancer in clinical chronic IBD patients. Therefore, we aim to investigated that vitexin whether possess benefic effects on CAC mice. PURPOSE: We aimed to determine the beneficial effects of vitexin on CAC mice and reveal its underlying mechanism. METHODS: The mouse CAC model was induced by Azoxymethane and dextran sodium sulfate (AOM/DSS) and CAC mice were treated with vitexin. At the end of this study, inflammatory cytokines of IL-1ß, IL-6, TNF-α, IL-10 as well as nitric oxide (NO) were detected by kits after long-term treatment of vitexin. Pathological changes and macrophage polarization were determined by H&E and immunofluorescence in adjacent noncancerous tissue and carcinomatous tissue respectively of CAC mice. RESULTS: Our results showed that oral administration of vitexin could significantly improve the clinical signs and symptoms of chronic colitis, relieve colon damage, regulate colonic inflammatory cytokines, as well as suppress tumor incidence and tumor burden. Interesting, vitexin caused a significant increase in serum level of NO and a higher content of NO in tumor tissue. In addition, vitexin significantly decreased M1 phenotype macrophages in the adjacent noncancerous tissue, while markedly up-regulated M1 macrophage polarization in the tumor tissue in the colon of CAC mice. CONCLUSION: Vitexin can attenuate chronic colitis-associated carcinogenesis induced by AOM/DSS in mice and its protective effects are partly associated with its alternations in macrophage polarization in the inflammatory and tumor microenvironment .

Monotropein alleviates secondary liver injury in chronic colitis by regulating TLR4/NF-κB signaling and NLRP3 inflammasome.

Recently, it has reported that many inflammatory bowel disease (IBD) patients were contracted secondary liver injury. Monotropein (MON), an iridoid glycoside, is demonstrated to possess protective effects on acute colitis mice due to its anti-inflammatory activities. However, it was remained unknown whether MON could inhibit secondary liver injury caused by IBD. The aim of the present study was to investigate the protective roles and mechanisms of MON on secondary liver injury in chronic colitis mice model. In this study, 2% Dextran sodium sulfate (DSS) was used to induce mice model of chronic colitis. The results showed that MON attenuated DSS-induced hepatic pathological damage, liver parameters, infiltration of macrophages and cytokines levels. Furthermore, we found that MON attenuated liver injury through suppressing the activation of the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and down-regulating the activity of NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome. All the data indicated that MON may be an effective therapeutic reagent to attenuate secondary liver injury induced by chronic colitis.

The effect of monotropein on alleviating cisplatin-induced acute kidney injury by inhibiting oxidative damage, inflammation and apoptosis.

Although cisplatin is a common drug in the treatment of malignant tumors, its clinical application is limited due to various side effects, especially acute kidney injury (AKI). Till now, few effective pharmacological strategies can be applied to inhibit cisplatin-induced AKI. Here, we aimed to investigate the protective effects and possible mechanisms of monotropein on cisplatin-induced AKI. In this study, an AKI model was established in cisplatin-treated mice, and serum level of inflammatory cytokines, protein expressions of biochemical indicators and renal pathology were analyzed. Our results showed that our results showed that monotropein could significantly attenuate cisplatin-induced nephrotoxicity and reduce the levels of blood urea nitrogen (BUN) and serum creatinine (CRE). Furthermore, monotropein inhibited cisplatin-induced oxidative stress by reducing MDA level and increasing the activities of GSH, SOD and CAT. The underlying mechanisms of monotropein on alleviating cisplatin-induced AKI were associated with the activation of Nrf2/HO-1 pathway against oxidative stress and the inhibition on NF-κB signaling to suppress inflammation as well as the regulation on the expressions of proteins in apoptosis pathway in this renal injury model. This study firstly provided the evidence that monotropein could significantly attenuate cisplatin-induced AKI and suggested that monotropein might be used as a potential agent to alleviate side effects of cisplatin.

Vitexin ameliorates chronic stress plub high fat diet-induced nonalcoholic fatty liver disease by inhibiting inflammation.

Evidences showed that chronic stress (CS) can aggravate the situation of nonalcoholic fatty liver disease (NAFLD). Vitexin is one of the major components in hawthorn, which is widely used to reduce blood lipid. This study was aimed to explore the therapeutic effects and potential mechanisms of vitexin on chronic stress mice with high-fat diet (CSHFD). The results showed that 5-week vitexin administration (40 mg/kg, i.g.) could obviously reduce hepatic fat deposition, alleviate lipid metabolism, and inhibit liver inflammation in CSHFD mice. In addition, vitexin significantly reduced hepatic macrophage infiltration, obviously down-regulated the mRNA and protein expressions of hepatic SREBP-1c, FAS, ACC. Moreover, we also found that vitexin treatment could significantly inhibit the expressions of TLR4/NF-κB signaling in CSHFD mice. This results suggested that vitexin could ameliorate chronic stress combined with high-fat diet induced NAFLD, and its mechanisms is closely related to inhibit TLR4/NF-κB signaling and reduce fatty acid synthesis proteins.

Curcumin attenuates potassium oxonate-induced hyperuricemia and kidney inflammation in mice.

Current evidences suggest that hyperuricemia is closely related to the overproduction or underexcretion of uric acid (UA). Curcumin (CUR), a natural polyphenol component extracted from the rhizome of Curcuma longa, has been reported to treat various symptoms such inflammation disease, seems to be efficacious in hyperuricemia. In this study, we aimed to investigate the effect of CUR on hyperuricemia and kidney inflammation in hyperuricemic mice. Administration with CUR (20 or 40 mg/kg) or allopurinol (ALL, 5 mg/kg) was given to mice orally one hour later after the injection of potassium oxonate (PO) (300 mg/kg, i.p.) for 14 days. CUR administration decreased the levels of uric acid (UA), creatinine (CRE) and blood urea nitrogen (BUN) in serum. Meanwhile, treatment with CUR effectively inhibited serum and liver xanthine oxidase (XOD) levels, and further renewed normal antioxidant enzymes activities (SOD, GSH-Px), reduced MDA accumulation in serum. Further studies showed that CUR decreased inflammatory cytokines productions (IL-1ß, IL-18) in serum, as well as inhibited PO-induced the activation of NLRP3 inflammasome signaling in the kidney. In conclusion, the study revealed that CUR exhibited anti-hyperuricemic and anti-inflammatory effects through suppressing NLRP3 inflammasome activation in kidney and provided the evidence for treating hyperuricemia and associated renal inflammation.

Investigation of Age Polyethism in Food Processing of the Fungus-Growing Termite Odontotermes formosanus (Blattodea: Termitidae) Using a Laboratory Artificial Rearing System.

Laboratory rearing systems are useful models for studying Rhinotermitid behavior. Information on the biology of fungus-growing termites, however, is limited because of the difficulty of rearing colonies in the laboratory settings. The physical structure of termite nests makes it impossible to photograph or to observe colonies in the field. In this study, an artificial rearing system for field-collected colonies of the fungus-growing termite Odontotermes formosanus (Shiraki) was developed to facilitate observation in the laboratory. We recorded colony activity within the artificial rearing system and documented a variety of social behaviors that occurred throughout the food processing of the colony. This complex miniature ecosystem was cooperatively organized via division of labor in the foraging and processing of plant materials, and the observed patterns largely resembled the caste and age-based principles present in Macrotermes colonies. This work extends our insights into polyethism in the subfamily Macrotermitinae.