Pharmaceutical Properties of a Tinted Formulation of a Biguanide Antiseptic Agent, Olanexidine Gluconate.

Olanexidine gluconate-containing preoperative antiseptic (OLG-C) is colorless, which makes it difficult to determine its area of application. To overcome this drawback, we realized a stable orange-tinted antiseptic (OLG-T) by adding new additives to OLG-C and investigated its pharmaceutical properties compared with OLG-C and povidone iodine (PVP-I). We evaluated the influence of the additives on the antimicrobial activity and adhesiveness of medical adhesives to OLG-T-applied skin by in vitro time-kill/ex vivo micropig skin assays and a peel test using excised micropig skin, respectively. In the in vitro time-kill assay, the bactericidal/fungicidal activity of OLG-T and OLG-C were equivalent. In the ex vivo micropig skin assay, their fast-acting and persistent bactericidal activities against vancomycin-resistant Enterococcus faecalis were higher than that of PVP-I. In the peel test, the adhesion force of the incise drape and the amount of stripped corneocytes on the peeled drape were comparable between OLG-T- and OLG-C-applied skin, but both were less than those of PVP-I-applied skin. The drapes for OLG-T- and OLG-C-applied skin had moderate adhesion force, and the drape-related injuries were expected to be weak. These results suggest that OLG-T performs no worse than OLG-C in terms of its antimicrobial activity and medical adhesive compatibility. Therefore, we expect OLG-T to lead to more convenient preoperative skin preparation and further contribute to lowering surgical site infection rates.

Protective mechanism of Erigeron breviscapus injection on blood-brain barrier injury induced by cerebral ischemia in rats.

This study investigates the protective effect of Erigeron breviscapus injection, a classic traditional Chinese medicine most typically used by Chinese minority to treat stroke, on cerebral ischemia-reperfusion injury and the related signaling pathways. Use network pharmacology methods to study the relationship between E. breviscapus (Vant.) Hand-Mazz. and ischemic stroke, predict the mechanism and active ingredients of E. breviscapus (Vant.) Hand-Mazz. in improving ischemic stroke disease. We study the protective effect of E. breviscapus injection on blood-brain barrier (BBB) injuries induced by cerebral ischemia in rats by regulating the ROS/RNS-MMPs-TJs signaling pathway. The rat model of focal cerebral ischemia-reperfusion injury has been prepared using the wire-suppository method. Firstly, the efficacy of E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid in protecting BBB injury caused by cerebral ischemia has been evaluated. Secondly, the following two methods have been used to study the mechanism of E. breviscapus injection in regulating the ROS/RNS-MMPS-TJS signaling pathway: real-time PCR and western blot for the determination of iNOS, MMP-9, claudin-5, occludin, ZO-1 mRNA and protein expression in brain tissue. We find that PI3K-Akt signaling pathway predicted by network pharmaology affects the blood-brain barrier function, so we chose the blood-brain barrier-related MMP-9, claudin-5, iNOS, occludin and ZO-1 proteins are used for research. The results of our research show that 3 drugs can reduce the rate of cerebral infarction in rats, relieve the abnormal neuroethology of rats, reduce the degree of brain tissue lesion, increase the number of the Nissl corpuscle cells and repair the neuron ultrastructure in injured rats. At the same time, it can obviously reduce the ultrastructure damage of the BBB in rats. All three drugs significantly reduced the content of Evans blue in the ischemic brain tissue caused by cerebral ischemia in rats with BBB injury. In addition, E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid can decrease the protein expression of iNOS and MMP-9 in rat ischemic brain tissue. In addition, 3,5-dicaffeoylquinic acid can increase the protein expression of claudin-5. We conclude that E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid have obvious therapeutic effects on BBB and neuron injury induced by cerebral ischemia in rats. Our results from studying the mechanism of action show that E. breviscapus injection and Scutellarin inhibited the activation of MMP-9 by inhibiting the synthesis of iNOS, 3,5-dicaffeoylquinic acid inhibits the expression and activation of MMP-9 by inhibiting the activation of iNOS and reducing the generation of free radicals, thus reducing the degradation of important cytoskeleton connexin claudin-5 in the tight junction (TJ) structure by inhibiting the expression and activation of MMP-9. Finally BBB structure integrity was protected.

Ingestion of xylooligosaccharides during the suckling period improve the feed efficiency and hindgut fermentation capacity of piglets after weaning.

Fiber ingestion during the suckling period is helpful for gut development and probiotic colonization. Xylooligosaccharides (Xos) and xylan (Xyl) were selected to investigate the effects of different polymerization degree fiber ingestion on the growth performance and microbiota fermentation capacity of pre- and post-weanling piglets. An in vitro fermentation trial was also conducted to verify the microbial fermentation capacity of weanling piglet fecal microbiota. Results showed that Xos and Xyl ingestion had no significant effect on the piglet body weight and D-lactate level in the plasma at 21 d during the suckling period. After weaning, piglets in the Xyl group had a lower average daily gain (ADG) (P < 0.05), vitro dry matter (DM) fermentability (P < 0.05) and activity of xylanase (P < 0.05) than the control and Xos groups. The Xos group had no significant difference in the ADG when compared with the control group, but a significantly lower feed conversion ratio (FCR) (P < 0.05) than the control group, which means a high feed efficiency in the Xos group. The highest carbohydrate digestion and absorption ability of fecal microbiota (P < 0.05) was found in the Xos group. Meanwhile, the Xos group had the highest butyrate production ability (P < 0.05) and activity of xylanase (P < 0.05) during in vitro fermentation. The ingestion of Xyl during the suckling period had negative effects on the feed efficiency and hindgut fermentation capacity of weanling piglets. Xylooligosaccharide ingestion to suckling piglets improves growth performance and feed efficiency after weaning through increasing the fermentation capacity of microbiota and fiber-degrading enzyme secretion.

Triglyceride-mimetic prodrugs of scutellarin enhance oral bioavailability by promoting intestinal lymphatic transport and avoiding first-pass metabolism.

The intestinal capillary pathway is the most common way to absorb oral drugs, but for drugs with poor solubility and permeability and high first-pass metabolism, this pathway is very inefficient. Although intestinal lymphatic transport of lipophilic drugs or prodrugs is a promising strategy to improve the oral delivery efficiency of these drugs. The prodrug strategy for modifying compounds with Log P > 5 to promote intestinal lymphatic transport is a common approach. However, transport of poor liposoluble compounds (Log P < 0) through intestinal lymph has not been reported. Herein, triglyceride-mimetic prodrugs of scutellarin were designed and synthesized to promote intestinal lymphatic transport and increase oral bioavailability. Lymphatic transport and pharmacokinetic experiments showed that two prodrugs did promote intestinal lymphatic transport of scutellarin and the relative oral bioavailability was 2.24- and 2.45-fold of scutellarin, respectively. In summary, triglyceride-mimetic prodrugs strategy was used for the first time to study intestinal lymphatic transport of scutellarin with Log P < 0, which could further broaden the application range of drugs to improve oral bioavailability with the assistance of intestinal lymphatic transport.

A study on distribution and stability of drugs at the interface of a scutellarin-loaded emulsion.

This work mainly studies the interfacial behaviors of scutellarin on a newly developed emulsion and establishes a three-phase distribution model. The results showed that the concentration of scutellarin could decrease the interfacial tension and the gel-liquid crystal phase transition temperature of phospholipids. By observing the micromorphology of the emulsion, it is inferred that the drug exists on the emulsion interface. The distribution of drugs in three phases at different pH was calculated. The results showed that when pH was in the range of 3.0-8.0, the content of scutellarin in the oil phase was less than 0.25%; when pH < 7.4, more than 88% of the drugs were on the interface; when pH > 7.4, the drugs were mainly distributed in the aqueous phase. Therefore, the behavior of emulsions (pH 6.0) in vitro and in vivo is mainly composed of the behavior of drugs on the interface. The study above can explain some properties of the emulsions after loading scutellarin. Including the decrease of particle size and stability constant Ke, the increase of zeta potential, and the decreased chemical stability after the pH value went higher.

Caffeinated energy drinks in the Canadian context: health risk assessment with a focus on cardiovascular effects.

In Canada, caffeinated energy drinks (CEDs) currently sold under Temporary Marketing Authorizations must meet strict eligibility criteria. These criteria, which include compositional and labelling requirements, were developed based on the outcome of a health risk assessment conducted by Health Canada (HC) in 2013. HC updated its assessment by reviewing new information with the focus on potential cardiovascular effects associated with the consumption of CEDs available for sale in Canada. Due to limited data on CED consumption among Canadians to derive accurate exposure information, the composition of a typical CED was characterized to assess the potential effects of single ingredients and synergistic interactions between ingredients on the cardiovascular system. Surveillance data on potential adverse effects related to CED consumption was also analyzed. After extensive review, HC's updated assessment confirms the current risk management approach for CEDs is health protective for Canadian consumers, including the potential for cardiovascular effects. The available evidence supports that moderate consumption (up to 500 mL per day) of a typical CED authorized for sale in Canada is safe for the general population of healthy adults and adolescents. It also re-confirms that vulnerable sub-populations (i.e., children, pregnant and/or breastfeeding women, and caffeine-sensitive individuals) should not consume CEDs. Novelty: Consumption up to 500 mL per day of a typical CED is not associated with an increased risk of cardiovascular effects. Children, pregnant and/or breastfeeding women, and caffeine-sensitive individuals should not consume CEDs.

Cyclodextrin pendant polymer as an efficient drug carrier for scutellarin.

A novel ß-cyclodextrin pendant polymer (ε-PL-CD), composed of poly(ε-lysine) (ε-PL) main chain and glycine-ß-cyclodextrin (Gly-CD) side chains, was prepared by a simple two-step procedure. The ε-PL-CD was investigated as a drug carrier of hydrophobic drug scutellarin (SCU). The characterization and complexation mode of the SCU:ε-PL-CD were researched in both solution and solid state by means of photoluminescence spectroscopy, 1H and 2D NMR, X-Ray powder diffraction (XRPD), thermal gravimetric analysis, Particle size and Zeta potential. The solubility test indicated that the solubilizing ability of SCU:ε-PL-CD was significantly improved compared with SCU:ß-CD and free SCU. Besides, in vitro cell experiment, it was found that SCU:ε-PL-CD has a strong inhibitory effect on the growth and invasion of tumor cells. The present study provides useful information for ε-PL-CD as a drug carrier material.

Prebiotic Xylo-Oligosaccharides Ameliorate High-Fat-Diet-Induced Hepatic Steatosis in Rats.

Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having only a minor impact on the GM composition. When supplemented with HFD, XOS ameliorated hepatic steatosis. The underlying mechanisms involved enhanced hepatic ß-oxidation and mitochondrial respiration. Nuclear magnetic resonance (1H-NMR) analysis of cecal metabolites showed that, compared to the HFD, the LFD group had a healthier cecal short-chain fatty acid profile and on the HFD, XOS reduced cecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Cecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, XOS supplementation can ameliorate NAFLD by improving hepatic oxidative metabolism and affecting GM.

Oral Supplements of Combined Bacillus licheniformis Zhengchangsheng® and Xylooligosaccharides Improve High-Fat Diet-Induced Obesity and Modulate the Gut Microbiota in Rats.

Gut dysbiosis induced by high-fat diet (HFD) may result in low-grade inflammation leading to diverse inflammatory diseases. The beneficial effects of probiotics and prebiotics on obesity have been reported previously. However, their benefits in promoting human health and the underlying mechanisms still need to be further characterized. This study is aimed at understanding how probiotic Bacillus licheniformis Zhengchangsheng® (BL) and prebiotic xylooligosaccharides (XOS) influence the health of a rat model with HF (60 kcal %) diet-induced obesity. Five groups of male Sprague Dawley (SD) rats were fed a normal fat diet (CON) or an HFD with or without BL and XOS supplementation for 3 weeks. Lipid profiles, inflammatory biomarkers, and microbiota composition were analyzed at the end of the experiment. Rats fed an HFD exhibited increased body weight and disordered lipid metabolism. In contrast, combined BL and XOS supplementation inhibited body weight gain and returned lipid metabolism to normal. Furthermore, BL and XOS administration changed the gut microbiota composition and modulated specific bacteria such as Prevotellaceae, Desulfovibrionaceae, and Ruminococcaceae. In addition, supplements of combined BL and XOS obviously reduced the serum LPS level, which was significantly related to microbial variations. Our findings suggest that modulation of the gut microbiota as a result of probiotic BL and prebiotic XOS supplementation has a positive effect on HFD-induced obesity in rats.

Synbiotic supplementation containing Bifidobacterium infantis and xylooligosaccharides alleviates dextran sulfate sodium-induced ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease whose prevalence is increasing globally. A synbiotic has probiotic and prebiotic components and is regarded as a promising candidate for alleviating UC-associated inflammation. The purpose of this study is to determine whether there is an additive efficacy between the probiotic Bifidobacterium infantis (B. infantis) and the prebiotic xylooligosaccharide (XOS) against UC. C57BL/6 mice were treated with B. infantis, XOS, or synbiotic (combination of B. infantis and XOS) for 21 d. During the final 7 d of treatment, the mice were administered dextran sulfate sodium (DSS) dissolved in drinking water to induce colitis. All treatments decreased the disease activity index (DAI) and pathological scores, and synbiotic treatment was more efficacious than either the probiotic or prebiotic alone. Compared with the DSS-induced colitis group, all treatment groups significantly downregulated the proinflammatory cytokines TNF-α and IL-1ß, and synbiotic treatment significantly upregulated the anti-inflammatory cytokine IL-10 in the colon tissues. Furthermore, all treatments significantly reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome mRNA level in the colon tissues. All treatments significantly inhibited oxidative stress and increased zonula occludens-1 (ZO-1), occludin, and claudin-1 tight junction (TJ) molecule mRNA levels in the colon tissues. Therefore, the observed efficacy of synbiotics against colitis may be explained by the additive combination of the direct anti-inflammatory effects of the probiotic and prebiotic components and their ability to fortify colonic epithelial barrier integrity. Our findings suggest that a synbiotic is a promising dietary supplement or functional food for the effective management of UC.

Probiotics, prebiotics, and synbiotics regulate the intestinal microbiota differentially and restore the relative abundance of specific gut microorganisms.

Fermented milk is an effective carrier for probiotics, the consumption of which improves host health. The beneficial effects of probiotics, prebiotics, and synbiotics on gut dysbiosis have been reported previously. However, the way in which specific probiotics, prebiotics, and synbiotics regulate intestinal microbes remains unclear. Therefore, the probiotics Lactobacillus rhamnosus AS 1.2466 and Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 and the prebiotics xylooligosaccharide and red ginseng extracts were fed to mice to determine their effects on the intestinal microbiota. Then, mice were administered xylooligosaccharide and L. rhamnosus (synthesis) by gavage, and the number of L. rhamnosus was determined in the intestine at different times. The results show that probiotics and prebiotics can quickly reduce the Firmicutes/Bacteroidetes ratio, inhibit harmful bacteria (such as Klebsiella and Escherichia coli), and accelerate the recovery of beneficial intestinal microorganisms (such as Lactobacillus). In a complex intestinal microecology, different probiotics and prebiotics have different effects on specific intestinal microorganisms that cannot be recovered in the short term. In addition, after 20 d of intragastric xylooligosaccharide addition at 0.12 g/kg of body weight, L. rhamnosus colonization in the mouse ileum was 7.48 log cfu/mL, which was higher than in the low-dose group, prolonging colonization time and increasing the number of probiotics in the intestine. Therefore, this study demonstrated that probiotics and prebiotics can promote the balance of intestinal microbiota by regulating specific microbes in the intestine, and the effects of a suitable combination of synbiotics are beneficial, laying the foundation for the development of new dairy products rich in synbiotics.

Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway.

Oroxindin is a flavonoid isolated from the traditional Chinese medicine Huang-Qin, which has shown various pharmacological activities including anti-inflammatory, antitumor, antioxidant, etc. Thus far, the effect of oroxindin on colonic inflammation and the underlying mechanism remain unknown. In this study, we investigated the tissue distribution of oroxindin and its therapeutic effects on ulcerative colitis (UC) as well as the underlying mechanisms. UC model was established in mice by administrating dextran sulfate sodium (DSS) in drinking water for 7 d. We first showed that oroxindin was largely absorbed by the colon as an active ingredient after normal mice received Huang-Qin-Tang, a traditional Chinese medicine decoction. UC mice were then treated with oroxindin (12.5, 25, 50 mg ·kg-1 ·d-1, i.g.) for 10 d. We found that oroxindin treatment greatly suppressed massive macrophages infiltration and attenuated pathological changes in colonic tissue. Furthermore, oroxindin treatment significantly inhibited the generation of IL-1ß and IL-18 in the colon via inhibiting the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome formation and activation. In cultured macrophages, LPS induced NLRP3 inflammasome formation and caspase-1 activation, which were suppressed by oroxindin (12.5-50 µM). In LPS-treated macrophages, oroxindin dose-dependently restored the expression of TXNIP protein, leading to suppressing TXNIP-dependent NF-κB activation. In conclusion, these results demonstrate that oroxindin could be absorbed by the colon and attenuate inflammatory responses via inhibiting NLRP3 inflammasome formation and activation, which is related to the inhibitory effect on TXNIP-dependent NF-κB-signaling pathway. Hence, oroxindin has the potential of becoming an effective drug for treating UC.

Boosted Growth Performance, Mucosal and Serum Immunity, and Disease Resistance Nile Tilapia (Oreochromis niloticus) Fingerlings Using Corncob-Derived Xylooligosaccharide and Lactobacillus plantarum CR1T5.

The present work, herein, studied the effects of corncob-derived xylooligosaccharides (CDXOS) and Lactobacillus plantarum CR1T5 (LP) integrated into fish diets (diet 1 (0-control), diet 2 (10 g kg-1 CDXOS), diet 3 (108 CFU g-1L. plantarum CR1T5), diet 4 (10 g kg-1 CDXOS +108 CFU g-1L. plantarum CR1T5)) on growth performance, innate immune parameters, and disease resistance of Nile tilapia (Oreochromis niloticus). Fingerlings, with average mean weight of 4.97 ± 0.04, were randomly distributed into 16 glass tanks (20 fish per tank) for 12 weeks. Growth performance, skin mucus, and serum immune parameters were evaluated at the conclusion of the experiment. Eight randomly selected fish were used for challenge test against Streptococcus agalactiae. The results indicated that fish fed CDXOS and LP had significantly improved final weight (FW), weight gain (WG), specific growth rate (SGR), and feed conversion ratio (FCR). However, no significant difference in survival rate was observed between specimens fed the supplemented diets and the control. Regarding skin mucus, the dietary inclusion of CDXOS and LP significantly increased lysozyme and peroxidase activities compared with the control (P < 0.05). Similarly, significant increases in serum lysozyme, peroxidase, alternative complement, phagocytosis, and respiratory burst activities were observed in the fish fed the supplemented diets. However, no significant differences were found in these parameters between fish fed CDXOS and LP diets. For the challenge test, diet 4 produced a higher relative percentage of survival (RPS) and resistance to S. agalactiae than fish from the other experimental groups (P < 0.05). The results suggested that CDXOS and L. plantarum CR1T5 are viable considerations for potential feed-additive sources.

Fermented soybean meal ameliorates Salmonella Typhimurium infection in young broiler chickens.

The present study was designed to investigate the effectiveness of dietary fermented soybean meal (FSBM) in comparison with prebiotic (Xylooligosaccharide; XOS) and probiotic (Lactic acid bacteria-based probiotic; LAC) for prevention of Salmonella Typhimurium (ST) infection in young broiler chickens from 1 to 24 d. The in vitro study revealed that soybean meal (SBM) fermentation increased the number of lactic acid bacteria (LAB) and lactic acid content and inhibited the growth of enterobacteria such as coliforms in SBM. A total of 450 day-old Ross 308 broiler chicks were placed in 30 pens (15 birds/pen) and allocated to 5 experimental treatments that consisted an un-supplemented basal diet and not infected (NC) or infected with ST (IC); IC plus 2 g XOS/kg; IC plus 0.2 g LAC/kg; and IC containing a complete replacement of SBM with FSBM. All birds (except NC) were orally administered with 0.5 mL of the ST solution (1 × 106 CFU/mL) at d 3 post-hatch. The ST challenge decreased body weight gain and feed intake (P < 0.05). The impairment of feed conversion ratio was alleviated by the addition of XOS, LAC, and FSBM in broiler diets compared with IC birds (P < 0.05). The ST infection reduced duodenum and jejunum villus height and increased Salmonella colonization throughout the gut as well as internal organ invasion compared with NC birds (P < 0.05). However, ST-infected broilers fed the XOS, LAC, and FSBM-containing diets showed a significant decrease in gut Salmonella colonization, and internal organ invasion, an increase in LAB counts, and improvement in intestinal mucosa morphology (P < 0.05). The tested feed additives or FSBM reduced heterophil to lymphocyte ratio compared with the IC group (P < 0.05). The results suggest that XOS, LAC, and FSBM improve growth performance, lower Salmonella colonization, and improve intestinal characteristics and immune response in ST-challenged broiler chicks. Therefore, fermented feeds due to having functional ingredients can be considered as an effective strategy to lessen the colonization of gut pathogens in broiler chickens.

Oligosaccharides as co-encapsulating agents: effect on oral Lactobacillus fermentum survival in a simulated gastrointestinal tract.

OBJECTIVES: Four kinds of oligosaccharides were used as co-encapsulating agents to test the effect of extrusion-based microencapsulation on protection of Lactobacillus fermentum L7 against exposure to simulated gastric and intestinal juices as well as long-term refrigeration storage at 4 °C. RESULTS: The combination of alginate with galacto-oligosaccharides, isomalto-oligosaccharides, fructo-oligosaccharides, and xylo-oligosaccharides, or alginate alone exhibited good properties of the beads. The diameters of the cell beads co-encapsulated with oligosaccharides and encapsulated with alginate alone were similar, in the range of 2.34-2.51 mm. However, the encapsulation yield of L. fermentum cells co-encapsulated with oligosaccharides, which was in the range of 79.52-89.75%, was significantly higher than that of cells encapsulated with alginate alone. The capsules were stable in gastric conditions and can disintegrated when exposed to intestinal conditions. Additionally, the viability of microencapsulated cells after exposure to the simulated gastric and intestinal juices as well as long-term refrigeration storage was better than that of free cells, and the viability of cells co-encapsulated with oligosaccharides was better than that of cells encapsulated with alginate alone. Furthermore, fructo-oligosaccharides used as co-encapsulating agent showed the best performance. CONCLUSIONS: Microencapsulating L. fermentum with oligosaccharides protected cells well at a low temperature and offered effective gastrointestinal delivery of probiotics, and thus has the potential to maintain bacterial survival in probiotic products and will provide the research basis for design of effective probiotic-prebiotic combinations to maximize host benefit.

Scutellarin inhibits human renal cancer cell proliferation and migration via upregulation of PTEN.

BACKGROUND: Scutellarin is a naturally flavone glycoside that has been shown to exhibit anti-proliferative and anti-apoptotic activities among various human malignancies. However, the anti-cancer effect of Scutellarin in Renal cell carcinoma (RCC) and the underlying mechanism remains unclear. METHODS AND MATERIALS: RCC cell lines ACHN and 786-O were treated with different concentrations (0-210 µM) of Scutellarin in vitro. Cell viability and proliferation were investigated by MTT and colony formation assays. Cell invasion and migration were detected by Transwell assays. Cell apoptosis and cell cycle distribution was measured by flow cytometry. Western blot was used to investigate the expression levels of crucial proteins. Xenograft tumor model was established to evaluate tumor growth in vivo. RESULTS: Scutellarin significantly inhibited RCC cell proliferation in a dose- and time- dependent manner. Treatment of RCC cells with Scutellarin (30, 60, and 90 µM) markedly induced apoptosis and cell cycle arrested at G0/G1 phase in a concentration-dependent characteristic. Cell invasion and migration capacities of RCC cells were also dose-dependently suppressed by Scutellarin treatment. Western blot assays revealed that the crucial proteins including cyclin D1, CDK2, Bcl2, MMP-2, and MMP-9 were significantly reduced while Bax, cleaved caspase 3 and p21 were increased by Scutellarin in RCC cells. In vivo assay indicated that Scutellarin possessed anti-cancer effect on xenograft without triggering toxic effect. Mechanically, Scutellarin dramatically increased the protein level of phosphatase and tensin homologue (PTEN) and inhibited the activity of P13K/AKT/mTOR signaling. Ectopic expression of PTEN enhanced the inhibitory effect of Scutellarin on RCC proliferation while knockdown of PTEN abrogated it through regulating its downstream P13K/AKT/mTOR signaling pathway. CONCLUSION: Scutellarin inhibited RCC cell proliferation and invasion partially by enhancing the expression of PTEN through inhibition of P13K/AKT/mTOR pathway, suggesting that Scutellarin might serve as a potential therapeutic agent in RCC treatment.

Scutellarin Ameliorates Learning and Memory Deficit via Suppressing ß-Amyloid Formation and Microglial Activation in Rats with Chronic Cerebral Hypoperfusion.

Chronic cerebral hypoperfusion is considered as a pivotal factor of cognitive impairment that occurs in cerebrovascular diseases. This study investigated the ameliorating effect of scutellarin (SCT) on spatial cognitive impairment and ß-amyloid (Aß) formation in rats with chronic cerebral hypoperfusion induced by permanent bilateral common carotid artery occlusion (pBCAO). SCT is a flavonoid in medicinal herb of Erigeron breviscapus (vant.) Hand. Mazz. known to have neuroprotective, antioxidative and anti-inflammatory effects. However, the beneficial effect and pivotal mechanism of SCT on cognitive impairment are still unclear. SCT was treated orally with two doses (10 or 30 mg/kg) for 4 weeks. Results of Morris water maze test performed on the ninth week after pBCAO revealed that SCT (30 mg/kg)-treated rats had significantly shortened escape latencies in acquisition training trials, significantly prolonged swimming time at the platform and its surrounding zone, significant increase in memory score, significant reduction in the number of target heading, and significant reduction in the time required for the first target heading during the retention trial compared to rats in the sham-control group. SCT significantly inhibited the production of Aß(1-40) and Aß(1­42) in brain tissues. However, SCT significantly upregulated the expression levels of amyloid precursor protein and ß-site APP-converting enzyme-1 in the hippocampus. In addition, SCT significantly inhibited the activation of Iba1-expressing microglia in brain tissues. The results suggest that SCT can exert ameliorating effect on spatial cognitive impairment caused by chronic cerebral hypoperfusion through suppressing Aß formation and microglial activation in brain tissues. Therefore, SCT can be used as a beneficial drug for vascular dementia and Alzheimer's disease.

Clinical benefits and pharmacology of scutellarin: A comprehensive review.

Stroke and myocardial infarction are among the most common causes of mortality and disability in the world. The ischemic injury underlying these illnesses is complex, involving intricate interplays among many biological functions including energy metabolism, vascular regulation, hemodynamics, oxidative stress, inflammation, platelet activation, and tissue repair that take place in a context- and time-dependent manner. The current drug therapy of choice is to timely resupply the blood to the ischemic tissue; but reperfusion may introduce additional harm to the tissue through a process known as ischemia/reperfusion injury. As such, new drugs that would complement reperfusion by providing neural and cardiovascular protection and by targeting multiple abnormalities in ischemia are receiving increased attention. Scutellarin is an herbal flavonoid glucuronide with multiple pharmacological activities. Owing to its multiple beneficial effects, such as anti-oxidant, anti-inflammation, vascular relaxation, anti-platelet, anti-coagulation, and myocardial protection, scutellarin has been used clinically to treat stroke, myocardial infarction, and diabetic complications. Over the past three decades, clinical and pharmacological studies have accumulated a body of evidence that not only demonstrated these therapeutic effects, but also provided significant insights into the pharmacokinetic behavior, therapeutic profile, and mode of action of scutellarin in humans and animal models. Medicinal modification and new drug delivery methods have led to the development of new derivatives and formulations of scutellarin with improved bioavailability, efficacy, and safety. Here we review the current literature on scutellarin to provide a comprehensive understanding of the pharmacological activity, mechanism of action, toxicity, and therapeutic potential of scutellarin for the treatment of ischemia, diabetic complications, and other chronic diseases.

Lactobacillus paracasei HII01, xylooligosaccharides, and synbiotics reduce gut disturbance in obese rats.

OBJECTIVES: The beneficial effects of pro-, pre-, and synbiotics on obesity with insulin resistance have been reported previously. However, the strain-specific effect of probiotics and the combination with various types of prebiotic fiber yield controversial outcomes and limit clinical applications. Our previous study demonstrated that the probiotic Lactobacillus paracasei (L. paracasei) HII01, prebiotic xylooligosaccharide (XOS), and synbiotics share similar efficacy in attenuating cardiac mitochondrial dysfunction in obese-insulin resistant rats. Nonetheless, the roles of HII01 and XOS on gut dysbiosis and gut inflammation under obese-insulin resistant conditions have not yet, to our knowledge, been investigated. Our hypothesis was that pro-, pre-, and synbiotics improve the metabolic parameters in obese-insulin resistant rats by reducing gut dysbiosis and gut inflammation. METHODS: Male Wistar rats were fed with either a normal or high-fat diet that contained 19.77% and 59.28% energy from fat, respectively, for 12 wk. Then, the high-fat diet rats were fed daily with a 108 colony forming unit of the probiotic HII01, 10% prebiotic XOS, and synbiotics for 12 wk. The metabolic parameters, serum lipopolysaccharide levels, fecal Firmicutes/Bacteroidetes ratios, levels of Enterobacteriaceae, Bifidobacteria, and gut proinflammatory cytokine gene expression were quantified. RESULTS: The consumption of probiotic L. paracasei HII01, prebiotic XOS, and synbiotics for 12 wk led to a decrease in metabolic endotoxemia, gut dysbiosis (a reduction in the Firmicutes/Bacteroidetes ratio and Enterobacteriaceae), and gut inflammation in obese-insulin resistant rats. CONCLUSIONS: Pro-, pre-, and synbiotics reduced gut dysbiosis and gut inflammation, which lead to improvements in metabolic dysfunction in obese-insulin resistant rats.