Study on the effects of microencapsulated Lactobacillus delbrueckii on the mouse intestinal flora

Abstract:

Objective: To evaluate the protective effects of microencapsulation on Lactobacillus delbrueckii by random, parallel experimental design. Materials and methods: Lincomycin hydrochloride-induced intestinal malfunction mouse model was successfully established; then the L. delbrueckii microcapsule was given to the mouse. The clinical behaviour, number of intestinal flora, mucous IgA content in small intestine, IgG and IL-2 level in peripheral blood were monitored. The histological sections were also prepared. Results: The L. delbrueckii microcapsule could have more probiotic effects as indicated by higher bifidobacterium number in cecal contents. The sIgA content in microcapsule treated group was significantly higher than that in non-encapsulated L. delbrueckii treated group (p?<?0.05). Intestine pathological damage of the L. delbrueckii microcapsule-treated group showed obvious restoration. Conclusion: The L. delbrueckii microcapsules could relieve the intestinal tissue pathological damage and play an important role in curing antibiotic-induced intestinal flora dysfunction.     

Effects of Maydis stigma polysaccharide on the intestinal microflora in type-2 diabetes

Context: Diabetes is a serious endocrine and metabolic disorder. Food supplements attract people’s attention in mitigating health problems from the aspect of gastrointestinal microflora. Maydis stigma (Zea mays subsp. mays L. [Poaceae]), has been used as water decoction for treating diabetes in folk medicine. It has great potential, and feasibly a stable form of Maydis stigma commercial products could be developed to fulfil the health food market.

Objective: To study the effects of Maydis stigma polysaccharide (MSP) on the intestinal microflora in type-2 diabetes (T2D).

Materials and methods: MSP was fractioned from Maydis stigma by distilled water, purified by DEAE-52 Cellulose chromatography and Sephadex G-200 gel column. Streptozotocin (160?mg/kg) was intraperitoneal injected for 3 days to build model. The diabetic mice were randomly divided into five groups together with control group (10 mice in each group). The doses of MSP were 400, 600 and 800?mg/kg, respectively. After 5 weeks of administration, antidiabetic effects and intestinal microflora balance restoring activities were evaluated by denaturing gradient gel electrophoresis.

Results: Blood glucose levels of MSP-treated groups showed extremely significant hypoglycemic effects (p?<?0.01), body weight increased showed extremely significant (p?<?0.01) differences. Bacteroides, Lactobacillus and Prevotella were dominant organisms in the intestinal tract. The quality and quantity of Lactobacillus and Bacteroides genus increased remarkably with increasing concentration of MSP.

Discussion and conclusion: Experimental results of this study suggest that MSP has the significant potential to be used as a natural agent for treating T2D and restoring the intestinal microflora balance.     

Factors associated with public injection and nonfatal overdose among people who inject drugs in street-based settings

Background: In 2016, BC Canada declared a public health emergency in response to increasing illicit drug overdose deaths. Previous research has shown that adverse social conditions including unstable housing and insufficient harm reduction services can exacerbate public injection and overdoses.

Methods: Cross-sectional interview data from Victoria (2008–2015) and Vancouver (2008–2012), BC (n?=?548) were analysed using multivariate logistic regression models to assess differences in risks and harms for people 19+ who inject drugs in street-based settings.

Results: Living in Victoria (OR: 5.55, 95%CI: 3.44–8.95; p?p?p?p?p?p?p?p?p?p?Conclusions: Mitigating risk environments for public injection and overdose requires attention to micro- and macro-level factors. Overall findings indicate that implementation of a supervised injection facility in Victoria would likely reduce public injection and overdoses.     

Antidiabetic mechanism of Coptis chinensis polysaccharide through its antioxidant property involving the JNK pathway

Abstract

Context: Antidiabetic activity of Coptis chinensis Franch (Ranunculaceae) polysaccharide (CCPW) has been reported. However, its molecular mechanism remains unclear.

Objective: An attempt was made to further verify the antidiabetic activity of CCPW on type 2 diabetes mellitus (T2DM) and elucidate the mechanism of antidiabetic activity.

Materials and methods: Male Wistar rats were fed with high-fat diet (HFD) and injected with streptozotocin (STZ) to generate a T2DM model. Effects of CCPW on fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), glutathione (GSH), glutathione peroxidases (GSH-Px), superoxide dismutases (SOD), catalase (CAT), malondialdehyde (MDA), c-jun n-terminal kinase (JNK), phosphorylated insulin receptor substrate 1 (phospho-IRS1), phosphorylated phosphatidylinositol 3 kinase (phospho-PI3Kp85) and glucose transporter 4 (Glut4) were investigated.

Results: FBG level of diabetic rats could be significantly inhibited by 51.2, 42.7, and 23.3% through administration of CCPW at doses of 200, 100, and 50?mg/kg b.w., respectively (p?<?0.01). CCPW also could significantly reduce TG by 19.2, 12.1, and 7.4%, and TC by 24.2, 20.9, and 18.7%, respectively (p?<?0.05 or p?<?0.01). CCPW showed an obvious antioxidant effect through increasing GSH-Px, SOD, and CAT activities, and decreasing GSH and MDA contents (p?<?0.05 or p?<?0.01). Furthermore, CCPW could inhibit JNK and phospho-IRS1 expression and promote the expression of phospho-PI3Kp85 and Glut4 compared with those in the DM group (p?<?0.05 or p?<?0.01).

Discussion and conclusion: CCPW can produce antidiabetic activity in rats with T2DM through its antioxidative effect, which is closely related to the JNK/IRS1/PI3K pathway.     

The anti-arthritic activity of total glycosides from Pterocephalus hookeri,a traditional Tibetan herbal medicine

Context: Pterocephalus hookeri (C. B. Clarke) Hock., a traditional Tibetan herbal medicine rich in glycosides, has been used to treat several diseases including rheumatoid arthritis.

Objective: To evaluate the anti-arthritic activity of total glycosides from P. hookeri, and its possible mechanisms of action.

Materials and methods: Anti-arthritic activity of total glycosides from P. hookeri (oral administration for 30 days at 14–56?mg/kg) was evaluated using paw swelling, arthritis scores and histopathological measurement in adjuvant-induced arthritis (AA) Sprague-Dawley rats. The NF-κB p65 expression in synovial tissues, and serum superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels was measured in AA rats, respectively. Further assessment of anti-inflammatory and analgesic activities of these glycosides were carried out using inflammation and hyperalgesia models induced by xylene, carrageenan, agar and acetic acid, respectively.

Results: Total glycosides (56?mg/kg) decreased the paw swelling (38.0%, p?p?p?p?p?p?p?Discussion and conclusion: Our findings confirmed the anti-arthritic property of the total glycosides from P. hookeri, which may be attributed to its inhibition on NF-κB signalling and oxidative stress.     

1H NMR-based metabolic study reveals the improvements of bitter melon (Momordica charantia) on energy metabolism in diet-induced obese mouse

Context: Obesity can be ameliorated by some natural products such as polyphenol, flavones and saponin. As a typical medicinal plant, Momordica charantia L. (Cucurbitaceae) (bitter melon, BM) contains these natural chemicals and reduces diet-induced obesity in mice.

Objective: This study evaluates the metabolic effects of dietary BM supplement, investigates a global metabolic profile and determines associated perturbations in metabolic pathways.

Materials and methods: Male C57BL/6 mice were fed with low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with 5% BM based on 37.6?g/kg body weight in average for 12 weeks, respectively. Then energy metabolism was quantified using PhenoMaster/LabMaster. The spectroscopy of urine was acquired by nuclear magnetic resonance and latent biomarkers were identified. Pattern recognition analysis was used to discriminate associated metabolic profiles.

Results: Dietary BM supplement reduced body weight gain (?0.15-fold, p?<?0.01) and blood glucose levels (?0.19-fold, p?<?0.01) in HFD-fed mice. Meanwhile, the levels of energy metabolism were enhanced (0.08–0.11-fold, p?<?0.01). According to pattern recognition analysis, dietary BM supplement changed metabolic profiles in HFD-fed mice and the modified profiles were similar to those in LFD-fed mice. Finally, the mapping of metabolic pathways showed that dietary BM supplement primarily affected glucose metabolism-associated pathways.

Discussion and conclusion: The results indicated that BM improves weight loss in diet-induced obesity and elevate energy expenditure in HFD-fed mice. The pattern recognition with metabolic study may be used as a noninvasive detection method to assess the effects of dietary BM supplement on mouse energy metabolism.     

Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated rat: decisive role of TNF-α, IL-1β, COX-II and iNOS

Context: Overdose of acetaminophen (APAP) is common in humans and is often associated with hepatic damage. Withania somnifera (L.) Dunal (Solanaceae) shows multiple pharmacological activities including antioxidant and anti-inflammatory potential.

Objective: To evaluate the possible mechanism of hepatoprotective activity of withanolide-rich fraction (WRF) isolated from a methanolic extract of Withania somnifera roots.

Materials and methods: Hepatotoxicity was induced by oral administration of APAP (750?mg/kg, p.o.) for 14 d. The control group received the vehicle. APAP-treated animals were given either silymarin (25?mg/kg) or graded doses of WRF (50, 100 and 200mg/kg) 2?h prior to APAP administration. Animals were killed on 15th day and blood and liver tissue samples were collected for the further analysis.

Results: In WRF-treated group, there was significant and dose-dependent (p?<?0.01 and p?<?0.001) decrease in serum bilirubin, ALP, AST and ALT levels with significant and dose-dependent (p?<?0.01 and p?<?0.001) increase in hepatic SOD, GSH and total antioxidant capacity. The level of MDA and NO decreased significantly (p?<?0.01) by WRF treatment. Up-regulated mRNA expression of TNF-α, IL-1β, COX-II and iNOS was significantly down-regulated (p?<?0.001) by WRF. Histological alternations induced by APAP in liver were restored to near normality by WRF pretreatment.

Conclusion: WRF may exert its hepatoprotective action by alleviating inflammatory and oxido-nitrosative stress via inhibition of TNF-α, IL-1β, COX-II and iNOS.     

Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin

Abstract

Purpose: The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin.

Methods: The formulation was optimized by Plackett–Burman screening design and Box–Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin.

Results: The optimized formulations showed an average size of 135.3?±?1.5?nm with a zeta potential value of ?24.7?±?2.1?mV and 91.09%?±?1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC_0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, T_max and t_1/2 of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p?<?0.01). The in situ intestinal absorption study revealed that the effective permeability (P_eff) value of curcumin for SLNs was significantly improved (p?<?0.01) comparing to curcumin solution.

Conclusion: Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.     

Biological activities of salvianolic acid B from Salvia miltiorrhiza on type 2 diabetes induced by high-fat diet and streptozotocin

Abstract

Context: Salvia miltiorrhiza Bge. (Labiatae) has been widely used for treating diabetes for centuries. Salvianolic acid B (SalB) is the main bioactive component in Salvia miltiorrhiza; however, its antidiabetic activity and possible mechanism are not yet clear.

Objective: To investigate the effects of SalB on glycometabolism, lipid metabolism, insulin resistance, oxidative stress, and glycogen synthesis in type 2 diabetic rat model.

Materials and methods: High-fat diet (HFD) and streptozotocin-induced diabetic rats were randomly divided into model group, SalB subgroups (50, 100, and 200?mg/kg), and rosiglitazone group.

Results: Compared with the model group, SalB (100 and 200?mg/kg) significantly decreased blood glucose (by 23.8 and 21.7%; p?<?0.05 and p?<?0.01) and insulin (by 31.3 and 26.6%; p?<?0.05), and increased insulin sensitivity index (by 10.9 and 9.3%; p?<?0.05). They also significantly decreased total cholesterol (by 24.9 and 27.9%; p?<?0.01), low-density lipoprotein cholesterol (by 56.2 and 64.6%; p?<?0.01), non-esterified fatty acids (by 32.1 and 37.9%; p?<?0.01), hepatic glycogen (by 41.3 and 60.5%; p?<?0.01), and muscle glycogen (by 33.2 and 38.6%; p?<?0.05), and increased high-density lipoprotein cholesterol (by 50.0 and 61.4%; p?<?0.05 and p?<?0.01), which were originally altered by HFD and streptozotocin. In addition, SalB (200?mg/kg) markedly decreased triglyceride and malondialdehyde (by 31.5 and 29.0%; p?<?0.05 and p?<?0.01), and increased superoxide dismutase (by 56.6%; p?<?0.01), which were originally altered by HFD and streptozotocin.

Discussion and conclusion: The results indicate that SalB can inhibit symptoms of diabetes mellitus in rats and these effects may partially be correlated with its insulin sensitivity, glycogen synthesis and antioxidant activities.     

Effects and mechanisms of pirfenidone,prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models

Context: Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown.

Objective: This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF.

Materials and methods: Rat IPF model was established by endotracheal injection of 5?mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100?mg/kg once daily), prednisone (H, 5?mg/kg once daily) and acetylcysteine (N, 4?mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay.

Results: After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p?p?p?r?=??0.506, p?r?=?-0.676, p?r?=??0.590, p?r?=??0.530, p?r?=??0.553, p?Discussion and conclusion: Pirfenidone, prednisone and acetylcysteine can inhibit airsacculitis and pulmonary fibrosis in rat IPF models, which may be related with enhanced caveolin-1, reduced TNF-α, TGF-β1, PDGF.