Positive Drug Control Group Research Articles

Pharmacodynamics Research on Danggui-Shaoyao-San through Body Fluid Indexes of Spleen Deficiency-water Dampness Rats using Bio-impedance Technology.

Spleen deficiency-water dampness symptom is closely related to body fluid-mediated organism metabolism and circulation. However, previous clinical evaluation of spleen deficiency-water dampness model was based only on body weight, D-xylose excretion rate, serum gastrin content, etc. Therefore, we established a large sample of normal rats and model rats experiment to verify the scientific nature of bio-impedance measuring body fluid indexes for evaluation of the modeling state. Pharmacodynamics research on Danggui-Shaoyao- San (DSS) was conducted through body fluid index changes of rats using bio-impedance technology. A spleen deficiency-water dampness symptom rat model was established through an inappropriate diet combined with excess fatigue. Experimental rats were divided into a normal control group, a model control group, a positive drug control group (hydrochlorothiazide), a blood-activating group, a water-disinhibiting group, and a DSS group. Total Body Water/Body Weight (TBW%), extracellular fluid/total body water content (ECF%), intracellular fluid/total body water content (ICF%), extracellular fluid/intracellular fluid (ECF/ICF), fat mass/body weight (FM%), fat-free mass/body weight (FFM%), and fat mass/fat-free mass (FM/FFM) of 150 rats were detected by a Bio-Imp Vet Body analyzer. The TBW% of the model control group increased significantly, and the FM/FFM was significantly reduced compared with the normal group (P < 0.05) (P < 0.01), showing symptoms of spleen deficiency and diarrhea; the TBW% of the blood-activating group, and the waterdisinhibiting group decreased significantly, and the FM/FFM increased significantly (P < 0.05) (P < 0.01). The TBW% and FM/FFM in the water-disinhibiting group had returned to nearnormal values compared with the model control group. The blood-activating and waterdisinhibiting split prescriptions in DSS are both effective in treating spleen deficiency-water dampness rats. Comparatively, the fluid-regulating effect of split prescriptions in DSS was even stronger than that of DSS as shown in the present study. These findings suggest that using bio-impedance technology to measure body fluid indexes can pave a road for further exploring the molecular mechanism of the reason why the blood-activating and disinhibit-water split prescriptions in DSS are both effective in treating spleen deficiency-water dampness rats.

Complex probiotics alleviate ampicillin-induced antibiotic-associated diarrhea in mice.

Antibiotic-associated diarrhea (AAD) is a common side effect during antibiotic treatment, which can cause dysbacteriosis of the gut microbiota. Previous studies have shown beneficial effects in AAD treatment with Bifidobacterium lactis XLTG11, Lactobacillus casei Zhang, Lactobacillus plantarum CCFM8661, and Lactobacillus rhamnosus Probio-M9. However, no studies have been conducted on the immunomodulatory effects and protective intestinal barrier function of four complex probiotics. The aim of our study is to investigate the alleviation effects of complex probiotics on ampicillin-induced AAD. Thirty-six BALB/c mice were randomly divided into six groups: normal control group (NC), model control group (MC), low-, medium-, and high-dose probiotics groups (LD, MD, and HD), and positive drug (Bifico, 1 × 107 cfu) control group (PDC; Bifico, also known as Bifidobacterium Triple Live Capsule, is composed of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis). An AAD model was established by intragastric administration of ampicillin, by gavage of different doses of complex probiotics and Bifico. The weight gain, fecal water content, loose stool grade, intestinal permeability, total protein and albumin levels, intestinal barrier, cytokine levels, and gut microbiota were determined. The results showed that complex probiotics significantly decreased the fecal water content, loose stool grade, intestinal permeability, and ileum tissue damage. Their application increased the weight gain, SIgA, TP, and ALB levels. Additionally, complex probiotics significantly decreased the levels of pro-inflammatory cytokines and increased those of anti-inflammatory cytokines. Meanwhile, the mRNA expression levels of ZO-1, occludin, claudin-1, and MUC2 were significantly upregulated in the probiotic-treated group. Furthermore, the complex probiotics increased the gut microbiota diversity and modulated the changes in the gut microbiota composition caused by ampicillin. At the phylum level, the abundance of Proteobacteria in the HD group was lower than that in the MC group, whereas that of Bacteroidetes was higher. At the genus level, the abundances of Klebsiella and Parabacteroides in the HD group were lower, whereas those of Bacteroides, Muribaculaceae, and Lactobacillus were higher than those in the MC group. Moreover, Spearman's correlation analysis also found that several specific gut microbiota were significantly correlated with AAD-related indicators. We found that complex probiotics improved the diarrhea-related indexes, regulated gut microbiota composition and diversity, increased the expression levels of intestinal protective barrier-related genes, preserved the intestinal barrier function, and relieved inflammation and intestinal injury, thereby effectively improving AAD-associated symptoms. Graphical Abstract.

Hippophae rhamnoides L. leaf extract diminishes oxidative stress, inflammation and ameliorates bioenergetic activation in full-thickness burn wound healing

BackgroundGlobally, burn wounds are the prominent cause of morbidity and occasionally mortality, besides psychological and financial burden to the patients and health care systems. Numerous medical complexities associated with burn injuries prompted the quest for novel, practical therapeutic healing approaches, which could potentially influence different phases of the repair process positively. PurposeThe present study investigates the influence of Seabuckthorn leaf aqueous lyophilized extract (SBTL-ALE) on full-thickness burn wounds in rats to establish its healing efficacy and to explore its possible mechanisms of action concerning molecular, cellular, and histopathological features. MethodsTransdermal burn wound created on the dorsal surface of the rat. Animals were randomly distributed into three different groups and topically treated with vehicle base (control group), 2.5% SBTL-ALE ointment (experimental group) and silver sulfadiazine cream (SSD, positive drug control group) twice daily for seven consecutive postwounding days. ResultsImmunohistochemical analyses revealed enhanced proliferation, re-epithelialization, neovascularization, dermal hydration as demonstrated by significantly up-regulated (p < 0.05) expression of PCNA, cytokeratin-14, CD31, and aquaporin3, respectively in SBTL-ALE treated group as compared with the control and SSD groups. Picrosirius red staining confirmed the deposition of well-aligned, densely-packed, mature collagen in the SBTL-ALE group. The signature markers of oxidative stress and inflammation (ROS, 3-nitrotyrosine, NOS-2, NF-κB, TNF-α, IL-1β, IL-6) were found to be significant (p < 0.05) decreased in the treated group as compared to the control. Immunoblot analysis exhibited that SBTL-ALE treatment conferred cytoprotection as evidenced by significantly (p < 0.05) up-regulated expression of GRP78, thermo-sensitive cation channel (TRPV3), and HIF-1α. Additionally, activation of energy metabolism and bioenergetics (increased hexokinase, citrate synthase, G6PD, cytochrome c oxidase, ATP, decreased LDH) was observed after SBTL-ALE treatment. ConclusionSBTL-ALE treatment confers cytoprotection, redox homeostasis, cellular proliferation, re-epithelialization, angiogenesis, and dermal hydration during repair of full-thickness burn wound healing in rats. Furthermore, its treatment attenuates oxidative stress, inflammatory responses and enhances bioenergetic activation. Taken together, SBTL-ALE topical application augments burn wound healing, which could be of high clinical significance. The leads from the present findings could serve as valuable information for further applications of SBTL-ALE in pharmaceuticals and cosmeceuticals.

Interventional effect of asiaticosdide on rats exposed to silica dust

Objective: To investigate the effect of asiaticoside for fibrosis in lung tissues of rats exposed to silica and to explore its possible mechanism. Methods: 144 SD male rats were randomly divided into control group, model group, positive drug control group, asiaticoside high-dose group, medium-dose group and low-dose group, each group included 24 rats. Rats in the control group were perfused with 1.0 ml of normal saline, and the other groups were given 1.0 ml 50 mg/ml SiO(2) suspension. Gavage of herbal was given from the next day after model establishment, once a day. Rats in the positive drug control group were administration with 30 mg/kg tetrandrine and rats in the low-dose group, medium-dose group and high-dose group were given 20 mg/kg, 40 mg/kg and 60 mg/kg asiaticoside for fibrosis respectively. Rats in the control group and the model group were given 0.9% normal saline. The rats were sacrificed in on the 14th, 28th and 56th day after intragastric administration and collect the lung tissues to detect the content of hydroxyproline, TGF-β(1) and IL-18, observe the pathological changes of the lung tissues by HE and Masson staining and determine the expressions of Col-I, a-SMA, TGF-β in lung tissues by Western Blot. Results: On the 14th day, 28th day and 56th day after model establishment, the lung tissues of rats in the model group showed obvious inflammatory response and accumulation of collagen fibers, and the degree of inflammation and fibrosis increased with time. The intervention of asiaticoside could effectively inhibit the pathological changes of lung tissues. The contents of hydroxyproline, IL-18 and TGF-β1 in lung tissues of model group were higher than those in the control group (P<0.05) , while the level of hydroxyproline, IL-18 and TGF-β1 in asiaticoside groups were significantly decreased, and the difference was statistically signicant (P<0.05) . Compared with the control group, the expression levels of Col-I, TGF-β1and α-SMA in lung tissue of model group were increased (P<0.05) , while the expression level of Col-I, TGF-β1 and α-SMA were decreased after the intervention of asiaticoside, and the difference was statistically signicant (P<0.05) . Conclusion: Asiaticoside can inhibit the increase of Col-I, TGF-β1 and α-SMA content in the SiO(2)-induced lung tissues of rats, reduce the release of TGF-β1 and IL-18 inflammatory factors in lung tissue, and then inhibit the synthesis and deposition of extracellular matrix in rat lung tissue, and improve silicosis fibrosis.

Effect of Xuebijing injection on endothelial microparticles and renal cortical microcirculation in septic rats

To clarify the characteristics of renal cortical microcirculation and its relationship with the expression of plasma endothelial microparticle (EMP) in septic rats, and to evaluate the effect of Xuebijing injection as an adjuvant therapy of antibiotics on septic AKI. The 8-10 weeks old specific pathogen free (SPF) male Sprague-Dawley (SD) rats were divided into sham operation group (Sham group), positive drug control group and Xuebijing group by the random number table method, with 10 rats in each group. The cecal ligation and puncture (CLP) with large ligation (ligated 75% of the cecum) was used to prepare a rat high-grade sepsis model; in the Sham group, the cecum was stretched without ligation or puncture. Due to the high mortality of CLP with large ligation, Xuebijing injection (4 mL/kg, 12 hours per time) and imipenem/cilastatin injection (90 mg/kg, 6 hours per time) were administered to the rats in the Xuebijing group via the tail vein immediately after the model was produced. Normal saline and imipenem/cilastatin were administered to the rats by the same methods in the positive drug control group. The rats in the Sham group were treated with the same volume of normal saline as any of the other two groups at the same frequency. At 48 hours after model reproduction, the mean arterial pressure (MAP) and blood lactic acid (Lac) of the rats were measured. The renal cortical microcirculation was monitored by using side stream dark-field imaging. Renal hypoxia signals were assessed by pimonidazole chloride immunohistochemistry. Plasma EMP levels were determined by using flow cytometry, and then the correlation between EMP and microcirculation parameters of renal cortex was analyzed. At the same time, the serum creatinine (SCr) was measured, and the renal injury score (Paller score) was used to evaluate the severity of renal tissue pathological damage. Compared with the Sham group, perfused vessel density (PVD), microvascular flow index (MFI) and MAP in the positive drug control group and the Xuebijing group decreased significantly, the positive expression of hypoxia probe (pimonidazole) increased, Lac, EMP, Paller score and SCr increased significantly. However, compared with the positive drug control group, the renal cortical microcirculation in the Xuebijing group was improved significantly, PVD and MFI were increased significantly [PVD (mm/mm2): 16.20±1.20 vs. 9.77±1.12, MFI: 2.46±0.05 vs. 1.85±0.15, both P < 0.05], Lac was reduced significantly (mmol/L: 4.81±1.23 vs. 6.08±1.09, P < 0.05), MAP increased slightly [mmHg (1 mmHg = 0.133 kPa): 84.00±2.00 vs. 80.00±2.00, P > 0.05], suggested that Xuebijing injection improved renal microcirculation perfusion in septic rats, and this effect did not depend on the change of MAP. The positive expression of pemonidazole in renal cortex of the Xuebijing group was significantly lower than that of the positive drug control group [(35.89±1.13)% vs. (44.93±1.37) %, P < 0.05], suggested that Xuebijing injection alleviated renal hypoxia. The plasma EMP levels of rats in the Xuebijing group were significantly lower than those in the positive drug control group (×106/L: 3.49±0.17 vs. 5.78±0.22, P < 0.05), and the EMP levels were significantly negatively correlated with PVD and MFI (r values were -0.94 and -0.95, respectively, both P < 0.05), indicated that the increase of plasma EMP was highly correlated with renal microcirculation disorder, and Xuebijing injection inhibited the increase of plasma EMP levels. The Paller score in the Xuebijing group was significantly lower than that in the positive drug control group (46.90±3.84 vs. 62.70±3.05, P < 0.05), and the level of SCr was also significantly lower than that in the positive drug control group (μmol/L: 121.1±12.4 vs. 192.7±23.9, P < 0.05), which suggested that Xuebijing injection relieved kidney injury and improved renal function in septic rats. As an adjuvant therapy of antibiotics, Xuebijing injection could inhibit the expression of plasma EMP in rats with sepsis, improve renal cortex microcirculation, and reduce kidney injury.

Xianglian Pill Suppresses Inflammation and Protects Intestinal Epithelial Barrier by Promoting Autophagy in DSS Induced Ulcerative Colitis Mice.

Xianglian pill (XLP) is a typical traditional Chinese herbal medicine prescription composed of Coptidis Rhizoma and Aucklandiae Radix. It has been used to treat gastrointestinal disease for centuries. In the present study, the potential mechanisms of XLP in the treatment of ulcerative colitis (UC) were predicted by integrative pharmacology-based approach. Then, the main compounds of XLP were detected by liquid chromatography-mass spectrometry (LC-MS/MS). Finally, we verified the mechanism of XLP in the treatment of UC in a dextran sulfate sodium (DSS) model. C57BL/6 mice were randomly divided into the control group, DSS group, 5-aminosalicylic acid (5-ASA) group which was used as the positive drug control, XLP low, medium, and high dose group, with 10 mice per group. Except for the control group, acute colitis model was induced in the other mice by administering 3% DSS for consecutive 7 days. Mice in 5-ASA and XLP groups were administered with 5-ASA (50 mg/kg) or XLP (0.8, 1.6, 3.2 g/kg) via oral gavage once per day respectively. Body wight and disease activity index were assay during drug intervention. On day 8, all animals in this experiment were sacrificed and colon tissues were collected for analysis after measurement of the length. The results showed that XLP alleviate DSS -induced acute colitis in mice, including inhibition the secretion of pro-inflammatory cytokines, repairing the dysfunction of intestinal epithelial barrier, enhanced autophagy, and blocked the activation of PI3K/Akt/mTOR pathway. Furthermore, inhibiting autophagy by 3-methyladenine attenuated the protective effects of XLP on colitis. The underlying mechanism may be that Xianglian pill promote autophagy by blocking the activation of PI3K/Akt/mTOR signaling pathway.

Preliminary study on effect of Phellinus igniarius ethanol extract on serum uric acid metabolism and gut microbiome in rats

The aim of this paper was to investigate the effect of ethanol extract of Phellinus igniarius in lowering uric acid and changing the gut microbiome in hyperuricemia rats. A total of 36 SD rats were randomly divided into normal control group, model control group, positive drug control group, and high-dose, middle-dose and low-dose P. igniarius ethanol extract groups, with 6 rats in each group. Hyperuricemia rats were established by D-fructose combined with oteracil potassium(OAPS). One week later, the positive control group was given allopurinol 50 mg·kg~(-1) intragastrically, and P. igniarius ethanol extract groups were treated with 30, 60 and 90 mg·kg~(-1) drugs for 14 consecutive days. Body weight, blood glucose and serum uric acid(SUA) were monitored every week. After the model rats were administered with the ethanol extracts of P. igniarius by gavage for two weeks, the activities of creatinine, BUN, xanthine oxidase(XOD) and adenosine deaminase(ADA) were detected. The right kidney was taken to analyze the histological and morphological changes and the degree of damage to main organs of the extract of P. igniarius. The 16 S rDNA gene sequence technique was used to analyze the guts microbiota composition in feces. The results indicated that ethanol extract of P. igniarius could significantly lower the SUA level(P&lt;0.01), while inhibiting the activities of XOD and ADA(P&lt;0.05, P&lt;0.01). Histological examination showed that the allopurine group showed slight renal tubular dilation and inflammatory cell infiltration compared with the normal group, with no significant difference between the P. igniarius ethanol extract groups and the normal group. The 16 S sequencing results showed that the composition of gut microbiota has changed in each group. Therefore, ethanol extracts of P. igniarius may reduce the level of SUA in rats by inhibiting the activities of XOD and ADA, with a certain effect on the composition of gut microbiota.

Guizhi Fuling Wan, Chinese Herbal Medicine, Ameliorates Insulin Sensitivity in PCOS Model Rats With Insulin Resistance via Remodeling Intestinal Homeostasis.

Polycystic ovary syndrome (PCOS) is a common endocrine disease with reproductive dysfunction and metabolic disorder in women of childbearing age. Gastrointestinal microbiome contributes to PCOS through mediating insulin resistance. Guizhi Fuling Wan, Chinese herbal medicine, can treat PCOS with insulin resistance (PCOS-IR), but the underlying mechanism is not clear. The aim of this study was to characterize the exact mechanism of Guizhi Fuling Wan action and whether it is related to the regulation of intestinal flora structure. We induced PCOS-IR rat model by means of letrozole sodium carboxymethyl cellulose (CMC-na) solution combined with high-fat emulsion administration and randomly divided it into blank control group (K), model control group (M), low dose of Guizhi Fuling Wan group (D), middle dose of Guizhi Fuling Wan group (Z), high dose of Guizhi Fuling Wan group (G) and positive drug (Metformin) control group (Y). After 36 days of modeling and treatment, serum and stool samples from all rats were collected for a follow-up analysis. The data display that, compared with K group, elevated testosterone and HOMA-IR, turbulent estrous cycles and polycystic ovaries in M group, indicating the PCOS-IR rat model is successfully established. Increased fasting insulin is associated with higher inflammation(plasma TNF-α, IL-6, and HS-CPR concentration were determined) in M group, and the altered intestinal flora (compared with the K group, in M group the relative abundance of Alloprevotella was decreased significantly, while the relative abundance of Lachnospiraceae UCG-008, Lachnospiraceae NK4A136, Lactobacillus, Ruminiclostridium 9, and Ruminococcaceae UCG-003 was increased significantly) induced the secretion of inflammatory markers. On the other hand, Guizhi Fuling Wan can alleviate inflammation, improve insulin resistence: Lower inflammation decreased fasting insulin can be seen in G group compared with M group, this effect is related to the regulating effect of Guizhi Fuling Wan on intestinal flora (in G group, the relative abundance of Alloprevotella, Ruminococcaceae UCG-003, and Lachnospiraceae UCG-008 was increased significantly, compared with M group). This research demonstrates Guizhi Fuling Wan improve insulin resistance in polycystic ovary syndrome with the underlying mechanism of regulating intestinal flora to control inflammation. It would be useful to promote the therapeutic effect of Guizhi Fuling Wan on PCOS-IR.

Thrombolytic effects of recombinant staphylokinase on coronary thrombosis in miniature pigs

To evaluate the thrombolytic effects of recombinant staphylokinase and compare it with those of recombinant streptokinase. Thirty Chinese experimental miniature pigs were divided into five groups, namely, solvent control group, positive drug control group and three recombinant staphylokinase groups, six in each group. The thrombus of coronary artery was formed by surgical thoracotomy and direct current stimulation in anesthetized animals. Intravenous administration was started after the thrombus of coronary artery was formed for 30 minutes, and the method of first injection and then constant speed infusion by peristaltic pump was used. The solvent control group was injected intravenously with solvent, the positive drug control group was given recombinant streptokinase 4 mg·kg-1 intravenously, and the three recombinant staphylokinase groups were given recombinant staphylokinase at the doses of 4, 2 and 1 mg.kg-1 intravenously. The volume of intravenous injection was 5 ml, which was completed within 1 min, the speed of infusion was 0.5 ml·min-1, which was completed within 60 min, and the animals were sacrificed 120 minutes later. Before and 30, 60 and 120 min after administration, the venous blood samples were collected. At the end of the experiment, the coronary artery segments of the thrombosis site were taken, and the euglobulin dissolution time (ELT), blood fibrinogen content (FBG), fibrinogen degradation product (FDP) and wound bleeding volume were measured respectively. The coronary thrombolysis rate, myocardial ischemia degree and ischemia range were measured. Compared with the solvent control group, ELT in the experimental group was significantly shortened (P＜0.05 or P＜0.01), FBG degradation in a few experimental animals was more than 20%, FDP was significantly increased (P＜0.05 or P＜0.01), and there was no significant effect on blood pressure and heart rate of small pigs. Compared with the control group, the maximum thrombus area was decreased by 34.3% and 15.4% (P＜0.05) in the high and middle dose groups of the experimental group. Compared with the same dose of recombinant streptokinase, recombinant staphylokinase had stronger thrombolytic effect (P＜0.05 or P＜0.01) on the coronary thrombus caused by electrical stimulation, less bleeding side effects and the same effect on the degree and range of myocardial infarction as recombinant streptokinase. Compared with recombinant streptokinase, recombinant staphylokinase has faster thrombolysis speed, higher fibrin specificity and less bleeding side effects. In general, 2 mg.kg-1 recombinant staphylokinase has better efficacy and safety.

The protective effect and mechanism of lentinan on acute kidney injury in septic rats.

This study aimed to investigate the protective effect and mechanism of lentinan (LNT) on acute kidney injury (AKI) in septic rats. A total 72 male SD rats were randomly divided into 6 groups with 12 rats in each group. Except for the sham group, all groups, including the burn sepsis group (BS group), the positive drug control group (dexamethasone, 5 mg/kg, PC group), the LNT low-concentration group (LNT-L group) (50 mg/kg), the LNT medium-concentration group (LNT-M group) (100 mg/kg), and the LNT high-concentration group (LNT-H group) (200 mg/kg), were intraperitoneally injected with the same amount of normal saline 30 min before injury. The levels of serum interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor alpha (TNF-α); the indexes of blood urea nitrogen (BUN) and creatinine (Cr); and the protein expression levels of inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM-1), and nuclear factor-κB (NF-κB) in renal tissue were detected 24 hours after the model was established. Compared with the sham group, the BUN and Cr of the other groups were significantly higher, while those of the LNT group with different concentrations were significantly lower than those of the BS group (P<0.05). Compared with the sham group, the protein expression levels of NF-κB, iNOS, and ICAM-1 along with the levels of pro-inflammatory factors TNF-α and IL-6 in serum were significantly increased, while the levels of anti-inflammatory factors IL-4 and IL-10 were obviously lower in the BS group. Compared with the BS group, the protein expression levels of NF-κB, iNOS, and ICAM-1 along with the levels of pro-inflammatory factors TNF-α and IL-6 in serum were significantly decreased, while the levels of anti-inflammatory factors IL-4 and IL-10 were obviously increased in the LNT group with different concentrations.. LNT has a certain protective effect on AKI in septic rats, and its mechanism may involve inhibiting the activation of NF-κB, which suppresses the expression of proinflammatory factors in turn, thus promoting the release of anti-inflammatory factors.

Effect of Shensong Yangxin on heart failure in preserved ejection fraction rat model

Purpose: To investigate the interventional effect of ShensongYangxin (SSYX) on heart failure (HF) using preserved ejection fraction (HFpEF) rat model.Methods: HFpEF rat model was established using abdominal aorta coarctation method and randomly divided into a positive drug control group; SSYX at high, medium, and low dosage groups; and normal control group. After 8 weeks oral treatment of SSYX, echocardiography and cardiac catheterization were used to investigate the effects of SSYX on HFpEF rat cardiac functions, including mean heart rate (HR), left ventricle anterior and posterior wall thicknesses at end diastole (LVAWd + LVPWd), left ventricular internal diameter at end diastole (LVIDd), and left ventricle mass (LVM).Results: SSYX markedly decreased heart weight and improved survival rate (p &lt; 0.01) after 12 weeks of treatment. The expression of NT-proBNP decreased in a dose-dependent manner and was significantly lower in SSYX treatment groups (p &lt; 0.01). Compared with normal control group, expression of CaMK II, PKA and RyR2 was significantly lower (p &lt; 0.005), while expression level of SERCA2a significantly increased after 4 g/kg/day SSYX treatment (p &lt; 0.01).Conclusion: SSYX significantly attenuates HFpEF-induced cardiac dysfunction and increases survival rate, suggesting that SSYX may prevent HF via regulation of cytoplasmic Ca2+ handling. SSYX reduces plasma NT-proBNP levels, lending support for its therapeutic potential in HF management.Keywords: Heart failure, Ejection fraction, ShensongYangxin

Protective effects of effective ingredients of Danshen (Radix Salviae Miltiorrhizae) and Honghua (Flos Carthami) compatibility after rat hippocampal neurons induced by hypoxia injury

OBJECTIVETo investigate the effective ingredients of Danshen (Radix Salviae Miltiorrhizae) and Honghua (Flos Carthami) (Danhong) on protective properties towards neonatal rat hippocampal neurons under hypoxia condition. METHODSPrimary culture of neonatal rat hippocampal neurons was used to model hypoxia damage on the hippocampus. Methyl thiazolyl tetrazolium (MTT) assay and preliminary experiments were conducted to identify the four effective ingredients of Danhong, along with the injection of positive drug onto hippocampal neurons at a non-toxic dosage level. The cultured cells were randomly divided into 12 groups: the normal group, model group, positive drug control group and nine compatibility groups of the four effective ingredients. Different test methods were applied to determine lactate dehydrogenasein (LDH), total superoxide dismutase (T-SOD), malondialdehyde (MDA), 6-keto prostaglandin Fla (6-keto-PGF1a), thromboxane B2 (TXB2), mitochondrial membrane potential (MMP), free calcium ions concentration ([Ca2+]i) and early onset cell apoptosis. RESULTSDifferent compatibility groups could inhibit the content of LDH and intracellular calcium overload, increase activity in T-SOD, decrease level of MDA and TXB2, improve level of 6-keto-PGF1a and MMP, and prevent the early onset cell apoptosis. CONCLUSIONThe compatibility of four effective ingredients of Danhong had protective effect toward hippocampi hypoxia. The mechanism might be related to inhibit oxidative stress damage and cell apoptosis, resist thrombosis, and reduce the intracellular calcium ion of overload.

Anti‐inflammatory Activity of Two New Indole Alkaloids from the Stems of Nauclea officinalis

Two new indole alkaloid derivatives (1, 2), together with six known indole alkaloids (3 – 8) were isolated from the 70% EtOH/H2O extract of the stem of Nauclea officinalis. Their structures were determined on the basis of extensive analyses of spectroscopic data (IR, MS, 1D‐ and 2D‐NMR). All the isolates were evaluated for their anti‐inflammatory activities on lipopolysaccharide (LPS)‐induced nitric oxide (NO) production in RAW 264.7, and all the compounds showed significant inhibitory activities with the IC50 values of 0.82, 6.45, 9.75, 1.34, 3.40, 2.69, 1.58, and 1.96 μm, compared to the positive drug control group aminoguanidine with an IC50 value of 1.80 μm, especially compound 1 had the most significant activity.

Berberine regulates glycemia via local inhibition of intestinal dipeptidyl peptidase-Ⅳ

Objective: To investigate the effect of berberine on glycemia regulation in rats with diabetes and the related mechanisms. Methods: Diabetic-like rat model was successfully induced by intraperitoneal injection of streptozotocin in 50 out of 60 male SD rats, which were then randomly divided into 5 groups with 10 rats in each:control group (received vehicle only), positive drug control group (sitagliptin 10 mg·kg-1·d-1), low-dose berberine group (30 mg·kg-1·d-1), moderate-dose berberine group (60 mg·kg-1·d-1), and high-dose berberine group (120 mg·kg-1·d-1). All animals were fed for 3 d, and fasting blood sampling was performed on day 3 of administration. Rats were given glucose (2 g/kg) by gavage 30 min after the last dose. Blood and intestinal samples were obtained 2 h after glucose loading. Fasting blood glucose (FBG) and 2-h postprandial plasma glucose (2h-PPG) were detected by using biochemical analyzer, and insulin, glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-Ⅳ(DPP-Ⅳ) were measured by using ELISA kit. Results: No significant difference in FBG and serum DPP-Ⅳ level were found between berberine groups and control group (all P>0.05). Compared with control group, serum levels of GLP-1 and insulin were increased in high-and moderate-dose berberine groups, while 2h-PPG was decreased (all P<0.05); GLP-1 levels in the intestinal samples were increased, while DPP-Ⅳ levels were decreased in all berberine groups (all P<0.05). Conclusions: Short-term berberine administration can decrease 2h-PPG level in streptozotocin-induced diabetic rat model through local inhibition of intestinal DPP-Ⅳ. The efficacy of DPP-Ⅳ inhibitor may be associated with its intestinal pharmacokinetics.

Effects of Kaixin Powder on melatonin receptor expression and (125)I-Mel binding affinity in a rat model of depression.

To explore the effects of Kaixin Powder (, KXP) on melatonin receptor (MR) expression and (125)I-Mel binding affinity in a depression rat model. Seventy-two male Wistar rats were divided into six groups: a blank control group, model group, ramelteon group, KXP high-dosage group (HKXP), medium-dosage group (MKXP) and low-dosage group (LKXP). To establish the depression model, all groups except the blank control group were singly housed and exposed to chronic unpredictable mild stress. Weight gain, sucrose consumption and the open-field test were used to evaluate induction of depression. KXP at 260, 130 and 65 mg/(kg•d) was also respectively administered to the rats in the HKXP, MKXP and LKXP groups for 21 days. Ramelteon [0.83 mg/(kg•d)] was given to the positive drug control group. An equivalent volume of physiological saline was given to the blank and model groups. The liquid chip method was used to measure the concentration of plasma melatonin (MT). Mel1a (MT1) and Mel1b (MT2) expression levels were determined by Western blotting. In addition, a radioactive ligand-binding assay was used to analyze the specific binding properties and dynamic characteristics between MR and (125)I-Mel. The results of weight gain, sucrose consumption and the open-field test showed that our model successfully produced depressive symptoms and depressive-like behavior. The concentration of plasma MT in the model group decreased significantly at night but increased in the MKXP group (P<0.05). The HKXP group showed significantly increased expression of MT1 (P<0.05); however, the expression of MT2 in all groups exhibited no significant differences (P>0.05). The maximum binding capacity (B(max)) for specific binding between MR and 125I-Mel in the MKXP group was significantly higher than that in the model group (P<0.05), but no significant differences were found in the equilibrium dissociation constant (K(d)) of each group (P>0.05). KXP may have a similar effect as ramelteon. KXP improved depressive-like behavior by increasing the concentration of plasma MT and MT1 expression, thereby increasing three B(max) of MR to achieve the desired antidepressant effect.

The Proteomic Research of the Cure of Experimental Diabetes Deafness by Granules of Eliminating Phlegm and Removing Blood Stasis

Observing the expression changes of serum proteome in model rats after intervention of the Granules of Eliminating Phlegm and Removing Blood Stasis ((see text) also known as GEPRB), screening outand identifying the differentially expressed proteins by mass spectrometry and bioinformatics analysis, discussing the molecular mechanism of control the Diabetes deafness by GEPRB. By use of proteomics technology, the serum protein serum proteome of the control group, model control group, Duxil and each observation group were observed for 2-DE gel pattern matching, and the difference in the relative content of 2 times was chosen for the differentially expressed proteins. Identification of differentially expressed proteins by MALDI-TOF MS/MS, the authors further analysis the phosphorylation, subcellular localization, interaction, direct regulation, and transmembrane of the differences proteins by the way of bioinformatics analysis. Sixty SPF level SD rats elected in diabetic rats model group (abbreviated as DM group) were be randomly divided into 5 groups based on random number sheet, namely model control group, positive drug control group (Du-ke-xi group) and Mai-tong-fang high, medium and low dose group respectively. In addition, set of normal control group. 10 rats in each group. By Coomassie brilliant blue staining, identified 51 differential protein spots dug from 2-D gel by mass spectrometry, successfully identified 13 non-redundant proteins. Most of the identified proteins were secreted protein and belong to different protein families. There were about 12 proteins have the transmembrane region from the authors' result, ten of them were plasma membrane proteins. It's suggesting that 13 differential proteins is most likely the protein response to GEPRB in vivo, these proteins may play key role for the treatment of GEPRB to Diabetes deafness. The two highly differentially expressed proteins Apolipoprotein E (apoE) and C3 may be a potential drug target of GEPRB.

Studies on biological effect of lycopene on Hippocampus of hyperlipemia rats

Objective: This study investigated into the ef-fect of lycopene on expression of APP, bax and bcl-2 in hippocampal CA1 region of rats with hyperlipidemia. Methods: By total cholesterol (TC) and body weight, 48 adult male SD rats were randomized into six groups, a normal control group, fed with basic feed; a high-fat model group, fed with high-fat feed; a positive drug control group, fed with high-fat feed and administrated with fluvastatin sodium at a dose of 10 mg?kg?bw-1?d-1 by gastric perfusion; and lycopene groups at three dose levels, fed with high-fat feed and administrated with lycopene at doses of 11, 22 and 44 mg?kg?bw-1?d-1 respec-tively also by gastric perfusion. Caudal venous blood samples of rats in all groups were taken at week 0, week 1 and week 3 after the experiment started so as to assay TC, TG, LDL-C and HDL-C; at the end of the experiment, rat brains were taken and sections of the hippocampal CA1 re-gion were prepared. Expression of APP, bax and bcl-2 in the CA1 region was determined by im-munohistochemical methods and morphologi-cal examination was carried out. Results: One week after fed with high-fat feed, models of hy-perlipidemia rats were established; at the end of experiment, hippocampal APP and bax expres-sion was enhanced while bcl-2 expression was significantly weakened (p<0.05); to rats with hyperlipidemia, both lycopene and fluvastatin sodium could reduce TC, TG and LDL-C, inhibit expression of hippocampal APP and bax and promote expression of bcl-2 (p<0.05). Conclu- sion: Lycopene down-regulates the expression of bax and up-regulates that of bcl-2 mainly by reducing serum TC and LDL-C and weakening expression of APP in the hippocampal CA1 re-gion of rats with hyperlipidemia, thereby main-taining normal morphology of hippocampal neurons and facilitating the protection of the brain.

Protective effect of epigallocatechin-3-gallate on inflammatory bowel disease: experiment with rat models of induced colitis

To explore the protective effect of epigallocatechin-3-gallate (EGCG) on ulcerative colitis (UC) and mechanism thereof. Sixty SD rats underwent enema of trinitrobenzene sulfonic acid (TNBS) to cause UC and then randomly divided into 6 groups: model group, undergoing enema of normal saline (NS) once a day for 2 weeks; positive drug control group, undergoing enema of 5-aminosalicylic acid (ASA), an anti-UC drug; high-dose EGCG group, undergoing enema of 100 mg/kg EGCG; low-dose EGCG group, undergoing 5 enema of 50 mg/kg EGCG; and EGCG pretreatment group, undergoing enema of 100 mg/kg once a day 3 days before the model establishment and then once a day for 2 weeks after the model establishment. Another 12 rats were used as normal controls. Two weeks later the rats were killed. The histological score of the colonic mucosa was evaluated. The cyclooxygenase-2 protein expression in the colonic mucosa was detected by immunohistochemistry and the cyclooxygenase-2 mRNA expression was assessed by semiquantitative reverse-transcription polymerase chain reaction. The histological score of the model group was 6.4 +/- 2.7, significantly higher than that of the normal control group (1.0 +/- 0.7, P < 0.01). The histological scores of the 5-ASA, and 100 mg/kg and 50 mg/kg EGCG groups were 3.4 +/- 1.8, 2.6 +/- 1.5, and 4.0 +/- 2.0 respectively, all significantly lower than that of the model group (all P < 0.05). The histological scores of the EGCG pretreatment group was the lowest (1.2 +/- 0.8), especially compared with the model group (P < 0.01). Cyclooxygenase -2 mRNA was not expressed in the normal control group, was highly expressed in the model group, and the expression levels of the 5-ASA and EGCG groups were all significantly lower than that of the model group (chi(2) = 22.017, P < 0.05). Preventing and ameliorating colitis by inhibiting cyclooxygenase-2 activity, EGCG may be a potential medicine in treating inflammatory bowel disease.