Hewei Jiangni granule alleviates visceral hypersensitivity in a rat model of non-erosive reflux disease via transient receptor potential channel signaling

ObjectiveTo uncover the underlying mechanism of Hewei Jiangni granule (HWJNG) on non-erosive reflux disease (NERD) treatment by examining histological changes, gastrointestinal neurochemicals release and visceral hypersensitivity-related receptor expression in NERD model rats.MethodsA NERD rat model was established via a combination of basal sensitization and acid perfusion. HWJNG treatments at different doses were then administered. Pathological changes to tissues, mast cell (MC) activation, serum levels of esophageal visceral hypersensitivity-related neurochemicals, and transient receptor potential (TRP) receptor mRNA and protein levels were investigated.ResultsCompared with the control group, the expression of tryptase in MCs, the changes of intercellular space, and the serum levels of substance P (SP), calcitonin gene-related peptides (CGRP) and proteinase-activated receptor 2 (PAR2) increased in the model group (all P < .05). The expression of TRP vanilloid 1 (Trpv1) mRNA decreased in esophagus and dorsal root ganglia (DRG) of the model group (P = .030 & P = .013), and the expression of TRP melastatin channel subfamily member 8 (Trpm8) mRNA decreased in the esophagus of model group (P < .01). The level of esophageal TRPV1 protein increased in the model group (P < .01) and the level of TRPM8 protein decreased in esophagus and DRG of the model group (both P < .05). Compared with the model group, the serum levels of SP, CGRP, and PAR2 in the medium-dose HWJNG group showed significant decreases (all P < .05). The expression of Trpv1 mRNA in esophagus and DRG of the HWJNG groups and the Omeprazole group remarkably decreased (all P < .05), as was the expression of Trpm8 mRNA in esophagus of the HWJNG groups (all P < .05).ConclusionHWJNG alleviated visceral hypersensitivity in NERD model rats by regulating TRP-mediated signaling. Our results indicate that HWJNG has potential as a therapeutic agent for NERD.     

Correlation of gut microbiota and neurotransmitters in a rat model of post-traumatic stress disorder

ObjectiveTo determine the effect of gut microbiota on a rat model of post-traumatic stress disorder (PTSD) and explore the correlation of gut microbiota with behavior and neurotransmitters.MethodsWe established a single prolonged stress (SPS) model to examine the pathogenesis of PTSD on rat behavior, gut microbiota, and neurotransmitter levels. Rats were separated into control and model groups, and neurotransmitter levels were measured using enzyme linked immunosorbent assay. Then, 16 S rRNA sequencing was used to compare the gut microbiota between the control and model groups.ResultsCompared with those in the control group, freezing time significantly increased, while number of standing upright, crossing frequency, time spent in the central arena, and total distance traveled were significantly reduced in the model group after exposure to SPS (all P < .05). Meanwhile, serotonin, or 5-hydroxytryptamine, levels in the brain in the model group were significantly lower than those the control group (P = .0332). In addition, changes were observed in the gut microbiota diversity and relative abundances of bacterial phyla, orders, families, and genera in the model group. Especially, changes in Firmicutes, Bacteroidetes, Cyanobacteria, and Proteobacteria levels were most pronounced after SPS exposure. Correlation analysis showed that the strongest positive correlation was found between Bacteroidaceae and 5-HT (P = .0009). Moreover, RF32 abundance was the most negatively related to 5-HT (P = .0009), crossing frequency (P = .0007), and total distance (P = .0003).ConclusionOur results suggest that SPS model rats showed differences in behavior, neurotransmitter levels, and gut microbiota with control rats. Moreover, Firmicutes, Bacteroidetes, Cyanobacteria, and Proteobacteria were most relevant to the exhibited fear-like and anxiety-like behaviors and significant serotonin content reduction in SPS model rats.     

Ganjiang granule regulates cecal microflora and serum biochemical components in a rat model of constipation-predominant irritable bowel syndrome

ObjectiveTo investigate the effects of Ganjiang granule (GG) on cecal microflora and serum biochemical components in rats with constipation-predominant irritable bowel syndrome (IBS–C).MethodsTwenty-four Sprague–Dawley rats were randomly divided into four groups: control, model, GG, and probiotics. Rats in the model, GG, and probiotics groups received 3 °C tap water intragastrically; rats in the GG group were treated with GG; rats in the probiotics group were treated with probiotics. For all rats, enzyme-linked immunosorbent assay and colorimetry were used to assess serum biochemical components related to gastrointestinal function; 16S rRNA high-throughput sequencing was used to analyze the cecal microflora.ResultsThe serum level of 5-hydroxytryptamine (HT) was higher in the model group than in the control group (Z = −2.082, P = .037). The model group exhibited changes in cecal microflora: the relative abundances of Lactobacillus decreased (Z = −2.882, P = .004) and Dorea increased (t = −3.030, P = .023), compared with the control group. The GG and probiotics groups exhibited normal serum levels of 5-HT. The GG and probiotics groups exhibited improved serum levels of gastrin; the probiotics group exhibited an improved serum level of vasoactive intestinal peptide. Compared with the model group, The GG group exhibited greater relative abundance of Ruminococcus (Z = −2.402, P = .016); the probiotics group exhibited greater relative abundance of SMB53 (Z = −2.823, P = .005) and lower relative abundances of Desulfovibrio (Z = −2.823, P = .005) and Facklamia (Z = −2.608, P = .009).ConclusionThe effects of GG on IBS-C may be related to regulation of the serum level of 5-HT, as well as elevated relative abundance of beneficial bacteria in cecal microflora.     

Hemostatic mechanism of the effect of Jianpi Yiqi Shexue decoction on vascular factors in immune thrombocytopenia model miceOA

Objective: To explore the hemostatic mechanism of Jianpi Yiqi Shexue decoction(JYSD) by regulating vascular factors in an immune thrombocytopenia(ITP) mouse model.Methods: An ITP mouse model was established by the passive-immune modeling method, and interventional drugs used were prednisone tablets and JYSD. The platelet count; vascular activity-related factors v WF, VCAM-1, and TM; and VEGF and b FGF were used as observational indicators.Results: On the 8th day of administration, compared with ...     

Seasonal photoperiodic influence of pineal melatonin on hypothalamic-pituitary-adrenal axis-hippocampal-receptor in male ratsOA

Background: Based on the effect of seasonal changes on human visceral function, this study investigated the impact of seasonal photoperiod of the pineal body on hypothalamic-pituitary-adrenal axis-hippocampal-receptor in rats, aiming to reveal the mechanism by which pineal gland melatonin regulates the seasonal secretion of hippocampal neurotransmitters.Methods: Vernal equinox, summer solstice, autumn equinox, and winter solstice were selected as four experimental time points, and rats were rand...     

Intervention of the Mahuang Lianqiao Chixiaodou decoction on immune imbalance in atopic dermatitis-like model mice

ObjectiveTo explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis (AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction (MLCD) on skin damage and inflammation factors in an AD-like mouse model.MethodsNinety-six male BALB/c mice were divided into normal, model, positive control (mometasone furoate), and traditional Chinese medicine treatment (MLCD) groups by a random number table. 2,4-dinitrofluorobenzene was used to induce AD-like mice in all groups except the normal group. The treatment or intervention was administered for seven consecutive days on days 4, 18, 32, and 39. The mRNA relative expressions of interleukin-4 (IL-4), IL-10, interferon-γ (IFN-γ), thymic stromal lymphopoietin (TSLP), and the TSLP receptor (TSLPR) were measured using quantitative real-time polymerase chain reaction, and the serum immunoglobulin E, IL-4, IL-10, and IFN-γ levels were detected using enzyme-linked immunosorbent assay.ResultsCompared with the normal group, the hematoxylin-eosin staining of the skin lesions of the mice in the model group was significantly thickened on days 11, 25, and 39. Compared with the model group, the epidermal thickness of the positive control group was significantly alleviated on day 39 (P < .001), and that of the MLCD group was significantly improved on days 25 and 39 (P < .001). Compared with the four observation time points, MLCD had the best treatment effect on day 39 of the experiment and significantly improved the skin damage performance and relieved pathological lesions. On day 39, compared with the model group, MLCD downregulated the skin mRNA relative expressions of IL-4 (P = .009), TSLP (P = .030), and TSLPR (P < .001), and reduced the mouse serum levels of IL-4 (P = .003). For other serum indicators, no significant difference was observed between the model and MLCD groups.ConclusionMLCD improved AD-like mice skin damage by regulating the Th1/Th2 immune imbalance.     

Analgesic effects and hemodynamic mechanisms of perpendicular and transverse needling at Sanyinjiao (SP 6) in patients with primary dysmenorrhea: A randomized controlled trial

ObjectiveTo explore the analgesic effects and uterine hemodynamics of perpendicular needling (PN) and transverse needling (TN) at SP 6 in patients with primary dysmenorrhea (PD).MethodsIn this randomized controlled trial, patients with PD diagnosed with cold-dampness congealing pattern were randomly assigned in a ratio of 1:1 to receive PN or TN at bilateral SP 6 for 10 min. Acupuncture was performed when the menstrual pain score was over 40 mm on the first day of menstruation, as measured using the visual analog scale for pain (VAS-P). The primary outcome was average menstrual pain (VAS-P). Secondary outcomes included the pulsatility index (PI), resistance index (RI), and systolic-diastolic peaks ratio (S/D) in uterine arteries as measured using color Doppler ultrasonography; anxiety as assessed using the Hamilton Anxiety Rating Scale (HAMA), blood pressure (BP), and heart rate (HR).ResultsForty-eight patients completed the study. The TN group exhibited a significant reduction in VAS-P scores (–5.71 mm, 95% confidence interval (CI): –8.78, –2.63, P = .001), RI values (–0.05, 95% CI: –0.09, –0.01, P = .015), and HAMA values (–2.50, 95% CI: –4.78, –0.22, P = .032) when compared with the PN group. No significant differences in PI, S/D, BP, or HR values were observed between the two groups (P > .05).ConclusionTN at SP 6 was superior to PN in alleviating menstrual pain and anxiety in patients with PD. This analgesic effect of TN may be due to its better ability to improve uterine arterial blood flow via decreases in RI values.     

Cardioprotective effect of Yiqi Huoxue granule through regulation of mitophagy after myocardial infarction in rats

ObjectiveTo investigate the cardioprotective effect of Yiqi Huoxue granule (YQHXG) in the regulation of autophagy in rats induced with myocardial infarction (MI).MethodsAn acute MI animal model was established by ligation of the left anterior descending branch of the coronary artery in Sprague-Dawley rats. Besides, 20 rats received sham operation were classified into a control group. The remaining 59 rats were randomly divided into MI model group (n = 19), YQHXG group (n = 20), and perindopril group (n = 20). Relevant indicators on days 7 and 28 were observed in each group. Left ventricular function was determined by echocardiography. The structure and morphology of mitochondria, and the number of autophagic vesicles, were observed by transmission electron microscopy. The mRNA and protein expression levels of LC3, FUNDC1, Beclin-1, and BNIP3 were examined in the tissue of the MI marginal area.ResultsCompared with the MI model group, YQHXG showed obvious improvements in cardiac functions. Observing the microscopic morphology of the heart tissue, myocardial tissue damage attenuated, autophagic signs of autophagosomes and autolysosomes reduced, vacuolization in mitochondria mitigated, and mitochondria arranged in order. YQHXG could reduce the degree of tissue lesion after MI and regulate the expression of autophagy-related molecules at different stages. On Day 7, YQHXG significantly downregulated the expression of Fundc1, Becn1, Bnip3 mRNA and reduced the levels of FUNDC1, Beclin-1, BNIP3, and LC3 B proteins expression (all P < .001). On Day 28, YQHXG could upregulate the expression of Becn1, Fundc1 and Bnip3 mRNA and increased the levels of the corresponding proteins expression (all P < .001). Besides, it also increased LC3 B protein expression level (P = .0344).ConclusionYQHXG regulated the expression of mitochondrial autophagy-related factors in myocardial tissue and mitochondrial autophagic activity at different stages to protect the heart following MI.     

胃元宁对功能性消化不良小鼠胃肠运动及胃肠激素分泌的影响

目的: 建立功能性消化不良(functional dyspepsia,FD)小鼠模型,研究胃元宁对FD小鼠胃肠运动及胃肠激素分泌的影响. 方法: 昆明种小鼠随机分为6组为正常组,胃元宁汤剂高、中、低剂量组(90,45,22.5 g·kg^-1),模型组,多潘立酮组 (10 mg·kg^-1),除正常组外,其他小鼠采用不规律进食联合左旋精氨酸(L-arginine,L-Arg)ip构建FD小鼠模型,造模成功后ig给予相应药物7 d,检测小鼠体重、胃内残留率和肠推进率;观测胃组织病理学变化;利用酶联免疫吸附测定法(ELISA)检测血清胃泌素(gastrin,GAS),血浆胃动素(motilin,MTL)的含量变化. 结果: 与正常组相比,各造模组小鼠体重及小肠推进率均明显下降 (P<0.01),胃内残留率均显著升高 (P<0.01);经治疗后,与模型组相比,胃元宁各剂量组均能显著增加小鼠体重及小肠推进率,并显著升高血清GAS、血浆MTL含量(P<0.05,P<0.01),同时可明显降低胃内残留率(P<0.05,P<0.01).治疗前后,与正常组相比,各实验组胃组织病理学表现均无差异. 结论: 不规律进食联合左旋精氨酸腹腔注射可成功构建FD小鼠模型;胃元宁能够促进胃肠运动,显著改善小鼠功能性消化不良,其机制可能与其升高血清GAS和血浆MLT水平有关.     

舒胃汤对功能性消化不良大鼠P物质与胃窦Cajal间质细胞的影响

目的:观察舒胃汤对肝郁脾虚型功能性消化不良( functional dyspepsia,FD)大鼠胃排空、P物质(substance P,sP)和胃窦Cajal间质细胞的影响,探讨舒胃汤治疗FD的机制.方法:60只SPF级SD大鼠分为6组,分别为舒胃汤低剂量组(舒低组)、舒胃汤高剂量组(舒高组)、中成药组(木香顺气丸组)、莫沙必利组、空白对照组、模型对照组,每组10只;舒低组、舒高组分别给予舒胃汤7.67 g·kg-1,30.68 g·kg -1,木香顺气丸组予木香顺气丸1.65 g·kg-1、莫沙必利组予莫沙必利1.37 mg·kg-1,采用夹尾刺激方法制造功能性消化不良造模7d,造模后第3d各组给予相应药液ig,对照组和模型组每日予以蒸馏水( 10 mL·kg-1 )ig,均为每日1次,持续14 d.检测大鼠胃排空、用放射免疫法检测血浆SP水平、透射电镜下观察Cajal间质细胞的结构变化.结果:大鼠模型组胃排空(48.12±10.17)％与空白组(89.00±7.59)％比较延迟(P＜0.05),血浆SP模型组(5.32±2.12)ng·L-1与空白组(19.56±5.01 )ng·L-1比较,显著降低(P＜0.05).大鼠胃排空中成药组(58.35±8.71)％、莫沙必利组(78.17±10.74)％、舒低组(60.39±3.48)％、舒高组(76.80±6.96)％与模型组(48.12±10.17)％比较改善(均P＜0.05);血浆SP含量中成药组(12.89±2.10)ng·L-1、莫沙必利组(17.86±3.56)ng·L-1、舒低组(8.03±2.51)ng·L-1、舒高组(13.79±2.58)ng·L-1与模型组(5.32±2.12)ng·L-1比较明显增加(均P ＜0.05),胃窦部Cajal间质细胞结构改善.结论:功能性消化不良大鼠胃肠运动抑制,舒胃汤能够提高SP水平,改善胃窦ICC细胞结构功能,促进胃排空,恢复胃肠道运动功能.     

Tangshenping granule inhibits pyroptosis in a rat model of streptozotocin-induced diabetic nephropathy via the NLRP3/caspase-1/GSDMD pathway

ObjectiveTo explore the inhibitory effect of Tangshenping (TSP) on pyroptosis in a streptozotocin-induced diabetic nephropathy (DN) rat model.MethodsDN was established in Sprague–Dawley rats. Rats were randomly divided into DN (model group), irbesartan, and TSP low-, medium-, and high-dose groups, besides the control group. The 24 h albuminuria content, and serum content of TC, TGs, Scr, IL-1β, UREA, LDLs, and IL-18 were assessed. Hematoxylin & eosin and Mallory staining were performed to examine pathological changes in the kidney. The mRNA and protein expression of NLRP3, caspase 1, and GSDMD in the kidney were also examined.ResultsThe 24 h albuminuria content was obviously lower in the treatment groups compared to the model group (all P < .01). Levels of TC, TGs, Scr, UREA, LDLs, and IL-18 after drug interventions were obviously lower compared to the model group (all P < .05). The serum content of IL-1β in the TSP medium- and high-dose groups were much lower compared to the model group (P = .013 and P = .001, respectively). Through immunohistochemistry and western blotting, we observed that the protein expressions of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 were lower after drug interventions compared to the model group (all P < .05). Using qPCR, we observed that the mRNA expressions of caspase-1, IL-1β, IL-18, and GSDMD after drug interventions were significantly lower compared to the model group (all P < .05). The mRNA expressions of NLRP3 in the TSP medium- and high-dose groups were both lower compared to the model group (all P < .05).ConclusionTSP downregulated mRNA and protein expressions of NLRP3, caspase-1, and GSDMD. Our findings demonstrate that the beneficial effects of TSP on renal function are at least partly mediated by the inhibition of micro-inflammation and modulation of the expression of pyroptosis-related factors.     

胃泰方对功能性消化不良肝郁脾虚型大鼠一氧化氮、神经降压素及胃窦5-羟色胺表达的影响

目的通过观察胃泰方、吗丁啉对功能性消化不良(FD)肝郁脾虚型大鼠一氧化氮(NO)、神经降压素(NT)及胃窦5-羟色胺(5-HT)表达的影响,从脑—肠轴途径探讨胃泰方治疗FD的作用机制。方法将40只SD大鼠随机分为4组,即空白组、模型对照组、吗丁啉组、胃泰组,每组10只。以32 mm蝴蝶夹夹鼠尾后1/3处,30 min后放开,每日1次;于每周二、四、六禁食,余日给足量饲料,持续4周。造模成功后第2 d起,胃泰方组大鼠以0.9 375 g/m L胃泰方浓缩液按2 m L/kg灌胃,吗丁啉组以0.5 mg/m L吗丁啉混悬液10 m L/kg灌胃,空白组、模型对照组以0.9%氯化钠注射液10 m L/kg灌胃,日1次,连续28 d。检测血清中NO、NT及胃窦5-HT的表达。结果与空白组比较,模型对照组NO含量减少,NT含量增加,胃窦5-HT阳性细胞数及灰度值明显降低(P0.05);与模型对照组比较,胃泰组、吗丁啉组NO含量增加,NT含量降低,胃窦5-HT阳性细胞数及灰度值明显增加,差异均有统计学意义(P0.05)。结论胃泰方能纠正NO、NT及胃窦5-HT的异常表达,其作用与吗丁啉基本相当,这可能是胃泰方治疗FD的关键所在。     

经皮耳迷走神经刺激干预功能性消化不良模型大鼠的效应及机制研究

ObjectiveTo explore the effect and its possible mechanism of the intervention of transcutaneous auricular vagus nerve stimulation (taVNS) for the functional dyspepsia (FD) model rats.MethodsOf the 25 male SD rats, 6 rats were set as blank group, the other 19 rats were established to be the functional dyspepsia (FD) model by iodoacetamide intragastric administration, and 18 FD models were successfully established. The 18 model rats were randomly divided into a model group, a sham-taVNS group, and taVNS group, with 6 rats in each group. There was no intervention applied to the rats in the blank and model groups. Whereas, the rats in sham-taVNS group received stimulation to the rim of auricular concha of both sides, and those in taVNS group received stimulation to the cavity of auricular concha of both sides, for 30 min each time, once a day, 7 days in succession. After the intervention, the gastric sensitivity of the rats in each group under different pressure conditions in the stomach, the expressions of serum brain-gut peptide motilin (MTL), cholecystokinin (CCK), glucagon-likepeptide1 (GLP-1), and inflammatory factors IL-4, IL-10, and IL-1β were detected.Results(1) Gastric sensitivity: compared with the blank group, the gastric sensitivity of the model group was higher (P <0.05). Compared with the model group, the gastric sensitivity of the taVNS group was lower (P < 0.05). Compared with the sham-taVNS group, the gastric sensitivity of the taVNS group was lower (P <0.05).(2) Expression of brain-gut peptide: compared with the blank group, MTL was lower, CCK and GLP-1 were higher in the model group (all P <0.05). Compared with the model group, MTL was higher, CCK and GLP-1 were lower in the taVNS group (all P <0.05). Compared with the sham-taVNS group, CCK and GLP-1 were lower in the taVNS group (both P<0.05). (3)Expression of inflammatory factors: compared with the blank group, IL-4 and IL-10 were lower and IL-1β was higher in the model group (all P <0.05). Compared with the model group, IL-10 was higher and IL-1β was lower in the sham-taVNS group (all P <0.05), while IL-4 and IL-10 were higher and IL-1β was lower in the taVNS group (all P <0.05). Compared with the sham-taVNS group, IL-4 and IL-10 were higher and IL-1β was lower in the taVNS group (all P <0.05).ConclusionTaVNS can reduce the gastric sensitivity of FD model rats by peripheral anti-inflammatory action and regulating the abnormal secretion of brain-gut peptide.     

Loganin regulates glycolipid metabolism by influencing intestinal microbiota and AMPK signaling in obese mice

ObjectiveWe aimed to observe the effects of loganin (Log) on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase (AMPK) signaling in obese mice.MethodsA high-fat diet was given for 12 consecutive weeks to generate the obesity model in institute of cancer research (ICR) mice. Body weight was measured weekly and fasting blood glucose (FBG) was determined every 2 weeks. Both the oral glucose tolerance test and the intraperitoneal insulin tolerance test were performed. The serum levels of total cholesterol (TC), triglyceride, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), and free fatty acids (FFA) were measured. The expression of key proteins in the AMPK signaling pathway in skeletal muscle tissue was detected by immunoblotting, and gut microbiota were characterized using 16S rDNA sequencing.ResultsLog significantly decreased the body weight and the FBG in obese mice (P < .05), and it could restore FBG to normal levels. The total cholesterol, LDL-C, and FFA levels were significantly reduced by Log compared with the obese controls (TC: P = .0020; LDL-C: P = .0233; FFA: P = .0127), and the glucose tolerance of animals was significantly improved (P = .0477). The western blot results showed that Log could upregulate the protein expression of Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPKα), Sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor-gamma coactivator -1alpha (PGC1α) in skeletal muscle tissue of obese mice. 16S rDNA sequencing indicated that Log reduced the diversity of the gut flora in feces and altered the floral composition of obese mice.ConclusionsLog was effective in reducing body weight and improving glucolipid metabolism in obese mice, probably through activating AMPK signaling and regulating intestinal microbial diversity.     

Effect of pediatric tuina on hypothalamic metabolites in young rabbits using liquid chromatography-mass spectrometryOA

Objective: To investigate the changes in the hypothalamic metabolites of lipopolysaccharide(LPS) febrile young rabbits after the treatment with pediatric tuina.Methods: A total of 30 young rabbits were randomly assigned into three groups: the normal group, the model group, and the tuina group. Both the model group and the tuina group were injected intravenously with LPS. “Six antipyretic manipulations”(pushing Tianmen, pushing Kangong, kneading Taiyang,kneading Erhougaogu, clearing Tianheshui, a...     

Assessment of traditional Chinese medicine pattern in a bleomycin-induced pulmonary fibrosis mouse model: A pilot studyOA

Objective:To initially explore traditional Chinese medicine patterns in a bleomycin-induced pulmonary fibrosis mouse model.Methods:Thirty-six C57 BL/6 mice were divided by the random number table method(with 12 rats per group) into three groups:a blank group,a model group,and a number 2 Feibi recipe(FBR-2) group.The pulmonary fibrosis mouse model was established by intratracheal instillation of bleomycin.The FBR-2 group was treated with FBR-2 for 4 weeks.Symptoms in the mice such as mental behav...     

Effects of a combination of Japanese Raisin Tree Seed and Flower of Lobed Kudzuvine against acute alcohol-induced liver injury in mice

ObjectiveThe Flower of Lobed Kudzuvine [Pueraria lobata (Willd.)Ohwi; Gehua in Chinese; GH] and Japanese Raisin Tree Seed (Hovenia dulcis Thunnb.; Zhijuzi in Chinese; ZJZ) are herbs that have been used in China for the treatment of alcohol intoxication and liver diseases. We aimed to evaluate the hepatoprotective potential of a combination of these in mice with acute alcohol-induced liver injury, and to elucidate the mechanisms involved.MethodsMale ICR mice were randomly allocated to six groups: a control group, an alcohol-administered group, and groups that were administered alcohol and one of silibinin, the GH, the ZJZ or a GH-ZJZ combination (at a ratio of 2:1). Animals were orally administered 56% alcohol (Er Guo-tou white spirit, 0.12 mL/10 g/d) for 10 days and at the end of this period, hepatic biochemical indicators, antioxidant parameters, alcohol metabolic enzymes, and histopathologic changes were evaluated. Moreover, the expression of the signaling molecules KEAP1, NRF2, and AQP9 were measured by qRT-PCR and western blotting.ResultsCompared with the model group, GH-ZJZ (2:1) had lower serum ALT (12.15 ± 0.39, P = .003), AST (104.07 ± 1.03, P = .001), and ALP (148.09 ± 2.55, P = .010) activities, and lower TC (1.97 ± 0.05, P = .001) and TG (1.54 ± 0.07, P = .002) concentrations. GH-ZJZ (2:1) also significantly increased the hepatic activities of SOD and GSH (4.24 ± 0.25 and 1.57 ± 0.06, respectively; both P < .01), reduced the ROS and MDA concentrations (97.50 ± 3.00 and 2.39 ± 0.19, respectively; both P < .01), and upregulated Nrf2 expression (P < .01). GH-ZJZ (2:1) significantly reduced the expression of KEAP1 and AQP9 in the liver, compared with alcohol-administered mice (P < .01). Importantly, the GH-ZJZ combination caused a more marked improvement in acute liver injury than GH or ZJZ alone.ConclusionWe have demonstrated protective effects of GH-ZJZ (2:1) against acute alcohol-induced hepatic injury, and shown that these effects may be associated with improvements in lipid and alcohol metabolism, antioxidant capacity, and lipid peroxidation.     

Tiaozhi Tongmai Granules reduce atherogenesis and promote the expression of ATP-binding cassette transporter A1 in rabbit atherosclerotic plaque macrophages and the liver

ObjectiveATP-binding cassette transporter A1 (ABCA1) is an integral membrane protein that plays a key role in cellular lipid metabolism, preventing the accumulation of lipids that contribute to the initiation and progression of atherosclerosis. Tiaozhi Tongmai Granules are a Chinese herbal compound that is capable of treating atherosclerosis. This study was designed to explore the potential pharmacological mechanism by which Tiaozhi Tongmai Granules protect against atherosclerosis.MethodsForty-nine male New Zealand rabbits were randomly divided into seven groups: normal control group, normal diet; model groups 1 and 2: balloon injury and high-fat diet for 6 or 12 weeks; statin groups 1 and 2: balloon injury and high-fat diet plus atorvastatin for 6 or 12 weeks; and Chinese herb groups 1 and 2: balloon injury and high-fat diet plus Tiaozhi Tongmai Granules for 6 or12 weeks. The granules were administered at a dose of 1.14 g/kg/d, with atorvastatin (1.14 mg/kg/d) serving as positive control. Serum lipid profiles and liver function indices were measured. Atherogenesis was viewed after H&E staining and quantified by thickened intimal area percentage and maximal intimal thickness percentage. The ABCA1 protein expression in atherosclerotic plaque macrophages of the common carotid arteries (CCA), thoracic aortae (TA), and liver tissues were observed by immunohistochemical staining and evaluated using mean optical density (OD) value in macrophages and ABCA1-positive hepatocyte number.ResultsCompared with model group 1 at week 6, Chinese herb group 1 and statin group 1 displayed significant reductions in total cholesterol (TC) (P = 0.027, 0.012) and low-density lipoprotein cholesterol (LDL-C) (P = 0.039, 0.028) levels, as well as marked increases in ABCA1-positive hepatocyte numbers (P all <0.001), and only statin group 1 displayed a markedly reduced maximal intimal thickness percentage in the CCA (P = 0.018). Compared with model group 2 at week 12, Chinese herb group 2 and statin group 2 all presented significant reductions in TC (P = 0.011, 0.003), LDL-C (P = 0.017, 0.010) and thickened intimal area percentage in the CCA (P = 0.001, 0.022), as well as prominent increases in the ABCA1 OD value of both the CCA (P = 0.001, 0.039) and TA (P = 0.001, 0.025) and positive hepatocyte number (P all <0.001). Chinese herb group 2 had a markedly reduced maximal intimal thickness percentage compared with model group 2 (P = 0.006) and a higher positive hepatocytes number than statin group 2 (P = 0.001).ConclusionsTiaozhi Tongmai Granules appear to have an anti-atherogenic effect that is most likely mediated by simultaneously upregulating the protein expression of ABCA1 in rabbit atherosclerotic plaque macrophages and in the liver.     

Tea polyphenols inhibit the growth and angiogenesis of breast cancer xenografts in a mouse model

ObjectiveTo investigate the anti-angiogenic effect of tea polyphenols (TP_S) on breast cancer and normal tissues in a mouse model.MethodsBreast cancer was successfully implanted into 48 BALB/c mice, which were then randomly divided into a TP oral gavage group, a TP local injection group, a ginsenoside Rg3 group, and a model control group according to a random number table. The tumor inhibitory rates of each group were calculated, while microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and tissue inhibitor of metalloproteinase (TIMP-2) were detected by immunohistochemistry.ResultsTPs could inhibit the growth of breast cancer xenografts in the mouse model. The tumor inhibition rates of the TP oral gavage and TP local injection groups were 37.43% and 40.94%, respectively. Compared with the model control group, MVD and VEGF and bFGF expression was downregulated (all P < .05), whereas TIMP-2 expression was elevated in the TP oral gavage and TP local injection groups (P = .015 and P = .032). TPs showed no significant effect on MVD and VEGF and TIMP-2 expression in the heart, brain, and kidney of the mouse model.ConclusionTPs can restrict the growth of breast cancer by specifically inhibiting the angiogenesis of breast tumor tissue while having little effect on the normal tissue of important organs including the heart, brain, and kidney.     

小儿感冒宁颗粒对脾虚型功能性消化不良大鼠胃肠运动及血清胃肠激素水平的影响

目的:考察小儿感冒宁颗粒对脾虚型功能性消化不良(FD)大鼠模型的药效作用。方法:特制饲料喂养制备SD大鼠脾虚型FD模型。造模前大鼠随机分为6组,即对照组,模型组,儿宝颗粒组(EB,7.10 g·kg^(-1)·d^(-1)),小儿感冒宁低、中、高剂量组(3.55、7.10、14.20 g·kg^(-1)·d^(-1)),每组10只。除对照组外,其余各组大鼠每日给予特制饲料喂养进行造模。持续造模1周后开始给药,连续20 d。每周2次测定各组大鼠一般状态评分、体质量、24 h进食量、24 h饮水量;给药结束后测定各组大鼠胃排空率、胃重指数、小肠推进率、胸腺指数、脾脏指数;苏木素-伊红(HE)染色法观察大鼠十二指肠、结肠、胃窦部位的组织病理学改变;Image J软件测量小肠绒毛高度、宽度、绒毛间隙、结肠固有层厚度、腺体横截面积、胃窦黏膜浅层破损厚度;酶联免疫吸附法(ELISA)测定血清胃泌素(GAS)、胃动素(MTL)、胆囊收缩素(CCK)、血管活性肠肽(VIP)及瘦素(LEP)含量。结果:与模型组比较,小儿感冒宁颗粒可降低脾虚型FD模型大鼠一般状态评分,缓解体质量增长缓慢及饮水减少,显著增加胃排空率、小肠推进率(P<0.05,P<0.01),改善十二指肠、结肠及胃窦组织病理学特征异常。此外,小儿感冒宁颗粒能够显著升高模型大鼠血清GAS、MTL水平(P<0.05,P<0.01),显著降低血清CCK、VIP、LEP水平(P<0.05,P<0.01)。结论:小儿感冒宁颗粒可通过促进胃排空和小肠推进、调节血清胃肠激素水平起到改善脾虚型FD的作用。