Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice

ObjectiveAbnormalities in the gut microbiota and intestinal short-chain fatty acid (SCFA) levels are implicated in the pathogenesis of functional constipation (FC). Electro-acupuncture (EA) has been shown to improve constipation-related symptoms and rebalance the gut microbiota. However, it is currently unknown whether the gut microbiota is a key mechanistic target for EA or how EA promotes gut motility by regulating the gut microbiota and SCFAs. Therefore, we assessed the effects of EA in FC mice and pseudo-germfree (PGF) mice to address these questions.MethodsForty female Kunming mice were randomly separated into a normal control group (n = 8), an FC group (n = 8), an FC + EA group (n = 8), a PGF group (n = 8) and a PGF + EA group (n = 8). The FC group and FC + EA group were treated with diphenoxylate to establish the FC model; the PGF group and PGF + EA group were given an antibiotic cocktail to initiate the PGF model. After maintaining the model for 14 d, mice in the FC + EA and PGF + EA groups received EA stimulation at the ST25 and ST37 acupoints, once a day, 5 times per week, for 2 weeks. Fecal parameters and intestinal transit rate were calculated to assess the efficacy of EA on constipation and gastrointestinal motility. Colonic contents were used to quantify gut microbial diversity using 16S rRNA sequencing, and measure SCFA concentrations using gas chromatography-mass spectrometry.ResultsEA significantly shortened the first black stool defecation time (P < 0.05) and increased the intestinal transit rate (P < 0.01), and fecal pellet number (P < 0.05), wet weight (P < 0.05) and water content (P < 0.01) over 8 h, compared with the FC group, showing that EA promoted gut motility and alleviated constipation. However, EA treatment did not reverse slow-transit colonic motility in PGF mice (P > 0.05), demonstrating that the gut microbiota may play a mechanistic role in the EA treatment of constipation. In addition, EA treatment restored the Firmicutes to Bacteroidetes ratio and significantly increased butyric acid generation in FC mice (P < 0.05), most likely due to the upregulation of Staphylococcaceae microorganisms (P < 0.01).ConclusionEA-mediated resolution of constipation occurs through rebalancing the gut microbiota and promoting butyric acid generation.Please cite this article as: Xu MM, Guo Y, Chen Y, Zhang W, Wang L, Li Y. Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice. J Integr Med. 2023; Epub ahead of print.     

Effects of Xiangsha Liujunzi decoction drug serum on gastric antrum smooth muscle cells from rats with functional dyspepsia by regulating gastrointestinal hormones

ObjectiveTo observe the effect and mechanism of Xiangsha Liujunzi decoction (XSLJZD) drug serum on gastric antrum smooth muscle cells (SMCs) in rats with functional dyspepsia (FD).MethodsGastric antrum SMCs from rats with FD were isolated, cultured, and then divided into six groups as follows: control, model, domperidone, low-dose XSLJZD (LXSLJZD), medium-dose XSLJZD (MXSLJZD), and high-dose XSLJZD (HXSLJZD). Each group was administered the corresponding drug serum for intervention. Drug serum intervention conditions and proliferative activity of SMCs were tested by cholecystokinin octapeptide. Ghrelin, gastrin, somatostatin, and substance P (SP) levels were measured by ELISA. Somatostatin and SP mRNA expression was measured by real-time PCR.ResultsA concentration of 10% drug serum for 24 h was decided to be the best intervention condition for later study. The mean optical density value in the model group was lower than that in the control group (P = .001). Optical density values in the domperidone and HXSLJZD groups were higher than those in the model group (P = .025, P = .032, respectively). Gastrin, SP, and ghrelin levels in the model group were lower (P = .007, P = .037, P = .005, respectively), but somatostatin levels were higher, compared with those in the control group (P = .031). Gastrin, SP, and ghrelin levels in the domperidone, MXSLJZD, and HXSLJZD groups were higher than those in the model group (all P<.05). Somatostatin levels in the four drug-treated groups were lower than those in the model group (P = .002, P = .007, P = .001, P = .009, respectively). SP mRNA levels in the model group were lower than those in the control, domperidone, MXSLJZD, and HXSLJZD groups (P = .037 P = .016, P = .025, P = .002, respectively). Somatostatin mRNA levels in the model group were higher than those in the control and MXSLJZD groups (P = .042, P = .035).ConclusionsXSLJZD and domperidone drug serum effectively promote proliferative activity of gastric antrum SMCs in an FD model. The mechanism of this activity may be regulated by gastrointestinal hormones.     

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 gastrointestinal heat retention syndrome on gut microbiota in children with upper respiratory tract infection and lung-heat syndrome

ObjectiveGastrointestinal heat retention syndrome (GHRS) is associated with lung-heat syndrome and is related to recurrent respiratory infection. Upper respiratory tract infection (URTI) lung heat syndrome is common in children. The study will explore the effect of GHRS on the structure and function of gut microbiota in children with URTI lung-heat syndrome.MethodsParticipants were divided into both groups using the self-developed URTI scale and the “GHRS Diagnostic Scale · Pediatric Part”: GHRS-positive children (LS group) and GHRS-negative children (L group). General information, clinical symptoms, and stool were collected. We used 16S rRNA amplicon sequencing technology to determine the gene sequence of the V3–V4 region in feces and measure the gut microbiota of the both groups at the genus level.ResultsA total of 23 children were included in the both groups. There were 12 cases in the LS group and 11 cases in the L group. There was no statistical difference between the both groups in age, gender, height, weight, and body mass index. The effective sequences shared by the both groups accounted for 85.66% of the total. In the gut microbiota, there was no difference in the α diversity and the β diversity between the both groups. Compared with the L group, the LS group had a significant increase in the relative abundance of the Ruminococcus gnavus group, Prevotella-9, Staphylococcus, and Actinomyces (P < .05). The functions of the both groups of microbiota primarily concentrate on metabolism, genetic information processing, and environmental information processing. The relative abundance of signaling molecules and interactions in the LS group were higher than that in the L group (P < .05). The redundancy analysis (RDA) showed that the URTI score had the greatest impact on the distribution of microbiota.ConclusionGHRS may affect the development of URTI lung-heat syndrome by changing the relative abundances of gut microbiota.     

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 ...     

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.     

药食同源中药复方改善肠道菌群结构和调节血清代谢物对高血压大鼠治疗作用

目的 探究药食同源中药复方（葛根、夏枯草、杜仲叶、菊花、山楂、芹菜）对两肾一夹（2 kidneys and 1 clip,2K1C）型高血压大鼠血压、肠道菌群结构和血清代谢物的调控作用。方法 2K1C型高血压大鼠随机分为模型组、氯沙坦（0.3 mg/kg）组和药食同源中药复方低、中、高剂量（0.5、2.5、5.0 mg/kg）组,每组7只。连续给药6周后,取眼周血,采用全自动生化分析仪检测各组大鼠血清相关指标;采用16S rDNA测序技术分析各组大鼠肠道菌群变化;采用苏木素-伊红（HE）染色观察各组大鼠肝脏和肾脏组织病理变化;采用高效液相质谱检测各组大鼠血清代谢产物变化。结果 药食同源中药复方干预6周后,大鼠血压明显下降（P<0.05、0.001）,血清中总胆红素（total bilirubin,TBIL）和直接胆红素（direct bilirubin,DBIL）水平显著降低（P<0.05）。16S rDNA测序结果显示,在门水平上,大鼠肠道微生物群落的主要结构由厚壁菌门（Firmicutes）、拟杆菌门（Bacteroidetes）、变形菌门（Proteobacteria...     

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...     

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.     

基于SNAIL信号通路及肠道菌群研究密点麻蜥抑制胃癌肝转移的作用机制

目的 基于SNAIL信号通路及肠道菌群研究密点麻蜥Eremias multiocellata对胃癌肝转移的抑制作用及机制。方法 36只BALB/c裸鼠随机分为对照组和造模组,造模组脾脏注射HGC-27胃癌细胞,造模4周剖腹探查验证造模成功。随后将造模组随机分为模型组、5-氟尿嘧啶（5-fluorouracil,5-FU,0.025 g/kg）组和密点麻蜥（2.6 g/kg）组,每组8只。对照组和模型组ig生理盐水,密点麻蜥组ig密点麻蜥水煎剂,5-FU组ip 5-FU,连续干预4周后,采用苏木素-伊红（HE）染色观察各组裸鼠肝组织病理变化;采用Western blotting检测各组裸鼠肝组织SNAIL及上皮间质转化（epithelial-mesenchymal transition,EMT）相关蛋白表达;取末次给药2 h后各组裸鼠新鲜粪便进行16S rRNA高通量测序检测肠道菌群的变化。结果 与对照组比较,模型组裸鼠肝组织出现肝小叶破坏、肝组织坏死,中性粒细胞浸润,癌细胞核大深染;肝组织SNAIL、N-cadherin蛋白表达水平显著升高（P＜0.001）,E-caherin蛋白水平显著降低（P＜0.001）。与模型组比较,密点麻蜥组肝细胞排列趋于整齐,结构完整,癌组织灶变小;肝组织中SNAIL、N-cadherin蛋白表达水平显著降低（P＜0.001）,E-cadherin蛋白表达水平显著升高（P＜0.001）。16S rRNA结果显示,与对照组比较,模型组裸鼠肠道菌群失调紊乱,厚壁菌门/拟杆菌门（Firmicutes/Bacteroidetes,F/B）值下降,经密点麻蜥干预后F/B值升高。门水平上,密点麻蜥主要对厚壁菌门进行调节,厚壁菌门在对照组中丰度占比40.9%,与对照组比较,模型组中厚壁菌门的丰度降低到26.4%。经密点麻蜥干预后厚壁菌门丰度提高到30.2%。属水平上,密点麻蜥主要对胃癌肝转移裸鼠肠道菌群中差异菌属（拟杆菌属Bacteroides、梭状芽孢杆菌属Clostridia_UCG-014、副拟杆菌属Parabacteroides、幽门螺旋杆菌Helicobacter）发挥调节作用。结论 密点麻蜥可能通过降低SNAIL蛋白表达,增加E-cadherin蛋白表达,降低N-cadherin蛋白表达,来抑制EMT发展进程,发挥对胃癌肝转移的抑制作用。此外,密点麻蜥通过调节厚壁菌门丰度,增加作用于癌细胞表面G蛋白偶联受体的短链脂肪酸（short-chain fatty acids,SCFAs）含量,调节机体自身免疫相关菌属（拟杆菌属、梭状芽孢杆菌属、副拟杆菌属）,降低致病菌幽门螺旋杆菌的丰度,发挥对胃癌肝转移的抑制作用。     

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.     

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.     

Effect of the pineal gland on 5-hydroxytryptamine and γ-aminobutyric acid secretion in the hippocampus of male rats during the summer and winter

ObjectiveThe present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision.MethodsTwo time points, the summer and winter solstice, which are the longest and shortest days of the year, respectively, were selected. Male Sprague–Dawley rats that underwent a sham operation without pineal excision were included as a control group. The concentrations of 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) were determined by radioimmunoassays and enzyme-linked immunosorbent assays, respectively.ResultsIn the winter, the 5-HT and GABA levels in normal rats exhibited a significant difference compared with those in the operation group (P < .01). A difference was also noted in GABA levels between the normal group and the sham operation group (P < .05). The concentrations of 5-HT and GABA in the hippocampal tissues of the normal group exhibited a seasonal rhythm consisting of elevation during the summer and reduction during the winter (P < .01), while the GABA levels in the sham operation group exhibited a significant difference, with elevation during the summer and reduction during the winter (P < .01). In the operation group, GABA showed the same trend (P < .01).ConclusionThe seasonal rhythm of neurotransmitter secretion by the hippocampus (5-HT and GABA) consisted of elevation during the summer and reduction during the winter. During the winter, the pineal gland exhibited a reverse regulatory effect on the secretion of 5-HT and GABA in the hippocampus, and it exhibited seasonal selectivity with regard to the regulation of 5-HT.     

远志提取物对抑郁大鼠肠道菌群的作用研究

目的探讨远志提取物对抑郁大鼠肠道菌群的影响及其可能的作用机制。方法采用孤养结合慢性不可预知性温和应激(chronic unpredictable mild stress,CUMS)方法建立抑郁大鼠模型,SD大鼠随机分为对照组、空白给药组、模型组、氟西汀(2mg/kg)组和远志提取物高、中、低剂量(1.5、1.0、0.5g/kg)组。观察各组大鼠行为学并检测海马组织单胺类神经递质及其代谢物水平;采用ELISA法检测大鼠血清中促肾上腺皮质激素释放因子(corticotropin-releasing factor,CRF)、促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、皮质酮(corticosterone,CORT)、白细胞介素-6(interleukin-6,IL-6)和脂多糖(lipopolysaccharide,LPS)水平;采用透射电镜(TEM)观察大鼠十二指肠和结肠上皮的超微结构变化;采用16S rRNA测序检测大鼠粪便肠道菌群的结构变化。结果与模型组比较,远志提取物可明显改善大鼠的抑郁样行为(P0.05、0.01、0.001),显著升高海马组织中去甲肾上腺素(norepinephrine,NE)、5-羟色胺(5-hydroxytryptamine,5-HT)、二羟基苯乙酸(dihydroxyphenyl acetic acid,DOPAC)和5-羟吲哚乙酸(5-hydroxyindoleacetic acid,5-HIAA)水平(P0.05、0.01、0.001),显著降低血清中CRF、ACTH、CORT、IL-6和LPS水平(P0.01、0.001),减轻其下丘脑-垂体-肾上腺皮质(hypothalamic-pituitary-adrenal,HPA)轴的功能亢进状态;同时远志提取物对大鼠肠道内的菌群失调具有调节作用。结论远志提取物可以通过改善肠道菌群结构、恢复肠屏障功能、降低肠源性内毒素释放、减轻机体炎症水平,从而发挥抗抑郁作用。     

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.     

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.     

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...     

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.