Traditional Chinese medicine Da-Cheng-Qi-Tang ameliorates impaired gastrointestinal motility and intestinal inflammatory response in a mouse model of postoperative ileus

Abstract Background Chinese medicine decoction Da-Cheng-Qi-Tang (DCQT) is effective for treating gastrointestinal (GI) disorders, including postoperative ileus (POI); however, the mechanism by which DCQT improves intestinal motility of POI remains unknown. Purpose The aim of this study is to explore the therapeutic effect and mechanism of the decoction with the traditional formula DCQT (T-DCQT) and a modified DCQT (M-DCQT) in an experimental POI mouse model. Methods Mice were divided into 5 experimental groups with 16 mice per group as follows: (1) control group; (2) sham group; (3) POI group; (4) T-DCQT group and (5) M-DCQT group. Each group was subdivided into 2 groups in which the therapeutic effect was examined at 24h and 48h after operation. POI was induced by classic intestinal manipulation operation and the gastrointestinal(GI) motility was measured with a charcoal marking mixture gavage. The intestinal tissues were collected for evaluation of the histopathological alteration, and analysis of the expression of inflammatory signal pathways, as NF-κB, p38 MAPK, and TLR4 by qPCR, immunohistochemical staining and western-blotting, respectively. Plasma inflammatory cytokines were determined using a high-throughput liquid chip. All analyses were performed with samples collected 24 and/or 48h after operation. Results GI transit was significantly reduced in mice with POI and this dysfunction was alleviated after administration of either T-DCQT or M-DCQT enema. When compared to controls, the pathological changes in the ileum mucosal of POI mice were significantly improved, and the increased expression of NF-κB, p38 MAPK, and TLR4 in the intestinal tissues were reversed, following T- DCQT or M-DCQT treatment. Plasma inflammatory cytokines, such as IL-1α, IL-6, MCP-1, MIP-1β and IL-17 levels were significantly highly expressed in POI group, and most of them, as IL-1α, IL-6, MIP-1β and IL-17 were significantly reduced after T-DCQT or M-DCQT treatment. Conclusion The current study indicated that administration of T-DCQT or M-DCOT could ameliorate the POI-associated inflammatory response and improve GI motility, by controlling inflammatory cytokines release and modulating the expression of some inflammatory signal pathways in the POI mouse model.

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Traditional Chinese Medicine Da-Cheng-Qi-Tang Ameliorates Impaired Gastrointestinal Motility and Intestinal Inflammatory Response in a Mouse Model of Postoperative Ileus

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9074069 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Chunqiu Chen ◽

Min Li ◽

Xiaohong Liu ◽

Jianwei Fan ◽

Hong Zhang ◽

...

Keyword(s):

Chinese Medicine ◽

Small Bowel ◽

Traditional Chinese Medicine ◽

Inflammatory Response ◽

Mouse Model ◽

Inflammatory Cytokines ◽

High Throughput ◽

Immunohistochemical Staining ◽

Postoperative Ileus ◽

Gastrointestinal Dysfunction

This study was to explore the therapeutic effect and mechanism of the traditional Chinese medicine with the formula Da-Cheng-Qi-Tang (T-DCQT) and a modified Da-Cheng-Qi-Tang (M-DCQT) in a postoperative ileus (POI) mouse model. POI was induced via small bowel manipulation, and T-DCQT or M-DCQT was given by enema. The intestinal motility was measured with a charcoal mixture gavage. The intestinal tissues were collected for further studies by histopathological, qPCR, immunohistochemical staining, and Western blotting. Levels of inflammatory cytokines in blood were determined using a high-throughput liquid chip. We found that gastrointestinal dysfunction was alleviated after administration of either a T-DCQT or M-DCQT enema. Increased expression of NF-κB, p38 MAPK, and TLR4 in the intestinal tissues of POI mice were reversed following treatment. IL-1α, IL-6, MIP-1β, and IL-17 levels were significantly reduced at 24 h and 48 h following treatment, while the MCP-1 level was only observed to be reduced at 24 h after the treatment. Furthermore, compared with the T-DCQT effect, M-DCQT treatment was more effective in alleviating the increased IL-6, MIP-1β, and IL-1α levels. So, we draw a conclusion that T-DCQT or M-DCOT could ameliorate the POI-associated inflammatory response and improve GI motility in a POI mouse model.

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Nigella A ameliorates inflammation and intestinal flora imbalance in DSS induced colitis mice

AMB Express ◽

10.1186/s13568-020-01114-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Xingjiang Hu ◽

Nana Xu ◽

Xi Yang ◽

Xi Hu ◽

Yunliang Zheng ◽

...

Keyword(s):

Ulcerative Colitis ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Inflammatory Response ◽

Therapeutic Effect ◽

Antioxidant Activities ◽

Intestinal Flora ◽

Signs And Symptoms ◽

Microbial Composition ◽

Bacterial Genus

Abstract Nigella A, also named Sieboldianoside A, has been extracted from many kinds of Traditional Chinese Medicine (TCM), such as Nigella glandulifera, Stauntonia chinensis DC., and the leaves of Acanthopanax sieboldianus. Nigella A exhibited potential analgesic, anti-inflammatory, anti-tumor, and antioxidant activities. However, whether Nigella A could treat ulcerative colitis (UC) is still unknown. As saponins always be regarded as the kinds of ingredients that could regulate immunity and intestinal flora. This research aimed to investigate the therapeutic effect of Nigella A on UC and explore its effect on intestinal flora. We noted that Nigella A and Sulfasalazine (SASP) could significantly improve the signs and symptoms, alleviate colonic pathological injury in DSS-induced mice. The changing of many specific bacterial genus such as Lactobacillus, Porphyromonadaceae, Bacteroides and Escherichia might closely related to the recovery of intestinal inflammatory response. This study initially confirmed the therapeutic effect of Nigella A and SASP on DSS-induced colitis by improving the diversity of intestinal microbial composition. Nigella A has the potential to be developed for the treatment of UC and other disorders related to the imbalance of intestinal flora.

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Acute lung injury inhibition by juglone in LPS induced sepsis mouse model involves Sirt1 activation

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i5.14 ◽

2020 ◽

Vol 19 (5) ◽

pp. 1001-1007

Author(s):

Qiong Hu ◽

Chunai Yang ◽

Fenshuang Zheng ◽

Hongdan Duan ◽

Yangshan Fu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Mouse Model ◽

Inflammatory Cytokines ◽

Alveolar Epithelial Cells ◽

Control Group ◽

Western Blot Assay ◽

Edema Formation ◽

Sirt1 Expression ◽

Treatment Groups

Purpose: To investigate the effect of juglone on LPS induced lung injury in a mouse model and in TC 1cell line.Methods: Edema formation in lungs were measured by determination of lung wet/dry weight. Expressions of various proteins were assessed by western blot assay, while Sirt1 level was assessed using immunohistochemistry. Mice were randomly assigned to nine groups of 10 mice each: normal control, untreated and seven juglone treatment groups. Acute lung injury was induced in mice by injecting LPS (10 mg/kg) via intraperitoneal route (ip). The treatment groups were given 10, 20, 30, 40, 50, 60 and 100 μM of juglone, ip, respectively.Results: The levels of MMP-9, IL-6, IL-1β and iNOS were significantly higher in acute lung injury induced mice compared than the control group (p < 0.05). Treatment of the mice with juglone significantly decreased LPS-induced up-regulation of inflammatory cytokines in a dose-dependentmanner. The production of inflammatory cytokines was almost completely inhibited in the mice treated with 100 mg/kg dose of juglone, while treatment of the LPS-stimulated TC 1 cells with juglone upregulated the expression of Sirt1 mRNA. Down-regulation of Sirt1 expression by siRNA inhibited the effect of juglone on LPS-induced increase in inflammatory cytokine production.Conclusion: Juglone prevents lung injury in mice via up-regulation of Sirt1 expression. Therefore, juglone might be useful for the development of a treatment strategy for lung injury. Keywords: Inflammatory, Sirtuin, Edema, Cytokines, Lung injury, TC 1 lung alveolar epithelial cells, Sirt1

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Determination of the Efficiencies of the Prokinetics in Ruminants with Postoperative Ileus Using Pro-Inflammatory Markers

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.81816 ◽

2018 ◽

Vol 46 (1) ◽

pp. 7

Author(s):

Semih Altan ◽

Kaan Dönmez ◽

Feray Altan ◽

Fahrettin Alkan

Keyword(s):

Smooth Muscle ◽

Inflammatory Response ◽

Inflammatory Markers ◽

Postoperative Ileus ◽

Transforming Growth Factor ◽

Smooth Muscles ◽

Control Group ◽

Important Indicator ◽

Amyloid A ◽

Prokinetic Drug

Background: Recently, the role of inflammation triggered by handling of the intestine various gastrointestinal (GI) surgeries is generally accepted as the key event in postoperative ileus (POI). Because, prokinetics have been increased the smooth muscle contractions and may act by attenuating the inflammatory process in the GI tract, they have been used the treatment of POI in human and animals. There are many in vivo analysis techniques of GI motility. However, there have not yet been studied associated with the evaluation of the inflammatory response. Therefore, it was aimed to evaluate the efficiencies of 3 different prokinetics from inflammatory response during experimentally-induced POI.Materials, Methods & Results: Twenty healthy lambs (30-45 days old) were randomly assigned to four groups. In all groups, enterotomy was performed on the ileum. Erythromycin and metoclopramide were administered to the ERT and MET groups before the surgery, respectively, while lidocaine was administered to the LID group as bolus before and continuous rate infusion during the surgery. Physiological saline was administered to the lambs in control group as placebo before the surgery. Blood samples were collected before surgery (~30-45 min), at the end of surgery (0 h), and at the postoperative 1, 3, 5, 10, 48, 72 and 96 h. The concentrations of serum amyloid A (SAA), haptoglobin (HPT), fibrinogen (FIB) as acute phase proteins (APPs), thiobarbituric acide reactant substrate (TBARs), myeloperoxidase (MPO) as reactive oxygen species, and transforming growth factor-beta (TGF- β) as a cytokine were measured with ELISA reader. In terms of time points, it was found that FIB was statistically higher in ERT group at the 1st h, in MET and LID groups at the 10th h, and in LID group at the 48th and in MET group at the 72 h (P < 0.05). It was found that SAA was higher in MET group at the 1st, 3rd, 5th, 10th, 24th, 48th and 72nd h. HPT was higher in CNTR group until 72th h and MET group at 48th, 72nd and 96th h. TBARs concentrations were statistically higher in MET and LID groups at 0 hour, in ERT and MET groups at the 1st h, in MET group at the 3rd h, in MET and LID groups at the 5th and 10th h, in MET group at the 48th, 72nd and 96th h (P < 0.05). MPO concentrations was higher in LID group at the 3rd, 5th, 10th and 96th h, and in ERT group at the 72nd h (P < 0.05). TGF-β concentrations were particularly high in MET group at the 3rd, 5th, 48th and 72nd h, and in LID group at the 10th, 24th, and 96th h (P < 0.05).Discussion: APPs (HPT, SAA, FIB), which are important regulators of inflammation in cows and sheep, were higher generally in MET and LID groups and inflammation persists in these two groups and, therefore, metoclopramide and lidocaine are less effective in early postoperative POI treatment. Because, significant increase in serum TBARs and MPO concentrations was considered as an important indicator of oxidative stress and inflammatory response MPO concentrations was particularly high until 10th h in LID group, and TBARs concentrations was high both MET and LID groups throughout the study, this was correlated with higher neutrophil infiltration in the postoperative early period than the other groups. It is known that TGF-β, an inflammatory cytokine, is correlated with various smooth muscle disorders in humans. In this study, TGF-β concentration were higher in the MET and LID groups. High concentration of this cytokine might have led to decrease contractions in smooth muscles, thereby slowing down the intestinal transition. In conclusion, based on the presence of pro-inflammatory markers in this study, erythromycin seems to be the most suitable prokinetic drug in lambs. Moreover, lidocaine and metoclopramide are not as successful in small ruminants as reported in other species.

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Huanglian Jiedu Decoction in the Treatment of the Traditional Chinese Medicine Syndrome “Shanghuo”–An Intervention Study

Frontiers in Pharmacology ◽

10.3389/fphar.2021.616318 ◽

2021 ◽

Vol 12 ◽

Author(s):

Keke Luo ◽

Haiyu Zhao ◽

Baolin Bian ◽

Xiaolu Wei ◽

Nan Si ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Therapeutic Effect ◽

Adenosine Triphosphate ◽

Stress Factors ◽

Healthy Control Group ◽

Sphingolipid Metabolism ◽

Control Group ◽

Clinical Biomarkers ◽

Healthy Control

“Shanghuo” (“excessive internal heat”) is caused by exuberant endogenous fire, which does not have a comprehensive and systematic traditional Chinese medicine theory. In previous study, we had evaluated the therapeutic effect of Huanglian Jiedu Decoction (HLJDD) (granule) on patients with “Shanghuo”, however, the specific mechanism was not clear, which need further exploration. To explain its intervention mechanism, we select 57 patients with oral diseases caused by “Shanghuo” and 20 health volunteers to divide into oral disease group, HLJDD intervention group and healthy control group. Firstly, biochemical indicators before and after HLJDD intervention are detected, such as inflammatory factors, oxidative stress factors and energy metabolism factors. The results exhibit that HLJDD significantly decreases indicators succinic acid (p < 0.001); tumor necrosis factor-alpha, adenosine triphosphate, citric acid (p < 0.01); interleukin-8 (IL-8), 4-hydroxynonenal, pyruvic acid, lactate dehydrogenase (p < 0.05). The levels of glucocorticoid, adrenocorticotropic hormone (p < 0.01); lactic acid, IL-4, IL-10 (p < 0.05) significantly increase after HLJDD intervention. In addition, we adopt multi-omics analysis approach to investigate the potential biomarkers. Nontargeted metabolomics demonstrate that the levels of 7 differential metabolites approach that in the healthy control group after HLJDD intervention, which are correlated with histidine metabolism, beta-alanine metabolism and sphingolipid metabolism through metabolic pathway analysis. Targeted lipidomics results and receiver operating characteristic curve analysis show that 13 differential lipids are identified in the three groups mainly focuse on lysophosphatidylcholines, lysophosphatidylethanolamines. Finally, the network associations of those differential biomarkers reveal the regulation of adenosine triphosphate and tricarboxylic acid cycle play essential role in the therapeutic effect mechanism of HLJDD in “Shanghuo”. The study has laid the foundation for further revealing the mechanism and finding clinical biomarkers related to “Shanghuo”.

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Regulatory effect of Garidisan on dysbiosis of the gut microbiota in the mouse model of ulcerative colitis induced by dextran sulfate sodium

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2750-y ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Ling-yan Pei ◽

Yu-shi Ke ◽

Huan-hu Zhao ◽

Wei-zhi Liu ◽

Lin Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Mouse Model ◽

Gut Microbiota ◽

Therapeutic Effect ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Control Group ◽

Group Model ◽

Regulatory Effect ◽

Model Group

Abstract Background Ulcerative colitis (UC) is a modern refractory disease, and its etiology has been difficult to discern. Studies have shown that UC is closely associated with the gut microbiota. Garidisan is composed of wild poppy and Artemisia frigida Willd and is commonly used for the treatment of UC in Inner Mongolia, China. In clinical settings, Garidisan has been found to treat UC effectively, with low recurrence. Previous studies have shown that Garidisan has a good therapeutic effect on mice with UC, but the therapeutic mechanism is still unclear. In this study, we investigated the regulatory effect of Garidisan on dysbiosis of the gut microbiota in a UC mouse model and explored the possible mechanism of the therapeutic effect of Garidisan on UC. Methods The UC mouse model was established by the dextran sulfate sodium (DSS) circulating free water drinking method, and the luminal contents were sampled under sterile conditions. High-throughput sequencing of the 16S rRNA gene V3 + V4 region of the luminal contents of the control group, model group, and Garidisan group was conducted, and clustering of operational taxonomic units (OTUs) and species annotation were performed. The differences in species composition and microbial community structure between individual groups of samples were analyzed using MetaStat, LefSe, rank sum test, and Bayesian causal network analysis. Results The UC mouse model was successfully established and the sequencing results were of adequate quality. There were significant differences in the diversity of luminal contents between the control group, model group, and Garidisan group, and the differences between groups were greater than those within any group. The therapeutic effect of Garidisan on UC is attributed to the direct effect on the Lachnospiraceae family of bacteria. Conclusion Garidisan has a good regulatory effect on the gut microbiota, and Lachnospiraceae could be an important direct target of Garidisan for the treatment of UC.

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The therapeutic effect of irreversible electroporation ablation in mouse model of gastrointestinal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.62 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 62-62

Author(s):

Hyuk Soon Choi ◽

Hoon Jai Chun ◽

In Kyung Yoo ◽

Jae Min Lee ◽

Seung Han Kim ◽

...

Keyword(s):

Cell Death ◽

Mouse Model ◽

Blood Vessels ◽

Therapeutic Effect ◽

Nude Mouse ◽

Gastrointestinal Cancer ◽

Irreversible Electroporation ◽

Control Group ◽

Cancer Tissue ◽

Caco2 Cells

62 Background: Irreversible electroporation (IRE) is a promising novel technique for the ablation of tumors. IRE has an advantage over other ablation technique in its mechanism to remove undesired cells by affecting the cell membrane without thermally destructing blood vessels, nerves and the surrounding tissues. Studies regarding the clinical application of IRE have been performed in humans, as well as in animals, for organs such as the liver, kidney, prostate, etc. and IRE is now accepted as a novel anti-cancer ablation modality. The aim of this study was to evaluate the therapeutic effect of IRE in mouse model of gastrointestinal cancer for the first time. Methods: The Caco2 cells (ATCC) were cultured in petri-dishes. Male nude mice (Immunodeficient (CAnN.Cg-Foxn1 nu/CrljBgi) 6 weeks old, Orient Inc., Korea) were introduced. Caco2 cells were each visually injected at 1.0 x 107cells/ml into both flakes (one for control, the other for IRE). We performed in vivo IRE procedures in the tumors of nude mouse model. Electrical pulses were applied to the tumor of nude mouse using a DC generator at 1~2kV/cm amplitude, 20~50 pulses, 100 µA length, with 1mm separation between two needle type electrodes. We analyzed the tissues with H&E staining and TUNEL assay immediately afterwards, and then 10 hours, 24 hours. Results: All mice were preserved during the experiment without significant complications. There was complete cell death within the IRE lesions without intervening live cells in 2KV after 24 hours. H& E statin and Tunnel stain at 10hr after 2KV IRE ablation revealed more severe apoptotic cell death comparing with control group. Apoptotic index peaks at 10 hours after IRE ablation, and decreases in 24hours. The framework of extracellular matrix and blood vessels were not affected by IRE. Conclusions: The present study demonstrated that IRE ablated colon cancer tissue very effectively through the induction of cellular apoptosis. This study suggests that IRE has the potentiality in treatment of gastrointestinal cancer patients.

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Caulis Sargentodoxae Prescription Plays a Therapeutic Role with Decreased Inflammatory Cytokines in Peritoneal Fluid in the Rat Endometriosis Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9627907 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Mengfei Zhuang ◽

Yang Cao ◽

Yan Shi ◽

Lin Yu ◽

Yanan Niu ◽

...

Keyword(s):

Chinese Medicine ◽

Inflammatory Cytokines ◽

Peritoneal Fluid ◽

Mrna Level ◽

Control Group ◽

Group Model ◽

Model Group ◽

Specific Expression ◽

Growth Inhibitory ◽

Anti Inflammatory

Caulis Sargentodoxae prescription has been confirmed by the gynecological clinical observation to be effective in the treatment of endometriosis (EMs), and inflammatory cytokines were involved in EMs. In this paper, animal experiments were designed to explain anti-inflammatory mechanisms of Caulis Sargentodoxae prescription on endometriosis. The EMs model was established by autoplastic transplantation, and rats were randomly divided into seven groups: normal control group, model group, ovariectomized group, gestrinone (Western medicine) group, Caulis Sargentodoxae prescription (Chinese medicine) group, celecoxib (inhibitor) group, and combination (Chinese medicine + inhibitor) group. After oral administration for 21 days, the growth inhibitory rates of the ectopic endometria in treatment groups were evaluated, and the levels of inflammatory cytokines in the serum and peritoneal fluid were determined by ELISA, as well as the expression of prostaglandin endoperoxide synthase 2 (PTGS2) in the ectopic endometrial tissues was detected by real-time polymerase chain reaction, immunohistochemistry, and western blotting. The growth inhibitory rates of the ectopic endometria were significantly higher in the Caulis Sargentodoxae prescription group and gestrinone group, in comparison with the model group p<0.05. In the Caulis Sargentodoxae prescription group, the levels of inflammatory cytokines including IL-1, IL-2, IL-6, TNF-α, and PGE2 were all reduced in the serum and peritoneal fluid p<0.05. In addition, the specific expression of PTGS2 in the ectopic endometrial tissues significantly decreased in the Caulis Sargentodoxae prescription group and PTGS2 inhibitor celecoxib group both at mRNA and protein levels, but in the steroid hormone drug gestrinone group not at the mRNA level. So, Caulis Sargentodoxae prescription has a reliable therapeutic effect on the EMs by its comprehensive anti-inflammatory roles, possibly in a way different from gestrinone.

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