Daucosterol combined with umbilical cord mesenchymal stem cell-derived exosomes can alleviate liver damage in liver failure mice by regulating the IL-6/STAT3 signaling pathway.

Daucosterol is a phytosterol glycoside with hepatoprotective properties. The objective of the present study was to confirm the role of daucosterol in liver failure. Exosomes were isolated from primary mouse umbilical cord mesenchymal stem cells (UCMSCs). A liver failure mouse model was generated by injecting lipopolysaccharide/D-galactosamine. Mice were treated with exosomes alone or in combination with daucosterol (5, 10, or 20 mg/kg). Liver tissue damage was examined by hematoxylin-eosin, Masson's trichrome, and TUNEL staining. The levels of genes, proteins, and inflammatory factors were determined using real-time qPCR, western blotting, and enzyme-linked immunosorbent assay, respectively. Compared with normal mice, we noted severe damage, fibrosis, and apoptosis in the liver tissues of liver failure-induced mice. UCMSC-derived exosomes effectively alleviated hepatic damage in the mouse model. Compared with exosome treatment alone, exosomes combined with daucosterol significantly and dose-dependently reduced pathological changes in model mice. Exosome treatment alone or combined with daucosterol also markedly decreased the liver index and reduced levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 in model mice. Exosome treatment alone or combined with daucosterol suppressed mRNA expression levels of IL-6 and signal transducer and activator of transcription (STAT3) and STAT3 protein expression in model mice. Our findings revealed that treatment with daucosterol combined with UCMSC-derived exosomes was superior to exosomes alone for alleviating hepatic damage in mice with liver failure by regulating the IL-6/STAT3 signaling pathway. Accordingly, daucosterol combined with UCMSC-derived exosomes may be a prospective treatment strategy for liver failure.

Therapeutic mechanism of steaming umbilical cord therapy with Chinese herbal medicine on a rat model of IBS-D via the PAR-2/TRVP1 pathway.

OBJECTIVE: This study aimed to investigate the PAR-2/TRVP1-based mechanism of steaming umbilical cord therapy with Chinese Herbal Medicine (SUCT-CHM) in IBS-D rat models. METHODS: Sixty-two IBS-D modeled rats were established, and were randomly assigned to the control group (n = 31) and the experimental group (n = 31). The model group did not receive intervention measures, and the experimental group was treated with SUCT-CHM. After 14 days of intervention, the two groups of rats were compared in terms of body weight, gastrointestinal function, Bristol stool score, wet/dry weight ratio of rat stool, and abdominal withdrawal reflex scores. The transient receptor potential vanilloid receptor 1 (TRPV1), protease-activated receptors-2 (PAR-2), calcitonin gene related peptide (CGRP) and Substance P (SP) protein expression were detected using ELISA. RESULTS: After 14 d of intervention, compared to the control group, the rats in the experimental group showed a significant increase in body mass indexes (P < 0.05); decreased Bristol stool scores (P < 0.05); less stagnation of the intestinal contents and greater intestine propulsion rate (P < 0.05), lower wet/dry weight ratio of rat stool (P < 0.05), abdominal withdrawal reflex scores (P < 0.05) as well as PAR-2, TRVP1, CGRP and SP expression levels (P < 0.05). CONCLUSION: SUCT-CHM was effective in treating IBS-D in rats. It improved gastrointestinal function and reduced visceral hypersensitivity in rats possibly via the PAR-2/TRVP1 pathway.

[Effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum GH and PG in chronic atrophic gastritis rats].

OBJECTIVE: To observe the effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum growth hormone (GH) and pepsinogen (PG) in chronic atrophic gastritis (CAG) rats, and to explore the potential mechanism of heat-sensitive moxibustion for CAG. METHODS: A total of 66 male SD rats were randomized into a blank group (12 rats) and a model establishment group (54 rats). No intervention was given in the blank group. Rats in the model establishment group were intervented with compound pathogeny method for 12 weeks to establish CAG model, which were further divided into a model group (11 rats), a vitacoenzyme group (11 rats) and a moxibustion group (22 rats). In the moxibustion group, suspending moxibustion was applied at "Zhongwan" (CV 12) for 40 min. After the intervention of moxibustion, 0.9% sodium chloride solution was given by gavage (2 mL·kg-1·d-1). According to the changes of tail temperature, rats in the moxibustion group were divided into a heat-sensitive moxibustion group (11 rats) and a non-heat-sensitive moxibustion group (8 rats). The vitacoenzyme group was given vitacoenzyme as the same dose by gavage. The intervention was adopted once a day for 28 days. Changes of body weight were observed among the groups. Expressions of serum GH, PGⅠand PGⅡwere detected by ELISA, and the ratio of PGⅠand PGⅡ (PGR) was calculated. The morphological changes of gastric mucosa were observed by macroscopy and light microscope. RESULTS: ①After modeling, the body weight of rats in the model establishment group was lower than the blank group (P<0.01). Compared with the model group, the body weight of rats in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group was increased after intervention (P<0.05), and there were no significant differences among the intervention groups (P>0.05). ②Under macroscopy and light microscope, gastric tissue of rats after modeling showed dark red and pale gastric mucosa, lower plica and mucosal congestion. The glands of lamina propria were atrophied or disappeared with sparse and disordered arrangement, in which, lymphoid follicles and inflammatory cells could be observed. After intervention, morphology of gastric mucosa was improved in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group. ③Compared with the blank group, the serum levels of GH, PGⅠ, PGⅡ and PGR were decreased in the model group (P<0.05, P<0.01). Compared with the model group, the serum levels of GH, PGⅠand PGⅡwere increased in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group (P<0.05, P<0.01), the levels of PGR were increased without statistical difference (P>0.05). Compared with the vitacoenzyme group and the non-heat-sensitive moxibustion group, the serum levels of GH and PGⅠwere increased in the heat-sensitive moxibustion group (P<0.05). CONCLUSION: Heat-sensitive moxibustion at "Zhongwan" (CV 12) can improve the morphology of gastric mucosa in chronic atrophic gastritis rats, its mechanism may be related to the up-regulation of serum GH and PGⅠ.