Shen-Fu Decoction could ameliorate intestinal permeability by regulating the intestinal expression of tight junction proteins and p-VASP in septic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-Fu Decoction (SFD), a classic Traditional Chinese paired herb formulation, has been widely used for the treatment of sepsis in China. This study was carried out to assess the effects of SFD in sepsis-induced intestinal permeability and intestinal epithelial tight junction damage in rats with sepsis. MATERIALS AND METHODS: A rat model of sepsis was created by cecal ligation and puncture (CLP). Rats in Sham and CLP + vehicle groups received equal distilled water, while rats in SFD group were treated by gavage of SFD (3 mg/kg, twice a day) for 72h. Mortality, sepsis-induced peritoneal inflammation, intestinal and liver histopathology damage, intestinal permeability (serum FITC-dextran and D-lactate), serum LPS, serum inflammation (PCT, TNF-α, and IL-6), and liver function (AST and ALT) were evaluated. The levels of zonula occluden (ZO-1), Occludin, Claudin-1 were analyzed by Real-time quantitative PCR and Western blotting (WB) respectively. Vasodilator-stimulated phosphoprotein (VASP) and p-VASP in intestinal epithelium were analyzed by WB. RESULTS: Our study showed that SFD markedly reduced the mortality rate of CLP rats, prevented intestine and liver damage, relieved sepsis-induced intestinal permeability and inflammation elevation, ameliorated sepsis-induced impaired intestinal permeability by regulating the expression of ZO-1, Occludin, Claudin-1 and p-VASP. CONCLUSIONS: The herbal formula SFD may be useful for reducing sepsis-induced organic damage and mortality by ameliorating the condition of sepsis-induced intestinal permeability by regulating tight junction proteins and p-VASP.

Polysaccharide from spore of Ganoderma lucidum ameliorates paclitaxel-induced intestinal barrier injury: Apoptosis inhibition by reversing microtubule polymerization.

Side effects of chemotherapy are burning questions for physicians and patients involved in cancers. Ganoderma lucidum is a widely consumed traditional Chinese medicine and edible mushroom with multiple functional properties. The present study aims to investigate the potential of polysaccharides from spore of G. lucidum (SGP) on small intestinal barrier function recovery against paclitaxel (PTX) challenge in a breast cancer mice model and IEC-6 cell line. The 4T1 tumor-bearing mice were treated with PTX together with four-week daily oral administration of SGP. Results indicated that combination of PTX and SGP reversed body weight lost and remolded the histology of small intestine, accompanied with promoted proliferation but suppressed apoptosis in intestinal cells. Intestinal barrier function was enhanced by the combination as indicated by reduced endotoxemia and the up-regulation of tight junction proteins, including Zonula occludens-1 (ZO-1), E-cadherin, ß-catenin and Occludin. The protection of SGP was further confirmed in IEC-6 cells affected by PTX in vitro. The combination treatment prevented PTX-induced apoptosis in IEC-6 by inhibiting microtubule polymerization, and the aforementioned tight junction proteins were also upregulated. These findings suggest a promising protective effect of SGP against small intestinal barrier injury caused by PTX, highlighting its clinical implication against the chemotherapy side effects.

Treatment with tanshinone IIA suppresses disruption of the blood-brain barrier and reduces expression of adhesion molecules and chemokines in experimental autoimmune encephalomyelitis.

Tanshinone IIA (TSIIA), one of the major bioactive components of the traditional Chinese herb Salvia miltiorrhiza, has been reported to have both anti-inflammatory and immunoregulatory effects. The effect of treatment with TSIIA in multiple sclerosis, an autoimmune inflammatory neurodegenerative disease, however, remains poorly understood. In the present study, experimental autoimmune encephalomyelitis (EAE), a classical experimental model of MS, was used to investigate the therapeutic effect of TSIIA. TSIIA attenuated motor dysfunction and improved inflammation and demyelination associated with EAE in a dose-dependent manner. TSIIA also significantly reduced the levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule-1 (Iba-1), and protected the integrity of the blood-brain barrier (BBB) by increasing the expression of critical endothelial tight junction (TJ) proteins. TSIIA also inhibited the expression of some adhesion molecules and chemokines, which are considered to be critical for adhesion of immune cells and migration across the BBB. TSIIA was thus shown to be effective in the treatment of EAE through preventing the infiltration of immune cells into the CNS, strengthening the integrity of the BBB and decreasing the numbers of adhesion molecules and chemokines.

Posttreatment with Ma-Xing-Shi-Gan-Tang, a Chinese medicine formula, ameliorates lipopolysaccharide-induced lung microvessel hyperpermeability and inflammatory reaction in rat.

OBJECTIVE: The aim of present study was to investigate the efficacy of MXSGT, a traditional Chinese medicine formula used for treatment of respiratory system diseases, in the LPS-induced rat ALI particularly with a focus on its effect on lung microvascular hyperpermeability and inflammatory reaction. METHODS: Male Sprague-Dawley rats were injected with LPS (7.5 mg/kg, 1.5 mg/mL) intraperitoneally. MXSGT (0.52 g or 2.61 g/kg) was given by gavage six hours after LPS injection. RESULTS: LPS stimulation resulted in a reduced survival rate, deteriorated vital signs, an increase in the number of leukocytes adhering to lung venules, the albumin leakage, the activity of MPO in lung tissues, the production of pro-inflammatory cytokines and lung perivascular edema. After LPS stimulation, western blot analysis revealed an increase in the expression of ICAM-1 and toll-like receptor 4, a decrease in tight junction proteins and an activation of cav-1, Src, and NF-κB. All the LPS-induced alterations were significantly attenuated by posttreatment with MXSGT. CONCLUSIONS: This study demonstrated MXSGT as a potential strategy for lung microvascular hyperpermeability and inflammatory reaction in ALI, and suggested that the beneficial role of MXSGT was correlated with toll-like receptor 4, Src, and NF-κB.

Activating the Nrf2-mediated antioxidant response element restores barrier function in the alveolar epithelium of HIV-1 transgenic rats.

The master transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates the expression of antioxidant and phase II-metabolizing enzymes by activating the antioxidant response element (ARE) and thereby protects cells and tissues from oxidative stress. Pulmonary complications remain the leading cause of death in human immunodeficiency virus (HIV)-1-infected individuals, who display systemic oxidative stress and glutathione deficiency that can be modeled in transgenic rats where HIV-1-related viral proteins decrease glutathione levels and cause epithelial barrier dysfunction within the alveolar space by as yet unknown mechanisms. We hypothesized that HIV-1-related proteins inhibit Nrf2-mediated antioxidant defenses and thereby disrupt the normally tight alveolar epithelial barrier. Nrf2 RNA silencing dampened Nrf2/ARE activity, decreased the expression of the tight junction proteins zonula occludens-1, occludin, and claudin-18, increased paracellular permeability of alveolar epithelial monolayers derived from wild-type rats, and therefore reproduced the effects of HIV-1 transgene expression on the epithelial barrier that we had previously described. In contrast, upregulating Nrf2 activity, either by plasmid-mediated overexpression or treatment with the Nrf2 activator sulforaphane, increased the expression of ARE-dependent antioxidants, including NAD(P)H dehydrogenase, quinone 1 and glutathione, improved the expression of tight junction proteins, and restored the ability to form tight barriers in alveolar epithelial cells from HIV-1 transgenic rats. Taken together, these new findings argue that HIV-1-related proteins downregulate Nrf2 expression and/or activity within the alveolar epithelium, which in turn impairs antioxidant defenses and barrier function, thereby rendering the lung susceptible to oxidative stress and injury. Furthermore, this study suggests that activating the Nrf2/ARE pathway with the dietary supplement sulforaphane could augment antioxidant defenses and lung health in HIV-1-infected individuals.