The in vivo and in vitro study of polysaccharides from a two-herb formula on ulcerative colitis and potential mechanism of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Lycium barbarum and Astragalus membranaceus are two traditional medicinal herbs widely used in China for nourishing Yin and reinforcing Qi. The purpose of the study was to investigate the prophylactic and curative effects of crude polysaccharides (QHPS) extracted from a two-herb formula composed of Lycium barbarum and Astragalus membranaceus at a ratio of 2:3 in colitis rats, and to further elucidate the potential mechanism of action in epithelial cell proliferation in vitro. MATERIALS AND METHODS: An acetic acid (AA)-induced ulcerative colitis rat model was applied in the study. Two independent protocols were used to assess the prophylactic and curative effects of QHPS, respectively, in which rats were either pre-treated with QHPS (0.18g/kg) for 14 days prior to AA induction, or post-treated with QHPS for 7 days after AA induction. The stool consistency and weight loss were used to evaluate disease activity. The morphological changes in intestinal mucosa at the end of the experiments were observed. The serum levels of endotoxin (EDT), diamine oxidase (DAO) and d-lactate (DLA), important biochemical markers for evaluating intestinal mucosal structure and function, were measured. In the in vitro mechanistic studies, rat intestinal epithelial cells (IEC-6) were used to access for epithelium regeneration. RESULTS: The intra-colonic instillation of AA induced ulcerative colitis in rat, as indicated by diarrhea, weight loss, and colonic mucosal damage. Both prophylactic and curative treatments effectively reduced the weight loss and diarrhea and attenuated the colonic mucosal damage associated with inducible colitis. The significant increase in serum levels of DAO, DLA and EDT was induced by AA and inhibited by QHPS treatment. Moreover, QHPS could significantly stimulate IEC-6 proliferation in a dose-dependent manner (p<0.05). CONCLUSION: The present study indicated for the first time that polysaccharides extracted from this two-herb formula can protect against experimental ulcerative colitis, presumably by promoting the recovery of the intestinal barrier.

Metabolic Signatures of Kidney Yang Deficiency Syndrome and Protective Effects of Two Herbal Extracts in Rats Using GC/TOF MS.

Kidney Yang Deficiency Syndrome (KDS-Yang), a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrometry. WKY1, a polysaccharide extract from Astragalus membranaceus and Lycium barbarum, and WKY2, an aqueous extract from a similar formula containing Astragalus membranaceus, Lycium barbarum, Morinda officinalis, Taraxacum mongolicum, and Cinnamomum cassia presl, were used separately for protective treatments of KDS-Yang. The changes of serum metabolic profiles indicated that significant alterations of key metabolic pathways in response to abrupt hydrocortisone perturbation, including decreased energy metabolism (lactic acid, acetylcarnitine), lipid metabolism (free fatty acids, 1-monolinoleoylglycerol, and cholesterol), gut microbiota metabolism (indole-3-propionic acid), biosynthesis of catecholamine (norepinephrine), and elevated alanine metabolism, were attenuated or normalized with different degrees by the pretreatment of WKY1 or WKY2, which is consistent with the observations in which the two herbal agents could ameliorate biochemical markers of serum cortisone, adrenocorticotropic (ACTH), and urine 17-hydroxycorticosteroids (17-OHCS).

[Preventive effect of ganlong capsule on chronic alcoholic hepatic injury in rats].

OBJECTIVE: To study the preventive effect of Ganlong capsule on chronic alcoholic hepatic injury in rats and its mechanism. METHOD: The rat chronic hepatic injury model was induced by intragastrically administered with gradient alcohol, once a day for 12 weeks. Efforts were made to detect the content of ALT, AST, TG, CHO, TNF-alpha in rat serum and GSH, SOD, MDA, ADH, Alb in hepatic tissues were detected, conduct a hepatic pathological examination, and pathological injury grading for livers. RESULT: Ganlong capsule could reduce the content of ALT, AST, TG in blood serum, MDA in hepatic tissues (P < 0.05), and enhance the activities of antioxidants such as SOD and GSH in hepatic tissues (P < 0.05). According to the liver histopathological observation, most structures of hepatic lobules in the model group were destroyed, with disordered liver cell cords, diffuse fat empty bubbles of different sizes in cytoplasm, focal necrosis and infiltration of inflammatory cells. All of treatment groups showed alleviation in rat liver injury to varying degrees. CONCLUSION: Ganlong capsule has a significant preventive effect to chronic alcoholic hepatic injury in rats.

Metabonomic strategy to the evaluation of chinese medicine compound danshen dripping pills interfering myocardial ischemia in rats.

Coronary heart disease (CHD) is one of the highest mortality diseases in the world. Traditional Chinese medicine compound Danshen dripping pills (CDDPs) have currently made a great achievement in treating CHD. However, the therapeutic mechanism of CDDP is often poorly interpreted. In this study, a GC-MS-based metabonomic study was conducted to assess the holistic efficacy of CDDP for myocardial infarction in male Sprague-Dawley rats, which were divided into the control group, the sham group, the model group, the control + CDDP group, and the model + CDDP, with CDDP at a dose of 107 mg/kg·d (equal to 1.8 mL/kg·d). The metabonomic findings demonstrated great differences of metabolic pattern among sham, model, and the model + CDDP in the orthogonal partial least squares discriminant analysis (OPLS-DA) models, which coordinated well with the assessment of plasma biochemistry and histopathological assay. Differentially expressed metabolites suggested that energy metabolism, glycolysis, and lipid metabolism might be disrupted by myocardial infarction. Both the potential metabolic biomarkers and the biochemical histopathological indices were regulated effectively by CDDP.

Odorranalectin is a small peptide lectin with potential for drug delivery and targeting.

BACKGROUND: Lectins are sugar-binding proteins that specifically recognize sugar complexes. Based on the specificity of protein-sugar interactions, different lectins could be used as carrier molecules to target drugs specifically to different cells which express different glycan arrays. In spite of lectin's interesting biological potential for drug targeting and delivery, a potential disadvantage of natural lectins may be large size molecules that results in immunogenicity and toxicity. Smaller peptides which can mimic the function of lectins are promising candidates for drug targeting. PRINCIPAL FINDINGS: Small peptide with lectin-like behavior was screened from amphibian skin secretions and its structure and function were studied by NMR, NMR-titration, SPR and mutant analysis. A lectin-like peptide named odorranalectin was identified from skin secretions of Odorrana grahami. It was composed of 17 aa with a sequence of YASPKCFRYPNGVLACT. L-fucose could specifically inhibit the haemagglutination induced by odorranalectin. (125)I-odorranalectin was stable in mice plasma. In experimental mouse models, odorranalectin was proved to mainly conjugate to liver, spleen and lung after i.v. administration. Odorranalectin showed extremely low toxicity and immunogenicity in mice. The small size and single disulfide bridge of odorranalectin make it easy to manipulate for developing as a drug targeting system. The cyclic peptide of odorranalectin disclosed by solution NMR study adopts a beta-turn conformation stabilized by one intramolecular disulfide bond between Cys6-Cys16 and three hydrogen bonds between Phe7-Ala15, Tyr9-Val13, Tyr9-Gly12. Residues K5, C6, F7, C16 and T17 consist of the binding site of L-fucose on odorranalectin determined by NMR titration and mutant analysis. The structure of odorranalectin in bound form is more stable than in free form. CONCLUSION: These findings identify the smallest lectin so far, and show the application potential of odorranalectin for drug delivery and targeting. It also disclosed a new strategy of amphibian anti-infection.