Gut microbiota controls the development of chronic pancreatitis: A critical role of short-chain fatty acids-producing Gram-positive bacteria.

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Identification of flavonoids in Dendrobium huoshanense and comparison with those in allied species of Dendrobium by TLC, HPLC and HPLC coupled with electrospray ionization multi-stage tandem MS analyses.

Dendrobium huoshanense, a unique species in the genus Orchidaceae, is only found in China and is known as "mihu". Due to the lack of quality control, the use of D. huoshanense in the herbal market has been limited. In this study, methods based on thin-layer chromatography, high-performance liquid chromatography and high-performance liquid chromatography coupled with electrospray ionization multi-stage tandem mass spectrometry were used to identify the flavonoids in D. huoshanense and distinguish this species from other Dendrobium species. Using thin-layer chromatography, a characteristic band was observed for D. huoshanense, and this band was absent from the thin-layer chromatography plates of other Dendrobium species. Then, using high-performance liquid chromatography, nine peaks of flavonoids were observed in the chromatograms of ten batches of D. huoshanense. Ultimately, 22 flavonoids in D. huoshanense were identified by multi-stage tandem mass spectrometry, and 11 of these compounds are being reported from D. huoshanense for the first time. In addition, two compounds both with molecular weights of 710, were identified as being unique to D. huoshanense; one of these compounds, apigenin-6-C-α-L-rhamnosyl-(1→2)-ß-D-glucoside-8-C-α-L-arabinoside, was proven to be responsible for the characteristic thin-layer chromatography band of D. huoshanense. These analysis methods can be applied for the identification and quality control of D. Huoshanense.

Practical method for the rapid screening of xanthine oxidase inhibitors in herbal extracts by high-performance liquid chromatography based on on-line precolumn enzymatic reaction.

A high-performance liquid chromatography method with on-line precolumn enzymatic reaction for the screening of xanthine oxidase inhibitors in natural extracts was developed. In this method, the enzymatic reaction occurred at the capillary inlet during a predetermined waiting period, after which the reaction product, uric acid, was separated and detected by liquid chromatography using ultraviolet absorption at 295 nm. Enzyme inhibition can be read out directly from the reduced peak area of uric acid in comparison to a reference chromatogram obtained in the absence of any inhibitor. In the present study, the availability of on-line precolumn enzymatic reaction with ultraviolet detection was firstly evaluated by determining the inhibitory mechanism and IC50 values of allopurinol, a commercially available positive drug. Then, the newly developed method was applied to screening of ten natural extracts from traditional Chinese medicine and as a result, the extract of Epimedium sagittatum (Sieb. et Zucc.) Maxim was found to be most positive for xanthine oxidase inhibition. The results obtained were compared with those obtained by offline enzyme assay and the effectiveness of the present method was confirmed. A rapid, low-cost, and fully automated method for xanthine oxidase inhibitor screening was proposed.

Efficacy and safety of Abelmoschus manihot for primary glomerular disease: a prospective, multicenter randomized controlled clinical trial.

BACKGROUND: Abelmoschus manihot, a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess its efficacy and safety in patients with primary glomerular disease. STUDY DESIGN: Prospective, open-label, multicenter, randomized, controlled, clinical trial. SETTING & PARTICIPANTS: From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. INTERVENTIONS: A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50mg/d. The duration of intervention was 24 weeks. OUTCOMES & MEASUREMENTS: The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. RESULTS: Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot, losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2, respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of -508, -376, and -545 mg/d, respectively (P=0.003 for A manihot vs losartan and P<0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups (P>0.05), and there were no severe adverse events in any group. LIMITATIONS: Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. CONCLUSIONS: A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.

A modified rat model of exercise-induced renal injury and the protective effects of losartan and yishen huanji decoction.

We modified a rat model of exercise-induced renal injury by forcing 4-week-old male Sprague-Dawley (SD) rats (the MOD group) running on a treadmill for 8 weeks under conditions of high temperature, high humidity, bearing weight with some additional stimulations. Compared with the control (CON) group, the traditional running group (TRA), the losartan potassium intervention running group (LOS) and the traditional Chinese medicine "Yishen Huanji Decoction" intervention running group (CHI), the urinary, biochemistry indicators, the concentrations of angiotensin II (Ang II) were significantly higher in the MOD group than in the TRA group. After 3--4 weeks and 8-week training program, the 24-h urine protein and NAG levels in the LOS group and CHI group were lower than in the MOD group respectively. The BUN and SCr levels in the CHI group were lower than in the MOD group and higher than in the LOS group. AngII concentrations in the LOS group were higher than the MOD group. The modified rat renal injury model induced greater lesions than the traditional model. High temperatures, humidity and weight bearing were critical factors to induce Ang II activation, which can aggravate renal injury. Losartan potassium and the "Yishen Huanji Decoction" can protect against renal injury.

[Preventive and therapeutic effects of Yishen Huanji Decoction on kidney injury in rats induced by simulation of military overtraining].

OBJECTIVE: To observe the preventive and therapeutic effects of Yishen Huanji Decoction (YSHJD), a compound traditional Chinese herbal medicine, on military overtraining-induced kidney injury in a rat model. METHODS: Thirty SD rats were randomly divided into normal control group, untreated group and YSHJD-treated group. The military overtraining-induced kidney injury in rats was established by forcing to run on the treadmill for 8 weeks. The rats in YSHJD-treated group were administered with YSHJD at the same time. The 24-hour urines were collected every weekend for detecting the contents of urinary sediment, 24-hour urine total protein, 24-hour urine albumin and activity of N-acetyl-beta-D-glucosaminidase (NAG). The blood and renal tissues were collected after 8-week training, and the levels of serum urea nitrogen (BUN) and creatinine (SCr) were detected. Angiotensin II (Ang II) was detected by radioimmunoassay and activity of Na(+), K(+)-ATPase in kidney was analyzed by chemical colorimetric method. RESULTS: Compared with the normal control group, after 8-week training, the contents of 24-hour urine protein, activities of NAG in urine, and the levels of BUN and SCr in rats in the untreated group and YSHJD-treated group were obviously increased (P<0.05), and these parameters of the YSHJD-treated group were lower than those of the untreated group (P<0.05). The contents of Ang II in blood plasma and kidney of rats in the untreated group and YSHJD-treated group were higher than those of the normal control group (P<0.05), and had no statistical difference between the untreated group and YSHJD-treated group. Compared with the normal control group, the activity of Na(+), K(+)-ATPase in kidney of rats in the untreated group was obviously decreased (P<0.05), and had no statistical difference between the normal control group and YSHJD-treated group. CONCLUSION: YSHJD can protect against military overtraining-induced kidney injury in rats by decreasing the contents of 24-hour urine protein, BUN and SCr, and the activity of NAG, and increasing the activity of Na(+), K(+)-ATPase.