Pharmacokinetic and gut microbiota analyses revealed the effect of Lactobacillus acidophilus on the metabolism of Olsalazine in ulcerative colitis rats.

Olsalazine is a typical 5-aminosalicylic acid (5-ASA) drug that depends on gut microbiota to liberate its anti-inflammatory moiety 5-ASA in the treatment of ulcerative colitis (UC). In recent decades, 5-ASA drugs combined with probiotics have achieved a better effective treatment for UC. Mechanisms of combination therapy have been widely discussed from a pharmacodynamic perspective. However, it is still unclear whether the better therapeutic efficacy of combination therapy was made by changing the metabolism of 5-ASA drugs in the colon under the regulation of probiotics. In the present study, combined with pharmacokinetic and gut microbiota analyses, we systematically evaluated the potential effect of Lactobacillus acidophilus (L. acidophilus) on the metabolism of Olsalazine at three levels (pharmacokinetic characteristics, metabolic microbiota, and metabolic enzymes) to offer some insights into this issue. As pharmacokinetic results showed, L. acidophilus barely had an influence on the pharmacokinetic parameters of Olsalazine, 5-ASA, and N-Ac-5-ASA. Notably, the colonic exposure of 5-ASA was not affected by L. acidophilus. Gut microbiota results also illustrated that L. acidophilus did not change the total abundance of azoreductase (azoR) and N-acetyltransferase (NAT) associated gut microbiota and enzymes, which are involved in the metabolism of Olsalazine. Both pharmacokinetic and gut microbiota results revealed that L. acidophilus did not increase the colonic exposure of 5-ASA to improve the efficacy of combination therapy. L. acidophilus played its role in UC treatment by regulating gut microbiota composition and amino acid, phenolic acid, oligosaccharide, and peptidoglycan metabolic pathways. There was no potential medication risk of combination therapy of Olsalazine and L. acidophilus. In summary, this research provided strong evidence of medication safety and a comprehensive understanding of therapeutic advantages for combination therapy of probiotics and 5-ASA drugs from the pharmacokinetic and gut microbiota perspectives.

Abietane diterpenoids from Dracocephalum moldavica L. and their anti-inflammatory activities in vitro.

Five undescribed abietane diterpenoids, dracocephalumoids A-E, together with six known analogues were isolated from the aqueous EtOH extract of aerial parts of Dracocephalum moldavica L.. The structures were elucidated through extensive analysis of spectroscopic data, and their absolute configurations were established by Mosher's method and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculation. Cell-based anti-inflammatory assays displayed that dracocephalumoid A, uncinatone, trichotomone F and caryopterisoid C showed potent suppressive effects against TNF-α, IL-1ß or NO production in LPS-induced RAW 264.7 cells, with IC50 values ranging from 1.12 to 5.84 µM. The structure-activity relationship of these compounds was also discussed.

Determination of the Absolute Configuration of Super-Carbon-Chain Compounds by a Combined Chemical, Spectroscopic, and Computational Approach: Gibbosols†A and B.

Marine dinoflagellates produce remarkable organic molecules, particularly those with polyoxygenated long-carbon-chain backbones, namely super-carbon-chain compounds (SCCCs), characterized by the presence of numerous stereogenic carbon centers on acyclic polyol carbon chains. Even today, it is a challenge to determine the absolute configurations of these compounds. In this work, the planar structures and absolute configurations of two highly flexible SCCCs, featuring either a C69 - or C71 -linear carbon backbone, gibbosols A and B, respectively, each containing thirty-seven stereogenic carbon centers, were unambiguously established by a combined chemical, spectroscopic, and computational approach. The discovery of gibbosols A and B with two hydrophilic acyclic polyol chains represents an unprecedented class of SCCCs. A reasonable convergent strategy for the biosynthesis of these SCCCs was proposed.

Jingshu Keli and its Components Notoginsenoside R1 and Ginsenoside Rb1 Alleviate the Symptoms of Cervical Myelopathy through Kir3.1 Mediated Mechanisms.

BACKGROUND & OBJECTIVE: Cervical Spondylotic Myelopathy (CSM) is one of the most serious spinal cord disorders in adults. Pharmacological modulation of ion channels is a common strategy to interfere with CSM and prevent neuronal damage. METHODS: Here, we investigated the effects of Jingshu Keli (JSKL), a traditional Chinese herbal formula, on CSM-related gait abnormality, mechanical allodynia and thermal hyperalgesia, and assessed the neuronal mechanisms of JSKL on cultured brainstem cells. Behavioral tests and patch clamp recordings were performed to make this assessment. RESULTS: In our study, we found that JSKL significantly recovered the gait performance (P<0.001) and decreased the levels of mechanical pain in 18.9% (P<0.01) and thermal pain in 18.1% (P<0.05). Further investigation suggested that JSKL and its containing ginsenoside Rb1 (GRb1), notoginsenoside R1 (NGR1) reduced the action potential frequency in 38.5%, 27.2%, 25.9%, and hyperpolarized resting membrane potential in 15.0%, 13.8%, 12.1%, respectively. Kir channels, not KV channels and KCa channels, were the major intermediate factors achieving treatment effects. Finally, immunostaining results showed that the phosphorylation of Kir3.1 was promoted, whereas the total expression level did not change. CONCLUSION: Our study reveals a novel strategy of treating CSM by using Traditional Chinese Medicines (TCMs) containing active components.

Phomopsols A and B from the Mangrove Endophytic Fungus Phomopsis sp. xy21: Structures, Neuroprotective Effects, and Biogenetic Relationships.

A polyketide-derived alkaloid featuring a unique 3,4-dihydro-2H-indeno[1,2-b]pyridine 1-oxide motif, named phomopsol A (1), and a highly oxidized polyketide containing a new 3,5-dihydro-2H-2,5-methanobenzo[e][1,4]dioxepine moiety, named phomopsol B (2), were isolated from the Thai mangrove endophytic fungus Phomopsis sp. xy21, together with the related biosynthetic polyketide 3. The structures of 1-3 were unambiguously established by single-crystal X-ray diffraction analysis (Cu Kα), and their neuroprotective effects in PC12 cells were evaluated. The biosynthetic origins of 1-3 are proposed.

The Role of Traditional Chinese Herbal Medicines and Bioactive Ingredients on Ion Channels: A Brief Review and Prospect.

Traditional Chinese Medicines (TCMs), particularly the Chinese herbal medicines, are valuable sources of medicines and have been used for centuries. The term "TCMs" both represents to the single drug agent like Salvia miltiorrhiza, Ligusticum chuanxiong and Angelica sinensis, and those herbal formulas like Jingshu Keli, Wenxin Keli and Danzhen powder. In recent years, the researches of TCMs developed rapidly to understand the scientific basis of these herbs. In this review, we collect the studies of TCM and their containing bioactive compounds, and attempt to provide an overview for their regulatory effects on different ion channels including Ca2+, K+, Na+, Cl- channels and TRP, P2X receptors. The following conditions are used to limit the range of our review. (i) Only the herbal materials are included in this review and the animal- and mineral-original TCMs are excluded. (ii) The major discussions in this review focus on single TCM agent and the herbal formulas are only discussed for a little. (iii) Those most famous herbal medicines like Capsicum annuum (pepper), Curcuma longa (ginger) and Cannabis sativa (marijuana) are excluded. (iv) Only those TCM herbs with more than 5 research papers confirming their effects on ion channels are discussed in this review. Our review discusses recently available scientific evidences for TCMs and related bioactive compounds that have been reported with the modulatory effects on different ion channels, and thus provides a new ethnopharmacological approach to understand the usage of TCMs.

A new caffeic acid tetramer from the Dracocephalum moldavica L.

A new caffeic acid tetramer compound, named (+) methyl rabdosiin (4), together with seven known caffeic acid multimers (1-3, 5-8) and one caffeic acid monomer (9), were isolated from the aerial parts of Dracocephalum moldavica L. The structures of these compounds were assigned on the basis of 1D and 2D NMR spectroscopic and mass spectrometry analyses. The protective effects of compounds 2-4 against hydrogen peroxide (H2O2)-induced apoptosis were evaluated in primary cardiomyocytes of SD neonatal rats in vitro by the MTT method. Three compounds exhibited potent protective activities at 12.5 µg/mL.

Comparison of the gas-liquid dual support fixation and Heitzman fixation techniques for preparing lung specimens.

The aim of the present study was to compare the gas-liquid dual support fixation and Heitzman fixation techniques for the preparation of lung specimens. A total of 40 fresh lung samples were surgically collected from 40 male patients with lung cancer by biopsy. Patients were recruited from the Affiliated Hospital of Qingdao University Medical College (Qingdao, China) between July 2007 and June 2014. Samples were prepared using either the gas-liquid dual support fixation method (group A; n=26) or the Heitzman fixation method (group B; n=14). High-resolution computed tomography (HRCT) scanning was performed prior to surgery and corresponding postoperative HRCT scanning was conducted for the lung specimens; the gross transverse specimen section, cord photography images and histological sections were evaluated. Morphological observations of lung specimens indicated that there were 22 cases in group A with grade I (84.6%) and 4 cases with grade II (15.4%), whereas, in group B, there were 5 cases with grade II (35.7%) and 9 cases with grade III (64.3%). Statistical analysis demonstrated that the grades of specimens between the two groups were significantly different (P<0.01). Results from imaging and histological studies found that the quality of lung specimens was superior in group A, compared with group B. In conclusion, the present study demonstrated that, compared with the Heitzman fixation method, gas-liquid dual support fixation may be a superior technique for the preparation of lung specimens. This finding may facilitate the improvement of lung HRCT and pathological studies.

Two new biflavonones from Coreopsis tinctoria.

Two new biflavonone compounds, sikokianin D (1) and sikokianin E (2), were isolated from the capitulum of Coreopsis tinctoria. The structures of these compounds were elucidated by spectroscopic techniques including NMR, HRESIMS and circular dichroism (CD).

An automated dual-gradient liquid chromatography-MS/MS method for the simultaneous determination of ferulic acid, ligustrazine and ligustilide in rat plasma and its application to a pharmacokinetic study.

An automated on-line SPE and innovative fast polarity switch bioanalysis method employing dual-gradient liquid chromatography (DGLC) coupled with mass spectrometry (DGLC-MS/MS) was established and validated for the simultaneous determination of ferulic acid, ligustrazine and ligustilide in rat plasma after administration of Rhizoma Chuanxiong, Angelica sinensis extract or monomer. The proteins in plasma samples were precipitated using acetonitrile: methanol (1:1, v/v). Sulfamethoxazole was used as an internal standard. The DGLC system contains two high-pressure pumps. The first pump was used for on-line solid phase extraction with a Cyclone™ SPE column. Chromatographic separations were performed with the other pump on a Syncronis C18 rapid analytical column. The analytical column was eluted by a gradient program that featured an acetonitrile/methanol/water gradient (flow-rate, 0.4ml/min). DGLC afforded greater convenience for bioanalysis. All analytes were simultaneously monitored in positive- and negative-ion mode by SRM (selective reaction monitoring) using the fast polarity switch speed of TSQ Vantage™. Method validation of the assay was implemented. No significant matrix effect was observed. The LLOQ of all analytes were <1.0ng/ml. The precision, recovery and linearity of the analysis met the pre-established requirements. The method was applied to the pharmacokinetics of ferulic acid, ligustrazine and ligustilide in Rhizoma Chuanxiong or Angelica sinensis extracts or monomers.

Comparative pharmacokinetics and bioavailability of four alkaloids in different formulations from Corydalis decumbens.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis decumbens, a Traditional Chinese Medicine listed in Chinese Pharmacopoeia, is clinically used for the treatment of paralytic stroke, headache, rheumatic arthritis and sciatica in China. AIM OF THE STUDY: This study was aimed to compare the pharmacokinetics and bioavailability of protopine, tetrahydropalmatine, bicuculline, and egenine in three formulations prepared from the rhizomes of Corydalis decumbens. MATERIALS AND METHODS: Alkaloid extract (CDAs-SFE) was prepared from the rhizomes of Corydalis decumbens by supercritical CO2 fluid extraction; CDAs-SFE/HPßCD (hydroxypropyl-ß-cyclodextrin inclusion complex), and CDAs-SFE/HCl (hydrochloride freeze-dried powder) were resulted from CDAs-SFE through complexation with HPßCD and hydrochloride, respectively. An UFLC-MS/MS method was developed for quantitative analysis of protopine, tetrahydropalmatine, bicuculline and egenine simultaneously in rat plasma after oral administration. The differences of pharmacokinetics and bioavailability of the four alkaloids in three formulations were determined by pharmacokinetics analyses. RESULTS AND CONCLUSIONS: The Cmax, AUC and bioavailability of protopine and tetrahydropalamatine (bioactive components) in CDAs-SFE/HCl were significantly higher than in CDAs-SFE and in CDAs-SFE/HPßCD. In contrast, in CDAs-SFE/HPßCD, AUC and bioavailability of tetrahydropalamatine were significantly lower, while those of bicuculline (toxic compound) appeared to be higher than both in CDAs-SFE and in CDAs-SFE/HCl. The results indicated that CDAs-SFE/HCl was the best beneficial formulation among the three formulations for the alkaloid extract prepared from the rhizomes of Corydalis decumbens, in which protopine and tetrahydropalamatine displayed higher bioavailability, but lower for bicuculline.