In vivo absorption, in vitro simulated digestion and fecal fermentation properties of polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine and their effects on human gut microbiota.

Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine (PPA) have various biological activities, but their properties after oral administration are not clear. In this study, the absorption, digestion and fermentation properties of PPA were studied using in vivo fluorescence tracking, in vitro simulated digestion and fecal fermentation experiments. The absorption experiment showed that fluorescence was only observed in the gastrointestinal system, indicating that PPA could not be absorbed. Simulated digestion results showed that there were no significant changes in the molecular weight, Fourier transform infrared spectroscopy (FT-IR) spectrum, monosaccharides and reducing sugar of PPA during the digestion process, showing that the overall structure of PPA was not damaged. However, the carbohydrate gel electrophoresis bands of PPA enzymatic hydrolysates after simulated digestion were significantly changed, indicating that simulated digestion might impact the configuration of PPA. In vitro fermentation showed that PPA could be degraded by microorganisms to produce short chain fatty acids, leading to a decrease in pH value. PPA can promote the proliferation of Bacteroideaceae, Megasphaera, Bacteroideaceae, and Bifidobacteriaceae, and inhibit the growth of Desulfobacteriota and Enterobacteriaceae. The results indicated that PPA could treat diseases by regulating gut microbiota, providing a scientific basis for the application and development of PPA.

The great potential of polysaccharides from natural resources in the treatment of asthma: A review.

Despite significant progress in diagnosis and treatment, asthma remains a serious public health challenge. The conventional therapeutic drugs for asthma often have side effects and unsatisfactory clinical efficacy. Therefore, it is very urgent to develop new drugs to overcome the shortcomings of conventional drugs. Natural polysaccharides provide enormous resources for the development of drugs or health products, and they are receiving a lot of attention from scientists around the world due to their safety, effective anti-inflammatory and immune regulatory properties. Increasing evidence shows that polysaccharides have favorable biological activities in the respiratory disease, including asthma. This review provides an overview of primary literature on the recent advances of polysaccharides from natural resources in the treatment of asthma. The mechanisms and practicability of polysaccharides, including polysaccharides from plants, fungus, bacteria, alga, animals and others are reviewed. Finally, the further research of polysaccharides in the treatment of asthma are discussed. This review can provide a basis for further study of polysaccharides in the treatment of asthma and provides guidance for the development and clinical application of novel asthma treatment drugs.

Characterization of Polysaccharides from the Pericarp of Zanthoxylum bungeanum Maxim by Saccharide Mapping and Their Neuroprotective Effects.

The pericarp of Zanthoxylum bungeanum maxim (PZM) is a commonly used spice and herbal medicine in China. In the present study, the structural characteristics of PPZM were investigated by saccharide mapping after enzymatic digestion by using high-performance thin layer chromatography (HPTLC) and polysaccharide analysis by using carbohydrate gel electrophoresis (PACE). The mechanisms of protective effects of PPZM on Aß25-35-induced oxidative damage were explored in PC12 cells. The results showed that PPZM contained 1,4-α-D-galactosidic, 1,4-α-D-galactosiduronic, and (1→4)-ß-D-glucosidic linkages. Pretreatment with PPZM significantly increased the cell viability of Aß25-35-injured PC12 cells. Flow cytometry and Hoechst/PI staining indicated that PPZM gradually relieved the apoptosis of the Aß25-25-treated cells. PPZM markedly decreased the ROS level of PC12 cells and suppressed Aß25-35-induced oxidative stress by increasing the SOD level, and decreasing the level of MDA and LDH. The mRNA expressions of caspase-3 and Bax were significantly downregulated, and Bcl-2 expression was upregulated by treatment with PPZM. PPZM significantly increased the mRNA expression of Nrf2 and HO-1 in Aß25-35 treated cells. The results indicated that PPZM alleviated apoptosis and oxidative stress induced by Aß25-25 through the inhibition of mitochondrial dependent apoptosis and activation of Nrf2/HO-1 pathway. PPZM can be used as a potential protective agent against Aß25-25-induced neurotoxicity.

Natural Medicines for the Treatment of Epilepsy: Bioactive Components, Pharmacology and Mechanism.

Epilepsy is a chronic disease that can cause temporary brain dysfunction as a result of sudden abnormal discharge of the brain neurons. The seizure mechanism of epilepsy is closely related to the neurotransmitter imbalance, synaptic recombination, and glial cell proliferation. In addition, epileptic seizures can lead to mitochondrial damage, oxidative stress, and the disorder of sugar degradation. Although the mechanism of epilepsy research has reached up to the genetic level, the presently available treatment and recovery records of epilepsy does not seem promising. Recently, natural medicines have attracted more researches owing to their low toxicity and side-effects as well as the excellent efficacy, especially in chronic diseases. In this study, the antiepileptic mechanism of the bioactive components of natural drugs was reviewed so as to provide a reference for the development of potential antiepileptic drugs. Based on the different treatment mechanisms of natural drugs considered in this review, it is possible to select drugs clinically. Improving the accuracy of medication and the cure rate is expected to compensate for the shortage of the conventional epilepsy treatment drugs.

The Effect of Protein-Rich Extract from Bombyx Batryticatus against Glutamate-Damaged PC12 Cells Via Regulating γ-Aminobutyric Acid Signaling Pathway.

Bombyx Batryticatus (BB) is a known traditional Chinese medicine (TCM) utilized to treat convulsions, epilepsy, cough, asthma, headaches, etc. in China for thousands of years. This study is aimed at investigating optimum extraction of protein-rich extracts from BB (BBPs) using response surface methodology (RSM) and exploring the protective effects of BBPs against nerve growth factor (NGF)-induced PC12 cells injured by glutamate (Glu) and their underlying mechanisms. The results indicated optimum process of extraction was as follows: extraction time 1.00 h, ratio of liquid to the raw material 3.80 mL/g and ultrasonic power 230.0 W. The cell viability of PC12 cells stimulated by Glu was determined by CCK-8 assay. The levels of γ-aminobutyric (GABA), interleukin-1ß (IL-1ß), interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT) and glucocorticoid receptor alpha (GR) in PC12 cells were assayed by ELISA. Furthermore, the Ca2+ levels in PC12 cells were determined by flow cytometry analysis. Protein and mRNA expressions of GABAA-Rα1, NMDAR1, GAD 65, GAD 67, GAT 1 and GAT 3 in PC12 cells were evaluated by real-time polymerase chain reaction (RT-PCR) and Western blotting assays. Results revealed that BBPs decreased toxic effects due to Glu treatment and decreased Ca2+ levels in PC12 cells. After BBPs treatments, levels of GABA and 5-HT were increased and contents of TNF-α, IL-4 and IL-1ß were decreased in NGF-induced PC12 cells injured by Glu. Moreover, BBPs up-regulated the expressions of GABAA-Rα1, GAD 65 and GAD 67, whereas down-regulated that of NMDAR1 GAT 1 and GAT 3. These findings suggested that BBPs possessed protective effects on NGF-induced PC12 cells injured by Glu via γ-Aminobutyric Acid (GABA) signaling pathways, which demonstrated that BBPs has potential anti-epileptic effect in vitro. These findings may be useful in the development of novel medicine for the treatment of epilepsy.

In silico drug design of inhibitor of nuclear factor kappa B kinase subunit beta inhibitors from 2-acylamino-3-aminothienopyridines based on quantitative structure-activity relationships and molecular docking.

Inhibitor of nuclear factor kappa B kinase subunit beta (IKK-ß), a specific regulator of nuclear factor-κB (NF-κB), is considered a valid target to design novel candidate drugs to treat rheumatoid arthritis and various cancers. In the present study, quantitative structure-activity relationships (QSAR) and molecular docking techniques were used to screen for new IKK-ß inhibitors from a series of 2-acylamino-3-aminothienopyridine analogs. During the two-dimensional QSAR phase, the statistical model partial least square was selected from among two alternatives (r2 = 0.868, q2 (cross-validation) = 0.630). Descriptors with positive or negative contributions were derived from the created model. To build of three-dimensional QSAR models, we used three different fingerprints as analysis precepts for molecular clustering and the subsequent division of training sets and test sets. The best model, which used fingerprint model definition language public keys, was selected for further prediction of the compounds' activities. Favorable physicochemical, structural, electrostatic, and steric properties were derived from the created QSAR models and then used for drug design with an in-house library. Amongst the designed compounds, compounds B01 and B02 showed good predicted activities. Furthermore, after a selecting the protein structure and docking method, docking studies were carried out to reveal the detailed interactions between the ligands and the target protein. Binding affinity was measured and sorted using the value of "-CDOCKER_ENERGY". The high -CDOCKER_ENERGY values of compounds B01 (41.6134 kcal/mol) and B02 (40.1366 kcal/mol) indicated their prominent docking affinities.

Extraction Optimization, Characterization, and Bioactivities of Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine Employing Ultrasound-Assisted Extraction.

In this study, the ultrasound-assisted extraction of polysaccharides (PSA) from Pinelliae Rhizoma Praeparatum Cum Alumine (PRPCA) was optimized by response surface methodology (RSM). The structural characteristics of PSA were analyzed by UV-vis spectroscopy, infrared spectroscopy, scanning electron microscopy, high performance gel permeation chromatography and high performance liquid chromatography, respectively. In addition, antioxidant and antimicrobial activities of PSA were studied by different in vitro assays. Results indicated that the optimal extraction conditions were as follows: the ratio of water to raw of 30 mL/g, extraction time of 46.50 min, ultrasonic temperature of 72.00 °C, and ultrasonic power of 230 W. Under these conditions, the obtained PSA yield (13.21 ± 0.37%) was closely agreed with the predicted yield by the model. The average molecular weights of the PSA were estimated to be 5.34 × 10³ and 6.27 × 105 Da. Monosaccharide composition analysis indicated that PSA consisted of mannose, galactose uronic acid, glucose, galactose, arabinose with a molar ratio of 1.83:0.55:75.75:1.94:0.45. Furthermore, PSA exhibited moderate antioxidant and antibacterial activities in vitro. Collectively, this study provides a promising strategy to obtain bioactive polysaccharides from processed products of herbal medicines.

Using the "target constituent removal combined with bioactivity assay" strategy to investigate the optimum arecoline content in charred areca nut.

Charred areca nut (CAN) is used to treat dyspepsia and abdominal distension in children. However, reports revealed that arecoline, the most important active constituent of CAN, possesses potential toxicities. This study was designed to investigate the optimum arecoline content in CAN, using the "target constituent removal combined with bioactivity assay" strategy. Based on PTLC method, we prepared CAN lacking all arecoline (WAC-100R) and a series of different ratios of arecoline-removed CAN samples (WAC-Rx). MTT and acute toxicity assays indicated that decreasing content by 50% decreased CAN toxicity significantly. Animal results revealed arecoline contents over 50% could guarantee the beneficial effects of CAN on gastrointestinal tract. Additionally, decreasing arecoline content in CAN by 50% decreased its pro-apoptotic effects significantly. Furthermore, decreasing 50% arecoline content in CAN down-regulated the expressions of Cleaved-Caspase-3, c-jun, c-fos, COX-2, PGE2, and IL-1α. Thus, our results revealed that CAN with 50% arecoline content (WAC-50R) has similar beneficial effects on the gastrointestinal tract to CAN, whereas its toxicity was decreased significantly. Collectively, our study suggested that the strategy of "target constituent removal combined with bioactivity assay" is a promising method to identify the optimum arecoline content in CAN, which is approximately 0.12%.

The pharmacology, toxicology and potential applications of arecoline: a review.

CONTEXT: Arecoline is an effective constituent of Areca catechu L. (Arecaceae) with various pharmacological effects. However, investigations also revealed that long use of arecoline could arouse some oral diseases. OBJECTIVE: The present review gathers the fragmented information available in the literature (before 1 October 2015) regarding pharmacology and toxicology of arecoline. We also discussed the potential developments and applications of arecoline in the future. METHODS: All the available information regarding the arecoline is compiled from scientific databases, including Science Direct, PubMed, Web of Science, Scopus, etc. RESULTS: Previous research demonstrated that arecoline is one of the major effective constituents in A. catechu. Additionally, arecoline has a wide spectrum of pharmacological activities including effects on nervous, cardiovascular, digestive and endocrine systems and anti-parasitic effects. What's more, arecoline is reported to be the primary toxic constituent of A. catechu, and the main toxic effects include oral submucous fibrosis (OSF), oral squamous cell carcinoma (OSCC) and genotoxicity. CONCLUSION: Arecoline has great potential to be a therapeutic drug for various ailments. However, further investigations are needed in the future to reduce or eliminate its toxicities before developing into new drug.

Hepatoprotective activity of total iridoid glycosides isolated from Paederia scandens (lour.) Merr. var. tomentosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Currently, human liver is susceptible to injury caused by alcohol and virus infiltration, resulting in hepatitis, cirrhosis, and even hepatocellular carcinoma. Paederia scandens (Lour.) Merr. var. tomentosa (Rubiaceae) has been used as traditional medicine in Asian countries to treat jaundice, dysentery, and abdominal mass. Furthermore, the abundance of iridoid glycosides in Paederia species indicates their notable hepatoprotective potential. MATERIALS AND METHODS: Total iridoid glycosides (TG) was prepared, and constituents of TG were analyzed by HPLC. TG and silymarin (positive) were orally administered for 15 days. Then, acute liver injury rats was induced by intraperitoneally injection (i.p.) of 10% CCl4 (0.12%, v/v, dissolved in olive oil, 10 mL/kg, body weight). Rats were sacrificed at 16 h after CCl4 injection. Liver tissues and blood were collected. Serum samples were prepared to determine the activities of alanine transaminase (ALT) and aspartate transaminase (AST), whereas liver tissue sections were prepared for the purpose of examining possible liver histopathological changes. In addition, antioxidant enzyme activities in liver tissues were also evaluated. RESULTS: Our results demonstrated that TG significantly decreased the levels of AST and ALT, compared with those in control rats. In addition, pre-treatment of the rats with TG clearly alleviated their liver tissue injuries. What's more, the activities of GSH, GAT and SOD in the groups of TG-treated rats were significantly increased compared with those of rats in the control group, whereas the levels of MDA were decreased. CONCLUSIONS: Our present research indicated that TG possessed notable hepatoprotective activity via decreasing oxidative stress level in liver tissues.