Improved direct compression properties of Gardeniae fructus water extract powders via fluid bed-mediated surface engineering.

Direct compression (DC) attracts increasing attention for tablet manufacturing; however, its application in medicinal plant tablets is still extremely limited. In this work, eight kinds of the Gardeniae fructus water extract powder (GF)-based composite particles (CPs) were prepared with different cohesive surface engineering materials, including dextran, inulin, hypromellose, and povidone, alone or in combination with mannitol and colloidal silica. Their physical properties and compacting parameters were characterized comprehensively. All the CPs showed marked improvement in tabletability, which is about 2-4 times higher than that of GF and physical mixtures (PMs). Specifically, the CPs showed a 7.45-26.48 times higher hardness (Ha) value and a 1.26-2.74 times higher cohesiveness (Co) value than PMs. In addition, all the CPs (angle of repose being from 34.27° to 38.46°) showed better flowability than PMs (35.49° to 53.53°) and GF (51.86°). These results demonstrated that (i) fluid-bed coating was not a simple process of superposition and transmission of the physical properties of raw materials; and (ii) all the surface engineering materials studied could improve the DC properties of problematic GF to some degree. As a whole, through the design of fluid-bed coating CPs, qualified tablets with high GF loadings (up to 93%) were produced via DC.

Blood-Enriching Effects and Immune-Regulation Mechanism of Steam-Processed Polygonatum Sibiricum Polysaccharide in Blood Deficiency Syndrome Mice.

Polygonatum sibiricum Red. has been used as a medicinal herb and nutritional food in traditional Chinese medicine for a long time. It must be processed prior to clinical use for safe and effective applications. However, the present studies mainly focused on crude Polygonatum sibiricum (PS). This study aimed to investigate the chemical properties, blood-enriching effects and mechanism of polysaccharide from the steam-processed Polygonatum sibiricum (SPS), which is a common form of PS in clinical applications. Instrumentation analyses and chemistry analyses revealed the structure of SPS polysaccharide (SPSP). A mice model of blood deficiency syndrome (BDS) was induced by acetylphenylhydrazine (APH) and cyclophosphamide (CTX). Blood routine test, spleen histopathological changes, serum cytokines, etc. were measured. The spleen transcriptome changes of BDS mice were detected by RNA sequencing (RNA-seq). The results showed that SPSP consists predominantly of Gal and GalA together with fewer amounts of Man, Glc, Ara, Rha and GlcN. It could significantly increase peripheral blood cells, restore the splenic trabecular structure, and reverse hematopoietic cytokines to normal levels. RNA-seq analysis showed that 122 differentially expressed genes (DEGs) were obtained after SPSP treatment. GO and KEGG analysis revealed that SPSP-regulated DEGs were mainly involved in hematopoiesis, immune regulation signaling pathways. The reliability of transcriptome profiling was validated by quantitative real-time PCR and Western blot, and the results indicated that the potential molecular mechanisms of the blood-enriching effects of SPSP might be associated with the regulating of JAK1-STAT1 pathway, and elevated the hematopoietic cytokines (EPO, G-CSF, TNF-α and IL-6). This work provides important information on the potential mechanisms of SPSP against BDS.

Combination of mulberry leaf active components possessed synergetic effect on SD rats with diabetic nephropathy by mediating metabolism, Wnt/ß-catenin and TGF-ß/Smads signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry leaf has attracted much attention due to its excellent curative effect on diabetes and its complications, whether the combination of its effective components have protective and synergistic effect on diabetic nephropathy (DN) in vivo remain unclear. AIM OF THE STUDY: The aim of this study was to investigate the protective and synergistic effect of the combination (MAF1:1 and MAF1:5) of mulberry leaf alkaloids (MA) and flavonoids extract (MF) on DN. MATERIALS AND METHODS: A step by step method consisted of network pharmacological prediction, animal in vivo validation and metabolic mechanism research was used to construct the multi-component-target-pathway network of mulberry leaf against DN. Firstly, the potential components and mechanism of mulberry leaf against DN was explored by network pharmacology analysis. Secondly, DN animal model was established to validate the anti-DN activity of these potential compounds. Thirdly, the metabolomics of serum and urine samples from animal experiments was analyzed to explore the anti-DN mechanism of these potential compounds. RESULTS: The results of network pharmacology demonstrated that a total of 7 compounds detected in MA and MF exhibited anti-DN activity, their mechanism were strongly in connection with metabolic pathways, arachidonic acid metabolism, sphingolipid signaling pathway, etc. The results of animal experiment indicated that MAF1:1 and MAF1:5 significantly relieved metabolic disorders through regulating Wnt/ß-catenin and TGF-ß/Smads signaling pathway, just like MF or MA alone. Metabolomics suggested they could regulate 16 serum and 7 urine endogenous metabolites through arachidonic acid metabolism, phenylalanine metabolism and sphingolipid metabolism, thus alleviated DN. Significantly, MAF1:1 and MAF1:5 might possess synergistic effect considering their therapeutic effects on DN rats were superior to the single use of MA or MF. CONCLUSIONS: MAF1:1 and MAF1:5 possessed protective and synergistic effect on DN rats through multi-target and multi-pathways. These findings were of great scientific significance and application value to reveal the advantage of mulberry leaf in preventing and treating DN.

[Scaled-up production and application of co-processed excipient mannitol-HPMC in traditional Chinese medicine].

Spray drying technology was used to produce co-processed excipients mannitol- hydroxypropyl methylcellulose (HPMC), and study the scaled-up production. The consistency of powder and tablet properties before and after scale-up of co-processed excipients was compared, and their applicability in traditional Chinese medicine (TCM) powder's direct compression was tested on five TCM extracts such as gardenia extract and Radix Paeoniae Alba extract. It was shown that after scaled-up production, the key properties of co-processed excipients had little changes (such as compactability, disintegrating time, and lubrication sensitivity) or improvement (such as flowability and yield). As compared to commercially available spray-dried mannitol, co-processed excipients achieved better compactability and higher drug loading for direction compression of TCM powder. In conclusion, the mannitol-HPMC co-processed excipient, with excellent physicomechanical properties, is promising to be explored as a new excipient for direct powder compression.

Optimization of Microwave-assisted Extraction of Silymarin from Silybum marianum Straws by Response Surface Methodology and Quantification by High-Performance Liquid Chromatograph Method.

BACKGROUND: Silybum marianum, a member of the Aster family, is a well-known Chinese herb and the source of a popular antioxidant that is extensively used in Asia. The abundant S. marianum straws are still underutilized and wastefully discarded to pollute the environment. OBJECTIVE: To solve the above problem and better utilize S. marianum straws, the objective of this study was to optimize the conditions for extraction of silymarin from S. marianum straws. MATERIALS AND METHODS: A combination of microwave-assisted extraction and response surface methodology (RSM) was used for silymarin from S. marianum straws and yield assessment by high-performance liquid chromatography method. The RSM was based on a five-level, four-variable central composite design (CCD). RESULTS: The results indicated that the optimal conditions to obtain highest yields of silymarin were microwave power of 146 W, extraction time of 117 s, liquid-to-solid ratio of 16:1 mL/g, and ethanol concentration of 43% (v/v). Validation tests indicated that under the optimized conditions, the actual yield of silymarin was 6.83 ± 0.57 mg/g with relative standard deviation of 0.92% (n = 5), which was in good agreement with the predicted yield. CONCLUSIONS: The exploitation of the natural plant resources present very important impact for the economic development. The knowledge obtained from this work should be useful to further exploit and apply this material. SUMMARY: Silymarin has been isolated from Silybum marianum straws by microwave-assisted extraction and response surface methodologyThe results obtained are helpful for the full utilization of S. marianum strawsThe microwave-assisted extraction is a very useful method for the extraction of important phytochemicals from plant materials. Abbreviations used: MAE: Microwave-assisted extraction, RSM: Response surface methodology, HPLC: High-performance liquid chromatography, CCD: Central composite design, ANOVA: Analysis of variance.

LBP-4a improves insulin resistance via translocation and activation of GLUT4 in OLETF rats.

Lycium barbarum polysaccharide (LBP) has been shown to ameliorate insulin resistance, but the identification of compounds from LBP and the mechanisms have not been clarified. In this study, LBP-4a was purified from Lycium barbarum by DEAE cellulose and Sephadex G-100 column chromatography, and the effects of LBP-4a on insulin resistance were investigated. The results indicated that LBP-4a caused translocation of the glucose transporter isoform 4 (GLUT4) to the cell surface, which in turn stimulated glucose uptake, and the effect was sensitive to wortmannin, an inhibitor of phosphoinositol 3-kinase (PI3-K), and SB203580, an inhibitor of p38 mitogen activated protein kinase (p38 MAPK (α, ß)). Furthermore, the effects of LBP-4a on p38 MAPK activities were abrogated by pretreatment of rat adipocytes using SB203580. In summary, LBP-4a improved insulin resistance via translocation and activation of GLUT4 in OLETF rats, and the activation of PI3-K and p38 MAPK contributed to these effects.

[Effect of berberine hydrochloride on the proliferation, apoptosis and cytokine secretion of splenocytes in mice].

OBJECTIVE: To investigate the effect of berberine hydrochloride (BBR) on the proliferation, apoptosis, TNF-α, IL-2 and IFN-γ secretion of splenocytes in mice. METHODS: The splenocytes isolated from the spleen of mice in a sterile environment were pretreated with BBR at the concentrations of 1, 2, 4 µg/mL for 60 min. Thereafter, the cells were stimulated with polyclonal activators ConA and cultured for 24, 48, 72 h, respectively. MTT assay was used to detect the proliferation of cells; flow cytometry was performed to detect the splenocyte apoptosis according to the fluorescence intensity of the splenocytes stained with PI and annexin V-FITC; the concentrations of TNF-α, IL-2 and IFN-γ in the culture supernate was quantificationally analyzed by the ELISA. RESULTS: Compared with the control group, BBR within the concentration range above significantly inhibited the splenocyte proliferation, TNF-α, IL-2 and IFN-γ secretion of the splenocytes activated by ConA in a dose- and time-dependent manner (P<0.05), but didn't significantly cause the apoptosis of splenocytes (P>0.05). CONCLUSION: BBR can have immunosuppressive influence on the splenocytes in mice and may act as a potential immunosuppressive drug.