Based on the charge repulsion and solution-diffusion effect in nanofiltration separation, the correlation among mass transfer behavior, solution environment and molecular structure of three typical alkaloids from medicine was analyzed by nanofiltration mass mathematical model. The experiment revealed a linear relationship between ln[(1-R_o)·J_v/R_o] and J_v, and the regression coefficients were all greater than 0.9. Compared with the ultrafiltration separation behavior conforming to molecular sieve, the mass transfer coefficient of three alkaloids under different pH was pH 3.00 < pH 7.00 < pH 10.00. As the pH changed, the state of alkaloid transit from ionic state to a free state, the alkaloid could easily approach the membrane surface and pass through the nanofiltration membrane with charge repulsion and solution-diffusion effects, and the results were verified by the membrane adsorption tendency. The nanofiltration mass transfer of alkaloids is related to the state and molecular weight. In the ionic state, the charge effect produces separation behavior, and the molecular state is related to the molecular weight. The separation mechanism of nanofiltration for alkaloids was clarified further by analyzing the correlation of nanofiltration mass transfer behavior and molecular structure. The results of nanofiltration technology provide references for separation of alkaloids at room temperature with fast separation and low energy consumption.

Tribbles homologous protein 3 (TRB3) has a wide range of biological functions, such as involvement in tumor regulation, the occurrence of insulin resistance, endoplasmic reticulum stress response, inflammation regulation and the regulation of cell growth and differentiation. TRB3, as a key "pressure regulating switch", is involved in the regulation of numerous diseases and serves as a biomarker and potential therapeutic target for many diseases. This paper gives an overview of the research on the biological function of TRB3 in recent years, in order to provide a theoretical basis for further research on TRB3 function.

The multiple drug delivery system of components of traditional Chinese medicine is a system composed of multiple components and multiple units. According to the characteristics of each component, different drug delivery units are designed and combined to achieve the purpose of improving bioavailability and enhancing drug efficacy. In this study, supercritical extracts, phenolic acids, and polysaccharides derived from Angelica sinensis were examined as research objects, and a pellet-based vehicle was applied to construct a multiple drug delivery system for the treatment and chemoprevention of colitis and colorectal cancer. The extrusion-spheronization method was used to prepare pellets of Angelica polysaccharides which should be released in the stomach. The yield in 18-24 mesh and plane critical angle served as the index. The Box-Behnken design and the orthogonal design were used to optimize the formulation and parameters of pellets. According to a previous study, the colon specific pellets loading supercritical extracts and phenolic acid extracts were prepared by the optimized process. These two units of pellets were combined into the multiple drug delivery system of effective components of Angelica sinensis, and the quality evaluation and in vitro release study were conducted. The dynamic observation of pellets in mice was evaluated using small animal in vivo imaging system. The prescription of the Angelica polysaccharides gastric releasing pellets was:microcrystalline cellulose 6.5 g, polysaccharide 3.3 g, silica 0.2 g and 7 mL of 60% ethanol as wetting agent. The process parameters were as follows:extrusion rate at 75 r·min^-1, rounding rate at 1 800 r·min^-1, and rounding time for 3 min. Both in vivo and in vitro studies indicate that the prepared multiple drug delivery system of effective components of Angelica sinensis produced good release properties. The polysaccharide pellets could be rapidly released in the artificial gastric fluid and in the stomach. The colon specific pellets showed good targeting. They released little in the artificial gastric fluid within 2 hours, released less than 20% in the artificial intestinal fluid for 4 hours, and released more than 90% in artificial colon fluid for 6 hours.

Traditional Chinese medicine (TCM) formula is one of the unique cultural treasures of Chinese. However, only a few studies have been carried out to deliver TCM formula with utilization of nanocarriers. The purpose of this study was to prepare the hydroxypropyl-β-cyclodextrin complex-over-a-poly(lactic-co-glycolic acid) nanoparticle (HP-β-CD-PLGA NP) for co-delivery and sequential release of five main effective ingredients of Danshen and Sanqi to a specific target, which can provide strategies for design of intelligent drug delivery system of TCM formula. PLGA can be employed as scaffolds for sustained release of both hydrophobic and hydrophilic drugs. HP-β-CD could encapsulate the hydrophobic drugs by forming inclusion complexes. Superparamagnetic iron oxide nanoparticles (SPION) embedded inside PLGA nanoparticles that allow a spatio-specific targeting. HP-β-CD inclusion complex was prepared by an unsaturated alcohol solution method. PLGA NP loaded with SPION was obtained through double emulsion-organic solvents evaporation. Then core-shell PLGA nanosystem was formed by co-incubation of the above two materials. The nanoparticulate system was characterized by confocal laser scanning microscopy (CLSM), laser particle size instrument and transmission electron microscope. Magnetic property was determined by magnet adsorption and vibrating sample magnetometer (VSM). Targeted distribution was investigated by cell uptake and sequential release of multiple components was observed by intracellular distribution of fluorescent probes. Release difference of five components between core and shell of HP-β-CD-PLGA NP was measured by high performance liquid chromatography. The results demonstrated that NP had a unique core-shell structure and possessed superpara-magnetism. Magnetic NP could be ingested site-specifically by L929 cells with the aid of magnetic field, and coumarin-6 and rhodamine B were released from NP sequentially in the L929 cells. In vitro release of multiple components of Danshen and Sanqi from NP exhibited double phase time-controlled release kinetics of quick-release shell and sustained-release core. Therefore, the spatio-temporal nanoplatform has a great capacity for unlocking the full therapeutic potential of displaying synergistic efficacy of TCM formula in the formulation design.

Annonaceous acetogenins (ACGs) are effective part extracted and separated from Annona squamosa seeds, they have good antitumor activity against a variety of tumor cells. However, the solubility of ACGs is poor with serious toxic and side effects, which greatly limits their application in clinical practice. In this study poloxamer 188 (P188) was selected as a drug carrier or a stabilizer to prepare ACGs nanosuspensions (ACGs-NSps) using anti-solvent precipitation. The nanosuspensions were examined via dynamic light scattering (DLS) method to examine size of the nanosuspensions. Transmission electron microscopy was used to observe their morphology. HPLC assay was used to measure their drug loading content and the in vitro drug release. The stability of ACGs-NSps at room temperature, in various physiological media and plasma, and the hemolytic test and lyophilization were all investigated. MTT assay was performed to study the cytotoxocity of ACGs-NSps against four tumor cell lines. 4T1 bearing tumor model was used to assess their in vivo antitumor therapeutic efficacy. The obtained ACGs-NSps were spherical, the average particle size was 169.4±1.25 nm, the polydispersity index (PDI) value was 0.130±0.020, the zeta potential was -19.8 mV and the drug loading content was 48.18%. ACGs-NSps were stable at room temperature for at least 15 days. They could be lyophilized in the presence of 0.5% glucose and 2.0% P188. ACGs-NSps showed sustained in vitro drug release, and the cumulative drug release reached 80.82% within 144 hours. ACGs-NSps maintained their particle size in various physiological media, and plasma with no hemolysis and then met demands of both oral and intravenous administration. In contrast to free ACGs, ACGs-NSps displayed significantly higher cytotoxicity against 4T1 (IC₅₀, 0.892±0.124 μg·mL^-1 vs 2.495±0.108 μg·mL^-1, P < 0.05), HeLa (IC₅₀, 0.747±0.051 μg·mL^-1 vs 2.204±0.064 μg·mL^-1, P < 0.01), HepG2 (IC₅₀, 2.265±0.081 μg·mL^-1 vs 4.159±0.071 μg·mL^-1, P < 0.01), and MCF-7 (IC₅₀, 0.473±0.024 μg·mL^-1 vs 1.196±0.022 μg·mL^-1, P < 0.05). The in vivo study demonstrated that the daily oral administration of ACGs-NSps (3 mg·kg^-1) resulted in higher tumor inhibition rate compared to ACGs/oil solution (67.23% vs 53.11%), comparable to the intravenous injection of 0.5 mg·kg^-1 ACGs-NSps every other day (70.34%). Nanosuspensions effectively solved the problem of ACGs insolubility and difficulty in drug delivery. Using P188, a pharmaceutic adjuvant approved by FDA for iv injection, the resultant ACGs-NSps appear promising as an anti-tumor drug that can be used in clinic.

The discovery and verification of components are prerequisites for developing of component preparations. The molecular docking technique and pharmacodynamic activity evaluation provide effective methods for the discovery and verification of the representative components of Chishao terpene glucoside components (CSTGC_S) against ischemia and hypoxia injury. The chemical constituents of CSTGC_S were analyzed qualitatively by UPLC-TOF/MS/MS. Main chemical constituents were docked with key receptor proteins of myocardial ischemia to preliminarily screen anti-ischemia active ingredients, and screening for main active ingredients with Libdockscore. Then a H9c2 cell hypoxia injury model was established, and creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) were determined to screen the representative combinations in CSTGC_S. In addition, apoptosis index, apoptotic protein expression and mitochondria-associated mRNA levels were determined to verify the inhibition of the representative components (RC_S) on the apoptosis of hypoxic cells. Eventually, the representative components of CSTGC_S were determined. The results showed that paeoniflorin, albiflorin, benzoyl paeoniflorin and oxypaeoniflorin were considered to be the main active components because of their high matching with target proteins (4TWT, 3O4O, 4KZN, 1M9J) in space and energy. There was no statistical difference in regulating CK, LDH, SOD, MDA levels and maintaining mitochondrial function as well as inhibiting cell apoptosis between CSTGC_S group and RC_S group (paeoniflorin + albiflorin + benzoyl paeoniflorin combination). Therefore, paeoniflorin, albiflorin and benzoyl paeoniflorin were selected as the most representative ingredients of CSTGC_S against ischemia and hypoxia injury, providing a basis for the overall properties of the components and formulation of CSTGC_S.

In this study, twenty containing ethylenediamine groups derivatives of oleanolic acid (OA) were synthesized, their structures were determined by ¹H NMR, ¹³C NMR and HR-MS. The anti-tumor activities in HepG2 and SGC7901 cells were evaluated by MTT assay. The results showed that all compounds exhibited anti-tumor activity, compounds Ⅰ₆, Ⅰ₈ and Ⅰ₉ exhibited significant anti-tumor activities with IC₅₀ values of 16.7, 9.8 and 6.3 μmol·L^-1, respectively. Molecular docking studies showed that compounds Ⅰ₆-Ⅰ₉ produce higher combining ability with VEGFR. Compound Ⅰ₆-Ⅰ₉ were further evaluated for the inhibitory activity against VEGFR-2, the result showed Ⅰ₉ had a strong inhibitory effect on VEGFR with IC₅₀ values of 0.56 μmol·L^-1.

Chemical investigation on the rice culture of an endophytic fungus Colletotrichum fioriniae F18, inhabiting in the stems of the medicinal plant Mahonia fortunei, led to the isolation of nine compounds. They included a new indole alkaloid, makomotindoline B (1), and two known indole derivatives, 3-indoleacetic acid methyl ester (2) and N-acetyltryptamine (3), together with six known aromatic compounds, 2-(4-hydroxyphenyl) acetic acid (4), 4-(2-hydroxyethyl)phenol (5), 2-(4-methoxyphenyl)acetic acid (6), 4-hydroxyphenethyl 2-(4-hydroxyphenyl)acetate (7), regiolone (8) and N-phenethylacetamide (9). The structures of these compounds were elucidated based on the analysis of spectroscopic data including MS and NMR. The absolute configuretion of compound 1 was determined by electronic circular dichroism (ECD) calculation. Antibacterial activity assay indicated that compounds 1-9 had no antibacterial activities against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, as well as no quorum sensing inhibitory (QSI) activity for Chromobacterium violaceum.

Tripterygium glycosides tablets (TGT) have good immunosuppressive activity, but they can also significantly injure the liver and kidney and its mechanism is unclear. In this study, delayed-type hypersensitivity (DTH) Balb/c mouse were administrated with different doses of TGT. Then the changes of sphingolipids levels in live, kidney and plasma as well as the mRNA expression levels of their metabolic enzymes were studied by the integrated targeted sphingolipidomics and transcriptomics methods to reveal the mechanism of efficacy and toxicity of TGT. It was found that low dose of TGT could significantly decrease levels of total ceramide in the plasma, long chain sphingolipids and saturate sphingolipids in the liver and kidney, but increase them in the plasma, which were related to the efficacy mechanism of TGT. High dose of TGT can significantly increase levels of total ceramide, Cer(d18:1/18:0)-1-P, long chain sphingolipids and decrease saturation sphingolipids mechanism. TGT can also cause significant changes of mRNA expression levels of various sphingolipid metabolic enzymes in the liver and kidney, which were correspond to the changes of sphingolipid levels. The efficacy and toxicity of TGT were related to the regulation of these key enzyme expression levels. In conclusion, the efficacy and toxic mechanism of TGT were closely related to the sphingolipids metabolism. A variety of potential biomarkers were found and they can provide valuable information for the evaluation of the efficacy and toxicity of TGT.

The toxicity of heavy metals and harmful elements is close related to their speciation. In the present study, the methods for mercury and arsenic speciation analysis based on high-performance liquid chromatography conjunction with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) were established and applied to the determination of 31 kinds of animal drugs, 29 of which were included in the Chinese Pharmacopeia (2015 edition). The results showed that the LODs for all the speciation were within 0.1-0.65 μg·kg^-1, and the recoveries were within 86.9%-116.6% with the RSD of 1.49%-4.23%. Inorganic mercury (Hg²⁺) was detected in all the 87 batches of samples that came from 31 kinds of animal drugs, and the contents were 2.39-6567 μg·kg^-1. Methylmercury (MeHg) was detected in 33 batches of samples that came from 12 kinds of animal drugs, and the contents were 2.83-319.7 μg·kg^-1. Ethylmercury (EtHg) were detected in none of the samples. The detection rates of As(Ⅲ), As(Ⅴ), monomethylarsononous acid (MMA), dimethylarsinic acid (DMA), arsenobetaine (AsB) and arsenocholine (AsC) in the 31 batches of animal drugs was 96.77%, 100%, 45.16%, 90.32%, 93.55% and 22.58%, respectively. According to the toxic level of different speciation, the animal drugs with high risks of mercury were Agkistrodon, Bungarus Parvus, Zaocys, and Scolopendra; the animal drugs with high risks were Pheretima, Agkistrodon, Zaocys, and Aspongopus. This study can provide important evidence for the risk assessment, setting and revision of the limit standards of heavy metals and harmful elements.