Mitochondrion is an important organelle in cells and plays a crucial role in tumor development. Therefore, improvement of the targeting ability of anticancer drugs to mitochondria will increase the treatment efficacy for tumor and reduce the side effect on normal tissues. Here, research progresses in mitochondrial targeting have been reviewed in three aspects for tumors treatment: the potential, permeability and translocase of mitochondrial membrane. The review provides a reference for the development of mitochondria targeted therapeutic systems.

Flexible liposomes are an excellent drug delivery nanocarrier, however, the leakage of drugs from liposomes has become common technical obstacle in the industry and also hindered its further application seriously. It is very urgent and necessary to avoid or reduce the leakage of drugs from liposomes. In this work, five kinds of essential oils such as Folium Artemisiae Argyi oil (FA), Folium Eucalypti oil (FE), Arabian Jasmine oil (AJ), Syzygium Aromaticum oil (SA) and Fructus Forsythiae oil (FF) were encapsulated in the lipid bilayer of palmatine chloride (PC) loaded flexible nano-liposomes (PFL), then the optimal essential oil and its dosage level were determined by the external leakage curve of PC. The female Japanese white rabbits were used to evaluate the vaginal irritancy potential of liposomes samples. The pharmaceutical properties such as encapsulation efficiency, particle size, zeta potential, deformability and structure of liposomes samples were evaluated. In order to investigate the permeability of liposomes samples to deliver PC across skin and mucous membrane in vitro, the side-by-side diffusion cells were used. The results showed that the leakage of hydrosoluble PC from PFL was reduced at different degrees by the essential oils in the lipid bilayer of PFL, however, the reduction in leakage degree was obviously higher for FA than thoses of FE, AJ, SA and FF (P < 0.05), and the highest reduction in leakage degree was obtained when the FA and lipid mass ratio was 1:6. The encapsulation efficiency, particle size, zeta potential and deformability of PFL were not significantly changed after FA was encapsulated in the lipid bilayer of the PFL (P > 0.05), so did the lamellar structure of PFL. In addition, the transdermal and transmucosal permeability of PC were also enhanced obviously by encapsulating FA in the lipid bilayer of PFL, and there was no vaginal/vulvar irritation observed in the rabbits. In summary, the drug leakage was reduced by encapsulating suitable essential oil (such as FA) in the lipid bilayer of flexible liposomes, and the vaginal mucosa permeability were improved for the drug. These results provide a novel technique in the improvement of flexible nano-liposomes for drug delivery.

This study was designed to establish a high performance liquid chromatography (diode array detector, DAD)-tandem mass chromatography (HPLC-DAD-MS/MS) method for the simultaneously screening 12 kinds of cough-relieving chemical drugs illegally added in anti-cough and antiasthmatic traditional Chinese medicines. This method involved liquid chromatography-tandem mass spectrometry. The separation was conducted by Kromasil100-5C18 (250 mm × 4.6 mm, 5 μm) and the mobile phase was consisted of 0.3% ammonium formate (pH 2.97) and methanol. After separated by HPLC, the suspected components were analyzed by MS/MS and DAD and ultra scan was used to identify these illegally added drugs. A fast and sensitive HPLC-DAD-MS/MS method for the simultaneously screening for illegal chemical compositions was established. The LOD of these substances were below 50 ng. The method was sufficiently selective and sensitive to detect illegal chemical compositions in anti-cough and antiasthmatic traditional Chinese medicines.

Two flavanone glucosides were isolated from the 80% ethanol extract of Glycyrrhiza uralensis using various chromatographic techniques, including macroporous adsorbent resin, RP-C₁₈, Sephadex LH-20, MCI and preparative HPLC. On the basis of chemical properties and spectra data, these compounds were identified as (2S)-liquiritigenin-4´-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranoside (1), (2R)-liquiritigenin-4´-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranoside (2), respectively. Compounds 1 and 2 are new compounds, and their aglycones are enantiomers.

IG-105, N-(2, 6-dimethoxypyridine-3-yl)-9-methylcarbazole-3-sulfonamide, a novel antimicrotubule agent, showed potent anticancer activity in a variety of human tumor cells in vitro and in vivo. In order to characterize the metabolism and the possible drug-drug interaction of IG-105, we carried out a series of experiments. Drug metabolizing enzymes involved in IG-105 metabolism were investigated by using pooled human liver microsomes (HLMs) and recombinant cytochrome P450 isoforms (rP450s) respectively. The possible metabolites were analyzed by liquid chromatography-orbitrap-mass spectrometry (LC-Orbitrap-MS). The inhibitory effect of IG-105 on main P450 enzymes was also evaluated. The results showed that IG-105 can be metabolized by a series of rP450s, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5, with the major contribution enzymes being CYP1A2, CYP2B6, CYP2C19, and CYP3A. Three metabolites (M1-M3) were identified and demethylation was the major phase I metabolic reaction for IG-105. IG-105 moderately inhibited CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A enzyme activities with IC₅₀ values of 6.42, 23.64, 0.39, 1.4, and 3.14 μmol·L^-1, respectively. Since the biotransformation of IG-105 involves multiple enzymatic pathways, the compound is less likely to be a victim of a concomitantly used medicine which inhibits activity of one of the CYPs. However, as IG-105 showed medium to strong inhibition on CYP1A2, CYP2D6, CYP3A, and CYP2C19, caution is particularly needed when IG-105 is co-administrated with other anticancer drugs which are mainly metabolized by the above enzymes.

Drug transporters play vital roles in absorption, distribution and excretion of drugs. Understanding the transport activity can improve the effectiveness and safety of drugs and guide clinical rational use of drugs. Metformin is a first-line drug in the treatment of type 2 diabetes mellitus, of which the pharmacokinetics involves several transporters. The changes in expression and function of these transporters affect directly the pharmacokinetics/pharmacodynamics of metformin. This paper reviews the research progress of pharmacokinetics of metformin based on transporters, and these transporters are organic cation transporters (OCTs), multidrug and toxin extrusion proteins (MATE), plasma membrane monoamine transporter protein (PMAT), serotonin reuptake transporter (SERT), thiamine transporter 2 (THTR-2), and carnitine/organic cation 1 (OCTN1).

This study was designed to establish a multiplex allele-specific polymerase chain reaction method for simultaneous identification of Dendrobium huoshanense, D. officinale and D. devonianum, which may resolve identification problems of caulis dendrobii. Internal transcribed spacer sequences and trnL-trnF sequences of the Dendrobium species were aligned by BioEdit software, then specific SNPs of the three species were analyzed for designing allele-specific primers and the multiplex allele-specific PCR reaction system was established. The different origin of Dendrobium huoshanense, D. officinale and D. devonianum was amplified and identified by the sizes of respective band. The results showed that 584 bp, 397 bp and 211 bp bands could be amplified by D. devonianum, Dendrobium officinale and Dendrobium huoshanense respectively, when the annealing temperature was 61 ℃ and the number of cycles was 35. The limit of detection (LOD) of D. devonianum and D. huoshanense were both 1.2 ng, while D. officinale was low than 0.24 ng. The detection limit of adulterates in D. devonianum, D. devonianum and D. huoshanense mixture sample was 1%, 1% and 5% respectively. This result suggests that the method of multiplex allele-specific PCR is useful to identify D. huoshanense, D. officinale and D. devonianum is accurate and specific.

Scorpion toxin BmK AngM1 has been reported to have a strong analgesic effect. However, its anti-inflammatory activity was unknown. In this study, the recombinant BmK AngM1 (rBmK AngM1) was expressed in Escherichia coli BL21 trxB (DE3). The purified rBmK AngM1 was obtained efficiently through the IMPACT^TM-TWIN system. The anti-inflammatory activity of the recombinant protein was investigated. In order to improve the anti-inflammatory activity of rBmK AngM1, the potential active sites (Y5, Y42, R58) were substituted with different amino acids. The results showed that rBmK AngM1 and its mutants all have significant anti-inflammatory activity. The activities were significantly increased in the single mutant R58N and mutants Y5F/R58N, Y42F/R58N over the wild type protein. The data suggest that position 58 in BmK AngM1 plays a functional role in the anti-inflammatory activity. This study lays a foundation for the protein engineering design of BmK AngM1 to improve its pharmacological activity.

This study was designed to investigate the chemical constituents of the anti-osteoporotic part of Lepidium meyenii Walp. (maca) produced in Heqing, Yunnan. Seven compounds were isolated from the n-BuOH extract of maca using combination of column chromatographies on MCI resin, silica gel, C₁₈ bonded silica gel, and Sephadex LH-20, followed by semi-preparative HPLC and recrystallization. The purified compounds were identified on the basis of their physicochemical properties and spectral data as macaolidine (1), tryptophan (2), daucosterol (3), (3S)-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylicacid (4), chlorogenic acid (5), luteolin (6), and hyperoside (7). Compound 1 is a new phenylacetamide alkaloid, and compounds 4-7 were isolated from Lepidium meyenii for the first time.

Although multiple studies have shown that matrine can inhibit the proliferation of hepatoma cells, its mechanism of action has not been systematically investigated. In this study, the effects of matrine on the proliferation and migration of human hepatoma SMMC-7721 cells were investigated. Based on this result, anti-hepatoma target-functionally related protein interaction network of matrine was constructed, and topological analysis and clustering analysis were performed to predict the crucial targets of matrine for the anti-hepatoma effects. Pathway enrichment analysis was performed on the validated targets to predict the crucial pathways of matrine. Parts of the crucial proteins were examined by Western blot. Cellular experiments showed that matrine at concentrations of 1, 2 and 4 mg·mL^-1 significantly inhibited the proliferation of SMMC-7721 cells, and matrine at concentrations of 0.5, 1 and 2 mg·mL^-1 significantly inhibited the migration of SMMC-7721 cells. The results of network pharmacology suggest that matrine exerts its anti-hepatoma effects through acting on the key validated targets of heparanase (HPSE), caspase 3 (CASP3), Myc proto-oncogene protein (MYC), matrix metalloproteinases 2 (MMP2) and predicted targets of carbonic anhydrase 1 (CA1), lithostathine 1 alpha precursor (REG1A), carboxylesterases 1 (CES1) and acetaldehyde dehydrogenase 2 (ALDH2), and invasion and migration associated pathways. Western blot results suggest that matrine can down-regulate the expression of MMP2 and up-regulate the expression of CASP3. In this paper, we applied network pharmacology to explain the targets and pathways of matrine against hepatoma. The results provide a scientific basis for elucidation of the mechanisms of matrine against hepatoma.