Essential oil of Ligusticum chuanxiong Hort. Regulated P-gp protein and tight junction protein to change pharmacokinetic parameters of temozolomide in blood, brain and tumor.

ETHNOPHARMACOLOGICAL RELEVANCE: The existence of the blood-brain barrier/blood tumor barrier (BBB/BTB) severely restricts the effectiveness of anti-tumor drugs, thus glioma is still an incurable disease with a high fatality rate. Chuanxiong (Ligusticum chuanxiong Hort., Umbelliferae) was used as a messenger drug to increase the distribution of drugs in brain tissue, and its application in Chinese herbal formula for treating glioma was also the highest. AIM OF THE STUDY: Our previous researches showed that essential oil (EO) of chuanxiong could promote temozolomide (TMZ) entry into glioma cells in vitro and enhance TMZ-induced anticancer efficiency in vivo, and therefore, the aim of this study was to investigate whether EO could increase the concentration accumulation of TMZ in brain or tumor of C6 glioma rats and the related mechanisms. MATERIALS AND METHODS: The pharmacokinetics were conducted in C6 glioma rats by administering either TMZ alone or combined with EO through oral routes. TMZ concentration in blood, brain and tumor was detected using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and then pharmacokinetic parameters were calculated. The changed expressions of P-gp protein, tight junction occludin, claudin-5 and zonula occludens-1 (ZO-1) in brain of glioma rats were studied by Western blot to clarify the mechanism. Finally, the chemical composition of EO was analyzed by gas chromatography-massspectrometry (GC-MS). RESULTS: The results showed that EO significantly affected the pharmacokinetic parameters such as Tmax, Cmax and CL (p < 0.01), but did not significantly change the AUC(0→∞) of TMZ in blood (p > 0.05). However, EO markedly improved the AUC(0→∞)of TMZ in brain and tumor (p < 0.01). The calculate drug targeting index was greater than 1, indicating that EO could promote the distribution of TMZ to the brain and tumor. Western blot analysis showed that EO significantly inhibited the expression of P-gp, tight junction protein claudin-5, occludin and ZO-1. And meanwhile, the expressions of P-gp, claudin-5 and occludin also markedly down-regulated in EO-TMZ co-administration treatment. GC-MS analysis of the TIC component of EO was (E)-Ligustilide (36.93%), Terpinolene (7.245%), gamma-terpinene (7.225%) etc. CONCLUSION: EO could promote the distribution of TMZ in the brain and tumor of C6 glioma rats, which may attribute to down-regulate the expression of P-gp, claudin-5 and occludin.

Traditional herbal medicine and nanomedicine: Converging disciplines to improve therapeutic efficacy and human health.

Traditional herbal medicine (THM), an ancient science, is a gift from nature. For thousands of years, it has helped humans fight diseases and protect life, health, and reproduction. Nanomedicine, a newer discipline has evolved from exploitation of the unique nanoscale morphology and is widely used in diagnosis, imaging, drug delivery, and other biomedical fields. Although THM and nanomedicine differ greatly in time span and discipline dimensions, they are closely related and are even evolving toward integration and convergence. This review begins with the history and latest research progress of THM and nanomedicine, expounding their respective developmental trajectory. It then discusses the overlapping connectivity and relevance of the two fields, including nanoaggregates generated in herbal medicine decoctions, the application of nanotechnology in the delivery and treatment of natural active ingredients, and the influence of physiological regulatory capability of THM on the in vivo fate of nanoparticles. Finally, future development trends, challenges, and research directions are discussed.

Fabrication and antibacterial evaluation of peppermint oil-loaded composite microcapsules by chitosan-decorated silica nanoparticles stabilized Pickering emulsion templating.

Novel peppermint oil (PO)-loaded composite microcapsules (CM) with hydroxypropyl methyl cellulose (HPMC)/chitosan/silica shells were effectively fabricated by PO Pickering emulsion, which were stabilized with chitosan-decorated silica nanoparticles (CSN). The surface modification of chitosan could improve the hydrophobicity of silica nanoparticles and favor their adsorption at the oil-water interface of PO Pickering emulsions. The microcapsule composite shells were formed dependent on the electrostatic adsorption of HPMC and CSN, and further subjected to spray-drying. The peppermint oil-loaded composite microcapsules with 100% HPMC as wall material (PO-CM@100%HPMC) seemed to be optimum formulation based on the prolonged release, acceptable entrapment efficiency (89.1%) and drug loading (25.5%). The PO-CM@100%HPMC could remarkably prolong the stability of PO. Moreover, the PO-CM@100%HPMC had a long-term antimicrobial activity (85.4%) against S. aureus and E. coli even after storage for 60 days. Therefore, the Pickering emulsions based microcapsules seemed to be a promising strategy for antibacterial application for PO.

Cellulose nanocrystals based clove oil Pickering emulsion for enhanced antibacterial activity.

An effective antibacterial system was developed by using clove essential oil Pickering emulsion (CO-PE). The carboxymethyl cellulose sodium modified cellulose nanocrystals (CNC) was used as the stabilizer of CO-PE, which were prepared by environmentally friendly approach of homogenization technology. The factors affecting the formation and stability of CO-PE were studied, such as CNC concentration, homogenization pressure, CO concentration and ionic concentration and pH. And the antibacterial performance of CO-PE against E. coli and S. aureus was investigated by determining the minimal inhibitory concentration (MIC). The results showed that 1% CNC stabilized CO-PE exhibited small droplet size and rough surface, and had good stability at high pH values or salt concentration, owing to the presence of CNC on interface of droplet. And the CNC-stabilized CO-PE exhibited higher antimicrobial activity at equivalent CO concentration, which might be attributed to efficiently adhere to bacterial membrane. Therefore, our research would provide new insights for antibacterial application of Pickering emulsions loading essential oils in the food and other industries.

The influence and mechanism of ligustilide, senkyunolide I, and senkyunolide A on echinacoside transport through MDCK-MDR1 cells as blood-brain barrier in vitro model.

Efficient transcytosis across the blood-brain-barrier is an important strategy for accessing drug targets within the central nervous system. Ligusticum chuanxiong Hort. was used as a messenger drug to increase the distribution of drugs in brain tissue in Traditional Chinese Medicine. The present study investigates the transport of echinacoside (ECH) through MDCK-MDR1 cell and the effects of ligustilide (LIG), senkyunolide A (SENA) and senkyunolide I (SENI) in chuanxiong on its transport. The results indicated that the absorption of ECH was relatively poor in MDCK-MDR1cells, and was concentration dependent and not saturable. The P-glycoprotein inhibitor verapamil could significantly increase the transport of ECH. It indicated that the transport mechanism might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased apparent permeability of ECH in A â†’ B direction by ethylenediaminetetraacetic acid-Na2 suggested that ECH was absorbed via the paracellular route. The transport of ECH in A â†’ B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. Western blot analysis and a decrease in transepithelial electrical resistance during the permeation experiment indicated that LIG, SENI and SENA had enhanced the transport of ECH in the BBB models attribute to down-regulate the expressions of claudin-5 and zonula occludens-1 expression.

[Status, problems and warranty strategy of quality uniformity for traditional Chinese medicine preparations].

The quality uniformity of traditional Chinese medicine (TCM) preparation is the base for guaranteeing the safety and effectiveness of clinical medication. At present, the quality of TCM preparation is uneven. At present, the same TCM preparation in different manufacturers, TCM preparations in the same manufacturer, and even different batches of a same TCM preparation in the same manufacturer have great differences in quality, which can not reach stability and uniformity. This paper would discuss the possible factors that influence the uniformity of quality in the whole process of pharmacy by means of consulting relevant literature on quality control of Chinese herbal preparations and analyzing the present situation and problems of the quality of TCM preparation. In addition, some strategies such as standardization of cultivation of TCM, processing standardization, standardization of pharmaceutical equipment, mixed batch feeding, and Quality by Design would be also put forward to provide references for the quality uniformity of TCM preparation.

[Effect and regulation of drying on quality of traditional Chinese medicine pills].

The dry quality of traditional Chinese medicine pills is the hot spot of pills research, because their quality has a crucial effect on the efficacy and development of dosage forms. Through literature research and statistical analysis, we would review the current problems on the drying of traditional Chinese medicine pills in this paper, and surrounding the evaluation system for traditional Chinese medicine pills, analyze the characteristics of common drying equipment and processes as well as their effect on quality of pills, discuss the problems in drying equipment and process as well as quality, and put forward the corresponding strategies, hoping to provide new ideas and new methods for the quality improvement of traditional Chinese medicine pills and quality standards.

Pharmacokinetic comparative study of gastrodin after oral administration of Gastrodia elata Bl. extract and its compatibility with the different indigents of Ligusticum chuanxiong Hort. to rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Da Chuan Xiong Decoction Compound preparation (DCXDCP) is a classic TCM formula of an aqueous extract made from Chuanxiong Rhizoma (Ligusticum chuanxiong Hort., umbelliferae) and Tianma Rhizoma (Gastrodia elata Bl., Orchidaceae). Gastrodin (GAS), a bioactive component of tianma, its pharmacokinetic (PK) behavior significantly changed after oral administration of DCXDCP compared with the extract of tianma. However, little is known about how the ingredients of chuanxiong influenced on the PK of GAS. AIM OF THE STUDY: To study the possible PK behavior differences of GAS after individually oral administration of tianma extract and tianma extract mixed with different active ingredients of chuanxiong to rats, as well as explore whether there were some herb-herb interactions. MATERIALS AND METHODS: Different DCXDCP suspensions were prepared by mixing tianma extract with different active ingredients of chuanxiong. The rats were randomly assigned to six groups and were orally treated with different DCXDCP. At different predetermined time points after administration, the concentrations of GAS in the rat plasma were determined using HPLC, and the main PK parameters were investigated. RESULTS: The results showed that tetramethylpyrazine had no significant effects on the PK parameters of GAS (p>0.05), whereas ferulic acid (FA), total phenolic acids and total alkaloids significantly increased AUC0-∞ (p<0.05). In general the observed changes in the PK parameters of GAS in DCXDCP could be closely related to the total phenolic acids and total alkaloids. CONCLUSION: It could be shown that total phenolic acids and total alkaloids present in Ligusticum chuanxiong in addition to other components not tested yet play an important role in affecting the PK of gastrodin in DCXDCP.

[Status and problem analysis of drying process and equipment for traditional Chinese medicinal materials and preparations].

Drying is the critical link during pharmaceutical process of traditional Chinese medicine (TCM), which is directly related to the quality of drugs. The key to technology upgrading of pharmaceutical equipment in Chinese materia medica enterprise is the development of new drying techniques, which concerns the modernization of TCM. The study provides new ideas for the drying technology and equipment by means of reviewing the research status of drying process for the traditional Chinese medicinal materials and preparations, and analyzing the traditional and modern drying methods and equipment, as well as their existing problems and corresponding measures for the drying processes and equipment. In addition, this paper expounds the development trend of traditional Chinese medicinal materials and preparations of drying process and equipment.

[Advance in studies on establishment methods of responsive drug delivery system].

Responsive drug delivery system can release drug at specific time and sites, and effectively overcome the drug resistance of organisms. With such advantages as drug protection, local targeting, inhibition of enzymatic activity, memory and expression, it has good prospect of application. So far, many chemical preparations have been launched in the market. This article mainly summarizes the advance in studies on establishment methods of responsive drug delivery system, while proposing research ideas for the traditional Chinese medicine component-based responsive drug delivery system according to the multi-component, multi-link and multi-target characteristics, in the expectation of providing reference and thought for the development of the drug delivery system.

[Analysis and study on quality control methods and modes of traditional Chinese medicine preparations].

The quality control of traditional Chinese medicine (TCM) preparations is a key issue related to their curative effect, safety and stability. The application of modern analytical means and the development of new disciplines improve the quality control of TCM preparations to some extent. For a long time, however, the quality control level of TCM preparations remains low and the quality standards exist in name only unable to effectively control drug quality and ensure therapeutic effect and safety. The essay makes a systematic analysis on possible factors impacting TCM preparations and current situation of quality control and discusses possible approaches and new methods for improving quality control of TCM preparations, in order to give an impetus to the quality control standards and the mode evolvement of TCM preparations and ensure safety, efficiency and quality controllability of TCM preparations.

Pharmacokinetics comparative study of a novel Chinese traditional herbal formula and its compatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Da Chuan Xiong Decoction Compound preparation (DCXDCP), the formulation of a classical Chinese prescription recorded in "Xuanminglunfang", was clinically employed to treat migraine's disease. AIM OF THE STUDY: In order to investigate the influence of compatibility on the pharmacokinetics of the active ingredient gastrodin (GAS), the comparative evaluations on pharmacokinetics of DCXDCP with various combinations of its constituent herbs in plasma after oral administration were studied. MATERIALS AND METHODS: The rats were randomly assigned to four groups and orally administered with different prescription proportion of Gastrodia elata Bl. and Ligusticum chuanxiong Hort. (1:0; 1:0.25; 1:2.1; 1:4.2), respectively. At different predetermined time points after administration, the concentrations of GAS in rat plasma were determined by using HPLC, and main pharmacokinetic parameters were investigated. RESULTS: The results showed that the pharmacokinetic parameters, AUC and C(max) of GAS were dramatically different (p<0.05) after oral administration of G. elata Bl. and the different combinations of its constituent herbs. CONCLUSIONS: These indicated that the compatibility effects of other ingredients present in DCXDCP could affect the pharmacokinetics of the prescription.

["Total amount" release kinetics evaluation of traditional Chinese medicine sustained-release preparations based on material rough set theory].

The release kinetics research of sustained-release formulations of traditional Chinese medicines (TCM) is an inalienable part of the chain of TCM modernization, which plays an important role in the development of modern compound TCM preparation. However, the research method or pattern in line with the specific characteristics of TCM, i.e., multi-component and multi-target, is still lacking. On the basis of material rough set theory, this paper reviewed the advantages and disadvantages of the existing evaluation patterns and methods, a tentative idea about the "total amount" release characteristics evaluation on TCM compound sustained-release preparation has suggested so as to evaluate the release kinetics and to promote the development of evaluation methodology on TCM sustained-release preparations.

Process optimization, characterization and pharmacokinetic evaluation in rats of ursodeoxycholic acid-phospholipid complex.

The purpose of this research was to study whether the bioavailability of ursodeoxycholic acid could be improved by administering ursodeoxycholic acid-phospholipid complex (UDCA-PLC) orally to rats. A central composite design approach was used for process optimization in order to obtain the acceptable UDCA-PLC. The physicochemical properties of the complex obtained by optimal parameters were investigated by means of scanning electron microscopy and X-ray diffraction. The pharmacokinetic parameters and bioavailability studies were conducted in rats of UDCA after oral administration of UDCA-PLC and UDCA tablet. Multiple linear regression analysis for process optimization revealed that the acceptable UDCA-PLC was obtained wherein the optimal values of X(1), X(2) and X(3) were 3, 60 degrees C and 3 h, respectively. The XRD studies of UDCA-PLC obtained by the optimal parameters demonstrated that UDCA and phospholipids in the UDCA-PLC were combined by non-covalent bonds, not form new compounds. But pharmacokinetic parameters of the complex in rats were T(max) 1.6 h, C(max) 0.1346 microg/ml, AUC(0-infinity) 11.437 microg x h/ml, respectively. The relative bioavailability of UDCA of UDCA-PLC was increased by 241%,compared with the reference ursodeoxycholic acid tablet.