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ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg-1·d-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg-1·d-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.
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Objective:To establish a method of evaluating the reproducibility of the preparation process of Xiaozheng-Zhitong cataplasm. Methods:Used fingerprint spectrum technology and in vitro release test to evaluate the reproducibility preparation process of Xiaozheng-Zhitong cataplasm. By using HPLC to establish the fingerprint of Xiaozheng-Zhitong cataplasm. The chromatographic column was an Agilent HC-C18 column (4.6 mm×250 mm, 5 μm); the detection wavelength was 280 nm; the flow rate was 1 ml/min; the column temperature was 25 ℃. The mobile phase was acetonitrile-0.2% phosphoric acid aqueous solution, used gradient elution method. An HPLC method for the determination of tetrahydropalmatine content was established, and the vertical Franz diffusion cell method was used to investigate its in vitro release. Results:The results showed that the similarity between the 10 batches of Xiaozheng-Zhitong cataplasm and the control map was above 0.95, indicating that the process of Xiaozheng-Zhitong cataplasm was stable and feasible; the cumulative release amount of tetrahydropalmatine was 0.23 mg in 24 hours, and the cumulative release rate in 8 hours was 91.54%, and the RSD of 6 samples at each time point was <3%. Conclusion:The method of evaluating the reproducibility of the preparation process of Xiaozheng-Zhitong cataplasm was established by using fingerprint technology and in vitro release; it can provide a reference and scientific basis for the evaluation of the reproducibility of the preparation process of the plaster.
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Objective In this paper, the extraction process of Xiaozhong-Zhitong granule (XZG) was investigated. Methods In Process 1, the Panax notoginseng (Burk.) F.H.Chen was extracted with other drugs, and in the process 2, the Panax notoginseng (Burk.) F.H.Chen was crushed and directly used as medicine. Rats were randomly divided into blank group, process 1 group, process 2 group and mixture group.The sample concentration of the process 1 group 1 for the stomach was 2.07 g/ml, and the sample concentration of the process 2 group 1 for the stomach was 1.06 g/ml, and the sample concentration of the mixture group for the stomach was 0.015 g/ml, and blank group gavaged equal volume saline. Anti-inflammatory and analgesic effects of acetic acid writhing test, hot plate test, auricle swelling test and egg white-induced plantar swelling test were evaluated. Results Compared with the blank group after 1, 2, 3, and 4 h after administration, the average writhing number of the mice in the process group 1 and the process 2 group (35.50％ ± 8.06％, 35.00％ ± 7.63％vs. 47.00％ ± 1.45％) significantly decreased (P<0.01), and the auricular swelling degree (46.31％ ± 22.25％, 45.41％ ± 21.43％ vs. 73.89％ ± 15.55％) significantly decreased. And compared with the blank group after 0.5, 1, 2, and 4 h after inflammation, the percentage of pain threshold in the first group and the second group increased (P<0.01). While there was no significant difference in the inhibition rate of paw swelling in each group (P>0.05). Conclusions The design of extraction process of XZG was reasonable; when treating swelling and pain, it was better to put the powder of Panax notoginseng (Burk.) F.H.Chen in XZG.
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Objective To study the effects of microemulsion/ethosomes on transdermal absorption properties and efficacy of Huoxue Zhitong Cataplasm. Methods The improved Franz diffusion cells were used for the in-vitro permeation experiment with rat skins as the barriers, which was used to evaluate the transdermal absorption properties. In the erxeriment, the contents of paeonol, eugenol and methyl salicylate were used as markers, and detected by ultra performance liquid chromatography to evaluate the transdermal absorption effects. The anti-inflammatory and analgesia activity were evaluated through the writhing plate experiments. Results The cumulative release rate of paeonol in Huoxue Zhitong Cataplasm, Microemulsion Huoxue Zhitong Cataplasm and Ethosomes Huoxue Zhitong Cataplasm were, in order, 65.30%, 61.30%and 60.20%in 24 h;eugenol were, in order, 51.08%, 54.71% and 55.66% in 24 h; methyl salicylate were, in order, 49.20%, 65.17% and 72.15% in 24 h. Furthermore, Microemulsion Huoxue Zhitong Cataplasm high-dose group and Ethosomes Huoxue Zhitong Cataplasm medium-dose group had good effects on reducing the inflammatory exudate of peritoneal capillary and capillary permeability (P<0.05) in animal models. Conclusion Huoxue Zhitong Cataplasm based on microemulsion/ethosomesnano-technology has good transdermal absorption properties and efficacy.
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Objective To optimize refinement of water extract from Bushen Yangxue Granules by chitosan flocculation.Methods According to the content of icariin detected by HPLC, the waters amount, extraction time and extraction times were evaluated by orthogonal design. The effects of the solution concentration, clarifying temperature and the amount of clarifying agent on the flocculation clarification processes were optimized with the content of icariin and polysaccharides.Results The optimum water extraction processes A2B1C3 were follows: 10 times amount of water, three times extraction and 1 h for each extraction process. The optimized flocculation clarification processes A1B2C3 were as follows: solution concentration was 0.4 g/mL, the clarifying temperature was 40℃ and the addition of chitosan was 0.1%.Conclusion The optimized refining process is stable and feasible.
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Artemisinin is the antimalarial active ingredient, which is discovered by Chinese scientists in 1970s. The chemical structure of artemisinin is modified or altered to obtain a series of analogues to satisfy the medication requirements. According to the physicochemical properties of medicines and actual clinical necessities, the preparations of artemisinins are developed and the common preparations include tablet, suppository, injection, etc.. With the developing of technology, researchers have conducted a large number of studies on the artemisinins nanoparticles injection, transdermal drug delivery systems, mucosal drug delivery systems and etc. This article systematically collected and discussed the recent studies on the antimalarial preparations of artemisinins in line with different administration routes.
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Objective To establish the determination method of gallic acid in Yuanhu Zhitong Soft Capsule by HPLC. Methods Chromatography was performed on a Unitary C18 column (250 mm× 4.6 mm, 5 μm) at 254 nm. The mobile phase consisted of a mixture of methanol and 0.5%phosphate acid (5∶95) at flow rate of 1.0 mL/min. Results The standard curve of linear relationship was 0.024 8-0.496 μg and r=0.999 9. The RSD of precision, repeatability and stability was 0.27%, 0.21%, 1.40%, respectively. The average recovery was 99.81%, RSD was 0.72%. Conclusion The established method was accurate and reliable for the determination of gallic acid in Yuanhu Zhitong Soft Capsule.
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Objective To analyze the composing principles of the prescriptions for the shell of Gelatin Soft Capsule (GSP). Methods Totally 41 articles related to shell of GSP published on journals, dissertation and patent literatures in recent 10 years were used to analyze the composing principles for the shell of GSP by TCM Inheritance Platform System. Results The core combination was glycerin-gelatin-water, and the peripheral combinations ingredients included sorbitol, lemon yellow, titaniaum dioxide, iron oxide, PEG400 and ethylparaben, et al. Conclusion TCM Inheritance Platform System can be used for analyzing the composing principles of GSP.
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<p><b>OBJECTIVE</b>To compare the pharmcoknetic parameters of six major alkaloids in the two drug delivery system of Zuojin Wan, by LC-MS assaying the six major alkaloids plasma concentration.</p><p><b>METHOD</b>The blood samples were collected at different time after transdermal administration. The plasma concentration of six major alkaloids were detected by LC-MS, then the concentration-time data are modulated by software WinNonlin.</p><p><b>RESULT</b>Took the six alkaloids (berberine palmatine coptisine jateorhizine evodiamine rutecarpine) as index components, the relative bioavailability were 131%, 127%, 108%, 121%, 92%, 109%, respectively, the ratio of Ka were 10.5, 5.1, 3.7, 0.8, 1.8, 1.5, respectively.</p><p><b>CONCLUSION</b>The LC-MS can be applied in the determination of six major alkaloids plasma concentration. The pharmcoknetic parameters indicated that Zuojin Wan microemulsion gel delivery system can accelerate the transdermal absorption rate of Zuojin Wan, compared with the hydrogel drug delivery system.</p>
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Animals , Female , Male , Rats , Alkaloids , Chemistry , Pharmacokinetics , Chromatography, Liquid , Drug Delivery Systems , Drugs, Chinese Herbal , Chemistry , Pharmacokinetics , Emulsions , Gels , Hydrogels , Chemistry , Mass SpectrometryABSTRACT
<p><b>OBJECTIVE</b>To optimize the matrix formulation of cataplasm.</p><p><b>METHOD</b>Face-centered design was used in the experimental design, and response surface was produced in quadratic polynomial after data fitting in order to explore the impacts of Sodium Polyacrylate, Carbomer and the cross-linking agent on stickiness of cataplasm, optimize the prescription of the cataplasm matrix and perform the evaluation analysis.</p><p><b>RESULT</b>The multiple correlation coefficient (R2) and adjusted R2 in the fitting method using quadratic polynomial were 0.970 and 0. 952 (F = 53.953, P = 0.0001), respectively, and the model was significant different. The ratio of optimum proportion of Sodium Polyacrylate, Carbomer and the cross-linking agent in the matrix of cataplasm was determined, which was proved efficaciously.</p><p><b>CONCLUSION</b>Face-centered design-response surface method is a simple method with good prediction result for the optimization of cataplasm matrix.</p>
Subject(s)
Chemistry, Pharmaceutical , Methods , Drugs, Chinese Herbal , Chemistry , Models, TheoreticalABSTRACT
<p><b>OBJECTIVE</b>To investigate the regularity of Yulian Cataplasm in vitro release and transdermal behaviors.</p><p><b>METHOD</b>Improved Franz diffusion devices was used with four index ingredients as evodiamine, rutaecarpine, palmatine and berberine that were determined by HPLC in one mobile phase.</p><p><b>RESULT</b>The release rates of evodiamine, rutaecarpine, palmatine and berberine were 0.0239, 0.0156, 0.0725, 0.8191 mg x cm(-2) x h(-1/2), respectivley. The transdermal rates of evodiamine, rutaecarpine, palmatine and berberine were 1.256, 1.0302, 2.8029, 20.919 microg x cm(-2) x h(-1), respectively.</p><p><b>CONCLUSION</b>The releasing process of all index is in accordance with Higuchi equation and the transdermal proccess is in accordance with zero-level equation.</p>