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This paper aims to investigate the intervention effect of Qufeng Gutong Cataplasm(QFGT) on myofascial pain syndrome(MPS) in rats and to preliminarily explain its mechanism from the perspective of improving muscle inflammation and pain. Male SD rats were divided into 6 groups, namely normal group, model group, positive control drug(Huoxue Zhitong Ointment, HXZT) group, and low, medium, and high-dose QFGT groups(75, 150, and 300 mg·d~(-1)). The rat model of MPS was established by striking combined with centrifugation for 8 weeks, during which QFGT and HXZT were used for corresponding intervention. Standard VonFrey fiber was used to evaluate the mechanical pain threshold, and acetone was used to detect the cold pain threshold. The electrophysiological activity of muscle at trigger point was detected, and the electromuscular analysis of trigger point was performed. CatWalk gait analyzer was used to detect pain-induced gait adaptation changes. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in muscle and skin tissues at the trigger point of rats. Immunohistochemistry was used to detect the expression of capsaicin receptor transient receptor potential vanilloid 1(TRPV1) in muscle tissues and interleukin(IL)-33 in skin tissues at the trigger point. The protein expression levels of TRPV1, protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), IL-1β, and tumor necrosis factor-α(TNF-α) in muscle tissues at the trigger point were detected by Western blot. The results showed that as compared with the model group, the mechanical pain threshold and cold pain threshold of rats in other groups were increased after treatment with QFGT. The spontaneous electromyography(EMG) activity was observed in the model group, but QFGT alleviated the EMG activity in a dose-dependent manner. Gait analysis showed that standing duration, average intensity, swing speed, maximum contact point, maximum contact area, paw print length, paw print width, and paw print area were significantly improved in all QFGT groups. Pathological results showed that the disorder of muscle arrangement at the trigger point was decreased, muscle fiber adhesion and atrophy were reduced, and inflammatory cell infiltration was alleviated after treatment with QFGT. In addition, QFGT and HXZT both inhibited the protein expression of TRPV1, PI3K, Akt, p-Akt, IL-1β, and TNF-α in the muscle tissues of rats with MPS. However, there was no significant difference in the pathological structure and expression of IL-33 in the treated skin as compared with the normal group. The related results have proved that QFGT can inhibit the release of inflammatory factors by inhibiting the TRPV1/PI3K/Akt signaling pathway in the muscle trigger point of rats with MPS and finally attenuate the atrophy and adhesion of local muscles and inflammatory infiltration, thereby relieving the muscle pain of rats with MPS, and local administration has no skin irritation.
Sujet(s)
Rats , Mâle , Animaux , Protéines proto-oncogènes c-akt , Rat Sprague-Dawley , Facteur de nécrose tumorale alpha , Phosphatidylinositol 3-kinases , Syndromes de la douleur myofasciale/traitement médicamenteux , DouleurRÉSUMÉ
Growing clinical evidence shows that Qufeng Gutong Cataplasm may exert a significant analgesic effect. However, the pharmacological characteristics and mechanisms underlying this prescription are still unclear. In the current study, a "disease-syndrome-symptom-formula" association network analysis was performed to explore the pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm against osteoarthritis (OA), neuropathic pain (NP), chronic inflammatory pain (CIP) and myofascial pain syndrome (MPS) by integrating clinical phenomics data, transcriptomics data and biological interaction network mining. As a result, the three functional modules (Qufeng Sanhan-QFSHG, Shujin Huoxue-SJHXG and Xiaozhong Zhitong-XZZTG) enriched by the drug network targets were all related to the pharmacological effects of Qufeng Gutong Cataplasm, including dispersing cold and relieving pain, activating blood and relieving pain, reducing swelling and relieving pain. In addition, the main pharmacological effects of QFSHG and XZZTG were dispelling wind and dispersing cold and dehumidifying, promoting Qi and reducing swelling and relieving pain, respectively. In terms of reversing the imbalance of "immune-inflammation-vascular axis", the main pharmacological effects of SJHXG were regulating the liver and promoting Qi, activating blood circulation and removing stasis. Mechanically, the key network targets of Qufeng Gutong Cataplasm against OA, NP, CIP and MPS may play a therapeutic role in relieving hyperalgesia and paresthesia by reversing the "neuro-endocrine-immune" imbalance system during the occurrence and progression of diseases. In conclusion, our data indicate that Qufeng Gutong Cataplasm may relieve the pain and wind-cold-dampness arthralgia syndrome related symptoms by regulating the "neuro-endocrine-immune" system, neurological and endocrine disorders and reversing the imbalance of "immunity-inflammation". The relevant results may provide a network-based evidence for clinical positioning of Qufeng Gutong Cataplasm, and offer a direction for further clinical and experimental validation.
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Objective To optimize the matrix formulation for Shaofu Zhuyu Cataplasm (SZC) by Plackett-Burman design combined with Box-Behnken response surface method and study its transdermal permeation properties in vitro. Methods In this paper, the appearance description, initial bonding strength, endurance bonding strength, and peel strength were taken as indexes. Based on the result of a single factor experiment, the formula for the SZC was optimized by Plackett-Burman combined with Box-Behnken method. Franz diffusing cells method was chosen to investigate the tansdermal infiltration capacity of SZC with different dosage penetration enhancers of azone in vitro, taking ferulic acid, paeoniflorin, isorhamnetin-3-O-neohesperidin, and typhaneoside as index components. Results NP-700, tartaric acid and kaolin had significant effects on the properties of SZC. The optimal ratio of the prescription was as follows: NP-700-tartaric acid-kaolin (2.42:0.16:0.96). The promoting effect of 3% concentration for index component was better, and the transdermal rates of ferulic acid, paeoniflorin, isorhamnetin-3-O-neohesperidin, and typhaneoside were 6.889 4, 1.917 4, 0.852 0, and 0.893 7 μg/(cm2∙h), respectively. Conclusion The SZC was uniform, without residual behavior in application. And it had a good release and transdermal properties, and transdermal actions were consistent with zero-order kinetics.
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Objective To study the effect of Shuangteng Bitong Cataplasm on TLR4, MyD88 and NF-κB and inflammatory cytokines in rats with collagen-induced arthritis; To discuss relevant mechanism of action. Methods A CIA model was made by subcutaneous injection of collagen emulsion from rat tail. Rats were randomly divided into normal group,model group,Shuangteng Bitong Cataplasm high-dose and low-dose groups.The contents of TNF-α, IL-1β and IL-6 in plasma were evaluated by ELISA, and the expression levels of TLR4, MyD88 and NF-κB in synovial tissues were evaluated by RT-PCR and Western blot. Results Compared with the model group, the contents of TNF-α, IL-1β and IL-6 in serum decreased remarkably in the Shuangteng Bitong Cataplasm low-dose and high-dose group, and the expression levels of TLR4, MyD88 and NF-κB in synovial tissues decreased remarkably. Conclusion Shuangteng Bitong Cataplasm can inhibit inflammatory reaction and regulate the expressions of relevant factors in synovial tissues to realize the anti-flammatory effects.
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Objective This study is designed to improve topical medication in the Department of Orthopedics in Kunming Municipal Hospital of Traditional Chinese Medicine by applying cataplasm made from the active ingredient (polyphyllin) of Paris polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz ("Dian Chonglou"in Chinese) and to study the mechanism of anti-inflammation. Methods SD male rats were randomly divided into two groups: control group and treatment group. The rats in two groups were all injected 50ul 5% sodium urate suspension into tibiotarsal joint cavity to duplicate the model of acute gouty arthritis.The rats in the control group were applied with cataplasm without polyphyllin, whereas those in the treatment group applied with cataplasm of polyphyllin. After 4,24,48,72 hours,the ankle diameter and circumference were measured. ELISA was used to test the interleukin-1β (IL-1β) andtumor necrosis factor (TNF) in peripheral blood. Western blotting was applied to detect the changes in TLR4 expression of monocyte.Results Compared with the control group, the added value of the diameter and circumference of ankle decreased significantly in the treatment group 4, 24,48 and 72 h after the treatment.IL-1β in the treatment group was lowered at 4,24 and 72 h. TLR4in the treatment group decreased at 48 h. Conclusion Cataplasm with polyphyllin can alleviate the acute inflammatory reaction in gouty joint of rat by reducing the expression of IL-1βand TLR4.
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Topically applied traditional Chinese medicines (TCM) generally show low transdermal rates and doses, leading to weak therapeutic efficacy. Here, cataplasm of white mustard seed varnish was prepared. The effects of iontophoresis and sonophoresis on the transdermal delivery of this TCM and its anti-asthma effect were evaluated. Active components of white mustard seed, rhizoma corydalis and Radix Kansui were obtained after alcohol extraction, respectively. The volatile oil in Asarum Heterotropoides were obtained with volatile oil extraction equipment. The drug loading ratio of cataplasms was 17% (w/w). Franz cell diffusion method was used to evaluate the accumulated permeation amount and the steady-state transdermal absorption rate of sodium thiocyanate. The improvement of sonophoresis on transdermal absorption was higher than that of iontophoresis.Asthma model of guinea pigs were established. Cataplasms of white mustard seed varnish were applied on the back of guinea pigs. Iontophoresis and sonophoresis obviously promoted the transdermal absorption and enhanced anti-asthma efficacy of white mustard seed varnish cataplasms. Pathological analysis showed that iontophoresis and sonophoresis significantly alleviated inflammation. Compared with the model group, IL-4 and IgE levels in the cataplasm group, cataplasm/iontophoresis group, cataplasm/sonophoresis group decreased obviously, although the IFN-γ levels markedly increased. Moreover, the therapeutic efficacy of cataplasm/sonophoresis group was the best in all the groups, even leading to levels similar to that of healthy animals. Iontophoresis and sonophoresis are effective methods to promote transdermal absorption of cataplasms. Moreover, the effect of sonophoresis is higher than that of iontophoresis. Physical penetration improvement techniques provide a novel insight for the wide application of transdermal TCM.
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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 study the safety of percutaneous administration of Hongzhi gutong cataplasm. METHODS:Rab-bits were taken for single dose in complete skin irritation test(n=4),single dose in damaged skin irritation test(n=4)and multi-ple doses in complete skin irritation test(n=4). The left and right sides of the skin respectively paste 3 cm×3 cm blank matrix and Hongzhi gutong cataplasm for 24 h(calculated by crude drug of 0.14 g). After removing tape 1,24,48,72 h,the erythema and edema in hair removal site of rabbits in the former 2 tests were observed;after 24 h of administration,the rabbits in the last group were administrated again after exposing the administration area for 1 h,repeated 3 times,the erythema and edema in hair removal site after removing tape the first,second time and 1,24,48,72 h in the third time were respectively observed. RESULTS:In the 3 experiments,the scores of erythema and edema of all rabbits were 0,and skin irritation was evaluated as no irritation. CONCLU-SIONS:Hongzhi gutong cataplasm has no skin irritation in rabbits.
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Objective: To optimize the matrix prescription of Compound Qingfengteng Cataplasm (CQC). Methods: Taking the comprehensive senses as evaluation index, the types and dosage of the matrix were investigated by single factor. Further combined with the initial viscosity and holding viscosity index to optimize the matrix prescription of CQC by orthogonal test, and in vitro transdermal absorption experiments were carried out by Franz diffusion pool method to screen penetration enhancers. Results: The optimal formulation of CQC was as follows: 2.5 g of NP-700, 11 g of glycerin, 0.08 g of glycine aluminum, 0.08 g of tartaric acid, 0.8 g of PVP K90, 0.5 g of PVPP, 20 g of water, and 4.2 g of dry extract. 3% nitrile as a penetration agent could enhance penetration action. Conclusion: The preferred matrix prescription is practicable; CQC adhesion is moderate, no residue, paste traits, skin followability are good.
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Objective:To optimize the extraction process of Guilong cataplasm .Methods:The yield of volatile oil was used as the index to optimize the volatile oil extraction technology by single factor tests. The yield of dry extract and the content of aconitine were used as the indices to optimize the water extraction technology by single factor tests and orthogonal test .Results:The optimal extraction conditions of volatile oil were as follows:the soaking time was 1h with 8-fold volume of water , and the extraction time was 6 hours.The optimal water extraction conditions were as follows:using 8-fold volume of water extracted for 3 times with 1 h for each time .Conclu-sion:The extraction process is simple , reasonable and reproducible ,which is suitable for the next research of Guilong cataplasm .
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Objective:To optimize the ethanol reflux extraction process for Aitong cataplasm .Methods: Orthogonal design was used to investigate the effect of solid-liquid ratio,extraction time and times on the extraction technology of Aitong cataplasm with the content of asarinin and dry extract yield as the indices .Results:The best extraction conditions were as follows:extracted 3 times with 8-fold amount of 70%ethanol, and 1 hour for each time.Conclusion: The optimized extraction process is stable and feasible , which can be used to extract Aitong cataplasm .
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OBJECTIVE:To investigate penetrative effects of a penetration enhancer and multiple penetration enhancers combi-nation with different proportions on Euodia rutaecarpa superfines cataplasm,so as to optimize enhancer and their concentrations. METHODS:Modified Franz diffusion cell was employed with isolated mice abdominal skin as barrier. HPLC method was adopted to detect the effects of a penetration enhancer (propanediol, azone, oleic acid), multiple penetration enhancers (propanedi-ol-azone,propanediol-oleic acid,propanediol-azone-oleic acid),their proportion and amount on accumulative permeation quantity (Qn) of evodiamine and rutaecarpin in Euodia rutaecarpa superfines cataplasm. RESULTS:The penetrative effect of a penetration enhancer propanediol was significantly better than that of other one penetration enhancers and multiple penetration enhancers;the higher proportion of propanediol in multiple penetration enhancer system was,the better penetrative effects of evodiamine and rutae-carpin had. Using 3%,5 % and 7 % propanediol as enhancer,Q36 h of evodiamine were 11.290,14.332 and 13.537 μg/cm2,and those of rutaecarpin were 11.965,14.856 and 13.901 μg/cm2. CONCLUSIONS:The penetrative effect of 5% propanediol is the best,and can be used as enhancer for E. rutaecarpa superfines cataplasm.
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OBJECTIVE:To determinate the release rate and in vitro transdermal rate of asarinin in Cancer pain cataplasm. METHODS:Using homemade devices and modified France diffusion,isolated skin of rats as barrier,normal saline as solvent,the content of asarinin was determined by HPLC. Release rate of Cancer pain cataplasm within 20,50,80 and 120 min and transder-mal amount within 2,4,8,12,24 h were investigated,and accumulative release rate and accumulative transdermal rate were cal-culated. RESULTS:Accumulative release rate by 120 min of asarinin in Cancer pain cataplasm was 73.01%;24 h in vitro transder-mal rate was 26.01%,and transdermal kinetics equation of asarinin was Q=5.717 7t1/2-0.385 4(r=0.979). CONCLUSIONS:Cancer pain cataplasm has good release and transdermal performance. Its transdermal kinetics is in line with Higuchi equation.
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Objective: To establish a comprehensive evaluation method based on principal component analysis (PCA) for the study of multiple indexes of Chinese medicine and to choose the best preparation technology of Gui-Shao Cataplasm with this method. Methods: The appearance description, initial bonding strength, endurance bonding strength, and peel strength were taken as indexes, the total factor scores were calculated using PCA and were employed to evaluate the quality of Gui-Shao Cataplasm, the uniform design test was used to optimize the amounts of sodium polyacrylate NP-700, aluminium glycinate, glycerin, etc. for Gui-Shao Cataplasm. Results: The optimal ratio of the prescription was as following: sodium polyacrylate NP-700-PVP K-30-aluminium glycinate-EDTA-2Na-tartaric acid-glycerin-extract (8∶1∶0.25∶0.07∶0.15∶25∶20). The foremost factors were tartaric acid, PVP K-30, sodium polyacrylate NP-700, aluminium glycinate, glycerin, and EDTA-2Na. Conclusion: The optimal prescription has easy ductility, uniform paste, and moderate adhesion, and it could provide the foundation for the development of new prescription of Gui-Shao Cataplasm; The PCA could be a reference for the Chinese medicine research of multiple indexes.
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Objective:To optimize the matrix formula of Qingre Zhitong cataplasm. Methods:An orthogonal test was performed to study the matrix formula of Qingre Zhitong cataplasm with the comprehensive score of continued adhesion and integrated sensory as the evaluation indices and the ratio of sodium polyacrylate, carboxymethylcellulose sodium, aluminum chloride hydrate and glycerin as the influencing factor. Results:The optimal matrix formula of Qingre Zhitong cataplasm was as follows: the ratio of sodium polyacrylate, carboxymethylcellulose sodium, aluminum chloride hydrate and glycerin was 14 ∶1 ∶1 ∶120. Conclusion: Qingre Zhitong cataplasm prepared with the optimal matrix formula has good continued adhesion and integrated sensory, and the process parameters are stable and feasible.
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OBJECTIVE:To optimize the matrix formula of Lanlian ertong qingre cataplasm. METHODS:Taking adhesion force,peel strength and sensory description as index,the ratio of matrix framework material(sodium polyacrylate-gan hydroxyl alu-minum-tartaric acid-glycerin) was optimized with orthogonal test. The single factor test was adopted to select adhesive and filler;the amount of penetrating agent azone was screened using the in vitro penetration amount of phillyrin. RESULTS:The best matrix ratio of Lanlian ertong qingre cataplasm was sodium polyacrylate-gan hydroxyl aluminum-tartaric acid-glycerin(4.0:0.8:0.4:15);PVP K-90 was used as adhesive,and bolus alba as filler;penetration enhancers azone accounted for 2.0%. Validation test showed, prepared cataplasm had good appearance,could stick on the 5th or the 6th ball;it's peel strength was 7.5 N;all RSDs of score were lower than 4%(n=3). CONCLUSIONS:The optimized matrix formula of Lanlian ertong qingre cataplasm is simple,stable and good in molding.
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Objective To develop the quality standard for evaluating Huangdi cataplasm. Methods Thin layer chromatography (TLC) was used to qualitatively identify Astragalus membranaceus (Fisch.) Bunge,Rheum palmatum Linn,Rhizoma Chuanxiong,Angelica sinensis and Resina Draconis in Huangdi cataplasm.HPLC method was used to determine astragaloside A and loureirin B in Huangdi cataplasm. Results The Astragalus membranaceus (Fisch.) Bunge,Rheum palmatum Linn,Rhizoma Chuanxiong,Angelica sinensis and Resina Draconis were well separated by TLC without interference in the negative control.content of Astragaloside A and loureirin B showed good liner relationships with respective peak area within the range of 6.96-23.2 μg,and 0.072-0.648 μg,with r = 0.999 5,r = 0.999 9, respectively;and the average recovery was 97.18%,and 96.93%,RSD was 1.21%(n= 6),1.53% (n = 6 ), respectively. Conclusion The established qualitative and quantitative detection method is simple, specific, reproducible, accurate and reliable, which can be used for quality control of Huangdi cataplasm.
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Objective To investigate the clinical efficacy of Pingchuan cataplasm combined with hyperthermia therapy for stable chronic obstructive pulmonary disease (COPD) with qi deficiency syndrome of both lung and spleen. Methods Sixty patients of stable COPD with TCM syndrome of qi deficiency of both lung and spleen were selected and randomized into treatment group and control group, 30 cases in each group. Based on conventional treatment, the treatment group was treated by Pingchuan cataplasm combined with hyperthermia, and the control group was given analog stick applicator without additional heat treatment. After 6 weeks of treatment, the TCM symptom score and the time of the first exacerbation after treatment were observed. Results Compared with the control group, Pingchuan cataplasm can reduce the patients’ TCM symptom score (F=9.843, P=0.003), and extend the interval of acute exacerbation after treatment (F=4.451, P=0.040). Conclusion Pingchuan cataplasm combined with hyperthermia applicator can improve symptoms and reduce the frequency of acute exacerbation, thus can treat and prevent the acute exacerbation of COPD.
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Objective: To optimize the matrix recipe of Compound Analgesic Cataplasm. Methods: Taking the early adhesion and appearance (paste traits, residue, and skin adhesive ability) as evaluation indexes, the optimal matrix recipe of Compound Analgesic Cataplasm was optimized by single factor test and central composite design-response surface method, and the optimal preparation process was determined at the same time. Results: The optimal ratio of the matrix is as follows: NP-700-carbopol 940-aluminium glycinate-silica-glycerin (5.34:0.63:0.2:6:30). Conclusion: The optimal matrix has the moderate adhesion without residue but with better paste traits and skin adhesive ability under the ideal preparation technology.
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Objective To optimize the matrix formulation of the extract of Chuanxiong Rhizoma cataplasm. Methods The optimal proportion of matrix formulation was selected by uniform design and response surface method. The primary adhesion force, lasting adhesion force, peel strength and residuals on the anti-sticking paper were used as test parameters. The optimal ratios of NP-700, glycinate aluminum, glycerin, tartaric acid, the concentration of drug, and the volume of drug were acquired. Results The matrix formulation of the cataplasm was made with NP-700∶glycinate aluminum∶glycerin∶tartaric acid∶concentration of drug∶volume of drug=1.1∶0.08∶7∶0.04∶4∶5. Conclusion Uniform design combined with response surface method can be used for the optimization of the matrix formulation of cataplasm. The optimal matrix prescription has higher drug-loading, with good spreadability, moisture-retention capability and adhesive force.