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OBJECTIVE To study the effects of self-assembled nanoparticles from Shaoy ao gancao decoction （SGD-SAN）on the in vitro release and intestinal absorption of the main components of Glycyrrhiza uralensis . METHODS Gancao single decoction （GSD），Shaoyao single decoction （SSD），mixed suspension of Shaoyao and Gancao single decoction （MSSGD）and SGD （i.e. Shaoyao-Gancao decoction ）were prepared ，and SAN was characterized. HPLC method was adopted to determine the contents of 7 main components （liquiritin apioside ， liquiritin， isoliquiritin apioside ， isoliquiritin， liquiritigenin， glycyrrhizic acid ， isoliquiritigenin）in G. uralensis . The dialysis bag method was used to investigate the effects of the formation of SGD-SAN on in vitro release of 7 main components in G. uralensis with pH 1.2 HCl solution and pH 6.8 phosphate buffered solution （PBS）as release media. Single-pass intestinal perfusion study was performed to investigate the effects of the formation of SGD-SAN on the intestinal absorption of 7 main components from G. uralensis . RESULTS SAN with particle size of 200-300 nm and polydispersity index of 0.3-0.5 was found in GSD ，MSSGD and SGD. GSD-SAN and MSSGD-SAN were in rod shape while SGD-SAN was irregularly spherical under transmission electron microscope. The results of in vitro release study showed that the formation of SGD-SAN could significantly increase in vitro release of liquiritigenin ，isoliquiritigenin and glycyrrhizic acid ，and had no effect on other components of G. uralensis in pH 1.2 HCl solution. The formation of SGD-SAN also had no effect on the release of each component from G. uralensis in pH 6.8 PBS. The results of intestinal perfusion experiments showed that the formation of SGD-SAN could significantly promote the absorption of each component from G. uralensis in the ileum. CONCLUSIONS- The formation of SGD-SAN significantly improves the in vitro release of poorly soluble components from G. uralensis and promotes the intestinal absorption of main components from G. uralensis ，which is the physical structure basis for the compatibility and synergy of Paeonia lactiflora and G. uralensis .
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OBJECTIVE To study the sp ectrum-effect relationship of anti-gastric ulcer effect of Shaoyao gancao decoction. METHODS Eleven batches of Shaoyao gancao decoction were prepared ；gastric ulcer model was established by anhydrous ethanol modeling method. Using Weikangling as positive control ，the effects of Shaoyao gancao decoction on the contents of defensive factors [nitric oxide （NO），epidermal growth factor （EGF），superoxide dismutase （SOD）] and attack factor [malondialdehyde （MDA）] in gastric tissue of model rats were investigated. HPLC fingerprints of 11 batches of Shaoyao gancao decoction were established and similarity evaluation was performed with Similarity Evaluation System of Traditional Chinese Medicine Chromatographic Fingerprint （2004A edition ）； common peaks were identified by comparing with mixed control. The spectrum-effect relationship of Shaoyao gancao decoction against gastric ulcer was analyzed based on the grey correlation analysis. RESULTS Eleven batches of Shaoyao ganyao decoction could significantly decrease the content of MDA in gastric tissue ，while increased the contents of NO ，EGF and SOD in gastric ulcer model rats （P＜0.01），and had a certain inhibitory effect on the gastric ulcer. There were 23 common peaks in chromatograms of 11 batches of samples ，and the similarity with the control fingerprint was not less than 0.9. By comparing with mixed control ，7 common peaks were identified ，namely gallic acid （peak 5），albiflorin（peak 9），paeoniflorin（peak 10），liquiritin（peak 12），isoliquiritin apioside （peak 14），isoliquiritoside（peak 15）， glycyrrhizic acid （peak 22）. The average correlation degree of 7 identified common peaks and pharmacodynamic indexes were greater than 0.6，of which peak 22（glycyrrhizic acid ），peak 10（paeoniflorin）and peak 12（liquiritin）had the largest correlation ， and their values were 0.807，0.772 and 0.770 respectively. RESULTS The anti-gastric ulcer effect of Shaoyao gancao decoction is the result of the synergistic effect of multiple components ，among which glycyrrhizic acid ，paeoniflorin and liquiritin may be the main pharmacodynamic components.
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To study the effect of self-assembled nanoparticles from Shaoyao Gancao Decoction(SGD-SAN) on the encapsulation, in vitro release and intestinal absorption of the main components of Baishao. Particle size analysis and morphological observation were used to verify the formation of SGD-SAN in the decoction. The entrapment efficiency(EE) of SGD-SAN on the main components of Baishao was determined by ultrafiltration centrifugation. The dialysis bag method was used to study the in vitro release of the main components of Baishao with pH 6.8 phosphate buffer solution as the release media. Single-pass intestinal perfusion study was performed to investigate the effect of SGD-SAN on the absorption of the main components of Baishao. The results showed that there were nanoparticles in the SGD, and the particle sizes and PDI of SGD-SAN were about 200 nm and 0.38, respectively. SGD-SAN was irregularly spherical under transmission electron microscope(TEM). The EEs of albiflorin, paeoniflorin and benzoylpaeoniflorin in SGD-SAN were 33.78%±1.03%,33.61%±0.90%,88.53%±0.58%, respectively. The release characteristics of albiflorin, paeoniflorin and benzoylpaeoniflorin from SGD-SAN showed a slow-release effect on pH 6.8 phosphate buffer solution media. SGD-SAN could significantly enhance the absorption of albiflorin, paeoniflorin and benzoylpaeoniflorin in the ileum. The results of this study indicated that SAN could be formed during the mixed decoction of Baishao and Gancao, and SGD-SAN could encapsulate the components of Baishao, with a certain slow-release effect, and the formation of SAN facilitated the absorption of drugs in the ileum.
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Drugs, Chinese Herbal , Intestinal Absorption , Intestines , NanoparticlesABSTRACT
The quality markers (Q-markers) of traditional Chinese medicine (TCM) have become a topic of interest in TCM research in recent years. Nonetheless, there is still no consensus on how to scientifically characterize TCM Q-markers. Our study establishes an identification method for TCM Q-markers based on the analytical hierarchy process (AHP) and the entropy weight comprehensive method. By constructing an evaluation system encompassing the target layer, the factor layer and the control layer, AHP can be used to analyze the weight of three core TCM quality attributes, including effectiveness, testability and specificity. Following that, the entropy weight method is employed to analyze the specific indicators for each attribute based on the literature and experimental data. Finally, the comprehensive weight of each index is obtained by combining the two weights, and the comprehensive weight and the specific value of each component is multiplied and summed to obtain the integrated score ranking, and thereby identify the TCM Q-markers. Taking Shaoyao Gancao decoction as an example, the analysis revealed that the top 8 components are as follows: paeoniflorin > quercetin > albiflorin > glycyrrhizic acid > naringenin > liquiritin > oxypaeoniflorin > benzoylpaeoniflorin, and can be identified as Q-markers of Shaoyao Gancao decoction. This study not only provides support for the establishment of quality standards and process quality control of TCM formulae, but also provides innovative ideas and methods for quantitative evaluation and accurate identification of TCM Q-markers.
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Objective: Using ultra-high performance liquid chromatography with diode array detection (UHPLC-DAD) and desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to analyze 15 batches of Shaoyao Gancao Decoction (SGD) substance benchmark and lyophilized powder in order to investigate the advantages of DESI-MSI in quality control of famous classical formulas. Methods: Taking SGD as the research model, fingerprints of the substance benchmark were established by UHPLC-DAD, and the content of index components (paeoniflorin, liquiritin, glycyrrhizic acid) and the yield of dry extract were also investigated. Meanwhile, as the research carrier, the lyophilized powder corresponding to SGD was dissolved in methanol and dotted on qualitative filter paper with quantitative capillary, and fixed it on the slide to make samples. The samples were analyzed on a DESI-MSI system in positive and negative ion mode with methanol-formic acid (1 000:1, flow rate of 3 μL/min) as spray solvent, N2 as spray gas (pressure of 0.5 MPa). The scanning range was m/z 100-1 200, the spatial resolution was 300 μm, the ion source temperature was 120 ℃. Results: DESI-MSI can detect not only the index components of paeoniflorin, liquiritin, glycyrrhizic acid, but also the common peaks of albiflorin. At the same time, DESI-MSI could detect 11 other components from Glycyrrhizae Radix et Rhizoma and Paeoniae Radix Alba, such as licoricesaponin G2, licoricesaponin J2, gallic acid, citric acid, p-hydroxybenzoic acid, and present their relative content visually. The qualitative analysis ability of DESI-MSI was much better than UHPLC-DAD. Conclusion: DESI-MSI can be used as the quality control method for substance benchmark and lyophilized powder and dispensing granules of classical famous formulas with advantages of high sensitivity, strong analytical ability, no complex sample pretreatment, qualitative and relative content analysis of complex samples without reference substance.
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Objective: To study the mechanism of Shaoyao Gancao Decoction in the treatment of rheumatoid arthritis (RA) based on network pharmacology. Methods: The active components of Shaoyao Gancao Decoction were obtained from traditional Chinese medicine systems pharmacology (TCMSP) database, and human target proteins corresponding to active components were searched in Swiss Target Prediction and TCMSP database. The targets of RA were collected through Therapeutic Target Database and Drugbank database. The key targets of Shaoyao Gancao Decoction to treat RA were screened by building the Venn diagram. And the key protein interaction (PPI) network model was constructed by STRING database. The gene ontology (GO) and pathway enrichment analysis were performed by DAVID database. All of the correlative results were visualized by Cytoscape 3.7.2, and the network feature analysis was made by Network Analyzer. Results: A total of 102 compounds were obtained from Shaoyao Gancao Decoction, with 310 corresponding targets, and 68 common targets of Shaoyao Gancao Decoction-RA were obtained. Herb-compound-target-pathway network showed that kaempferol, quercetin, formononetin, naringenin, isorhamnetin were the key compounds of Shaoyao Gancao Decoction in the treatment of RA, and PTGS2, NOS2, MAPK14, PPARG, IL-6, TNF, and IL-1β were the key targets. GO entries included 28 biological process entries, two cellular component entries, and 13 molecular function entries. There were 40 pathways involving TNF signaling pathway, osteoclast differentiation, T cell receptor signaling pathway, MAPK signaling pathway, steroid hormone biosynthesis and toll-like receptor signaling pathway. Conclusion: The results of this study verify the multi-component, multi-target and multi-pathway regulation characteristics of Shaoyao Gancao Decoction, preliminarily predict material basis and mechanism of Shaoyao Gancao Decoction in the treatment of RA, which provides reference for further research.
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OBJECTIVE@#To investigate the mechanism of cAMP-PKA signaling pathway mediated by Chinese medicine formula Shaoyao Gancao Decoction (, SGD) on the regulation of aquaporin 5 (AQP5) and muscarinic receptor 3 (M3R) levels in Sjögren's syndrome (SS).@*METHODS@#Of the 30 mice, 5 were randomly selected as control, and others were used for creating SS model. After successful modeling, mice were randomly divided into 5 groups (n=5 per group) and intragastrically administered with saline (8 mL/kg), pilocarpine (1.4 mg/kg), or low, medium and high doses SGD (0.14, 0.21, 0.35 g/kg Radix paeoniae with 0.01 g/kg Radix glycyrrhizae, respectively) for 6 weeks. Human labial gland acinar cells were treated with pilocarpine or varying doses of SGD with saline as the placebo. Hematoxylin and eosin staining was used to observe the histopathological changes of the submandibular glands of mice. The serum levels of anti-SS antigen A (SS-A), anti-SS antigen B (SS-B), M3R, and α-fodrin in submandibular glands of mice were measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to observe the spatial localization of AQP5 and M3R in acinar cells. Reverse transcriptase polymerase chain reaction and Western blot were used to detect the expressions of PKA, cAMP, Epac1, AQP5, M3R, nuclear factor kappa-B (NF-κB), and tumor necrosis factor (TNF)-α in submandibular gland tissues and cells of each group.@*RESULTS@#Compared to normal mice, body weight, 5-min salivary secretion, 30-min secretion of tears and breakup time of tear film of model mice decreased at 1-6 weeks after immunization (all P<0.05), whereas water intake increased (all P<0.05). In the model group, glands of the submandibular glands showed atrophy, accompanied by acini of different sizes, decreased numbers and loose arrangement, with catheter dilatation and different degrees of lymphocyte infiltration. Conditions of mice in SGD groups were improved. The positive expression of AQP5 and M3R were higher in the acinar cells treated with all doses SGD compared to the normal group; serum levels of SS-A, SS-B, and α-fodrin were lower, and that of M3R was higher in all doses SGD treated animals than the model or pilocarpine treated ones (all P<0.05). Compared to the model and pilocarpine groups, the mRNA and protein levels of NF-κB and TNF-α were lower in mice or cells treated with medium or high-dose SGD (all P<0.05), while those of PKA, Epac1, AQP5 and M3R were higher (all P<0.05).@*CONCLUSION@#SGD can improve symptoms of SS by regulating the cAMP-PKA signaling pathway and increasing AQP5 and M3R levels.
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The most common manifestations of eosinophilic gastroenteritis (EG) are abdominal pain and diarrhea. Glucocorticoid is currently used in the treatment for EG, but the adverse reactions are relatively large. Banxia Xiexin Decoction is the famous Zhongjing prescription can be used to treat many kinds of gastrointestinal diseases. This article introduced. Banxia Xiexin Decoction combined with Shaoyao Gancao Decoction in the treatment of abdominal pain predominant based EG, as well as Banxia Xiexin Decoction combined with Gegen Qinlian Decoction in treating diarrhea predominant based EG have achieved satisfactory efficacy.
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[Objective] To study the basis of treating constipation with Shaoyao Gancao Decoction.[Method] Ancient and modern herbal and experience of famous doctors literature of Shaoyao Gancao decoction,Shaoyao(Peony) and Gancao(licorice) are reviewed and summed up.[Results] Shaoyao(Peony) and Gancao(licorice) themself have a certain purgative effect.Shaoyao is good at regulating abdominal qi and blood,"removing blood stasis and lump accumulation",eliminating abdominal evil,and thus plays a laxative effect.Gancao is good at detoxification,eliminating the toxin of stool,and thus plays a antitoxic and laxative effect.For constipation Shaoyao Gancao decoction is composed of raw Shaoyao and raw Gancao at a ratio of 3:1 to 2:1,and the general amount of raw Shaoyao is about 30g.[Conclusion]Shaoyao Gancao decoction has a good laxative effect,alone or its modified is suitable for a variety of constipation syndrome types.
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<p><b>OBJECTIVE</b>To investigate the effect of Shaoyao Gancao Decoction (, SGD) on the pharmacokinetics of intravenously administered paclitaxel in rats.</p><p><b>METHODS</b>Paclitaxel was intravenously administered to rats (3 mg/kg) with or without the concomitant administration of SGD (752 mg/kg, a single day or 14 consecutive days pretreatment). The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography (UPLC) method for the pharmacokinetic study. The pharmacokinetic parameters were calculated via a non-compartment model using the computer program DAS 2.0.</p><p><b>RESULTS</b>The pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD. The area under the curve (AUC, from 4 820±197 to 4 205±186 ng·mL·) and AUC(from 5 237±280 to 4 514±210 ng·mL·) significantly decreased in response to the 14-day pretreatment with SGD. The values of V(L/kg) were 10.74±1.08 and 9.35±0.49, those of CL (L/kg) were 0.67±0.03 and 0.57±0.03 and the t(h) values were 11.17±0.84 and 11.32±0.93, respectively, for the 14-day SGD pretreatment and intravenous paclitaxel alone. The AUCand AUCvalues decreased by 13% and 14% (P<0.01), respectively. The area under the curve decreased signifificantly (P<0.01), and the total clearance increased by 1.2-fold (P<0.01), after 14 consecutive days of pretreatment with SGD. A single-day pretreatment with SGD did not signifificantly affect the pharmacokinetic parameters of paclitaxel.</p><p><b>CONCLUSIONS</b>SGD administration for 14 consecutive days increased the metabolism of paclitaxel, while a 1-day pretreatment had little effect. The results would contribute important information to the study on interaction between Chinese medicines and chemotherapy and also help to utilize SGD better in the adjunctive therapy of cancer patients.</p>
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Animals , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Therapeutic Uses , Injections, Intravenous , Male , Paclitaxel , Blood , Chemistry , Pharmacokinetics , Rats, Sprague-Dawley , Reference Standards , Time FactorsABSTRACT
Objective To investigate the clinical effect of Shaoyao Gancao Decoction (SGD) combined with conventional therapy in treatment of neck cervical spondylosis.Methods 119 cases of neck cervical spondylosis from Jiaxing Hospital of Zhejiang Armed Police Hospital during January 2013 to January 2015 were retrospective analysis, 68 patients were treated with SGD combined with conventional physical therapy (combination group), 51 patients were only adapted conventional physical therapy (physiotherapy group).The clinical efficacy between two groups were compared.Results After treatment, the cervical curvature, neck pain, neck tenderness, cervical flexing function,cervical lateral curvature function,affect the condition of work, the impact of the disease on sleep scores of combination group were significantly lower than physiotherapy group (P<0.05).NPQ and McGill scores of two groups were significantly lower than pre-treatment ( P<0.05 ) , and NPQ, McGill scores of combined group were significantly lower than physiotherapy group (P<0.05).Therapy cure rate of combined group was 32.35%, which higher than 19.61%of physiotherapy group (P<0.05). Conclusion SGD combined with conventional therapy in treatment of neck cervical spondylosis was better than conventional therapy alone.
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To explore the effects of Shaoyao Gancao decoction on contents of amino acids and expressions of receptors in the brains of spastic paralysis rats, the spastic paralysis rat models of stroke convalescence were made by line tethering method. Baclofen was used as the control group, and the experiment group received Shaoyao Gancao decoction at 3∶1 proportions. After 3 weeks, the neurobehavioral scores, muscular tension and pain threshold were measured and compared. High performance liquid chromatography (HPLC) was used to detect the contents of GABA, Gly, Glu, Asp in cerebral cortex. The protein expressions of GABA receptors Aα1, B； NMDA receptor NR1, NR2A and NR2B in cerebral cortex were determined by immunohistochemistry assay. The results showed that the Shaoyao Gancao decoction at 3∶1 proportion could improve the spastic paralysis state after stroke, significantly improve neurological symptoms (P<0.01), decrease muscular tension (P<0.01) and improve pain threshold (P<0.05) as compared with model group. Simultaneously, the contents of inhibitory amino acids GABA and Gly were increased significantly (P<0.01), while with a decrease tendency in excitatory amino acids Glu and Asp (with no statistical significance). In addition, it could significantly increase the protein expressions of neurotransmitter GABA receptors Aα1, and B (P<0.05); reduce the expressions of neurotransmitter NMDA receptors NR1, NR2A and NR2B (P<0.05). These results suggested that the Shaoyao Gancao decoction at 3：1 proportion could effectively relieve spasm and pain. The mechanism might be associated with increasing the contents of inhibitory amino acids and increasing the expressions of their receptors in spastic paralysis rats after stroke, which would consequently enhance the signal transduction of inhibitory amino acids. Meanwhile, there was a decrease tendency in excitatory amino acids, although no significant effect was observed, and it could suppress the expressions of excitatory amino acids receptors, thus weaken the excitatory signal transduction. Thereby the neurotoxicity was relieved eventually. These findings indicated that Shaoyao Gancao decoction could regulate the balance of neurotransmitter system to relieve the spasticity, and eventually achieve tendon tonifying and spasm relieving effect.
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Objective] To observe the clinical effect of Shaoyao Gancao Decoction on treating children functional abdominal pain to offer reference for further observation. [Method] Choose 200 children patients in pediatric outpatient department of Changxing County TCM Hospital, randomly divide them into treatment and control groups in order, n=100. The treatment one was administered revised Shaoyao Gancao Decoction, the control one orally took Medilac-Vita; both for 4 courses, then observe the cure effects. [Result] In treatment group, total effective rate 94.00%; for control one, it was 86.00%. The comparison of both had difference of statistical meaning( P<0.05). On comparing their abdominal pain relieve, in treatment group, there's more in first 2w and showed marked summit value in the first week; while in control one, there's no marked summit value; so the treatment group was more obvious than other one on relieving pain in the first 2w(P<0.05). The side effect occurrence rate of treatment group was less than other one, the difference between them had statistical meaning(P<0.05). [Conclusion] The revised Saoyao Gancao Decoction has marked cure effect on children functional abdominal pain, worth clinical promotion.
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Objective To Observe the effects of treating primary trigeminal neuralgia with modified Shaoyao-Gancao decoction and carbamazepine. Methods 76 patients with primary trigeminal neuralgia were randomly divided into a treatment group and a control group, 38 patients in each. The treatment group was treated with modified Shaoyao-Gancao decoction and carbamazepine; and the control group was treated with carbamazepine only. Clinical curative effect, pain improvements and adverse reactions were observed after the treatment and 6 week follow-up. Results The total effective rate was 89.3%and 75.5%in the treatment group and the control group respectively, the difference was statistically significant(P=0.043). The onset frequency, duration, degree of pain were all improved in both groups after the treatment and 6 week follow-up[treatment group after the treatment is (0.54±0.78), (2.15±1.73), (1.58±1.26), 6 week follow-up is (0.24±0.63), (1.36±1.03),0.86±1.95);control group after the treatment is (1.98±1.68), (3.96±1.49), (3.02±1.45), 6 week follow-up is (1.06±1.78), (1.97±1.69), (2.13±1.54), P<0.05],and the treatment group was better than the control group(P=0.040 and 0.039 respectively). Conclusion Modified Shaoyao-Gancao decoction combined carbamazepine has good clinical curative effect in treating primary trigeminal neuralgia.
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OBJECTIVE:To study the compatible rationality of Shaoyao gancao decoction by serum HPLC fingerprint. METHODS:The serum HPLC fingerprints of Paeonia lactiflora,Glycyrrhiza uralensis and Shaoyao gancao decoction were compared to determine the number and quantity change of their component in serum. RESULTS:There were eight components in serum of P. lactiflora,23 components in serum of G. uralensis and 32 components in serum of Shaoyao gancao decoction. Some peak areas of serum samples were obviously increased,such as SGT6,SGT7,SGT10,SGT11,SGT14,SGT15,SGT16,SGT17,SGT18,SGT24,SGT25,SGT26,SGT27,SGT28,SGT29 and SGT32. CONCLUSION:The bioavailability is obviously improved after combination of P. lactiflora with G. uralensis,which shows synergism between them. Serum HPLC fingerprint certify the compatible rationality of combination of P. lactiflora and G. uralensis. Established method is simple,accurate and stable.