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ObjectiveTo investigate the anti-inflammatory effect of the component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma on the rat model of rheumatoid arthritis （RA） and the mechanism. MethodSeventy-two SPF-grade SD rats （male and female） aged 5 to 6 weeks were selected. Except the blank group， the rat model of collagen-induced arthritis （CIA） was replicated by the type Ⅱ collagen induction method. The 64 rats after successfully modeling were randomly divided into model group， methotrexate group （0.375 mg·kg-1）， gentianoside with magnoflorine group （150.454 1 mg·kg-1+5.061 8 mg·kg-1）， gentianoside with clematichinenoside AR group （150.454 1 mg·kg-1+16.433 1 mg·kg-1）， sweroside with magnoflorine group （3.455 8 mg·kg-1+5.061 8 mg·kg-1）， sweroside with clematichinenoside AR group （3.455 8 mg·kg-1+16.433 1 mg·kg-1）， swertiamarin with magnoflorine group （9.303 2 mg·kg-1+5.061 8 mg·kg-1）， and swertiamarin with clematichinenoside AR group （9.303 2 mg·kg-1+16.433 1 mg·kg-1）， with 8 rats in each group. Each group was given the corresponding medicinal solution or normal saline by gavage for 15 d. During the experiment， the general status， of rats in each group were observed and recorded. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， rheumatoid factor （RF）， C reactive protein （CRP）， prostaglandin E2 （PGE2）， and anti-cyclic peptide containing citrulline antibody （anti-CCP Ab） in the serum of rats were measured by enzyme-linked immunosorbent assay （ELISA）. The histopathological changes in rat ankle joints were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） and Western blot were used to detect the protein expression of nuclear factor-κB （NF-κB） and vascular endothelial growth factor （VEGF） in rat ankle joints. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of NF-κB and VEGF in rat ankle joints. ResultCompared with those in the blank group， rats in the model group were in poor general conditions with significant foot-plantar swelling， and the content of CRP， anti-CCP Ab， and IL-1β in the rat serum was significantly increased （P<0.01）. In the model group， the tissue structure of the ankle joint was severely damaged， and the protein and mRNA expression of NF-κB and VEGF in the rat ankle joints were significantly up-regulated （P<0.01）. As compared with the model group， the general status of rats in each administration group was significantly improved. The levels of serum TNF-α， IL-1β， RF， CRP， PGE2， and anti-CCP Ab were reduced to different degrees in these administration groups， among which the effects of the gentianoside with clematichinenoside AR group on down-regulating serum TNF-α and IL-1β， the gentianoside with magnoflorine group on down-regulating serum RF and CRP， the sweroside with magnoflorine group on down-regulating serum PGE2， and the swertiamarin with clematichinenoside AR group on lowering serum anti-CCP Ab were better than those of administration groups. The histopathological changes in the ankle joint were improved to different degrees. The protein and mRNA expression of NF-κB and VEGF in rat ankle joints in the administration groups was significantly down-regulated （P<0.05， P<0.01）， and the swertiamarin paired with clematichinenoside AR group had the most significant effect. ConclusionThe component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma exerts a good therapeutic effect on the rat model of RA， and the compatibility of components from the two medicines has a multi-channel， multi-target， and synergistic effect. The five component compatibility patterns， namely gentiobioside with magnoflorine， gentiobioside with clematichinenoside AR， sweroside with clematichinenoside AR， swertiamarin with magnoflorine， and swertiamarin with clematichinenoside AR， all have potential advantages. The mechanism may be related to the reduction of inflammatory factor secretion and the inhibition of abnormal protein and mRNA expression of NF-κB and VEGF.
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In this paper， through consulting relevant records in materia medica， medical and prescription books， and combining with modern literature， the name， origin， producing area， collection and processing of Gentianae Macrophyllae Radix in famous classical formulas from The Catalogue of Ancient Famous Classical Formulas （The First Batch） was systematically sorted out and textual research was carried out， in order to provide a basis for the development of the famous classical formulas containing Gentianae macrophyllae Radix. After textual research， it was found that Gentianae Macrophyllae Radix was the rectification of name in the past dynasties. In addition， there were other names such as Qinjiao， Qingua and Qinzhua. Gentiana macrophylla， G. straminea， G. dahurica and G. siphonantha were the main origin of this herb in ancient literature. Among them， G. macrophylla is the mainstream. In the Southern and Northern dynasties， G. straminea and G. macrophylla produced in northern Sichuan were recommended as the best. In the early Tang dynasty， G. macrophylla from the Liupan Mountain area at the border of Shanxi and Gansu provinces was the mainstream. During the Northern Song dynasty， G. siphonantha from Linxia and Qilian Mountain of Gansu province and G. macrophylla from eastern Shaanxi province were two new producing areas. In the Ming and Qing dynasties， the abundant base and production areas of Gentianae Macrophyllae Radix were gradually formed. In the past dynasties， harvesting was carried out in spring and autumn， and stored mainly by aeration drying or shade drying treatment. The processing methods are mainly the raw products after the net selection， cutting and drying， in addition to the frying， processing with wine and milk. G. macrophylla is recommended as the first choice for the herbal medicine involved in the famous classical formulas. Among them， wild products produced in Gansu and Shaanxi are the best， and raw products are recommended to be used. At the same time， it is suggested that G. siphonantha should be added to the subsequent edition of Chinese Pharmacopoeia as one of origins of Gentianae Macrophyllae Radix.
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Gentianae Macrophyllae Radix is a Chinese medicinal material with unique efficacy and rich resources, which is widely distributed in northwest China. Gentianae Macrophyllae Radix contains a variety of chemical components, including iridoids, lignans, flavonoids, triterpenes, alkaloids, and other components, with anti-inflammatory and analgesic, liver protection, anti-virus, anti-tumor, immunosuppression, antihypertensive and other activities. Because of its various chemical components and wide range of pharmacological activities, it can be used as a kind of medicinal plant with great development and utilization value. With the great increase in the demand for Gentianae Macrophyllae Radix resources, the wild Gentianae Macrophyllae Radix resources are extremely shrinking. There are many medicinal sources of Gentiana Macrophylla Radix, and the medicinal parts are different, resulting in mixed sources of Gentianae Macrophyllae Radix. Not only the medicinal ingredients are unstable, the market chaos is also very serious, and the quality standard needs to be improved urgently. Based on the analysis of the present situation of Gentianae Macrophyllae Radix resources, chemical composition and pharmacological action, combined with the concept of quality markers, the quality markers of Gentianae Macrophyllae Radix were predicted and analyzed from the aspects of chemical composition and traditional medicinal properties, traditional efficacy, clinical efficacy, different compatibility and so on, in order to provide reference for the establishment of quality evaluation system of Gentianae Macrophyllae Radix.
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Pre-formulation physicochemical properties of the component-based Chinese medicine of Qinqi Fengshi Fang were investigated to provide a research basis for the design of the dosage form for component-based Chinese medicine of Qinqi Fengshi Fang. The macroporous resin adsorption and refining technology was used to prepare the total glycosides extract of Gentianae Macrophyllae Radix, Panacis Majoris Rhizome and Corni Fructus respectively in the prescription of Qinqi Fengshi Fang. Their physicochemical properties were investigated, including solubility, wettability, hygroscopicity, equilibrium solubility, oil-water partition coefficient, and stability. The results showed that the total glycosides of Gentianae Macrophyllae Radix, Panacis Majoris Rhizome and Corni Fructus all had good solubility and wettability. The solubility index of each total glycoside component was greater than 85%, and the water absorption index was greater than 50%. In the range of pH 2.0-7.4, the equilibrium solubility of three kinds of total glycosides all increased with the increase of pH, showing a consistent change trend of solubility. The hydrophilicity was also suitable and similar. Overall, three kinds of total glycosides showed good stability, but strong hygroscopicity. The degree of hygroscopicity was as follows: total glycosides of Gen-tianae Macrophyllae Radix > total glycosides of Corni Fructus > total glycosides of Panacis Majoris Rhizome. Therefore, the hygroscopi-city needed to be considered in the preparation of the component-based Chinese medicine of Qinqi Fengshi Fang. The excipients and packaging materials can be properly selected to reduce the hygroscopicity of the preparation. This study provides a reference for the dosage form design of the component-based Chinese medicine of Qinqi Fengshi Fang.
Subject(s)
Cornus , Drugs, Chinese Herbal , Glycosides , Medicine, East Asian Traditional , RhizomeABSTRACT
Gentianae Macrophyllae Radix is a Chinese traditional Tibetan herb, belonging to Sect. Cruciata Gaudin of Gentiana genus. Which originated from Qinghai-Tibetan Plateau and adjacent regions and had significant pharmaceutical effect on lots of disease. In this review, we summarized the research advance studies on morphologic, biochemical, and genetic diversity on this species in the past 20 years, which could provide the help for germplasm protection, identification, and evolutionary adaptation works in the future.
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Objective:To establish the fingerprints of standard decoction of Gentianae Macrophyllae Radix-dried products by different methods,and to evaluate the quality correlation. Method:HPLC,InertSustain C18 chromatographic column(4.6 mm×250 mm,5 μm),Gradient elution was performed for the mobile phase of acetonitrile-phospho,detection wavelength at 240 nm and flow rate of 0.8 mL·min-1,and column temperature was 40℃. The quality correlation analysis of different methods for different kinds of Gentianae Macrophyllae Radix standard decoction was carried out from the aspects of chemical composition consistency,common chemical composition consistency,main chemical composition content and transfer rate. Result:The control fingerprint of Gentianae Macrophyllae Radix standard decoction was established. According to the peak matching data,there were 10 common peaks in the fingerprint of 15 batches of Gentianae Macrophyllae Radix standard decoction.Among the 10 common peaks,5 chemical constituents of loganic acid,6'-O-β-D-glucosyl gentiopicroside,swertiamarin,gentiopicroside and swertia glycosides were identified. The results of quality correlation analysis showed that the three different drying methods were consistent with the chemical composition and quantity of Gentianae Macrophyllae Radix standard decoction. But in terms of the content consistency of common chemical components and the transfer rate of main chemical components,the quality correlation between the products obtained from vacuum drying and the standard decoction was lower than that obtained from spray drying and freeze-drying. Conclusion:The fingerprint of different method of Gentianae Macrophyllae Radix standard decoction was established. Through the analysis of the mass correlation of chemical composition consistency,common chemical composition content consistency,main chemical composition content and transfer rate,the mass correlation between them was comprehensively reflected. It is suggested that spray drying or freeze drying should be used for the key drying process of Gentianae Macrophyllae Radix granules. This study provides a reference for the preparation process and quality control of Gentianae Macrophyllae Radix granules.
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Objective: To observe the effects of different combinations of Gentianae Macrophyllae Radix (Qinjiao) on the ankle joint matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) of rheumatoid arthritis (RA) model rats with wind-cold-dampness arthralgia.Method: Eighty healthy SD rats were randomly divided into 8 groups, namely blank control group, collage Ⅱ model group, wind-cold-dampness syndrome model group, positive control group, single-taste Gentianae Macrophyllae Radix group, Gentianae Macrophyllae Radix-Clematidis Radix et Rhizoma group (GC group), Gentianae Macrophyllae Radix-Taxilli Herba group (GT group), Gentianae Macrophyllae Radix-Stephanlae Tetrandrae Radix group (GS group), with 10 rats in each group. Rat model of wind-cold-dampness RA was induced through the injection with type Ⅱ collagen emulsion and wind-cold-dampness stimulation. After the establishment of the model, the blank control group, collage Ⅱ model group and wind-cold-dampness syndrome model group were given normal saline, and the corresponding liquid medicine was given to each administration group. In the experiment, the thickness of the left posterior metatarsal of rats was measured every 3 days, and the swelling degree of metatarsal was calculated. The arthritis index (AI) was evaluated on the 38th day of the experiment. The serum rheamatoid factor(RF) content of rats was detected by enzyme linked immunosorbent assay (ELISA). The expressions of MMP-3 and TIMP-1 in ankle joint were detected by Western blot. The expressions of MMP-3 and TIMP-1 mRNA in ankle joint were detected by real-time fluorescence quantitative PCR (Real-time PCR).Result: Compared with the blank group, the swelling degree, AI score, serum RF content, MMP-3 protein expression and MMP-3 mRNA expression in ankle joints of coll age Ⅱ model group and model wind-cold-dampness syndrome group were significantly increased (PPPPPPConclusion: For rheumatoid arthritis with wind-cold-dampness arthralgia, mild and warm traditional Chinese medicine (TCM) has a better effect than the combination of mild and cold TCM or mild TCM drugs. The experimental results are basically consistent with the principle of "treating cold diseases with hot medicine". The mechanism of the compatibility in treating rheumatoid arthritis due to wind-cold-dampness arthralgia may be related to the reduction of MMP-3, the increase of TIMP-1 expression and the reduction of articular cartilage damage.
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Gentianae Macrophyllae Radix, widely distributed in northwest districts of China, is rich in resources, and is a kind of medicinal plants with great utilization value. From the phytochemical view, the second metabolites such as secoiridoids, iridoids, lignans, flavonoids, and triterpenoids had been reported from this species. Its pharmacological research mainly focused on the anti- inflammatory and analgesic, hepatoprotective, hypotensive, antiviral, and antineoplastic activities. The present paper reviews the phytochemistry and biological activities of Gentianae Macrophyllae Radix through accessing Web of Science and multiple databases for biomedical sciences.
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Objective: To establish an HPLC fingerprint of Qinqi Rheumatism Formula (QRF) for its quality control and effective components determination. Methods: HPLC method was performed on Inert Sustain C18 (150 mm × 4.6 mm, 5 μm) column with gradient elution composed of acetonitrile-aqueous solution containing 0.1% phosphoric acid at the flow rate of 1.0 mL/min. The column temperature was set at 30℃, while the detective wavelength was set at 203 nm. The common mode of HPLC fingerprint for 10 batches of QRF was established with Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (2004 A edition) and the common peaks were identified by reference compounds. Results: Fingerprints of QRF were established. The similarities of the 10 batches of samples were above 0.99. A total of 19 common peaks were found. Eight mutual peaks were from Panacis Majoris Rhizoma, eight mutual peaks were from Gentianae Macrophyllae Radix, and five mutual peaks were from Corni Fructus (Peak 1 was the common peak from Panacis Majoris Rhizoma, Gentianae Macrophyllae Radix, and Corni Fructus). Based on the retention time of reference substances, eight constituents including loganic acid (peak 2), morroniside (peak 3), gentiopicroside (peak 5), loganin (peak 6), ginsenoside Ro (peak 12), ginsenoside F1 (peak 13), panax japonicus IVa (peak 14), and ginsenoside F2 (peak 17) were indentified. Conclusion: The method is stable, specific, and reproducible, and can be used for the quality control of QRF and the study of its effective components.
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Objective: To observe the effects of Gentianae Macrophyllae Radix (Qinjiao) in different combinations on the expression of MMP-3, TIMP-1, and ankle pathological changes in rheumatoid arthritis (RA) model rats, and to explore the relationship between medicinal properties-disease-efficacy and explore the mechanism of traditional Chinese medicine in the treatment of RA. Methods: Eighty SD rats were randomly divided into blank group, collage II model group, rheumatic fever model group, tripterygium group, single Qinjiao group, Qinjiao-Weilingxian (Clematidis Radix et Rhizoma) group, Qinjiao-Sangjisheng (Taxilli Herba) group, and Qinjiao-Fangji (Stephanlae Tetrandrae Radix) group. Rheumatic fever arthralgia model was induced by collage II and exposed in rheumatic fever environment. After modeling, each administration group was ig administrated with corresponding drug solution. The paw thickness was observed every 3 d, and swelling was calculated; The arthritis index was scored in the early, middle, and late stages. Rats were sacrificed on day 39. The expression of MMP-3 and TIMP-1 in the ankle joint of rats was detected by immunohistochemistry, and the pathological changes of ankle joint were observed by HE staining. Results: Compared with the blank group, the paw edema, AI, and expression of MMP-3 in collage II model group and rheumatic fever model group was significantly higher, the expression of TIMP-1 were significantly lower, the articular surface of two groups was rough and damaged, and the articular cartilage was severely damaged. A large number of granulation tissues proliferated, accompanied by a large number of inflammatory cell infiltration and neovascularization. After treatment, compared with rheumatic fever model group, the paw edema, AI, and expression of MMP-3 in all treatment groups were reduced to varying degrees, in which the Qin-Fang group were lower most significant; The serum levels of TNF-α and IL-1β in all treatment groups were significantly decreased in varying degrees, especially in the Qin-Fang group; The expression of TIMP-1 was significantly increased in varying degrees, especially in the Qin-Fang group. HE staining results showed that the area of articular cartilage destruction and the degree of destruction were reduced, the inflammatory cells and neovascularization decreased, the number of repair fibers increased, and the scar tissue increased. Conclusion: For the rheumatic fever arthralgia RA, the combined effect of mild and cold Chinese materia medica (CMM) is better than the combined effect of mild and warm CMM, the combined effect of mild CMMs. Experimental results are consistent with the principles of traditional Chinese medicine clinical treatment of "treating the hot diseases should use the cold medicine", the mechanism of the compatibility drug relieving rheumatic fever arthralgia RA may be related to its ability, which can reduce the expression of MMP-3, increase the expression of TIMP-1, reduce articular cartilage destruction, and reduce inflammatory cell infiltration and vascular proliferation.
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Objective: To study the effects of Gentianae Macrophyllae Radix in cold and heat compatibility in rheumatic fever arthralgia rheumatoid arthritis (RA) model rats by principal component analysis and cluster analysis. Methods: Eighty SD rats were randomly divided into blank group, collage II model group, rheumatic fever arthralgia model group, tripterygium group, single Qinjiao group, Qinjiao-Weilingxian (Clematidis Radix et Rhizoma) group, Qinjiao-Sangjisheng (Taxilli Herba) group, and Qinjiao-Fangji (Stephaniae Tetrandrae Radix) group; rheumatic fever arthralgia model were induced by collage II and being exposed in rheumatic fever environment, each administration group was gavaged with 15 mL/kg corresponding drug solution after modeling. The weight, paw thickness, arthritis index, pain threshold, cold pain tolerance time and pressure pain tolerance value were measured. The serum contents of RF, CRP, TNF-α, IL-1β, and PGE2 were detected by ELISA. Results: Principal component analysis selected two principal components, which carried 89.6% of the original information, the first principal component reflected all information in expect weight, the second principal component mainly reflected the weight. The total factor score F (the greater the F value, the more severe the disease) was obtained by the sum of the principal component factor score and its weight (variance contribution) product. The F value of rheumatic fever arthralgia model group was the highest and the score of the blank group was the lowest, the F value of Qin-Fang group was significantly lower than those of Qin-Wei group and Qin-Sang group. Cluster analysis divided eight groups into three categories according to the blank, model and administration, which was consistent with the theory; In the control group, Qin-Fang group was clustered into one group, and the other groups were clustered into one group. Conclusion: For the rheumatic fever arthralgia RA, the combined effect of mild and cold traditional Chinese medicine (TCM) is better than the combined effect of mild and warm TCM and the combined effect of mild TCMs. Experimental results are consistent with the principles of TCM clinical treatment of "treating the hot diseases should use the cold medicine"; Principal component analysis and cluster analysis are simple and reliable, and can be used to evaluate the animal model and drug efficacy.
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The study is aimed to analyze the commercial specifications and grades of wild and cultivated Gentianae Macrophllae Radix based on multi-indicative constituents. The seven kinds of main chemical components containing in Gentianae Macrophyllae Radix were determined by UPLC, and then the quality levels of chemical component of Gentianae Macrophyllae Radix were clustered and classified by modern statistical methods (canonical correspondence analysis, Fisher discriminant analysis and so on). The quality indices were selected and their correlations were analyzed. Lastly, comprehensively quantitative grade division for quality under different commodity-specifications and different grades of same commodity-specifications of wild and planting were divided. The results provide a basis for a reasonable division of specification and grade of the commodity of Gentianae Macrophyllae Radix. The range of quality evaluation of main index components (gentiopicrin, loganin acid and swertiamarin) was proposed, and the Herbal Quality Index (HQI) was introduced. The rank discriminant function was established based on the quality by Fisher discriminant analysis. According to the analysis, the quality of wild and cultivated Luobojiao, one of the commercial specification of Gentianae Macrophyllae Radix was the best, Mahuajiao, the other commercial specification, was average , Xiaoqinjiao was inferior. Among grades, the quality of first-class cultivated Luobojiao was the worst, of second class secondary, and the third class the best; The quality of the first-class of wild Luobojiao was secondary, and the second-class the best; The quality of the second-class of Mahuajiao was secondary, and the first-class was the best; the quality of first-class Xiaoqinjiao was secondary, and the second-class was the better one between the two grades, but not obvious significantly. The method provides a new idea and method for evaluation of comprehensively quantitative on the quality of Gentianae Macrophyllae Radix.
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The 79 samples of Gentianae Macrophyllae Radix were collected based on the distributed information by document literature. Based on sample information, and using the regression model of Gentianae Macrophyllae Radix index component and environmental factors, and combined with the prediction results of ecological suitability by MaxEnt and principal component analysis results of index component, the space distribution of Gentianae Macrophyllae Radix was estimated with the spatial analysis function of ArcGIS. The results showed that it had a higher comprehensive quality in south of Shaanxi, south of Gansu, middle of Sichuan and southeast of Xizang. The study results were coinciding with the producing regions of Gentianae Macrophyllae Radix. It can provide reference for Gentianae Macrophyllae Radix resource conservation, development and utilization.