UPLC-Q-TOF/MS analysis of chemical components of single decoction and combined decoction of Qige decoction reveals the differences between various preparation processes.

The aim of this work was to explore the differences between various pharmaceutical processes in combined solutions of a single decoction (QGHBY) and a combined decoction (QGHJY) of Qi-Ge decoction from the perspective of chemical composition changes, so as to further guide the clinical application of drugs. A combined solution of a single decoction and a combined decoction of Astragali Radix, Puerariae Lobatae Radix and Citri Reticulatae Chachiensis Pericarpium was prepared with the same technological parameters. The chemical components of the two were detected and identified based on UPLC-Q-TOF/MS, and the different components were determined by principal component analysis. Eighty-eight compounds were identified in the pharmaceutical solution of Qi-Ge decoction. Principal component analysis revealed 11 different components of QGHBY and QGHJY with the conditions of Variable Importance in Projection (VIP) ≥ 1, fold change ≥ 2 and p < 0.05, among which hesperidin, hesperitin, isosinensetin, sinensetin and 5-demethylnobiletin were the components of Citri Reticulatae Chachiensis Pericarpium. The levels of these 11 different components in QGHJY were higher than those of QGHBY. The combined decoction is beneficial for the dissolution of flavonoids and other chemical components, and there is a significant difference in the content of chemical components between modern herbal concentrate granules and traditional decoctions.

[Equivalence of combined decoction and mixed single decoctions of Gegen Qinlian Decoction in alleviating chemotherapy-associated diarrhea].

This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.

Equivalence of combined decoction and mixed single decoctions of Gegen Qinlian Decoction in alleviating chemotherapy-associated diarrhea / 中国中药杂志

This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.

Comparative Analysis of Effect of Houpu Wenzhongtang Combined Decoction and Simple Decoction on Urine Metabonomics of Rats with Deficiency-cold of Spleen and Stomach / 中国实验方剂学杂志

Objective:To study the effect of combined decoction and single decoction of Houpu Wenzhongtang on rats with deficiency-cold of spleen and stomach from the perspective of metabonomics, to find out the relevant potential biomarkers and metabolic pathways, and to explore the similarities and differences between the combined decoction and single decoction, so as to provide reference for the feasibility analysis of replacing traditional decoction with single dispensing granule of this formula. Method:SD rats were randomly divided into normal group, model group, Houpu Wenzhongtang combined decoction group and simgle decoction group. Rats in the normal group were given distilled water by intragastric administration, rats in the other three groups were given cold vinegar at 4 ℃ in the morning and refined lard in the afternoon for 10 days (the dosage of 10 mL·kg-1). After the model was successfully established, rats in the combined decoction group and the single decoction group were given corresponding decoction with dosage of 1.8 g·kg-1 (according to the amount of crude drugs), once a day for 7 days. Ultra-high liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) technique was used to analyze the small molecular endogenous metabolites in urine. Orthogonal partial least squares-discriminant analysis (OPLS-DA) and principal component analysis (PCA) were used to compare the changes of differential metabolites among the normal group, model group, Houpu Wenzhongtang combined decoction group and single decoction group, and the differential metabolites were introduced into Kyoto Encyclopedia of Genes and Genomes (KEGG) for metabolic pathway analysis. Result:Compared with the model group, the Houpu Wenzhongtang combined decoction group and single decoction group jointly regulated 13 potential biomarkers, including phosphatidylcholine(PC), lysophosphatidic acid(LysoPA) and cholic acid, etc. They played a role in treating deficiency-cold of spleen and stomach by influencing metabolic pathways such as glycerophospholipid metabolism, glycerolipid metabolism, phosphatidylinositol signaling system and so on. The combined decoction and single decoction of Houpu Wenzhongtang could obviously restore the body weight, motilin and gastrin contents of rats with deficiency-cold of spleen and stomach to normal levels. Conclusion:According to biochemical indexes, there is no obvious difference between combined decoction and single decoction of Houpu Wenzhongtang, but according to metabonomics, the combined decoction may be slightly better than the single decoction. The research shows that it is feasible to replace traditional decoction with single dispensing granule of Houpu Wenzhongtang in clinical application.

Difference of Copper ，Lead，Cadmium，Mercury and Arsenic in the Single Decoction and Combined Decoction of Huangqi Jianzhong Decoction / 中国药房

OBJECTIVE： To study the difference of the contents of copper， lead， cadmium， mercury and arsenic in the single decoction and combined decoction of Huangqi jianzhong decoction （containing Astragali radix， Cinnamomi ramulus， Paeoniae radix alba， prepared Glycyrrhiza uralensis， Zingiberis rhizoma recens， Jujubae fructus）， and to provide reference for safe use of TCM in clinic. METHODS： Samples of medicinal materials， single decoction and combined decoction were prepared from different medicinal materials； the contents of copper， lead， cadmium， mercury and arsenic in various samples were determined by atomic absorption spectrophotometry， which were compared with the limits of copper （＜20 mg/kg）， lead （＜5 mg/kg）， cadmium （＜0.3 mg/kg）， mercury （＜0.2 mg/kg） and arsenic （＜2 mg/kg） content stated in 2015 edition of Chinese Pharmacopeia and Green Trade Standards of Importing Exporting Medicinal Plants Preparations. The difference of 5 elements contents were compared between single decoction and combined decoction. RESULTS： Among the 6 medicinal materials， the cadmium content of Cinnamomi ramulus and Zingiberis rhizoma recens exceeded the standard， 0.32， 0.74 mg/kg， respectively （copper， lead， mercury and arsenic all met the requirements）， and the 5 elements content of other medicinal materials all met the requirements； the contents of copper， lead， cadmium， mercury and arsenic in the single and combined decoction meet the requirements； compared with the medicinal materials， the contents of copper， lead， cadmium， mercury and arsenic in the single decoction were lower （P＜0.01）； compared with mixture of single decoction， the contents of copper and mercury in combined decoction were lower （P＜0.01）， while the contents of lead， cadmium and arsenic in the decoction were higher （P＜0.01）. CONCLUSIONS： For Huangqi jianzhong decoction， combined decoction can reduce the dissolution of copper and mercury， and increase the dissolution of lead， cadmium and arsenic. The possible reason is that the interaction of various components in the co-decoction process changes the solubility of copper， lead， cadmium， mercury and arsenic.

Current situation and new ideas on future trends of Chinese materia medica granules for prescriptions / 中草药

Chinese materia medica (CMM) granules for prescriptions is one of the improved products of decoction pieces, which is easy to use its most prominent advantage. However, lack of unified quality standards, non-systematic basic research on equivalences that is difficult to evaluate the equivalence on ingredients and treatment outcome between granules for prescriptions from single decocting and traditional decoction from combined decocting, which are the most prominent problems and controversial issues. Therefore, establishing unified and perfect national standards, achieving quality control and standardized management throughout the whole process, carrying out systematic treatment outcome equivalence comparison research between combined decoction and single decoction, developing (compound) granules of classical prescriptions, strengthening treatment guidance by traditional Chinese medicine (TCM) theory, and realizing extraction on the place of origin will be conducive in ensuring safety and efficacy of CMM granules for prescriptions, promoting healthy and sustainable development of the industry, and leading TCM into the world. Through understanding the history and present situation of CMM granules for prescriptions, analyzing deeply its advantages, existing problems and controversies, the new ideas for future development are proposed.

Chemical composition differentiation of Shen-Shuai-Ning granule between combined decoction and separated decoction using HPLC-DAD-ESI-QTOF-MS.

Shen-Shuai-Ning (SSN) granule, a traditional Chinese medicine formula, is widely used in clinical practice for treating chronic renal failure. However, its detailed chemical profile is unknown. Here, HPLC-ESI-QTOF-MS was employed for the systematic chemical analysis of SSN. A total of 52 compounds were identified and the characteristic ions of the compounds were described. Furthermore, chemical consistency between the combined decoction and the separated decoction of SSN was evaluated using HPLC-DAD. A chemical comparison between two preparations of SSN granule (combined decoction and separated decoction of Coptides Rhizoma) indicated a significant difference in the content of many compounds, including salvianolic acid A, salvianolic acid B, berberine, palmatine and epiberberine. As a result, separated decoction of Coptides Rhizoma would lead to a significantly decrease in depsides in Salviae Miltiorrhizae Radix et Rhizoma and an increase in alkaloids in Coptidis Rhizoma.

Comparative Study on Decoction Rates of Active Ingredients in Volatile Oil after Curcuma phaeocaulis Sin-gle Decoction and Combined Decoction with Sparganium stoloniferum / 中国药房

OBJECTIVE:To study the decoction rate changes of 4 active ingredients in the volatile oil of Curcuma phaeocaulis before and after combined with Sparganium stoloniferum,and provide reference for showing the compatibility mechanism of C. pha-eocaulis and S. stoloniferum. METHODS:HPLC was used to simultaneously determine the contents of 4 active ingredients(curdi-one,curcumol,germacrone and β-elemene) in the volatile oil of C. phaeocaulis after C. phaeocaulis single decoction and com-bined decoction with S. stoloniferum. And the fried rates of each ingredient were compared. RESULTS:Compared with C. phaeo-caulis single decoction,there was significant difference in the fried amounts of curdione,curcumol,germacrone in the volatile oil after combined decoction(P0.05). CONCLUSIONS:The com-bined decoction of C. phaeocaulis and S. stoloniferum can effectively improve the dissolution of curdione,curcumol,germacrone in the volatile oil. It may be the reason for the enhancement of efficacy after compatibility.

Decoction Amount Changes of Verbascoside and Gallic Acid in Single Decoction and Combined Decoction of Rehmanniae Radix Preparata,Corni Fructus and Poria / 中国药房

OBJECTIVE:To investigate the decoction amount changes of verbascoside,gallic acid in single decoction and com-bined decoction of rehmanniae radix preparata,corni fructus and poria,and provide scientific basis for further study of effective substance basis. METHODS:The single decoction,combined decoction with each 2 medicine and combined decoction with the 3 medicines of rehmanniae radix preparata,corni fructus and poria,were respectively prepared. HPLC was adopted to detect and com-pare the decoction amount of active component verbascoside in rehmanniae radix preparata and active component gallic acid in cor-ni fructus in each group. RESULTS:Compared with single decoction of rehmanniae radix preparata,the decoction amount of ver-bascoside was decreased in combined decoction of poria+rehmanniae radix preparata(P<0.01),decoction amount of verbascoside was increased in combined decoction of corni fructus+rehmanniae radix preparata or combined decoction with the 3 medicines(P<0.01). Compared with single decoction of corni fructus,the decoction amount of gallic acid in each combined decoction was de-creased (P<0.01). CONCLUSIONS:The combined decoction of rehmanniae radix preparata,corni fructus and poria has certain promotion and inhibition effects on the decoction of verbascoside in rehmanniae radix preparata and inhibition effect on the decoc-tion of gallic acid in corni fructus. It is speculated verbascoside may be one of the main components in combined decoction playing the role of effectiveness.