Experimental study of cardioprotective effects of Cinnamomi Ramulus and Cinnamomi Cortex formula granules on myocardial ischemia/reperfusion injury in rats based on efficacy of "warming and coordinating heart Yang" / 中国中药杂志

This study aimed to parallelly investigate the cardioprotective activity of Cinnamomi Ramulus formula granules(CRFG) and Cinnamomi Cortex formula granules(CCFG) against acute myocardial ischemia/reperfusion injury(MI/RI) and the underlying mechanism based on the efficacy of "warming and coordinating the heart Yang". Ninety male SD rats were randomly divided into a sham group, a model group, CRFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, and CCFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, with 15 rats in each group. The sham group and the model group were given equal volumes of normal saline by gavage. Before modeling, the drug was given by gavage once a day for 7 consecutive days. One hour after the last administration, the MI/RI rat model was established by ligating the left anterior descending artery(LAD) for 30 min ischemia followed by 2 h reperfusion except the sham group. The sham group underwent the same procedures without LAD ligation. Heart function, cardiac infarct size, cardiac patho-logy, cardiomyocyte apoptosis, cardiac injury enzymes, and inflammatory cytokines were determined to assess the protective effects of CRFG and CCFG against MI/RI. The gene expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3(NLRP3) inflammasome, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate specific proteinase-1(caspase-1), Gasdermin-D(GSDMD), interleukin-1β(IL-1β), and interleukin-18(IL-18) were determined by real-time quantitative polymerase chain reaction(RT-PCR). The protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD were determined by Western blot. The results showed that both CRFG and CCFG pretreatments significantly improved cardiac function, decreased the cardiac infarct size, inhibited cardiomyocyte apoptosis, and reduced the content of lactic dehydrogenase(LDH), creatine kinase MB isoenzyme(CK-MB), aspartate transaminase(AST), and cardiac troponin Ⅰ(cTnⅠ). In addition, CRFG and CCFG pretreatments significantly decreased the levels of IL-1β, IL-6, and tumor necrosis factor-α(TNF-α) in serum. RT-PCR results showed that CRFG and CCFG pretreatment down-regulated the mRNA expression levels of NLRP3, caspase-1, ASC, and downstream pyroptosis-related effector substances including GSDMD, IL-18, and IL-1β in cardiac tissues. Western blot revealed that CRFG and CCFG pretreatments significantly decreased the protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD in cardiac tissues. In conclusion, CRFG and CCFG pretreatments have obvious cardioprotective effects on MI/RI in rats, and the under-lying mechanism may be related to the inhibition of NLRP3/caspase-1/GSDMD signaling pathway to reduce the cardiac inflammatory response.

Preparation and Quality Control of Cinnamomi Ramulus Formula Granules based on Traditional Standard Decoction / 中国药学杂志

OBJECTIVE: To prepare Cinnamomi Ramulus standard decoction according to the traditional decoction method, and study the preparation process and quality control of Cinnamomi Ramulus formula granules. METHODS: The standard decoctions of 16 batches of Cinnamomi Ramulus were prepared using decocting pot. The extracting rate, contents and transfer rates of cinnamic acid and cinnamaldehyde were calculated. The preparation process of Cinnamomi Ramulus dispensing granules was improved based on the parameters of standard decoction. The volatile oil was collected while extracting, and the β-cyclodextrin inclusion technology was applied in the granulation process. Based on the parameters of standard decoction, the quality standard of Cinnamomi Ramulus formula granules was established. RESULTS: The extracting rate of Cinnamomi Ramulus standard decoction was 3.58%-6.10%; the cinnamic acid content was 0.99%-2.59% and the transfer rate was 39.56%-62.28%; while the cinnamaldehyde content was 1.95%-4.69% and the transfer rate was 4.76%-7.85%. According to the standard decoction, 1 g of Cinnamomi Ramulus formula granules was equivalent to 14 g of pieces, containing cinnamic acid (0.50%-1.43%) and cinnamaldehyde (0.98%-3.50%). Six characteristic peaks in specific spectra were confirmed, including protocatechuic acid (1), coumarin (2), cinnamic acid (3), 2-methoxycinnamic acid (4), cinnamaldehyde (5) and 2-methoxycinnamaldehyde (6). CONCLUSION: In this study, the quality parameters of Cinnamomi Ramulus standard decoction are determined by traditional decocting pot. The strategy of establishing the preparation process and quality standard of Cinnamomi Ramulus formula granules based on standard decoction is proposed. It can provide reference for the research of Cinnamomi Ramulus dispensing granules and other Chinese medicine preparations containing volatile oil.

Study on chemical constituents of Cinnamomi Ramulus / 中国中药杂志

The chemical constituents of Cinnamomi Ramulus were investigated in this study. Twenty-two compounds were isolated by silica gel, Sephadex LH-20 gel column chromatographies and preparative HPLC and their structures were identified by various spectral analyses as dihydrorosavin(1), rosavin(2), 1-phenyl-propane-1,2,3-triol(3), patchoulol(4), graphostromane B(5),(+)-lyoniresinol-3 a-O-β-D-glucopyranoside(6),(-)-lyoniresinol-3 a-O-β-D-glucopyranoside(7), cinnacaside(8), subaveniumin A(9), 3-phenyl-2-propenyl-6-O-L-arabinopyranosyl-β-glucopyranoside(10), 2-phenylethyl-β-vicianoside(11), cinnacasol(12), [(2R,3S,4S,5R,6R)-6-(benzyloxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl] methyl hydrogen sulfate(13), coniferyl aldehyde(14),(2R,3R)-5,7-dimethoxy-3',4'-methylenedioxyflavan-3-ol(15), cinnacassin L(16), E-cinnamic alcohol(17),(E)-3-(2-methoxyphenyl)-2-propen-1-ol(18), 2-hydroxyphenylpropanol(19), cinnamomulactone(20),(+)-syringaresinol(21) and cinnamomumolide(22), respectively. Among them, 1 is a new compound and 3-7, 9-11, 13, 15, 18 and 19 were isolated from the plant for the first time.

Research Process on Chemical Constituents and Pharmacological Effect of Four Kinds of Couplet Medicine of Cinnamomi Ramulus / 中国实验方剂学杂志

Cinnamomi Ramulus is a dry tender branch of <italic>Cinnamomum cassia</italic> Presl, which is a multifunctional traditional Chinese medicine(TCM). Cinnamomi Ramulus has different efficacy under different compatibility environment. Complet medicine is a commonly used and relatively fixed compatibility form of two drugs, and it is the smallest unit in the compatibility of TCM. The four kinds of complet medicine commonly used in Cinnamomi Ramulus were as follows: the diaphoretics pungent in flavour and warm in property pairs include Cinnamomi Ramulus Ephedrae Herba and Cinnamomi Ramulus Bupleuri Radix complet medicine. The stasis dredge collaterals pairs involve Cinnamomi Ramulus Poria and Cinnamomi Ramulus Persicae Semen complet medicine. The regulation Qi and Blood Cinnamomi Ramulus Paeoniae Radix Alba complet medicine. Wenda Tongyang pairs consist of Cinnamomi Ramulus Aconiti Lateralis Radix Praeparaia, Cinnamomi Ramulus Astragali Radix, and Cinnamomi Ramulus Glycyrrhizae Radix et Rhizoma complet medicine. After compatibility, some changes have taken place in the chemical composition of complet medicines. For example, after compatibility of Cinnamomi Ramulus and Ephedrae Herba, the content of effective components of both herbs decreases, and the chemical constituents that are not found in single herbs are produced. After compatibility of Cinnamomi Ramulus and Bupleuri Radix, the dissolution of active ingredients is related to compatibility ratio. The active ingredients of Cinnamomi Ramulus Poria, Cinnamomi Ramulus Paeoniae Radix Alba pair and Cinnamomi Ramulus Aconiti Lateralis Radix Praeparaia have also changed to some extent.The content of active ingredients in Astragali Radix and Glycyrrhizae Radix et Rhizoma both increase after compatibility with Cinnamomi Ramulus. Different complet medicine have different pharmacological effects, Cinnamomi Ramulus Ephedrae Herba complet medicine have the effect of transpiration and antipyretic, Cinnamomi Ramulus Bupleuri Radix complet medicine can analgesia. Cinnamomi Ramulus Poria complet medicine have the effect of diuretic, improve myocardial ischemia and so on. Cinnamomi Ramulus Persicae Semen complet medicine have the anti-coagulation action.Cinnamomi Ramulus Paeoniae Radix Alba complet medicine have the anti-inflammatory and analgesic activities. Cinnamomi Ramulus Aconiti Lateralis Radix Praeparaia complet medicine have the effect of dispelling cold to relieve pain. Cinnamomi Ramulus Astragali Radix complet medicine have the many effects in relieving anti-coagulation, antioxidation and anti-myocardial ischemia. Cinnamomi Ramulus Glycyrrhizae Radix et Rhizoma complet medicine displays diverse activities, including antiarrhythmic, antithrombosis. In this paper, the chemical constituents and pharmacology of four kinds of complet medicine of Cinnamomi Ramulus were reviewed, which provided a reference for the better open utilization of Cinnamomi Ramulus complet medicine.

Q-marker prediction analysis of Cinnamomi Ramulus in Danggui Sini Decoction based on fingerprint and network pharmacology / 中草药

Objective: To analyze and predict the Q-marker of Cinnamomi Ramulus in Danggui Sini Decoction based on fingerprint and network pharmacology. Methods: The fingerprints of Cinnamomi Ramulus Decoction and Danggui Sini Decoction were established, and analyzed by using the similarity evaluation system software for chromatographic fingerprint of traditional Chinese medicine (2012 edition); The network pharmacology was used to screen and analyze the function target and pathway of related components of Cinnamomi Ramulus, and the "component-target-pathway" network was constructed to predict the potential Q-marker of Cinnamomi Ramulus in Danggui Sini Decoction. Results: The fingerprints of 15 batches of Cinnamomi Ramulus Decotion and 15 batches of Danggui Sini Decoction were established. The similarity of fingerprints was more than 0.96, and seven common components were identified, including protocatechuic acid, coumarin, cinnamic acid, cinnamaldehyde, cinnamyl alcohol, 2-methoxy cinnamic acid, and 2-methoxy cinnamaldehyde. A total of five active components, seven core target sites and 15 key pathways of Cinnamomi Ramulus were screened out through network pharmacology system, and based on the "Five Principles" of quality markers, 2-methoxy cinnamaldehyde, cinnamaldehyde, and cinnamic acid were predicted as potential quality markers. Conclusion: In this study, the quality markers of Cinnamomi Ramulus in Danggui Sini Decoction are analyzed by fingerprint and network pharmacology, which provides a basis for comprehensive control of the quality of Danggui Sini Decoction, reference for further study on the mechanism of Danggui Sini Decoction, and demonstration for the correlation study of quality markers of compound and single medicine in the classic prescription.

Molecular docking combined with network pharmacology to study molecular mechanism of Guizhi Shaoyao Zhimu Decoction in treatment of rheumatoid arthritis / 中草药

Objective: To predict the active constituents and targets of Guizhi Shaoyao Zhimu Decoction (GSZD) in the treatment of rheumatoid arthritis by using molecular docking and network pharmacology, and to analyze the effect of multi component-multi target-multi pathway combined with the theory of compatibility of TCM prescriptions. Methods: The main chemical constituents of nine kinds of Chinese herbal medicines (Cinnamomi Ramulus, Paeoniae Radix Alba, Anemarrhenae Rhizoma, Glycyrrhizae Radix et Rhizoma, Ephedrae Herba, Zingiberis Rhizoma Recens, Atractylodis Macrocephalae Rhizoma, Saposhnikoviae Radix and Aconiti Lateralis Radix Praeparata) were collected from TCMSP, TCM-Datebas@Taiwan and PubChen Compound database. The protein targets to the treatment of rheumatoid arthritis are found through DrugBank and TTD databases and uploaded to the String online database to build the network relationship of protein interaction. Appropriate crystal structures of protein targets were downloaded from PDB database, and molecular docking between compounds and targets was performed by using Discovery studio 4.5.0 software. A drug-compound-target visualization network was constructed by using Cytoscape 3.6.1 software to elucidate the main mechanism of GSZD against rheumatoid arthritis. Results: The results of molecular docking showed that there were 316 potential anti-arthritis active components in GSZD, acting on 26 targets, among which MAPK1, ZADH2, P38, AKR1C2, DHODH, CA2, MMP3, MMP9, RANKL, and other proteins were the main targets. Biological function and pathway analysis indicated that the mechanism of GSZD mainly involved in bone absorption (28%), histone kinase activity (20%), peptide tyrosine phosphorylation (20%), prostaglandin metabolism (12%), and other biological processes. The main pathway was osteoclast differentiation (94.12%). Conclusion: In this study, molecular docking combined with network pharmacology was used to study the pharmacodynamic material basis and molecular mechanism of GSZD in the treatment of rheumatoid arthritis from the perspective of multi-target and multi-approach, providing reference and basis for better clinical use.

Isolation and Identification of Chemical Constituents from Cinnamomi Ramulus / 中国实验方剂学杂志

Objective:The research group found in the early stage that the 75%alcohol extract of the Cinnamomi Ramulus had a significant physiological activity in inhibiting necroptosis by screening out the self-built sample library of 100 kinds of traditional Chinese medicines in Jiangxi. To identify the active components and find the target compounds,the 75%alcohol extracts of Cinnamomi Ramulus were isolated and studied systemically in chemistry. Method:The 20 kg dry Cinnamomi Ramulus was crushed into coarse powder,and extracted with 75%alcohol for four times, one time every 7 d. Then total extracts were obtained after solvent was recycled under decompression. The extract was separated by D101 macroporous resin column chromatography and eluted by water,30%ethanol,50%ethanol,70%ethanol,90%ethanol,so as to get the corresponding fraction finally. The compounds in the 30%ethanol and 50%ethanol fraction were isolated and purified by chromatography on silica gel,Sephadex LH-20 column and high pressure preparative chromatography,and their structures were determined according to physicochemical properties and spectral analysis. Result and Conclusion:Thirteen compounds were isolated and identified as (+)-syringaresinol (1),(+)-lyoniresinol (2),spicatolignan B (3),(-)-secoisolariciresinol (4),ovafolinin B (5),protocatechualdehyde (6),protocatechuic acid (7),syringaldehyde (8),vanillic acid (9),ethyl protocatechuate (10),syringic acid (11),ethyl gallate (12),2-(3',4'-dihydroxyphenyl)-1,3-pepper ring-5-aldehyde (13). Compounds 1-5,10-13 were isolated from this plant for the first time.

Traditional Chinese Medicine Cognition and Modern Pharmaceutical Research on Effect of Cassia Twig and Cinnamomum Cassia in Treating Paralysis / 中国实验方剂学杂志

Cinnamomi Ramulus and Cinnamomi Cortex are widely used to treat paralysis in traditional Chinese medicine (TCM). There are numerous and complicated relative records in ancient literatures. Doctors often use Cinnamomi Ramulus to dispel wind and cold, remove blood stasis and combine with warm-natured and heat-natured herbs to treat excess paralysis and early-stage paralysis. And Cinnamorni Cortex is used to warm and invigorate kidney Yang and combine with warm-benefiting herbs to treat deficiency paralysis and chronicle paralysis. However, modern pharmaceutical studies reported that their active substances are almost the same. The active substances in Cinnamomi Cortex are more than those in Cinnamomi Ramulus. The mechanisms of treating paralysis include:suppressing inflammation and regulating immunity by down-regulating nuclear factors(NF)-κB, mitogen activated protein kinase(MAPK), Janus kinase-signal transducers/activators of transcription(JAK/STAT) signaling pathways, regulating cell proliferation by inhibiting the proliferation of fibroblasts, osteoclasts and bone marrow mesenchymal stem cells and promoting the proliferation of osteoblast, resisting oxidation by scavenging oxygen free radicals, regulating pain by mediating TRPA1 and TRPV1,and enhancing substance metabolism and losing weight by regulating the secretion of intestinal hormones (Ghrelin, GLP-1) and improving insulin resistance. The main active ingredient Cinnamaldehyde is unstable in vivo and easily oxidized to cinnamic acid. The toxicity of the two medicines and their components are relatively low. This paper reviews and analyses relative records in ancient literatures, traditional Chinese medicine cognition of their effects in treating paralysis, the achievements and problems of chemical,pharmacological,pharmacokinetic and toxicological researches in recent years, with the aim to provide theoretical basis for further research and application.

Chemical constituents of carboxylic acid and its derivatives in Cinnamomi Ramulus / 中草药

Objective To investigate the chemical constituents of Cinnamomi Ramulus. Methods Silica gel, Sephadex LH-20 column, and sp-HPLC chromatographies were applied to separate and purify the chemical constituents, followed by various spectral analyses to determine the chemical structures. Results Fifteen carboxylic acids and its derivatives were isolated, and their structures were identified as guizhi acid A (1), dihydrophaseic acid (2), rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo [3,2,1]-oct- 8-yl)-3-methyl-2Z,4E-pentadienoic acid (3), vanillic acid (4), syringic acid (5), 4-hydroxybenzoic acid (6), E-cinnamic acid (7), E-o-hydroxycinnamic acid (8), erythro-guaiacylglycerol-8’-vanillic acid ether (9), salicylic acid (10), decumbic acid (11), hydroxyphenylpropionic acid (12), protocatechuic acid (13), E-melilotoside (14), and cryptamygin-B (15), respectively. Conclusion Fifteen compounds were successfully identified from Cinnamomi ramulus, among which 1 is a new compound and compounds 2, 3, 9-12 are isolated from the plant for the first time.

Establishment of UPLC/Q-TOF-MS chromatographic fingerprint of triterpenoic acids in Guizhi Fuling Capsule / 中草药

Objective: To construct the fingerprint of the triterpenoic acid in Guizhi Fuling Capsule (GFC) by UPLC/Q-TOF-MS, and give a new method for its quality control. Methods: The triterpenoic acid were isolated by UPLC and detected by Q-TOF- MS. The established fingerprint was an atlas of UPLC/Q-TOF-MS. Results: The UPLC/Q-TOF-MS fingerprints of triterpenoids in GFC were established, which preserved high precision, selectivity, and specificity. A total of 26 common peaks were selected as the fingerprint peaks of GFC, of which a total of 18 mutual peaks (3, 5-18, 20, 23, and 24) from Poria, peak 2 was from Paeoniae Radix Alba and Moutan Cortex. Peak 4 was from Poria, Moutan Cortex, Paeoniae Radix Alba, and Cinnamomi Ramulus. Peak 19 was from Moutan Cortex, Paeoniae Radix Alba, and Cinnamomi Ramulus, peak 21 was from Moutan Cortex and Paeoniae Radix Alba, peaks 22 and 25 were from Poria, Moutan Cortex, Persicae Semen, Paeoniae Radix Alba, and Cinnamomi Ramulus, peak 26 was from Cinnamomi Ramulus, Paeoniae Radix Alba, and Persicae Semen. The similarity among the 10 batches of GFC was above 0.90. The Results: of validation met technical requirement of fingerprints. Sixteen chemical components were identified by UPLC-Q-TOF-MS, which were 16α-hydroxydehydrotrametenolic acid, 16α-hydroxychalcic acid, 3-oxo-6,16α-dihydroxy-lanosta-7,9(11),24(31)-trien-21- oic acid, dehydrotumulosic acid, tumulosic acid, 3-oxo-6,16α-dihydroxy-lanosta-8,24-diene-21-oic acid, eburicoic acid, polyporenic acid C, 3-epidehydrotumulosic acid, 3-O-acetyl-16α-hydroxydehydrotrametenolic acid, 3-epidehydropachymic acid, 3-O-acetyl-16α- hydroxyplugymic acid, dehydropachymic acid, pachymic acid, dehydrotrametenolic acid, and dehydroeburicoic acid. Conclusion: The method is rapid, accurate, and has desirable precision, reproducibility, and stability, which could be applied to the quality control of GFC.

Molecular mechanism of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair against sepsis based on integrative pharmacology platform of traditional Chinese medicine / 中国中药杂志

Guizhi Decoction is a resolving agent,which is a classic prescription for traditional Chinese medicine. It is effective in the treatment of sepsis in clinical practice. However,due to the complexity of the prescription,its anti-sepsis mechanism is difficult to be clarified. The " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair,as the classic compatibility for medicinal and medicinal herbs,is the core of Guizhi Decoction. In this study,Cinnamomi Ramulus-Paeoniae Radix Alba drug pair was used as the research object and the molecular mechanism of its treatment of sepsis was investigated by analyzing the chemical compositions with integrative pharmacology platform( TCMIP,http://www.tcmip.cn/),predicting disease target,analyzing gene function and pathway of " Cinnamomi Ramulus-Paeoniae Radix Alba" in treatment of sepsis,and establishing a multi-dimensional network relationship of " Chinese medicine-chemical components-core targets-key pathways". The prediction results of " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair showed that its anti-sepsis effect was associated with 45 active components,and the active components played an anti-sepsis role through multiple targets and pathways,involving inflammatory targets such as PF4,MyD88,TLR4,BDKRB2,CD14,and NOS3. The sepsis was relieved mainly by regulating Toll like signaling pathway,Fox O signaling pathway,chemokines signaling pathway,thyroid and insulin endocrine signaling pathways and biological processes. This study provides a scientific basis for further development of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair and Guizhi Decoction against sepsis.

Mechanism of Cinnamomi Ramulus improving rat model of intrahepatic cholestasis induced by ANIT by regulating FXR pathway / 中国中药杂志

To study the mechanism and action of Cinnamomi Ramulus in ameliorating intrahepatic cholestasis induced by α-isothiocyanate( ANIT) in rats by regulating FXR pathway. Forty SD rats were randomly divided into normal group,model group,positive control( ursodeoxycholic acid) group( 60 mg·kg~(-1)),Cinnamomi Ramulus treatment( 60 mg·kg~(-1)·d~(-1)) group,and Cinnamomi Ramulus treatment( 20 mg·kg~(-1)·d~(-1)) group,with 8 rats in each group. Except for the normal control group,the other groups were intragastrically administered with the corresponding concentrations of continuous aqueous solution( 0. 005 m L·g~(-1)),once a day,for 7 days.Except for the normal group,the other groups were treated with ANIT( 100 mg·kg~(-1)),once a day,for 3 days. Blood was taken from the abdominal aorta 24 hours after the last administration,and serum alanine aminotransferase( ALT),aspartate aminotransferase( AST),total bilirubin( TBi L),and total bile acid( TBA) were measured. 1. 5-2 cm of rat liver tissue was taken. After fixation with10% formaldehyde,paraffin-embedded sections were taken,HE staining was performed,and immunohistochemistry( IHC) was used to analyze the expression of FXR. RNA and protein were extracted from rat liver tissue to detect FXR mRNA expression,as well as bile acid synthesis and detoxification,transport related SHP,UGT2 B4,BSEP protein expressions at downstream of FXR. Compared with the normal group,serum ALT,AST,TBi L,and TBA levels were elevated in the model group( P<0. 01),liver damage was severe,FXR protein's optical density decreased,FXR mRNA expression decreased,and SHP,UGT2 B4,BSEP protein expressions were decreased( P<0. 05,P<0. 01). Compared with the model group,the drug group could reduce serum ALT,AST,TB,TBA levels to different degrees( P<0. 05,P<0. 01),alleviate liver tissue damage,increase the optical density of FXR protein,and promote the expressions of FXR mRNA and FXR,SHP,BSEP and UGT2 B4 proteins( P<0. 05,P<0. 01). Cinnamomi Ramulus can alleviate ANIT-induced intrahepatic cholestasis,and reduce hepatocyte injury and serum ALT,AST,TBi L and TBA levels. The mechanism may be through FXR-SHP,FXR-UGT2 B4,FXR-BSEP signaling pathways. Therefore,in the pathogenesis of intrahepatic cholestasis,we can try to further explore in alleviating intrahepatic cholestasis with Cinnamomi Ramulus,so as to provide effective drugs for clinical treatment of intrahepatic cholestasis.

Discussion on Medication Rules of Cinnamomi Ramulus inShang Han Lun from Dose-Response Relationship / 中国中医药信息杂志

Objective To provide references for clinical medication through the analysis on the dose-response relationship and compatibility medication rules of Cinnamomi Ramulus.Methods It systematically arranged the provisions containing Cinnamomi Ramulus inShang Han Lun. Relationship between the dose of Cinnamomi Ramulus and the related factors were analyzed by single factor logistic regression analysis and binary correlation analysis by SPSS20.0 statistical software.Results After screening, 40 prescriptions including Cinnamomi Ramulus were selected, accounting for 35.40% in the total prescriptions ofShang Han Lun. The taken dose of every time of Cinnamomi Ramulus had a close relationship with the number of medicine and water consumption, with statistical significance (P=0.000,P=0.004). However, it had no relationship with residual water, water consumption per time and use frequency, without statistical significance (P>0.05). Single factor logistic regression analysis showed whether Cinnamomi Ramulus as a mainmedicine had the close relationship with the taken dose of every time of Cinnamomi Ramulus and use frequency (P=0.008,P=0.043). When Cinnamomi Ramulus and Glycyrrhizae Radix et Rhizoma Praeparata cum Mella were in compatibility, compared with when Cinnamomi Ramulus was not the main medicine, the taken dose of every time of Cinnamomi Ramulus as the main medicine in the group was more frequently used, with statistical significance (P=0.046); however, the number of medicine was statistically lower than when Cinnamomi Ramulus was not main medicine (P=0.043). When Cinnamomi Ramulus and Ephedrae Herba were in compatibility, there was no statistical difference in the taken dose of every time of Cinnamomi Ramulus or the number of medicine (P>0.05). When Cinnamomi Ramulus was the main medicine, it was not in compatibility with Poria or Bupleuri Radix.ConclusionFrom the dose-response relationship, it can be found that the use and compatibility of Cinnamomi Ramulus inShang Han Lun are strict and flexible, and dose law can provide a basis for clinical application.

Correlation of HPLC Fingerprint Chromatograms of Cinnamomi Ramulus Formula Granules, Decoction Pieces and Water Decoction / 中国中医药信息杂志

Objective To study the correlation of fingerprint chromatograms of Cinnamomi Ramulus formula granules, decoction pieces and water decoction by HPLC; To investigate the difference of main chemical constituents among different forms. Methods The Diamonsil C18 column (4.6 mm × 250 mm, 5 μm) was used with mobile phase of acetonitrile and 0.1% phosphoric acid at the flow rate of 1.0 mL/min, with detection wave of 280 nm and temperature of 30 ℃. The detection of 10 batches of Cinnamomi Ramulus formula granules, 10 batches of decoction pieces and 10 batches of water decoction were established respectively. Results Totally 12 peaks in the HPLC fingerprint chromatogram from 10 batches of formula granules could be tracked in the water decoction; 10 peaks in the HPLC fingerprint chromatogram could be tracked in the decoction pieces. Three components, such as protocatechuic acid, coumarin and cinnamic acid were verified. Conclusion The main chemical components of Cinnamomi Ramulus formula granules and water decoction are basically the same, and the common component contents have similar proportion.

Research on quality standard of Cinnamomi Ramulus standard decoction / 中草药

Objective: To prepare Cinnamomi Ramulus standard decoction and to study the quality standard of Cinnamomi Ramulus. Methods: Fifteen batches of Cinnamomi Ramulus standard decoctions were prepared according to the standardization method. With cinnamon acid as the detection index, the transfer rate and extraction rate were calculated and the HPLC fingerprint analysis method was established. Results: According to the measurement of 15 batches of standard decoctions, the transfer rate ranged from 56.93% to 94.06% and extractum rate was at the range of 3.30%-9.40%. Besides, the Similarity Evaluation System for Chromatographic Fingerprint of traditional Chinese medicine TCM (2012A) was used to analyze and compare the fingerprint, nine commom peaks were determined and four were calibrated including protocatechuic acid (peak 1), coumarin (peak 4), cinnamic acid (peak 6), and cinnamaldehyde (peak 7). Moreover, the similarity was over 0.95. Conclusion: This study established an HPLC fingerprint analysis method of Cinnamomi Ramulus standard decoction. The method displays good precision, stability, and repeatability in fingerprint analysis. Therefore, this study has some identified significance and can provide a reference for the quality control of Cinnamomi Ramulus dispensing granules.

Establishment of quality standard and discussion on standard decoction containing volatile oil pieces-Cinnamomi Ramulus pieces / 中国中药杂志

To prepare Cinnamomi Ramulus pieces standard decoction and establish its quality standard, provide quality reference for formula granules and other clinic non-traditional forms of medicines, and lay a foundation for standard decoction research for the pieces containing essential oil. 14 batches of Cinnamomi Ramulus pieces with different quality were collected from market and their extraction process was further improved based on the preparation principle of standard decoction to prepare the standard decoction of Cinnamomi Ramulus pieces. Then its transfer rate of Cinnamaldehyde, dry extract rate and pH value were calculated to evaluate its process stability; and a method for chromatographic fingerprint and content determination was also established. Results revealed that the dry extract rate for standard decoction of Cinnamomi Ramulus pieces was from 6.06%-8.95%, with an average value of 7.18%; the transfer rate of cinnamaldehyde was at the range of 29.6%-54.3%, with an average of 43.2%; and the pH value was at the range of 4.33-4.82. The fingerprint similarities between 14 batches of standard decoction of Cinnmomi Rammulus pieces and reference fingerprint were all>0.9. The established method for standard decoction was stable and its quality standard was perfect, suitable for evaluating the quality of standard decoction of Cinnanomi Ramulus pieces.

UPLC fingerprint of triterpenoids in Guizhi Fuling Capsule / 中草药

Objective: To establish the UPLC fingerprint of triterpenoids in Guizhi Fuling Capsule (GFC) and give a new method for quality control. Methods: UPLC was used on an Agilent Zorbox Eclipse Plus HD C18 (100 mm × 2.1 mm, 1.8 μm) column with the gradient elution solvent system composed of acetonitrile-0.1% H3PO4 water solution as mobile phase, the flow rate was 0.2 mL/min, the column temperature was 30℃, and the detection wavelength was 210 nm. The common peaks were identified by Q-TOF/MS. Results: The UPLC fingerprints of triterpenoids in GFC were established. Totally 20 common peaks were selected as the fingerprint peaks of GFC, of which a total of 13 mutual peaks (1-7, 10, 12, and 14-17) from Poria, the peaks of number 8 and 11 were from Cinnamomi Ramulus, the peak of number 9 was from Paeoniae Radix Alba and Moutan Cortex, and the peak of number 13 was from Persicae Semen, Paeoniae Radix Alba, Moutan Cortex, and Cinnamomi Ramulus. The similarity among the fingerprint of 10 batches of GFC samples were 0.90. Fifteen chemical components were identified by UPLC-Q-TOF/MS, which were 1-hederagenin, 2-dehydrotumulosic acid, 3-tumulosil acid, 4-polyporenic acid C, 6-3-epidehydrotumulosic acid, 7-poricoic acid D, 9-α-linolenic acid, 10-dehydropachymic acid, 11-oleanolic acid, 12-pachymic acid, 13-linolic acid, 15-methylcis-9-hexadecenoate, 16-palmitic acid, 17-palmitic acid ethyl ester, and 18-daucosterol. Conclusion: The established UPLC fingerprint has desirable precision, reproducibility, and stability, and could be applied to the quality control of GFC.

Effect of Cinnamomi Ramulus on distribution kinetics of ephedrine and pseudoephedrine from Ephedrae Herba in brain tissues of mice / 中草药

Objective: To observe the effect of Cinnamomi Ramulus on the distribution kinetics of ephedrine (E) and pseudoephedrine (PE) from Ephedrae Herba in brain tissues of mice. Methods: Mice were ig adminstered by Cinnamomi Ramulus and codecoction of Cinnamomi Ramulus combined with Ephedrae Herba. Brain tissues of mice were collected at different time after drug administration. The variation of E and PE with time was determined by GC-MS method. The non compartmental kinetic was fitted and the parameters were calculated by Kinetica 5.0.11 software, so as to evaluate the effect of Cinnamomi Ramulus on the distribution kinetics of E and PE from Ephedrae Herba in brain tissues of mice. Results: Compared with the Ephedrae Herba group, in the group with the codecoction of Cinnamomi Ramulus combined with Ephedrae Herba, the tmax of E and PE distributed in the brain tissues of mice was delayed, the AUC0-∞ of E and PE in the brain tissues of mice under the drug concentration curve was smaller and the MRT0-∞ of E was reduced. Conclusion: Cinnamomi Ramulus combined with Ephedrae Herba has the propertis of delaying the distribution process of E and PE, reducing the cumulative distribution volume, and accelerating the elimination of E and PE in the brain tissues of mice. Above all, Cinnamomi Ramulus can relieve the neurotoxicity of Ephedrae Herba, and there is the combination function of mutual restraint and mutual supression between the two drugs.

Mechanism of anti-influenza virus of volatile oil in Cinnamomi Ramulus and cinnamaldehyde / 中草药

Objective: To study the anti-influenza virus A/PR/8/34 (H1N1) activity of the volatile oil in Cinnamomi Ramulus (VOCR) and cinnamaldehyde in vitro, and to reveal the effect of TLR7 signaling pathway in anti-influenza. Methods: The IC50 and therapeutic index (TI) of VOCR and cinnamaldehyde in vitro were determined using influenza virus-infected Madin-Darby canine kidney (MDCK) cell line. ELISA was conducted to determine the level of interferon-β (IFN-β) in MDCK cells. The real-time RT-PCR was used to determine the mRNA expresstion of TLR3, TLR7, TRAF-3, interleukin-1 related acceptor kinase-4 (IRAK-4), and IFN-β. Results: Both VOCR and cinnamaldehyde had the direct virucidal activities on influenza virus; The IC50 values were 1.85 × 10-7 and 5.77 × 10-7 g/mL, respectively. The TI values were 27.04 and 9.51, respectively. Compared with the virus group, VOCR and cinnamaldehyde (0.25 × 10-5 g/mL) had the significant effects on increasing the serum level of IFN-β in infected MDCK cells (P < 0.05) and the mRNA expression of TLR7, IRAK-4, and IFN-β (P < 0.05). Conclusion: VOCR and cinnamaldehyde have good anti-influenza virus activities in the cellular level. The mechanisms are related to the activiation of TLR7 signaling pathway and IRAK-4, and leading to the high expression of IFN-β.