This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

PURPOSE: This study aims to investigate the additive effect of the Hedera helix (HH) and Rhizoma coptidis (RC) extracts mixture on antitussive and expectorant activities in animals. MATERIALS AND METHODS: The expectorant assay was performed with phenol red secretion in mice trachea. Mice or guinea pigs were randomly divided into groups of 8 each, including negative and positive control groups. After gastric administration of the test extracts in mice, 2.5% phenol red solution (0.2 mL) was intraperitoneally injected. Trachea was dissected and optical density of tracheal secretion was measured. After gastric administration of the test extracts in guinea pigs, the antitussive activities were assessed using a citric acid-induced cough measurement. RESULTS: The extracts of HH and RC significantly increased tracheal secretion and inhibited cough. The mixture of HH and RC extracts in a 1:1 concentration at a dose of 200 mg/kg showed a more potent effect on phenol red secretion (25.25+/-3.14) and cough inhibition (61.25+/-5.36) than the individual use of each extracts [phenol red secretion; HH 13.39+/-4.22 (p=0.000), RC 20.78+/-2.50 (p=0.010), cough inhibition; HH 9.89+/-4.14 (p=0.010), RC 30.25+/-7.69 (p=0.000)]. A 3:1 ratio mixture of HH to RC demonstrated an optimal expectorant effect (p<0.001), and this mixture showed expectorant and antitussive effects in a dose-dependent manner. CONCLUSION: This study provides evidence for antitussive and expectorant effect of a 3:1 mixture of HH and RC, which may be a useful therapeutic option for respiratory diseases.
Animals ; Antitussive Agents/*administration & dosage/pharmacology/therapeutic use ; *Behavior, Addictive ; Cough/*drug therapy ; Drugs, Chinese Herbal/*administration & dosage/pharmacology/therapeutic use ; Ethanol ; Expectorants/*administration & dosage/pharmacology/therapeutic use ; Guinea Pigs ; Hedera/*chemistry/metabolism ; Male ; Mice ; Phytotherapy ; Plant Extracts/*pharmacology ; Plant Roots/chemistry ; Trachea/drug effects/metabolism

OBJECTIVETo study the analgesic, expectorant and antitussive effects of the compatible use of Aconiti Radix Cocta and Fritillaria cirrhosa or F. thunbergii with different matching ratio or dose in mice.

METHODThe two-factor, seven-level uniform design method was adopted to observe the analgesic, expectorant and antitussive effects of the oral administration with the two combined decoctions in rats, with frequency of body torsions induced by acetum, secretion of phenol red in tracheas and frequency of coughs as indexes. Significant matching proportions and doses were collected for verification.

RESULTThe effect on the frequency of body torsions: The combined decoctions could effectively reduce the frequency of body torsions. According to a regression analysis, Aconiti Radix Cocta and F. cirrhosa had the synergistic effect, which was maximized with a ratio of 1: 1. The 1: 1 combined decoction played the least role in reducing the frequency of body torsions with a total dose of more than 5 g x kg(-1). The effect on the secretion of phenol red in tracheas. The combined decoctions could effectively increase the secretion of phenol red in tracheas. According to a regression analysis, Aconiti Radix Cocta and F. thunbergii had the antagonism, which was maximized at the ratio of 1: 1, and minimized with a total dose of less than 10 g x kg(-1) and a ratio of 5: 1 between F. thunbergii and Aconiti Radix Cocta. The effect on the frequency of coughs. The combined decoctions could effectively reduce the frequency of coughs. According to a regression analysis, Aconiti Radix Cocta and F. cirrhosa had the antagonism, which was maximized at the ratio of more than 1: 5 and less than 10: 1. There was no interaction between Aconiti Radix Cocta and F. thunbergii. F. thunbergii could reduce the frequency of coughs, whereas Aconiti Radix Cocta showed no effect.

CONCLUSIONThe compatible application of Aconiti Radix Cocta and F. cirrhosa could enhance the analgesic effect of Aconiti Radix Cocta and reduce the expectorant and antitussive effects of F. cirrhosa, which vary according to different matching ratio and dose. The compatible application of Aconiti Radix Cocta and F. thunbergii shows no effect on the antitussive effect of F. thunbergii. This study provides experimental basis for in-depth studies on the combined effect of Aconiti Radix Cocta and Fritillaria--two of eighteen incompatible pairs.

Aconitum ; chemistry ; Analgesics ; pharmacology ; Animals ; Antitussive Agents ; pharmacology ; Behavior, Animal ; drug effects ; Drug Synergism ; Drugs, Chinese Herbal ; pharmacology ; Expectorants ; pharmacology ; Fritillaria ; chemistry ; Male ; Mice ; Phenolsulfonphthalein ; metabolism ; Trachea ; drug effects ; metabolism

The antitussive activity assay for the root extraction of Disporum cantoniense was carried out with coughing mice induced by ammonia liquor. The results showed that the ethanol and water extractions of D. cantoniense possess strong antitussive activity, and the high dose of the former was better than positive control, and then the constituents of the ethanol extraction were separated and purified by various modern chromatographic techniques. Their structures were identified by physico-chemical properties and spectroscopic data. As a result, eight compounds were isolated and identified as stigmast-4-en-3-one(1), (22E, 24R)-ergosta-5, 7, 22-trien-3beta-ol(2), obtucarbamate A(3), obtucarbamate B(4), neotigogenin(5), azo-2, 2'-bis[Z-(2,3-dihydroxy-4-methyl-5-methoxy) phenyl ethylene] (6),dimethyl {[carbonylbis (azanediyl)] bis( 2-methyl-5, 1-phenylene) j dicarbamate (7) , and quercetin-3-O-pB-D-glucopyranoside(8). All compounds were isolated from this plant for the first time, and the result of bioactivity-directed isolation showed that compounds 3, 4, and 6 had obvious effect on antitussive activity, and compound 6 had the same level as positive control.
Animals ; Antitussive Agents ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Ethanol ; chemistry ; Female ; Liliaceae ; chemistry ; Male ; Mice

Family Schisandraceae is composed of two genera Schisandra and Kadsura, which are quite different in regard to the used part and medical function. Traditionally, the fruits of Schisandra plants were called 'Wuweizi' used as tonic for neurasthenia, antitussive, and sedative agents. The stems and roots of Kadsura plants, with names related to 'XueTeng', possess activating blood circulation and eliminating stasis and are used for the treatment of rheumatism, fractures and irregular menstruation. The dried fruit of Schisandra chinensis was recorded in Chinese Pharmacopoeia (2010 Edition) as 'Wuweizi', while the dried fruit of S. sphenanthera was recorded as an official origin of 'Nanwuweizi'. Historically, there was no evidence that the fruits of Kadsura plants were substituted as 'Wuweizi' either in ancient literatures or contemporary marketing. However, genus Kadsura is still popularly called 'Nanwuweizi' and plant K. longipedunculata is regarded as the origin of 'Nanwuweizi', thus this will cause confusion as well as misunderstanding of genus Kadsura. The authors recommended, therefore, the Chinese name of genus Kadsura should be 'Lengfantengshu' and K. longipedunculata with the name of 'Lengfanteng' in order to guarantee the drug authenticity.
Anticoagulants ; isolation & purification ; Antitussive Agents ; isolation & purification ; Drug Contamination ; Drugs, Chinese Herbal ; isolation & purification ; Fruit ; chemistry ; Kadsura ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Plants, Medicinal ; classification ; Schisandra ; classification ; Terminology as Topic

OBJECTIVETo investigate the cough-relieving, analgesic and antibiotic effects of durian shell extract (DSE) in relieving cough and its analgesic and antibiotic effects.

METHODSThe effect of DSE in relieving cough was assessed in mice challenged with ammonia and SO(2) to induce coughing. The analgesic and antibiotic effects of DSE in mice were evaluated by hot plate test and twisting reaction induced by acetic acid, and by minimal inhibitory concentration (MIC) and disc-agar diffusion tests, respectively.

RESULTSCompared with the control group, the mice treated with 300 and 900 mg/kg DSE showed significantly prolonged latency with decreased number of coughing induced by ammonia and SO(2), and the effect was dose-dependent. DSE markedly prolonged the latency and decreased the twisting number of the mice induced by acetic acid without affecting the pain threshold in hot plate test. DSE produced no significant inhibitory effects against Staphylococcus aureus, Staphylococcus epidermidis, or E. coli, and showed a week inhibition against Bacillus aeruginosus.

CONCLUSIONDSE shows obvious effect in relieving cough and produces better analgesic effect against chemical factor-induced pain than against physical agent-induced pain sensation. DSE has a moderate inhibitory effect against Bacillus aeruginosus.

Analgesics ; pharmacology ; Animals ; Anti-Bacterial Agents ; pharmacology ; Antitussive Agents ; pharmacology ; Bombacaceae ; chemistry ; Male ; Mice ; Plant Extracts ; pharmacology ; Random Allocation

OBJECTIVETo compare the antitussive activity of three kinds of Stemonae Radix specified in the Chinese Pharmacopoeia, including roots of Stemona sessilifolia, S. japonica and S. tuberosa.

METHODThe antitussive activity was determined in mouse after cough induction by ammonia aerosol stimulation and the number of cough in 2 min were detected with codeine as positive control.

RESULTAll the decoctions, the total alkaloid fractions and non-alkaloid fractions of S. sessilifolia, S. japonica and three chemical types of S. tuberosa showed significant antitussive effect and exhibited a dose-dependent inhibition of coughing. The ED50 values showed that the antitussive activity strength for both total alkaloid fractions and the decoctions are: S. tuberosa (Type I) > S. sessilifolia > S. japonica. The total alkaloid fractions had more potent atitussive activity than the decoctions and non-alkaloid fractions. The antitussive activity strength for the three chemical types of S. tuberosa is: Type I > Type III > Type II. The samples from different producing areas for the same species of Stemonae Radix had no significant differences in antitussive activity. The result also showed that the honey-processed slice had much stronger antitussive activity than raw slice.

CONCLUSIONThe antitussive efficacies of Stemonae Radix were influenced by chemical diversity both in same species and among different species, different fractions and processed method.

Animals ; Antitussive Agents ; administration & dosage ; Cough ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Stemonaceae ; chemistry

OBJECTIVETo research the effects of Alligator Zhikegao on relieving cough, dispelling phlegm and anti-inflammation.

METHODThe coughing tests in mice, the phenol red secreting tests in mice, ear edema tests in mice,and paw edema tests and subcutaneous cotton ball granuloma in rats were adopted for observing the related pharmacological effects of Alligator Zhikegao.

RESULTAlligator Zhikegao could obviously prolong the latent period and decrease the times of mouse coughing, and remarkably inhibit the mouse ear edema (P < 0.001), the rat paw edema and the hyperplasia of subcutaneous cotton ball granuloma in rats. Alligator Zhikegao 11.70 g x kg(-1) could significant improve the carbonic clearances of macrophages (P <0.05) and the hemolysin level in serum (P <0.01).

CONCLUSIONAlligator Zhikegao has significant effects on relieving cough, dispelling phlegm, anti-inflammation and immunological regulation.

Alligators and Crocodiles ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; isolation & purification ; therapeutic use ; Antitussive Agents ; isolation & purification ; therapeutic use ; Cough ; drug therapy ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; therapeutic use ; Ear Diseases ; drug therapy ; Edema ; drug therapy ; Expectorants ; isolation & purification ; therapeutic use ; Female ; Glycosaminoglycans ; isolation & purification ; therapeutic use ; Granuloma ; drug therapy ; Male ; Materia Medica ; isolation & purification ; therapeutic use ; Medicine, Chinese Traditional ; Mice ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo establish a HPLC fingerprint for quantitative analysis of the active constituents of jizhi syrup.

METHODHPLC analysis was performed on a Zorbax Sb C18 column (4.6 mm x 250 mm, 5 microm), the mobile phase in gradient elution was composed of (A) 1% acetic acid solution (including 0.2% triethylamine) and (B) acetonitrile, at a flow rate of 1.0 mL x min(-1). The column temperature was 30 degrees C and the wavelength was 280 nm.

RESULT21 common peaks were tested in 10 batches of samples. Compared with the standard fingerprint, the similarity of each sample was greater than 0.99. At the same time, protocatechuic acid, protocatechu aldehyde, chlorogenic acid, caffeic acid, naringin and neohesperidin were found in all samples.

CONCLUSIONThe established method can be used for the quality control of jizhi syrup.

Antitussive Agents ; chemistry ; Benzaldehydes ; analysis ; Catechols ; analysis ; Chlorogenic Acid ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Flavanones ; analysis ; Hydroxybenzoates ; analysis ; Plants, Medicinal ; chemistry ; Reproducibility of Results

To search for potential drugs with potent antitussive, expectorant, antiasthmatic activities and low toxicity, a series of verticinone-bile acids salts were prepared based on the clearly elucidated antitussive, expectorant and antiasthmatic activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. The antitussive, expectorant and antiasthmatic activities of these verticinone-bile acid salts were then screened with different animal models. Ver-CA (verticinone-cholic acid salt) and Ver-CDCA (verticinone-chenodeoxycholic acid salt) showed much more potent activities than other compounds. The bioactivities of Ver-CA and Ver-CDCA are worthy to be intensively studied, and it is also deserved to pay much attention to their much more potent antitussive effects than codeine phosphate. In order to elucidate whether they have synergistic effect and attenuated toxicity, their activities will be continuously compared with single verticinone, cholic acid and chenodeoxycholic acid at the same doses on different animal models. The application of "combination principles" in traditional Chinese medicinal formulations may be a novel way in triditional Chinese medicine research and discovery.
Animals ; Anti-Asthmatic Agents ; chemistry ; pharmacology ; Antitussive Agents ; chemistry ; pharmacology ; Asthma ; prevention & control ; Bile Acids and Salts ; chemistry ; pharmacology ; Cevanes ; chemistry ; isolation & purification ; pharmacology ; Chenodeoxycholic Acid ; chemistry ; pharmacology ; Cholic Acid ; chemistry ; pharmacology ; Cough ; prevention & control ; Drug Combinations ; Drug Compounding ; methods ; Drug Synergism ; Expectorants ; chemistry ; pharmacology ; Female ; Fritillaria ; chemistry ; Guinea Pigs ; Male ; Mice ; Plants, Medicinal ; chemistry ; Random Allocation ; Snakes