The antipyretic effects of Qingkailing soft capsules and hard capsules were compared based on metabonomics technology,so as to provide basis for clinical rational use and quality control evaluation of its preparations. By using ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry( UPLC-LTQ/Orbitrap),and multivariate tatistical methods such as principal component analysis( PCA),partial least squares-discriminate analysis( PLS-DA) and orthogonal signal correction partial least square discriminant analysis( OPLS-DA),the changes of plasma endogenous metabolites in rat fever model induced by dry yeast were studied,so as to look for biomarkers related to fever. Based on these results,the antipyretic effects of two types of Qingkailing preparations were compared. The results indicated that metabolic profiles of the experimental groups could be distinguished distinctly,and 8 endogenous metabolites showed differences as compared with the normal control group( P<0. 05),including nicotinic acid,choline,hippuric acid,phosphocholine,Lyso PC( 14 ∶ 0),Lyso PC [16 ∶ 1( 9 Z) ],Lyso PC( 18 ∶ 0) and Lyso PC [20 ∶ 3( 5 Z,8 Z,11 Z) ]. They could be regarded as biomarkers related to fever. Qingkailing soft capsule and hard capsule had different effects on the regulation of plasma metabolites in yeast-induced fever model rats. Qingkailing soft capsule had different degrees of callbacks on eight biomarkers,including significant callbacks on nicotinic acid( P<0. 05),hippuric acid( P< 0. 01),phosphocholine( P< 0. 05),and Lyso PC [20 ∶3( 5 Z,8 Z,11 Z) ]( P<0. 05),while hard capsule only had significant callbacks on nicotinic acid( P<0. 05),hippuric acid( P<0. 01),and phosphocholine( P< 0. 05),with no callbacks on choline,Lyso PC( 14 ∶ 0),Lyso PC [16 ∶ 1( 9 Z) ],Lyso PC( 18 ∶0),and Lyso PC [20 ∶3( 5 Z,8 Z,11 Z) ]. This indicated that Qingkailing soft capsule had better callback effect than hard capsule. In this study,Qingkailing soft capsules and hard capsules were used to intervene the changes of related biomarkers in yeast-induced fever rat models,and then the antipyretic effect and mechanism between these two kinds of capsules were compared. The two dosage forms played an antipyretic role mainly by regulating lipid metabolism and controlling inflammation. The callback effect of soft capsule on the potential biomarkers of lysophosphatidylcholine was significantly higher than that of hard capsule. The differences in antipyretic effect of Qingkailing soft capsule and hard capsule were expounded from the point of metabonomics,providing experimental data and theoretical basis for the selection of clinical dosage forms.
Animals ; Antipyretics/pharmacology* ; Biomarkers/blood* ; Capsules ; Drugs, Chinese Herbal/pharmacology* ; Metabolomics ; Rats

OBJECTIVEOur study aims to evaluate the antiviral effects of Ouyi antipyretic detoxicate soft capsule against influenza A virus H1N1 in vivo, so as to find an effective Chinese medicinal formulae for the treatment of the virus infection, which may lay a theoretical foundation for clinic treatment of patient infected with Influenza A Virus H1N1.

METHODWith the observation of cytopathic effect (CPE) that induced by virus ,we investigated viral inhibition rate by MTT colorimetric assay and valued antiviral activity of drugs by therapeutic index (TI) . Meanwhile, Oseltamivir phosphate capsule (Tamiflu) was used as positive control , we carried out experiments through the three ways of preventive effect, direct inactivation and propagation inhibition.

RESULTOuyi antipyretic detoxicate soft capsule could effectively inhibit cytopathic effect (CPE) that induced by Influenza A Virus H1N1. The preventive effect, direct inactivation , and inhibition of endogenous multiplication of Ouyi antipyretic detoxicate soft capsule and Tamiflu against influenza A virus H1N1 were observed. And three types of action therapeutic index (TI) from Ouyi antipyretic detoxicate soft capsule were (15.5 +/- 0.71), (0.55 +/- 0.071), (6.4 +/- 1.27) severally, comparing Tamiflu with (0.4 +/- 0.14), (1.88 +/- 0.29), (4.6 +/- 0.15), respectively.

CONCLUSIONOuyi antipyretic detoxicate soft capsule showed more remarkable preventive effect than Tamiflu in vitro (P<0.01). The possible mechanism of the antiviral activity observed in our study might be the protection of the MDCK cells from viral infection by inhibiting the viral absorption. We need a further study to certify three effects in vivo.

Animals ; Antipyretics ; pharmacology ; Antiviral Agents ; pharmacology ; Capsules ; Cell Line ; Dogs ; Influenza A Virus, H1N1 Subtype ; drug effects ; Inhibitory Concentration 50

OBJECTIVEThe main objectives of this study were to qualitatively evaluate the profile of phytochemical constituents present in methanolic extract of Microcos paniculata bark (BME) and fruit (FME), as well as to evaluate their anti-inflammatory, analgesic and antipyretic activities.

METHODSPhytochemical constituents of BME and FME were determined by different qualitative tests such as Molisch's test, Fehling's test, alkaloid test, frothing test, FeCl3 test, alkali test, Salkowski's test and Baljet test. The anti-inflammatory, analgesic and antipyretic activities of the extracts were evaluated through proteinase-inhibitory assay, xylene-induced ear edema test, cotton pellet-induced granuloma formation in mice, formalin test, acetic acid-induced writhing test, tail immersion test and Brewer's yeast-induced pyrexia in mice.

RESULTSM. paniculata extracts revealed the presence of carbohydrates, alkaloids, saponins, tannins, flavonoids and triterpenoids. All of the extracts showed significant (P<0.05, vs aspirin group) proteinase-inhibitory activity, whereas the highest effect elicited by plant extracts was exhibited by the BME (75.94% proteinase inhibition activity) with a half-maximal inhibitory concentration (IC50) of 61.31 μg/mL. Each extract at the doses of 200 and 400 mg/kg body weight showed significant (P<0.05, vs control) percentage inhibition of ear edema and granuloma formation. These extracts significantly (P<0.05, vs control) reduced the paw licking and abdominal writhing of mice. In addition, BME 400 mg/kg, and FME at 200 and 400 mg/kg showed significant (P<0.05, vs control) analgesic activities at 60 min in the tail immersion test. Again, the significant (P<0.05, vs control) post-treatment antipyretic activities were found by BME 200 and 400 mg/kg and FME 400 mg/kg respectively.

CONCLUSIONStudy results indicate that M. paniculata may provide a source of plant compounds with anti-inflammatory, analgesic and antipyretic activities.

Analgesics ; pharmacology ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Antipyretics ; pharmacology ; Female ; Fruit ; chemistry ; Male ; Mice ; Plant Bark ; chemistry ; Plant Extracts ; pharmacology ; Tiliaceae ; chemistry

OBJECTIVETo study the screening of essential oils of Skimmia laureola leaves (SLO) for acute toxicity, antinociceptive, antipyretic and anticonvulsant activities in various animal models.

METHODSSLO were extracted using modified Clevenger type apparatus. Acute toxicity test was used in mice to observe its safety level. Antinociceptive activity of SLO was evaluated in acetic acid induced writhing and hot plate tests. Yeast induced hyperthermic mice and pentylenetetrazole induced convulsive mice were used for the assessment of its antipyretic and anticonvulsant profile respectively.

RESULTSSubstantial safety was observed for SLO in acute toxicity test. SLO showed a high significant activity in acetic acid induced writhing test in a dose dependent manner with maximum pain attenuation of 68.48% at 200 mg/kg i.p. However, it did not produce any relief in thermal induced pain at test doses. When challenged against pyrexia evoked by yeast, SLO manifested marked amelioration in hyperthermic mice, dose dependently. Maximum anti-hyperthermic activity (75%) was observed at 200 mg/kg i.p. after 4 h of drug administration. Nevertheless, SLO had no effect on seizures control and mortality caused by pentylenetetrazole.

CONCLUSIONSIn vivo studies of SLO showed prominent antinociceptive and antipyretic activities with ample safety profile and thus provided pharmacological base for the traditional uses of the plant in various painful conditions and pyrexia. Additional detail studies are required to ascertain its clinical application.

Analgesics ; pharmacology ; Animals ; Anticonvulsants ; pharmacology ; Antipyretics ; pharmacology ; Body Temperature ; drug effects ; Female ; Male ; Mice ; Oils, Volatile ; pharmacology ; toxicity ; Plant Leaves ; chemistry ; toxicity ; Rutaceae ; chemistry ; Toxicity Tests

AIMTo investigate the possible central mechanism of antipyretic effects of Chinese medicine gypsum.

METHODSGypsum was injected after the fever model was established. The firing rate of thermosensitive neurons in preoptic-anterior hypothalamus(PO/AH) region was recorded by using extracellular microelectrode technique.

RESULTSThe injection of pyrogen evoked decrease in firing rate of the warm-sensitive neurons and increase in the cold-sensitive neurons in the region of PO/AH; the changes of the firing rate of pyrogen- treated warm-sensitive and cold-sensitive neurons could be reversed by the injection of gypsum.

CONCLUSIONThe result may suggest that antipyretic action of gypsum is mediated by its influences on the thermosensitivity neurons in the region of PO/AH.

Action Potentials ; Animals ; Antipyretics ; pharmacology ; Calcium Sulfate ; pharmacology ; Cats ; Fever ; physiopathology ; Hypothalamus, Anterior ; physiopathology ; Male ; Materia Medica ; pharmacology ; Neurons ; physiology ; Preoptic Area ; physiopathology ; Pyrogens

To observe the antipyretic effect of Reduning injection (RDN) on lipopolysaccharide (LPS)-induced fever rats and its impact on centric fever medium. Rats were randomly divided into the blank control group, the model group, the Metamizole group, and high and low-dose RDN groups. Except for the blank control group, all of the rats were injected intraperitoneally with LPS (80 microg x kg(-1)) to observe their body temperature changes. The double-antibody sandwich ELSIA method was adopted to determine cAMP content in hypothalamus and MPO in lung tissues of fever peak rats. The high-dose RDN group can obviously reduce the temperature rise in fever rats, and cAMP and MPO content in hypothalamus. RDN showed significant antipyretic effect, which may be related with the reduction of cAMP content in hypothalamus and MPO in lung tissues.
Animals ; Antipyretics ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Fever ; chemically induced ; drug therapy ; Lipopolysaccharides ; Male ; Plants, Medicinal ; Random Allocation ; Rats ; Rats, Sprague-Dawley

A combination of LC-MS technology and activity evaluation was used to identify the antipyretic ingredients in rhubarb. The rat model of fever was established with dried yeast and then was administered ethanol extract and different polar fractions of rhubarb. Next, the anal temperature of these rats was measured and recorded at 0.5, 1, 2, 3, 4 and 5 h after administration, and the inhibition rate of each part on the rise of body temperature was calculated. The inhibition rate is higher and the antipyretic effect is better. The chemical composition of the effective fraction was analyzed with UPLC-ESI-Orbitrap-MS/MS technology. Compared with the model group, the increase of body temperature of ethanol extract group all reduced at each measurement time especially after 3 h, and the inhibition rate were 38.7%(P<0.05), 78.2%(P<0.01) and 72.4%(P<0.01) at 3 h, 4 h, and 5 h after administration, respectively. Both n-butanol and water fraction showed some antipyretic activity in the early stage, with the inhibition rate of 28.1%(P<0.01) and 24.9%(P<0.05) at 1 h after administration, respectively, while other fractions were not active. Thirty-three and twelve compounds were identified from n-butanol and water fraction by LC-MS/MS analysis, respectively, including ten tannins, fifteen anthraquinone glycosides, four anthrone glycosides, one phenolic glycoside, one naphthaline derivative, one anthraquinone and one sucrose. These results revealed that rhubarb had antipyretic activity on rats, and tannin and anthraquinone glycosides were the main active ingredients inside.
Animals ; Anthraquinones ; Antipyretics/pharmacology* ; Chromatography, Liquid ; Fever/drug therapy* ; Glycosides ; Plant Extracts/pharmacology* ; Plants, Medicinal/chemistry* ; Rats ; Rheum/chemistry* ; Tandem Mass Spectrometry ; Tannins

OBJECTIVETo investigate the antipyretic and anticonvulsant activities of n-hexane fraction of Viola betonicifolia (V. betonicifolia).

METHODSThe antipyretic effect was scrutinized using brewer's yeast induced pyrexia and anticonvlsion effect was tested using pentylenetetrazol and strychnine induced convulsion in mice.

RESULTSN-hexane fraction of V. betonicifolia demonstrated highly significant antipyretic activity during various assessment times (1-5 h) when challenged in yeast induced pyrexia test. The effect was in a dose dependent manner with maximum attenuation (82.50%) observed at 300 mg/kg i.p. When tested in pentylenetetrazol induced convulsion test, the 1st stage (Ear and facial twitching) and 2nd stage (Convulsive wave through the body) was 100% protected during 24 h at all the test doses (300, 400 and 500 mg/kg i.p.), while the latency time of remaining stages was significantly increased. The maximum effect was observed by n-hexane fraction of V. betonicifolia at 400 and 500 mg/kg i.p., as the latency time for generalized clonic-tonic seizure (5th stage) was increased up to 25.34 min. However, n-hexane fraction of V. betonicifolia had no protection in strychnine induced convulsion test.

CONCLUSIONSIn conclusion, phytopharmacological studies provide scientific foundation to the folk uses of the plant in the treatment of pyrexia and neurological disorders.

Animals ; Anticonvulsants ; administration & dosage ; chemistry ; pharmacology ; Antipyretics ; administration & dosage ; chemistry ; pharmacology ; Disease Models, Animal ; Female ; Fever ; drug therapy ; etiology ; Hexanes ; chemistry ; Male ; Mice ; Plant Extracts ; administration & dosage ; chemistry ; pharmacology ; Seizures ; chemically induced ; drug therapy ; Viola ; chemistry

Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate the antipyretic and anti-inflammatory activities of T. luteostoma. T. luteostoma was divided into shell (TLSH) and soft tissue (TLST) samples in the present study. The rat model of yeast-induced fever was used to investigate their antipyretic effects; and the rat model of hind paw edema induced by carrageenan was utilized to study their anti-inflammatory activities, and at the same time, the concentration variations of the central neurotransmitter [prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP)], inflammatory mediators [tumor necrosis factor (TNFα), interleukin-1β (IL-1), interleukin-2 (IL-2) and interleukin-6 (IL-6)] and ion (Na(+) and Ca(2+)) were also tested. The results showed that TLSH and TLST extracts significantly inhibited yeast-induced pyrexia in rats (P < 0.05), and exhibited more lasting effects as compared to aspirin, and TLSH had the better antipyretic activity than TLST, and that TLSH and TLST could significantly prevent against carrageenan induced paw edema in rats (P < 0.05); and markedly reduced levels of PGE2, cAMP, TNFα, IL-1β, IL-2, IL-6, and Na(+)/Ca(2+). In fever model, TLST could significantly reduce the levels of PGE2 (P < 0.01) in rats' homogenate and TNFα (P < 0.05), IL-1β (P < 0.01) in the plasma than TLSH, whereas TLSH could reduce the content of IL-2 (P < 0.01) and IL-6 (P < 0.01) in plasma and increase the content of Ca(2+) (P < 0.01) in plasma and homogenate more significantly than TLST. In conclusion, T. luteostoma extract has antipyretic and anti-inflammatory activities, which may be mediated through the suppression of production of PGE2, cAMP, Na(+)/Ca(2+), TNFα, IL-1β, IL-2, and IL-6.
Animal Shells ; chemistry ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Antipyretics ; pharmacology ; Carrageenan ; Complex Mixtures ; pharmacology ; Edema ; chemically induced ; drug therapy ; Fever ; chemically induced ; drug therapy ; Hindlimb ; Inflammation Mediators ; blood ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharomyces cerevisiae ; Snails ; chemistry

OBJECTIVETo evaluate the analgesic, anti-inflammatory and antipyretic activity of methanolic Tecomaria capensis (T. capensis) leaves extract using different models in rats.

METHODSMethanolic T. capensis leaves extract (100, 300, 1000 and 2000 mg/kg body weight) was given to rats orally to observe acute toxicity, and observed for 14 days. Analgesic activity was evaluated using tail immersion and formalin induced paw licking models in rats. Anti-inflammatory activity was evaluated using carrageenan induced paw edema model in rats. Antipyretic activity was evaluated using brewer's yeast induced pyrexia model in rats. Methanolic T. capensis leaves extract were given at dose of 100, 200 and 500 mg/kg p.o.

RESULTSResults demonstrated that the no mortality was reported even after 14 days. This indicated that the methanol extract was safe up to a single dose of 2 000 mg/kg body weight. Methanolic T. capensis leaves extract (100, 200 and 500 mg/kg p.o.) significantly increased the latency period in the tail immersion test, reduced the licking time in both the neurogenic and inflammatory phases in the formalin test. Methanolic T. capensis leaves extract (100, 200 and 500 mg/kg p.o.) significantly prevented increase in volume of paw edema. Methanolic T. capensis leaves extract at the doses of (100, 200 and 500 mg/kg p.o.) significantly decreased the rectal temperature of the rats.

CONCLUSIONSThis study exhibites that methanolic T. capensis leaves extract possesses analgesic, anti-inflammatory and antipyretic activity which may be mediated by the central and peripheral mechanisms.

Analgesics ; chemistry ; pharmacology ; therapeutic use ; toxicity ; Animals ; Anti-Inflammatory Agents ; chemistry ; pharmacology ; therapeutic use ; toxicity ; Antipyretics ; chemistry ; pharmacology ; therapeutic use ; toxicity ; Behavior, Animal ; drug effects ; Bignoniaceae ; chemistry ; Disease Models, Animal ; Edema ; Female ; Fever ; Male ; Pain Management ; methods ; Pain Measurement ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; toxicity ; Plant Leaves ; chemistry ; Rats