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Cressa cretica is a widely grown halophytic plant traditionally used for the treatment of different ailments. Previous investigations reported its biological activity on a wide spectrum of diseases. In this study, in vivo antinociceptive, anti-inflammatory, and antipyretic activities of C. cretica aqueous extract whole plant were evaluated. In addition, the total polyphenol content, the total flavonoid content, and the chemical characterization of the extract were performed. C. cretica showed writhing inhibition in acetic acid-induced peripheral nociception of 43 and 48 % at doses of 50 and 100 mg/kg, respectively. The same doses increased latency time in a hot plate model of central analgesia by 66 and 78 % compared to the control group, respectively. The acute anti-inflammatory effect of the extract was explored in the carrageenan-induced rat hind paw test. The inhibition of paw volume was better than that of the standard drug indomethacin. C. cretica significantly decreased rectal temperature in the rats injected with Brewerʼs yeast. C. cretica aqueous extract showed both central and peripheral antinociceptive activities and was effective as an anti-inflammatory and antipyretic. Phenolic compounds, including chlorogenic acids and flavonol glycosides, were identified by HPLC-PDA-ESI-MS techniques. These findings indicate the medicinal importance of this traditionally used plant as a therapeutic remedy for different ailments.

Nectarine (Prunus persica var. nucipersica) is a worldwide appreciated edible subspecies, with a high nutritional value and benefits on human health due to its phenolic content. Despite the large consumption of the fruit, the potential use of its kernel is poorly studied. Herein, the potential pharmacological activities and the phenolic constituents of an alcoholic extract of kernel nectarine fruits were investigated. Administering nectarine kernel extract (50 and 100 mg/kg, respectively) in rats reduced paw edema after carrageenan injection by 11 and 47% in 1 h, 24 and 33% in 2 h, and 23 and 32% in 4 h, when compared to the controls. At the higher dose (100 mg/kg), nectarine kernel extract increased the reaction time in the hot-plate model and produced a significant decrease in the rectal temperature of the pyretic rats, while both doses produced 52 and 59% of writhing inhibition compared to the control group. Total polyphenolic (55.91 ± 5.78 mg/g) and flavonoid (29.89 ± 0.55 mg/g) content indicated that the extract is a promising source of these constituents. HPLC-ESI-MS/MS analysis demonstrated the presence of flavonoids, such as naringenin and apigenin glycosides. The cyanogenic glycosides amigdalin and prunasin were also detected. These results highlight the anti-inflammatory, analgesic, and antipyretic activities of nectarine kernel alcoholic extract, together with significant phenolic content, promoting its exploitation as a source of bioactive molecules.

The anti-inflammatory and related activities of bukittinggine were evaluated in comparison with reference drugs. The results obtained revealed that bukittinggine exhibited a significant inhibitory effect in carrageenin-induced hind paw edema and adjuvant-induced arthritis in rats. Its anti-inflammatory activity in both test models was comparable to that of acetylsalicylic acid. Bukittinggine also showed an inhibitory effect on the late proliferative phase of the inflammatory process in cotton pellet-induced granuloma formation in rats. In carrageenin-induced rat pleurisy, bukittinggine exhibited marked inhibitory activity on exudative formation, accumulation of leukocytes and on PGE 2 -like activity in the exudate. Furthermore bukittinggine could significantly reduce fever in yeast-induced hyperthermic rats and possessed analgesic activity comparable to that of acetylsalicylic acid when tested in acetic acid-induced writhing response in mice. However, bukittinggine exhibited only a weak effect in the tail-flick test when compared with morphine. It is likely that bukittinggine possesses a mechanism of anti-inflammatory, analgesic and antipyretic action similar to that of acetylsalicylic acid.

The dried aqueous extract of leaves of Buddleia cordata (loganiaceae) and its main flavonoid glycoside, linarin, have been evaluated for analgesic and antipyretic effects in mice and rats, respectively. Both the extract and linarin exerted significant and dose-dependent analgesic and antipyretic activities, the first being obtained against a chemical stimulus (writhing a test in mice) and the second being obtained by a pyretogenic stimulus (yeast-induced hyperthermia test). Furthermore, the response of the animals in the hot plate test was modified by linarin and an aqueous extract. These activities were similar to that showed by morphine sulfate (MS) and they were inhibited by naxolone pretreatment, a specific morphinic antagonist compound. These findings lead to the conclusion that the aqueous extract and linarin exert central analgesic properties. On the other hand, linarin was shown to be responsible for the antipyretic activity of this species.

Aethiopinone (1), an o-naphthoquinone diterpene from Salvia aethiopis L. roots and two hemisynthetic derivatives 2 and 3 have been evaluated for toxicity, anti-inflammatory, analgesic, antipyretic, and haemostatic activities. The compounds tested showed low toxicity and a pharmacological profile similar to other NSAI substances on reducing the edema induced by carrageenan and contractions induced by phenyl-p-quinone; the most active compounds were 1 and 2. In the same way and as expected with these types of substances, the bleeding time increased. In the TPA-induced ear inflammation model, the three compounds showed a moderate reduction of edema, and 1 produced a significant increase in the reaction time against thermal painful stimuli in the tail immersion test. The results demonstrated strong anti-inflammatory, peripheral and central analgesic properties for 1, as well as antiedematose topical action and peripheral analgesic properties for 2 and 3.

The analgesic, antipyretic and anti-inflammatory effects of the aqueous extract of Mezoneuron benthamianum (MB) were evaluated in mice, rats and rabbits using the mouse writhing, tail flick, hot plate and formalin-induced pain tests; 2-4-Dinitrophenol (DNP), D-Amphetamine and E-coli Lipopolysaccharide-induced pyrexia and carrageenan, egg albumin and xylene-induced oedema. The extract (400-1600 mg/kg) and acetylsalicylic acid (100 mg/ kg) produced a significant (P < 0.05) inhibition of the second phase response in the formalin pain model, while only the highest dose (1600 mg/kg) of the extract showed a comparable antinociceptive effect in the first phase. The extract also showed a dose-dependent inhibition of acetic acid induced abdominal writhing. The tail flick latency and the hot plate pain threshold were dose dependently enhanced by the extract but these were significantly lower than that produced by morphine (2 mg/kg). The 2,4-DNP and D-Amphetamine (10 and 5 mg/kg, i.p.respectively) increased the rectal temperatures of rats within 30 minutes of their administration. The extract at doses of 400,800 and 1600 mg/kg produced significant lowering of the elevated body temperature in rats. The extract (800 mg/ kg) administered orally to rabbits passaged with E. coil lipopolysacharride was able to relieve the pyrogen induced fever. The antipyretic effect produced by the extract was comparable to a standard antipyretic drug, aspirin. The extract (400-1600 mg/kg) administered 1h after carrageenan-induced paw swelling did not inhibit the oedema. No inhibitions were observed with the egg albumin and xylene induced oedema models. Phytochemical analysis revealed the presence of flavonoids, tannins, cardiac glycosides, anthraquinones, and saponins. Administration of the extract up to 2 g/kg (orally) did not produce any toxic effect in the acute toxicity studies in mice. The LD50 of the extract when administered intraperitoneally was 1021.31 mg/kg. The data obtained show that MB extract possesses analgesic and antipyretic activities but lacks an anti-inflammatory property.

Diffractaic acid and usnic acid were identified as the analgesic and antipyretic components of a lichen, Usnea diffracta. Both compounds showed an analgesic effect by the acetic acid-induced writhing and tail-pressure methods in mice. Regarding the effect on normal body temperature and LPS-induced hyperthermia in mice, diffractaic acid showed a significant effect only on the former and usnic acid only on the latter.

Pharmacokinetic and pharmacological studies were performed to compare the antipyretic effects of salicin (SL), saligenin (SG, an aglycone of SL) and salicylic acid (SA, an active metabolite of SL) in rats. When SL was administered orally to rats, SA appeared slowly in the plasma and levels increased gradually, in contrast to the rapid appearance observed after oral administration of sodium salicylate (SANa) or SG. Orally administered SL did not affect the rectal temperatures of afebrile rats at a dose of 5 mmol/kg; at this dose, SANa and SG lowered body temperature significantly. However, it significantly reduced yeast-induced fever, producing a normal body temperature, and completely prevented fever when administered simultaneously with yeast. SL did not induce gastric lesions even at a dose of 5 mmol/kg; conversely, SANa and SG induced severe gastric lesions in a dose-dependent manner at 1, 2.5 and 5 mmol/kg. Poor absorption of SL and rapid absorption of SA and SG were confirmed in an in vivo system, as well as in an in vitro system using everted rat jejunal sacs. Only small amounts of SA and SG were detected in the intestinal tracts of rats 1 h after oral administration, whereas more than 50 % of an SL dose was recovered as SL and SG from the intestinal tracts 1 h after treatment and 15.8 % of the dose was still present as SG 4 h after administration. When given to germ-free rats, 19.8 % of the SL dose was recovered intact, mainly from the cecum, and no SG was detected even at 4 h after treatment. These results indicate that SL is a prodrug which is gradually transported to the lower part of the intestine, hydrolyzed to SG by intestinal bacteria, and converted to SA after absorption. It thus produces an antipyretic action without causing gastric injury.

Extracts from the roots of Peucedanum ostruthium (L.) Koch were investigated for their antiphlogistic and antipyretic effects as well as for their influence on arachidonic acid metabolism. On carrageenan-induced rat paw edema, oral administration of 10% ethanolic extracts led to a marked inhibition of the edema. By means of bioassay-oriented fractionation of extract, 6-(3-carboxybut-2-enyl)-7-hydroxycoumarin proved to be the most important anti-inflammatory principle of the plant. 30 micrograms/kg of this compound inhibited the formation of edema to an extent of 50%. On the perfused rabbit ear and on polymorphonuclear leukocytes the extract and the active compound have been characterized as dual inhibitors of cyclooxygenase and 5-lipoxygenase activities. Moreover, an antipyretic effect of i.p. administered extract and compound were evaluated in rats with comparable hyperthermia after s.c. injection of brewer's yeast.

Lapidin, a bicyclic sesquiterpene from Ferula linkii Webb, has been evaluated for antinociceptive, anti-inflammatory, and antipyretic activities in mice and rats. Lapidin, vehicle, or the appropriate reference analgesic and anti-inflammatory compounds (acetylsalicylic acid [ASA] and indomethacin) were injected i.p. The more conspicuous effects of lapidin were: 1) a significant protective effect (17-62%; 2.5-20 mg/kg) towards writhings and stretchings induced by acetic acid in mice; 2) a significant antinociceptive effect on jumping responses in the hot-plate test (120 seconds at 15 mg/kg vs. 40 and 85 seconds in vehicle and ASA-treated mice, respectively); 3) a significant dose-dependent (5-15 mg/kg) antinociceptive effect against mechanical noxious stimuli; 4) a dose-dependent anti-inflammatory effect in the carrageenan-induced edema which, at the higher dose (20 mg/kg), was comparable (65% inhibition of paw swelling at 3 hours) to that obtained after indomethacin (10 mg/kg); and 5) a moderate antipyretic effect against yeast-induced hyperthermia. Present results demonstrate that lapidin possesses antinociceptive, anti-inflammatory, and less pronounced antipyretic effects comparable to those of classical non-steroid anti-inflammatory drugs, which make it worthy of further investigations as an antinociceptive and anti-inflammatory drug.

Lyophilised aqueous extract of Euphorbia hirta L. (Euphorbiaceae) has been evaluated for analgesic, antipyretic and anti-inflammatory properties in mice and rats, in order to complete its activity profile, after the confirmation of the existence of a central depressant activity particularly expressed by a strong sedative effect, associated with anxiolytic effects. This study leads us to the conclusion that this plant extract exerts central analgesic properties. Such a dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, from the doses of 20 and 25 mg/kg and it was inhibited by a naloxone pretreatment, a specific morphinic antagonist compound. An antipyretic activity was obtained at the sedative doses of 100 and 400 mg/kg, on the yeast-induced hyperthermia. Finally, significant and dose-dependent anti-inflammatory effects were observed on an acute inflammatory process (carrageenan-induced edema test in rats) from the dose of 100 mg/kg. On the other hand, plant extract remained inactive on chronic processes such as Freund's adjuvant-induced rheumatoid arthritis, after a chronic treatment during fourteen days at the daily dose of 200 or 400 mg/kg; however, if inefficacy was observed on rat backpaws edema and on loss of weight, the aqueous extract reduced the inflammatory hyperalgia.

Erythraea centaurium is a plant which is used in the treatment of various inflammatory conditions in popular medicine. The aqueous extract of the plant has been examined for its antiinflammatory, analgesic, and antipyretic effects in several animal models. The extract exhibited antiinflammatory and antipyretic activity although no analgesic activity was observed.

We have isolated matrine, an active ingredient from the root of SOPHORA SUBPROSTRATA and studied its antipyretic activity in rats. Subcutaneous injection of the yeast suspension (10 ml/kg) increased the rectal temperature at the 19th h after administration. Matrine, in doses of 20 or 30 mg/kg, either given intraperitoneally or orally, produced a dose-dependent inhibition on yeast-provoked elevation of body temperature. This antipyretic effect was not prevented by atropine or methysergide but was completely antagonised by haloperidol pretreatment which also decreased the antipyretic activity of dopamine. Both matrine and dopamine possessed a hypothermic action. These results indicate that the antipyretic activity of matrine may possibly be mediated by dopamine release or through dopaminergic receptor blockade.

Ethanolic extract of the whole plant of TRIANTHEMA PORTULACASTRUM L. (Aizoaceae) showed the following activities: antipyretic (against yeast pyrexia in rats) onset: 5 hr: analgesic (against chemical and electrical stimuli): antiinflammatory (30.43% inhibition of formaldehyde induced arthritis in rats): IN VITRO antibacterial (particularly against gram positive bacteria): also CNS depressant properties.

The anti-inflammatory and antipyretic activities, as well as the acute toxicity of AZADIRACHTA INDICA (Neem tree) extract were studied. It was found to have a pronounced anti-inflammatory (rat paw oedema) and a fairly good antipyretic effect (pyrogen induced hyperpyrexia in rabbits) . The acute oral toxicity test in mice showed a very low range of approximately 13 g/kg body weight.