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Background: In recent years, 1, 2, 4-triazole and its derivatives have been reported to be pharmacologically significant scaffolds. They possess analgesic, anti-tubercular, anti-inflammatory, anti-convulsant, anti-oxidant, anti-fungal, anti-cancer, anxiolytic and anti-depressant activity. This study was designed and conducted to evaluate the potential anti-inflammatory, analgesic and antipyretic activities of Triazole derivatives., Methods: Swiss albino (male and female) mice weighing 20-30 g (10-24 weeks female), (5-14 weeks male) and Wister Kyoto rats (male and female) weighing 200-300 g (8-10 weeks old) were used for the present study. Anti-inflammatory activity was checked using Lambda carrageenan (λ) and egg albumin-induced paw edema models. Analgesic via Writhing Reflex induced by acetic acid and formalin, furthermore anti-pyretic activity was assessed by yeast induced pyrexia., Results: Both of the test compounds exhibited encouraging anti-inflammatory analgesic and antipyretic results when compared with standard drug ibuprofen. The maximum inhibition of edema for the compound (S)-1-(4-Amino-5-mercapto-4H-1,2,4-triazole-3-yl) ethanol [3] was found to be (91)% as compared to reference drug ibuprofen (82)%, while (S)-1-(6-Phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)ethanol [5e] showed equipotent results to ibuprofen (81)%. The derivatives were also screened for their anti-nociceptive activity by Acetic acid writhing and tail immersion test. Compound 3 showed a significant reduction in wriths (83)% as compared to standard drug ibuprofen 71.5% and [5] showed comparable results to ibuprofen by exhibiting 70% reduction in writh at the same dose as that of standard drug, moreover, there were no signs of toxicity being observed after administration of high doses of test compounds to mice., Conclusions: It is evident from the results that compounds 3(compound A) and 5(compound B) are a potential candidate for anti-inflammatory, analgesic and anti-pyretic and the scaffold could be used for further structural modifications. Further studies would help to evaluate their molecular mechanism of action regarding these beneficial activities., (© 2021. The Author(s).)

Background: Rocuronium-associated injection pain/withdrawal response (RAIPWR) was non-ideal but occurred frequently when injection intravenously during anesthesia induction. Many studies had reported that pretreating with antipyretic analgesics (AAs) could reduce the occurrence of RAIPWR, but there was no consensus yet. Therefore, this meta-analysis was designed to systematically evaluate the benefits of AAs on RAIPWR in patients., Methods: PubMed, Cochrane Library, Ovid, EMbase, Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data were searched by January 1st 2019 for randomized controlled trials (RCTs) applying AAs to alleviate RAIPWR in patients who underwent elective surgery under general anesthesia. Two investigators assessed quality of RCTs and extracted data respectively and the meta-analysis was carried on Revman 5.3 software. Moreover, we compared AAs in pros and cons directly with lidocaine, the most reported medicine to prevent RAIPWR., Results: Data were analyzed from 9 RCTs totaling 819 patients. The results of Meta-analysis showed that compared to the control group, pretreating with AAs could prevent the total occurrence of RAIPWR [Risk ratio (RR), 0.52; 95% confidence interval (CI), 0.42 to 0.66; P < 0.0001], and took effect on moderate (RR, 0.56; 95%CI, 0.43 to 0.73; P < 0.0001) and severe RAIPWR (RR = 0.14; 95%CI, 0.08 to 0.24; P < 0.00001). When compared to lidocaine, the preventive effect was not so excellent as the latter but injection pain induced by prophylactic occurred less., Conclusion: The currently available evidence suggested that pretreating with AAs intravenously could alleviate RAIPWR., Trial Registration: PROSPERO CRD42019129776.

Background: In 2014, an outbreak of adenoviral pneumonia occurred in the Korean military training center. However, there are limited data on the characteristics of the fever and its response to antipyretic therapy in immunocompetent adults with adenovirus-positive community-acquired pneumonia (CAP)., Methods: The medical records of the patients who were admitted to the Armed Forces Chuncheon Hospital for the treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. The patients were divided into three groups, namely, the adenovirus-positive (Adv) group, the adenovirus-negative (Non-Adv) group and the unknown pathogen group, according to the results of a polymerase chain reaction (PCR) test and sputum culture used to measure adenovirus and other bacteria or viruses in respiratory specimens. We evaluated and compared the demographics, clinicolaboratory findings and radiological findings upon admission between the two groups., Results: Out of the 251 military personnel with CAP during the study periods, 67 were classified into the Adv group, while 134 were classified into the Non-Adv group and 50 were classified into the unknown pathogen group. The patients in the Adv group had a longer duration of fever after admission (3.2 ± 1.6 vs. 1.9 ± 1.2 vs. 2.2 ± 1.5 days, P = 0.018) and symptom onset (5.8 ± 2.2 vs. 3.9 ± 2.5 vs. 3.7 ± 2.0 days, P = 0.006) than patients in the Non-Adv and unknown pathogen groups, respectively. The patients in the Adv group had a higher mean temperature at admission (37.8 ± 0.3 vs. 37.3 ± 0.3 vs. 37.3 ± 0.3, P = 0.005), and more patients were observed over 40 and 39 to 40(14.9% vs. 2.2% vs. 4.0%, 35.8% vs. 3.7% vs. 6.0%, P <  0.001) than those in the Non-Adv and unknown pathogen groups, respectively. The Adv group more commonly had no response or exhibited adverse events after antipyretic treatment compared to the Non-Adv group (17.9% vs. 1.5%, 35.0% vs. 4.3%, P <  0.001, P = 0.05, respectively). In addition, the time from admission to overall clinical stabilization was significantly longer in the patients in the Adv group than in those in the Non-Adv group (4.3 ± 2.8 vs. 2.9 ± 1.8 days, P = 0.034, respectively). Furthermore, no significant difference in the length of hospital stay was observed between the two groups, and no patient died in either group., Conclusion: In this study, Adv-positive CAP in immunocompetent military personnel patients had distinct fever characteristics and responses to antipyretic treatment.

Background: Leakage following colorectal anastomosis surgery causes various complications associated with high morbidity and mortality, especially in pediatric patients. It might be caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs) as postoperative analgesics. This study aimed to compare the effect of metamizole and paracetamol on colonic anastomosis and fibroblast activities, including proliferation, migration, and collagen synthesis, in Wistar rats., Methods: Rats were divided into control, paracetamol and metamizole groups. The colonic anastomosis was evaluated by determining the integrity of the muscle layers, the formation of granulation tissue, and mucosal anastomosis. Fibroblast activities were analyzed by measuring the proliferation, migration, and collagen synthesis., Results: Metamizole caused more damage to muscle layer integrity, more inhibition of granulation tissue formation in the anastomosis area and lower mucosal anastomosis compared with paracetamol and control groups. Metamizole had a higher cytotoxic effect than paracetamol, which suppressed the proliferation and migration of fibroblasts. Furthermore, both drugs did not affect the synthesis of collagen., Conclusion: Metamizole shows worse effects on the integrity of muscle layers, inhibition of granulation tissue formation, mucosal anastomosis, fibroblast proliferation, and migration, but not collagen synthesis, than paracetamol in Wistar rat intestines following colonic anastomosis. These findings might indicate that paracetamol is safer than metamizole as analgesic following colonic anastomosis.

Background: Saponins are the main constituents of genus Sapindus and have the therapeutic potential for inflammatory disorders. In this study the antioxidant, anti-inflammatory, analgesic and antipyretic potential of the stem bark of soap nut (Sapindus mukorossi) methanol extract and its derived fractions has been investigated., Methods: Powder of stem bark of the S. mukorossi was extracted with methanol (SMM) and fractionated in order of n-hexane (SMH), chloroform (SMC), ethyl acetate (SME), n-butanol (SMB) and the remaining as aqueous fraction (SMA). Quantitative estimation for the total phenolic and total flavonoid content was carried out in all the extract/fractions. Further, various in vitro antioxidant assays were also performed. Anti-inflammatory (Carrageenan induced paw edema), analgesic (hot plate latency test) and antipyretic (rectal temperature) were determined in Sprague-Dawley rat., Results: Quantitative estimation of total phenolic contents in extract/fractions varied between 252.3 ± 2.41 mg of GAE/g - 594.16 ± 4.3 mg of GAE/g while the total flavonoids estimated were from 11.02 ± 1.3 mg of RUE/g to 96.9 ± 3.2 mg of RUE/g. Standard antioxidant assays such as scavenging of DPPH, hydroxyl radical, nitric oxide, phosphomolybdenum assay, reducing power, inhibition of β-carotene bleaching, iron chelation activity and inhibition of heat induced protein denaturation indicated the antioxidant potential of the extract/fractions. Carrageenan induced paw edema of rat was effectively inhibited by SMA at 300 mg/kg administration to rat (84.19 ± 1.48%) after 3 h and analgesia (latency time) in hot plate test (55.78 ± 1.22%) after 120 min. SMA at 300 mg/kg distinctly decreased the rectal temperature in brewer's yeast (Saccharomyces cerevisiae) induced pyrexia in rat., Conclusion: The resulted obtained in this study suggested the therapeutic importance of stem bark of S. mukorossi in inflammatory related disorders.

Background: As aerial parts of Rubus ulmifolius contains phytochemicals like flavonoids and tannins. And whereas flavonoids and tannins have antioxidant and antipyretic activity, hence, current work is carried out to screen crude methanolic extract of aerial parts of Rubus ulmifolius (Ru.Cr) and crude flavonoids rich extract of Rubus ulmifolius (Ru.F) for possible antioxidant and antipyretic activity. Ru.Cr and Ru.F are also tested for brine shrimps lethality bioassay. Ru.F is tested for the first time for possible antioxidant and antipyretic activity., Methods: Preliminary phytochemical screening of Ru.Cr and Ru.F was performed as it provides rapid finger printing for targeting a pharmacological activity. Acute toxicity and Brine shrimps' cytotoxicity studies of Ru.Cr and Ru.F were performed to determine its safe dose range. Antioxidant and antipyretic studies were also performed as per reported procedures., Results: Ru.Cr tested positive for presence of tannins, alkaloids, flavonoids and steroids. Ru.Cr is safe up to 6 g/kg following oral doses for acute toxicity study. Ru.Cr is safe up to 75 μg/kg (p.o), LC 50 for Ru.Cr and Ru.F are 16.7 ± 1.4 μg/ml 10.6 ± 1.8 μg/ml, respectively (n = 3). Both Ru.Cr and Ru.F demonstrated comparable antioxidant activity using vitamin C as standard (p ≤ 0.05). In test dose of 300 mg of Ru.Cr, rectal temperature was reduced by 74% (p ≤ 0.05) on 4 th hour of the administration. More, Ru.F produced 72% reduction in pyrexia (p ≤ 0.05) on 4 th hour of administration of paracetamol in Westar rats., Conclusions: The current work confirms that aerial parts of Rubus ulmifolius contain flavonoids that are safe up to 6 g/kg (p.o). Crude methanolic extract and flavonoids rich fraction of Rubus ulmifolius have significant antioxidant and antipyretic activity. Further work is required to isolate the pharmacologically active substances for relatively safe and effective antipyretics and antioxidants.

Background: Medicinal plants have proven their importance as a valuable source of molecules with therapeutic potential. Monotheca buxifolia (Falc.) A. DC. (family: Sapotaceae) is traditionally used as a hematinic, laxative, digestive, anthelmintic, antipyretic, and in the treatment of gastro-urinary disorders. To provide scientific evidence for its folkloric use, the present study investigated Monotheca buxifolia fruit hydro-ethanolic extract (MBHE) for its prospective antinociceptive, anti-inflammatory and antipyretic activities. MBHE was eluted through column chromatography to isolate the bioactive secondary metabolites which may probably involve in its beneficial properties., Methods: The phytochemical constituents in MBHE was elucidated using UV, IR, (1)H-NMR, (13)C NMR, 2D-NMR spectra in combination with EIMS and FAB-MS spectrometric techniques and comparison with literature data of related compounds. The antinociceptive activity of MBHE was evaluated in the acetic acid induced abdominal constriction assay; the anti-inflammatory potential was assessed in the carrageenan induced paw edema, while the antipyretic effect was tested against brewer's yeast induced pyrexia in BALB/c mice at doses of 50, 100 and 150 mg/kg., Results: Elution of MBHE along with various characterization techniques led to the isolation of oleanolic acid and isoquercetin. Significant attenuation of chemical induced nociception was observed with MBHE at tested doses of 50 mg/kg (P < 0.01, 68.87 %), 100 mg/kg (P < 0.01, 68.87 %) and 150 mg/kg (P < 0.001, 83.02 %). During a duration of 1-5 h in the carrageenan induced paw edema assay, significant ameliorative effect (P < 0.01, P < 0.001) was demonstrated by MBHE at 50 mg/kg (22.94-20 %), 100 mg/kg (33.23-21.13 %) and 150 mg/kg (38.23-25 %). MBHE also significantly alleviated the brewer's yeast induced pyrexic response when tested at doses of 50 mg/kg (P < 0.05 in 2nd h), 100 mg/kg (P < 0.05, P < 0.01 and P < 0.001 in 1-5 h) and 150 mg/kg (P < 0.01 and P < 0.001 in 1-5 h)., Conclusion: These findings suggest that Monotheca buxifolia possess pain, inflammation and pyrexia ameliorating properties, probably mediated by the presence of oleanolic acid and isoquercetin contents, though the involvement of other important phytochemicals constituents cannot be ignored.

Background: Nefang is a polyherbal anti-malarial composed of Mangifera indica ( MiB and MiL; bark and leaf), Psidium guajava ( Pg ), Carica papaya ( Cp ), Cymbopogon citratus ( Cc ), Citrus sinensis ( Cs ) and Ocimum gratissimum ( Og ) (leaves). Previous studies have demonstrated its in vitro and in vivo antiplasmodial activities, antioxidant properties and safety profile. This study aimed at evaluating the antipyretic, anti-inflammatory and antinociceptive activities of the constituent plants of Nefang which are relevant to the symptomatic treatment of malaria fever., Methods: Antipyretic activities were determined by the D-Amphetamine induced pyrexia and Brewer's Yeast induced hyperpyrexia methods. Anti-inflammatory activities were investigated using the carrageenan-induced rat paw edema method. Antinociceptive activities were determined by mechanical nociception in the tail pressure and thermal nociception in the radiant heat tail flick and hot plate methods. Data was analysed using the one way ANOVA followed by Neuman-Keuls multiple comparison test., Results: Best percentage inhibition of induced pyrexia (amphetamine/brewer's yeast; p < 0.05) was exhibited by Cc (95/97) followed by Og (85/94), MiL (90/89), MiB (88/84) and Cs (82/89). Cc and Og exhibited comparable activities to paracetamol (100/95). Anti-inflammatory studies revealed paw edema inhibition (%) as follows (p < 0.05): Indomethacin (47), MiL (40), Cp (30), MiB (28) and Og (22), suggesting best activity by MiL. Antinociceptive studies revealed significant (p < 0.01) pain inhibition (%) as follows: Paracetamol (97), Og (113), MiL (108), Pg (84) and MiB (88). Og and MiL exhibited the best activities., Conclusion: The results obtained suggest that the constituent plants possess biologically active compounds with antipyretic, anti-inflammatory and antinociceptive activities. These activities are essential in the symptomatic treatment of malaria fever, thereby justifying the folk use of Nefang. This would be useful in its subsequent development for clinical application.

Background: Inflammation and pain underlies several pathological conditions. Synthetic drugs used for the management of these conditions carry severe toxic effects. Globally efforts are ongoing to introduce novel medicinal plants to develop effective, economic and innocuous drugs. The current study was aimed at investigating the antipyretic, anti-inflammatory and analgesic activity of methanol extract of A. hydaspica aerial parts (AHM) and its active fraction. Furthermore identification and isolation of polyphenolic compounds was carried out to identify the active principles., Methods: Yeast induced pyrexia, Paw edema, acetic acid-induced writhing and hot plate test were carried out in vivo. HPLC-DAD analysis and combination of different chromatographic techniques, involving vacuum liquid chromatography (VLC) and flash chromatography (FC) were carried out for chemical characterization. The structural heterogeneity of flavanols was characterized by ESI- MS, (1)H NMR, (13)C NMR and (2)D NMR spectroscopic analyses, and also by comparison with reported literature., Results: Oral administration of A. hydaspica methanol extract (AHM) and A. hydaspica ethyl acetate fraction (AHE), showed dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, Paracetamol. AHM and AHE (150 mg/kg) significantly (p < 0.001) inhibit pain sensation in various pain models, i.e. acetic acid induced writhing and hot plate test. Similarly AHM and AHE demonstrated an anti-inflammatory effect in carrageenan-induced paw edema in rats and 150 mg/kg dose being distinctly more effective (91.92% inhibition). When studied on prostaglandin E2 (PGE2) induced edema in rats, AHM and AHE showed maximum inhibition of edema at 150 mg/kg after 4 h. HPLC chromatogram of AHM revealed the presence of gallic acid, catechin, rutin and caffeic acid. Chromatographic separation and structure characterization of AHE, has led to the identification of three flavan-3-ol derivative including 7-O-galloyl catechin, +catechin and methyl gallate, which have been reported for the first time in A. hydaspica., Conclusion: These results revealed that the presence of bioactive compounds in A. hydaspica might be responsible for the pharmacological activities, confirming the indigenous utility of A. hydaspica against inflammatory disorders.

Background: Fever and pain management is a very challenging job for the clinician as the available synthetic agents are causing serious side effects. The present research article deals with the antipyretic and antinociceptive activity of extract/fractions of Potentilla evestita and acacetin isolated from the chloroform fraction of the plant., Methods: Various chromatographic and spectroscopic techniques were used for the isolation and characterizion of compound. In-vivo yeast induced fibrile mice were used for antipyretic activity while acetic acid induced writhing and formalin tests were used for antinociceptive., Results: The extract/fractions of P. evestita caused marked antipyretic effect during various assessment times in which chloroform was the most prominent followed by ethyl acetate. When acacetin was injected, it produced marked effect with maximum activity of 33.28% and 55.01% at 5 and 10 mg/kg i.p respectively. When studied in acetic acid induced writhing test, the extract/fractions evoked significant antinociceptive effect in which chloroform was the most effective fraction followed by ethyl acetate. Acacetin showed significant antinociceptive effect with 44.77% and 67.03% reduction in abdominal constriction at 5 and 10 mg/kg i.p., respectively. Similarly, it evoked significant dose dependent reduction in noxious stimulation with 42.07% and 64.57% pain attenuation at 5 and 10 mg/kg i.p., respectively in initial phase. In the late phase, it illustrated more dominant effect with 46.32% and 67.29% reduction of painful sensation., Conclusions: In conclusion, the extract/fractions of P. evestita as well as the isolated compound, acacetin showed strong antipyretic and antinociceptive activity in various animal models possibly mediated through both peripheral and central mechanism.

Background: Isodon rugosus is used in folk Pakistan traditional practices to cure ailments related to gastrointestinal, respiratory and cardiovascular problems. Present study was undertaken to validate these folkloric uses., Methods: A crude methanol extract of the aerial parts of Isodon rugosus (Ir.Cr.) was used for both in vitro and in vivo experiments. The plant extract was tested on isolated rabbit jejunum preparations for possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. Acetylcholinesterase and butyrylcholinesterase inhibitory activities of Ir.Cr were also determined as well as its antioxidant activity. The in vivo antiemetic activity of the extract was evaluated by using the chick emesis model, while the analgesic and antipyretic activities were conducted on albino mice., Results: The application of the crude extract of I. rugosus to isolated rabbit jejunum preparations exhibited relaxant effect (0.01-0.3 mg/ml). The Ir.Cr also relaxed K+(80 m M)-induced spastic contractions in isolated rabbit jejunum preparations and shifted the Ca+2 concentration response curves towards right (0.01-0.3 mg/ml). Similarly, the extract, when applied to the isolated rabbit tracheal preparations relaxed the carbachol (1 μM)--as well as K+ (80 mM)-induced contractions in a concentration range of 0.01-1.0 mg/ml. Moreover, it also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit aorta preparations. The Ir.Cr (80 mg/kg) demonstrated antipyretic activity on pyrogen-induced pyrexia in rabbits as compared to aspirin as standard drug. The Ir.Cr also exhibited anti-oxidant as well as inhibitory effect on acetyl- and butyryl-cholinesterase and lipoxygenase (0.5 mg/ml)., Conclusions: The observed relaxant effect on isolated rabbit jejunum, trachea and aorta preparations caused by Ir.Cr is possibly to be mediated through Ca+2 channel blockade and therefore may provided scientific basis to validate the folkloric uses of the plant in the management of gastrointestinal, respiratory and cardiovascular ailments. The observed antioxidant activity as well as the lipoxygenase inhibitory activity may validate its traditional use in pain and inflammations.

Background: In the care of feverish children, symptomatic management is pivotal. Thus, the Italian Pediatric Society has recently published guidelines on fever management in children. Our aim was to investigate whether pediatric hospitalists, community pediatricians and pediatric residents differ in their every-day clinical practice with respect to symptomatic management of feverish children., Methods: 79 out of 118 physicians involved in pediatric care in an area of Northern Lombardy (Italy) filled in a modified version of the questionnaire derived from the Swiss national survey on symptomatic fever management., Results: Pediatric hospitalists (N = 29), community pediatricians (N = 30) and pediatric residents (N = 20) did not differ with respect to temperature threshold for symptomatic fever treatment, role of general appearance in modulating the threshold for fever management, first choice antipyretic drug, frequency of ibuprofen prescription, prescription of physical antipyresis, influence of exaggerated fear of fever on its management and potential to reassure families about this fear.On the other side, some significant differences were found. Pediatric residents more frequently lower the treatment threshold in children with a past history of febrile seizures (P < 0.001) and prescribe an aggressive treatment for fever not responding to the first antipyretic drug (P < 0.01) than their more experienced colleagues. Community pediatricians represent the unique investigated group using homeopathic remedies, both in the acute setting (P < 0.001) as well as a prophylaxis (P < 0.0001). Finally, paediatric residents less often (P < 0.05) stated to encounter exaggerated fear of fever among parents than their more experienced colleagues., Conclusions: The present explorative inquiry globally shows limited discordance among pediatric residents, community pediatricians and pediatric hospitalists with respect to symptomatic fever management.

Background: Pyrexia, algesia and inflammation are associated with several pathological conditions. Synthetic drugs available for the treatment of these conditions cause multiple unwanted effects. Several studies are ongoing worldwide to find natural healing agents with better safety profile. The current study was thus aimed at evaluating antipyretic, analgesic and anti-inflammatory activities of the methanolic extract of whole plant of V. betonicifolia (VBME)., Methods: VBME was employed to assess antipyretic activity in yeast induced hyperthermia. Analgesic profile was ascertained in acetic acid induced writhing, hot plat and tail immersion test. Nevertheless, the anti-inflammatory activity was tested in carrageenan induced paw edema and histamine induced inflammatory tests. BALB/c mice were used at test doses of 100, 200 and 300 mg/kg body weight intra peritoneally (i.p)., Results: In yeast induced pyrexia, VBME demonstrated dose dependently (78.23%) protection at 300 mg/kg, similar to standard drug, paracetamol (90%) at 150 mg/kg i.p. VBME showed a dose dependent analgesia in various pain models i.e. acetic acid, hot plat and tail immersion having 78.90%, 69.96% and 68.58% protection respectively at 300 mg/kg. However, the analgesic action of VBME was completely antagonized by the injection of naloxone like opiate antagonists. Similarly carrageenan and histamine induces inflammation was significantly antagonized by VBME, 66.30% and 60.80% respectively at 300 mg/kg., Conclusions: It is concluded that VBME has marked antipyretic, analgesic and anti-inflammatory activities in various animal models and this strongly supports the ethnopharmacological uses of Viola betonicifolia as antipyretic, analgesic and anti-inflammatory plant.