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The characterization of NSAIDs in reducing pain, inflammation, and fever by inhibiting cyclooxygenase (COX) leads to the inhibition of prostaglandin synthesis, which is the primary mechanism; still, there are other mechanisms of NSAIDs to produce these effects. In this study, we report a comparison between nimesulide (NIM) (selective COX-2) and aspirin (ASP) (non-selective COX-2) inhibitors in mice model at the molecular level on the caspase-3, peroxisome proliferation-activated receptors-alpha (PPAR-α) and gene expression of COX-2. Individual ED100 doses of NIM and ASP (15.8 and 424.5 mg/kg, i.m.) were injected in mice for 5 consecutive days with and without acetic acid. This study reports new pharmacological mechanisms for NIM and ASP to contribute as anti-inflammatory drugs by other important intracellular mechanisms. NIM outperforms ASP for caspase-3 inhibition in the kidney, liver, and plasma (anti-apoptotic and anti-inflammatory effects). Also, NIM was better than ASP in molecular effects at the PPAR-α reducing inflammation and producing its antinociceptive effects. NIM and ASP in therapeutic doses reduced the COX-2 gene expression in the kidney (down-regulation), which causes the potentiation effect as an anti-inflammatory and analgesic drug. This research provided that NIM outperforms ASP in efficacy for the new mechanisms of NIM and ASP for inhibition of caspase-3 and binding with PPAR-α which worked as an anti-inflammatory action and reduced pain plus the suppression of COX-2 gene expression (down-regulation), which all contributing to reducing inflammation, pain and fever.

Background: Fever remains a common clinical indicator of disease, accounting alone for over 25% of paediatric emergency rooms consultations. Perception of this important sign is a crucial prelude and determinant of outcome in febrile children. The aim was to determine knowledge and attitudes of parents regarding fever in their children. Methods: The study is a crosssectional descriptive study carried out at the Emergency Paediatric Unit of the University of Ilorin Teaching Hospital (UITH). Fourhundred under-five children presenting with fever were recruited along with their caregivers. A semi-structured questionnaire was administered to collect information on sociodemographics, and caregiver’s knowledge and attitudes regarding fever in their wards. Results: The mean age of the caregivers was 29.5 ± 4.46 years (Range 21 – 41 years). Only 30.3% of caregivers could correctly describe what fever was. The most frequently utilised fever detection method was tactile assessment. Only 3.2% of the caregivers used a thermometer to detect fever. Social class, maternal age and religion significantly influenced the decision to use thermometers. The most common remedies caregivers would use for fever in their children were to give paracetamol (96.3%), sponging (73.2%) and a warm bath (63.8%). About 61% of caregivers had a wrong perception of the possible complications of fever. Conclusions: Caregivers in this study had a poor knowledge of fever, and parental educational and socioeconomic status impacted on their responses to fever. There is a need for education of caregivers at all contacts with the healthcare system on fever, and its management.

Background and purpose: Inflammation, fever, and pain can be associated with several diseases, and the synthetic drugs used in the treatment of these conditions often have severe side effects. As a result, there is a need for effective, economical, and safe alternative drugs, such as those derived from medicinal plants. Therefore, this study aimed to evaluate the anti-inflammatory, antipyretic, analgesic, and antioxidant activities of Castanopsis costata leaf fractions (CcLF), as well as its acute toxicity. Experimental approach: For anti-inflammatory, antipyretic, and analgesic tests, rats were given CcLF (WFCC, EAFcC, and n-HFCC) at 50 and 100 mg/kg, diclofenac sodium (10 mg/kg), paracetamol (150 mg/kg), aspirin (100 mg/kg), and tramadol (20 mg/kg). For the antioxidant activity test, various concentrations of CcLF were used ranging from 25 to 200 μg/mL. This study also looked into whether there could be any acute toxicity and histopathology of the liver, stomach, and kidneys in experimental animals. Findings/Results: The administration of CcLF significantly inhibited the increase in foot edema volume, and CcLF (EAFCC at 100 mg/kg) considerably decreased rectal temperature and was proportional to the standard drug paracetamol, and significantly inhibited pain sensation in various models. Additionally, CcLF showed strong antioxidant activity, and its administration at a dose limit of 5000 mg/kg/day did not show any toxic effects or death in test animals. Conclusions and implications: The results of the current confirmed that CcLF has demonstrated anti-inflammatory, antipyretic, analgesic, and antioxidant properties in experimental models, and is practically non-toxic.

Background: Indigofera gerardiana (IG) is traditionally used for its medicinal properties, but scientific validation is limited. This study aimed to evaluate its pharmacological effects, specifically anti-inflammatory, analgesic, and antipyretic activities, using established animal models. Methods: This experimental study was conducted at the Pharmacology Department of Khyber Medical College and University, Peshawar between Feb 2022 and Aug 2023. The n-hexane fraction of IG was tested at concentrations of 100mg/kg, 150mg/kg, and 200mg/kg in in-vivo animal models. Anti-inflammatory effects were assessed with paw edema models in 30 rats, analgesic effects in 30 mice using writhing and hot plate tests, and antipyretic activity in 30 rabbits with yeast-induced fever. Data were analyzed using one-way ANOVA with Dunnett’s post hoc test. Results: The n-hexane fraction of IG showed a dose-dependent anti-inflammatory effect, reducing carrageenan-induced edema by 12.5% and histamine-induced edema by under 15% at 200 mg/kg i.p. after 3 hours. Analgesic activity was also dose-dependent, with pain inhibition in the acetic acid-induced writhing model of 16.9% at 100 mg/kg, 20.76% at 150 mg/kg, and 26.13% at 200 mg/kg. In the hot plate test, maximum pain inhibition occurred at 200 mg/kg after 90 minutes (p < 0.001). However, IG extract did not show significant antipyretic effects compared to paracetamol, which effectively reduced fever at all doses (p < 0.001). Conclusion: The study findings suggest that the n-hexane portion of IG exhibits significant anti-inflammatory and analgesic activities across various animal models while showing no substantial impact on yeast-induced pyrexia.

The current study was aimed to investigate the ethno-pharmacology, diversity, biological potentials of different mushrooms species from District Swabi, Pakistan. Ethno-pharmacological data was collected from 73 respondents based on interview, group discussion and field visits. Quantitative analysis such as informant consent factor (ICF), Use value (UV), Relative Frequency of Citation (RFC) were done. Morphological identification of mushrooms, extract preparation, phytochemical screening and statistical analysis of data was conducted. Phytochemical analysis of six mushroom species revealed that saponins, alkaloids, glycosides, flavonoids and phenols were present in six selected mushrooms, while tannin and steroids (−) present in Agaricus arvensis. In Morchella conica only steroids (−) was absent, Qunion (−) in Polyporus tuberaster, Pleurotus ostreatus and Omphalotus olearius were found absent. Moisture contents (10.17 ± 1.27) and crude fats (5.26 ± 1.50) present in Omphalotus olearius. Highest content of crude fibers (26.57 ± 0.86) and carbohydrates (62.18 ± 0.73) were found in Pleurotus ostreatus. Highest ash contents (12.62 ± 0.46) were reported in Polyporus tuberaster. The respondents’ consensus factor values ranged from 1.66 to 61.74 in which highest ICF value was 61.74 while the lowest was 1.66. The high RFC was recorded for Agaricus (0.67) while lowest RFC was observed in Clitocybe frondasa (0.05). The results of analgesic activity were compared to the diclofenac (Standard drug). The extracts of aqueous and methanolic extract were most active at the level of (400 mg/kg). As antipyretic agents, methanolic and aqueous extracts of Agaricus species were analyzed for anti-inflammatory activity compare to diclofenac (Standard drug) where the aqueous (200 mg/kg) and methanolic (400 mg/kg) were found to be very active. Finally, mushrooms with high (ICF and UV) were further investigated for phytochemicals and pharmacological analysis which revealed significant biological potentials. This provides basic ground information which can be used to explore novel mushroom-based medicines for the treatment of various diseases. The commercial cultivation of mushrooms represents a promising opportunity to leverage their diverse health benefits and nutritional properties. By prioritizing research and cultivation methods while educating the public, the potential of mushrooms as vital components of both nutrition and medicine can be significantly realized, impacting health outcomes and contributing to sustainable agricultural practices.

Malaria claims over 600,000 deaths annually with a disproportionately high burden in the WHO African Region. The development of parasite resistance has warranted the search for novel anti-plasmodial drug candidates. This research aimed at validating the efficacy of Senegalia ataxacantha and tracking down its bioactive constituents. In vivo antiplasmodial activity of the extract was assessed using suppressive and curative protocols. Yeast-induced pyrexia was employed to evaluate the antipyretic activity of the extract. In vitro anti-plasmodial activity of isolated compounds was done using SYBR green I fluorescence assay on chloroquine sensitive (3D7) and resistant (Dd2) strains of P falciparum. In silico pharmacokinetic and interactions with parasites lactate dehydrogenase predictions of isolated compounds was conducted through molecular docking studies. Ethanol (70 %) extract of the plant showed in vitro and in vivo anti-plasmodial effect. The extract demonstrated significant (p < 0.05) dose-dependent suppression of 63.39 % and 63.32 % respectively at the highest dose (300 mg kg-1). Artesunate (4 mg kg-1/day) had considerably better curative potential (85.25%). The compounds showed in vitro anti-plasmodial activity in the order lupeol> friedelin/ friedelinol mixture>friedelin>β-sitosterol based on IC50 measurement. Friedelinol and lupeol exhibited higher binding affinities with pfLDH compared to Chloroquine. The extract and acetaminophen (positve control) showed significant (p < 0.05) reduction in rectal temperature compared to the control group. In silico studies of the compounds revealed moderate interactions with some cytochrome P450 metabolizing enzymes. S. ataxacantha stem extract shows anti-plasmodial and antipyretic activities which may be due to its pentacyclic triterpenoid constituents inhibiting pfLDH.

Uncontrolled inflammation is a crucial factor in the development of many diseases. Anti-inflammatory molecules based on natural sources are being actively studied, among which Aristida depressa Retz (Ar.dp) has been traditionally used as a paste to heal inflammation. The present study aimed to evaluate the anti-inflammatory, analgesic, and antipyretic potential of an ethanolic extract of A. depressa through a battery of in vivo and in vitro models. The ethanolic extract of A. depressa was prepared by maceration and chemically characterized using high-performance liquid chromatography, which revealed the presence of quercetin, vanillic acid, chlorogenic acid, p-coumaric acid, m-coumaric acid, ferulic acid, cinnamic acid, and sinapic acid; its antioxidant capacity was then screened with the DPPH in vitro assay, which indicated moderate scavenging capacity. A protein denaturation assay was next performed to evaluate the in vitro anti-inflammatory potential of Ar.dp, which showed significant inhibition (44.44%) compared to the standard drug (diclofenac sodium), with 89.19% inhibition at a concentration of 1 mg/mL. The in vivo safety profile of Ar.dp was evaluated in accordance with the OECD-425 acute toxicity guidelines and found to be safe up to 5 g/kg. The in vivo anti-inflammatory potentials of Ar.dp were evaluated at three different doses (125, 250, and 500 mg/kg) in acute (carrageenan-induced edema: 84.60%, histamine-induced paw edema: 84%), sub-chronic (cotton-pellet-induced granuloma: 57.54%), and chronic (complete-Freund’s-adjuvant-induced arthritis: 82.2%) models. Our results showed that Ar.dp had significant (p < 0.05) anti-inflammatory effects over diclofenac sodium in the acute and chronic models. Histopathology studies indicated reduced infiltration of paw tissues with inflammatory cells in Ar.dp-treated animals. Similarly, Ar.dp showed significant (p < 0.05) analgesic (yeast-induced-pyrexia model: 23.53%) and antipyretic (acetic-acid-induced writhing model: 51%) effects in a time-dependent manner. In silico studies on the interactions of COX-1 and COX-2 with the eight ligands mentioned earlier confirmed the inhibition of enzymes responsible for inflammation and fever. Based on the findings of the present study, it is concluded that Ar.dp has anti-inflammatory, analgesic, and antipyretic properties that are likely linked to its pharmacologically active phenolic bioactive molecules.

An analgesic-antipyretic drug widely used is paracetamol, which has various health benefits and several adverse effects. Therefore, various natural products have been extensively studied as alternative analgesic-antipyretics, one of which is sweet orange peel. This study aimed to investigate sweet orange peel's analgesic and antipyretic activity by in vivo methods. This experimental study evaluated the analgesic and antipyretic effects of sweet orange peel extract extracted by the maceration method. The analgesic effect was evaluated by tail immersion (Maximum Possible Analgesia) and acetic acid-induced writhing method (total abdominal writhing). Meanwhile, the antipyretic effect was evaluated by the brewer yeast-induced hyperpyrexia (body temperature) method. This study showed that sweet orange peel methanol extract significantly increased the maximum possible analgesia value (132.79%) and reduced the number of abdominal writhing (44.05%) at the highest dose of 750 mg/kg BW. It indicated analgesic activity from sweet orange peels. Meanwhile, the antipyretic effect of sweet orange peel methanol extract was observed from 1-4 hours after administration, and the highest percentage inhibition of body temperature 4 hours after administration was found in a moderate dose, that was 5.98% (P value: 0.042). Therefore, it can be concluded that sweet orange peel methanol extract has analgesic and antipyretic effects with an optimal dose range of 500-750 mg/kg BW.

The objective of the current study was to evaluate the anti-inflammatory, analgesic, and antipyretic potential of Oxystelma esculentum using different animal models. The phytochemical profile was determined by assessing its total phenolic content (TPC) and total flavonoid content (TFC), followed by the high-performance liquid chromatography (HPLC) technique. The in vitro anti-inflammatory potential of O. esculentum ethanolic extract (OEE) was evaluated by lipoxygenase enzyme inhibition activity and a human red blood cell (HRBC) membrane stability assay. The in vivo anti-inflammatory potential of the plant was determined by the carrageenan-induced paw edema test, and the analgesic potential by the hot plate test, tail-flick test, formalin-induced analgesia, acetic acid-induced writhing activities, and yeast-induced elevation of body temperature. The values of total phenolic content (212.6 ± 3.18 µg GAE/g) and total flavonoid content (37.6 ± 1.76 µg QE/g) were observed. The results showed that OEE exhibited significant antioxidant capacity in DPPH (2,2-diphenyl-1-picrylhydrazyl) (266.3 ± 7.35 μmol TE/g), ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (1,066.3 ± 7.53 μmol TE/g), and FRAP (ferric reducing antioxidant power) (483.6 ± 3.84 μmol TE/g) assays. The HPLC analysis demonstrated phytocompounds with anti-inflammatory potential, such as chlorogenic acid, gallic acid, 4-hydroxybenzoic acid, caffeic acid, ferulic acid, and coumarin. The plant showed in vitro anti-inflammatory activity through the inhibition of lipoxygenase enzyme with a high percentage (56.66%) and HRBC membrane stability (67.29%). In in vivo studies, OEE exhibited significant (p < 0.05) anti-inflammatory (carrageenan-induced paw edema model), analgesic (hot plate test, tail-flick test, formalin-induced analgesia, and acetic acid-induced writhing), and antipyretic (rectal temperature reduction) responses at different doses (100, 300, and 500 mg/kg). Molecular docking studies showed significant binding affinities of phytocompounds compared to indomethacin and predicted various binding interactions for stable conformations. The results of in vitro, in vivo, and in silico studies supported the anti-inflammatory, analgesic, and antipyretic potential of O. esculentum.

Abstract Background Paracetamol (acetaminophen) is recommended as a first‐line drug in the management of pain and pyrexia in humans due to its minor gastrointestinal, renal and vascular side effects. Objectives To explore the perceptions and use of paracetamol in dogs by UK veterinarians. Methods Veterinarians were invited to complete an online survey. Questions addressed career history, previous use, and personal perceptions of the use of paracetamol in dogs. Results A total of 450 veterinarians were included in the survey; 96% (n = 431) of whom worked in small animal practice only. The majority reported a frequency of use of 1–3 times a week (n = 197), with oral dosing being the most common route of administration (n = 440). Only 8 had never prescribed paracetamol. Paracetamol was more commonly used to provide analgesia (n = 431) than for the treatment of pyrexia (n = 292) and was predominantly used as an alternative to NSAIDs (n = 408) or as part of multimodal analgesia (n = 406). Hepatotoxic (n = 311) and gastrointestinal (n = 120) side effects were a common concern, although the majority perceived a low risk of side effects and felt they were likely to be mild if they did occur (n = 279). Only 5% (n = 24) of respondents reported having experienced side effects, with gastrointestinal signs (n = 14) and hepatotoxicity (n = 6) being the most common. Conclusions Paracetamol is widely used by veterinarians working in the UK. Most veterinarians have changed their perception on the use of paracetamol over the last decade and consider it to be associated with fewer side effects and with more effective analgesic and antipyretic effects than they had previously believed.

The green synthesis of zinc oxide nanoparticles (ZnO NPs) using plants has grown in significance in recent years. ZnO NPs were synthesized in this work via a chemical precipitation method with Jasminum sambac (JS) leaf extract serving as a capping agent. These NPs were characterized using UV-vis spectroscopy, FT-IR, XRD, SEM, TEM, TGA, and DTA. The results from UV-vis and FT-IR confirmed the band gap energies (3.37 eV and 3.50 eV) and the presence of the following functional groups: CN, OH, C=O, and NH. A spherical structure and an average grain size of 26 nm were confirmed via XRD. The size and surface morphology of the ZnO NPs were confirmed through the use of SEM analysis. According to the TEM images, the ZnO NPs had an average mean size of 26 nm and were spherical in shape. The TGA curve indicated that the weight loss starts at 100 °C, rising to 900 °C, as a result of the evaporation of water molecules. An exothermic peak was seen during the DTA analysis at 480 °C. Effective antibacterial activity was found at 7.32 ± 0.44 mm in Gram-positive bacteria (S. aureus) and at 15.54 ± 0.031 mm in Gram-negative (E. coli) bacteria against the ZnO NPs. Antispasmodic activity: the 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by (78.19%), acetylcholine (at a concentration of 1 µM) by (67.57%), and nicotine (at a concentration of 2 µg/mL) by (84.35%). The antipyretic activity was identified using the specific Shodhan vidhi method, and their anti-inflammatory properties were effectively evaluated with a denaturation test. A 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by 78.19%, acetylcholine (at a concentration of 1 µM) by 67.57%, and nicotine (at a concentration of 2 µg/mL) by 84.35%. These results underscore the sample solution’s potential as an effective therapeutic agent, showcasing its notable antispasmodic activity. Among the administered doses, the 150 mg/kg sample dose exhibited the most potent antipyretic effects. The anti-inflammatory activity of the synthesized NPs showed a remarkable inhibition percentage of (97.14 ± 0.005) at higher concentrations (250 µg/mL). Furthermore, a cytotoxic effect was noted when the biologically synthesized ZnO NPs were introduced to treated cells.

The chitin and chitosan biopolymers are extremely valuable because of their numerous industrial and pharmacological uses. Chitin and chitosan were extracted from the exoskeleton of Periplaneta americana (cockroaches) and termites using various acid and alkali techniques. The extraction process involves an initial demineralization step, during which integument dry powder was subjected to 500 mL (2.07 mol/L) of concentrated HCl at 100 degrees Celsius for 30 min, followed by meticulous rinsing with distilled water to restore the pH to its baseline. Deproteinization was conducted at 80 degrees Celsius using 500 mL (1 mol/L) of NaOH solution, which was repeated for 24 h. A total of 250 mL (0.06 mol/L) of NaOH was added at 100 degrees Celsius for 4 h to obtain chitosan, followed by extensive washing and subsequent drying. FTIR analysis was used to identify the functional groups in Periplaneta americana and termites. The crystallinity of these biopolymers, which have a face-centered cubic structure, was determined by X-ray diffraction analysis. This study assessed the analgesic properties of chitin and chitosan via an acetic-acid-induced writhing test in mice, revealing a significant reduction in writhing behavior following the chitin and chitosan extract. Notably, chitin exhibits the highest degree of analgesic activity compared to chitosan. Both chitin and chitosan show anti-inflammatory effects, with chitosan absorbing proton ions at sites of inflammation, while chitin effectively inhibits ear edema and elicits an analgesic response in mice. Furthermore, the present study revealed antipyretic activity, with termite chitin demonstrating the most significant effect at a concentration of 500 µL/mL, followed by chitosan and chitin at 100 µL/mL. These findings indicate the potential of using chitin and chitosan derived from termites and Periplaneta americana as natural anti-inflammatory compounds, implying prospective uses in anti-inflammatory, antipyretic, and analgesic capabilities.

Red dragon fruit (Hylocereus polyrhizus) is a tropical fruit that is currently cultivated in all tropical parts of the world. It is popular to consume its fruit flesh, while the peel is often thrown away. This red dragon fruit peel (RDFPE) is known to possess lots of phytochemical compounds with multitudes of usage, amongst them as an analgesic and antipyretic. Therefore, the active compounds of RDFPE play an important role in the natural product. This study aims to observe and analyze the analgetic and antipyretic activity possessed by red dragon fruit peel. This study is an in-vivo experiment on 25 white male rats divided into five groups, in which each group receive Na CMC, acetaminophen, and the other three groups will receive three different doses of RDFPE (500 mg/kg, 750 mg/kg, and 1000 mg/kg), respectively. Acetic acid writhing and tail immersion methods were performed to induce inflammation and Brewer’s yeast injection performed induced pyrexia. In the investigation of the acetic acid writhing test, the intervention was administered before induction, and for the tail immersion test, induction was given before and after the intervention was administered. Meanwhile, in brewer’s yeast-induced pyrexia, the rectal temperature was measured before induction, 24 hours after induction, and each hour for five four after the intervention; intervention was administered 24 hours after induction. This study found that RDFPE at the dose of 750 mg/kg and 1000 mg/kg are effective as an analgesic by reducing the average writhing and delaying the tail retraction of the experiment subject and also effective as an antipyretic by reducing the elevated temperature of the experiment subject (p

Background: Artabotrys hexapetalus is a rare plant in the Indian subcontinent. This plant is used for different therapeutic purposes in folk medicine and many bioactive compounds are reported in this plant. Considering its traditional uses and the presence of medicinal compounds, we aimed to evaluate some pharmacological properties of its leaves along with in silico analysis in scientific ways. Methods: Antioxidant tests were conducted in both qualitative and quantitative ways. 2,2-Diphenyl-1-picryl hydrazyl (DPPH), hydrogen peroxide, and superoxide radicals scavenging with FeCl3 reducing properties of A. hexapetalus extract were carried out. Acetic acid-induced writhing, tail immersion, formalin-induced paw edema, and Brewer's yeast-induced pyrexia methods were followed to conduct peripheral analgesic, central analgesic, anti-inflammatory, and antipyretic potentialities, respectively. Finally, molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of reported compounds were conducted. Results: The A. hexapetalus extract was found to possess a quite good amount of phenolics, flavonoids, and tannins. This extract also revealed good radical scavenging effects along with ferric chloride-reducing capabilities. In the analgesic tests, the extract showed excellent responses in writhing inhibition and elongation in tail withdrawal time. The extract also significantly lessened paw edema over time at both doses. A notable decrease in body temperature was also observed. Those responses revealed nice pharmacological potentialities. Along with these findings and conducting in silico analysis, we finally proposed seven molecules as lead compounds. Conclusion: Our analysis revealed that A. hexapetalus leaves are highly enriched with antioxidants and the extract showed good pharmacological characteristics.

Abstract Background Chukrasia velutina is an enthnomedicinally used plant reported to have significant medicinal values. The present study aimed to explore the pharmacological activities of bark methanol extract using in vitro, in vivo and in silico models. Methods The study was designed to investigate the pharmacological effects of methanol extract of Chukrasia velutina bark (MECVB) through in vitro, in vivo and in silico assays. Analgesic activity was tested using formalin‐induced nociception and acetic acid‐induced writhing assays while the antipyretic effect was tested using yeast‐induced hyperthermia in mice model. The antioxidant effect was tested using the DPPH and reducing power assay and the cytotoxic screening was tested using the brine shrimp lethality bioassay. In addition, in silico studies were conducted using computer aided methods. Results In the acetic acid‐induced writhing assay, the extract showed 28.36% and 56.16% inhibition of writhing for doses of 200 and 400 mg/kg, respectively. Moreover, a dose‐dependent formalin‐induced licking response was observed in both early and late phase. In yeast‐induced pyrexia, the MECVB exhibited (p

Antipyretic drugs such as suspensions of mefenamic acid (ponstan), Ibuprofen and paracetamol (acetaminophen) are the most common drugs that wildly used in children to decrease the fever, pain and inflammation. From clinical observations of children using these drugs, they cause gastrointestinal complications and from this, the idea of this research was to find the effect of these drugs on the mucous membrane of the gastrointestinal tract in Swiss albino mice. In the present study, we used 30 mice classified into five groups including G1 as control group, G2 received 15 mg/kg/day panadol, G3, 30 mg/kg/day ibuprofen, G4, 5 mg/kg/day ponstan and G5, a combination of panadol and ibuprofen in the same previously- mentioned doses for 7 days respectively. The gastric histological sections of G2 exhibited normal mucosal; G4 displayed mild mucosal glandular hyperplasia; while G3 and G5 e appeared flat mucosal surface with submucosal hyperplasia of gland mild atypical cells; and G2 revealed mucosal glandular hyperplasia. The intestine histological sections of G2 appeared normal intestinal villi with mild inflammatory cells infiltration; G3 showed dispersed slight shortening of intestinal villi with mild inflammatory cells infiltration; finally, G4 and G5 indicated villi hyperplasia with a slight widening of villi with mild inflammatory cells infiltration. NSAIDs are available over-the-counter drugs for adult and in paediatric population and are considered as a safe medicine if used in properly dose in the short-term. The decision to pick an antipyretic should be dictated by safety, efficacy, effectiveness, duration of action and the integrity of the patient gut.

Objective: To compare the clinical effectiveness of Paracetamol with Ibuprofen as an antipyretic, fever relief and linked discomfort in children. Study Design: Comparative cross-sectional study. Place and Duration of Study: Combined Military Hospital, Abbottabad Pakistan from Apr to Nov 2019. Methodology: Children aged six months to five years, who reported fever between 38-41°C were included. Two temperature groups were developed, i.e., 37.8–38.9ºC and 39–41ºC with baseline temperatures of 38.60±0.56 for Paracetamol-Group and 38.58± 0.56ºC for Ibuprofen-Group. The prescriptions were given over to the parents with clarification about the dose of the medication. The medication had active and placebo forms. Information was gathered until saturation was done. Results: A total of 104 children were taken in the study. Of these, 77(74.08%) were females, and 27(24.96) were males. Comparing Ibuprofen-treated children with Paracetamol-Group, the final result showed that the extent of children's temperature management was greater in the Ibuprofen-Group 37(71%) than in the Paracetamol-Group 34(65%). Conclusion: Doctors, attendants and guardians wishing to use medications to treat children suffering from fever should be encouraged to use Ibuprofen first and to consider the relative risks and advantages of using Ibuprofen in addition to Paracetamol for fever. Comparatively, Ibuprofen is more effective than Paracetamol.

Context: The anti-nociceptive and anti-pyretic properties of the crude aqueous extract of Anogeissus leiocarpa (DC). Guill. & Perr. leaves have been reported. Aims: To investigate the anti-inflammatory, anti-nociceptive, and anti-pyretic properties of aqueous extract of A. leiocarpa leaves (AEAL) and its fractions to identify the bioactive compound(s). Methods: AEAL was fractionated successively and eluted in gradients of solvent mixture (n-hexane, ethylacetate, and methanol). Eluates, which showed similar TLC profiles were pooled to afford 5 fractions (F1-F5). AEAL and the fractions were subjected to phytochemical analysis and investigated for anti-inflammatory, anti-nociceptive, and anti-pyretic effects using carrageenan-induced paw edema and Brewer’s yeast-induced pyrexia in rats, and acetic acid-induced writhing in mouse models, respectively. Results: Phytochemical analysis indicated presence of terpenoids, saponins, steroids, glycosides, flavonoids, tannins and alkaloids. At 200 mg/kg b.w, AEAL and F1-F5 recorded significant (p

Dimethyl dimethoxy biphenyl (DDB) dicarboxylate has been applied as a therapeutic modality for curing liver diseases, particularly hepatitis virus. The objective of this study was to assess the protective potential against Triton X-100 induced abnormal fat metabolism in addition to anti-inflammatory, analgesic, and antipyretic effects of DDB. The anti-inflammatory, antinociceptive, and antipyretic of DDB were investigated through induction of paw edema, pain, and fever in experimental rats. DDB decreased cholesterol and triglyceride contents. DDB resulted in inhibition of inflammation, nociception, and fever in the experimental models. DDB improved lipid profile, as evidence of hypolipidemic potential. It also showed anti-inflammatory, analgesic, and antipyretic properties.

The eco-friendly green bio-synthesis of Ephedra-AuNPs was constructed from Ephedra plant extract. The synthesis process was optimized using different volumes of Ephedra-extract, 10-3M (HAuCl4·3H2O) solution, reaction temperature, time, and pH of the solution. Where, 4 mL of Ephedra-extract, 6 mL of 10-3M (HAuCl4·3H2O) solution at 25 °C for 3 h at a pH of 4 are showed the optimum reaction parameters respectively. The characterization of AuNPs was verified by UV–vis. spectrophotometer, FTIR, microscopic techniques (TEM, HRTEM), Zeta potential, and X-ray techniques (XRD, EDX, XPS). The nanoparticles are extremely important materials in emerging the future sustainable technologies for the living beings. The AuNPs were employed in biological assays where ABTS assay used to investigate the antioxidant activity. The in-vivo study of AuNPs was executed to study the anti-pyretic and anti-asthma activities of Ephedra-AuNPs. Ephedra-AuNPs of 1.3 nm to 15.6 nm size were achieved which have as importance as proficient to bind with the biological systems. The Ephedra-AuNPs prepared exploiting Ephedra-extract which is considered to be influential anti-asthma agent and antipyretic agent reduced the fever by 83.3 % at 32μg/g/day. Further the Ephedra-AuNPs used to scrutinize the anti-bacterial activities for Staphylococcus aureus, Listeria moncytogenes, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium, and anti-fungal activities on Candida albicans, Aspergillus nigra and Aspergillus flavus. The synthesized Ephedra-AuNPs exhibited great potential activities comparable to the standard drugs in case of Staphylococcus aureus, Escherichia coli, Candida albicans with the zone of inhibition of 25 ± 0.5 nm, 26 ± 0.6 nm and 24 ± 0.7 nm respectively. It is believed that the synthesized Ephedra-AuNPs to be a hopeful option intended for diverse biological applications.

The relation between pre-vaccination antipyretic use and antibody responses to SARS-CoV-2 vaccination has been unclear. We measured the pre- and post-BNT162b2 booster spike-specific IgG titers and recorded antipyretic use and adverse reactions for SARS-CoV-2-naive hospital healthcare workers. The data of 20 cases who used antipyretics within 24 h before vaccination were compared to that of 281 controls. The post-booster geometric mean IgG titers were 15,559 AU/mL (95 % CI, 11,474–21,203) for the cases and 16,850 AU/mL (95 % CI, 15,563–18,243) for the controls (p = 0.622). No significant reduction in the frequency or severity of any of the solicited adverse reactions was found for the cases. Similar results were obtained after adjustment with propensity-score matching for demographic characteristics, baseline IgG titer, and post-vaccination antipyretic use. Antipyretic use within 24 h before vaccination would not affect mRNA COVID-19 vaccine-induced specific antibody responses and that postponement of vaccination due to pre-vaccination antipyretic use would be unnecessary.

Abstract Background Macropanax dispermus is traditionally used to treat various diseases by ethnic people. The present research reports the pharmacological properties with phytochemical profiling of the crude extracts of M. dispermus leaves (MDML), its n-hexane (MDHL), carbon tetrachloride (MDTL), chloroform (MDCL), ethyl acetate (MDEL), and aqueous (MDAL) fractions, and crude methanol extracts of its stem barks (MDMS). The in vitro thrombolytic activity was done on human erythrocytes whereas the cytotoxic activity was done by brine shrimp lethality assay. The in vivo analgesic activity was examined by acetic acid-induced writhing, tail immersion, and formalin-induced paw licking method. In contrast, antipyretic activity was done by the brewer’s yeast-induced pyrexia method. Results MDHL and MDMS showed 37.05% and 42.21% of significant (p

Dillenia pentagyna Roxb. is traditionally used to treat cancer, wound healing, diabetes, and diarrhea in local tribes. This study was designed to evaluate the pharmacological potentiality of this plant. In vivo analgesic, anti-inflammatory, and antipyretic studies of the methanol extracts of D. pentagyna (MEDP) leaves were performed by using acetic acid-induced nociception, formalin-induced paw licking, and yeast-induced pyrexia assay methods, respectively. In vivo antidiarrheal activity was carried out in mice by following castor oil-induced diarrhea and gastrointestinal transit manner. In vitro thrombolytic experiment was performed employing the clot lysis activity. Besides, a molecular docking study was performed by executing the software (PyRx, Discovery Studio, and UCSF Chimera). In the acetic acid-induced writhing study, MEDP possesses significant writhing inhibition in a dose-dependent manner. It showed 50.86% of maximum inhibition of pain in the case of MEDP at a dose of 400 mg/kg body weight. In the anti-inflammatory study, maximum inhibition rate was observed at a value of 59.98 and 41.29% in early and late phases, respectively, at the dose of 400 mg/kg body weight. In the case of yeast-induced hyperpyrexia, MEDP reduced hyperpyrexia in a dose-dependent manner. In the antidiarrheal assay, MEDP moderately inhibited the occurrence of diarrhea in all the experiments. In the thrombolytic study, a moderate (17.76%) clot lysis potency has been yielded by MEDP. Again, the molecular docking simulation revealed strong binding affinities with almost all the targeted proteins. The present study suggests that the MEDP possesses remarkable pharmacological activity and this finding validated the ethnobotanical significance of D. pentagyna as the source of pain, fever, and diarrhea management agent.

Nowadays, there has been increased awareness that the therapeutic effects of natural medicines on inflammatory diseases may be achieved by regulating the gut microbiota. Shuanghuanglian oral liquid (SHL), the traditional Chinese medicine preparation, has been shown to be effective in clearing heat-toxin, which is widely used in the clinical treatment of respiratory tract infection, mild pneumonia, and common cold with the wind-heat syndrome. Yet the role of gut microbiota in the antipyretic and anti-inflammatory effects is unclear. In this study, a new strategy of the 16S rRNA gene sequencing and serum metabolomics that aims to explore the role of SHL in a rat model of the systemic inflammatory response induced by lipopolysaccharide would be a major advancement. Our results showed that the gut microbiota structure was restored in rats with inflammation after oral administration of SHL, thereby reducing inflammation. Specifically, SHL increased the relative abundance of Bacteroides and Faecalibacterium and decreased the abundance of Bifidobacterium, Olsenella, Aerococcus, Enterococcus, and Clostridium in the rat model of inflammatory disease. Serum metabolomic profile obtained by the orbitrap-based high-resolution mass spectrometry revealed significant differences in the levels of 39 endogenous metabolites in the inflammatory model groups, eight metabolites of which almost returned to normal levels after SHL treatment. Correlation analysis between metabolite, gut microbiota, and inflammatory factors showed that the antipyretic and anti-inflammatory effects of SHL were related to the recovery of the abnormal levels of the endogenous metabolites (N-acetylserotonin and 1-methylxanthine) in the tryptophan metabolism and caffeine metabolism pathway. Taken together, these findings suggest that the structural changes in the gut microbiota are closely related to host metabolism. The regulation of gut microbiota structure and function is of great significance for exploring the potential mechanism in the treatment of lipopolysaccharide-induced inflammatory diseases with SHL.

Objective(s): The present study determines the chemical constituents of Persea americana using gas chromatography-mass spectrometry (GC-MS) and its different activities. Materials and Methods: Air-dried powdered leaves of Persea americana were extracted by 95% methanol and fractionated consecutively with petroleum ether, chloroform, and ethyl acetate. The saponifiable matter, EtOAc and aqueous fractions were subjected to GC-MS. The analgesic, anti-inflammatory, antipyretic, and antihyperglycemic properties of extracts, different fractions, and crude polysaccharide were determined by hot plate, carrageenan-induced paw edema, yeast-induced pyrexia, and alloxan-induced hyperglycemia methods, respectively. Results: Fourteen fatty acid methyl esters were identified in GC-MS-based profiling of the saponifiable matter. Alongside, 13 compounds were determined from EtOAc fraction and 6 compounds from the aqueous fraction of P. americana leaves. The ethyl acetate fraction and total stem extract displayed high anti-inflammatory potential with percentage of paw edema reduction by 48.99 and 47.54 %, respectively, compared with that of indomethacin (42.90 %). The ethyl acetate fraction and total stem extract revealed the highest analgesic activity with 137.95 and 137.12 % percent of protection against external stimulus, respectively. Investigation of antipyretic efficiency showed the total stem extract and crude polysaccharides attained normal temperature after 3 hr, which was very close to that of acetylsalicylic acid. The total leaf and stem extracts displayed significant antihyperglycemic activity with significant reduction in the level of blood glucose by 76.67 and 59.05 %, respectively.Conclusion: P. americana had analgesic, anti-inflammatory, antipyretic, and antihyperglycemic properties, which refer to its bioactive metabolites.

Abstract Background The study sought to investigate the biological efficacy of methanol leave extract of Acacia auriculiformis (MEAA) via in vitro, in vivo, in silico approaches. The in vitro cytotoxicity was evaluated through brine shrimp lethality assay, and anti-inflammatory activity was determined by membrane stabilisation and protein denaturation methods (BSA and egg albumin). The in vivo antipyretic activity was examined via Brewer’s yeast induced pyrexia model. Results A. auriculiformis extract unveiled moderate cytotoxicity with significant anti-inflammatory efficacy (p < 0.001) compared to standard drug. This extract also exhibited dose-dependent time of paralysis and death for the worm (p < 0.001) in the anthelmintic test which was directly proportional to employed concentrations. A notable percentage of clot lysis effect (36.42 ± 1.95%, p < 0.001) was also observed for MEAA in human blood compared to control. However, this extract significantly (p < 0.05) reduced fever in a dose-dependent manner during the antipyretic experiment. Besides, in computer-aided investigations, two compounds (2,4-ditert-butylphenol and 3-hydroxy-β-damascone) revealed the best binding interaction with six proteins for cytotoxicity, inflammation, helminthic, thrombolytic and pyretic effect. Moreover, these two compounds satisfy Lipinski’s ‘Rule of Five’ and revealed drug-likeness profiles in the toxicological study. Conclusions These findings disclosed that methanol leaves extract of A. auriculiformis might be a potent source for anti-inflammatory, anti-helminthic, thrombolytic and antipyretic agents.

Polystichum lonchitis L. is a fern belonging to the family Dryopteridaceae. The present study was conducted to evaluate its pharmacological, antioxidant, and phytochemical properties, and to conduct GC–MS screening of P. lonchitis. The acetic acid-induced writhing test, yeast-induced hyperpyrexia method, carrageenan-induced rat paw edema model, and charcoal meal test model were carried out to assess analgesic, antipyretic, anti-inflammatory, and antispasmodic activity, respectively. DPPH was used as an antioxidant, while the phytochemical screening was conducted using standard scientific methods. Among the pharmacological activities, the most significant effects were observed in the analgesic and anti-inflammatory activities, followed by the antipyretic and antispasmodic activities, at a dose of 450 mg/kg after the 4th hour, compared with 150 mg/kg and 300 mg/kg. For the evaluation of antioxidant activities, the most significant results were detected in the methanolic and aqueous extracts. The detection of flavonoids and phenol occurred most significantly in the methanolic extract, and then in the ethanolic and aqueous extracts. The main compounds detected using GC–MS analysis with a high metabolic rate was 𝛼-D-Galactopyranoside, which had a metabolic rate of 0.851, and methyl and n-hexadecanoic, which had a metabolic rate of 0.972. Overall, the results suggested that P. lonchitis had a strong potential for pharmacological activities. The suggested assessment provided a way to isolate the bioactive constituents and will help to provide new medicines with fewer side effects. Due to the fern’s effectiveness against various diseases, the results provide clear evidence that they also have the potential to cure various diseases.

Abstract Background Naturally occurring substances of plant origin have long been used in folk medicine for curing various ailments including fever, pain, and inflammation etc. After careful evaluation on scientific bases, a large number of those substances provides cheaper alternative to currently used synthetic or semi-synthetic agents. Thus, with an aim of discovering alternative medicine for treatment of such ailments, current study was carried out. Euphorbia granulata Forssk. had long been used as a therapeutic agent against various morbid conditions, e.g., anthelmintic, snake bite, scorpion sting, purgative, and diuretic, and as blood purifying agent in folk medicine. The purpose of the current study was to determine the extended therapeutic use of Euphorbia granulata Forssk. based upon scientific evaluation, to explore the potential of its anti-proliferative, analgesic, antipyretic, and anti-inflammatory activities while using an aqueous methanol extract of the whole plant. Results In vivo study was performed on female rats of specie Rattus norvegicus weighing (100–150 g). Anti-inflammatory activity of the plant extract was calculated against using carrageenan induced paw edema. Analgesic potential both central and peripheral was assessed by using Eddy’s hot plate method and acetic acid-induced writhing model, respectively. The antipyretic potential was appraised using brewer’s yeast suspension, injected under the nape of the neck, and body temperature was measured using a digital thermometer. The plant extract strengths used for in vivo experiments were 50 mg, 100 mg, and 200 mg/kg (diluted in normal saline) and were administered through intra-peritoneal route. MTT assay was performed to estimate in vitro anti-proliferative potential. For this assay, a serial dilution of the plant extract was used with 100 μg/ml as the highest concentration. In vivo results demonstrated that plant extract at dose strength of 200 mg/kg, showed significant (p* < 0.05) anti-inflammatory, analgesic, and antipyretic activities. In case of MTT assay, however, no significant anti-proliferative activity (p > 0.05) was observed up to 100 μg/ml dose strength. Conclusion It can be concluded that aqueous methanol extract of Euphorbia granulata (whole plant) have shown significant anti-inflammatory, analgesic, and anti-pyretic activity in animal model. Therefore it can be a potential candidate, as a therapeutic alternative against treatment of algesia, pyrexia, and inflammation of various pathological origin. However, the plant extract did not demonstrate any significant anti-proliferation activity at doses used in this study.

Objective: To explore the anti-inflammatory and antipyretic effects of methanolic leaf extract from Arbutus andrachne and its mechanism of action. Methods: Paw edema was induced by intraplantar (i.pl.) injection of λ-carrageenan (1% w/v, 100 μL/paw) while pyrexia was evoked by intraperitoneal (i.p.) injection of 20% baker’s yeast (20 mL/kg body wt) in male Wistar rats. The anti-inflammatory and antipyretic effects of Arbutus andrachne methanolic leaf extract were explored by injecting rats with different doses of the plant extract (150, 300, and 600 mg/kg body wt, i.p.). Selective antagonists for transient receptor potential vanilloid-1 (TRPV1), cannabinoid receptor 1 (CB1), and alpha-2 adrenergic receptor (a2-AR) were used to unravel the extracts’ mechanism of action. Blood samples were collected from the heart of rats to measure the levels of interleukin-6 (IL-6) and prostaglandin E2 (PGE2) by enzyme-linked immunosorbent assay. Results: The extract exhibited potent anti-inflammatory activity by decreasing paw thickness and IL-6 levels. In addition, yeast-evoked pyrexia was attenuated by the extract treatment via TRPV1 and CB1 receptors and a reduction in PGE2 levels. No significant effects were found for a2-AR. Moreover, the rats that received the plant extract demonstrated similar responses to the positive control group. Conclusions: Arbutus andrachne can be a good candidate for treating inflammation and pyrexia and should be further investigated.

Prasachandaeng (PSD) remedy from the Thailand National List of Essential Medicines (NLEM) has been used as an antipyretic for chronic fever in both adults and children for centuries. Its therapeutic effect in treating fever and its safety have not been studied in animal models. We evaluated its antipyretic activity on lipopolysaccharide (LPS)-induced fever and safety in the liver in comparison with acetaminophen (ACP). Correlation between biochemistry of liver function and the level of cytochrome P450 (CYP2E1) was also evaluated using an ELISA kit. All doses of PSD powder (PSDP) and a 95% ethanol extract of PSD (PSDE) (50, 200, and 400 mg/kg) showed a significant antipyretic effect (* p

Fever is a condition where the body temperature rises above normal or more than 37o C and also tend to be an initial clinical manifestation of the use of antipyretic drugs thatcause toxicity such as on the liver due to prolonged usage. Particularly, the bangle (Zingiber purpureum Roxb.) is one of the Zingiberaceae plants that contain essential oils used for the treatment of fever. Therefore, this researchaimed to identify active compounds which have antipyreticspotential with the in silico approach. The simulation of molecular docking showed 1,4-naphthalenedione-2-ethyl-3-hydroxy was able to attach to the binding site of cyclooxygenase-2 (COX-2) and interact withmain residues that constituted the active cavity of COX-2. While the simulation of molecular dynamics suggested thatthe bound compound was stable at 4 ns, that is the time taken. The binding free energiesexpected by the MM-PBSA method indicated the 1,4-naphthalenedione-2-ethyl-3-hydroxy had a higher affinity than a native ligand (2-[(2,6-dichloro-3-methyl-phenyl)-amino] benzoic acid, JMS) and paracetamol. This suggested its capacity for advancing as a new COX-2 inhibitor.

Background: Medicinal plants make up a vital component of therapeutics. The pharmacologic effect of medicinal plants can be said to be related to the nature of their phytochemical constituents or secondary metabolites. Combretum bauchiense is an African folk plant of the family Combretaceae. Over the years Species of the Combretaceae family has been associated with native us as antipyretic and analgesic substances. Aim: This study aims to determine the phytochemical composition and evaluate the analgesic and anti-pyretic activity of the methanol extract of Combretum bauchiense (MECB) leaves. Materials and Methods: The phytochemical analysis and acute toxicity study of MECB was done using standard procedures. The analgesic and antipyretic activity of MECB was investigated using two models each, with Morphine (10 mg/kg) as the standard reference drug for analgesic activity and Paracetamol (150 mg/kg) for antipyretic activity. The analgesic activity of the extract was evaluated using formalin induced pain and tail flick analgesic method and the antipyretic activity was evaluated using baker's yeast and turpentine induced pyrexia. The study was investigated at doses of 100, 200 and 400 mg/kg body weight of the extract. Data was analyzed using One-way Anova followed by Tukey's Post-hoc test and P

Bauhinia scandens L. (Family, Fabaceae) is a medicinal plant used for conventional and societal medication in Ayurveda. The present study has been conducted to screen the chemical, pharmacological and biochemical potentiality of the methanol extracts of B. scandens stems (MEBS) along with its related fractions including carbon tetrachloride (CTBS), di-chloromethane (DMBS) and n-butanol (BTBS). UPLC-QTOF–MS has been implemented to analyze the chemical compounds of the methanol extracts of Bauhinia scandens stems. Additionally, antinociceptive and anti-inflammatory effects were performed by following the acetic acid-induced writhing test and formalin-mediated paw licking test in the mice model. The antipyretic investigation was performed by Brewer Yeast induced pyrexia method. The clot lysis method was implemented to screen the thrombolytic activity in human serum. Besides, the in silico study was performed for the five selected chemical compounds of Bauhinia scandens, found by UPLC-QTOF–MS By using Discover Studio 2020, UCSF Chimera, PyRx autodock vina and online tools. The MEBS and its fractions exhibited remarkable inhibition in dose dependant manner in the antinociceptive and antiinflammatory investigations. The antipyretic results of MEBS and DMBS were close to the standard drug indomethacin. Investigation of the thrombolytic effect of MEBS, CTBS, DMBS, and BTBS revealed notable clot-lytic potentials. Besides, the phenolic compounds of the plant extracts revealed strong binding affinity to the COX-1, COX-2, mPGES-1 and plasminogen activator enzymes. To recapitulate, based on the research work, Bauhinia scandens L. stem and its phytochemicals can be considered as prospective wellsprings for novel drug development and discovery by future researchers.

The medicinal plant Haloxylon salicornicum is utilized for therapeutic purposes. We previously reported the antioxidant potential of hexane fraction and methanol extracts of the same species. However, since these solvents could be clinically toxic, the current findings investigated the pharmacological effects of the water fraction. The pain relieving, antioxidant, anti-inflammatory, and antipyretic potential of H. salicornicum water extract (HEW) were studied at two concentrations (250 and 500 mg/kg) in rodents. The carrageenan stimulated rat paw edema assay was exercised to assess anti inflammatory potential in rats; yeast-stimulated hyperthermia was utilized to test antipyretic activity in mice; analgesic properties were assessed based on acetic acid-induced writhing, tail flicking, and hot-plate test; and antioxidant potential was examined with the 2,2-diphenyl-1-picrylhydrazyl assay. We found that 500 mg/kg HEW inhibited edema by 44.03%. Yeast-induced hyperthermia in mice was reduced by 250 and 500 mg/kg HEW after 30, 60, and 120 min with significant level of (P < 0.001) compared to rectal temperature of yeast administered group. The high dose of HEW (500 mg/kg) improved the reaction time of mice in the hot-plate test from 6.66 ± 0.33 to 11.33 ± 0.49 s after 120 min. In the acetic acid-stimulated writhing test, 250 and 500 mg/kg HEW decreased writhing by 32.71% and 51.40%, respectively, after 20 min. HEW also showed antioxidant effects. These results demonstrate that HEW is bioactive and has therapeutic potential for treating a variety of ailments.

Abstract Background The study was conducted to evaluate the analgesic, anti-inflammatory, antipyretic properties of ethanolic extract of Tacca integrifolia rhizome (EETI) in mice and cytotoxic effects in brine shrimp nauplii followed by a PASS prediction study for some isolated compounds of T. integrifolia. Additionally, this experiment included the in silico molecular docking and ADME/T property analyses of some phytochemicals. Methods Formalin- induced paw licking test and acetic acid-induced writhing test for analgesic activity, carrageenan-induced paw edema test for anti-inflammatory potential and Brewer’s yeast-induced pyrexia test for antipyretic activity were applied. Antinociceptive and antineoplastic activity for breast cancer were revealed with PASS program. Schrodinger suite 2015 was used to evaluate the binding interaction and ADME/T properties of selected phytoconstituents with estrogen receptor alpha. Results In formalin-induced paw licking test, EETI at the doses of 200 and 400 mg/kg BW showed highly significant inhibition of writhing in both neurogenic and inflammatory phases. While EETI also exhibited highly significant, compared to control, writhing inhibition for both the doses in acetic acid-induced writhing test. Moderate anti-inflammatory effect at a dose of 400 mg/kg BW was noticed in paw-edema test. It also showed 77.51% of maximum antipyretic effect which was significantly effective compared to standard drug paracetamol (150 mg/kg) in Brewer’s yeast-induced pyrexia test. The EETI showed potential cytotoxic activity with LC50 value of 114.46 μg/mL. The PASS prediction revealed the potential antinociceptive and antineoplastic activity of target compounds. The compounds betulinic acid, quercetin-3-α-arabinoside, catsanogenin were found to be effective in molecular docking study. Conclusion It is evident that the EETI possesses highly significant analgesic activity with remarkable anti-inflammatory and antipyretic activity. The phytoconstituents have potential antinociceptive and antineoplastic (breast cancer) activity. Graphical abstract

The coronavirus disease, 2019 (COVID-19), has spread rapidly around the world and become a major public health problem facing the world. Traditional Chinese medicine (TCM) has been fully committed to treat COVID-19 in China. It improved the clinical symptoms of patients and reduced the mortality rate. In light of the fever was identified as one of leading clinical features of COVID-19, this paper will first analyze the material basis of fever, including pyrogenic cytokines and a variety of the mediators of fever. Then the humoral and neural pathways of fever signal transmission will be described. The scattered evidences about fever recorded in recent years are connected in series. On this basis, the understanding of fever is further deepened from the aspects of pathology and physiology. Finally, combining with the chemical composition and pharmacological action of available TCM, we analyzed the mechanisms of TCMs to play the antipyretic effect through multiple ways. So as to further provide the basis for the research of antipyretic compound preparations of TCMs and explore the potential medicines for the prevention and treatment of COVID-19.

Background: Fever is suppressed with drugs due to discomfort and risk of organ damage. However, there is some compelling evidence for the benefits of fever. The elderly are a special population in this regard as they have a blunted fever response. The benefit-harm balance of antipyretic use in this population is unclear. This study aims to provide the synthesized best evidence regarding long-term health effects of antipyretic treatment in the elderly during infections, investigating the onset/worsening of common chronic diseases, for e.g., thyroid disorders, connective tissue diseases and chronic obstructive pulmonary disease/asthma. Methods: A systematic review will be performed to establish the best evidence available regarding antipyretic treatment in the elderly, searching databases such as Medline, Embase and Cochrane CENTRAL from their inception till date for all types of studies. Studies that consider the drugs in analgesic role will be excluded. The search will be reported following the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ (PRISMA) guidelines. Randomized control trials, quasi experimental studies, observational studies, case series and reports will be included. The primary outcome measure being onset/worsening of chronic inflammatory diseases. Other outcomes include relief of symptoms, length of hospital stay, patient satisfaction, mortality, blood/immune parameters indicative of morbidity and complications of the infection. Risk of biases in randomized studies will be assessed through the Cochrane risk of bias tool. For other study types, appropriate tools such as CASP/QUIPS/Cochrane non-randomised studies tool will be used. Meta-analysis will be conducted on the Cochrane RevMan software and where pooling of data is not possible, a narrative synthesis will be performed. Overall certainty of evidence will be assessed through the GRADE approach. Discussion: The study aims to provide evidence regarding benefit-harm balance of antipyretic use in the elderly population to inform clinical practice and future research. Systematic review registration: PROSPERO CRD42020160854

Periplaneta americana is a common traditional Chinese medicinal material which has been used to treat arthritis, fever, aches, pains, and inflammation of the extremities for several hundred years. However, little scientific data exists in literature to support its use. The purpose of this study was to evaluate the antipyretic, anti-inflammatory and analgesic activities of Periplaneta americana extract (PAE) and explore its underlying mechanism. The antipyretic, anti-inflammatory and analgesic activities were evaluated by LPS-induced fever, carrageenan-induced paw edema, abdominal writhing, hot plate and formalin tests, respectively. The mechanism of action was explored by antioxidant activity analysis, inflammatory cytokines expression and febrile mediator measurement, and pathway activation analysis. The results from UHPLC-HRMS indicated that the extract was found to contain dopamine, coumarin, dipeptide, vitamin, organic acid, amino acid and its metabolites, and other organic compounds. PAE showed in a dose-dependent manner antioxidant activity and reduced the protein production and mRNA expression of NO, IL-1β, IL-6, and TNF-α in RAW 264.7 cells in vitro. Moreover, PAE significantly and dose-dependently inhibited the writhing responses and licking time in formalin tests, increased response latency in the hot plate test, reduced carrageenan-induced paw edema and inflammation in mice, decreased LPS-induced rT increase in rats. Furthermore, PAE treatment markedly inhibited the increase in the levels of NO, IL-6, IL-1β, TNF-α, PGE2 and cAMP in plasma of fevered rat, greatly suppressed the activation of inflammatory response pathway and the change of MDA and GSH concentration, MPO and SOD activity as well as FRAP capacity in paw induced by carrageenan injection. In conclusion, the findings suggested that PAE produced potential antinociceptive, anti-inflammatory and antipyretic effects by reducing production of endogenous inflammatory mediators and blocking the MAPK/NF-κB signaling pathway which support the claim for its traditional use in the treatment of various diseases.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as cyclooxygenase (Cox)-1/2 inhibitor, have emerged as potent antipyretics and analgesics. However, few herbs with Cox-1/2 inhibitory activity are commonly used for heat-clearing in China. Although these are known to have antipyretic activity, there is a lack of molecular data supporting their activity. Using the traditional Chinese medicine herb honeysuckle (Hon) as an example, we explored key antipyretic active compounds and their mechanisms of action by assessing their metabolites and metabolomics. Mitogen-activated protein kinase (MAPK) 3 and protein kinase B (AKT) 1 were suggested as key targets regulated primarily by chlorogenic acid (CA) and swertiamarin (SWE). CA and SWE synergistically inhibited the production of interleukin (IL)-1 and IL-6, alleviated generation of prostaglandin E2, and played an antipyretic role equivalent to honeysuckle extract at the same dose contents within 3 h. Collectively, these findings indicated that lipopolysaccharide-induced fever can be countered by CA with SWE synergistically, allowing the substitution of a crude extract of complex composition with active compounds. Our findings demonstrated that, unlike the traditional NSAIDs, the Hon extract showed a remote and indirect mechanism for alleviating fever that depended on the phosphatidylinositol-3-kinase–AKT and MAPK pathways by regulating the principal mediator of inflammation.

Abstract Background Lathyrus sativus L. (Fabaceae) has long been used as a traditional medicine for the treatment of several ailments such as Scabies, eczema, and allergy. The aim of the study was to evaluate the phytochemical nature with Central Nervous System (CNS) depressant, analgesic, antipyretic activities of the methanolic plant extract of Lathyrus sativus L. seeds in different experimental models. Methods Preliminary phytochemical screening and proximate analysis was carried out using different standard methods. CNS depressant activity was evaluated observing the effects of plant extract on Swiss albino mice using open field and hole-cross method. Acetic acid induced writhing and formalin induced paw licking methods were used for the appraisal of analgesic activity while 2,4-dinitrophenol (DNP) induced pyrexia model was used to investigate the antipyretic activity. The data were analyzed by one way ANOVA followed by Dunnett’s test using SPSS (version 20). Results The phytochemical analysis revealed the presence of wide range of phytoconstituents in the plant extract. Our investigation demonstrated that the methanolic plant extract significantly (p

Abstract Background Many plants of genus Abutilon are traditionally used for treatment of inflammation, bronchitis, piles, gonorrhea, diabetes and fever. Abutilon hirtum is traditionally used to ease the pain of kidney gravel, to treat diarrhoea, cough and toothache, to cure bladder inflammations, wounds and ulcers and as an antipyretic, demulcent, diuretic and mouth wash. The aim of the study is to evaluate the anti-inflammatory, analgesic, antipyretic and antidiabetic effects of the total ethanolic extract and different fractions of Abutilon hirtum (Lam.) Sweet leaves. Methods Air dried powder of A. hirtum leaves were extracted using 95% ethanol and fractionated successively with petroleum ether, chloroform and finally with ethyl acetate. The extracts were concentrated to afford petroleum ether, chloroform, ethyl acetate and aqueous fractions and were investigated for their anti-inflammatory, analgesic, antipyretic and antidiabetic activities using carrageenan-induced paw edema, hot plate, yeast -induced pyrexia and streptozotocin-induced hyperglycemia methods, respectively. Results The total ethanolic extract and the chloroform fraction exhibited the highest anti-inflammatory activity with a percentage of inhibition 50.8% which is close to that of indomethacin (52.4%). The aqueous extract exhibited the maximum analgesic activity (216.6%) with a rapid onset and a longer duration followed by petroleum ether and chloroform fractions and total extract (189.8, 186.9 and 183.0%, respectively), which is almost similar to that of acetylsalicylic acid (186.4%). The total ethanolic extract showed higher activity compared to the used standard acetylsalicylic acid with a rapid onset (30 min) and a longer duration exhibiting the maximum activity. The crude polysaccharides fraction showed a significant lowering in blood glucose level (81.08%). The total extract and petroleum ether, chloroform, ethyl acetate and aqueous fractions exhibited a significant anti-diabetic activity after 5 h (47.49, 47.79, 50.04, 49.80 and 46.36%, respectively) compared with that of metformin (55.45%). Conclusion Abutilon hirtum extract and fractions exhibited anti-inflammatory analgesic, antipyretic and antipyretic activities which may be attributed by the presence of active phytoconstituents.

The extensive use of antibiotics has caused the global spread of multidrug-resistant bacteria and genes, seriously reducing antibiotic efficacy and threatening animal and human health. As an alternative, traditional Chinese veterinary medicine (TCVM) was used in this study for its lack of drug resistance and low toxicity. Huangqin-honghua-pugongying-jinyinhua extract (HHPJE), a novel TCVM, consists of the extracts of Huangqin (Scutellaria baicalensis), Honghua (Carthami Flos), Pugongying (Taraxacum) and Jinyinhua (Lonicerae Japonicae Flos), and was developed to treat bovine mastitis. In this study, we evaluated the toxicity, bacteriostatic, analgesic, anti-inflammatory, and antipyretic activities of HHPJE. Our results show that HHPJE did not show any acute oral toxicity and can be considered safe for oral administration. Additionally, HHPJE possessed a dose-dependent antibacterial effect on Staphylococcus aureus, Escherichia coli, Streptococcus agalactiae and Streptococcus dysgalactiae. HHPJE (60, 30 and 15 g/kg) can reduce the abdominal pain by 44.83 ± 7.69%, 43.15 ± 9.50% and 26.14 ± 4.17%, respectively. The percentages of anti-inflammation inhibition (60, 30 and 15 g/kg) were 35.34 ± 2.17%, 22.29 ± 2.74% and 12.06 ± 3.61%, respectively. The inhibition rates (60, 30 and 15 g/kg) of antipyretic activity were 82.05%, 65.71% and 52.80%, respectively. The evaluation of pharmacodynamics and toxicity indicate that HHPJE possesses significant bacteriostatic, analgesic, anti-inflammatory and antipyretic potential, and also that it is safe for acute oral toxicity, which means it has potential value for treating bovine mastitis in future and alleviating clinical symptoms with no drug resistance or side effects.

Abstract 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.

Natural antioxidants, especially those of plant origins, have shown a plethora of biological activities with substantial economic value, as they can be extracted from agro-wastes and/or under exploited plant species. The perennial hydrophyte, Potamogeton perfoliatus, has been used traditionally to treat several health disorders; however, little is known about its biological and its medicinal effects. Here, we used an integrated in vitro and in vivo framework to examine the potential effect of P. perfoliatus on oxidative stress, nociception, inflammatory models, and brewer’s yeast-induced pyrexia in mice. Our results suggested a consistent in vitro inhibition of three enzymes, namely 5-lipoxygenase, cyclooxygenases 1 and 2 (COX-1 and COX-2), as well as a potent antioxidant effect. These results were confirmed in vivo where the studied extract attenuated carrageenan-induced paw edema, carrageenan-induced leukocyte migration into the peritoneal cavity by 25, 44 and 64% at 200, 400 and 600 mg/kg, p.o., respectively. Moreover, the extract decreased acetic acid-induced vascular permeability by 45% at 600 mg/kg, p.o., and chemical hyperalgesia in mice by 86% by 400 mg/kg, p.o., in acetic acid-induced writhing assay. The extract (400 mg/kg) showed a longer response latency at the 3 h time point (2.5 fold of the control) similar to the nalbuphine, the standard opioid analgesic. Additionally, pronounced antipyretic effects were observed at 600 mg/kg, comparable to paracetamol. Using LC-MS/MS, we identified 15 secondary metabolites that most likely contributed to the obtained biological activities. Altogether, our findings indicate that P. perfoliatus has anti-inflammatory, antioxidant, analgesic and antipyretic effects, thus supporting its traditional use and promoting its valorization as a potential candidate in treating oxidative stress-associated diseases.

Sterculia foetida, also known as jangli badam in Bangladesh, is a traditionally used plant that has pharmacological activities. A qualitative phytochemical analysis was performed to assess the metabolites in a methanolic extract of S. foetida seeds (MESF), and the cytotoxic, thrombolytic, anti-arthritics, analgesic, and antipyretic activities were examined using in vitro, in vivo, and in silico experiments. Quantitative studies were performed through gas chromatography-mass spectroscopy (GC-MS) analysis. The brine shrimp lethality bioassays and clot lysis were performed to investigate the cytotoxic and thrombolytic activities, respectively. The anti-arthritics activity was assessed using the albumin denaturation assay. Analgesic activity was determined using the acetic acid-induced writhing test and the formalin-induced paw-licking test. A molecular docking study was performed, and an online tool was used to perform ADME/T (absorption, distribution, metabolism, and excretion/toxicity) and PASS (Prediction of Activity Spectra for Substances). GC-MS analysis identified 29 compounds in MESF, consisting primarily of phenols, terpenoids, esters, and other organic compounds. MESF showed moderate cytotoxic activity against brine shrimp and significant thrombolytic and anti-arthritics activities compared with the relative standards. The extract also showed a dose-dependent and significant analgesic and antipyretic activities. Docking studies showed that 1-azuleneethanol, acetate returned the best scores for the tested enzymes. These findings suggested that MESF represents a potent source of thrombolytic, anti-arthritic, analgesic, antipyretic agents with moderate cytotoxic effects.

Moringa oleifera Lam. or munga is one of the most important plant widely cultivated in India. It belongs to family Moringaceae. This plant is widely used as nutritional herb and contains valuable pharmacological action like anti-asthmatic, anti-diabetic, hepatoprotective, anti-inflammatory, anti- fertility, anti-cancer, antimicrobial, anti-oxidant, cardiovascular, anti-ulcer, CNS activity, anti-allergic, wound healing, analgesic, and antipyretic activity, Moringa oleifera Lam. The plant is also known as Horse - radish tree, Drumstick tree. Every part of this plant contains a valuable medicinal feature. It contain rich source of the vitamin A, vitamin C and milk protein. Different types of active phytoconstituents like alkaloids, protein, quinine, saponins, flavonoids, tannin, steroids, glycosides, fixed oil and fats are present. This plant is also found in the tropical regions. Some other constituents are niazinin A, niazinin B and niazimicin A, niaziminin B. The present review discusses the phytochemical composition, medicinal uses & pharmacological activity of this plant.

Introduction: In most parts of Africa, Ximenia americana is used in folklore to treat various disorders such as oedema, pain, fever, helminthiasis, diarrhoea, burns among other diseases. This study tested the antipyretic activities of dichloromethane-methanolic (DCM-MeOH) stem bark and leaf extracts of X. americana in rats. Qualitative phytochemical screening was also done to evaluate the presence of alkaloids, flavonoids, steroids, saponins, cardiac glycosides, phenolics and terpenoids in the extract. Methods: The plant materials were collected from Mbeere North sub-county, Embu county, Kenya. Methanol and dichloromethane in the ratio of 1:1 was used to extract the active compounds. Two to three months old male Wister rats were employed for the antipyretic studies. Animals were divided into six groups of five rats each: normal, negative, reference and three experimental groups (50, 100 and 150 mg/kg body weight). Pyrexia was induced experimentally using turpentine. The experimental groups were treated with predetermined dose quantities of prepared extracts. Aspirin was used as the reference drug. Data were analyzed using one-way analysis of variance (ANOVA). Results: The extracts from the leaves lowered rectal temperature by 0.45% to 2.11% while the stem bark extracts lowered rectal temperature in the range of 0.71% to 2.13%. Aspirin lowered the rectal temperature in the range of 0.74% and 1.67%. Qualitative phytochemical screening showed presence of alkaloids, flavonoids, steroids, saponins, cardiac glycosides, phenolics and terpenoids in the extract. Conclusion: DCM-MeOH leaf and stem bark extracts of X. americana is effective in management of fever and therefore it can be explored as a possible bio-resource in the development of herbal antipyretic medicines.

Cocor Bebek (Kalanchoe pinnata L.) is a medicinal plant that has been used as traditional medicine for long period, used to fight fever, but it empirically leaves of Tembelekan (Lantana camara L.) are also generally primarily used to treat fever. Research on the effects of the combination of Cocor Bebek’s leaf extract (Kalanchoe pinnata L.) and the leaf extract of tembelekan (Lantana camara L.) Pers on male guinea pig (Cavia porcellus) is induced peptone 5% at a dose of 150 mg / kg body weight. With the aim to determine the effect of the combination and determine the effects of the most effective as an antipyretic. Extracts prepared by maceration method using ethanol 95%. Marmots were divided into 4 groups. Each guinea pig was induced using peptone 5%. The first group was given Na CMC as a negative control group 2nd given a combination of one dose combinations (50 + 720). Group 3 was given a second dose combination (100 + 720). Group-4 were given a 3-dose combination (150 + 720). Temperature measurement is carried out for 2 hours with a 30 minute interval. Data were analyzed temperature measurements were statistically analyzed using ANOVA (Analisys Of Variance). The research result was addressing, that the combination of extracts can reduce fever. The combination is most effective as an antipyretic is cocor duck leaf extract 50 mg and 720 mg tembelekan leaf extract (50 + 720).

Cleome scaposa has been associated with the prevention of many diseases as fever, abdominal complaints and cancer. But its antipyretic effect is not reported so far. The aim of this study was to assess the efficacy of C. scaposa in reducing temperature in Baker's yeast-induced fever model of rabbits. Rabbits were randomized into 4 groups (n = 24). Fever was induced in by Saccharomyces cerevisae (3 mL/kg of 10% suspension subcutaneous) in all study groups. Afterward, group 1, 2, 3 and 4 were orally administered with paracetamol 150 mg/kg b. wt., distilled water, C. scaposa 250 and 500 mg/kg b. wt. respectively. 500 mg/kg dosage was selected after dose fixation study. The standard control was paracetamol. Rectal temperature was recorded with the help of a digital thermometer. ANOVA followed by post hoc test was applied for statistical analysis of results. Results of the study indicate that C. scaposa possesses antipyretic activity comparable to that of standard drug paracetamol as it exhibited comparable antipyretic potential against baker's yeast-induced fever in rabbits. This study confirms the traditional use of C. scaposa in fever. So, it can be an alternative therapeutic choice in fever. However, specific constituents responsible for its antipyretic activity should be evaluated.

The study was conducted to evaluate the antioxidant and antipyretic activity of Adansonia digitata (African Baobab) fruit, leaf and bark extracts. Antioxidant activity of plant part extracts were determined by free radical Diphenylpicrylhydrazyl (DPPH) assay while the antipyretic activity was assessed using experimental animals. Antioxidant activity of leaf extract showed a value of 13.40±0.77, bark extract 29.23±1.69 while fruit extract gave a value of 39.21±2.26. For the Antipyretic activity results, the average temperature of Albino Wister rats was 21.65±0.96 oC before fever inducement and 30.64±1.37 oC after inducement. Following the administration of the leaf extract (400 mg/kg and 800 mg/kg), bark extract (400 mg/kg and 800 mg/kg) and fruit extract (400 mg/kg and 800 mg/kg), the body temperature of the albino rats fell to25.96±1.16 oC vs. 25.28±1.13 oC, 26.06±1.17 oC vs. 25.02±1.12 oC, and 25.78±1.15 oC vs. 24.30±1.09 oC respectively. The results showed that the fruit extract has a higher antioxidant and antipyretic activity than bark and leaf extracts.