Polysaccharides from bile Arisaema exert an antipyretic effect on yeast-induced fever rats through regulating gut microbiota and metabolic profiling.

In our previous study, bile Arisaema was elucidated to have a significant anti-febrile effect, but the pharmacodynamic material basis of this effect remains uncertain. Herein, we found that the soluble polysaccharide fraction from bile Arisaema presents a remarkable antipyretic effect through balancing the gut microbiota and regulating metabolic profiling. Bile Arisaema polysaccharide (BAP) was characterized for its monosaccharide composition with arabinose, galactose, glucose, mannose and xylose (0.028:0.072:0.821:0.05:0.029, molar ratios) and amino acid composition with arginine, threonine, alanine, glycine, serine, proline and tyrosine (109.33, 135.78, 7.22, 8.86, 21.07, 4.96, 12.31 µg/mg). A total of 50 peptides were identified from BAP using Ltq-Orbitrap MS/MS. The oral administration of 100 mg/kg BAP significantly increased the antipyretic effect in yeast-induced fever rats by comparing the rectal temperature. Mechanistically, the inflammation and disorders of neurotransmitters caused by fever were improved by treatment with BAP. The western blotting results suggested that BAP could suppress fever-induced inflammation by down-regulating the NF-κB/TLR4/MyD88 signaling pathway. We also demonstrated that BAP affects lipid metabolism, amino acid metabolism and carbohydrate metabolism and balances the gut microbiota. In summary, the present study provides a crucial foundation for determining polysaccharide activity in bile Arisaema and further investigating the underlying mechanism of action.

Chemical composition combined with network pharmacology and quality markers analysis for the quality evaluation of Qing-fei-da-yuan granules.

Qing-fei-da-yuan granules (QFDYGs) had been proved to be an effective TCM prescription for treating coronavirus disease 2019 (COVID-19), which are composed of a variety of TCMs, and characterized by multiple components, multiple targets and overall regulation. It is meaningful to further study the chemical composition and pharmacology of QFDYGs for quality evaluation. However, due to the complexity of the components of QFDYGs, there are no reliable and simple analytical methods for current quality evaluation. In this work, antipyretic activity assessment of QFDYGs in the LPS-induced New Zealand rabbit model was carried out to verify the efficacy firstly. It was proved that QFDYGs can be used to relieve fever to help preventing or controlling the prevalence of influenza and pneumonia. Subsequently, UHPLC-ESI-QTOF-MS/MS combined with network pharmacology, quality markers and fingerprint analysis were used to establish the quality control condition. The chemical compositions were analyzed by UHPLC-ESI-QTOF-MS/MS, and 79 of them were identified, such as arecoline, mangiferin, paeoniflorin, etc. Then, the network pharmacology strategy based on 45 candidate components (CCs) in conjunction with influenza and pneumonia diseases was employed to screen the potential active ingredients. According to the drug-CCs-genes-diseases (D-CCs-G-D) networks, baicalein, honokiol, baicalin, paeoniflorin, saikosaponin A, glycyrrhizic acid and hesperidin were selected as quality markers. And a method for content determination of the 7 quality markers was established by optimizing extraction methods, chromatographic conditions and methodological verification. Finally, the quality of 15 batches of QFDYGs was evaluated by using the 7 quality markers combined with fingerprints and principal component analysis (PCA). The analyzed results showed that baicalin, paeoniflorin, glycyrrhizic acid and hesperidin were the high content and stable quality markers. QFDYGs were characterized by overall consistency and individual ingredient differences among the 15 batches. Our quality evaluation study will provide reference for the further development and research of QFDYGs.

Acetaminophen and Ibuprofen in Pediatric Central Nervous System Malaria: A Randomized Clinical Trial.

Importance: A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae. Objective: To compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher. Design, Setting, and Participants: This randomized clinical trial was conducted at inpatient pediatric services of 1 tertiary care and 1 district hospital in Zambia and a tertiary care center in Malawi. Included were children aged 2 to 11 years with CNS malaria (excluding those with creatinine >1.2 mg/dL), who were enrolled from 2019 to 2022. Data analysis took place from December 2022 to April 2023. Intervention: The aggressive antipyretic group received acetaminophen (30 mg/kg load, then 15 mg/kg) plus ibuprofen, 10 mg/kg, every 6 hours, regardless of clinical temperature for 72 hours. The usual care group received 15 mg/kg of acetaminophen as needed every 6 hours for a temperature of 38.5 °C or higher. Main Outcomes and Measures: The primary outcome variable was Tmax over 72 hours, the total duration of follow-up. Secondary outcomes included seizures and parasite clearance. Results: Five hundred fifty-three patients were screened, 226 (40.9%) were ineligible, and 57 (10.3%) declined. A total 256 participants (n = 128/group) had a mean (SD) age of 4.3 (2.1) years; 115 (45%) were female, and 141 (55%) were male. The aggressive antipyretic group had a lower Tmax, 38.6 vs 39.2 °C (difference, -0.62 °C; 95% CI, -0.82 to -0.42; P < .001) and lower odds of experiencing multiple or prolonged seizures, 10 (8%) vs 34 children (27%) in the usual care group (odds ratio [OR], 0.26; 95% CI, 0.12 to 0.56). No group difference in parasite clearance time was detected. Severe adverse events occurred in 40 children (15%), 25 (20%) in the usual care group and 15 (12%) in the aggressive antipyretic group, including 13 deaths (10 [8%] and 3 [2%], respectively). Increased creatinine resulted in study drug discontinuation in 8 children (6%) in the usual care group and 13 children (10%) in the aggressive antipyretic group (OR, 1.74; 95% CI, 0.63 to 5.07). Conclusions and Relevance: This study found that aggressive antipyretic therapy reduced mean Tmax to temperature levels comparable with the Tmax among children without neurological impairments in prior observational studies and improved acute seizure outcomes with no prolongation of parasitemia. Trial Registration: ClinicalTrials.gov Identifier: NCT03399318.

[Actual Access and Usage of Antipyretic Analgesics before and after COVID-19 Vaccination: Pharmacist's Roles in Promoting Proper Use of Medicines during the Infodemic].

An overwhelming surge of information regarding preparedness for postvaccination side effects had caused widespread confusion approximately since April 2021, when the coronavirus disease 2019 (COVID-19) vaccination had started for the general population in Japan. Notably, this resulted in a remarkably increased shortage of OTC acetaminophen formulations. The aim of this study was to elucidate the actual responses of the public in such an environment, how individuals acquired and understood information related to the management of postvaccination side effects, and how they obtained and used antipyretic analgesics before and after COVID-19 vaccination. We conducted a web-based survey in January 2022, targeting 400 individuals aged ≥20 years, who had received two COVID-19 vaccine doses, and excluded qualified professionals such as physicians and pharmacists. The results revealed that 67% of the respondents had obtained antipyretic analgesics in anticipation of adverse effects after vaccination, whereas 38% had taken these medicines before and/or after the second vaccination. Possible misappropriation of medicines from others, preventive administration, and lack of dosage and administration confirmation are the problems identified in medication acquisition and usage. Additionally, avoidance of antipyretic analgesics based on information without scientific evidence was observed. This study revealed no small amount of inappropriate use of medicines in situations, such as the COVID-19 pandemic, where there is an "infodemic" of mixed-quality information. Pharmacists, as experts in medication, should play a crucial role in promoting appropriate medication usage by consistently staying updated with the latest scientific evidence and proactively supporting OTC drug selection and counseling medication.

Antitussive, Expectorant and Antipyretic Effect of the Ethanolic Extract of the Leaves of Momordica charantia L.

The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300 mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300 mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.

Rectal versus intravenous administration of acetaminophen; Clinical investigation of plasma level, analgesic, and antipyretic effects on 6-month to 6-year-old children in Zabol city, Iran.

OBJECTIVES: Acetaminophen is the most widely antipyretic analgesic medicine used in adults and children worldwide. Rectal acetaminophen is widely used in children who resist or cannot take oral medications. This study was designed to compare the efficacy of rectal and IV acetaminophen in children with fever and mild to moderate pain. PATIENTS AND METHODS: Total 60 children aged six months to 6 years, with fever and pain, that were treated with rectal or intravenous acetaminophen were selected and assigned in two groups. The IV group received 10mg/kg paracetamol as an IV infusion, and the rectal group received a 15mg/kg dose immediately after admission. Pain score was calculated using the FLACC method, and the axillary temperature was recorded at baseline and then 0.5, 1, 2, 4, and 6hours after drug administration. Blood samples were collected at baseline and then at 30min-intervals for the first 90minutes. RESULTS: The trend of changes in mean pain score at different time intervals was significantly different between the two groups. Body temperature decrease was more prominent in the IV group. The plasma concentration increased in both groups significantly with time. This increase was sharper in the IV group, just in the first 60minutes after drug administration. CONCLUSIONS: IV acetaminophen has more rapid onset of action, while rectal dosage form control fever and pain for longer duration. Considering its favorable effects with ease of administration and lower cost, rectal acetaminophen can be a reasonable option in selected patients with pain or fever.

Antipyretic and anti-inflammatory effects of inosine, an active component of Kangfuxin.

Kangfuxin has been widely recognized for its use in treating ulcerative conditions and mucositis, primarily due to its anti-inflammatory properties, which promote cell proliferation, granulation tissue growth, and angiogenesis. However, the exact mechanisms underlying these effects remain poorly understood. In this study, we employed high-throughput mass spectrometry to identify 11 compounds in Kangfuxin, including uracil, hypoxanthine, xanthine, inosine, glutamic acid, glycine, alanine, valine, isoleucine, leucine, and lysine. Notably, the antipyretic and anti-inflammatory properties of inosine, one of these compounds, have not been well characterized. To address this gap, we induced fever in vivo using lipopolysaccharide (LPS) and conducted various experiments, including the analysis of endogenous mediators, inflammatory factors, quantitative polymerase chain reaction (QPCR), Western blotting, and hematoxylin and eosin (HE) staining. Our findings indicate that inosine significantly reduces LPS-induced fever, inhibits the expression of inflammatory factors, and alleviates the inflammatory response. These results suggest that inosine may serve as a potential therapeutic target for inflammatory diseases.

Almond fixed oil from Syagrus coronata (Mart.) Becc. has antinociceptive and anti-inflammatory potential, without showing oral toxicity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Syagrus coronata, a palm tree found in northeastern Brazil, popularly known as licuri, has socioeconomic importance for the production of vegetable oil rich in fatty acids with nutritional and pharmacological effects. Licuri oil is used in traditional medicine to treat inflammation, wound healing, mycosis, back discomfort, eye irritation, and other conditions. AIM OF THE STUDY: The study aimed to evaluate the antinociceptive, anti-inflammatory, and antipyretic effects of treatment with Syagrus coronata fixed oil (ScFO), as well as to determine the safety of use in mice. MATERIALS AND METHODS: Initially, the chemical characterization was performed by gas chromatography-mass spectrometry. Acute single-dose oral toxicity was evaluated in mice at a dose of 2000 mg/kg. Antinociceptive activity was evaluated through abdominal writhing, formalin, and tail dipping tests, and the anti-inflammatory potential was evaluated through the model of acute inflammation of ear edema, peritonitis, and fever at concentrations of 25, 50, and 100 mg/kg from ScFO. RESULTS: In the chemical analysis of ScFO, lauric (43.64%), caprylic (11.7%), and capric (7.2%) acids were detected as major. No mortality or behavioral abnormalities in the mice were evidenced over the 14 days of observation in the acute toxicity test. ScFO treatment decreased abdominal writhing by 27.07, 28.23, and 51.78% at 25, 50, and 100 mg/kg. ScFO demonstrated central and peripheral action in the formalin test, possibly via opioidergic and muscarinic systems. In the tail dipping test, ScFO showed action from the first hour after treatment at all concentrations. ScFO (100 mg/kg) reduced ear edema by 63.76% and leukocyte and neutrophil migration and IL-1ß and TNF-α production in the peritonitis test. CONCLUSION: Mice treated with ScFO had a reduction in fever after 60 min at all concentrations regardless of dose. Therefore, the fixed oil of S. coronata has the potential for the development of new pharmaceutical formulations for the treatment of pain, inflammation, and fever.

The antipyretic effect of the famous classical formula Qingwanzi Pills on a rabbit model and its serum metabolomic study.

Qingwanzi Pills (QP) were first mentioned in the "Puji Fang" of the Ming Dynasty, with a history of approximately 600 years. The formula consisted of Gypsum Fibrosum and Indigo Naturalis. It is a famous classical formula with antipyretic effects frequently utilized in ancient China, although our knowledge about the overall antipyretic mechanism of QP remains limited. Therefore, we replicated the fever model in New Zealand rabbits induced by lipopolysaccharide, performed the pharmacodynamic evaluation of QP, identified the differential metabolites among QP groups, and performed pathway enrichment analysis to comparatively analyze the effects of QP on fever-related metabolic pathways by ultra-performance liquid chromatography-mass spectrometry. The results showed that the antipyretic effect of QP was superior to that of each disassembled prescription, with Gypsum Fibrosum primarily contributing to the efficacy, followed by Indigo Naturalis and Junci Medulla. QP had an effective antipyretic effect, which was related to lowering the levels of TNF-α, IL-6, IL-1ß, and calcium in rabbit serum, lowering the levels of PGE2 and cAMP in rabbit cerebrospinal fluid, and increasing the level of calcium in rabbit cerebrospinal fluid. A total of 27 endogenous biomarkers were screened by serum metabolomics for the treatment of fever with QP. It is hypothesized that the antipyretic mechanism of QP may be related to regulating α-linolenic acid, sphingolipid, tryptophan, and bile acid metabolism. In summary, QP exhibited a significant antipyretic effect in rabbits with lipopolysaccharide-induced fever.

A Study on the Antibacterial, Antispasmodic, Antipyretic, and Anti-Inflammatory Activity of ZnO Nanoparticles Using Leaf Extract from Jasminum sambac (L. Aiton).

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.

Kaempferol 3-O-Rutinoside, a Flavone Derived from Tetrastigma hemsleyanum Diels et Gilg, Reduces Body Temperature through Accelerating the Elimination of IL-6 and TNF-α in a Mouse Fever Model.

Fever is a serious condition that can lead to various consequences ranging from prolonged illness to death. Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum) has been used for centuries to treat fever, but the specific chemicals responsible for its antipyretic effects are not well understood. This study aimed to isolate and identify the chemicals with antipyretic bioactivity in T. hemsleyanum extracts and to provide an explanation for the use of T. hemsleyanum as a Chinese herbal medicine for fever treatment. Our results demonstrate that kaempferol 3-rutinoside (K3OR) could be successfully isolated and purified from the roots of T. hemsleyanum. Furthermore, K3OR exhibited a significant reduction in rectal temperature in a mouse model of fever. Notably, a 4 µM concentration of K3OR showed more effective antipyretic effects than ibuprofen and acetaminophen. To explore the underlying mechanism, we conducted an RNA sequencing analysis, which revealed that PXN may act as a key regulator in the fever process induced by lipopolysaccharide (LPS). In the mouse model of fever, K3OR significantly promoted the secretion of IL-6 and TNF-α during the early stage in the LPS-treated group. However, during the middle to late stages, K3OR facilitated the elimination of IL-6 and TNF-α in the LPS-treated group. Overall, our study successfully identified the chemicals responsible for the antipyretic bioactivity in T. hemsleyanum extracts, and it answered the question as to why T. hemsleyanum is used as a traditional Chinese herbal medicine for treating fever. These findings contribute to a better understanding of the therapeutic potential of T. hemsleyanum in managing fever, and they provide a basis for further research and development in this field.

Physicochemical Evaluation and Pharmacological Screening of Fernando Adenophylla Steenis Fruits.

The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000 mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200 mg/kg extract dose exhibited %age pain inhibition of 55.12 % and reduced body temperature from 39.78±0.03 °C to 37.22±0.02 °C in hyperthermic rats. A decrease in blood glucose levels up to 57.88 % was observed on the 21st day of the treatment with 500 mg/kg ethanolic extract.

Protocol for a magnetic resonance imaging study of participants in the fever RCT: Does fever control prevent brain injury in malaria?

BACKGROUND: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy. METHODS: This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury. DISCUSSION: Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.

Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models. AIM OF STUDY: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms. MATERIALS AND METHODS: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining. RESULTS: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway. CONCLUSION: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

A randomized controlled trial of oral antipyretic treatment to reduce overheating during exercise in adults with multiple sclerosis.

BACKGROUND: Some people with multiple sclerosis (pwMS) avoid exercise due to overheating. Evidence from a variety of cooling treatments shows benefits for pwMS. OBJECTIVE: Conduct a randomized controlled trial of antipyretic treatment before exercise in pwMS. METHODS: Adults over age 18 diagnosed with relapsing-remitting MS reporting heat sensitivity during exercise were randomly assigned to one of six sequences counterbalancing aspirin, acetaminophen, placebo. At each of three study visits separated by ≥ one week, participants received 650-millograms of aspirin, acetaminophen, or placebo before completing a maximal exercise test. Primary outcomes were body temperature change and total time-to-exhaustion (TTE), secondary outcomes were physiological and patient-reported outcomes (PROs). RESULTS: Sixty participants were enrolled and assigned to treatment sequence; 37 completed ≥ one study visit. After controlling for order effects, we found that body temperature increase was reduced after aspirin (+ 0.006 ± 0.32 degrees Fahrenheit, p < 0.001) and after acetaminophen (+ 0.31 ± 0.35; p = 0.004) compared to placebo (+ 0.68 ± 0.35). TTE after aspirin (331.6 ± 76.6 s) and acetaminophen (578.2 ± 82.1) did not differ significantly from placebo (551.0 ± 78.4; p's > 0.05). Aspirin benefited all secondary outcomes compared to placebo (all p's < 0.001); acetaminophen showed broadly consistent benefits. CONCLUSION: These results support antipyretic treatment as effective for reducing overheating during exercise in pwMS and failed to support antipyretics for increasing TTE in the context of a maximal exercise test. Benefits were shown for physiological markers of exercise productivity and PROs of fatigue, pain, and perceived exertion.

The oral administration of Lacticaseibacillus casei Shirota alleviates acetaminophen-induced liver injury through accelerated acetaminophen metabolism via the liver-gut axis in mice.

Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin, and hepatic cell necrosis. Moreover, LcS alleviated acetaminophen-induced intestinal mucosal permeability, decreased serum IL-1α and lipopolysaccharide levels, and elevated serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol, and sugars in the gut. Additionally, the transcriptomic and proteomic results showed that LcS mitigated the decrease in metabolic and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.IMPORTANCEAcetaminophen is the most frequently used antipyretic analgesic worldwide. As a result, overdoses easily occur and lead to drug-induced acute liver injury, which quickly progresses to liver failure with a mortality of 60%-80% if not corrected in time. The current emergency treatment for overused acetaminophen needs to be administered within 8 hours to avoid liver injury or even liver failure. Therefore, developing preventive strategies for liver injury during planned acetaminophen medication is particularly important, preferably nonpharmacological methods. Lacticaseibacillus casei Shirota (LcS) is a famous probiotic that has been used for many years. Our study found that LcS significantly alleviated acetaminophen-induced acute liver injury, especially acetaminophen-induced liver injury toward fulminant hepatic failure. Here, we elucidated the function and potential mechanisms of LcS in alleviating acetaminophen-induced acute liver injury, hoping it will provide preventive strategies to people during acetaminophen treatment.

Anti-inflammatory, analgesic, antitussive and antipyretic activities of polyphenol-enriched fraction from Nymphaea candida.

ETHNOPHARMACOLOGICAL RELEVANCE: "Snow-white waterlily" (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. AIM OF THE STUDY: Polyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. MATERIALS AND METHODS: The polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. RESULTS: NCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1ß, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. CONCLUSION: The experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.

Antipyretic effect of inhaled Tetrastigma hemsleyanum polysaccharide on substance and energy metabolism in yeast-induced pyrexia mice via TLR4/NF-κb signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg, is one of the perennial evergreen plants with grass vine, which has obvious curative effect on severe infectious diseases. Although Tetrastigma hemleyanum has long been recognized for its capacity of antipyretic and antitoxic, its specific mechanism is unknown. AIM OF THE STUDY: To evaluate the antipyretic effect of Tetrastigma hemleyanum polysaccharide (THP) on mice with dry yeast-induced fever, and to explore its specific antipyretic mechanism. METHODS: In this study, THP was administered by aerosol in febrile mice. The rectal temperatures of treated animals were monitored at different time points. Histopathological evaluation and various inflammatory indexes were used to assess inflammatory damage. The concentration variations of the central neurotransmitter, endocrine system, substance and energy metabolism indicators were measured to explore the physiological mechanism. Quantitative real-time PCR, Western bolt and Immunohistochemistry were performed to identify the correlation between antipyretic and TLR4/NF-κB signaling pathway. RESULTS: THP reduced the body temperature of febrile mice induced by dry yeast, as well as the levels of thermogenic cytokines and downregulated the contents of thermoregulatory mediators. THP alleviated the pathological damage of liver and hypothalamus caused by fever. In addition, THP decreased the secretion of thyroid hormone, substance and energy metabolism related indicators. Furthermore, THP significantly suppressed TLR4/NF-κB signaling pathway-related indicators. CONCLUSIONS: In conclusion, our results suggest that inhaled THP exerts antipyretic effect by mediating the thermoregulatory mediator, decreasing the content of pyrogenic factors to lower the body temperature, and eventually restoring the high metabolic level in the body to normal via inhibiting TLR4/NF-κB signaling pathway. The study provides a reasonable pharmacodynamic basis for the treatment of polysaccharide in febrile-related diseases.

Association between use of antipyretics and antibody titers after two doses of the BNT162b2 SARS-CoV-2 vaccine in adolescents and young adults with underlying diseases.

There are few reports on the association between antipyretic use and antibody titers in adolescents and young adults following SARS-CoV-2 vaccination. Multivariable linear regression analyses were performed to examine the association between antipyretic use and antibody titers. The use of antipyretics was not associated with antibody titers (ß coefficient [95% CI] = -0.107 [-0.438 to 0.224]).

Classes of medications prescribed to malnourished children and their relationship with time to recovery.

OBJECTIVE: There is conflicting evidence around prescription practices in the management of malnutrition; the study objective was to explore medication classifications prescribed and their relationship between time-to-recovery and specific demographic characteristics among children with malnutrition in Guatemala. DESIGN: Descriptive correlational study of data obtained in a retrospective record review. SAMPLE: Children aged 0-5 years with malnutrition treated in a Guatemalan Nutrition Rehabilitation Center between 2019 and 2020 (N = 155). MEASURES: Variables assessed were medication classification of prescribed medications, age, gender, time-to-recovery, malnutrition severity, and COVID cohort. RESULTS: The most frequently used medication classifications were vitamins (95%), respiratory (75%), antipyretic (68%), antibiotic (61%), and gastrointestinal agents (54%). Antibiotic, respiratory, corticosteroid, antipyretic, and gastrointestinal agents were prescribed significantly more in cases with a time-to-recovery of 6 weeks or greater. CONCLUSIONS: Medication classifications prescribed most often were related to common comorbidities of malnutrition and illnesses affecting children in Guatemala, such as respiratory and diarrheal diseases. The medication used in cases with a time-to-recovery of ≥6 weeks suggest these cases may have had more comorbidities, which could explain the longer recovery times. Caution is suggested in routine prophylactic antibiotic use in public health settings, given the lack of association with improved recovery times, the potential for antibiotic drug resistance, and the negative effects on renal function among children.