Anti-inflammatory, antipyretic efficacy and safety of inhaled Houttuynia cordata thunb. essential oil formulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (H. cordata) is a well-known folk traditional Chinese medicine that is renowned for its use in the management of inflammatory respiratory diseases and pneumonia. Its essential oils have demonstrated their anti-inflammatory efficacy in vitro, however, their in vivo biological effects via inhalation have not been elucidated. AIM OF THE STUDY: This study aims to evaluate the anti-inflammation and toxicology of H. cordata essential oil-containing formulation, H16 aerosol in vivo. MATERIALS AND METHODS: A laser diffraction particle size analyser and a Next Generation Impactor were used to measure the mass median aerodynamic diameter (MMAD) of the H16 aerosol. The anti-inflammatory and antipyretic effects of the H16 aerosol were evaluated in the xylene-evoked ear oedema and Brewer's yeast-induced fever models, respectively. The biological safety of the H16 aerosol was evaluated by acute toxicity and local toxicity tests in animal models. RESULTS: Our data showed that the MMAD of the bioactive aerosol was 3-5 µm, which implied tracheal and pharyngeal deposits. Significant anti-inflammatory and antipyretic effects were also observed in the animal models treated with H16 aerosol. The maximum tolerable dose of H16 in rats was >2.5 mL/kg. Irritation was not found on respiratory tract mucosa in the local toxicity test. CONCLUSIONS: Taken together, the present study suggested that H16 could be delivered in the form of aerosol and possessed its antipyretic and anti-inflammatory effects. This study provides a new perspective for the development of a new herbal aerosol therapy and herbal modernization.

Chemical, biological and protein-receptor binding profiling of Bauhinia scandens L. stems provide new insights into the management of pain, inflammation, pyrexia and thrombosis.

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.

Drug-induced liver injury in Australia, 2009-2020: the increasing proportion of non-paracetamol cases linked with herbal and dietary supplements.

OBJECTIVE: To compare the characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements. DESIGN: Retrospective electronic medical record data analysis. SETTING, PARTICIPANTS: Adults admitted with DILI to the Gastroenterology and Liver Centre at the Royal Prince Alfred Hospital, Sydney (a quaternary referral liver transplantation centre), 2009-2020. MAIN OUTCOME MEASURES: 90-day transplant-free survival; drugs implicated as causal agents in DILI. RESULTS: A total of 115 patients with paracetamol-related DILI and 69 with non-paracetamol DILI were admitted to our centre. The most frequently implicated non-paracetamol medications were antibiotics (19, 28%), herbal and dietary supplements (15, 22%), anti-tuberculosis medications (six, 9%), and anti-cancer medications (five, 7%). The number of non-paracetamol DILI admissions was similar across the study period, but the proportion linked with herbal and dietary supplements increased from 2 of 13 (15%) during 2009-11 to 9 of 19 (47%) during 2018-20 (linear trend: P = 0.011). Despite higher median baseline model for end-stage liver disease (MELD) scores, 90-day transplant-free survival for patients with paracetamol-related DILI was higher than for patients with non-paracetamol DILI (86%; 95% CI, 79-93% v 71%; 95% CI, 60-82%) and herbal and dietary supplement-related cases (59%; 95% CI, 34-85%). MELD score was an independent predictor of poorer 90-day transplant-free survival in both paracetamol-related (per point increase: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.09-3.74) and non-paracetamol DILI (aHR, 1.24; 95% CI, 1.14-1.36). CONCLUSION: In our single centre study, the proportion of cases of people hospitalised with DILI linked with herbal and dietary supplements has increased since 2009. Ninety-day transplant-free survival for patients with non-paracetamol DILI, especially those with supplement-related DILI, is poorer than for those with paracetamol-related DILI.

Pharmacological evaluation of analgesic, anti-inflammatory and antipyretic activities of ethanolic extract of Indigofera argentea Burm. f.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigofera argentea Burm. f.; commonly known as neel, jantari, hathio; is traditionally used for the treatment of headache, fever, inflammation and body pain. Local communities also used this plant for the treatment of malaria, jaundice, vertigo and gastric disorders. AIM OF THE STUDY: This study is aimed to evaluate the toxicity and possible analgesic, anti-inflammatory and antipyretic activities of the ethanolic crude extract of Indigofera argentea (IaCr) to support its use in folk medicine and to screen the phytochemical constituents and antioxidant activity. MATERIALS AND METHODS: Aqueous ethanolic (30:70) extract of whole plant of Indigofera argentea (IaCr) was prepared and phytochemical study was performed by preliminary methods followed by HPLC and DPPH method. In vivo experiments were performed in Wistar albino rats including hot plate, tail immersion, formalin and capsaicin-induced pain tests in rats and acetic acid-induced writhing test in mice. Anti-inflammatory activity was assessed by using in vitro human red blood cell (HRBC) membrane stabilization and carrageenan-induced rat paw edema test, while antipyretic activity was evaluated by Brewer's yeast-induced pyrexia test. RESULTS: The crude extract of Indigofera argentea confirmed the presence of flavonoids, glycosides, alkaloids, saponins and tannins as soluble ethanolic constituents in preliminary study. The maximum quantity of gallic acid equivalent (GAE) phenolics, and quercetin equivalent (QE) flavonoid content found was 81 ± 2 mg GAE/g and 56 ± 1.4 mg QE/g of extract respectively. Quantification based on HPLC exposed the presence of phenols and flavonoids, quercetin, gallic acid, caffeic acid, chlorogenic acid, benzoic acid, ferulic acid and coumaric acid. In vivo experiments revealed significant P < 0.05) dose-dependent inhibition in hot plate, tail immersion and capsaicin-induced pain test. IaCr showed significant inhibition of pain latency against both phases in formalin test and considerably decreased the number of writhes caused by acetic acid at the doses of 30, 100 and 300 mg/kg. In the in vitro anti-inflammatory (HRBC) assay, IaCr showed good membrane stability with maximum percentage hemolysis inhibition of 49.29% while in carrageenan-induced paw edema test in rats the IaCr showed significant anti-inflammatory action in a dose-dependent fashion. Statistical significant reduction in rectal temperature was observed at the doses of 100 and 300 mg/kg in yeast-induced pyrexia test in rats. CONCLUSION: The results of the experimental studies proved the analgesic, anti-inflammatory and antipyretic activities of Indigofera argentea and supported the traditional use of this plant.

Antipyretic potential of herbal coded formulation (Pyrexol).

The antipyretic effect of the aqueous extract of herbal coded formulation containing equal amount of Salix alba, Emblica officinalis, Glycyrrhiza glabra, Adhatoda vasica, Viola odorata, Thea sinensis, Veleriana officinalis, Foeniculum vulgare, Sisymbrium irrio and Achillea millefolium was investigated using the yeast induced pyrexia model in rabbits. Paracetamol was used as a control group. Rectal temperatures of all rabbits were recorded immediately before the administration of the extract or paracetamol and again at 1 hour, after this, temperature was noted at 1 hrs interval for 5 hrs using digital thermometer. At 240mg/kg dose the extract showed significant reduction in yeast-induced elevated temperature as compared with that of standard drug paracetamol (150mg/kg). It is concluded that herbal coded medicine at a dose of 240mg/kg has marked antipyretic activity in animal models and this strongly supports the ethno pharmacological uses of medicinal plants of this formulation.

An evaluation of the anti-inflammatory, antipyretic and analgesic effects of hydroethanol leaf extract of Albizia zygia in animal models.

CONTEXT: The leaves of Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) are used in Ghanaian traditional medicine for the treatment of pain, inflammatory disorders and fever (including malaria). OBJECTIVES: The present study evaluated the anti-inflammatory, antipyretic and analgesic effects of the hydroethanol leaf extract of Albizia zygia (AZE) in animal models. MATERIALS AND METHODS: The anti-inflammatory and antipyretic effects of AZE were examined in the carrageenan-induced foot oedema model and the baker's yeast-induced pyrexia test respectively. The analgesic effect and possible mechanisms of action were also assessed in the formalin test. RESULTS: AZE (30-300 mg/kg, p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot edema in 7-day-old chicks (ED50 values; preemptive: 232.9 ± 53.33 mg/kg; curative: 539.2 ± 138.28 mg/kg). Similarly, the NSAID diclofenac (10-100 mg/kg, i.p.) significantly reduced the oedema in both preemptive (ED50: 21.16 ± 4.07 mg/kg) and curative (ED50: 44.28 ± 5.75 mg/kg) treatments. The extract (30-300 mg/kg, p.o.) as well as paracetamol (150 mg/kg, p.o.) also showed significant antipyretic activity in the baker's yeast-induced pyrexia test (ED50 of AZE: 282.5 ± 96.55 mg/kg). AZE and morphine (1-10 mg/kg, i.p.; positive control), exhibited significant analgesic activity in the formalin test. The analgesic effect was partly or wholly reversed by the systemic administration of naloxone, theophylline and atropine. CONCLUSION: The results suggest that AZE possesses anti-inflammatory, antipyretic and analgesic properties, which justifies its traditional use. Also, the results show the involvement of the opioidergic, adenosinergic and the muscarinic cholinergic pathways in the analgesic effects of AZE.

Ninety-Day Subchronic Oral Toxicity Study of Senecio scandens Extract in Rats.

The present study assessed the safety/toxicity of Senecio scandens, a well-known Chinese herb that is used as an anti-inflammatory, antibiosis, and antipyretic drug. A 90-d subchronic oral toxicity study of S. scandens was performed in Wistar rats. The extract of S. scandens was administered orally to male and female rats at a single dose of 225, 450, and 900 mg/kg/d. There was no obvious toxicity. Certain changes in hematology and coagulation parameters (red cell distribution width (RDW), platelet count (PLT), monocyte percentage (Mo%), activated partial thromboplastin time (APTT), prothrombin time (PT)) were observed in some administration groups. In regards to the blood biochemical parameters, the levels of creatinine (CRN), potassium, and chloride were increased in a number of the treated rats. There were no significant changes in other hematology, coagulation, or biochemical parameters in rats orally administered S. scandens. S. scandens has a slight effect on rat coagulation and metabolism systems. The herb was safe at all doses tested, but caution should be taken when administering S. scandens at higher doses.

Effect of ethanolic extracts of Justicia neesii Ramam. against experimental models of pain and pyrexia.

OBJECTIVE: The main objective of this study is to evaluate the analgesic and anti-pyretic activities of ethanolic extracts of Justicia neesii Ramam. by different experimental models. MATERIALS AND METHODS: The analgesic activity of plant extract was evaluated against thermal and chemical stimulus induced by Eddy's hot plate and acetic acid respectively in mice. Brewer's yeast induced pyrexia was used to evaluate the antipyretic activity in rats and TAB vaccine induced pyrexia was used to evaluate the antipyretic activity in rabbits. RESULTS: In the hot plate model 400 mg/kg p.o. dose of J. neesii has shown its maximal effect at 3 h. The results are significant (P < 0.05) and comparable to the values of standard drug pentazocine (30 mg/kg i.p.). In acetic acid induced writhing model 400 mg/kg p.o. of plant extracts have shown highly significant activity (P < 0.001) and better than standard drug indomethacin (10 mg/kg p.o.). The 400 mg/kg p.o. dose of plant extract has given significant results against both yeast induced pyrexia and TAB vaccine induced pyrexia (P< 0.01 and 0.05 respectively). These values are comparable to that of paracetamol 100 mg/kg p.o. standard dose. CONCLUSION: This study shows that the ethanol extract of J. neesii has significant analgesic and antipyretic activity.

Pharmacological and safety evaluation of fibrous root of Rhizoma Coptidis.

The aim of this study was to investigated the pharmacological activities and safety of fibrous root of Rhizoma Coptidis (FRC). FRC not only protected Kunming mice from the minimal lethal dose of Escherichia coli, but also protected rabbits from hyperpyrexia induced by lipopolysaccharid (LPS). The acute toxicity study showed that oral medial lethal dose (LD50) of FRC was greater than 7000mg/kg body weight in Kunming mice. The sub-chronic toxicity study showed that the no-observed-adverse effect level (NOAEL) of FRC was 1.88g/kg body weight in Sprague-Dawley rats, whereas FRC at higher dose (3.76g/kg body weight) resulted in damage to liver and lung. Negative results were present in Ames test, mouse micronucleus test and mouse sperm abnormality test. These finding support the use of FRC in veterinary medicine.

Protective effect of Baccharis trimera extract on acute hepatic injury in a model of inflammation induced by acetaminophen.

BACKGROUND: Acetaminophen (APAP) is a commonly used analgesic and antipyretic. When administered in high doses, APAP is a clinical problem in the US and Europe, often resulting in severe liver injury and potentially acute liver failure. Studies have demonstrated that antioxidants and anti-inflammatory agents effectively protect against the acute hepatotoxicity induced by APAP overdose. METHODS: The present study attempted to investigate the protective effect of B. trimera against APAP-induced hepatic damage in rats. The liver-function markers ALT and AST, biomarkers of oxidative stress, antioxidant parameters, and histopathological changes were examined. RESULTS: The pretreatment with B. trimera attenuated serum activities of ALT and AST that were enhanced by administration of APAP. Furthermore, pretreatment with the extract decreases the activity of the enzyme SOD and increases the activity of catalase and the concentration of total glutathione. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by APAP. CONCLUSIONS: The hepatoprotective action of B. trimera extract may rely on its effect on reducing the oxidative stress caused by APAP-induced hepatic damage in a rat model. General Significance. These results make the extract of B. trimera a potential candidate drug capable of protecting the liver against damage caused by APAP overdose.

Saikosaponin d protects against acetaminophen-induced hepatotoxicity by inhibiting NF-κB and STAT3 signaling.

Overdose of acetaminophen (APAP) can cause acute liver injury that is sometimes fatal, requiring efficient pharmacological intervention. The traditional Chinese herb Bupleurum falcatum has been widely used for the treatment of several liver diseases in eastern Asian countries, and saikosaponin d (SSd) is one of its major pharmacologically-active components. However, the efficacy of Bupleurum falcatum or SSd on APAP toxicity remains unclear. C57/BL6 mice were administered SSd intraperitoneally once daily for 5days, followed by APAP challenge. Biochemical and pathological analysis revealed that mice treated with SSd were protected against APAP-induced hepatotoxicity. SSd markedly suppressed phosphorylation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) and reversed the APAP-induced increases in the target genes of NF-κB, such as pro-inflammatory cytokine Il6 and Ccl2, and those of STAT3, such as Socs3, Fga, Fgb and Fgg. SSd also enhanced the expression of the anti-inflammatory cytokine Il10 mRNA. Collectively, these results demonstrate that SSd protects mice from APAP-induced hepatotoxicity mainly through down-regulating NF-κB- and STAT3-mediated inflammatory signaling. This study unveils one of the possible mechanisms of hepatoprotection caused by Bupleurum falcatum and/or SSd.

Anti-inflammatory, analgesic and antipyretic activity of methanolic Tecomaria capensis leaves extract.

OBJECTIVE: To evaluate the analgesic, anti-inflammatory and antipyretic activity of methanolic Tecomaria capensis (T. capensis) leaves extract using different models in rats. METHODS: Methanolic T. capensis leaves extract (100, 300, 1000 and 2000 mg/kg body weight) was given to rats orally to observe acute toxicity, and observed for 14 days. Analgesic activity was evaluated using tail immersion and formalin induced paw licking models in rats. Anti-inflammatory activity was evaluated using carrageenan induced paw edema model in rats. Antipyretic activity was evaluated using brewer's yeast induced pyrexia model in rats. Methanolic T. capensis leaves extract were given at dose of 100, 200 and 500 mg/kg p.o. RESULTS: Results demonstrated that the no mortality was reported even after 14 days. This indicated that the methanol extract was safe up to a single dose of 2 000 mg/kg body weight. Methanolic T. capensis leaves extract (100, 200 and 500 mg/kg p.o.) significantly increased the latency period in the tail immersion test, reduced the licking time in both the neurogenic and inflammatory phases in the formalin test. Methanolic T. capensis leaves extract (100, 200 and 500 mg/kg p.o.) significantly prevented increase in volume of paw edema. Methanolic T. capensis leaves extract at the doses of (100, 200 and 500 mg/kg p.o.) significantly decreased the rectal temperature of the rats. CONCLUSIONS: This study exhibites that methanolic T. capensis leaves extract possesses analgesic, anti-inflammatory and antipyretic activity which may be mediated by the central and peripheral mechanisms.

Anti-inflammatory, analgesic and antipyretic properties of Thespesia populnea Soland ex. Correa seed extracts and its fractions in animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: Thespesia populnea Sol. ex Correa (Malvaceae) is commonly known as "Indian tulip tree". The plant has been used as an astringent, antibacterial, anti-inflammatory, antinociceptive and hepatoprotective in Indian system of traditional medicine. MATERIALS AND METHODS: Thespesia populnea seeds were successively extracted by soxhlet extraction using petroleum ether (40-60 °C) (TPO) and ethanol (TPE). Unsaponifiable matter (TPOUM) and fatty acids were separated from seed oil. A GC-MS analysis of fatty acid methyl esters was carried out. Ethanolic extract was fractionated using CHCl(3), EtOAc, n-BuOH and H(2)O. Acute arthritis was induced by sub-plantar injection of carrageenan into the left hind paw of rats. The paw volume was measured using plethysmometer. Analgesic activity was assessed by heat induced pains (tail immersion model) and antipyretic activity assessed using brewers yeast-induced pyrexia model. RESULTS: Oral administration of TPO and TPE at 200 and 400 mg/kg b.w. and tested fractions at 200mg/kg significantly reduced carrageenan induced paw edema and brewers yeast-induced pyrexia. In tail immersion method also extracts and fractions showed significant analgesic activity. Amongst all fractions EtOAc showed most significant results. TPOUM showed significant anti-inflammatory and analgesic activity. GC-MS analyses showed the presence of fourteen fatty acids, predominant fatty acids were palmitic and stearic acid. CONCLUSION: These results highlighted anti-inflammatory, analgesic and antipyretic effects of Thespesia populnea seeds.

Analgesic, anti-inflammatory, and antipyretic activities of the ethanol extract from Desmodium caudatum.

CONTEXT: In folk medicine in China, Desmodium caudatum (Thunb.) DC (Leguminosae) has been used to treat febrile diseases, rheumatic arthritis, and bacillary dysentery; nevertheless, there have been no reports on the analgesic, antipyretic, and anti-inflammatory effects of this plant in animals. OBJECTIVE: To investigate the analgesic, anti-inflammatory, and antipyretic activities of D. caudatum extract (DCE) in animals. MATERIALS AND METHODS: The analgesic effect of DCE was measured in mice using the acetic acid-induced writhing test and the hot-plate test. The anti-inflammatory activity was assessed using the carrageenan-induced rat paw edema model and the dimethylbenzene-induced mouse inflammation model. The antipyretic effect was estimated using the lipopolysaccharide (LPS)-induced rat fever model. In addition, the acute oral toxicity of DCE was studied. RESULTS: DCE significantly and dose-dependently inhibited the writhing responses in mice, increased reaction time in mice in the hot-plate test, reduced carrageenan-induced paw edema in rats and the dimethylbenzene-induced ear edema in mice, and attenuated LPS-induced fever in rats. Furthermore, no death was observed when mice were orally administered DCE up to 40 g/kg. DISCUSSION AND CONCLUSION: DCE possesses evident analgesic, anti-inflammatory, and antipyretic activities, and has a favorable safety, which supports the use of D. caudatum as an analgesic, anti-inflammatory and antipyretic drug in folk medicine.

Anti-inflammatory, analgesic and antipyretic activities of Linum usitatissimum L. (flaxseed/linseed) fixed oil.

The fixed oil of L. usitatissimum (flaxseed/linseed) inhibited PGE2-, leukotriene-, histamine- and bradykinin-induced inflammation. The oil also inhibited arachidonic acid-induced inflammation, suggesting its capacity to inhibit both cyclooxygenase and lipoxygenase pathways of arachidonate metabolism. In tail immersion model, the oil raised the pain threshold to a lesser extent than morphine but showed excellent peripherally acting, analgesic activity comparable to aspirin, against acetic acid-induced writhing in mouse. In typhoid paratyphoid A/B vaccine-induced pyrexia, the oil showed antipyretic activity comparable to aspirin. The oil contains 57.38% alpha-linolenic acid. Dual inhibition of arachidonic acid metabolism, antihistaminic and antibradykinin activities of the oil could account for the biological activity and the active principle could be alpha-linolenic acid an omega-3 (18:3, n-3) fatty acid.