Tyramine exerts hypolipidemic and anti-obesity effects in vivo

Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine

A pilot study on effectiveness of oral mucositis pain control in hematopoietic stem cell transplant patients

Effectiveness of oral mucositis (OM) pain control with the current standard of care management was assessed usingclinician and self-reported scales in hematopoietic stem cell transplant (HSCT) patients. A prospective observationalstudy was performed using clinician-assessed [World Health Organization (WHO)] Oral Toxicity Scales and selfreported scales [Oral Mucositis Daily Questionnaires (OMDQ)]. A total of 23 HSCT patients were included in thestudy. There were 100 recorded days of OM using WHO scores, and 144 recorded days of OM using OMDQ. A totalof 14/23 (60.9%) patients experienced mucositis. The presence of OM was significantly associated with increase inactual body weight [t(21) = 2.15, p = 0.044], body surface area (BSA) [t(21) = 2.31, p = 0.031] and body mass index(BMI) [t(21) = 2.13, p = 0.044], longer hospital stays [t(21) = 2.45, p = 0.023], and busulphan-based regimens (χ = 4.32,p = 0.038). The degree of pain relief was significantly inversely correlated to both the degree of WHO graded OMseverity (ρ = −0.586; p < 0.001) and the severity of self-reported pain (ρ = −0.375; p < 0.001). Both WHO and OMDQsignificantly positively correlated in the clinical setting (p < 0.001). In conclusion, this study highlights the potentialadvantages of using patient self-reported scales in the local clinical setting. The use of the OMDQ self-reported scalescould lead to earlier changes in therapy and may prove useful in HSCT patients.

A pilot study on effectiveness of oral mucositis pain control in hematopoietic stem cell transplant patients

Effectiveness of oral mucositis (OM) pain control with the current standard of care management was assessed usingclinician and self-reported scales in hematopoietic stem cell transplant (HSCT) patients. A prospective observationalstudy was performed using clinician-assessed [World Health Organization (WHO)] Oral Toxicity Scales and selfreported scales [Oral Mucositis Daily Questionnaires (OMDQ)]. A total of 23 HSCT patients were included in thestudy. There were 100 recorded days of OM using WHO scores, and 144 recorded days of OM using OMDQ. A totalof 14/23 (60.9%) patients experienced mucositis. The presence of OM was significantly associated with increase inactual body weight [t(21) = 2.15, p = 0.044], body surface area (BSA) [t(21) = 2.31, p = 0.031] and body mass index(BMI) [t(21) = 2.13, p = 0.044], longer hospital stays [t(21) = 2.45, p = 0.023], and busulphan-based regimens (χ = 4.32,p = 0.038). The degree of pain relief was significantly inversely correlated to both the degree of WHO graded OMseverity (ρ = −0.586; p < 0.001) and the severity of self-reported pain (ρ = −0.375; p < 0.001). Both WHO and OMDQsignificantly positively correlated in the clinical setting (p < 0.001). In conclusion, this study highlights the potentialadvantages of using patient self-reported scales in the local clinical setting. The use of the OMDQ self-reported scalescould lead to earlier changes in therapy and may prove useful in HSCT patients.

Evaluation of Haematological Alterations in Intraperitoneal and Oral Rotenone Induced Parkinson’s Disease Wistar Rats

This study was aimed at developing a single RP-HPLC method for determination of Natamycin in 20 different cheesesamples purchased from local Turkish supermarkets. Chromatographic separation was achieved on a X-Terra RP18column (250 mm x 4.6 mm x 5 µm) with a mobile phase of acetonitrile: water (30:70 v/v/v), at 0.8 mL/min flow rate withDAD detection at 305 nm. In twenty cheese samples, Natamycin was analyzed by using sample preparation method of ISO9233-2, 2007 (IDF 140-2, 2007). The results of analysis have been fully validated statistically and recovery studiesconfirmed the accuracy of the proposed method. The precision (intra-day & inter-day) of method was found within limits(RSD < 2%). The sensitivity of the method was assessed by determining limit of detection and limit of quantification.Findings dealing with the presence of Natamycin in cheese samples are presented.

Different processing methods change the oral toxicity induced by Sophora alopecuroides seeds and the contents of five main toxic alkaloids from the ethanol extracts determined by a validated UHPLC-MS/MS assay

Abstract This study investigated the influence of different processing methods on the oral toxicity of Sophora alopecuroides L., Fabaceae, seeds in mice and on the contents of five known toxic-effective quinolizidine alkaloids from the ethanol extracts quantified by ultra-performance liquid chromatography coupled to tandem quadrupole mass spectrometry. It provides an evidence to elucidate the possible reasons why vinegar-processing and parching methods significantly decrease the acute oral toxicity induced by S. alopecuroides and why wine-processing method increases it instead (demonstrated by measurement of LD50 and histopathological analysis). The analytical performance for the determination of the five analytes was evaluated by linearity, stability, repeatability, precision and accuracy, and recovery test. The lowest limit of quantification was determined to be 5 ng/ml for each substance and the precision and accuracy at lowest limit of quantification were below 20%. Cytisine, the most toxic alkaloid among the five alkaloids, declined 11.26, 3.98, and 2.73 folds after being vinegar-processed and fried in a ceramic or iron pan, respectively and had a very close correlation with the toxicity of S. alopecuroides seeds (r = 0.8589). Other matrine-type alkaloids with lower toxicity including matrine, sophcarpine, and sophoridine decreased after being wine-processed and fried in a ceramic pan, but increased 4.44, 7.20, and 7.23 folds when being processed by vinegar. Oxymatrine declined in all groups. It, therefore, reveals that vinegar-processing method reduces the oral toxicity of S. alopecuroides mainly due to a sharp decrease of cytisine, thus improves its clinical safety.

Safety Evaluation of Lactobacillus casei C1 in Wistar Rats / Jurnal Sains Kesihatan Malaysia

Nowadays, probiotics have been widely consumed as supplementary food for their health benefits. However, safetyevaluation for many probiotic bacteria is still lacking. Furthermore, health benefits conferred by probiotics depend onthe strains used in producing probiotic products. Therefore, it is important to examine oral toxicity of newly isolatedLactobacillus casei (Lb. casei) C1. A total of 32 Wistar (WIS) rats were divided into acute (single dose) and subacuteoral toxicity (28-days repeated dose) groups. Rats in each group were further divided into control group which receivedphosphate buffer saline (PBS) orally and treatment group that was administered orally with Lb. casei C1 (1011 CFU/ml).For acute oral toxicity, treatment was performed on day-1 and the effects were monitored subsequently for 14 days. Forsubacute oral toxicity, treatment was given daily for 28 days and the effects were observed throughout the experimentalperiod. Body weight, food and water intake of the rats were recorded. Rats in acute and subscute groups were sacrificedon day-15 and day-29, respectively. Serum was collected to determine the levels of total protein, malondialdehyde (MDA),alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) and creatinine. Organs were alsoharvested for histological examination. There were no significant differences (p > 0.05) in body weight, food and waterintake between the control and treated rats in acute oral toxicity group. There were also no significant differences in theblood cell count, levels of total protein, MDA, LDH and creatinine between the control and treated rats. Similar findingswere recorded for the subacute oral toxicity group, except that the levels of ALT and AST which were significantly different(p < 0.05). When observed under a light microscope, there were no morphological changes detected in the kidney, liverand ileum of treated rats as compared to control rats in both of the experimental groups. In conclusion, Lb. casei C1exhibited no toxic effects in Wistar rats hence safe to be consumed orally.

Safety Evaluation of Methoxyflavones Mixture (Ⅱ) from Kempferia parviflora：28-day Repeated Dose Oral Toxicity Test / 日本補完代替医療学会誌

Kaempferia parviflora rhizome is used folk medicines for treatment of various symptoms in Thailand since anticent times.Several types of methoxyflavones has been identified in this plant and their physiological functions have been reported.We determined that six kinds of methoxyflavones (5,7,3',4'-tetramethoxyflavone, 3,5,7,3',4'-pentamethoxyflavone, 5,7-dimethoxyflavone, 5,7,4'-trimethoxyflavone, 3,5,7-trimethoxyflavone, 3,5,7,4'-tetramethoxyflavone) were included in the 80% ethanol extract of K. parviflora rhizome.The safety of six methoxyflavones mixture was evaluated with 28-day repeated oral dose toxicity test in mice.These results indicated no significant toxicity on body weight, blood analyses, organ weight, blood biochemical analyses.

Preclinical safety assessment of glycosides based standardized fenugreek seeds extract: Acute, subchronic toxicity and mutagenicity studies.

Objective: To evaluate acute oral toxicity (AOT), subchronic toxicity, and mutagenic potential of glycosides based standardized fenugreek (Trigonella foenum graecum L.) seeds extract (SFSE-G). Materials and Methods: The AOT, subchronic (90-day repeated dose) toxicity and mutagenicity (reverse mutation test) of oral administration of SFSE-G were evaluated using Sprague-Dawley (SD) rats as per OECD guideline no. 423, No. 408 and 471 respectively. Results: The SFSE-G did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-days repeated dose of 250, 500 and 1000 mg/kgwith 28 days of recovery period) administration. The SFSE-G showed oral median lethal dose (LD50) more than 2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of SFSE-G was 1000 mg/kg in male rats and 500 mg/kg in female rats during subchronic toxicity study. Furthermore, SFSE-G did not show mutagenic potential in vitro. Conclusions: SFSE-G was found safe for acute and subchronic (90 days repeated dose) administration in rats with no mutagenic potential.

Experimental Studies on Acute Oral Toxicity, Skin Irritation and Skin Allergy of Thuja Essential Oil / 中国药师

Objective:To evaluate the acute oral toxicity , skin irritation and skin allergy of Thuja essential oil ( TEO) , and pro-vide experimental basis for the clinical use of TEO .Methods:The acute oral toxicity was measured by Horn ’ s assay .Totally 40 KM mice were divided into four groups and intragastrically administered with TEO at different dose of 21.50, 10.00, 4.64 and 2.15 g · kg-1 .After the 14-day observation, the death number and toxic manifestations were recorded and observed , and LD50 was calculated by checking the Horn's form of LD50 .The skin irritation test was performed on healthy adult white rabbits .Totally 9 rabbits were divid-ed into 3 groups randomly , and TEO at the concentration of 100%, 50%and 25%was painted on the skin of the rabbits .Edible vege-table oil was used as the negative control .The erythema and edema of the treated skin were evaluated and scored .Delayed skin hyper-sensitivity reaction was used to investigate the allergy of TEO .Totally 30 white guinea pigs were randomly divided into 3 groups:TEO group, the negative control (edible vegetable oil) and the positive group (1%2, 4-dinitrochlorobenzene).After the intracutaneous in-duction stage and local induction stage , TEO was used to activate the hypersensitive reaction .The skin response was observed and scored after the 24-hour and 48-hour activation.Results:The mice in 21.50 g · kg-1 TEO treatment group were all dead , while only a part of the mice in 10.00 and 4.64 g · kg-1 TEO treatment groups were dead , and no mice died in 2.15 g · kg-1 TEO treatment group.According to the Horn's form of LD50 , LD50 of TEO was 9.26 g · kg -1 for male mice and 7.94 g · kg -1 for female mice.The results of skin irritation test indicated the strong irritation effects of TEO .However , the irritation of TEO was reduced after the dilution , and 25%TEO showed no irritation to the skin of rabbits .The results of delayed skin hypersensitivity reaction showed obvious erythema and edema induced by 2, 4-dinitrochlorobenzene , while no obvious erythema and edema were found in TEO treated guinea pigs , indi-cating non-allergic effect of TEO .Conclusion:TEO has strong skin irritation in rabbits , while no obvious oral toxicity in mice and skin allergy in guinea pigs .

Acute oral toxicity and genotoxicity of Rosa laxa Retz. var. mollis Yu et Ku cynarrhodion extracts / 国际药学研究杂志

Objective To study the acute oral toxicity and genotoxicity of Rosa laxa Retz. var. mollis Yu et Ku cynarrhodion extracts. Methods The acute oral toxicity in mice and rats (maximal tolerance dose, MTD) were observed for 14 days after administration. Genetictoxicity was evaluated on Salmonella typhimurium reverse mutation assay (Ames test), in vivo mammalian erythrocyte micronucleus assay, sperm malformation assay in mice and single cell gel electrophoresis (Comet assay). Results In acute oral toxicity study, the behavior, clinical signs and body changes were normal in all experimental animals. LD50 > 15.0 g/kg (rats) and 20.0 g/kg (mice). In the test dose range, results of the four genotoxicity tests were negative. Conclusions In accordance with internationally recognized animal ethics and technical specifications for the experiments using SPF animals in our lab, the acute oral toxicity of R. laxa Retz. var. mollis Yu et Ku cynarrhodion extracts is classified as nontoxic, and genotoxicity is not observed under the test condition.

Isolation of the intracellular and extracellular polysaccharides of Ganoderma neojaponicum (Imazeki) and characterization of their immunomodulatory properties

Background The role of polysaccharides isolated from the Ganoderma species of fungi in innate immunity has recently become a topic of research. Although some work has been conducted concerning Ganoderma lucidum, the characteristics of polysaccharides isolated from Ganoderma neojaponicum (Imazeki) as immunomodulatory agents are largely unknown. The aims for this study were to isolate and characterize the intracellular polysaccharides (IPSs) and extracellular polysaccharides (EPSs) of G. neojaponicum from STR reactor. Results The production of EPS and IPS was optimized on day 4 of the cultivation time in 2 L STR reactor based on the amount of biomass yield, total carbohydrate, β-glucan and a-glucan content. Further analysis, both the EPSs and IPSs showed the enhancement on proliferation and increment of phagocytosis activities of macrophage (RAW264.7) cell lines. Using an oral toxicity test, we also observed that 2000 mg/kg body weight/day dosage of dried G. neojaponicum mycelium does not cause any significant toxic effects on Sprague-Dawley rats in 14 d of administration. Conclusion The findings of this study indicate that the IPSs and EPSs of G. neojaponicum have the potential to be used as immunomodulating agents to stimulate the innate immune system for fighting infectious diseases. The polysaccharides from G. neojaponicum have to be further commercially explored as an alternative for medicinal Ganoderma variety of G. lucidum production.

Safety Evaluation of Methoxyflavones Mixture (Ⅰ)from <i>Kempferia parviflora</i>; 28-day Repeated Dose Oral Toxicity Test and Mouse Micronucleus Test / 日本補完代替医療学会誌

Kaempferia parviflora rhizome is used in traditional folk medicines for the treatments of various symptoms in Thailand since ancient times. Several types of methoxyflavones were identified from that plant and the functions of some of those were reported. We determined that five kinds of methoxyflavones (5-hydroxy-3,7,3’,4’-tetramethoxyflavone, 5-hydroxy-7-methoxyflavone, 5-hydroxy-3,7-dimethoxyflavone, 5-hydroxy-3,7,4’-trimethoxyflavone, 5-hydroxy-7,4’-dimethoxyflavone) were included the following treatments of K. parviflora rhizome. The 80 %ethanol extract of that were adsorbed resin, removed 70 % ethanol elution and the rest adsorbed materials were eluted with 99.5 % ethanol. The safety of that five methoxyflavones mixture was evaluated. We performed a 28-day repeated dose of oral toxicity test and a mouse micronucleus test. The former results showed no significant toxicity on body weight, blood analyses, organ weight, blood biochemical analyses. The latter results showed negative, believed that the sample has no mutagenicity for living bodies.

SUBACUTE ORAL TOXICITY STUDIES OF BCDMH EFFERVESCENT TABLETS FOR HOS-PITAL SEWAGE / 现代医院

Objective To study subacute oral toxicity of a disinfectant for hospital sewage which contained 1-bromo -3 -chloro -5, 5 -dimethylhydantoin (BCDMH) in order to know about its toxicological safety .Methods Animal test and biochemical examination methods were adopted to evaluate its subacute toxicity .Results During the subacute toxicity test, none of the rats died.At the end of the experiment , urine routine and hematological exami -nation were in the normal ranges .There were no difference compared with the control (p >0.05).But serum alanine aminotransferase in both sexes as well as creatinine in male SD rats of the high dose group were increased obviously compared with the control (p <0.05).Mild steatosis and spotty necrosis of liver cells were found in the high dose group during the pathological examination .Conclusion The BCDMH effervescent tablets'no -observed -adverse -effect -level (NOAEL) is 84 mg? kg-1 for male SD rats, and 98 mg? kg-1 for female SD rats.

Acute oral toxicity of Celtis iguanaea (Jacq. ) Sargent leaf extract (Ulmaceae) in rats and mice / Toxicidade oral aguda do extrato de folhas de Celtis iguanaea (Jacq. ) Sargent em ratos e camundongos

RESUMO Celtis iguanaea (Jacq.) Sargent is popularly used to treat urinary infections, kidneys, breast, body aches, rheumatism, asthma, cramps, poor digestion and as a diuretic medicine. This study aims to determine the acute toxicity of the aqueous leaf extract of Celtis iguanaea (Jacq.) Sargent in rodents. After the collection processes, identification, drying and grinding, the lyophilized powder of the leaves produced, by infusion, the aqueous extract and it was dissolved in saline 0.9%. The administration was made by gavage at a dose of 2000 mg kg-1to rats and mice of both genders. The oral toxicity was determined according to the OECD 423 guide. Signs of toxicity were observed for 15 days and classified from 0 to 4 respectively as missing, rare, mild, moderate and severe. The weight of the animals and the physiological parameters such as food intake and excrements production were observed. All animal tissue samples were collected for histological analysis. The extract was included in Type 5 (substance with LD50 higher than 2000 mg kg-1 and less than 5000 mg kg-1), being considered of low toxicity, but the histopathologycal findings suggested nephrotoxicity and cardiotoxicity. The absolute weight of the kidneys and the heart of the male rats and mice increased, but there was no significant raise in the relative weight of the animals’ organs.

RESUMO Celtis iguanaea (Jacq.) Sargent é uma planta usada popularmente para tratar infecções do trato urinário, rim, mama, dores no corpo, reumatismo, asma, cólicas, má digestão e também é usada como diurético. Este trabalho objetivou determinar a toxicidade aguda do extrato aquoso de folhas de Celtis iguanaea (Jacq.) Sargent em roedores. Após os processos de coleta, identificação, secagem e moagem, o pó liofilizado das folhas da planta foi utilizado para produzir o seu extrato aquoso por infusão e então dissolvido em solução salina a 0.9 %. A administração foi feita por gavagem na dose de 2000 mg kg-1 em ratos e camundongos de ambos os sexos. A toxicidade oral foi determinada de acordo com o guia 423 da OECD. Sinais de toxicidade foram observados por 15 dias e tabulados de 0 a 4, respectivamente, como ausentes, raros, leves, moderados e graves. Foi acompanhado o peso dos animais e parâmetros fisiológicos tais como alimentação e excreções. Amostras do tecido de todo o animal foram coletadas para análise histológica. A toxicidade encontrada para o extrato foi incluída na classe 5 (substâncias com DL50 superior a 2000 mg kg-1 e menor que 5000 mg kg-1) sendo considerada baixa, porém, as observações histopatológicas sugerem nefrotoxicidade e cardiotoxicidade. O peso absoluto dos rins e coração de ratos e camundongos machos aumentou, porém, não houve aumento significativo no peso relativo dos órgãos dos animais.

Assessment of acute toxicity of the ethanolic extract of Lychnophora pinaster (Brazilian arnica)

Species of the Lychnophora genus are plants native to Brazil, popularly known as "Brazilian arnica" and used in folk medicine as alcoholic and hydro-alcoholic preparations for the treatment of bruises, inflammation, pain, rheumatism and insect bites. The present study aimed to evaluate the safety of the use of Lychnophora pinaster Mart., Asteraceae. Acute toxicity of the crude ethanolic extract was evaluated by administration of the extract by oral route to male and female Swiss mice. A single extract dose of 125, 250 or 500 mg/kg was administered and the effects on spontaneous locomotor activity, exploratory behavior, muscle strength, body weight, food and water consumption, relative organ weight, histology, as well as hematological and biochemical parameters were evaluated. The three doses administered to the animals did not cause muscle tone alterations, but doses of 250 and 500 mg/kg induced a significant inhibition of the spontaneous locomotor activity and exploratory behavior of the animals in open-field test. There was no alteration to hematological parameters and consumption of water and food, body weight variation and organs relative weight. Changes were observed in AST and ALT during assessment of biochemical parameters. The histopathological evaluation showed that the extract provoked cellular alterations, such as vacuolar degeneration and inflammation in kidneys and liver at all doses. Liver morphometric analyses of male and female mice showed that the extract did not have dose-dependent effects. Although females showed a significant increase in inflammatory cells, the effect was not dose-dependent.

Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats

BACKGROUND: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. RESULTS: Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04±0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment. CONCLUSIONS: Our results reveal for first time that compounds contained in the hydroalcoholic extract ofLampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These findings also justify the traditional use of the plant for treating pain.

Anti-Inflammatory Potential of Ethanolic Extracts from Aerial Parts of Ipomoea Pes-Caprae (L.) R.Br Using Cotton Pellet Induced Granuloma Model.

Ipomoea Pes-caprae (L.) R.Br (IP) is a valuable medicinal plant, distributed in the tropics and subtropics regions and used in folk and tribal medicines. Traditionally IP is used in inflammatory conditions such as arthritis and also used to treat pain, ulcer, cancer and wounds. The acute anti-inflammatory activity of IP has been previously reported. The present study aims to discover the anti-inflammatory effect of ethanolic extracts from aerials parts of IP by sub-acute anti-inflammatory model. Completely dried leaves and stems of I.pes-caprae were extracted using ethanol by hot percolation method. The EELIP & EESIP (Ethanolic extract of Leaves & Stems of IP) thus obtained were subjected to preliminary phytochemical analysis and revealed the presence of alkaloids, carbohydrates, glycosides, flavonoids, tannins, sterols and terpenoids both in leaf and stem extracts. The LD50 of both EELIP & EESIP were found to be >2000 mg/kg by acute oral toxicity study. Both EELIP & EESIP exhibited significant anti-inflammatory activities in dose dependent manner.

Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves

OBJECTIVE: Ficus deltoidea leaves have been used in traditional medicine in Southeast Asia to treat diabetes, inflammation, diarrhea, and infections. The present study was conducted to assess the genotoxicity and acute and subchronic toxicity of a standardized methanol extract of F. deltoidea leaves. METHODS: Sprague Dawley rats were orally treated with five different single doses of the extract and screened for signs of toxicity for two weeks after administration. In the subchronic study, three different doses of the extract were administered for 28 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological parameters were monitored during the study. Genotoxicity was assessed using the Ames test with the TA98 and TA100 Salmonella typhimurium strains. Phytochemical standardization was performed using a colorimeter and high-performance liquid chromatography. Heavy metal detection was performed using an atomic absorption spectrometer. RESULTS: The acute toxicity study showed that the LD50 of the extract was greater than 5000 mg/kg. In the subchronic toxicity study, there were no significant adverse effects on food consumption, body weight, organ weights, mortality, clinical chemistry, hematology, gross pathology, or histopathology. However, a dose-dependent increase in the serum urea level was observed. The Ames test revealed that the extract did not have any potential to induce gene mutations in S. typhimurium, either in the presence or absence of S9 activation. Phytochemical analysis of the extract revealed high contents of phenolics, flavonoids, and tannins. High-performance liquid chromatography analysis revealed high levels of vitexin and isovitexin in the extract, and the levels of heavy metals were below the toxic levels. CONCLUSION: The no-observed adverse effect level ...

Toxicología subcrónica de infusión de Chenopodium ambrosioides (epazote) por administración oral en ratones NIH / Subchronic toxicology of Chenopodium ambrosioides (epazote) infusion orally administered to NIH mice

Introducción: las plantas medicinales constituyen una valiosa alternativa terapéutica y su validación científica es una necesidad. Objetivo: identificar los posibles efectos tóxicos producidos por la infusión de Chenopodium ambrosioides L. (Chenopodiaceae) sobre el modelo biológico utilizado. Métodos: para determinar la toxicidad subcrónica de la infusión se emplearon ratones albinos suizos NIH de los 2 sexos, a los que se les administró por vía oral infusiones de la especie estudiada a concentraciones de 32, 64 y 134 mg/mL por 90 días. Al mismo tiempo se realizaron observaciones clínicas diarias con el fin de identificar algún efecto tóxico posadministración de la sustancia. Después fueron sacrificados para realizar los exámenes hematológicos (hematocrito, hemoglobina, glóbulos rojos, glóbulos blancos, neutrófilos y linfocitos) y bioquímicos (alanino aminotransferasa y creatinina), así como estudios macroscópicos e histológicos de los órganos internos (riñón, hígado, pulmón e intestino). Resultados: se encontró que la infusión de Chenopodium ambrosioides a las dosis administradas no causó efectos determinantemente significativos en los parámetros toxicológicos, en el peso corporal, en hematología y química sanguínea, al igual que tampoco provocó alteraciones anatomopatológicas sobre los órganos y tejidos evaluados. Conclusiones: la infusión de Chenopodium ambrosioides bajo estas condiciones experimentales no presentó actividad tóxica.

Introduction: medicinal plants represent a valuable therapeutic alternative and their scientific validation is a must. Objectives: to determine the possible toxic effects produced by the infusion of Chenopodium ambrosioides L. (Chenopodiaceae) on the used biological model. Methods: to determine the subchronic toxicity of the infusion, NIH Swiss albino mice of both sexes were used, to which infusions from the tested species, at concentrations of 32, 64, and 134 mg/mL , were orally administered for 90 days. At the same time, daily clinical observations were performed in order to identify any toxic post-dose administration. Afterwards, they were sacrificed for conduction of hematological tests (hematocrit, hemoglobin, red blood cells, white cells, neutrophils and lymphocytes) and biochemical (alanine aminotransferase and creatinine) and macroscopic and histological studies of the internal organs (kidney, liver, lung and intestine.). Results: the infusion of Chenopodium ambrosioides at the tested doses caused neither decisively significant effects on the toxicological parameters, body weight, hematology and blood chemistry nor pathological changes on organs and tissues. Conclusions: the infusion of Chenopodium ambrosioides under our experimental conditions showed no toxic activity.

Safety Evaluation of <i>Ashitaba</i> (<i>Angelica Keiskei</i>) on Mutagenic Test, Single and 13-Weeks Oral Toxicity Tests / 日本補完代替医療学会誌

We evaluated the safety of <i>Ashitaba</i> (<i>Angelica keiskei</i>) in bacterial reverse mutation test as well as single and 13-weeks oral toxicity tests. In the bacterial reverse mutation test, ethanol extract of <i>Ashitaba</i> had no reverse mutation inducing activity on five bacterial strains with or without S9 metabolic activation. In the single oral toxicity test, <i>Ashitaba</i> powder (3,500 mg/kg/day) showed no adverse effects in male and female SD rats. In the 13-week repeated oral toxicity test, <i>Ashitaba</i> powder (875 and 1,750 mg/kg/day) showed no adverse effects on body weight, food consumption, blood biochemistry, hematology, urinalysis, ophthalmoscopy, organ weight and histopathology in male and female SD rats. These results indicate that<i> Ashitaba</i> is very safe foodstuff under the conditions of this study.<br>