Phenolic Profile, Acute Toxicity, Hepatoprotective and Antiproliferative Activities of Algerian Ruta tuberculata forssk

Objective: Ruta tuberculata forssk. (Rutaceae) is an aromatic plants widely used in Algerian traditionally medicine due to its pharmaceutical virtues against various disorders. This study aims to determine the phenolic profile of aqueous (RAE) and methanol (RME) extracts of R. tuberculata aerial parts and to investigate their acute oral toxicity, as well as their possible antiproliferative and hepatoprotective effects. Methods: Polyphenols were identified by quantitative LC-MS/MS analysis. Oral acute toxicity was performed according to OCDE guidelines. The hepatoprotective activity was evaluated by paracetamol-induced hepatotoxicity and supported by biochemical and histological analysis of liver and kidneys. The antiproliferative activity against human colorectal HT-29 and ovarian OV2008 cancer cell lines was determined using SRB assay. Results: LC-MS/MS analysis revealed that RME has higher phenols and flavonoids content than RAE, however, it’s major identified flavonoids namely Kaempferol, rutin and naringenin. R. tuberculata seems mildly toxic at several doses, with oral LD50 greater than 5000 mg/kg. the significant increase in hepatic markers enzymes activities as well as cholesterol, triglycerides and glycemia levels, caused by PCM-administration, was potentially reduced following the co-treatments with vitamin C and RME, respectively, compared to RAE. Moreover, RME-treatment markedly prevented all histological changes. Compared to RAE, RME (100 μg/mL) exhibited excellent antiproliferative activity against both tested cancer lines (% inhibition ≥ 80 %). Conclusion: Both R. tuberculata extracts (200 mg/kg/daily) were non-toxic and exerted a potential hepatoprotective effect against PCM-induced hepatotoxicity. Accordingly, RME may be considered a good candidate for the development of new therapies against colorectal and ovarian cancers.

28 Days Sub Acute Toxicity Studies of the Methanol Stem Bark Extract of Combretum hypopilinum Diels (Combretacea) in Rats

The aim of this study was to evaluate the safety profile of Combretum hypopilinum stem bark extracted with Methanol (70%v/v). Preliminary Phytochemical screening of the crude methanol stem bark extract was carried out, and revealed the presence of secondary metabolites such as steroids, flavonoids and alkaloids. Initial oral acute toxicity test was carried out using the Limit Dose Test to ascertain the safety of the extract in rats. Sub-acute toxicity testing was conducted by 28 days oral administration of 400 mg/kg, 800 mg/kg and 1600 mg/kg body weight to three groups of ten rats. The fourth group was administered distilled water 10 ml/kg. No major changes were observed in body weight of the animals following 28 days of daily oral administration. Biochemical parameters such as Total Protein, Total Bilirubin, Creatinine, Aspartate Transaminase (AST) and Alanine Transaminase (ALT), were found to be within normal ranges. The levels of marker enzymes in the vital organs did not show any significant changes between control and treated groups. Histopathological examination of the major vital organs (liver, brain, and kidney) revealed no significant pathological changes in the treated groups of rats. The results of the present work suggested that the methanol stem bark extract of Combretum hypopilinum is relatively safe for use at the tested doses.

Effects of Zinc Sources and Levels on Growth Performance, Zinc Status, Expressions of Zinc Transporters, and Zinc Bioavailability in Weaned Piglets

The present study was conducted to explore the bioavailability of chitosan–zinc chelate (CS–Zn) in weaned piglets, and its characteristics of prepared and oral safety were also involved. A total of 210 crossbred weaned piglets (Duroc × Landrace × Large White) with a mean body weight of 6.30 kg were randomly assigned into seven dietary treatments involving a 2 × 3 factorial arrangement with two Zn sources (CS–Zn and ZnSO4) and three levels of added Zn (50, 100, 150 mg Zn/kg) plus a Zn-unsupplemented control diet. The feeding trial lasted 42 days. The AFM image of CS–Zn showed a rougher appearance and smaller size particles. The changes in spectrum peaks evidenced the successful chelating of Zn2+ with chitosan. The XRD patterns revealed the formation of a new crystalline phase. Moreover, the oral acute toxicity test of CS–Zn showed no lethal effects on mice. Weaned piglets fed dietary CS–Zn showed improved weight gain and decreased diarrhea incidence. Additionally, the bioavailability of CS–Zn was higher than that of ZnSO4 in piglets. Taken together, these results indicate that the prepared CS–Zn chelate, with rough surface and crystalline phase, is non-toxic and show enhanced bioavailability.

Anti-inflammatory Effect of the Alkaloid-rich Fraction of Landolphia owarensis

Background: Plants have several chemical compounds acclaimed to be responsible for the pharmacological actions produced when herbal products are administered to biological systems.Objectives: This study was designed to investigate the anti-inflammatory effect of the alkaloid-rich fraction of the ethanol leaf extract of Landolphia owariensis.Methods: Qualitative phytochemical analyses were carried on the crude extract using standard methods. The alkaloid-rich fraction was obtained from the crude ethanol extract, using the classical acid/base shake-up method and the obtained fraction tested positive to Dragendorf’s reagent. Oral acute toxicity was evaluated by OECD method (No 423). Anti-inflammatory effect of the fraction was evaluated using xylene-induce ear oedema and carrageenan-induced paw inflammation in mice at doses of 100, 200 and 400 mg/kg.Results: Phytochemical screening revealed presence of alkaloids, flavonoids, tannins, saponins, steroids/terpenes and glycosides. Acute toxicity studies showed no adverse symptoms of toxicity during the 14-day observation period and no mortality was recorded, thus the LD50 was estimated to be greater than 2000 mg/kg. The alkaloid-rich fraction dose-dependently inhibited inflammation induced by xylene and carrageenan. In the xylene test, the fraction produced significant inhibition of 41.70 % at 400 mg/kg (p ≤ 0.05) while in the carrageenan test 55.69 % significant inhibition (p ≤ 0.001) was recorded with 400 mg/kg at 60 mins after induction of inflammation.Conclusion: This study showed the anti-inflammatory potentials of the alkaloid-rich fraction of Landophia owariensis.

ORAL ACUTE TOXICITY TEST OF RED BETEL LEAF (Piper crocatum) AS PERIODONTAL POCKET THERAPY (As Seen From Mortality Rate, Weight Changing, And Relative Organ Index Of Swiss Webster Mice)

Red betel leaf (Piper crocatum) contains useful chemical compounds like alkaloid, saponin, tannin, and flavonoid which have an anti-inflammatory and antibacterial characteristics. Previous research shows red betel leaf has a better bactericidal profile than the green ones. The red betel leaf extract is already proven to disturbing the growth of periodontal causative bacteria in an earlier study. Any ingredient or chemical contents on food and drug shall run a toxicity test before permitted to use generally. This study’s purpose is to investigate the acute toxicity effect of red betel leaf extract as a periodontal pocket therapy ingredient. The acute toxicity experimental is conducted on Swiss webster mice which divided into six groups consisting of 4 males and four females each. The dose given to the subject is a single dose by the oral route as amount as the twice maximal tolerated dose that is 10000, 5000, 2500, 1250, and 625 mg/kg BW. The weight of mice is measured every day from day-1 until day-14 after that (on day-15) the mice are cut to counting relative organ index. The collected data is analyzed using The One-way ANOVA test and continues with the posthoc Tucay test. This study result shows that red betel leaf extract with doses 10000, 5000, 2500, 1250, and 625 mg/kg BW given acutely doesn’t generate a significant change in weight and relative organ index of the test’s subject. Based on this result, it can be concluded that red betel leaf extract is not toxic.

Hydromethanolic Crude Extract of the Leaf of Urtica simensis Hochst. ex. A. Rich. (Urticaceae) Acquires Appreciable Antiulcer Effect: Validation for In Vivo Antiulcer Activity

Background. Urtica simensis has been used for the treatment of peptic ulcer disease in Ethiopian folkloric medicine by drinking its juice after boiling the semicrushed leaf. To our latest understanding, no in vivo study was available regarding its antiulcer activity. The present study was done to appraise the ulcer-protective and ulcer healing activity of hydromethanolic crude extract of leaf of U. simensis in rats. Methods. Preliminary qualitative phytochemical screening and oral acute toxicity were carried out using a standard protocol. To validate U. simensis in vivo antiulcer potential pyloric ligature, cold restraint stress and acetic acid-induced ulcer models were employed. The extracts (100, 200, and 400 mg per kg of body weight per day), standard treatment (omeprazole 20 mg/kg/day), and vehicle (distilled water 10 ml/kg/day) were given to treatment, positive, and negative controls by oral gavage, respectively. Parameters were then evaluated accordingly after the humane scarification of rats. Results. Any sign of toxicity was not observed in the oral acute toxicity test. The crude extracts exerted a significant ( P < 0.05 ) inhibition of ulcer risk compared to the negative control. In the pylorus ligation-induced ulcer model, its antisecretory activity was in a dose-dependent manner. The highest gastroprotective effect (67.68%) was exhibited by the 400 mg/kg/day dose of 80% methanolic crude extract. Regarding the chronic ulcer model, treatment at a dosage of 100, 200, and 400 mg/kg/day cures ulcers by 33.54%, 58.33%, and 67.07%, respectively, as compared to the negative control groups remarkably. Conclusion. The findings of the present study confirmed the safety and a promising in vivo ulcer healing and antiulcerogenic activity of U. simensis, thus supporting the traditional claim. In-depth investigations on the plant, however, are highly recommended.

Acute toxicity of Siltac EC to the honey bee (Apis mellifera)

<b>Different types of pesticides are commonly used in modern agriculture. Honey bees (Apis mellifera) are sensitive indicators of environmental contamination with these substances. Exposure of honey bees to pesticides can lead to changes in their behaviour and increase mortality, so it is important to develop formulations that provide alternatives to common (‘chemical’) pesticides. The preparation Siltac EC, that has recently been developed (patent no. WO 2016/061259), shows promise as an effective substitute. This preparation is based on a physical interaction with the pest. It does not contain chemicals classified as pesticides. The aim of the current study was to evaluate the toxicity of Siltac EC to adult honeybee workers. The experiments showed that both contact and oral acute toxicity were very low and the preparation can be initially considered safe for honey bees.

Anti-nociceptive, anti-inflammatory and antipyretic activities of the ethanol root bark extract of Salacia lehmbachii in rats and mice

Background: The decoction of the roots of Salacia lehmbachi is used in traditional medicine for the treatment different diseases such as malaria pains diabetes and microbial infections.Methods: Phytochemical screening and oral acute toxicity tests were carried out on the ethanol root extract of the plant. Anti-nocicetive activity using acetic acid induced writhing and tail immersion method in mice, anti-inflammatory activity using carrageenan induced paw oedema in rats and xylene induced ear oedema test in mice and antipyretic activity using Brewer’s yeast and D-amphetamine induced pyrexia in rats were determined at 50 mg/kg, 100 mg/kg and 200 mg/kg doses of the root extract.Results: The ethanol root extract contain alkaloids, saponins, tannins, flavonoids, terpenoids, steroids and cardiac glycosides. The oral acute toxicity tests was found to be greater than 5000 mg/kg. The root extract and the standard drug (Aspirin) significantly (p<0.05 and p<0.01) decreased the number of writhes caused by acetic acid. The extract and morphine significantly (p<0.05 and p<0.01) prolonged reaction time in tail immersion model. The extract produced significant (p<0.05 and p<0.01) dose dependent inhibition of oedema which was comparable to aspirin in carrageenan induced paw oedema model. The root extract also demonstrated significant (p<0.05 and p<0.01) effect in xylene induced mouse ear oedema test compared to dexamethasone. The extract significantly decreased high temperature in both Brewer’s yeast and d-amphetamine induced pyrexia.Conclusions: Findings show that S. lehmbachii may provide a good source of plant compounds with analgesic, anti-inflammatory and antipyretic activities.

EVALUATION OF TOXICITY AND ANTIASTHMATIC POTENTIAL OF AN AYURVEDIC FORMULATION ON EXPERIMENTAL ANIMALS

The aim of this study was to explore acute and chronic toxicity as well as antiasthmatic potential of the ayurvedic formulation Nayopayam Kashayam on experimental animals. The present study was targeted for the study of its toxicity profile along with its antiasthmatic activity. The acute toxicity study was carried out using OECD 425 CPCSEA guideline in albino wistar rats. Oral acute toxicity study was performed at 2000mg/kg orally, which was considered as limit dose. The chronic toxicity study was carried out with administration of Nayopayam Kashayam at three therapeutic equivalent doses i.e. TED (45mg/kg, orally), TEDx5 (225 mg/kg, orally) and TEDx10 (450 mg/kg, orally) for 90 days. Further, antiasthmatic study was carried out using histamine-induced bronchospasm in guinea pig model. The results of acute toxicity studies showed that drug did not create any signs and symptoms of toxicity and no mortality was shown to an oral dose of 2000 mg/kg in rats. The results of chronic toxicity study showed that the drug even at level as high as dose of TEDx10 had no significant effect at all on hematological and body weight parameters, however mild to moderate unfavorable changes in kidney and liver were indicated. The experiential changes were not seen at the lower dose levels. The drug also showed a marked decrease in hiccups of asthma during antiasthmatic study. Hence, it is suggested that the Nayopayam Kashayam, prepared as per the traditional method, is secured/safe for utilization and treatment of asthma at the therapeutic dose level.