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

2021 ◽  
Vol 17 ◽  
Author(s):  
Asma Saidi ◽  
Leila Hambaba ◽  
Burak Kucuk ◽  
Ercan Cacan ◽  
Ramazan Erenler

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.

2019 ◽  
Vol 5 (1) ◽  
pp. 79-93
Author(s):  
Dharma Prasad Khanal ◽  
Rupa Rana ◽  
Bechan Raut ◽  
Rabindra Prasad Dhakal

Objective: The aim of the research work was to carry out the extraction of areal parts of Biden pilosa L by hydroalcholic and Hexane, ethyl acetate and acetone mixture followed by qualitative phytochemical analysis, acute oral toxicity test, anti-inflammatory test and GC-MS analysis of the extracts. Method: The hydro-alcoholic and HEA(n-hexane, ethyl acetate and acetone) extraction was done from aerial parts using ethanol and water in the ratio 70:30 and n-hexane, ethyl acetate and acetone in the ratio of 1:1:1 (HEA extract)  respectively. Acute oral toxicity testwas performed OECD guidelines. The single spot in TLC was obtained using n-hexane as solvent for HEA fraction and finally phytocomponents were identified by GC-MS present in that spot.In vitro anti-inflammatory activity was performed by human RBC membrane stabilization method. Result: The phytochemical test results obtained indicate that hydro-alcoholic extract of aerial part of Bidens pilosa L. possess alkaloids, tannins, terpenoids and saponins whereas HEA extract possess alkaloids, flavonoids, tannins. Both hydro-alcoholic and HEA extracts were found to be safe up to the dose of 2000 mg/kg BW of the mice. Both extracts showed significant in vitro anti-inflammatory activity in a concentration dependent manner. The GC-MS analysis of HEA extract of aerial parts showed the presence of the sixteen different compounds from partially separated extract from TLC plates. Conclusion: Hydro-alcoholic extract of aerial part of Bidens pilosa L. possess alkaloids, tannins, terpenoids and saponins whereas HEA extract possess alkaloids, flavonoids, tannins. Both hydro-alcoholic and HEA extracts were found to be safe up to the dose of 2000 mg/kg BW of the mice. The GC-MS analysis of HEA extract of aerial parts showed the presence of the sixteen different compounds.


Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Jobi Xavier ◽  
Kshetrimayum Kripasana

The present study was focused on the concentration-dependent changes in oral acute toxicity of leaf extracts of E. fluctuans in zebrafish. The study was also aimed at the details of histopathological changes in the gill, liver, brain, and intestine of zebrafish exposed to the leaf extracts of the plant E. fluctuans. Enydra fluctuans Lour is an edible semiaquatic herbaceous plant used widely for the alleviation of the different diseases. Since there were no toxicity studies conducted on this plant, the present study was an attempt to look into the elements of toxicity of the plants. Two types of experiments are conducted in the present study. First, the acute oral toxicity study was conducted as per the OECD guidelines 203. Second, histopathological changes were observed in the fishes exposed to the lethal concentrations of plant extract. The oral acute toxicity studies conducted on Zebrafish have revealed that the leave extracts of E. fluctuans were toxic to the tested fish at the concentration of 200 mg/kg body weight. The histopathological studies conducted on the intestine of treated fishes showed that treatment has induced rupturing of the villi structure and fusion of villi the membrane and detachment of the villi structure from the basal membrane of the intestine. The histology of the liver also showed severe vacuolization in the cells while it is not affected in control. The studies on gills showed the detachment of the basal epithelial membrane in the gills compared to control which might have led to death of the fish. The histopathological observations of brain tissues treated with test samples also revealed the marked impingement in the brain parenchyma while the control is normal without impingement of the brain.


2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Uchechi E. Enenebeaku ◽  
Nnamdi C. Ukwandu ◽  
Ifeyinwa C. Mgbemena ◽  
Harriet C. Nwigwe ◽  
Conrad K. Enenebeaku ◽  
...  

Abstract Background Malaria is one of the tropical diseases of universal concern particularly with continuous appearance of resistant strains of P.falciparum. This calls for continous screening of traditional plants such that new and effective antimalarial agents will be developed. This study therefore explored the oral acute toxicity and antimalarial potentials of aqueous and methanolic extracts of roots, leaves and stem of Dictyandra arborescens on Plasmodium berghei infected mice. Results No mortality was recorded in any of the experimental animal groups even at the highest tested dose (5000 mg/kg b.wt) of the extract after monitoring them for 4hrs and subsequently for 7 days. Out of the six extracts, methanolic extracts of the roots and leaves exhibited more antimalarial activity than others. A significant difference (P < 0.05) was statistically observed in the parasite count of groups that received methanol extracts of roots and leaves of D. arborescens. This observation was made when these two extracts were compared with other groups as well as the negative control. However, activity of the standard antimalarial drug (artesunate) was higher (p˂0.05) than those of the extracts. Phytochemicals such as tannins, alkaloids, saponins, terpenoids, flavonoids etc. were present in the extracts in varying quantities. GC–MS analysis of methanol extract of the root of this plant showed different chemical compounds. Conclusion Administration of aqueous and methanol extracts of roots, leaves and stem of D. arborescens in mice is not harmful at any dose less than or equal to 5000 mg/kg. Methanol extracts exhibited more antimalarial activity than aqueous extracts suggesting that antimalarial activity of the plant parts could be affected by the solvent used for extraction and antimalarial activity may be more in a particular part of a plant. The presence of different bioactive compounds identified in phytochemical and GC–MS analysis could be the fundamental scientific evidence for the antimalarial activity exhibited by this plant especially in the root.


2020 ◽  
Author(s):  
Jobi Xavier ◽  
Kshetrimayum Kripasana

AbstractThe present study was focused on the concentration dependent changes in oral acute toxicity of leaf extracts of E. fluctuans in zebrafish. The study was also aimed at the details of histopathological changes in gill, liver, brain and intestine of zebrafish exposed to the leaf extracts of the plant E. fluctuans. Enydra fluctuans Lour is an edible semi-aquatic herbaceous plant used widely for the alleviation of the different diseases. Since there were no toxicity studies conducted on this plant the present study was an attempt to look into the elements of toxicity of the plants. Two types of experiments are conducted in the present study. First, the acute oral toxicity study was conducted as per the OECD guidelines 203. Second, histopathological changes were observed in the fishes exposed to the lethal concentrations of plant extract. The oral acute toxicity studies conducted on Zebrafish have revealed that the leave extracts of E. fluctuans were toxic to the tested fish at the concentration of 200 mg/kg body weight. The histopathological studies conducted on intestine of treated fishes showed that treatment has induced rupturing of villi structure and fusion of villi membrane and detachment of villi structure from basal membrane of intestine. The histology of the liver also showed severe vacuolization in the cells while it is not affected in control. The studies on gills showed the detachment of basal epithelial membrane in gills compared to control which might have led to death of the fish. The histopathological observations of brain tissues treated with test samples also revealed the marked impingement in brain parenchyma while the control is normal without impingement of brain.


2020 ◽  
Vol 19 (9) ◽  
pp. 1895-1901
Author(s):  
Fairouz Belhadi ◽  
Saida Ouafi ◽  
Nadia Bouguedoura

Purpose: To determine the phytochemical composition, acute toxicity, as well as analgesic and antiinflammatory properties of extracts of the aerial parts and callus cultures of Asteriscus graveolens.Methods: Different standard chemical tests were used for the screening of bioactive compounds in aqueous extracts of aerial parts of Asteriscus graveolens (PAE) and callus (CAE). High-performance liquid chromatography (HPLC) analysis was performed to identify the constituents of the glycosidic extract (GE). Acute oral toxicity test was carried out to ascertain the safety of the plant material. The analgesic and anti-inflammatory properties of the extracts were determined using acetic acid-induced writhing test and carrageenan-induced edema test, respectively.Results: Phytochemical analysis showed some differences in composition between the aerial parts and callus cultures. Results from HPLC analysis revealed the presence of 12 phenolic compounds in the GE of adult plants. In addition to being orally safe (no mortality), all extracts showed significant inhibition of acetic acid-induced chemical pain: PAE and GE produced 63 and 68 % reductions in pain, respectively, relative to 60.26 % pain reduction by aspirin. All extracts exerted potent anti-inflammatory effects, with PAE producing the highest effect (73 %) at a dose of 100 mg/mL.Conclusion: Asteriscus graveolens extracts possess potent pharmacological properties due to the presence of some phenolic compounds, especially flavonoids. These findings provide a scientific basis for the traditional uses of Asteriscus graveolens, and indicate that it is a potential source of antiinflammatory agents. Keywords: Acute toxicity, Anti-nociceptive, Anti-inflammatory, Aqueous extract, Callus, Flavonoids


2020 ◽  
Vol 10 (3) ◽  
pp. 207-216
Author(s):  
A. Ikechukwu Onah ◽  
C. Franklin Kenechukwu ◽  
P. Dinebari Berebon ◽  
A. Akeem Agboke ◽  
E. Chinedum Ibezim ◽  
...  

Establishment of safety and toxicity profiles of metabolites of endophytic organisms from known medicinal plants are crucial in their pharmacological and biological applications. The aim of this study was to evaluate the oral acute toxicity (LD50) of crude extract of endophytic fungi isolated from Annona senegalensis Pers. The endophytic fungal metabolite was extracted with ethyl acetate. The LD50 was estimated following the method described by Lorke. Three dose levels (10, 100, and 1000 mg/kg) of the crude extract were administered to three mice each for the first phase using oral gavage needle in a single dose disposable syringe. The animals were observed for possible deaths or other side effects of the test substance in each group within 24 hours of the treatment. In the second phase, which was deduced from the first phase, eight mice were sub-divided into four groups of two mice each and they were treated with doses of 1200, 1600, 2900 and 5000 mg/kg orally. They were also observed within 24 hours and final LD50 value was determined. Results showed that the endophytic fungal extract exhibited no mortality or any histological defect in the liver tissues of the mice. More so, the immunological parameter tested showed significant increase in neutrophils and lymphocytes relative to the control in all the fungal isolates. Additionally, the LD50 for the crude metabolites was > 5000 mg/kg. This study has revealed that crude extract of endophytic fungi isolated from Annona senegalensis Pers did not show oral acute toxicity in mice. Further studies will evaluate long term-toxicity of the crude extract. Keywords: Endophytes, LD50, Annona senegalensis, Metabolites, Fungi


Author(s):  
Sunil Mistry

Sida cordata (Burn. f.) Borss. Waalk is highly distributed in entire part of India. The various parts of the plant are used in folklore medicine for the management of multiple diseases.  So,the present study was performed to examine the  hepatoprotective activity study of ethanolic extract of S. cordata leaves (SCLE) on alcohol mediated  hepatotoxicity in a rat model. Ethanol intoxicated rats showed noteworthy elevation of liver weight and volume. Further, ethanol insulted rats also showed significant elevation in the level of biochemical markers such as AST, ALT, TG, TB, and DB) and marked variation in the histological structure of liver. Oral administration of SCLE at the dose of 200 and 400 mg/kg for 30 days) significantly reduced the liver weight, hepatic markers level and restored the histological changes annoyed by ethanol thus indicating its hepatoprotective potential. Furthermore, HPTLC analysis was performed for the identification and quality estimation of S. cordata leaves.


2020 ◽  
Vol 9 (1) ◽  
pp. 19-27
Author(s):  
Tamires Meira Menezes ◽  
Wyndly Daniel Cardoso Gaião ◽  
Larissa Caroline de Almeida Sousa Lima ◽  
Ana Katarina Bezerra da Silva ◽  
Laísa Wanessa Santos Lima ◽  
...  

Abstract Ethnopharmacobotanical information reports that Parkinsonia aculeata infusion is used to control diabetes-related complications and dyslipidemia. However, few studies are reported on the safe use of this species. The aim of this study is to evaluate the acute toxicity, embryotoxicity and cytotoxicity of a polar fraction obtained from hydroethanolic extract of P. aculeata (PfrHEPA). For the acute toxicity test, we considered the Up and Down method which the guidelines are described by the Organization for Economic Cooperation and Development (OECD N°425). The animals were treated with PfrHEPA (2000 mg/kg) or with distilled water (10 ml/kg) by gavage and observed from Day 1 to14. For embryotoxicity assay, zebrafish embryos were exposed to PfrHEPA (100 mg/L) and toxicity parameters were observed during four consecutive days. The cytotoxicity of PfrHEPA (5, 10, 25, 50, 75 and 100 μg/ml, respectively) was performed on normal cell lines (mesenchymal stem cells, African green monkey renal cells and mouse pre-adipocytes 3 T3-L1 using the MTT salt reduction assay. In the acute toxicity test, no mortality was observed in mice treated with PfrHEPA (2000 mg/kg), as well as behavioral changes, histopathological abnormalities and hematological and biochemical variables. In the embryotoxicity test, no abnormal changes related to the toxicological parameters were observed in the period of 96 h. Regarding the cytotoxicity assay, PfrHEPA showed no cytotoxic effect on the normal cell lines tested, with an IC50 value &gt; 100 μg/ml. These results suggest the safe use of P. aculeata, however, more trials are needed for PfrHEPA to be presented as new safe therapeutic proposal for the control of metabolic disorders.


2020 ◽  
pp. 31-32
Author(s):  
Mikhail A. Levchenko ◽  
◽  
Natalia A. Sennikova ◽  

Toxicological assessment is a mandatory research step in the development of new insecticidal drugs. At the All-Russian Research Institute of Veterinary Entomology and Arachnology, a prototype of the insecticidal bait Mukhnet IF was obtained with an active ingredient content of 0.06% ivermectin and 0.015% fipronil, which showed a highly effective effect against houseflies. This work presents the results of the study of acute oral toxicity of the above agent. For this, male white mice with a live weight of 16-26 g were selected. They were kept on a starvation diet for one day in individual houses with water. The drug was given in mg/kg body weight the next day. A total of 33 doses have been tested, ranging from 100 mg/kg to 40,000 mg/kg. The animals were observed for 14 days. According to the research results, it was revealed that at doses up to 20,000 mg/kg there were no signs of intoxication, but when tested at 25,000 mg/kg in some mice, these signs were noted, and at 30,000, 35,000 and 40,000 mg/kg deaths were recorded 20±10, 45±30 and 60±20%, respectively. It was not possible to test the drug over the last above dose due to incomplete eaten by mice. According to the degree of danger for warm-blooded animals, the drug belongs to the 4th class of low-hazard drugs (average lethal dose of 5000 mg/kg or more) in accordance with the classification of GOST 12.1.007-76. When analyzing the literature data on the toxicological characteristics of preparations containing ivermectin and chlorfenapyr, it was revealed that the insecticidal agent in its acute toxicity for warm-blooded animals is comparable to known analogues.


Author(s):  
Mina Kianpour ◽  
Esmat Mohammadinasab ◽  
Tahereh Momeni Esfahani

: The aim of the present study was to develop quantitative structure-activity relationship (QSAR) models, based on molecular descriptors to predict the oral acute toxicity (LD50) of organophosphate compounds. The QSAR models based on genetic algorithm-multiple linear regression (GA-MLR) and back-propagation artificial neural network (BP-ANN) methods were proposed. The prediction experiment showed that the BP-ANN method was a reliable model for screening molecular descriptors, and molecular descriptors obtained by BP-ANN models could well characterize the molecular structure of each compound. It was indicated that among molecular descriptors to predict the LD50 (mgkg-1) of organophosphates, ALOGP2, RDF030u, RDF065p and GATS5m descriptors have more importance than the other descriptors. Also BP-ANN approach with the values of root mean square error (RMSE= 0.00168), square correlation coefficient (R2= 0.9999) and absolute average deviation (AAD=0.6981631) gave the best outcome, and the model predictions were in good agreement with experimental data. The proposed model may be useful for predicting LD50 (mgkg-1) of new compounds of similar class.


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