Genoprotective Effect of New Triazine Derivatives in Endosulfan Mediated Toxicity, an In vivo and In vitro Study

2018 ◽  
Vol 16 (1) ◽  
pp. 52-57
Author(s):  
Nima Naderi ◽  
Seyed Mostafa Ghasemi Najarkolaee ◽  
Mona Modanlookordi ◽  
Mohammad Shokrzadeh ◽  
Hamid Irannejad

Background: Recently, we reported synthesis and neuroprotective activity of some new 1,2,4-triazine derivatives against H2O2 and &#946;-amyloid toxicity in two neurotic cell lines, SHSY5Y and PC12. Methods: The promising results obtained prompted us to further study on these potent neuroprotective agents. In the current study, in vivo anti-inflammatory effect and also genoprotective activity of these compounds in endosulfan-mediated toxicity were investigated. Compounds RT and SMO exhibited high anti-inflammatory effect at 3 and 4 hours after injection in 20 mg/kg, and were even more effective than Indomethacin (20 mg/kg). Results: Interestingly, compound SMO in 200 &#181;M was the best compound in reducing micronuclei significantly (P value <0.0001) in lymphocytes treated with endosulfan compared to control group. Conclusion: Herein, we report SMO as a genoprotective agent and a new drug candidate for endosulfan mediated toxicity.

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Asmaa Oubihi ◽  
Hanae Hosni ◽  
Issmail Nounah ◽  
Abdessamad Ettouil ◽  
Hicham Harhar ◽  
...  

Thymus leptobotrys is a medicinal plant belonging to the Lamiaceae family, endemic in Morocco, and used in traditional medicine. The present work aims to study the phenolic compounds, the antioxidant activity, the anti-inflammatory effect, and the toxicity of two ethanolic and methanolic extracts of Thymus leptobotrys aerial part. The yield of the methanolic extraction (22.2%) is higher than that of the ethanolic extraction (15.8%) and is characterized by higher contents of polyphenols 243.08 mg/g GAE (mg/g of gallic acid), flavonoids 179.28 mg/g RE (mg/g of rutin), and tannins 39.31 mg/g CE (mg/g of catechin). The in vitro measurement of antioxidant activity with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical reduction test and Trolox equivalent antioxidant capacity (TEAC) test demonstrates the higher performance of the methanolic extract. The evaluation of the anti-inflammatory effect in vivo on adult Wistar female rats leads to a very significant decrease in the inflammation of the edema compared to the standard drug (indomethacin) and the control group. The toxicity test reveals that both extracts showed no toxicity within an LD50 above 2000 mg/kg body weight of the rats.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2037
Author(s):  
Ágota Pető ◽  
Dóra Kósa ◽  
Ádám Haimhoffer ◽  
Pálma Fehér ◽  
Zoltán Ujhelyi ◽  
...  

BGP-15 is a Hungarian-developed drug candidate with numerous beneficial effects. Its potential anti-inflammatory effect is a common assumption, but it has not been investigated in topical formulations yet. The aim of our study was to formulate 10% BGP-15 creams with different penetration enhancers to ensure good drug delivery, improve bioavailability of the drug and investigate the potential anti-inflammatory effect of BGP-15 creams in vivo. Since the exact mechanism of the effect is still unknown, the antioxidant effect (tested with UVB radiation) and the ability of BGP-15 to decrease macrophage activation were evaluated. Biocompatibility investigations were carried out on HaCaT cells to make sure that the formulations and the selected excipients can be safely used. Dosage form studies were also completed with texture analysis and in vitro release with Franz diffusion chamber apparatus. Our results show that the ointments were able to reduce the extent of local inflammation in mice, but the exact mechanism of the effect remains unknown since BGP-15 did not show any antioxidant effect, nor was it able to decrease LPS-induced macrophage activation. Our results support the hypothesis that BGP-15 has a potential anti-inflammatory effect, even if it is topically applied, but the mechanism of the effect remains unclear and requires further pharmacological studies.


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.


2021 ◽  
Vol 22 (3) ◽  
pp. 1222
Author(s):  
Cristina Cuello ◽  
Cristina A. Martinez ◽  
Josep M. Cambra ◽  
Inmaculada Parrilla ◽  
Heriberto Rodriguez-Martinez ◽  
...  

This study was designed to investigate the impact of vitrification on the transcriptome profile of blastocysts using a porcine (Sus scrofa) model and a microarray approach. Blastocysts were collected from weaned sows (n = 13). A total of 60 blastocysts were vitrified (treatment group). After warming, vitrified embryos were cultured in vitro for 24 h. Non-vitrified blastocysts (n = 40) were used as controls. After the in vitro culture period, the embryo viability was morphologically assessed. A total of 30 viable embryos per group (three pools of 10 from 4 different donors each) were subjected to gene expression analysis. A fold change cut-off of ±1.5 and a restrictive threshold at p-value < 0.05 were used to distinguish differentially expressed genes (DEGs). The survival rates of vitrified/warmed blastocysts were similar to those of the control (nearly 100%, n.s.). A total of 205 (112 upregulated and 93 downregulated) were identified in the vitrified blastocysts compared to the control group. The vitrification/warming impact was moderate, and it was mainly related to the pathways of cell cycle, cellular senescence, gap junction, and signaling for TFGβ, p53, Fox, and MAPK. In conclusion, vitrification modified the transcriptome of in vivo-derived porcine blastocysts, resulting in minor gene expression changes.


2021 ◽  
Author(s):  
Reinier Gesto-Borroto ◽  
Gabriela Meneses ◽  
Alejandro Espinosa-Cerón ◽  
Guillermo Granados ◽  
Jacquelynne Cervantes-Torres ◽  
...  

Abstract The genus Galphimia is widely distributed in Mexico, and is represented by 22 species, including medicinal species. The sedative and anti-inflammatory effects of galphimines produced by the species Galphimia glauca have been documented. Formerly, molecular studies using DNA barcodes demonstrated that nine populations botanically classified as Galphimia glauca belong to four different species of the genus Galphimia, and that only one exhibited the sedative properties; however, all the collected species showed anti-inflammatory activity. Other bioactive compounds like quercetin, galphins, galphimidins and glaucacetalins have been identified from methanolic extracts of plants botanically classified as Galphimia glauca. The aim of this work was to determine the anti-inflammatory activity of methanolic extracts of nine collected Galphimia spp. populations grown in Mexico. The possible modes of action were analyzed by evaluating the inhibition of LPS-induced inflammation processes both in vitro and in vivo. The nine populations were evaluated by an in vitro model using RAW 264.7 murine macrophage cells, and two populations (a galphimine-producing and a non-galphimine-producing population) were selected for the in vivo experiments of systemic inflammation and neuroinflammation in mice. Results suggest that an anti-inflammatory in vitro effect was present in all the studied populations, evidenced by the inhibition of nitrite production. An inhibitory systemic inflammation in mice was exerted by the two analyzed populations. In the neuroinflammation model, the anti-inflammatory effect was demonstrated in methanolic extract of the non-galphimine-producing population. For the populations of Galphimia spp. studied herein, the anti-inflammatory effect could not be correlated to the presence of galphimines.


Author(s):  
Asmaa Nabil-Adam ◽  
Mohamed A. Shreadah

Background: This study aimed to investigate the potential bioactivity and the ameliorative role of Galaxaura oblongata (G. oblongata) against LPS-induced toxicity by using hematological parameters. Objective: It is aimed also to examine its protective effect using the immunohistochemistry of liver and lungs as biomarkers in male BALB/C albino mice. Materials and Methods: the current study carried out using different in-vitro and in-vivo assays such as phytochemical, antioxidants, anti-inflammatory for in-vitro where the hematological and immunohistochemistry for lung and liver were investigated in vivo. Results: There are no previous studies were performed to investigate the in vivo and in vitro effects of the G. oblongata extracts as antioxidant and anti-inflammatory due to their rareness compared to other red algae. LPS treated mice revealed a significant decrease in total number of WBCs, RBCs, platelets, and HGB%, MPV, MCV and MCHC compared to the control group. On contrast, the HCT and MCHC were increased in the induction group which was treated with LPS compared to the control group. Furthermore, the immunohistochemistry results of the present study revealed the protective effect of G. oblongata compared to the induction group. G. oblongata can be used as protective marine natural products against the toxicity induced by LPS. Conclusion: It exhibited a significant ameliorative role against the alterations in the hematological parameters and immunohistochemistry of liver and lungs, and helps to reduce as well as coordinate the acute inflammations caused by TNF.


Author(s):  
Boussoualim Naouel ◽  
Trabsa Hayat ◽  
Krache Imane ◽  
Ouhida Soraya ◽  
Arrar Lekhmissi ◽  
...  

Background: Anchusa azurea Mill. (AA) is a medicinal plant largely used traditionally in folk medicine in Algeria, it is locally named: hamham. It is effective in the treatment of various diseases. Objectives: The aim of the present study is to determine the antioxidant, anti-inflammatory and anti-hemolytic effects of phenolic fractions from Anchusa azurea Mill. Methods: In this study, various extracts from Anchusa azurea Mill. (AA) using solvents with increasing polarity were prepared. The quantification of polyphenols and flavonoids was determined. The anti-radical activity of the different extracts was evaluated using DPPH and by measuring the inhibition of the oxidative degradation of β-carotene. The In vitro antihemolytic effect of the plant extracts is determined (CrE, ChE, AcE and AqE). For each extract, four concentrations were tested: 10.59, 21.18, 42.37, 84.74 µg/ml. Vitamin C is used as a standard. Free-radical attack was measured by measuring the HT50 (Half-Hemolysis Time). The anti-inflammatory effect using PMA on mice of the methanolic extract (CrE) was evaluated. Results: The quantification of polyphenols and flavonoids showed that ethyl acetate extract (AcE) contains a higher amount of polyphenols. However, chloroform extract (ChE) presents a higher amount of flavonoids. AcE showed an important scavenging activity using the DPPH radical (IC50= 68.35 µg/ml). The results showed that AcE also exhibited very great inhibition on the oxidation of β-carotene/linoleic acid (84.33%). All extracts increased the HT50 values (Half-Hemolysis Time) in a dose-dependent manner. The three highest concentrations (21.18, 42.37 and 84.74 µg / ml) of ChE caused a very significant delay (p ≤ 0.001) of hemolysis compared to the negative control and the positive control "VIT C". The anti-inflammatory effect using PMA on mice showed that the methanolic extract (CrE) of AA reduced the weight of the ear edema. Conclusions: This plant has a strong pharmacological power, which supports its traditional medicinal use.


2021 ◽  
Vol 18 ◽  
Author(s):  
Akash Ved ◽  
Shweta Gupta ◽  
Namrata Singh ◽  
Karuna S. Shukla ◽  
Om Prakash ◽  
...  

Background: Operculina turpethum (Linn.) Silva Manso, family- convolvulaceae, is an important plant in Indian conventional system of medicine which is extensively employed by different tribes in many countries to cure edema and painful conditions like arthritis, back pain; hyperlipidemia, diabetes mellitus, liver disorders, skin disorders and to regulate bowel functions. Objective: The roots of O. turpethum (Linn.) was subjected to physicochemical, phytochemical standardization, the chromatographic separation which was accomplished by column chromatography, TLC, and HPTLC, further, the acute toxicity, cytotoxic and anti-inflammatory activities of Operculina turpethum roots were estimated by in vivo and in vitro models. Materials and Methods: This study includes percentage yield of extraction, organoleptic evaluation along with the analysis of its physicochemical investigations & preliminary phytochemical estimation. The isolation of active phytoconstituents was done by column chromatography, and the isolated compound was then exposed to TLC and HPTLC analysis. Cytotoxic activity was tested by WST-1 based cell viability assay on HepG2 cells. Anti-inflammatory activity of methanol extract (ME) was evaluated against inflammation occur by both in vitro and in vivo method. Results: The methanolic extract exhibited the presence of most of the phytoconstituents out of all the extracts, the phytoconstituent phytosterol, i.e., β-sitosterol was isolated by column chromatography, identified and quantified by TLC and HPTLC, which is liable for anti-inflammatory activity. The amount of β-sitosterol was estimated to be 14.09 µg in 10.00 mg fraction of MEOT. MEOT is devoid of toxicity up to 2000 mg/kg in Wistar albino rats. It was analysed that in vitro anti-inflammatory activity of MEOT by egg albumin denaturation method exhibited a incredible decrement in turbidity and increasing the percentage inhibition of albumin denaturation (60.52%) in MEOT treated group as compared with control group. In egg albumin-induced edema in rats, MEOT at the dose of 400 mg/kg reduced the edema formation (3.03 ± 0.02) induced by egg albumin at 4th h. In cotton pellet-induced granuloma in rats, MEOT at the dose of 400 mg/kg displayed maximum granuloma inhibition (51.06%) which is similar to that of indomethacin. Conclusion: From the obtained findings it is confirmed that O. turpethum contains β-sitosterol which is responsible for potent anti-inflammatory activity without causing cytotoxicity to the plant. The results suggested that ME of O. turpethum roots had high potential for application as an anti-inflammatory agent. The recognization and confirmation of the plant can be obtaineded from the study and will present data which is aidful in determining the quality and purity of a crude drug which further helps in preventing its adulteration.


2021 ◽  
Vol 16 (10) ◽  
pp. 1934578X2110559
Author(s):  
Le Minh Ha ◽  
Ngo Thi Phuong ◽  
Nguyen Thi Thu Hien ◽  
Pham Thi Tam ◽  
Do Thi Thao ◽  
...  

In this study, we aimed at evaluating in vitro and in vivo anti-inflammatory activity of various extracts of the rhizomes of Globba pendula Roxb. Three extracts ( n-hexane, ethyl acetate, and water) were screened for their inhibitory effect on NO production by lipopolysaccharide-stimulated RAW 264.7 macrophages. The ethyl acetate extract of G. pendula rhizomes (EGP) showed a potential effect with an IC50 value of 32.45 µg/mL. For in vivo study, the ethyl acetate extract was further investigated for its anti-inflammatory effect using collagen antibody-induced arthritic mice (CAIA). The level of arthritis in experimental mice significantly reduced ( P < .05) after treatment with EGP at a dose of 500 mg/kg body weight (b.w.). This study also revealed that EGP is orally non-toxic. Ethyl p-methoxy cinamate was identified as the main constituent of EGP, which may result in its anti-inflammatory effect.


Author(s):  
Tatyana S. Khlebnicova ◽  
Yuri A. Piven ◽  
Fedor A. Lakhvich ◽  
Iryna V. Sorokina ◽  
Tatiana S. Frolova ◽  
...  

Background: Prevention and treatment of chronic inflammatory diseases require effective and low-toxic medicines. Molecular hybridization is an effective strategy to enhance the biological activity of new compounds. Triterpenoid scaffolds are in the focus of attention owing to their anti-inflammatory, antiviral, antiproliferative, and immunomodulatory activities. Heteroprostanoids have different pleiotropic effects in acute and chronic inflammatory processes. Objective: The study aimed to develop structurally new and low toxic anti-inflammatory agents via hybridization of betulinic acid with azaprostanoic acids. Methods: A series of betulinic acid-azaprostanoid hybrids was synthesized. The synthetic pathway included the transformation of betulin via Jones' oxidation into betulonic acid, reductive amination of the latter and coupling obtained by 3β-amino-3-deoxybetulinic acid with the 7- or 13-azaprostanoic acids and their homo analogues. The hybrids 1-9 were investigated in vivo on histamine-, formalin- and concanavalin A-induced mouse paw edema models and two models of pain - the acetic acid-induced abdominal writhing and the hotplate test. The hybrids were in vitro evaluated for cytotoxic activity on cancer (MCF7, U- 87 MG) and non-cancer humane cell lines. Results: In the immunogenic inflammation model, the substances showed a pronounced anti-inflammatory effect, which was comparable to that of indomethacin. In the models of the exudative inflammation, none of the compounds displayed a statistically significant effect. The hybrids produced weak or moderate analgesic effects. All the agents revealed low cytotoxicity on human immortalized fibroblasts and cancer cell lines compared with 3β- amino-3-deoxybetulinic acid and doxorubicin. Conclusion: The results indicate that the principal anti-inflammatory effect of hybrids is substantially provided with the triterpenoid scaffold and in some cases with the azaprostanoid scaffold, but the latter makes a significant contribution to reducing the toxicity of hybrids. Hybrid 1 is of interest as a potent low toxic agent against immune-mediated inflammation.


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