Thymoquinone ameliorates Pachycondyla sennaarensis venom-induced acute toxic shock in male rats

Abstract Background For many decades, the sting of Samsun ant (Pachycondyla sennaarensis) has been a serious clinical challenge for the people living in some of the major Middle East and Asian countries. In the present study, the therapeutic potential of Nigella sativa derived plant extract component, thymoquinone (TQ) has been tested against the Samsun ant venom (SAV) at the toxic dose in the rats. Methods The adult male rats were divided into four groups (n = 10): control, SAV treated, SAV + TQ treated and TQ alone treated. It was found that the sub-lethal dose of SAV alters not only many of the kidney and liver function markers but also induces oxidative stress in the animals. Moreover, the SAV also disturbs various immunological parameters including expression of PMNs, CD-80, CD-86, interleukins and other cytokines compromising the affected organism towards mild to severe allergic reactions including life-risking anaphylaxis. Results The plant extract, TQ, effectively restores many of the biochemical and oxidative stress parameters comparable to the normal concomitant with improving the immunological aspects that might attributive in relieving from SAV-induced toxicity and allergic reactions in the affected organism to a greater extent. Conclusion Hence, TQ has an excellent antidote property against SAV-induced toxicities in vivo. Although the study is a vivid indication of the potential therapeutic potential of TQ against the SAV induced in vivo toxicity, yet the actual mechanism of interaction translating the toxicity amelioration warrants further investigations.

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Antioxidant Activity of an Aqueous Leaf Extract from Uncaria tomentosa and Its Major Alkaloids Mitraphylline and Isomitraphylline in Caenorhabditis elegans

Molecules ◽

10.3390/molecules24183299 ◽

2019 ◽

Vol 24 (18) ◽

pp. 3299 ◽

Cited By ~ 14

Author(s):

Bruna C. Azevedo ◽

Mariana Roxo ◽

Marcos C. Borges ◽

Herbenya Peixoto ◽

Eduardo J. Crevelin ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activity ◽

Transcription Factor ◽

Caenorhabditis Elegans ◽

Leaf Extract ◽

Therapeutic Potential ◽

Lethal Dose ◽

Uncaria Tomentosa ◽

Aqueous Leaf Extract

Uncaria tomentosa (Rubiaceae) has a recognized therapeutic potential against various diseases associated with oxidative stress. The aim of this research was to evaluate the antioxidant potential of an aqueous leaf extract (ALE) from U. tomentosa, and its major alkaloids mitraphylline and isomitraphylline. The antioxidant activity of ALE was investigated in vitro using standard assays (DPPH, ABTS and FRAP), while the in vivo activity and mode of action were studied using Caenorhabditis elegans as a model organism. The purified alkaloids did not exhibit antioxidant effects in vivo. ALE reduced the accumulation of reactive oxygen species (ROS) in wild-type worms, and was able to rescue the worms from a lethal dose of the pro-oxidant juglone. The ALE treatment led to a decreased expression of the oxidative stress response related genes sod-3, gst-4, and hsp-16.2. The treatment of mutant worms lacking the DAF-16 transcription factor with ALE resulted in a significant reduction of ROS levels. Contrarily, the extract had a pro-oxidant effect in the worms lacking the SKN-1 transcription factor. Our results suggest that the antioxidant activity of ALE in C. elegans is independent of its alkaloid content, and that SKN-1 is required for ALE-mediated stress resistance.

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Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

Current Pharmaceutical Design ◽

10.2174/1381612825666190110145151 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4626-4638 ◽

Cited By ~ 13

Author(s):

Reyhaneh Moradi-Marjaneh ◽

Seyed M. Hassanian ◽

Farzad Rahmani ◽

Seyed H. Aghaee-Bakhtiari ◽

Amir Avan ◽

...

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Therapeutic Potential ◽

Vegf Signaling ◽

Anticancer Effects ◽

Inhibition Of Angiogenesis ◽

Underlying Mechanisms ◽

Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

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NEPHRO-PROTECTIVE ACTIVITY OF ISOLATED METHANOL FRACTIONS PHYTO-COMPOUND FROM BARK OF TERMINALIA ARJUNA

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i12.21274 ◽

2017 ◽

Vol 9 (12) ◽

pp. 175

Author(s):

Shreya Mandal ◽

Arpita Patra ◽

Shrabani Pradhan ◽

Suchismita Roy ◽

Animesh Samanta ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Property ◽

Male Rats ◽

In Vivo Study ◽

Terminalia Arjuna ◽

Total Phenolic ◽

Methanol Fraction ◽

Group I ◽

And Oxidative Stress

Objective: The aim of this study was to evaluate the antioxidant property of the isolated phytocompounds from TA (Terminalia arjuna) bark and in vivo study for nephro-protective and oxidative stress reducing activity in experimentally induced albino male rats.Methods: Fractions from methanol crude TA extract were collected by column chromatography and F27, F28, F29 fractions were selected on the basis of antioxidant property by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. The in vivo study performed by 30 albino male rats which were randomly divided into five groups: Group I (control)were taken normal food and water, Groups II (uremic) were injected acetaminophen intraperitoneally at the dose of 500 mg/kg/d for 10 d, Group III, IV and V(extract treatment) acetaminophen intraperitoneally at the dose of 500 mg/kg/d for 10 d with co-administered orally of methanol fraction F27, F28, F29 at the dose of 100 mg/kg/d for 15 d respectively.Results: After scarification of rats, the uremic marker plasma urea (80%), creatinine (85%) were elevated and antioxidant enzyme marker such as plasma SOD and catalase level were significantly increased (p<0.05)in Group IV compared to Group II. The total phenolic content of the F28 methanolic fraction was (815.48±8.11) mg gallic acid equivalent/g of extract. For isolation of available compound by 1H NMR study in F28 methanol fraction of TA bark was arjunoside IV which contained olefinic proton (a pair of carbon atom linked with double bond).Conclusion: Among the three methanolic fraction of TA bark, F28 was shown best antioxidative, nephron-protective and oxidative stress reducing property.

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Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6746907 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 12

Author(s):

Kaifeng Li ◽

Mengen Zhai ◽

Liqing Jiang ◽

Fan Song ◽

Bin Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Diabetic Cardiomyopathy ◽

High Glucose ◽

Therapeutic Potential ◽

Ros Generation ◽

Protective Effects ◽

Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

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Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPKα Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/7901735 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Yan-Yan Meng ◽

Yu-Pei Yuan ◽

Xin Zhang ◽

Chun-Yan Kong ◽

Peng Song ◽

...

Keyword(s):

Oxidative Stress ◽

Therapeutic Potential ◽

Cell Loss ◽

Protective Role ◽

Protective Effects ◽

Morphological Examination ◽

Heart Injury ◽

Amp Activated Protein Kinase

Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase α (AMPKα) in vivo and in vitro. Moreover, inhibition of AMPKα could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPKα. GE has therapeutic potential for the treatment of DOX cardiotoxicity.

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Blue laser light inhibits biofilm formation in vitro and in vivo by inducing oxidative stress

npj Biofilms and Microbiomes ◽

10.1038/s41522-019-0102-9 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 10

Author(s):

Katia Rupel ◽

Luisa Zupin ◽

Giulia Ottaviani ◽

Iris Bertani ◽

Valentina Martinelli ◽

...

Keyword(s):

Oxidative Stress ◽

Biofilm Formation ◽

Mammalian Cells ◽

Bacterial Infections ◽

Laser Light ◽

Therapeutic Potential ◽

Blue Laser ◽

Data Set

Abstract Resolution of bacterial infections is often hampered by both resistance to conventional antibiotic therapy and hiding of bacterial cells inside biofilms, warranting the development of innovative therapeutic strategies. Here, we report the efficacy of blue laser light in eradicating Pseudomonas aeruginosa cells, grown in planktonic state, agar plates and mature biofilms, both in vitro and in vivo, with minimal toxicity to mammalian cells and tissues. Results obtained using knock-out mutants point to oxidative stress as a relevant mechanism by which blue laser light exerts its anti-microbial effect. Finally, the therapeutic potential is confirmed in a mouse model of skin wound infection. Collectively, these data set blue laser phototherapy as an innovative approach to inhibit bacterial growth and biofilm formation, and thus as a realistic treatment option for superinfected wounds.

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Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells

Pharmaceutics ◽

10.3390/pharmaceutics13122093 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2093

Author(s):

Elisa Landucci ◽

Francesca Bonomolo ◽

Chiara De Stefani ◽

Costanza Mazzantini ◽

Domenico Edoardo Pellegrini-Giampietro ◽

...

Keyword(s):

Epithelial Cells ◽

Therapeutic Potential ◽

Nigella Sativa ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Fold Increase ◽

Prolonged Release ◽

Liposomal Formulations

Thymoquinone (TQ) is the main constituent of Nigella sativa L. essential oil. In vitro studies have shown its protective effect against H2O2-induced oxidative stress in human retinal pigment epithelium cells, and in vivo experiments have demonstrated its effect in decreasing corneal neovascularization and reducing the inflammation in an experimental dry eye model in mice. Its therapeutic use is limited by poor bioavailability, low solubility, and scarce permeability. In this study, two liposomal formulations have been developed, both of which consist of phosphatidylcholine and Plurol Oleique, a liquid lipid, and one of which is coated with 0.1% w/v hyaluronic acid (HA) to increase both TQ solubility and its ocular therapeutic potential. Each formulation has a size <200 nm and an EE% around 70%, determined by scattering techniques and the HPLC-DAD analytical method, respectively, and they result in a 2-fold increase in TQ solubility. HA-coated liposomes are stable over 2 months at +4 °C, and coated and uncoated liposomes present a gradual and prolonged release of TQ. Two cell lines, human corneal epithelial cells (HCEC-2) and human conjunctival epithelial cells (HConEC) were used to investigate the safety of the liposomal formulations. Uptake studies were also performed using fluorescent liposomes. Both liposomes and, in particular, HA-coated liposomes reduce the TQ toxicity observed at high doses in both HCEC-2 and HConEC cells, and both formulations increase the absorption at the cellular level and especially at the nucleus level, with a more pronounced effect for HA-coated liposomes.

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In vivo evidences of Curcuma longa on oxidative stress in STZ-induced diabetes on sperm parameters in male wistar rats

Anatomy Journal of Africa ◽

10.4314/aja.v6i3.163509 ◽

2017 ◽

Vol 6 (3) ◽

pp. 1045-1051

Author(s):

A.J. Olanrewaju ◽

S.Y. Olatunji ◽

J.O. Owolabi ◽

A.T. Oluwatosin ◽

W.C. Amaechi ◽

...

Keyword(s):

Oxidative Stress ◽

Sperm Quality ◽

Curcuma Longa ◽

Diabetic Control ◽

Positive Control ◽

Sperm Parameters ◽

Male Rats ◽

Control Group ◽

Alternative Source

Several conditions such as chemotherapy and toxins can interfere with spermatogenesis and reduce sperm quality and production. In the case where natural antioxidant response cannot manage oxidative stress and free radical overload, oxidative damage occurs and this begins the genesis of many diseases of which diabetes is one of them. This has awakened the interest of researchers to the use of an alternative source of medicine and herbal medicine. Medicinal use of Curcuma longa dates back to ancient China and India; its constituents are stated to have anti-hepatotoxic, anti-inflammatory, stimulant, and antioxidant and used since ancient time as medicinal and nutritive origins knowing to possess androgenic activities and have well effect in diseases treatment in more countries world-wide. As an antioxidant Curcuma longa possible has a useful effect on spermatogenesis and sperm parameters. Wistar male rats (n=24) were allocated into six groups, positive control (n=4), diabetic control (n=4) and experimental groups (n=20), that subdivided into groups of 4 that received treatment of Curcuma longa rhizome powder with or without STZ-induced diabetes in the dosages (25 and 100mg/kg/day) for 21 consecutive days. In twenty-second day, the testes were removed and semen was collected from epididymis and prepared for analysis. The percentage of sperm viability and motility in the treatment groups increased mildly with a significance of: (p<0.05) in comparison to control group and with the diabetic group being critically lower than those in control group. This suggested that Curcuma longa may be promising in enhancing sperm health parameters.Keywords: Turmeric, oxidative stress, semen, STZ-induced diabetes, antioxidant

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Phytochemical profile, toxicological evaluation of Rhipsalis baccifera (Sol.) Stearn (Cactaceae) extract and their antitumor activity in Ehrlich carcinoma-bearing mice

10.53365/nrfhh/142159 ◽

2021 ◽

Author(s):

Jéssica Alves Cavalcantea ◽

Luiz da Silva Maia Neto ◽

Anna Lígia de Castro Figueiredo ◽

Weslley Oliveira ◽

José Roberto Pimentel Cabral de Seixas ◽

...

Keyword(s):

Antitumor Activity ◽

Therapeutic Potential ◽

Lethal Dose ◽

Artemia Salina ◽

Subsequent Treatment ◽

Ehrlich Carcinoma ◽

Toxicological Evaluation ◽

Phytochemical Profile

Rhipsalis baccifera (Sol.) Stearn is a typical cactus from tropical regions with wide geographic distribution, and its therapeutic potential is not yet fully understood, such as antitumoral property. Thus, this study evaluated the cytotoxic ethanolic extract of R. baccifera (EERB) and its antitumor activity against Erlich's tumor in mice. The EERB was obtained, and its phytochemical profile was filed by thin-layer chromatography. The toxicity was evaluated in vitro and in vivo using the microcrustacean Artemia salina Leach and mice. The lethal dose was determined after implantation of a tumor cell suspension, with subsequent treatment with EERB (200 mg/kg and 100 mg/kg) 48h after implantation. These values represent the tenth part of the DL50 and CL50, respectively. The presence of phenols, tannins and triterpenes were demonstrated in the phytochemical results. Toxicity was dose-dependent, and the tumor inhibition was 84.1% and 75.8% at doses of 200 mg/kg and 100 mg/kg, respectively. We can highlight that the growth of Erlich's carcinoma suffered inhibitory effects against the EERB. EERB was found to have low acute toxicity and a high potential for use in antitumor therapy. Thus, new studies involving pre-clinical and clinical analyses of the extract are essential to determine the safe dose.

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Tannic Acid Exhibits Adjuvant Activity by Enhancing Humoral and Cell-Mediated Immunity Against BSA as a Protein Antigen

Protein and Peptide Letters ◽

10.2174/0929866528666211125110701 ◽

2021 ◽

Vol 28 ◽

Author(s):

Nidia Cabral-Hipólito ◽

Brenda Sarahí Molina-Ramírez ◽

Irais Castillo-Maldonado ◽

Rocío Meza-Velázquez ◽

Rubén García-Garza ◽

...

Keyword(s):

Tannic Acid ◽

Wistar Rats ◽

Lethal Dose ◽

Peritoneal Macrophages ◽

Protein Antigen ◽

Cell Mediated Immunity ◽

Vaccine Adjuvants ◽

Adjuvant Activity ◽

Toxic Dose

Background: Immunization or vaccination is the process of inducing artificial immunity against an antigen taking advantage of the mechanisms of immunological memory. Current vaccines include substances known as adjuvants, which tend to improve the immunogenicity of the antigen, reduce the antigen quantity employed, and boost the immune response in weak responders. Unfortunately, only a few vaccine adjuvants are approved for human use. Objective: Thus, the objective of this study was to investigate the effect of Tannic acid on humoral and cell-mediated immunity against bovine serum albumin (BSA) as a protein antigen in Wistar rats. Method: In order to establish the Tannic acid concentration to test it as an adjuvant, the lethal dose 50 and maximum non-toxic dose were calculated through cytotoxicity and hemolytic assays with J774 A.1 cell line and rat erythrocytes by resazurin reduction method and UV/vis spectrophotometry. Thirty Wistar rats were divided into 5 groups that included two controls without antigen and three treatment groups of adjuvants plus BSA as a protein antigen. The rats were immunized in a 30-day scheme. Blood samples were collected for humoral immunity analysis by means of immunoglobulin quantification, isotyping and antigen-antibody precipitation inhibition analysis. Rat peritoneal macrophages and splenocytes were isolated for cell-mediated immunity analysis by means of nitric oxide quantification from adjuvant stimulated peritoneal macrophages and lymphocytes proliferation assay. Results: Tannic acid was capable of increasing the immunogenicity of the antigen; besides, it was able to stimulate cell-mediated immunity by means of increased lymphocyte proliferation. Moreover, Tannic acid improved the humoral response by means of increased specific antibodies titers. These activities may be attributed to pattern recognition receptors stimulation. Conclusion: Tannic acid was considered biocompatible when tested in vivo because the concentration tested did not show cytotoxicity or hemolytic effect, and there was no detrimental effect observed on the animals’ health. These results show Tannic acid as a promising candidate for vaccine adjuvant.

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