Nauclea orientalis (L.) Bark Extract Protects Rat Cardiomyocytes from Doxorubicin-Induced Oxidative Stress, Inflammation, Apoptosis, and DNA Fragmentation.

The therapeutic efficacy of anthracycline antibiotic, doxorubicin (Dox), is hampered due to the dose-dependent cardiotoxicity. The objective of the study was to explore the counteraction of aqueous bark extract of Nauclea orientalis in Dox-induced cardiotoxicity in Wistar rats. The acute and subchronic toxicity study performed with 2.0 g/kg of the plant extract revealed biochemical and haematological parameters to be within the physiological range, and no histological alterations were observed in any organs isolated. Screening of plant extract for the protection of the myocardium from Dox-induced oxidative stress, inflammation, and apoptosis was performed on five groups of rats: control, plant extract control, Dox control (distilled water (D.H2O) 2 weeks + on the 11th day single injection of Dox, 18 mg/kg), plant + Dox (2.0 g/kg plant extract 2 weeks + on the 11th day Dox, 18 mg/kg), and positive control, dexrazoxane. A significant increase in cardiac biomarkers and lipid peroxidation (p < 0.001) and a significant decrease in antioxidant parameters (p < 0.001) were observed in the Dox control group. All these parameters were reversed significantly (p < 0.05) in the plant-pretreated group. The histopathological assessment of myocardial damage provided supportive evidence for the biochemical results obtained. Inflammatory markers, myeloperoxidase, expression of TNFα and caspase-3, and DNA fragmentation (TUNEL positive nuclei) were significantly elevated (p < 0.05), and expression of Bcl-2 was significantly decreased (p < 0.05) in the Dox control; however, all these parameters were significantly reversed in the plant extract-treated group. In conclusion, the aqueous bark extract of Nauclea orientalis (2.0 g/kg) has the ability to attenuate the Dox-induced oxidative stress, inflammation, apoptosis, and DNA fragmentation in Wistar rats.

Combination of selol nanocapsules and magnetic hyperthermia hinders breast tumor growth in aged mice after a short-time treatment.

Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.

Vitexin isolated from Prosopis cineraria leaves induce apoptosis in K-562 leukemia cells via inhibition of the BCR-ABL-Ras-Raf pathway.

OBJECTIVES: Leukemia is one of the severe cancer types all around the globe. Even though some chemotherapeutic drugs are available for treating leukemia, they have various side effects. As an alternative approach, herbal drugs are focused on current research to overcome leukemia. The present work was conducted to investigate the antileukemic mechanism of active phytochemical vitexin, which was isolated from ethno-medicine (Prosopis cineraria leaf) used by traditional healers of West Bengal, India. METHODS: Antiproliferative mechanisms of selected phyto-compound against K-562 cells were evaluated using cellular uptake, morphological changes, DNA fragmentation, mitochondrial membrane potential and signaling pathways analysis. KEY FINDINGS: Vitexin exhibited cytotoxicity by reducing mitochondrial membrane potential (32.40%) and causing DNA fragmentation (84.15%). The western blotting study indicated inhibition of cell survival proteins (BCR, ABL, H-RAS, N-RAS, K-RAS and RAF) and expression of apoptotic proteins (p38, BAX and caspase-9) in leukemia cells upon treatment with vitexin. CONCLUSIONS: Based on the results, presently investigated phyto-compound vitexin could be considered for developing safe and natural drugs to treat leukemia after conducting suitable preclinical and clinical trials.

Selenium and silver nanoparticles: A new approach for treatment of bacterial and viral hepatic infections via modulating oxidative stress and DNA fragmentation.

Nanoparticles are recently playing a potential role in improving drug uptake and the treatment of diseases. A variety of nanoparticles, such as selenium nanoparticles (SeNPs) and silver nanoparticles (AgNPs) have been used as drug carriers in various ways for treatment of cancers and liver diseases. Our aim in this study is to investigate the ability of AgNPs and SeNPs to target and treat the viral and bacterial infection of the liver in rats and cell lines. For assessment of antioxidant activity of AgNPs in rats with induced liver bacterial infection, six adult male albino rats were included in this study, liver slices were taken and assigned to 6 groups. Markers of hepatic functions, oxidative stress, and inflammation in liver slices are carried out. Although for assessment of antiviral activity of SeNPs, hepatitis B virus transfected (HBV)-replicating human cell line HepG2 and normal hepatocyte cells were used, hepatic and inflammatory alterations are determined through quantitative polymerase chain reaction and comet assay techniques. The effect of AgNPs on interleukin-6 and tumor necrosis factor levels were reduced in different treated groups with AgNPs compared with the control and diseased groups. On the other hand, SeNPs revealed significant alterations in the inflammatory markers as well as DNA damage in the treated HBV-human cell line HepG2 compared to the diseased ones. AgNPs have the ability for producing various hepatic alterations and can inhibit the proliferation of hepatic stellate cells (HSCs) in a dose and size-dependent manner. On the other hand, SeNPs showed excellent selectivity towards viral cells in the HepG2 cell lines. Both AgNPs and SeNPs might be promising drug designs for treating viral and bacterial liver diseases.

Methyl Jasmonate Effect on Betulinic Acid Content and Biological Properties of Extract from Senna obtusifolia Transgenic Hairy Roots.

It is known that Senna obtusifolia has been used in medicine since ancient times due to the content of many valuable compounds with a pro-health effect. One of them is betulinic acid, which is a pentacyclic triterpene with antimalarial, antiviral, anti-inflammatory and anticancer properties. In this work, a continuation of our previous research, an attempt was made to increase the level of betulinic acid accumulation by the cultivation of transgenic hairy roots that overexpress the squalene synthase gene in a 10 L sprinkle bioreactor with methyl jasmonate elicitation. We present that the applied strategy allowed us to increase the content of betulinic acid in hairy root cultures to the level of 48 mg/g dry weight. The obtained plant extracts showed a stronger cytotoxic effect on the U87MG glioblastoma cell line than the roots grown without elicitors. Additionally, the induction of apoptosis, reduction of mitochondrial membrane potential, chromosomal DNA fragmentation and activation of caspase cascades are demonstrated. Moreover, the tested extract showed inhibition of topoisomerase I activity.

Gum acacia PEG iron oxide nanocomposite (GA-PEG-IONC) induced pharmacotherapeutic activity on the Las R gene expression of Pseudomonas aeruginosa and HOXB13 expression of prostate cancer (Pc 3) cell line. A green therapeutic approach of molecular mechanism inhibition.

Among the diverse nanomaterials, polymer-based nanocomposites are gained more attention due to their high efficacy, target biological activities, biodegradability and biocompatibility-gum acacia (GA) - a polymer obtained from acacia trees-is considering the multifunctional nanocomposite synthesis. Distinctive Physico-chemical and biocompatibility properties of gum acacia are utilised to prepare a highly stable, biologically active, eco-friendly Nanocomposite. In this current investigation, gum acacia - poly ethylene glycol grafted iron oxide nanocomposite (GA-PEG-IONC) was synthesised by in situ green science principles. The synthesised Nanocomposite was evaluated against the molecular mechanism of urinary tract pathogenic bacterial strains and prostate cancer cells (Pc 3). Nanocomposite prepared in this examination exhibited notable structural, functional stability with nanoarchitecture which was affirmed by Fourier transform infrared spectroscopy (FTIR), electron microscopic studies, atomic force microscopy (AFM), vibrating sample magnetometric analysis (VSM) and X-ray diffraction (XRD), Synthesised Nanocomposite brought about notable antibacterial activity against urinary tract pathogenic strains by recording potential inhibitory effect on the expression of Las R gene. Inhibition of Las R gene expression reduced notable effect on biofilm development. Anticancer activity against prostate cancer cells (Pc3) was investigated by measurement of HOXB13 gene expression level. Inhibition of HOXB13 gene expression by the IONC brought about structural, functional changes. HOXB13 gene expression inhibition reveals a remarkable cytotoxic effect by recording decreased cell viability. Morphometric analysis by phase-contrast and DAPI fluorescence staining demonstrates that the Nanocomposite prompted cell morphology anomalies or apoptotic changes. Nanocomposite treatment brought about a good sign of Apoptosis by recording enhanced caspase 3 and 9 activities, DNA fragmentation and elevated reactive oxygen species generation (ROS). Hemocompatibility studies were carried out to determine the biocompatibility of the Nanocomposite. Spectrophotometric estimation of plasma haemoglobin, microscopic examination of whole blood cells shows the Nanocomposite was not inciting any indication of toxicity. These findings infer that IONC synthesised in the present study is the promising contender for a broad scope of biomedical applications, especially as an antibacterial and anticancer agent.

Parasitological and Biochemical Efficacy of the Active Ingredients of Allium sativum and Curcuma longa in Schistosoma mansoni Infected Mice.

The active ingredients allicin and curcumin have a wide range of actions against fungi, bacteria, and helminths. Therefore, the study was aimed to evaluate the efficacy of allicin (AL) and curcumin (CU) as antischistosomal drugs and their biochemical effects in normal and Schistosoma mansoni-infected mice. Praziquantel (PZQ) was administrated for two successive days while AL or CU was given for two weeks from the week 7th postinfection (PI). The possible effect of different regimens on Schistosoma worms was evaluated by measuring the percentage of the recovered worms, tissue egg load, and oogram pattern. Serum alanine transaminase activity and levels of triglycerides, cholesterol, and uric acid were measured. Liver tissue malondialdehyde and reduced glutathione levels besides, the activities of glutathione-S-transferase, superoxide dismutase and catalase were assessed for the oxidative/antioxidant condition. DNA electrophoresis of liver tissue was used to indicate the degree of fragmentation. There was a significant reduction in the recovered worms and egg load, with a marked change of oogram pattern in all treated groups with PZQ, AL, and CU in comparison with infected-untreated mice. PZQ, AL, and CU prevented most of the hematological and biochemical disorders, as well as significantly improved the antioxidant capacity and enhanced DNA fragmentation in the liver tissue of schistosomiasis mice compared to the infected-untreated group. These promising results suggest that AL and CU are efficient as antischistosomal drugs, and it would be beneficial to test their combination to understand the mechanism of action and the proper period of treatment leading to the best result.

Toxicological assessment of Opuntia dillenii (Ker Gawl.) Haw. cladode methanol extract, fractions and its alpha pyrones: Opuntiol and opuntioside.

ETHNOPHARMACOLOGICAL RELEVANCE: The edible plant Opuntia dillenii (Ker Gawl.) Haw. commonly known as Nagphana, belongs to the Cactaceae family. It is traditionally used to treat various ailments including inflammation, gastric ulcers, diabetes, hepatitis, asthma, whooping cough and intestinal spasm. AIM OF THE STUDY: Despite its traditional use in various countries, detailed toxicological studies of O. dillenii cladode are few. Thus in the current study, toxicity of O. dillenii cladode derived methanol extract, fractions and its α-pyrones: opuntiol and opuntioside have been addressed. METHODS: The test agents were assessed using both in vitro and in vivo toxicity assays. MTT on human embryonic kidney cell line (HEK-293), tryphan blue exclusion in rat neutrophils, Cytokinesis-B block micronucleus (CBMN) in human lymphocytes and genomic DNA fragmentation using agarose gel electrophoresis were performed. In acute toxicity test, mice orally received extract (5 g/kg) for 7 days followed by measurements of relative organ weight, biochemical (blood profile, liver and kidney function test) and histological studies (liver and kidney) were carried out. Rat bone marrow micronucleus genotoxicity assay was also conducted. RESULTS: O. dillenii derived test agents were non-cytotoxic and had no effect on the integrity of DNA. Methanol extract (5 g/kg) orally administered in mice did not cause any significant change in relative organ weights, biochemical parameters and liver and kidney histology as compared to vehicle control. In parallel, extract did not stimulate micronuclei formation in rat bone marrow polychromatic erythrocytes. CONCLUSION: These results led to conclude that edible O. dillenii extract is non-toxic via the oral route and appears to be non-cyto-, hepato-, nephro- or genotoxic, thereby supporting its safe traditional use against various ailments. Therefore, opuntiol and opuntioside may serve as lead compounds in designing new drug(s) derived from edible plants.

Apoptotic mechanisms of myricitrin isolated from Madhuca longifolia leaves in HL-60 leukemia cells.

Myricitrin, a naturally occurring flavonoid in Madhuca longifolia, possesses several medicinal properties. Even though our earlier work revealed its role against the proliferation of acute myelogenous leukemia cells (HL-60), its molecular mechanisms have not yet been revealed. The current study aims to explore the molecular mechanisms of myricitrin (isolated from an ethnomedicinal drug Madhuca longifolia) to induce apoptosis in HL-60 cells. Treatment with IC-50 dose of myricitrin (353 µM) caused cellular shrinkage and cell wall damage in HL-60 cells compared to untreated control cells. Myricitrin treatment reduced the mitochondrial membrane potential (22.95%), increased DNA fragmentation (90.4%), inhibited the cell survival proteins (RAS, B-RAF, & BCL-2) and also induced pro-apoptotic proteins (p38, pro-caspase-3, pro-caspase-9 and caspase-3) in the HL-60 cells. The present study provides scientific evidence for the apoptosis caused by myricitrin in HL-60 leukemia cells. Hence, the phytochemical myricitrin could be considered as a potential candidate to develop an anticancer drug after checking its efficacy through suitable pre-clinical and clinical studies.

The effect of micronutrient supplementation on spermatozoa DNA integrity in subfertile men and subsequent pregnancy rate.

BACKGROUND: Male infertility has been related to an increased sperm DNA fragmentation index (DFI). Nutritional factors may improve sperm nuclear DNA integrity and thus pregnancy rates. Objective: To evaluate the effect of micronutrient supplementation on sperm DNA integrity in subfertile men and subsequent pregnancy rates. METHODS: In this retrospective comparative study 339 subfertile males were included on whom a sperm chromatin dispersion test (SCD) was performed as a method to detect DNA fragmentation, as well as an initial semen analysis. Of all, n = 162 received a nutritional management program for three months, consisting of two daily capsules of a standardized combined micronutrient formulation together with a guidance to diet modification and to lifestyle changes (study group). Each capsule contained L-carnitine, L-arginine, coenzyme Q10, zinc, vitamin E, folic acid, glutathione, and selenium. The control group consisted of those patients who did not receive the active treatment (n = 177), yet were instructed to engage in a healthy lifestyle, including a modification of their regular diet. The SCD test was repeated for both groups after three months. As part of the routine follow up, pregnancy rate was assessed six months after the second SCD test. Males with complete follow up and healthy female partners (aged 18 to 40 years) where included. RESULTS: Data of men with an initial mean DFI of >15% were analyzed first (n = 81;46 study and 35 control patients). After three months, both groups displayed a significant decrease of mean DFI values; however, the mean percent difference was higher in the study group (10.46 ± 1.20 % vs. 5.29 ± 0.57 %; p < .001). Then, the entire population was considered (n = 339). After three months, only the study group displayed a significant decrease of mean DFI initial values (10.48 ± 7.76 % to 6.51 ± 4.61%; p < .001); and the percent difference was higher in the study group (3.97 ± 0.28 % vs. 0.91 ± 0.28 %; p < .001). At six months follow-up, pregnancy rate was higher in the study group (27.78% vs. 15.25%, p = .002). CONCLUSION: Both regimes significantly reduced sperm DNA fragmentation among subfertile men with a DFI >15%; however, when any baseline DFI value was considered, only micronutrient supplementation achieved a better result on DFI and thus pregnancy rate was higher.

In Vivo and In Vitro Assays Evaluating the Biological Activity of Taurine, Glucose and Energetic Beverages.

Taurine is one of the main ingredients used in energy drinks which are highly consumed in adolescents for their sugary taste and stimulating effect. With energy drinks becoming a worldwide phenomenon, the biological effects of these beverages must be evaluated in order to fully comprehend the potential impact of these products on the health due to the fact nutrition is closely related to science since the population consumes food to prevent certain diseases. Therefore, the aim of this study was to evaluate the biological effects of taurine, glucose, classic Red Bull® and sugar-free Red Bull® in order to check the food safety and the nutraceutical potential of these compounds, characterising different endpoints: (i) Toxicology, antitoxicology, genotoxicology and life expectancy assays were performed in the Drosophila melanogaster model organism; (ii) The in vitro chemopreventive activity of testing compounds was determined by assessing their cytotoxicity, the proapoptotic DNA-damage capability to induce internucleosomal fragmentation, the strand breaks activity and the modulator role on the methylation status of genomic repetitive sequences of HL-60 promyelocytic cells. Whereas none tested compounds showed toxic or genotoxic effect, all tested compounds exerted antitoxic and antigenotoxic activity in Drosophila. Glucose, classic Red Bull® and sugar-free Red Bull® were cytotoxic in HL-60 cell line. Classic Red Bull® induced DNA internucleosomal fragmentation although none of them exhibited DNA damage on human leukaemia cells. In conclusion, the tested compounds are safe on Drosophila melanogaster and classic Red Bull® could overall possess nutraceutical potential in the in vivo and in vitro model used in this study. Besides, taurine could holistically be one of the bioactive compounds responsible for the biological activity of classic Red Bull®.

Glycine alleviates fluoride-induced oxidative stress, apoptosis and senescence in a porcine testicular Sertoli cell line.

Glycine is a well-known free radical scavenger in the cellular antioxidant system that prevents oxidative damage and apoptosis. Excessive fluoride exposure is associated with multiple types of cellular damage in humans and animals. The objective of the present study was to investigate the protective effects of glycine on sodium fluoride (NaF) exposure and the possible underlying mechanisms in a porcine testicular Sertoli cell line model. Cellular viability and proliferation were examined following NaF exposure and glycine supplementation, and glycine dramatically ameliorated the decreases in NaF-induced porcine testicular Sertoli cell viability and proliferation. Further investigations revealed that glycine decreased NaF-induced intracellular reactive oxygen species production, DNA fragment accumulation and the apoptosis incidence in the porcine testicular Sertoli cell line; in addition, glycine improved mitochondrial function and ATP production. Notably, results of the SPiDER-ß-Gal analysis suggested that glycine alleviated NaF-induced cellular senescence and downregulated P53, P21, HMGA2 and P16INK4a gene expression in the porcine testicular Sertoli cell line. Collectively, the beneficial effects of glycine alleviate NaF-induced oxidative stress, apoptosis and senescence, and together with our previous findings, support the hypothesis that glycine plays an important role in protecting against NaF exposure-induced impairments in the porcine testicular Sertoli cell line.

The Effect of Indian Fig Fruit Extract on Human Papilloma Virus containing Cervical Cancer Cells (HeLa) by Decreasing the HPV18 L1 Gene Load.

BACKGROUND: Global trend is moving towards the use of natural phytochemicals to fight against pathogens. Human cervical cancer is directly associated with onco-potent type of Human Papilloma Virus (HPV). There is no known medicine for clearance of HPV type whose persistence is the cause of occurrence and re-occurrence of cervical cancer. The different species of fig fruit and their latex are reported to have HPV associated genital warts clearance capability. METHODS: In the current investigation, the effect of the methanol extract of Ficus benghalensis L. fruits on HPV type18 viral load in HeLa cell line was tested by doing PCR using HPV L1 primers (MY09/My011) and the cytotoxicity was also analysed by MTT assay. The induction of apoptotic activity in terms of DNA fragmentation and hyper-chromic effects of DNA was analysed. RESULTS: The PCR results showed a reduction in the HPV18 DNA and also the treatment exhibited a promising cytotoxicity with IC50 value at 211.86 µg/ml. The DNA samples from treated HeLa cells showed DNA shearing and laddering as a mark of apoptotic DNA fragmentation (Fig. 2) and the UV absorbance value at 260 nm was found to be significantly (p <0.01) higher in the DNA sample treated with fruit extract compared to the untreated DNA sample. CONCLUSION: The Ficus benghalensis L. fruit extract reduced the HPV viral load in HPV18 containing HeLa cells and showed an effective cytotoxicity on HeLa cell line. It also could induce the apoptotic activity in HeLa cell line and this study results suggest that the Ficus benghalensis L. fruits can be used to fight against cervical carcinoma, acting on HPV load.

The effectiveness and safety of traditional Chinese herbal medicine for the treatment of male infertility associated with sperm DNA fragmentation: A protocol for systematic review and meta-analysis.

BACKGROUND: Sperm DNA fragmentation (SDF) may hinder embryonic development and growth, increasing the risk of spontaneous miscarriage, and is considered an important factor affecting male infertility (MI). Traditional Chinese herbal medicine is considered effective in the treatment of MI due to SDF by nourishing kidney essence or promoting blood circulation for removing blood stasis. The objective of this systematic review protocol is to evaluate the effectiveness and safety of traditional Chinese herbal medicine on the treatment of MI associated with SDF. METHODS: We searched the PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP Chinese Science, Technology Journal Database, and Wanfang Database until the end of 2020 for English and Chinese published literature. Randomized controlled trials (RCTs) to evaluate the effectiveness and safety of traditional Chinese herbal medicine for the treatment of MI associated with SDF will be included. Study selection and data extraction were performed independently by 2 reviewers, and the quality evaluation and risk assessment were assessed by the Cochrane collaboration's tool, and use the RevMan 5.3 software for meta-analysis. CONCLUSION: This study will evaluate the efficacy and safety of traditional Chinese herbal medicine for the treatment of MI due to SDF, which may provide some help for the clinician's decision. PROSPERO REGISTRATION NUMBER: CRD42020221053.

Anticancer potential of rhizome extract and a labdane diterpenoid from Curcuma mutabilis plant endemic to Western Ghats of India.

Zingiberaceae plants are well known for their use in ethnomedicine. Curcuma mutabilis Skornick., M. Sabu & Prasanthk., is an endemic Zingiberaceae species from Western Ghats of Kerala, India. Here, we report for the first time, the anticancer potential of petroleum ether extract from C. mutabilis rhizome (CMRP) and a novel labdane diterpenoid, (E)-14, 15-epoxylabda-8(17), 12-dien-16-al (Cm epoxide) isolated from it. CMRP was found to be a mixture of potent bioactive compounds including Cm epoxide. Both the extract and the compound displayed superior antiproliferative activity against several human cancer cell lines, without any display of cytotoxicity towards normal human cells such as peripheral blood derived lymphocytes and erythrocytes. CMRP treatment resulted in phosphatidylserine externalization, increase in the levels of intracellular ROS, Ca2+, loss of mitochondrial membrane potential as well as fragmentation of genomic DNA. Analyses of transcript profiling and immunostained western blots of extract-treated cancer cells confirmed induction of apoptosis by both intrinsic and extrinsic pathways. The purified compound, Cm epoxide, was also found to induce apoptosis in many human cancer cell types tested. Both CMRP and the Cm epoxide were found to be pharmacologically safe in terms of acute toxicity assessment using Swiss albino mice model. Further, molecular docking interactions of Cm epoxide with selected proteins involved in cell survival and death were also indicative of its druggability. Overall, our findings reveal that the endemic C. mutabilis rhizome extract and the compound Cm epoxide isolated from it are potential candidates for development of future cancer chemotherapeutics.

Effect of Ceratonia siliqua L. extract on DNA Fragmentation of Sperm in Adult Male Mice Treated with Cyclophosphamide.

This study was conducted to determine the effects of Ceratonia siliqua L. (CS) extract on sperm parameters and DNA damage in adult male mice treated with cyclophosphamide (CP). Based on an initial dose response experiment on Ceratonia siliqua L. extract, five treatment groups were set up: control, sham (normal saline: 0.2 ml per day, IP), CP (15 mg kg-1 per week; IP), Ceratonia siliqua L. (100mg l-1 per day; IP), and group of Ceratonia siliqua L. along with CP for 35 days. After euthanizing the animals, sperms from caudal part of epididymis were collected, and their parameters, Malone Di-Aldehyde (MDA) level, and DNA fragmentation were analyzed. In the mice exposed to cyclophosphamide, reduction in the sperm count and viability and increase in the abnormal sperm and MDA levels were detected (p < .05). In addition, an increase in sperms with damaged DNA was detected in CP group, while the use of Ceratonia siliqua L. Extract significantly recovered these disturbances in the treatment group (p < .05). This study suggested the competence of Ceratonia siliqua L. extract in the improvement of sperm parameters and DNA fragmentation in animals treated with CP.

Synergistic protective effect of Beta vulgaris with meso-2,3-dimercaptosuccinic acid against lead-induced neurotoxicity in male rats.

Lead (Pb) toxicity is one of the most prevalent causes of human neurotoxicity. The available chelator drugs used now have many adverse effects. So, in this study, the protective role of Beta vulgaris juice (BVJ) on rat neurotoxicity induced by Pb was evaluated and the results were compared with the results of dimercaptosuccinic acid (DMSA, as used drug). Additionally, the synergistic effect of BVJ and DMSA against Pb-induced neurotoxicity was assessed. The study focused on the determination of the antioxidant, anti-inflammatory, and neurological potential of BVJ (alone, and with DMSA) towards lead-induced neurotoxicity. Also, the characterization of BVJ was studied. The results showed that BVJ contains considerable quantities of polyphenols, triterpenoids, and betalains which play an important role as antioxidants and anti-inflammatory. BVJ exhibited a protective effect against neurotoxicity via the reduction of Pb levels in blood and brain. Moreover, BVJ decreased the oxidative stress, inflammation, and cell death induced by Pb. Also, BVJ regulated the activities of acetylcholine esterase and monoamine oxidase-A which changed by Pb toxicity. BVJ and DMSA combination displayed a synergistic antineurotoxic effect (combination index ˂ 1). These results were in harmony with brain histopathology. Conclusion: BVJ has a powerful efficacy in the protection from brain toxicity via diminishing Pb in the brain and blood circulation, resulting in the prevention of the oxidative and inflammatory stress. Treatment with BVJ in combination with DMSA revealed a synergistic effect in the reduction of neurotoxicity induced by Pb. Also, the antioxidant and anti-inflammatory effects of the BVJ lead to the improvement of DMSA therapy.

Antiproliferative Activity and Apoptotic Efficiency of Syzygium cumini Bark Methanolic Extract against EAC Cells In Vivo.

BACKGROUND: Syzygium cumini is one of the evidence-based traditional medicinal plant used in the treatment of various ailments. OBJECTIVES: Herein, the antioxidant property and anticancer property of Syzygium cumini against Ehrlich Ascites Carcinoma (EAC) cells were examined to find effective chemotherapeutics. METHODS: In vitro assays, and phytochemical and chromatographic analyses were used to determine antioxidant properties and chemical constituents of Syzygium cummini Bark Methanolic Extract (SCBME). Functional assays were used to measure the anticancer activity of SCBME. Fluorescence microscopy and RT-PCR were used to examine morphological and molecular changes of EAC cells followed by SCBME treatment. RESULTS: Phytochemical and GC-MS analyses confirmed the presence of compounds with antioxidant and anticancer activities. Accordingly, we have noted a strong antioxidant activity of SCBME with an IC50 value of ~10µg/ml. Importantly, SCBME exerted a dose-dependent anticancer activity with significant inhibition of EAC cell growth (71.08±3.53%; p<0.001), reduction of tumor burden (69.50%; p<0.01) and increase of life span (73.13%; p<0.001) of EAC-bearing mice at 75mg/kg/day. Besides, SCBME restored the blood toxicity towards normal in EAC-bearing mice (p<0.05). DISCUSSION: SCBME treated EAC cells showed apoptotic features under a fluorescence microscope and fragmented DNA in DNA laddering assay. Moreover, up-regulation of the tumor suppressor p53 and pro-apoptotic Bax and down-regulation of NF-κB and anti-apoptotic Bcl-2 genes implied induction of apoptosis followed by SCBME treatment. CONCLUSION: The antiproliferative activity of SCBME against EAC cells is likely due to apoptosis, mediated by regulation of p53 and NF-κB signaling. Thus, SCBME can be considered as a useful resource in cancer chemotherapy.

Resveratrol improves sperm DNA quality and reproductive capacity in type 1 diabetes.

BACKGROUND: In the coming decades, diabetes mellitus might affect 628 million individuals. Its final impact on male fertility and reproductive outcomes should be considered since the number of adolescents and young adults presenting diabetes is rising. Resveratrol (RES), a polyphenol, is a biological modulator with multitarget and multi-action characteristics. OBJECTIVES: to evaluate if RES is effective against the male reproductive damage caused by type 1 diabetes (DM1), focusing on sperm DNA integrity and reproductive outcome. MATERIALS AND METHODS: At 30 dpp (days postpartum), male rats were divided into 7 groups: Sham control (SC); RES vehicle (RV); RES (R); STZ-diabetic (D; induced at 30dpp with 65 mg/kg of streptozotocin); STZ-diabetic + insulin (DI); STZ-diabetic + RES (DR); STZ-diabetic + insulin +RES (DIR). DR, DIR, and R groups received 150mg RES/kg b.w./day by gavage (from 33 to 110dpp). DI and DIR received insulin (from day 5 after DM1 induction until 110dpp). Blood glucose was monitored in different time points. Animals were mated with healthy females. Euthanasia occurred at 110 dpp. RESULTS: DM1 increased lipid peroxidation (testis and epididymis) and sperm DNA fragmentation, alterations of chromatin structure, reduced mitochondrial mass and acrosome integrity, causing a decline in fertility and pregnancy rates. RES improved the parameters. DISCUSSION: RES, as an adjuvant, activates specific reactions against hyperglycemia, the main trigger of most complications of diabetes, by controlling oxidative stress, probably as a result of SIRT1 activation. We present here more evidences showing its valuable role in diminishing diabetes seriousness to male reproduction, not only to spermatogenesis in the first instance, but also to sperm overall quality and fertility outcomes, regardless of insulin treatment. CONCLUSION: RES attenuated lipid peroxidation and sperm DNA damage in DM1-induced animals, which positively reflected on male fertility. Our results show RES potential against DM1 complications in male reproduction.

In vitro effects of Capparis spinosa L. extract on human sperm function, DNA fragmentation, and oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Oxidative stress is one of the underlying causes of male infertility. Medicinal plants have many benefits for infertility treatment in men. AIM OF THE STUDY: In the present study, we evaluated in vitro effects of Capparis spinosa leaf extract on human sperm function, DNA fragmentation, and oxidative stress. MATERIALS AND METHODS: We conducted this study on the hydroalcoholic extract of C. spinosa. Polyphenol compounds and antioxidant effects of the leaf and fruit extract were determined by HPLC and DPPH method, respectively. Flavones and flavonols, total flavonoid, total phenolic content, tannin, and the total carbohydrate content were determined calorimetrically. Semen samples from 50 healthy men (20-45 years) were divided into control and experimental (15, 30, and 45 ppm of C. spinosa leaf extract) groups. Motility, viability, lipid peroxidation, and DNA fragmentation were evaluated 24 h after incubation. RESULTS: The antioxidant effect of leaf extract was six times greater than fruit. Progressive and total motility of caper-treated groups (30 and 45 ppm) were crucially higher than the control group. Viability in all treatments was significantly higher than the control group. There was no significant difference in lipid peroxidation. DNA fragmentation in the caper-treated group (45 ppm) was significantly lower than the control group. CONCLUSIONS: Our results suggest the potential positive in vitro effect of C. spinosa leaf extract on human sperm function. The use of C. spinosa leaf extract or its active metabolites in the sperm culture medium may be beneficial for maintaining motility, vitality, and sperm DNA. Since these effects were observed at very low concentrations of caper, other non-antioxidant mechanisms must be considered.