Naringenin mitigates aluminum toxicity-induced learning memory impairments and neurodegeneration through amelioration of oxidative stress.

Aluminum chloride (AlCl3) is a potent neurotoxic substance known to cause memory impairment and oxidative stress-dependent neurodegeneration. Naringenin (NAR) is a dietary flavonoid with potent antioxidant and anti-inflammatory properties which was implemented against AlCl3-induced neurotoxicity to ascertain its neuroprotective efficacy. Experimental neurotoxicity in mice was induced by exposure of AlCl3 (10 mg/kg, p.o.) followed by treatment with NAR (10 mg/kg, p.o.) for a total of 63 days. Assessed the morphometric, learning memory dysfunction (novel object recognition, T- and Y-maze tests), neuronal oxidative stress, and histopathological alteration in different regions of the brain, mainly cortex, hippocampus, thalamus, and cerebellum. AlCl3 significantly suppressed the spatial learning and memory power which were notably improved by administration of NAR. The levels of oxidative stress parameters nitric oxide, advanced oxidation of protein products, protein carbonylation, lipid peroxidation, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and the activity of acetylcholine esterase were altered 1.5-3 folds by AlCl3 significantly. Treatment of NAR remarkably restored the level of oxidative stress parameters and maintained the antioxidant defense system. AlCl3 suppressed the expression of neuronal proliferation marker NeuN that was restored by NAR treatment which may be a plausible mechanism. NAR showed therapeutic efficacy as a natural supplement against aluminum-intoxicated memory impairments and histopathological alteration through a mechanism involving an antioxidant defense system and neuronal proliferation.

Autonomic neuronal modulations in cardiac arrhythmias: Current concepts and emerging therapies.

The pathophysiology of atrial fibrillation and ventricular tachycardia that result in cardiac arrhythmias is related to the sustained complicated mechanisms of the autonomic nervous system. Atrial fibrillation is when the heart beats irregularly, and ventricular arrhythmias are rapid and inconsistent heart rhythms, which involves many factors including the autonomic nervous system. It's a complex topic that requires careful exploration. Cultivation of speculative knowledge on atrial fibrillation; the irregular rhythm of the heart and ventricular arrhythmias; rapid oscillating waves resulting from mistakenly inconsistent P waves, and the inclusion of an autonomic nervous system is an inconceivable approach toward clinical intricacies. Autonomic modulation, therefore, acquires new expansions and conceptions of appealing therapeutic intelligence to prevent cardiac arrhythmia. Notably, autonomic modulation uses the neural tissue's flexibility to cause remodeling and, hence, provide therapeutic effects. In addition, autonomic modulation techniques included stimulation of the vagus nerve and tragus, renal denervation, cardiac sympathetic denervation, and baroreceptor activation treatment. Strong preclinical evidence and early human studies support the annihilation of cardiac arrhythmias by sympathetic and parasympathetic systems to transmigrate the cardiac myocytes and myocardium as efficient determinants at the cellular and physiological levels. However, the goal of this study is to draw attention to these promising early pre-clinical and clinical arrhythmia treatment options that use autonomic modulation as a therapeutic modality to conquer the troublesome process of irregular heart movements. Additionally, we provide a summary of the numerous techniques for measuring autonomic tone such as heart rate oscillations and its association with cutaneous sympathetic nerve activity appear to be substitute indicators and predictors of the outcome of treatment.

Naringenin suppresses aluminum-induced experimental hepato-nephrotoxicity in mice through modulation of oxidative stress and inflammation.

Aluminum is a widely used metal substance in daily life activities that has been shown to cause severe hepato-nephrotoxicity with long-term exposure. Natural dietary flavonoids are being utilized as a newer pharmaceutical approach against various acute and chronic diseases. Naringenin (NAR) has shown efficient therapeutic properties, including effects against metal toxicities. However, the protective efficacy of NAR on aluminum chloride (AlCl3)-induced hepato-renal toxicity needs investigation as aluminum has shown serious environmental toxicity and bioaccumulation behavior. In this study, mice were treated with AlCl3 (10 mg/kg b.w./day) to assess toxicities, and a group of mice were co-treated with NAR (10 mg/kg b.w./day) to assess the protective effects of NAR against hepato-nephrotoxicity. The levels of blood serum enzymes, oxidative stress biomarkers, inflammatory cytokines, and the apoptosis marker caspase-3 were measured using histological examinations. NAR treatment in AlCl3-treated mice resulted in maintained levels of liver and kidney function enzymes and lipid profiles. NAR treatment attenuated oxidative stress by regulating the levels of nitric oxide, advance oxidation of protein products, protein carbonylation, and lipid peroxidation. NAR also replenished reduced antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and reduced the levels of glutathione and oxidized glutathione. NAR regulated the levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and elevated the levels of anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ). The histological study further confirmed the protective effects of NAR against AlCl3-induced hepato-renal alterations. NAR decreased the expression of caspase-3 as a mechanism of protective effects against apoptotic damage in the liver and kidney of AlCl3-treated mice. In summary, this study demonstrated the antioxidant and anti-inflammatory properties of NAR, leading to the suppression of AlCl3-triggered hepato-renal apoptosis and histological alterations. The results suggest that aluminum toxicity needs to be monitored in daily life usage, and supplementation of the natural dietary flavonoid naringenin may help maintain liver and kidney health.

Naringenin ameliorates aluminum toxicity-induced testicular dysfunctions in mice by suppressing oxidative stress and histopathological alterations.

Environmental aluminum intoxication has shown increasingly alarming negative consequences on reproductive health. This needs mechanistic exploration and preventive management using medicines like herbal supplementation. The ameliorative effects of naringenin (NAR) against AlCl3-induced reproductive toxicity were thus evaluated in this study by assessing testicular dysfunction in albino male mice. A group of mice was treated with AlCl3 (10 mg/kg b.w./day) and then with NAR (10 mg/kg b.w./day) for a total of sixty-two days. Results show that treatment of AlCl3 significantly reduced the body weight and testis weight of mice. AlCl3 caused oxidative damage in mice as evidenced by an increase in the concentration of nitric oxide, advanced oxidation of protein product, protein carbonylation, and lipid peroxidation. Furthermore, diminished activity of antioxidant moieties included superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced glutathione, and oxidized glutathione. Several histological changes, such as spermatogenic cell degeneration, germinal epithelium detachment, and structural abnormalities in seminiferous tubules, were observed in AlCl3-treated mice. Oral administration of NAR was found to restore body weight and testes weight and ameliorated reproductive dysfunctions. NAR decreased oxidative stress, replenished the antioxidant defense system, and improved histopathological alterations in the AlCl3-treated testes. Therefore, the present study suggests that the supplementation of NAR may be a beneficial strategy to mitigate AlCl3-induced reproductive toxicity and testicular dysfunction.

Capsicum annuum L. and its bioactive constituents: A critical review of a traditional culinary spice in terms of its modern pharmacological potentials with toxicological issues.

Capsicum annuum L., commonly known as chili pepper, is used as an important spice globally and as a crude drug in many traditional medicine systems. The fruits of C. annuum have been used as a tonic, antiseptic, and stimulating agent, to treat dyspepsia, appetites, and flatulence, and to improve digestion and circulation. The article aims to critically review the phytochemical and pharmacological properties of C. annuum and its major compounds. Capsaicin, dihydrocapsaicin, and some carotenoids are reported as the major active compounds with several pharmacological potentials especially as anticancer and cardioprotectant. The anticancer effect of capsaicinoids is mainly mediated through mechanisms involving the interaction of Ca2+ -dependent activation of the MAPK pathway, suppression of NOX-dependent reactive oxygen species generation, and p53-mediated activation of mitochondrial apoptosis in cancer cells. Similarly, the cardioprotective effects of capsaicinoids are mediated through their interaction with cellular transient receptor potential vanilloid 1 channel, and restoration of calcitonin gene-related peptide via Ca2+ -dependent release of neuropeptides and suppression of bradykinin. In conclusion, this comprehensive review presents detailed information about the traditional uses, phytochemistry, and pharmacology of major bioactive principles of C. annuum with special emphasis on anticancer, cardioprotective effects, and plausible toxic adversities along with food safety.

A systematic assessment of stress insomnia as the high-risk factor for cervical cancer and interplay of cervicovaginal microbiome.

Cervical cancer is a dreaded form of cancer in women, the fourth most common cancer, with around 0.3 million females suffering from this disease worldwide. Over the past several decades, global researches have focused on the mitigation of cervical lesions and cancers and have explored the impact of physiological and psychological stress and insomnia on cervical pathogenesis. Furthermore, disruption of the cervicovaginal microbiome profiles is identified as an added high-risk factor for the occurrence of cervical cancer. The physiological regulation of stress has an underlying mechanism controlled via hypothalamic pituitary adrenal (HPA) and sympatho-adrenal medullary (SAM) axes. Disruptions in these axes have been identified as the factors responsible for maintaining the homeostasis balance. Recent studies on microbiomes have offered novel ways to combat cervical cancer and cervix infection by exploring the interplay of the cervicovaginal microbiome. Moreover, the integration of various immune cells and microbiome diversity is known to act as an effective strategy to decipher the cervix biological activity. Cytokine profiling and the related immune competence, and physiological stress and insomnia impart to the regulatory networks underlying the mechanism which may be helpful in designing mitigation strategies. This review addressed the current progress in the research on cervical cancer, HPV infection, immune cell interaction, and physiological stress and insomnia with the cervicovaginal microbiome to decipher the disease occurrence and therapeutic management.

Inonotus obliquus aqueous extract prevents histopathological alterations in liver induced by environmental toxicant Microcystin.

Environmental toxicants like microcystins are known to adversely impact liver physiology and lead to the increased risk for abnormal liver function and even liver carcinoma. Chaga mushroom (Inonotus obliquus) is reported for various properties mainly antibacterial, antiallergic, anti-inflammatory, antioxidant, and anticancer properties. This study was aimed to assess the effect microcystin (MC-LR) on histopathology of liver in mice and a preventive measure by using aqueous extract of Inonotus obliquus (IOAE). Adult Balb/c mice were administered with MC-LR at 20 â€‹µg/kg body weight, per day, intraperitoneal (i.p.) for 4 weeks. IOAE was treated to one group of MC-LR mice at 200 â€‹mg/kg body weight, per oral, for 4 weeks. Histological staining for liver structural details and biochemical assays for functions were assessed. The results of the study showed that MC-LR drastically reduced the body weight of mice which were restored close to the range of control by IOAE treatment. MC-LR exposed mice showed 1.9, 1.7 and 2.2-fold increase in the levels of SGOT, SGPT and LDH which were restored by IOAE treatment as compared to control (one-fold). MC-LR exposed mice showed reduced level of GSH (19.83 â€‹± â€‹3.3 â€‹µM) which were regained by IOAE treatment (50.83 â€‹± â€‹3.0 â€‹µM). Similar observations were noted for catalase activity. Histological examinations show that MC-LR exposed degenerative changes in the liver sections which were restored by IOAE supplementation. The immunofluorescence analysis of caspase-3 counterstained with DAPI showed that MC-LR led to the increased expression of caspase-3 which were comparatively reduced by IOAE treatment. The cell viability decreased on increasing the concentration of MC-LR with 5% cell viability at concentration of 10 â€‹µg MC-LR/mL as that of control 100% Cell viability. The IC50 was calculated to be 3.6 â€‹µg/ml, indicating that MC-LR is chronic toxic to AML12 mouse hepatocytes. The molecular docking interaction of NF-κB-NIK with ergosterol peroxidase showed binding interaction between the two and showed the plausible molecular basis for the effects of IOAE in MC-LR induced liver injury. Collectively, this study revealed the deleterious effects of MC-LR on liver through generation of oxidative stress and activation of caspase-3, which were prevented by treatment with IOAE.

Andrographolide Induces Apoptosis in Gastric Cancer Cells through Reactivation of p53 and Inhibition of Mdm-2.

Andrographolide is a labdane diterpenoid isolated from Andrographis paniculata. The plant extract and andrographolide has long been used in traditional medicine practices mainly for gastrointestinal diseases and improving liver function. Andrographolide has shown various pharmacological properties including anti-inflammatory, antioxidant and anticancer activity. This study evaluated the effect of andrographolide on proliferation of human gastric carcinoma cells in relevance to p53 and Mdm-2 pathways. Andrographolide inhibited the proliferation of SGC7901 and AGS cells in a dose-dependent manner with estimated IC50 values 38 and 44 µM respectively. Effect of andrographolide on p53 activity was ascertained by using a p53 activator (RITA) which showed synergistic inhibition of cell proliferation. While andrographolide when used in combination with a p53 inhibitor (pifithrin-α) showed potent restriction over its response. Andrographolide caused decrease in mitochondrial membrane potential as an indicator of apoptotic activity. Andrographolide activated the expression of p53 protein and gene and downregulated the levels of Mdm-2 (negative regulator of p53). Andrographolide inhibited the colony formation abilities in SGC7901 in a p53-dependent manner followed by induction of mitochondrial intrinsic apoptosis through activation of caspases-9 and -3, cleavage of PARP, and inhibition of pro-apoptotic Bcl-2. Andrographolide induced p53 mediated apoptosis in gastric carcinoma cells which adds to a novel approach in anticancer therapies.

The phytochemical, biological, and medicinal attributes of phytoecdysteroids: An updated review.

The phytoecdysteroids (PEs) comprise a large group of biologically-active plant steroids, which have structures similar to those of insect-molting hormones. PEs are distributed in plants as secondary metabolites that offer protection against phytophagus (plant-eating) insects. When insects consume the plants containing these chemicals, they promptly molt and undergo metabolic destruction; the insects eventually die. Chemically, ecdysteroids are a group of polyhydroxylated ketosteroids that are structurally similar to androgens. The carbon skeleton of ecdysteroids is termed as cyclopentanoperhydro-phenanthrene with a ß-side chain at carbon-17. The essential characteristics of ecdysteroids are a cis-(5ß-H) junction of rings A and B, a 7-en-6-one chromophore, and a trans-(14α-OH) junction of rings C and D. Plants only synthesize PEs from mevalonic acid in the mevalonate pathway of the plant cell using acetyl-CoA as a precursor; the most common PE is 20-hydroxyecdysone. So far, over 400 PEs have been identified and reported, and a compilation of 166 PEs originating from 1998 has been previously reviewed. In the present review, we have summarized 212 new PEs reported between 1999 and 2019. We have also critically analyzed the biological, pharmacological, and medicinal properties of PEs to understand the full impact of these phytoconstituents in health and disease.

Targeting cancer cells with nanotherapeutics and nanodiagnostics: Current status and future perspectives.

Nanotechnology is reshaping health care strategies and is expected to exert a tremendous impact in the coming years offering better healthcare facilities. It has led to not only therapeutic drug delivery feasibility but also to diagnostics. Materials in the size of nano range (1-100 nm) used in the design, fabrication, regulation, and application of therapeutic drugs or devices are classified as medical nanotechnology and nanopharmacology. Delivery of more complex molecules to the specific site of action as well as gene therapy has pushed forward the nanoparticle-based drug delivery to its maximum. Areas that benefit from nano-based drug delivery systems are cancer, diabetes, infectious diseases, neurodegenerative diseases, blood disorders and orthopedic-related ailments. Moreover, development of nanotherapeutics with multi-functionalities has a considerable potential to fill the gaps that exist in the present therapeutic domain. In cancer treatment, nanomedicines have superiority over current therapeutic practices as they can effectively deliver the drug to the affected tissues, thus reducing drug toxicities. Along this line, polymeric conjugates of asparaginase and polymeric micelles of paclitaxel have recently been recommended for the treatment of various types of cancers. Nanotechnology-based therapeutics and diagnostics provide greater effectiveness with less or no toxicity concerns. Similarly, diagnostic imaging holds promising future applications with newer nano-level imaging elements. Advancements in nanotechnology have emerged to a newer direction which use nanorobotics for various applications in healthcare. Accordingly, this review comprehensively highlights the potentialities of various nanocarriers and nanomedicines for multifaceted applications in diagnostics and drug delivery, especially the potentialities of polymeric nanoparticle, nanoemulsion, solid-lipid nanoparticle, nanostructured lipid carrier, self-micellizing anticancer lipids, dendrimer, nanocapsule and nanosponge-based therapeutic approaches in the field of cancer. Furthermore, this article summarizes the most recent literature pertaining to the use of nano-technology in the field of medicine, particularly in treating cancer patients.

A Perspective on Emerging Therapeutic Interventions for COVID-19.

Coronaviruses are enveloped positive-sense RNA viruses with an unusual large RNA genome and a unique replication mechanism, which are characterized by club-like spikes that protrude from their surface. An outbreak of a novel coronavirus 2019 infection has posed significant threat to the health and economies in the whole world. This article reviewed the viral replication, pathogenicity, prevention and treatment strategies. With a lack of approved treatment options for this virus, alternative approaches to control the spread of disease is in urgent need. This article also covers some management strategies which may be applied to this virus outbreak. Ongoing clinical studies related to possible treatments for COVID-19, potential vaccines, and alternative medication such as natural compounds are also discussed.

Goldenseal (Hydrastis canadensis L.) and its active constituents: A critical review of their efficacy and toxicological issues.

Goldenseal (Hydrastis canadensis L.) is a medicinal plant widely used in various traditional systems of medicine and as a food supplement. It has been traditionally used by Native Americans as a coloring agent and as medicinal remedy for common diseases and conditions like wounds, digestive disorders, ulcers, skin and eye ailments, and cancer. Over the years, goldenseal has become a popular food supplement in the USA and other regions. The rhizome of this plant has been used for the treatment of a variety of diseases including, gastrointestinal disorders, ulcers, muscular debility, nervous prostration, constipation, skin and eye infections, cancer, among others. Berberine is one of the most bioactive alkaloid that has been identified in different parts of goldenseal. The goldenseal extract containing berberine showed numerous therapeutic effects such as antimicrobial, anti-inflammatory, hypolipidemic, hypoglycemic, antioxidant, neuroprotective (anti-Alzheimer's disease), cardioprotective, and gastrointestinal protective. Various research finding suggest the health promoting effects of goldenseal components and their extracts. However, few studies have also suggested the possible neurotoxic, hepatotoxic and phototoxic activities of goldenseal extract and its alkaloids. Thus, large randomized, double-blind clinical studies need to be conducted on goldenseal supplements and their main alkaloids to provide more evidence on the mechanisms responsible for the pharmaceutical activity, clinical efficacy and safety of these products. Thus, it is very important to review the scientific information about goldenseal to understand about the current scenario.

Antitumoral effects of [6]-gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] in sarcoma 180 cells through cytogenetic mechanisms.

BACKGROUND: [6]-Gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] is a phenolic substance reported for several ethnopharmacological usage by virtue of its antioxidant, antiemetic, anti-inflammatory and anticancer properties. This study assessed the antitumoral effects of [6]-Gingerol in primary cells of Sarcoma 180 as well as in peripheral blood lymphocytes of mice. METHODS: The effect of [6]-Gingerol was assessed by applying cytogenetic biomarkers as indicative of genotoxicity, mutagenicity and apoptosis. Ascitic liquid cells were treated with [6]-Gingerol at concentrations of 21.33, 42.66 and 85.33 µM and subjected to the cytotoxicity assays using Trypan blue test and the comet assay, as well as the cytokinesis-block micronucleus assay. Doxorubicin (6 µM) and hydrogen peroxide (85.33 µM) were used as positive controls. RESULTS: [6]-Gingerol, especially at concentrations of 42.66 and 85.33 µM, showed notable cytotoxicity in Sarcoma 180 cells by reducing cell viability and cell division rates via induction of apoptosis. Genotoxicity at the concentrations used was punctuated by the increase in the index and frequency of DNA damage in tested groups. [6]-Gingerol, at all concentrations tested, did not induce significant aneugenic and/or clastogenic effects. It did, however, induced other nuclear abnormalities, such as nucleoplasmic bridges, nuclear buds and apoptosis. The genotoxic effects observed in the cotreatment with H2O2 (challenge assay) employing neoplastic and healthy cells, indicated that [6]-Gingerol may induce oxidative stress. CONCLUSIONS: Observations suggest that [6]-Gingerol may be a candidate for pharmaceutical antitumoral formulations due to its cytotoxicity and to mechanisms associated with genetic instability generated by nuclear alterations especially by apoptosis.

Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts.

Chemosensitization of cancer cells with small molecules may improve the therapeutic index of antitumoral agents by making tumor cells sensitive to the drug regimen and thus overcome the treatment resistance and side effects of single therapy. Cell membrane lipid rafts are known to transduce various signaling events in cell proliferation. Sensitizing cancer cells may cause modulation of membrane lipid rafts which may potentially be used in improving anticancer drug response. Cedrol, a natural sesquiterpene alcohol, was used to treat human leukemia K562 and colon cancer HT-29 cell lines, and effects were observed. Cedrol decreased the cell viability by inducing apoptosis in both cell lines by activation of pro-apoptosis protein BID and inhibition of anti-apoptosis proteins Bcl-X L , Bcl-2, and XIAP. Cedrol activated the caspase-9-dependent mitochondrial intrinsic pathway of apoptosis. Furthermore, cedrol inhibited the levels of pAKT, pERK, and pmTOR proteins as well as nuclear and cytoplasmic levels of the p65 subunit of NF-κB. Cedrol caused redistribution of cholesterol and sphingomyelin contents from membrane lipid raft, which was confirmed by a combined additive effect with methyl-ß-cyclodextrin (lipid raft-disrupting agent). Lipid raft destabilization by cedrol led to the increased production of ceramides and inhibition of membrane-bound NADPH oxidase 2 enzyme activity. Cholesterol/sphingomyelin-redistributing abilities of cedrol appear as a novel mechanism of growth inhibition of cancer cells. Cedrol can be classified as a natural lipid raft-disrupting agent with possibilities to be used in general studies involving membrane lipid raft modifications.

Effect of Diets, Familial History, and Alternative Therapies on Genomic Instability of Breast Cancer Patients.

This study evaluates a correlation between family history, micronutrients intake, and alternative therapies with genetic instability, before and during breast cancer treatment. For this study, a total of 150 women were selected. Among those, 50 women were breast cancer patients on chemotherapy, while 50 breast cancer patients were on radiotherapy, and 50 were healthy females. All the participants signed the informed consent form and answered the public health questionnaire. Samples of buccal epithelial and peripheral blood cells were collected and analyzed through micronucleus and comet assays. The cells were evaluated for apoptosis and DNA damage. Results showed the association of patients' family history with an increase in toxicogenetic damage before and during cancer therapy. On the other hand, patients with late-onset cancer also presented genetic instability before and during therapy, along with those who did not take sufficient vegetables and alternative therapies. A positive correlation was observed between the genetic instability and alternative therapies, while inverse correlation was recorded with the vegetable consumption. Results clearly explain that the nutritional aspects and alternative therapies influence the genetic instability before and during cancer therapies especially in radiotherapy treated patients. Our data could be used for the monitoring therapies and management of breast cancer patients.

A systematic review on the neuroprotective perspectives of beta-caryophyllene.

Beta (ß)-caryophyllene (BCAR) is a major sesquiterpene of various plant essential oils reported for several important pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, antimicrobial, and immune-modulatory activity. Recent studies suggest that it also possesses neuroprotective effect. This study reviews published reports pertaining to the neuropharmacological activities of BCAR. Databases such as PubMed, Scopus, MedLine Plus, and Google Scholar with keywords "beta (ß)-caryophyllene" and other neurological keywords were searched. Data were extracted by referring to articles with information about the dose or concentration/route of administration, test system, results and discussion, and proposed mechanism of action. A total of 545 research articles were recorded, and 41 experimental studies were included in this review, after application of exclusion criterion. Search results suggest that BCAR exhibits a protective role in a number of nervous system-related disorders including pain, anxiety, spasm, convulsion, depression, alcoholism, and Alzheimer's disease. Additionally, BCAR has local anesthetic-like activity, which could protect the nervous system from oxidative stress and inflammation and can act as an immunomodulatory agent. Most neurological activities of this natural product have been linked with the cannabinoid receptors (CBRs), especially the CB2R. This review suggests a possible application of BCAR as a neuroprotective agent.

Mycotoxin-assisted mitochondrial dysfunction and cytotoxicity: Unexploited tools against proliferative disorders.

Mitochondria are the powerhouse of cells, which upon dysfunctions may lead to several diseases. Mycotoxins are the toxic secondary metabolites from fungi which are capable of causing diseases and death in humans and animals. They have a versatile mechanism of action in biological systems and can be used as lead compounds to treat some diseases including cancer. The present work encompasses analysis on the effects of mycotoxins on mitochondrial dysfunction. Electronic databases such as PubMed, ScienceDirect, Scopus, Web of Science, and Google Scholar were thoroughly searched for up-to-date published information associated with those mycotoxins and their effect on mitochondrial dysfunction. Findings suggest that mycotoxins such as citrinin, aflatoxin, and T-2 toxin exert multi-edged sword-like effects in test systems causing mitochondrial dysfunction. Mycotoxins can induce oxidative stress even at low concentration/dose that may be one of the major causes of mitochondrial dysfunction. On the other hand, activation of apoptotic caspases and other proteins by mycotoxins may lead to apoptotic cell death. Thus, mycotoxins-mediated mitochondrial dysfunction may be related to several chronic diseases which also makes these mycotoxins considerable as lead compounds for inducing toxic effects in cells. Their cytotoxic effects on cancer cells suggest their possible application as chemotherapeutic tools. © 2018 IUBMB Life, 70(11):1084-1092, 2018.

Protective and therapeutic potential of ginger (Zingiber officinale) extract and [6]-gingerol in cancer: A comprehensive review.

Natural dietary agents have attracted considerable attention due to their role in promoting health and reducing the risk of diseases including cancer. Ginger, one of the most ancient known spices, contains bioactive compounds with several health benefits. [6]-Gingerol constitutes the most pharmacologically active among such compounds. The aim of the present work was to review the literature pertaining to the use of ginger extract and [6]-gingerol against tumorigenic and oxidative and inflammatory processes associated with cancer, along with the underlying mechanisms of action involved in signaling pathways. This will shed some light on the protective or therapeutic role of ginger derivatives in oxidative and inflammatory regulations during metabolic disturbance and on the antiproliferative and anticancer properties. Data collected from experimental (in vitro or in vivo) and clinical studies discussed in this review indicate that ginger extract and [6]-gingerol exert their action through important mediators and pathways of cell signaling, including Bax/Bcl2, p38/MAPK, Nrf2, p65/NF-κB, TNF-α, ERK1/2, SAPK/JNK, ROS/NF-κB/COX-2, caspases-3, -9, and p53. This suggests that ginger derivatives, in the form of an extract or isolated compounds, exhibit relevant antiproliferative, antitumor, invasive, and anti-inflammatory activities.

Toxicogenetic study of omeprazole and the modulatory effects of retinol palmitate and ascorbic acid on Allium cepa.

Omeprazole (OME) is a proton pump inhibitor used for the treatment of various gastric and intestinal disease; however, studies on its effects on the genetic materials are still restricted. The present study aimed to evaluate possible toxicogenic effects of OME in Allium cepa meristems with the application of cytogenetic biomarkers for DNA damage, mutagenic, toxic and cytotoxic effects. Additionally, retinol palmitate (RP) and ascorbic acid (AA) were also co-treated with OME to evaluate possible modulatory effects of OME-induced cytogenetic damages. OME was tested at 10, 20 and 40 µg/mL, while RP and AA at 55 µg/mL and 352.2 µg/mL, respectively. Copper sulphate (0.6 µg/mL) and dechlorinated water were used as positive control and negative control, respectively. The results suggest that OME induced genotoxicity and mutagenicity in A. cepa at all tested concentrations. It was noted that cotreatment of OME with the antioxidant vitamins RP and/or AA significantly (p < 0.05) inhibited and/or modulated all toxicogenic damages induced by OME. These observations demonstrate their antigenotoxic, antimutagenic, antitoxic and anticitotoxic effects in A. cepa. This study indicates that application of antioxidants may be useful tools to overcome OME-induced toxic effects.