Natural Isatin Derivatives Against Black Fungus: In Silico Studies.

During this coronavirus pandemic, when a lot of people are already severely afflicted with SARS-CoV-19, the dispersion of black fungus is making it worse, especially in the Indian subcontinent. Considering this situation, the idea for an in silico study to identify the potential inhibitor against black fungal infection is envisioned and computational analysis has been conducted with isatin derivatives that exhibit considerable antifungal activity. Through this in silico study, several pharmacokinetics properties like absorption, distribution, metabolism, excretion, and toxicity (ADMET) are estimated for various derivatives. Lipinski rules have been used to observe the drug likeliness property, and to study the electronic properties of the molecules, quantum mechanism was analyzed using the density functional theory (DFT). After applying molecular docking of the isatin derivatives with sterol 14-alpha demethylase enzyme of black fungus, a far higher docking affinity score has been observed for the isatin sulfonamide-34 (derivative 1) than the standard fluconazole. Lastly, molecular dynamic (MD) simulation has been performed for 100 ns to examine the stability of the proposed drug complex by estimating Root Mean Square Deviation (RMSD), Radius of gyration (Rg), Solvent accessible surface area (SASA), Root Mean Square Fluctuation (RMSF), as well as hydrogen bond. Listed ligands have precisely satisfied every pharmacokinetics requirement for a qualified drug candidate and they are non-toxic, non-carcinogenic, and have high stability. This natural molecule known as isatin derivative 1 has shown the potential of being a drug for fungal treatment. However, the impact of the chemicals on living cells requires more investigation and research.

A mechanistic insight into the anticancer potentials of resveratrol: Current perspectives.

Resveratrol is a widely recognized polyphenolic phytochemical found in various plants and their fruits, such as peanuts, grapes, and berry fruits. It is renowned for its several health advantages. The phytochemical is well known for its anticancer properties, and a substantial amount of clinical evidence has also established its promise as a chemotherapeutic agent. This study focuses on assessing the anticancer properties of resveratrol and gaining insight into the underlying molecular mechanisms. It also evaluates the biopharmaceutical, toxicological characteristics, and clinical utilization of resveratrol to determine its suitability for further development as a reliable anticancer agent. Therefore, the information about preclinical and clinical studies was collected from different electronic databases up-to-date (2018-2023). Findings from this study revealed that resveratrol has potent therapeutic benefits against various cancers involving different molecular mechanisms, such as induction of oxidative stress, cytotoxicity, inhibition of cell migration and invasion, autophagy, arresting of the S phase of the cell cycle, apoptotic, anti-angiogenic, and antiproliferative effects by regulating different molecular pathways including PI3K/AKT, p38/MAPK/ERK, NGFR-AMPK-mTOR, and so on. However, the compound has poor oral bioavailability due to reduced absorption; this limitation is overcome by applying nanotechnology (nanoformulation of resveratrol). Clinical application also showed therapeutic benefits in several types of cancer with no serious adverse effects. We suggest additional extensive studies to further check the efficacy, safety, and long-term hazards. This could involve a larger number of clinical samples to establish the compound as a reliable drug in the treatment of cancer.

An Insight of Plant Source, Toxicological Profile, and Pharmacological Activities of Iridoid Loganic Acid: A Comprehensive Review.

This study evaluates the pharmacological effects of iridoid glucoside loganic acid, a plant constituent with diverse properties, based on literature, and explores the underlying cellular mechanisms for treating several ailments. Data were collected from reliable electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar, etc. The results demonstrated the anti-inflammatory, anti-oxidant, and other protective effects of loganic acid on metabolic diseases and disorders such as atherosclerosis, diabetes, and obesity, in addition to its osteoprotective and anticancer properties. The antioxidant activity of loganic acid demonstrates its capacity to protect cells from oxidative damage and mitigates inflammation by reducing the activity of inflammatory cytokines involving TNF-α and IL-6, substantially upregulating the expression of PPAR-γ/α, and decreasing the clinical signs of inflammation-related conditions related to hypertriglyceridemia and atherosclerosis. Meanwhile, loganic acid inhibits bone loss, exhibits osteoprotective properties by increasing mRNA expression levels of bone synthesizing genes such as Alpl, Bglap, and Sp7, and significantly increases osteoblastic proliferation in preosteoblast cells. Loganic acid is an anti-metastatic drug that reduces MnSOD expression, inhibits EMT and metastasis, and prevents cellular migration, proliferation, and invasion in hepatocellular carcinoma cells. However, additional clinical trials are required to assess its safety, efficacy, and human dose.

Therapeutic Promises of Ferulic Acid and its Derivatives on Hepatic damage Related with Oxidative Stress and Inflammation: A Review with Mechanisms.

Ferulic acid (FA) is a naturally occurring phenolic compound commonly found in the plant Ferula communis. This study aims to investigate the hepatoprotective effect of FA and its derivatives (methyl ferulic acid and trans-ferulic acid) against oxidative stress and inflammation-related hepatotoxicity due to toxicants based on the results of different non-clinical and preclinical tests. For this, data was collected from different reliable electronic databases such as PubMed, Google Scholar, and ScienceDirect, etc. The results of this investigation demonstrated that FA and its derivatives have potent hepatoprotective effects against oxidative stress and inflammation-related damage. The findings also revealed that these protective effects are due to the antioxidant and anti-inflammatory effects of the chemical compound. FA and its analogues significantly inhibit free radical generation and hinder the effects of proinflammatory markers and inflammatory enzymes, resulting in diminished cytotoxic and apoptotic hepatocyte death. The compounds also prevent intracellular lipid accumulation and provide protective effects.

Efficacy of Rotundic Acid and Its Derivatives as Promising Natural Anticancer Triterpenoids: A Literature-Based Study.

Rotundic acid (RA) is a naturally occurring pentacyclic triterpene with a multitude of pharmacological activities. The primary emphasis of this study is on summarizing the anticancer properties with the underlying mechanisms of RA and its derivatives, as well as the pharmacokinetic features. Data was collected (up to date as of November 10, 2023) from various reliable and authentic literatures by searching in different academic search engines, including PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. The findings imply that RA and its synthetic derivatives possess promising anti-cancer properties against breast, colorectal, liver, and cervical cancers in various preclinical pharmacological test systems. The results also indicate that RA and its derivatives demonstrated anticancer effects via a number of cellular mechanisms, including apoptotic cell death, inhibition of oxidative stress, anti-inflammatory effect, cytotoxicity, cell cycle arrest, anti-proliferative effect, anti-angiogenic effect, and inhibition of cancer cell migration and invasion. It has been proposed that RA and its derived compounds have the capability to serve as a hopeful chemotherapeutic agent, so further extensive clinical research is necessary.

Pharmacological Activities of Plant-Derived Fraxin with Molecular Mechanisms: A Comprehensive Review.

Fruits and vegetables serve not only as sources of nutrition but also as medicinal agents for the treatment of diverse diseases and maladies. These dietary components are significant resources of phytochemicals that demonstrate therapeutic properties against many illnesses. Fraxin is a naturally occurring coumarin glycoside mainly present in various species of Fraxinus genera, having a multitude of therapeutic uses against various diseases and disorders. This study focuses to investigate the pharmacological activities, botanical sources, and biopharmaceutical profile of the phytochemical fraxin based on different preclinical and non-clinical studies to show the scientific evidence and to evaluate the underlying molecular mechanisms of the therapeutic effects against various ailments. For this, data was searched and collected (as of February 15, 2024) in a variety of credible electronic databases, including PubMed/Medline, Scopus, Springer Link, ScienceDirect, Wiley Online, Web of Science, and Google Scholar. The findings demonstrated favorable outcomes in relation to a range of diseases or medical conditions, including inflammation, neurodegenerative disorders such as cerebral ischemia-reperfusion (I/R) and depression, viral infection, as well as diabetic nephropathy. The phytochemical also showed protective effects such as osteoprotective, renoprotective, pulmoprotective, hepatoprotective, and gastroprotective effects due to its antioxidant capacity. Fraxin has a great capability to diminish oxidative stress-related damage in different organs by stimulating the antioxidant enzymes, downregulating nuclear factor kappa B and NLRP3, and triggering the Nrf2/ARE signaling pathways. Fraxin exhibited poor oral bioavailability because of reduced absorption and a wide distribution into tissues of different organs. However, extensive research is required to decipher the biopharmaceutical profiles, and clinical studies are necessary to establish the efficacy of the natural compound as a reliable therapeutic agent.

Recent Insights into the Antimicrobial Properties of Phyllanthus emblica L.: A Comprehensive Review of Wonder Berry.

Phyllanthus emblica L., or Amla, is known for its therapeutic properties and has been used as a medicinal plant. It is rich in vitamin C and other bioactive phytochemicals like polyphenols, gallic acid, chebulagic acid, leutolin, quercetin, etc. Different parts of this plant are used to treat various viral, bacterial, and fungal diseases. This review article summarizes the recent literature relevant to the antiviral, antibacterial, and antifungal effects of P. emblica. A variety of bacteria (Staphylococcus aureus, Bacillus subtillus, Enterococcus faecalis, Salmonella typhi, and Escherichia, etc.), fungi (Alternaria alternate Botroyodiplodia theobromae, Colletotrichum corcori, Curvularia lunata, Fusarium exquisite, Fusarium solanii, Aspergillus niger, Candida albicans, Colletotrichum gleosparoitis, and Macrophomina phaseolina) and viruses, like Influenza A virus strain H3N2, hepatitis B, Human Immunodeficiency virus type-1 (HIV-1), Simplex virus type 1 (HSV-1) and type 2 (HSV-2) have experimented. Different techniques were used based on the way of identification. 'For example, disc diffusion, dilution methods, sound diffusion, Immuno-peroxidase monolayer assay, serum HBV and HBsAg assay, enzyme immunoassay, etc. The present review analyzed and summarized the antimicrobial activities of P. emblica and possible mechanisms of action to provide future directions in translating these findings clinically.

Allium cepa as a Toxicogenetic Investigational Tool for Plant Extracts: A Systematic Review.

Toxicological studies are important to investigate the genotoxic effects of various substances. Allium cepa can be used as test model for this purpose. This review summarizes the scope and applications for this A. cepa test model. For this, an up-to-date (April 2023) literature search was made in the Science Direct, PubMed, and Web of Science databases to find published evidence on studies performed using A. cepa as a test model. Out of 3,748 studies, 74 fit the inclusion criteria. The results showed that the use of the test model A. cepa contributed considerably to measuring the toxicological potential of plant extracts, proving the efficacy of the test as a potent bioindicator of toxic effects. In addition, 27 studies used more than one test system to verify the toxicological potential of extracts and fractions. Studies have shown that the A. cepa model has the potential to replace other test systems that make use of animals and cell cultures, besides having other advantages such as low cost, ease of execution, and good conditions for the observation of chromosomes. In conclusion, the A. cepa test can be considered one of the potential biomonitoring systems in toxicological studies of crude extracts.

Assessment of sedative activity of fraxin: In vivo approach along with receptor binding affinity and molecular interaction with GABAergic system.

Insomnia is a sleep disorder in which you have trouble falling and/or staying asleep. This research aims to evaluate the sedative effects of fraxin (FX) on sleeping mice induced by thiopental sodium (TS). In addition, a molecular docking study was conducted to investigate the molecular processes underlying these effects. The study used adult male Swiss albino mice and administered FX (10 and 20 mg/kg, i.p.) and diazepam (DZP) (2 mg/kg) either separately or in combination within the different groups to examine their modulatory effects. After a period of 30 min, the mice that had been treated were administered (TS: 20 mg/kg, i.p.) to induce sleep. The onset of sleep for the mice and the length of their sleep were manually recorded. Additionally, a computational analysis was conducted to predict the role of gamma-aminobutyric acid (GABA) receptors in the sleep process and evaluate their pharmacokinetics and toxicity. The outcomes indicated that FX extended the length of sleep and reduced the time it took to fall asleep. When the combined treatment of FX and DZP showed synergistic sedative action. Also, FX had a binding affinity of -7.2 kcal/mol, while DZP showed -8.4 kcal/mol. The pharmacokinetic investigation of FX demonstrated favorable drug-likeness and strong pharmacokinetic characteristics. Ultimately, FX demonstrated a strong sedative impact in the mouse model, likely via interacting with the GABAA receptor pathways.

Amentoflavone derivatives significantly act towards the main protease (3CLPRO/MPRO) of SARS-CoV-2: in silico admet profiling, molecular docking, molecular dynamics simulation, network pharmacology.

SARS-CoV-2 is the foremost culprit of the novel coronavirus disease 2019 (nCoV-19 and/or simply COVID-19) and poses a threat to the continued life of humans on the planet and create pandemic issue globally. The 3-chymotrypsin-like protease (MPRO or 3CLPRO) is the crucial protease enzyme of SARS-CoV-2, which directly involves the processing and release of translated non-structural proteins (nsps), and therefore involves the development of virus pathogenesis along with outbreak the forecasting of COVID-19 symptoms. Moreover, SARS-CoV-2 infections can be inhibited by plant-derived chemicals like amentoflavone derivatives, which could be used to develop an anti-COVID-19 drug. Our research study is designed to conduct an in silico analysis on derivatives of amentoflavone (isoginkgetin, putraflavone, 4''''''-methylamentoflavone, bilobetin, ginkgetin, sotetsuflavone, sequoiaflavone, heveaflavone, kayaflavone, and sciadopitysin) for targeting the non-structural protein of SARS-CoV-2, and subsequently further validate to confirm their antiviral ability. To conduct all the in silico experiments with the derivatives of amentoflavone against the MPRO protein, both computerized tools and online servers were applied; notably the software used is UCSF Chimera (version 1.14), PyRx, PyMoL, BIOVIA Discovery Studio tool (version 4.5), YASARA (dynamics simulator), and Cytoscape. Besides, as part of the online tools, the SwissDME and pKCSM were employed. The research study was proposed to implement molecular docking investigations utilizing compounds that were found to be effective against the viral primary protease (MPRO). MPRO protein interacted strongly with 10 amentoflavone derivatives. Every time, amentoflavone compounds outperformed the FDA-approved antiviral medicine that is currently underused in COVID-19 in terms of binding affinity (- 8.9, - 9.4, - 9.7, - 9.1, - 9.3, - 9.0, - 9.7, - 9.3, - 8.8, and - 9.0 kcal/mol, respectively). The best-selected derivatives of amentoflavone also possessed potential results in 100 ns molecular dynamic simulation (MDS) validation. It is conceivable that based on our in silico research these selected amentoflavone derivatives more precisely 4''''''-methylamentoflavone, ginkgetin, and sequoiaflavone have potential for serving as promising lead drugs against SARS-CoV-2 infection. In consequence, it is recommended that additional in vitro as well as in vivo research studies have to be conducted to support the conclusions of this current research study.

The efficacy of natural bioactive compounds against prostate cancer: Molecular targets and synergistic activities.

Globally, prostate cancer (PCa) is regarded as a challenging health issue, and the number of PCa patients continues to rise despite the availability of effective treatments in recent decades. The current therapy with chemotherapeutic drugs has been largely ineffective due to multidrug resistance and the conventional treatment has restricted drug accessibility to malignant tissues, necessitating a higher dosage resulting in increased cytotoxicity. Plant-derived bioactive compounds have recently attracted a great deal of attention in the field of PCa treatment due to their potent effects on several molecular targets and synergistic effects with anti-PCa drugs. This review emphasizes the molecular mechanism of phytochemicals on PCa cells, the synergistic effects of compound-drug interactions, and stem cell targeting for PCa treatment. Some potential compounds, such as curcumin, phenethyl-isothiocyanate, fisetin, baicalein, berberine, lutein, and many others, exert an anti-PCa effect via inhibiting proliferation, metastasis, cell cycle progression, and normal apoptosis pathways. In addition, multiple studies have demonstrated that the isolated natural compounds: d-limonene, paeonol, lanreotide, artesunate, and bicalutamide have potential synergistic effects. Further, a significant number of natural compounds effectively target PCa stem cells. However, further high-quality studies are needed to firmly establish the clinical efficacy of these phytochemicals against PCa.

Anticancer Potential of the Plant-Derived Saponin Gracillin: A Comprehensive Review of Mechanistic Approaches.

With the increasing prevalence of cancer and the toxic side effects of synthetic drugs, natural products are being developed as promising therapeutic approaches. Gracillin is a naturally occurring triterpenoid steroidal saponin with several therapeutic activities. It is obtained as a major compound from different Dioscorea species. This review was designated to summarize the research progress on the anti-cancer activities of gracillin focusing on the underlying cellular and molecular mechanisms, as well as its pharmacokinetic features. The data were collected (up to date as of May 1, 2023) from various reliable and authentic literatures comprising PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. The findings demonstrated that gracillin displays promising anticancer effects through various molecular mechanisms, including anti-inflammatory effects, apoptotic cell death, induction of oxidative stress, cytotoxicity, induction of genotoxicity, cell cycle arrest, anti-proliferative effect, autophagy, inhibition of glycolysis, and blocking of cancer cell migration. Additionally, this review highlighted the pharmacokinetic features of gracillin, indicating its lower oral bioavailability. As a conclusion, it can be proposed that gracillin could serve as a hopeful chemotherapeutic agent. However, further extensive clinical research is recommended to establish its safety, efficacy, and therapeutic potential in cancer treatment.

Hirsutine, an Emerging Natural Product with Promising Therapeutic Benefits: A Systematic Review.

Fruits and vegetables are used not only for nutritional purposes but also as therapeutics to treat various diseases and ailments. These food items are prominent sources of phytochemicals that exhibit chemopreventive and therapeutic effects against several diseases. Hirsutine (HSN) is a naturally occurring indole alkaloid found in various Uncaria species and has a multitude of therapeutic benefits. It is found in foodstuffs such as fish, seafood, meat, poultry, dairy, and some grain products among other things. In addition, it is present in fruits and vegetables including corn, cauliflower, mushrooms, potatoes, bamboo shoots, bananas, cantaloupe, and citrus fruits. The primary emphasis of this study is to summarize the pharmacological activities and the underlying mechanisms of HSN against different diseases, as well as the biopharmaceutical features. For this, data were collected (up to date as of 1 July 2023) from various reliable and authentic literature by searching different academic search engines, including PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. Findings indicated that HSN exerts several effects in various preclinical and pharmacological experimental systems. It exhibits anti-inflammatory, antiviral, anti-diabetic, and antioxidant activities with beneficial effects in neurological and cardiovascular diseases. Our findings also indicate that HSN exerts promising anticancer potentials via several molecular mechanisms, including apoptotic cell death, induction of oxidative stress, cytotoxic effect, anti-proliferative effect, genotoxic effect, and inhibition of cancer cell migration and invasion against various cancers such as lung, breast, and antitumor effects in human T-cell leukemia. Taken all together, findings from this study show that HSN can be a promising therapeutic agent to treat various diseases including cancer.

Anticancer Potentials of the Lignan Magnolin: A Systematic Review.

Magnolin is a naturally occurring, multi-bioactive lignan molecule with inherent anticancer effects. This study aims to summarize the botanical origins and anticancer properties of magnolin. For this, a recent (as of March 2023) literature review was conducted using various academic search engines, including PubMed, Springer Link, Wiley Online, Web of Science, Science Direct, and Google Scholar. All the currently available information about this phytochemical and its role in various cancer types has been gathered and investigated. Magnolin is a compound found in many different plants. It has been demonstrated to have anticancer activity in numerous experimental models by inhibiting the cell cycle (G1 and G2/M phase); inducing apoptosis; and causing antiinvasion, antimetastasis, and antiproliferative effects via the modulation of several pathways. In conclusion, magnolin showed robust anticancer activity against many cancer cell lines by altering several cancer signaling pathways in various non- and pre-clinical experimental models, making it a promising plant-derived chemotherapeutic option for further clinical research.

Quercetin Antagonizes the Sedative Effects of Linalool, Possibly through the GABAergic Interaction Pathway.

Sedatives promote calmness or sleepiness during surgery or severely stressful events. In addition, depression is a mental health issue that negatively affects emotional well-being. A group of drugs called anti-depressants is used to treat major depressive illnesses. The aim of the present work was to evaluate the effects of quercetin (QUR) and linalool (LIN) on thiopental sodium (TS)-induced sleeping mice and to investigate the combined effects of these compounds using a conventional co-treatment strategy and in silico studies. For this, the TS-induced sleeping mice were monitored to compare the occurrence, latency, and duration of the sleep-in response to QUR (10, 25, 50 mg/kg), LIN (10, 25, 50 mg/kg), and diazepam (DZP, 3 mg/kg, i.p.). Moreover, an in silico investigation was undertaken to assess this study's putative modulatory sedation mechanism. For this, we observed the ability of test and standard medications to interact with various gamma-aminobutyric acid A receptor (GABAA) subunits. Results revealed that QUR and LIN cause dose-dependent antidepressant-like and sedative-like effects in animals, respectively. In addition, QUR-50 mg/kg and LIN-50 mg/kg and/or DZP-3 mg/kg combined were associated with an increased latency period and reduced sleeping times in animals. Results of the in silico studies demonstrated that QUR has better binding interaction with GABAA α3, ß1, and γ2 subunits when compared with DZP, whereas LIN showed moderate affinity with the GABAA receptor. Taken together, the sleep duration of LIN and DZP is opposed by QUR in TS-induced sleeping mice, suggesting that QUR may be responsible for providing sedation-antagonizing effects through the GABAergic interaction pathway.

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.

Recent advances and limitations of mTOR inhibitors in the treatment of cancer.

The PI3K-Akt-mechanistic (formerly mammalian) target of the rapamycin (mTOR) signaling pathway is important in a variety of biological activities, including cellular proliferation, survival, metabolism, autophagy, and immunity. Abnormal PI3K-Akt-mTOR signalling activation can promote transformation by creating a cellular environment conducive to it. Deregulation of such a system in terms of genetic mutations and amplification has been related to several human cancers. Consequently, mTOR has been recognized as a key target for the treatment of cancer, especially for treating cancers with elevated mTOR signaling due to genetic or metabolic disorders. In vitro and in vivo, rapamycin which is an immunosuppressant agent actively suppresses the activity of mTOR and reduces cancer cell growth. As a result, various sirolimus-derived compounds have now been established as therapies for cancer, and now these medications are being investigated in clinical studies. In this updated review, we discuss the usage of sirolimus-derived compounds and other drugs in several preclinical or clinical studies as well as explain some of the challenges involved in targeting mTOR for treating various human cancers.

Targeting Ras-ERK cascade by bioactive natural products for potential treatment of cancer: an updated overview.

MAPK (mitogen-activated protein kinase) or ERK (extracellular-signal-regulated kinase) pathway is an important link in the transition from extracellular signals to intracellular responses. Because of genetic and epigenetic changes, signaling cascades are altered in a variety of diseases, including cancer. Extant studies on the homeostatic and pathologic behavior of MAPK signaling have been conducted; however, much remains to be explored in preclinical and clinical research in terms of regulation and action models. MAPK has implications for cancer therapy response, more specifically in response to experimental MAPK suppression, compensatory mechanisms are activated. The current study investigates MAPK as a very complex cell signaling pathway that plays roles in cancer treatment response, cellular normal conduit maintenance, and compensatory pathway activation. Most MAPK inhibitors, unfortunately, cause resistance by activating compensatory feedback loops in tumor cells and tumor microenvironment components. As a result, innovative combinatorial treatments for cancer management must be applied to limit the likelihood of alternate pathway initiation as a possibility for generating novel therapeutics based on incorporation in translational research. We summarize current knowledge about the implications of ERK (MAPK) in cancer, as well as bioactive products from plants, microbial organisms or marine organisms, as well as the correlation with their chemical structures, which modulate this pathway for the treatment of different types of cancer.

Evaluation of mutagenesis, necrosis and apoptosis induced by omeprazole in stomach cells of patients with gastritis.

BACKGROUND: Gastritis is a superficial and prevalent inflammatory lesion that is considered a public health concern once can cause gastric ulcers and gastric cancer, especially when associated with Helicobacter pylori infection. Proton pump inhibitors, such as omeprazole, are the most widely used drugs to treat this illness. The aim of the study was evaluate cytogenetic effects of omeprazole in stomach epithelial cells of patients with gastritis in presence and absence of H. pylori, through cytogenetic biomarkers and catalse and superoxide dismutase analysis. METHODS: The study included 152 patients from the Gastroenterology Outpatient Clinic of Hospital Getúlio Vargas, Teresina-Brazil, that reported continuous and prolonged omeprazole use in doses of 20, 30 and 40 mg/kg. The participants were divided into groups: (1) patients without gastritis (n = 32); (2) patients without gastritis but with OME use (n = 24); (3) patients with gastritis (n = 26); (4) patients with gastritis undergoing OME therapy (n = 26); (5) patients with gastritis and H. pylori (n = 22) and (6) patients with gastritis and H. pylori on OME therapy (n = 22). RESULTS: OME induced cytogenetic imbalance in the stomach epithelium through the formation of micronuclei (group 6 > 1, 2, 3, 4, 5; group 5 > 1, 2, 3; group 4 > 1, 2, 3); bridges (groups 4 and 6 > 1, 2, 3, 5 and group 2 > 3, 5); buds (groups 2,4,6 > , 1, 3, 5); binucleated cells (group 6 > 1, 2, 3, 4, 5; group 4 > 1, 2, 3); (groups 2 and 3 > 1); picnoses (group 6 > 1, 2, 3, 4, 5), groups 2 and 5 > 1, 3; group 4 > 1, 2, 3, 5); cariorrexis (groups 6 and 4 > 1, 2, 3, 5; groups 2, 3, 5 > 1) and karyolysis (groups 2, 4, and 6 > 1, 3, 5; groups 3 and 5 > 1). The OME cytogenetic instability was associated with H. pylori infection, indicating clastogenic/aneugenic effects, chromosomes alterations, gene expression changes, cytotoxicity and apoptosis. CONCLUSIONS: The cytogenetic changescan be attributed to several mechanisms that are still unclear, including oxidative damage, as observed by increased catalase and superoxide dismutase expresion. Positive correlations between antioxidant enzymes were found with micronuclei formation, and were negative for picnoses. Thus, the continuous and prolonged omeprazole use induces genetic instability, which can be monitored through cytogenetic analyzes, as precursor for gastric cancer.

Redox Activity of Flavonoids: Impact on Human Health, Therapeutics, and Chemical Safety.

The cost-effectiveness of presently used therapies is a problem in overall redox-based management, which is posing a significant financial burden on communities across the world. As a result, sophisticated treatment models that provide notions of predictive diagnoses followed by targeted preventive therapies adapted to individual patient profiles are gaining global acclaim as being beneficial to patients, the healthcare sector, and society as a whole. In this context, natural flavonoids were considered due to their multifaceted antioxidant, anti-inflammatory, and anticancer effects as well as their low toxicity and ease of availability. The aim of this review is to focus on the capacity of flavonoids to modulate the responsiveness of various diseases and ailments associated with redox toxicity. The review will also focus on the flavonoids' pathway-based redox activity and the advancement of redox-based therapies as well as flavonoids' antioxidant characteristics and their influence on human health, therapeutics, and chemical safety. Research findings indicated that flavonoids significantly exhibit various redox-based therapeutic responses against several diseases such as inflammatory, neurodegenerative, cardiovascular, and hepatic diseases and various types of cancer by activating the Nrf2/Keap1 transcription system, suppressing the nuclear factor κB (NF-κB)/IκB kinase inflammatory pathway, abrogating the function of the Hsp90/Hsf1 complex, inhibiting the PTEN/PI3K/Akt pathway, and preventing mitochondrial dysfunction. Some flavonoids, especially genistein, apigenin, amentoflavone, baicalein, quercetin, licochalcone A, and biochanin A, play a potential role in redox regulation. Conclusions of this review on the antioxidant aspects of flavonoids highlight the medicinal and folk values of these compounds against oxidative stress and various diseases and ailments. In short, treatment with flavonoids could be a novel therapeutic invention in clinical trials, as we hope.