Phenytoin causes behavioral abnormalities and suppresses kisspeptin expression, reducing reproductive performance in Japanese medaka.

Phenytoin, an antiepileptic drug, induces neurotoxicity and abnormal embryonic development and reduces spontaneous locomotor activity in fish. However, its effects on other endpoints remain unclear. Therefore, we investigated the effects of phenytoin on the swimming behavior and reproductive ability of Japanese medaka. Abnormalities in swimming behavior, such as imbalance, rotation, rollover, and vertical swimming, were observed. However, when phenytoin exposure was discontinued, the behavioral abnormality rates decreased. Phenytoin exposure also significantly reduced reproductive ability. By investigating reproduction-related gene expression of gnrh1, gnrh2, fshb, and lhb remained unchanged in males and females. In contrast, kiss1 expression was significantly suppressed due to phenytoin exposure in males and females. kiss2 expression was also significantly suppressed in females but not in males. We filmed videos to examine phenytoin exposure effects on sexual behavior. Females showed no interest in the male's courtship. As the kisspeptin 1 system controls sexual behavior in Japanese medaka, phenytoin exposure may have decreased kiss1 expression, which decreased female reproductive motivation; hence, they did not spawn eggs. This is the first study to show that phenytoin exposure induces behavioral abnormalities, and suppresses kiss1 expression and reproductive performance in Japanese medaka.

Exploring the Therapeutic Effect of Neurotrophins and Neuropeptides in Neurodegenerative Diseases: at a Glance.

Neurotrophins and neuropeptides are the essential regulators of peripheral nociceptive nerves that help to induce, sensitize, and maintain pain. Neuropeptide has a neuroprotective impact as it increases trophic support, regulates calcium homeostasis, and reduces excitotoxicity and neuroinflammation. In contrast, neurotrophins target neurons afflicted by ischemia, epilepsy, depression, and eating disorders, among other neuropsychiatric conditions. Neurotrophins are reported to inhibit neuronal death. Strategies maintained for "brain-derived neurotrophic factor (BDNF) therapies" are to upregulate BDNF levels using the delivery of protein and genes or compounds that target BDNF production and boosting BDNF signals by expanding with BDNF mimetics. This review discusses the mechanisms of neurotrophins and neuropeptides against acute neural damage as well as highlighting neuropeptides as a potential therapeutic agent against Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), and Machado-Joseph disease (MJD), the signaling pathways affected by neurotrophins and their receptors in both standard and diseased CNS systems, and future perspectives that can lead to the potent application of neurotrophins and neuropeptides in neurodegenerative diseases (NDs).

Insights into the promising prospect of medicinal chemistry studies against neurodegenerative disorders.

Medicinal chemistry is an interdisciplinary field that incorporates organic chemistry, biochemistry, physical chemistry, pharmacology, informatics, molecular biology, structural biology, cell biology, and other disciplines. Additionally, it considers molecular factors such as the mode of action of the drugs, their chemical structure-activity relationship (SAR), and pharmacokinetic aspects like absorption, distribution, metabolism, elimination, and toxicity. Neurodegenerative disorders (NDs), which are defined by the breakdown of neurons over time, are affecting an increasing number of people. Oxidative stress, particularly the increased production of Reactive Oxygen Species (ROS), plays a crucial role in the growth of various disorders, as indicated by the identification of protein, lipid, and Deoxyribonucleic acid (DNA) oxidation products in vivo. Because of their inherent nature, most biological molecules are vulnerable to ROS, even if they play a role in metabolic parameters and cell signaling. Due to their high polyunsaturated fatty acid content, low antioxidant barrier, and high oxygen uptake, neurons are particularly vulnerable to oxidation by nature. As a result, excessive ROS generation in neurons looks especially harmful, and the mechanisms associated with biomolecule oxidative destruction are several and complex. This review focuses on the formation and management of ROS, as well as their chemical characteristics (both thermodynamic and kinetic), interactions, and implications in NDs.

An Insight into COVID-19 and Traditional Herbs: Bangladesh Perspective.

SARS-CoV-2 was first discovered in Wuhan in late 2019 and has since spread over the world, resulting in the present epidemic. Because targeted therapeutics are unavailable, scientists have the opportunity to discover new drugs or vaccines to counter COVID-19, and therefore a number of synthetic bioactive compounds are now being tested in clinical studies. Due to its broad therapeutic spectrum and low adverse effects, medicinal herbs have been used as traditional healing medication in those countries for ages. Due to a lack of synthetic bioactive antiviral medications, pharmaceutical and alternative therapies have been developed using a variety of herbal compositions. Due to the widespread availability of herbal and dietary products worldwide, people frequently use them. Notably, the majority of Bangladeshi people continue to use a variety of natural plants and herbs to treat various types of diseases. This review article discusses how previous research has shown that some herbs in Bangladesh have immunomodulatory and antiviral effects and how their active ingredients have been gathered. Even though FDA-approved medications and vaccines are available for the treatment of COVID-19, the purpose is to encourage the use of herbal medicine as immunomodulators and vaccine adjuvants for the treatment of COVID-19 prevention.

Colon cancer and colorectal cancer: Prevention and treatment by potential natural products.

Colon cancer affects both men and women and is the world's second most significant cause of cancer-related mortality. Colon cancer death rates have risen worldwide due to the current food habit and lifestyle, which include a lot of meat, alcohol, and not enough physical exercise. As a result, novel, less harmful pharmacological treatments for colon cancer are needed now more than ever before. Colorectal cancer (CRC) affects a significant portion of the world's population. Chemotherapy's limits, as demonstrated by side effects and resistance in CRC patients, are now being sought after despite recent breakthroughs that have improved patient care and survival. Numerous chemical compounds present in medicinal herbs have shown anti-tumor and anti-apoptotic properties against various cancers, including CRC, in animal experiments. These chemicals, which come from several phytochemical families, activate several signaling pathways. This article discusses research on the anti-CRC benefits of many plants conducted in vitro, as well as the phytochemical components of plants that may play a role in the study. Researchers are also looking into the impact of these compounds on various pathways involved in cancer signaling. According to this review, anti-CRC compounds may be generated from medicinal plants. That's why we're looking at how natural items can help treat cancer while lowering the risk of developing it.

Exposure of metal toxicity in Alzheimer's disease: An extensive review.

Metals serve important roles in the human body, including the maintenance of cell structure and the regulation of gene expression, the antioxidant response, and neurotransmission. High metal uptake in the nervous system is harmful because it can cause oxidative stress, disrupt mitochondrial function, and impair the activity of various enzymes. Metal accumulation can cause lifelong deterioration, including severe neurological problems. There is a strong association between accidental metal exposure and various neurodegenerative disorders, including Alzheimer's disease (AD), the most common form of dementia that causes degeneration in the aged. Chronic exposure to various metals is a well-known environmental risk factor that has become more widespread due to the rapid pace at which human activities are releasing large amounts of metals into the environment. Consequently, humans are exposed to both biometals and heavy metals, affecting metal homeostasis at molecular and biological levels. This review highlights how these metals affect brain physiology and immunity and their roles in creating harmful proteins such as ß-amyloid and tau in AD. In addition, we address findings that confirm the disruption of immune-related pathways as a significant toxicity mechanism through which metals may contribute to AD.

Perspectives on the Molecular Mediators of Oxidative Stress and Antioxidant Strategies in the Context of Neuroprotection and Neurolongevity: An Extensive Review.

Molecules with at least one unpaired electron in their outermost shell are known as free radicals. Free radical molecules are produced either within our bodies or by external sources such as ozone, cigarette smoking, X-rays, industrial chemicals, and air pollution. Disruption of normal cellular homeostasis by redox signaling may result in cardiovascular, neurodegenerative diseases and cancer. Although ROS (reactive oxygen species) are formed in the GI tract, little is known about how they contribute to pathophysiology and disease etiology. When reactive oxygen species and antioxidants are in imbalance in our bodies, they can cause cell structure damage, neurodegenerative diseases, diabetes, hypercholesterolemia, atherosclerosis, cancer, cardiovascular diseases, metabolic disorders, and other obesity-related disorders, as well as protein misfolding, mitochondrial dysfunction, glial cell activation, and subsequent cellular apoptosis. Neuron cells are gradually destroyed in neurodegenerative diseases. The production of inappropriately aggregated proteins is strongly linked to oxidative stress. This review's goal is to provide as much information as possible about the numerous neurodegenerative illnesses linked to oxidative stress. The possibilities of multimodal and neuroprotective therapy in human illness, using already accessible medications and demonstrating neuroprotective promise in animal models, are highlighted. Neuroprotection and neurolongevity may improve from the use of bioactive substances from medicinal herbs like Allium stadium, Celastrus paniculatus, and Centella asiatica. Many neuroprotective drugs' possible role has been addressed. Preventing neuroinflammation has been demonstrated in several animal models.

Naphthoquinones and derivatives as potential anticancer agents: An updated review.

One of the leading global causes of death is cancer; even though several treatment methods have improved survival rates, the incidence and fatality rates remain high. Naphthoquinones are a type of quinone that is found in nature and has vital biological roles. These chemicals have anticancer (antineoplastic), analgesic, anti-inflammatory, antimalarial, antifungal, antiviral, antitrypanosomal, antischistosomal, leishmanicidal, and anti-ulcerative effects. Direct addition of a substituent group to the 1,4-naphthoquinone ring can alter the naphthoquinone's oxidation/reduction and acid/base characteristics, and the activity can be altered. Because of their pharmacological properties, such as anticancer activity and probable therapeutic application, naphthoquinones have greatly interested the scientific community. Some chemicals having a quinone ring in malignant cells have been found to have antiproliferative effects. Naphthoquinones' deadly impact is connected with the inhibition of electron transporters, the uncoupling of oxidative phosphorylation, the creation of ROS, and the formation of protein adducts, notably with -SH enzyme groups. This review article aims to discuss naphthoquinones and their derivatives, which act against cancer and their future perspectives. This review covers several studies highlighting the potent anticancer properties of naphthoquinones. Further, various proposed mechanisms of anticancer actions of naphthoquinones have been summarized in this review.

Investigating Polyphenol Nanoformulations for Therapeutic Targets against Diabetes Mellitus.

Diabetes mellitus (DM) is a fatal metabolic disorder, and its prevalence has escalated in recent decades to a greater extent. Since the incidence and severity of the disease are constantly increasing, plenty of therapeutic approaches are being considered as a promising solution. Many dietary polyphenols have been reported to be effective against diabetes along with its accompanying vascular consequences by targeting multiple therapeutic targets. Additionally, the biocompatibility of these polyphenols raises questions about their use as pharmacological mediators. Nevertheless, the pharmacokinetic and biopharmaceutical properties of these polyphenols limit their clinical benefit as therapeutics. Pharmaceutical industries have attempted to improve compliance and therapeutic effects. However, nanotechnological approaches to overcome the pharmacokinetic and biopharmaceutical barriers associated with polyphenols as antidiabetic medications have been shown to be effective to improve clinical compliance and efficacy. Therefore, this review highlighted a comprehensive and up-to-date assessment of polyphenol nanoformulations in the treatment of diabetes and vascular consequences.

Multifaceted role of natural sources for COVID-19 pandemic as marine drugs.

COVID-19, which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread over the world, posing a global health concern. The ongoing epidemic has necessitated the development of novel drugs and potential therapies for patients infected with SARS-CoV-2. Advances in vaccination and medication development, no preventative vaccinations, or viable therapeutics against SARS-CoV-2 infection have been developed to date. As a result, additional research is needed in order to find a long-term solution to this devastating condition. Clinical studies are being conducted to determine the efficacy of bioactive compounds retrieved or synthesized from marine species starting material. The present study focuses on the anti-SARS-CoV-2 potential of marine-derived phytochemicals, which has been investigated utilizing in in silico, in vitro, and in vivo models to determine their effectiveness. Marine-derived biologically active substances, such as flavonoids, tannins, alkaloids, terpenoids, peptides, lectins, polysaccharides, and lipids, can affect SARS-CoV-2 during the viral particle's penetration and entry into the cell, replication of the viral nucleic acid, and virion release from the cell; they can also act on the host's cellular targets. COVID-19 has been proven to be resistant to several contaminants produced from marine resources. This paper gives an overview and summary of the various marine resources as marine drugs and their potential for treating SARS-CoV-2. We discussed at numerous natural compounds as marine drugs generated from natural sources for treating COVID-19 and controlling the current pandemic scenario.

Microbiome in cancer: Role in carcinogenesis and impact in therapeutic strategies.

Cancer is the world's second-leading cause of death, and the involvement of microbes in a range of diseases, including cancer, is well established. The gut microbiota is known to play an important role in the host's health and physiology. The gut microbiota and its metabolites may activate immunological and cellular pathways that kill invading pathogens and initiate a cancer-fighting immune response. Cancer is a multiplex illness, characterized by the persistence of several genetic and physiological anomalies in malignant tissue, complicating disease therapy and control. Humans have coevolved with a complex bacterial, fungal, and viral microbiome over millions of years. Specific long-known epidemiological links between certain bacteria and cancer have recently been grasped at the molecular level. Similarly, advances in next-generation sequencing technology have enabled detailed research of microbiomes, such as the human gut microbiome, allowing for the finding of taxonomic and metabolomic linkages between the microbiome and cancer. These investigations have found causative pathways for both microorganisms within tumors and bacteria in various host habitats far from tumors using direct and immunological procedures. Anticancer diagnostic and therapeutic solutions could be developed using this review to tackle the threat of anti-cancer medication resistance as well through the wide-ranging involvement of the microbiota in regulating host metabolic and immunological homeostasis. We reviewed the significance of gut microbiota in cancer initiation as well as cancer prevention. We look at certain microorganisms that may play a role in the development of cancer. Several bacteria with probiotic qualities may be employed as bio-therapeutic agents to re-establish the microbial population and trigger a strong immune response to remove malignancies, and further study into this should be conducted.

Natural Small Molecules in Breast Cancer Treatment: Understandings from a Therapeutic Viewpoint.

Breast cancer (BrCa) is the most common malignancy in women and the second most significant cause of death from cancer. BrCa is one of the most challenging malignancies to treat, and it accounts for a large percentage of cancer-related deaths. The number of cases requiring more effective BrCa therapy has increased dramatically. Scientists are looking for more productive agents, such as organic combinations, for BrCa prevention and treatment because most chemotherapeutic agents are linked to cancer metastasis, the resistance of the drugs, and side effects. Natural compounds produced by living organisms promote apoptosis and inhibit metastasis, slowing the spread of cancer. As a result, these compounds may delay the spread of BrCa, enhancing survival rates and reducing the number of deaths caused by BrCa. Several natural compounds inhibit BrCa production while lowering cancer cell proliferation and triggering cell death. Natural compounds, in addition to therapeutic approaches, are efficient and potential agents for treating BrCa. This review highlights the natural compounds demonstrated in various studies to have anticancer properties in BrCa cells. Future research into biological anti-BrCa agents may pave the way for a new era in BrCa treatment, with natural anti-BrCa drugs playing a key role in improving BrCa patient survival rates.

The Multifunctional Role of Herbal Products in the Management of Diabetes and Obesity: A Comprehensive Review.

Obesity and diabetes are the most demanding health problems today, and their prevalence, as well as comorbidities, is on the rise all over the world. As time goes on, both are becoming big issues that have a big impact on people's lives. Diabetes is a metabolic and endocrine illness set apart by hyperglycemia and glucose narrow-mindedness because of insulin opposition. Heftiness is a typical, complex, and developing overall wellbeing worry that has for quite some time been connected to significant medical issues in individuals, all things considered. Because of the wide variety and low adverse effects, herbal products are an important hotspot for drug development. Synthetic compounds are not structurally diverse and lack drug-likeness properties. Thus, it is basic to keep on exploring herbal products as possible wellsprings of novel drugs. We conducted this review of the literature by searching Scopus, Science Direct, Elsevier, PubMed, and Web of Science databases. From 1990 until October 2021, research reports, review articles, and original research articles in English are presented. It provides top to bottom data and an examination of plant-inferred compounds that might be utilized against heftiness or potentially hostile to diabetes treatments. Our expanded comprehension of the systems of activity of phytogenic compounds, as an extra examination, could prompt the advancement of remedial methodologies for metabolic diseases. In clinical trials, a huge number of these food kinds or restorative plants, as well as their bioactive compounds, have been shown to be beneficial in the treatment of obesity.

Exploring the Journey of Zinc Oxide Nanoparticles (ZnO-NPs) toward Biomedical Applications.

The field of nanotechnology is concerned with the creation and application of materials having a nanoscale spatial dimensioning. Having a considerable surface area to volume ratio, nanoparticles have particularly unique properties. Several chemical and physical strategies have been used to prepare zinc oxide nanoparticles (ZnO-NPs). Still, biological methods using green or natural routes in various underlying substances (e.g., plant extracts, enzymes, and microorganisms) can be more environmentally friendly and cost-effective than chemical and/or physical methods in the long run. ZnO-NPs are now being studied as antibacterial agents in nanoscale and microscale formulations. The purpose of this study is to analyze the prevalent traditional method of generating ZnO-NPs, as well as its harmful side effects, and how it might be addressed utilizing an eco-friendly green approach. The study's primary focus is on the potential biomedical applications of green synthesized ZnO-NPs. Biocompatibility and biomedical qualities have been improved in green-synthesized ZnO-NPs over their traditionally produced counterparts, making them excellent antibacterial and cancer-fighting drugs. Additionally, these ZnO-NPs are beneficial when combined with the healing processes of wounds and biosensing components to trace small portions of biomarkers linked with various disorders. It has also been discovered that ZnO-NPs can distribute and sense drugs. Green-synthesized ZnO-NPs are compared to traditionally synthesized ones in this review, which shows that they have outstanding potential as a potent biological agent, as well as related hazardous properties.