Comprehensive review of the repositioning of non-oncologic drugs for cancer immunotherapy.

Drug repositioning or repurposing has gained worldwide attention as a plausible way to search for novel molecules for the treatment of particular diseases or disorders. Drug repurposing essentially refers to uncovering approved or failed compounds for use in various diseases. Cancer is a deadly disease and leading cause of mortality. The search for approved non-oncologic drugs for cancer treatment involved in silico modeling, databases, and literature searches. In this review, we provide a concise account of the existing non-oncologic drug molecules and their therapeutic potential in chemotherapy. The mechanisms and modes of action of the repurposed drugs using computational techniques are also highlighted. Furthermore, we discuss potential targets, critical pathways, and highlight in detail the different challenges pertaining to drug repositioning for cancer immunotherapy.

Revisiting luteolin: An updated review on its anticancer potential.

Numerous natural products found in our diet, such as polyphenols and flavonoids, can prevent the progression of cancer. Luteolin, a natural flavone, present in significant amounts in various fruits and vegetables plays a key role as a chemopreventive agent in treating various types of cancer. By inducing apoptosis, initiating cell cycle arrest, and decreasing angiogenesis, metastasis, and cell proliferation, luteolin is used to treat cancer. Its anticancer properties are attributed to its capability to engage with multiple molecular targeted sites and modify various signaling pathways in tumor cells. Luteolin has been shown to slow the spread of cancer in breast, colorectal, lung, prostate, liver, skin, pancreatic, oral, and gastric cancer models. It exhibits antioxidant properties and can be given to patients receiving Doxorubicin (DOX) chemotherapy to prevent the development of unexpected adverse reactions in the lungs and hematopoietic system subjected to DOX. Furthermore, it could be an excellent candidate for synergistic studies to overcome drug resistance in cancer cells. Accordingly, this review covers the recent literature related to the use of luteolin against different types of cancer, along with the mechanisms of action. In addition, the review highlights luteolin as a complementary medicine for preventing and treating cancer.

Edible mushrooms as potential functional foods in amelioration of hypertension.

Edible mushrooms are popular functional foods attributed to their rich nutritional bioactive constituent profile influencing cardiovascular function. Edible mushrooms are omnipresent in various prescribed Dietary Approaches to Stop Hypertension, Mediterranean diet, and fortified meal plans as they are rich in amino acids, dietary fiber, proteins, sterols, vitamins, and minerals. However, without an understanding of the influence of mushroom bioactive constituents, mechanism of action on heart and allergenicity, it is difficult to fully comprehend the role of mushrooms as dietary interventions in alleviating hypertension and other cardiovascular malfunctions. To accomplish this endeavor, we chose to review edible mushrooms and their bioactive constituents in ameliorating hypertension. Hypertension and cardiovascular diseases are interrelated and if the former is managed by dietary changes, it is postulated that overall heart health could also be improved. With a concise note on different edible varieties of mushrooms, a particular focus is presented on the antihypertensive potential of mushroom bioactive constituents, mode of action, absorption kinetics and bioavailability. Ergosterol, lovastatin, cordycepin, tocopherols, chitosan, ergothioneine, γ-aminobutyric acid, quercetin, and eritadenine are described as essential bioactives with hypotensive effects. Finally, safety concerns on allergens and limitations of consuming edible mushrooms with special reference to chemical toxins and their postulated metabolites are highlighted. It is opined that the present review will redirect toxicologists to further investigate mushroom bioactives and allergens, thereby influencing dietary interventions for heart health.

Exploring the nutritional and health benefits of pulses from the Indian Himalayan region: A glimpse into the region's rich agricultural heritage.

Pulses have been consumed worldwide for over 10 centuries and are currently among the most widely used foods. They are not economically important, but also nutritionally beneficial as they constitute a good source of protein, fibre, vitamins and minerals such as iron, zinc, folate and magnesium. Pulses, but particularly species such as Macrotyloma uniflorum, Phaseolus vulgaris L., Glycine max L. and Vigna umbellate, are essential ingredients of the local diet in the Indian Himalayan Region (IHR). Consuming pulses can have a favourable effect on cardiovascular health as they improve serum lipid profiles, reduce blood pressure, decrease platelet activity, regulate blood glucose and insulin levels, and reduce inflammation. Although pulses also contain anti-nutritional compounds such as phytates, lectins or enzyme inhibitors, their deleterious effects can be lessened by using effective processing and cooking methods. Despite their great potential, however, the use of some pulses is confined to IHR regions. This comprehensive review discusses the state of the art in available knowledge about various types of pulses grown in IHR in terms of chemical and nutritional properties, health effects, accessibility, and agricultural productivity.

The medicinal chemistry of Urtica dioica L.: from preliminary evidence to clinical studies supporting its neuroprotective activity.

Urtica dioica is a perennial herb from the family of Urticaceae that is commonly known as stinging nettle. This plant is widespread in Europe, Africa, America, and a part of Asia, as it adapts to different environments and climatic conditions. The leaves, stalk, and bark of U. dioica found applications in the field of nutrition, cosmetics, textile, pest control and pharmacology. In this connection, bioactive chemical constituents such as flavonoids, phenolic acids, amino acids, carotenoids, and fatty acids have been isolated from the plant. With this review, we aim at providing an updated and comprehensive overview of the contributions in literature reporting computational, in vitro, pre-clinical and clinical data supporting the therapeutic applications of U. dioica. Experimental evidence shows that U. dioica constituents and extracts can provide neuroprotective effects by acting through a combination of different molecular mechanisms, that are discussed in the review. These findings could lay the basis for the identification and design of more effective tools against neurodegenerative diseases.

Mechanistic Insight into the Binding of Huperzine a with Human Transferrin: Computational, Spectroscopic and Calorimetric Approaches.

Huperzine A (HupA), an alkaloid found in the club moss Huperzia Serrata, has been in use for centuries in Chinese traditional medicine to treat dementia owing to its ability to inhibit the cholinergic enzyme acetylcholinesterase (AChE), thus acting as an acetylcholinesterase inhibitor (AChEI). An imbalance of metal ions in the brain is linked to Alzheimer's disease (AD) pathology. Transferrin (Tf) is a crucial player in iron homeostasis, thus highlighting its significance in AD. This study explores the plausible binding of HupA with Tf using molecular docking, molecular dynamics (MD) simulation, and free energy landscape (FEL) analyses. The docking results show that HupA binds to the functionally active region of Tf by forming three hydrogen bonds with Thr392, Glu394, and Ser688 and several hydrophobic interactions. The MD simulation analyses show that HupA binding is stable with Tf, causing minimal changes to the protein conformation. Moreover, principal component analysis (PCA) and FEL also depict the stable binding of HupA with Tf without any significant fluctuations. Further, fluorescence-based binding suggested excellent binding affinity of HupA with Tf affirming in silico observations. Isothermal titration calorimetry (ITC) advocated the spontaneous binding of HupA with Tf. This study provides an insight into the binding mechanism of HupA with Tf, and overall, the results show that HupA, after required experimentations, can be a better therapeutic agent for treating AD while targeting Tf.

Ethnobotanical Survey of Medicinal Plants Used in the Treatment of COVID-19 and Related Respiratory Infections in Ogbomosho South and North Local Government Areas, Oyo State, Nigeria.

Coronavirus disease 2019 (COVID-19) has extensively spread worldwide with high mortality. Besides vaccination, the United States Food and Drug Administration approved only one oral medication as a treatment. Medicinal plants with antiviral and immunomodulatory properties could be explored as complementary treatments for COVID-19. Ogbomosho is home to such plants traditionally used to treat infectious diseases in Nigeria, making it relevant in complementary medicine. An ethnobotanical survey of medicinal plants used to treat COVID-19 and related ailments, including cough and flu in Ogbomosho South and North Local Government Areas, Nigeria, was conducted using a semi-structured questionnaire. Information was obtained from 56 participants, consisting of different groups of individuals with native knowledge of medicinal plants, and ethnobotanical indices, including the frequency of citation (FC), relative frequency of citation (RFC), and fidelity level (FL) were computed. Twenty-six medicinal plants (17 families) were used to treat COVID-19, 31 (20 families) for cough, and 29 (19 families) for flu. The most cited plant was Zingiber officinale (FC = 10; RFC = 0.18; FL = 18%) for treating COVID-19, Citrus limon (FC = 13; RFC = 0.23; FL = 23%) for cough, and Zingiber officinale (FC = 9; RFC = 0.16; FL = 16%) for flu. Leaves were the most used plant part for treating COVID-19 and flu, while the bark was the most used for cough. Trees and herbs were the most cited plant growth forms. The herbal remedies were mostly prepared by decoction and infusion and were mainly administered orally. Further research should be conducted on the identified species for the scientific validation of their antiviral and immunomodulatory efficacies and safety for use.

Nanoparticles in clinical trials of COVID-19: An update.

Once the World Health Organization (WHO) declared the COVID-19 (Coronavirus Infectious Disease-19) outbreak to be pandemic, massive efforts have been launched by researchers around the globe to combat this emerging infectious disease. Strategies that must be investigated such as expanding testing capabilities, developing effective medicines, as well as developing safe and effective vaccines for COVID-19 disease that produce long-lasting immunity to human system. Now-a-days, bio-sensing, medication delivery, imaging, and antimicrobial treatment are just a few of the medical applications for nanoparticles (NPs). Since the early 1990s, nanoparticle drug delivery methods have been employed in clinical trials. Since then, the discipline of nanomedicine has evolved in tandem with expanding technological demands to better medicinal delivery. Newer generations of NPs have emerged in recent decades that are capable of performing additional delivery tasks, allowing for therapy via novel therapeutic modalities. Many of these next generation NPs and associated products have entered clinical trials and have been approved for diverse indications in the present clinical environment. For systemic applications, NPs or nanomedicine-based drug delivery systems have substantial benefits over their non-formulated and free drug counterparts. Nanoparticle systems, for example, are capable of delivering medicines and treating parts of the body that are inaccessible to existing delivery systems. As a result, NPs medication delivery is one of the most studied preclinical and clinical systems. NPs-based vaccines delivering SARS-CoV-2 antigens will play an increasingly important role in prolonging or improving COVID-19 vaccination outcomes. This review provides insights about employing NPs-based drug delivery systems for the treatment of COVID-19 to increase the bioavailability of current drugs, reducing their toxicity, and to increase their efficiency. This article also exhibits their capability and efficacy, and highlighting the future aspects and challenges on nanoparticle products in clinical trials of COVID-19.

Neuroinflammatory Markers: Key Indicators in the Pathology of Neurodegenerative Diseases.

Neuroinflammation, a protective response of the central nervous system (CNS), is associated with the pathogenesis of neurodegenerative diseases. The CNS is composed of neurons and glial cells consisting of microglia, oligodendrocytes, and astrocytes. Entry of any foreign pathogen activates the glial cells (astrocytes and microglia) and overactivation of these cells triggers the release of various neuroinflammatory markers (NMs), such as the tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-1ß (IL-10), nitric oxide (NO), and cyclooxygenase-2 (COX-2), among others. Various studies have shown the role of neuroinflammatory markers in the occurrence, diagnosis, and treatment of neurodegenerative diseases. These markers also trigger the formation of various other factors responsible for causing several neuronal diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), ischemia, and several others. This comprehensive review aims to reveal the mechanism of neuroinflammatory markers (NMs), which could cause different neurodegenerative disorders. Important NMs may represent pathophysiologic processes leading to the generation of neurodegenerative diseases. In addition, various molecular alterations related to neurodegenerative diseases are discussed. Identifying these NMs may assist in the early diagnosis and detection of therapeutic targets for treating various neurodegenerative diseases.

Superoxide dismutase: an updated review on its health benefits and industrial applications.

Many short-lived and highly reactive oxygen species, such as superoxide anion (O2-) and hydrogen peroxide (H2O2), are toxic or can create oxidative stress in cells, a response involved in the pathogenesis of numerous diseases depending on their concentration, location, and cellular conditions. Superoxide dismutase (SOD) activities as an endogenous and exogenous cell defense mechanism include the potential use in treating various diseases, improving the potential use in treating various diseases, and improving food-stuffs preparation dietary supplements human nutrition. Published work indicates that SOD regulates oxidative stress, lipid metabolism, inflammation, and oxidation in cells. It can prevent lipid peroxidation, the oxidation of low-density lipoprotein in macrophages, lipid droplets' formation, and the adhesion of inflammatory cells into endothelial monolayers. It also expresses antioxidant effects in numerous cancer-related processes. Additionally, different forms of SOD may also augment food processing and pharmaceutical applications, exhibit anticancer, antioxidant, and anti-inflammatory effects, and prevent arterial problems by protecting the proliferation of vascular smooth muscle cells. Many investigations in this review have reported the therapeutic ability and physiological importance of SOD. Because of their antioxidative effects, SODs are of great potential in the medicinal, cosmetic, food, farming and chemical industries. This review discusses the findings of human and animal studies that support the advantages of SOD enzyme regulations to reduce the formation of oxidative stress in various ways.

Nutritional and health beneficial properties of saffron (Crocus sativus L): a comprehensive review.

Saffron (Crocus sativus L., family Iridaceae) is used traditionally for medicinal purpose in Chinese, Ayurvedic, Persian and Unani medicines. The bioactive constituents such as apocarotenoids, monoterpenoids, flavonoids, phenolic acids and phytosterols are widely investigated in experimental and clinical studies for a wide range of therapeutic effects, especially on the nervous system. Some of the active constituents of saffron have high bioavailability and bioaccessibility and ability to pass the blood-brain barrier. Multiple preclinical and clinical studies have supported neuroprotective, anxiolytic, antidepressant, learning and memory-enhancing effect of saffron and its bioactive constituents (safranal, crocin, and picrocrocin). Thus, this plant and its active compounds could be a beneficial medicinal food ingredient in the formation of drugs targeting nervous system disorders. This review focuses on phytochemistry, bioaccessibility, bioavailability, and bioactivity of phytochemicals in saffron. Furthermore, the therapeutic effect of saffron against different nervous system disorders has also been discussed in detail.

Iturin: cyclic lipopeptide with multifunction biological potential.

Iturin, a metabolite produced by Bacillus subtilis, has a broad-spectrum antibacterial effect, and because they are secreted in the rhizosphere of plants, iturins are often mixed with many organic molecules. In recent years, people have improved their separation and purification methods but still cannot achieve simple and effective procedures, making Iturins an ideal biological control agent for insects and bacteria; commercial value still cannot be realized. With the in-depth studies of Iturins, its anti-cancer, hemolysis and other biological activities have gradually been discovered. This article reviews the branches of the Iturin family, structural features of these metabolite, separation and purification methods used for producing it, culture optimization, and various biological activities of the Iturin family, such as insecticidal, antibacterial, hemolytic and anticarcinogenic properties, among others have been summarized. Furthermore, this review revealed some commercial applications of Iturins and their relevance in research works. For example, in food packaging, clean water has good development potential.This can promote the commercial application of Iturins instead of other chemical and biological control agents that are environmentally friendly, pollution-free and have no side effects on humans. Furthermore, work documented anticancer, hemolytic and other biological activities of Iturin.

Garlic (Allium sativum L.): Its Chemistry, Nutritional Composition, Toxicity, and Anticancer Properties.

The current review discuss the chemistry, nutritional composition, toxicity, and biological functions of garlic and its bioactive compounds against various types of cancers via different anticancer mechanisms. Several scientific documents were found in reliable literature and searched in databases viz Science Direct, PubMed, Web of Science, Scopus, and Research Gate were carried out using keywords such as "garlic", "garlic bioactive compounds", "anticancer mechanisms of garlic", "nutritional composition of garlic", and others. Garlic contains several phytoconstituents with activities against cancer, and compounds such as diallyl trisulfide (DATS), allicin, and diallyl disulfide (DADS), diallyl sulfide (DAS), and allyl mercaptan (AM). The influence of numerous garlic- derived products, phytochemicals, and nanoformulations on the liver, oral, prostate, breast, gastric, colorectal, skin, and pancreatic cancers has been studied. Based on our search, the bioactive molecules in garlic were found to inhibit the various phases of cancer. Moreover, the compounds in this plant also abrogate the peroxidation of lipids, activity of nitric oxide synthase, epidermal growth factor (EGF) receptor, nuclear factor-kappa B (NF-κB), protein kinase C, and regulate cell cycle and survival signaling cascades. Hence, garlic and its bioactive molecules exhibit the aforementioned mechanistic actions, and thus, they could be used to inhibit the induction, development, and progression of cancer. The review describes the nutritional composition of garlic, its bioactive molecules, and nanoformulations against various types of cancers, as well as the potential for developing these agents as antitumor drugs.

Hepatoprotective Screening of Seriphidium kurramense (Qazilb.) Y.R. Ling.

Investigation on medicinal plants' therapeutic potential has gained substantial importance in the discovery of novel effective and safe therapeutic agents. The present study is aimed at investigating the hepatoprotective potential of Seriphidium kurramense methanolic extract (SKM) against carbon tetrachloride- (CCl4-) induced hepatotoxicity in rats. S. kurramense is one of the most imperative plants for its various pharmacological activities. Therefore, this study was aimed at evaluating the hepatoprotective potential against CCl4-induced liver toxicity. The serum samples were analyzed for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) together with the oxidative stress mediator levels as nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), reduced glutathione (GSH), and superoxide dismutase (SOD) as well as peroxidation and H2O2 activity. CCl4 administration resulted in an elevated free radical generation, altered liver marker (AST and ALT) enzymes, reduced antioxidant enzyme, and increased DNA damage. Methanolic extract of S. kurramense decreased CCl4-induced hepatotoxicity by increasing the antioxidant status and reducing H2O2 and nitrate content generation as well as reducing DNA damage. Additionally, SKM reversed the morphological alterations induced by CCl4 in the SKM-treated groups. These results demonstrated that SKM displayed hepatoprotective activity against CCl4-induced hepatic damage in experimental rats.

Cancer and diabetes: the interlinking metabolic pathways and repurposing actions of antidiabetic drugs.

Cancers are regarded as one of the main causes of death and result in high health burden worldwide. The management of cancer include chemotherapy, surgery and radiotherapy. The chemotherapy, which involves the use of chemical agents with cytotoxic actions is utilised as a single treatment or combined treatment. However, these managements of cancer such as chemotherapy poses some setbacks such as cytotoxicity on normal cells and the problem of anticancer drug resistance. Therefore, the use of other therapeutic agents such as antidiabetic drugs is one of the alternative interventions used in addressing some of the limitations in the use of anticancer agents. Antidiabetic drugs such as sulfonylureas, biguanides and thiazolidinediones showed beneficial and repurposing actions in the management of cancer, thus, the activities of these drugs against cancer is attributed to some of the metabolic links between the two disorders and these includes hyperglycaemia, hyperinsulinemia, inflammation, and oxidative stress as well as obesity. Furthermore, some studies showed that the use of antidiabetic drugs could serve as risk factors for the development of cancerous cells particularly pancreatic cancer. However, the beneficial role of these chemical agents overweighs their detrimental actions in cancer management. Hence, the present review indicates the metabolic links between cancer and diabetes and the mechanistic actions of antidiabetic drugs in the management of cancers.

Honokiol: A review of its pharmacological potential and therapeutic insights.

BACKGROUND: Honokiol is a pleiotropic compound which been isolated from Magnolia species such as Magnolia grandiflora and Magnolia dealbata. Magnolia species Magnolia grandiflora is used in traditional medicine for the treatment of various diseases. PURPOSE: The objective of this review is to summarize the pharmacological potential and therapeutic insights of honokiol. STUDY DESIGN: Honokiol has been specified as a novel alternative to treat various disorders such as liver cancer, neuroprotective, anti-spasmodic, antidepressant, anti-tumorigenic, antithrombotic, antimicrobial, analgesic properties and others. Therefore, this study designed to represent the in-depth therapeutic potential of honokiol. METHODS: Literature searches in electronic databases, such as Web of Science, Science Direct, PubMed, Google Scholar, and Scopus, were performed using the keywords 'Honokiol', 'Health Benefits' and 'Therapeutic Insights' as the keywords for primary searches and secondary search terms were used as follows: 'Anticancer', 'Oxidative Stress', 'Neuroprotective', 'Antimicrobial', 'Cardioprotection', 'Hepatoprotective', 'Anti-inflammatory', 'Arthritis', 'Reproductive Disorders'. RESULTS: This promising bioactive compound presented an wide range of therapeutic and biological activities which include liver cancer, neuroprotective, anti-spasmodic, antidepressant, anti-tumorigenic, antithrombotic, antimicrobial, analgesic properties, and others. Its pharmacokinetics has been established in experimental animals, while in humans, this is still speculative. Some of its mechanism for exhibiting its pharmacological effects includes apoptosis of diseased cells, reduction in the expression of defective proteins like P-glycoproteins, inhibition of oxidative stress, suppression of pro-inflammatory cytokines (TNF-α, IL-10 and IL-6), amelioration of impaired hepatic enzymes and reversal of morphological alterations, among others. CONCLUSION: All these actions displayed by this novel compound could make it serve as a lead in the formulation of drugs with higher efficacy and negligible side effects utilized in the treatment of several human diseases.

Diversity, molecular mechanisms and structure-activity relationships of marine protease inhibitors-A review.

Marine habitats are well-known for their diverse life forms that are potential sources of novel bioactive compounds. Evidence from existing studies suggests that these compounds contribute significantly to the field of pharmaceuticals, nutraceuticals, and cosmeceuticals. The isolation of natural compounds from a marine environment with protease inhibitory activity has gained importance due to drug discovery potential. Despite the increasing research endeavours focusing on protease inhibitors' design and characterization, many of these compounds have failed to reach final phases of clinical trials. As a result, the search for new sources for the development of protease inhibitors remains pertinent. This review focuses on the diverse marine protease inhibitors and their structure-activity relationships. Furthermore, the potential of marine protease inhibitors in drug discovery and molecular mechanism inhibitor binding are critically discussed.

COVID-19 Pandemic: Epidemiology, Etiology, Conventional and Non-Conventional Therapies.

Coronavirus disease 2019 (COVID-19), which reported in an outbreak in 2019 in Wuhan, Hubei province, China, is caused by the SARS-CoV-2 virus. The virus belongs to the beta-coronavirus class, along with the Middle East Respiratory Syndrome coronavirus and Severe Acute Respiratory Syndrome coronavirus. Interestingly, the virus binds with angiotensin-converting enzyme-2 found in host cells, through the spike (S) protein that exists on its surface. This binding causes the entry of the virus into cells of the host organism. The actual mechanism used by the COVID-19 virus to induce disease is still speculative. A total of 44,322,504 cases, a 1,173,189 death toll and 32,486,703 recovery cases have been reported in 217 countries globally as of 28 October 2020. Symptoms from the infection of the virus include chest pain, fever, fatigue, nausea, and others. Acute respiratory stress syndrome, arrhythmia, and shock are some of the chronic manifestations recorded in severe COVID-19. Transmission is majorly by individual-to-individual through coughing, sneezing, etc. The lack of knowledge regarding the mechanism of and immune response to the virus has posed a challenge in the development of a novel drug and vaccine. Currently, treatment of the disease involves the use of anti-viral medications such as lopinavir, remdesivir, and other drugs. These drugs show some efficacy in the management of COVID-19. Studies are still on-going for the development of an ideal and novel drug for treatment. In terms of natural product intervention, Traditional Chinese Medicines (TCM) have been employed to alleviate the clinical manifestation and severity of the disease and have shown some efficacy. This review presents an updated detailed overview of COVID-19 and the virus, concerning its structure, epidemiology, symptoms and transmission, immune responses, and current interventions, and highlights the potential of TCM. It is anticipated that this review will further add to the understanding of COVID-19 and the virus, hence opening new research perspectives.