Sesamol as a potent anticancer compound: from chemistry to cellular interactions.

Sesamol (SM), a well-known component isolated from sesame seeds (Sesamum indicum), used in traditional medicines in treating numerous ailments. However, numerous molecular investigations revealed the various mechanisms behind its activity, emphasizing its antiproliferative, anti-inflammatory, and apoptosis-inducing properties, preventing cancer cell spread to distant organs. In several cells derived from various malignant tissues, SM-regulated signal transduction pathways and cellular targets have been identified. This review paper comprehensively describes the anticancer properties of SM and SM-viable anticancer drugs. Additionally, the interactions of this natural substance with standard anticancer drugs are examined, and the benefits of using nanotechnology in SM applications are explored. This makes SM a prime example of how ethnopharmacological knowledge can be applied to the development of contemporary drugs.

The Pharmacological Implications of Flavopiridol: An Updated Overview.

Flavopiridol is a flavone synthesized from the natural product rohitukine, which is derived from an Indian medicinal plant, namely Dysoxylum binectariferum Hiern. A deeper understanding of the biological mechanisms by which such molecules act may allow scientists to develop effective therapeutic strategies against a variety of life-threatening diseases, such as cancer, viruses, fungal infections, parasites, and neurodegenerative diseases. Mechanistic insight of flavopiridol reveals its potential for kinase inhibitory activity of CDKs (cyclin-dependent kinases) and other kinases, leading to the inhibition of various processes, including cell cycle progression, apoptosis, tumor proliferation, angiogenesis, tumor metastasis, and the inflammation process. The synthetic derivatives of flavopiridol have overcome a few demerits of its parent compound. Moreover, these derivatives have much improved CDK-inhibitory activity and therapeutic abilities for treating severe human diseases. It appears that flavopiridol has potential as a candidate for the formulation of an integrated strategy to combat and alleviate human diseases. This review article aims to unravel the potential therapeutic effectiveness of flavopiridol and its possible mechanism of action.

Comprehensive overview of 2022 human monkeypox outbreak and its pathology, prevention, and treatment: A strategy for disease control.

The 2022 Monkeypox virus, an evolved DNA strain originating in Africa, exhibits heightened human-to-human transmissibility and potential animal transmission. Its host remains unidentified. While its initial slow transmission rate restrained global impact, 2022 saw a surge in cases, causing widespread concern in over 103 countries by September. This virus's distinctive human-to-human transmission marks a crucial shift, demanding a prompt revaluation of containment strategies. However, the host source for this shift requires urgent research attention. Regrettably, no universal preventive or curative methods have emerged for this evolved virus. Repurposed from smallpox vaccines, only some vaccinations offer a partial defense. Solely one therapeutic drug is available. The article's essence is to provide a comprehensive grasp of the virus's epidemiology, morphology, immune invasion mechanisms, and existing preventive and treatment measures. This knowledge equips researchers to devise strategies against its spread and potential public health implications.

Wogonin, as a potent anticancer compound: From chemistry to cellular interactions.

Chinese native medicine Scutellaria baicalensis Georgi, also referred to as Chinese skullcap or Huang-Qin, is frequently used to treat cancer, viral infections, and seizures. This plant's abundance of flavones (wogonoside) and their related aglycones (wogonin) is responsible for many of its pharmacologic effects. A significant ingredient in S. baicalensis that has been the subject of the most research is wogonin. Numerous preclinical investigations revealed that wogonin suppresses tumor growth by cell cycle arrest, stimulating cell death and preventing metastasis. This review focuses on a complete overview of published reports that suggest chemopreventive action of wogonin and the mechanistic insights behind these neoplastic activities. It also emphasizes the synergistic improvements made by wogonin in chemoprevention. The factual data in this mini-review stimulate additional research on chemistry and toxicological profile of wogonin to confirm its safety issues. This review will encourage researchers to generalize the merits of wogonin to be used as potential compound for cancer treatment.

Genistein: a promising modulator of apoptosis and survival signaling in cancer.

Genistein, a commonly occurring isoflavone, has recently gained popularity owing to its ever-expanding spectrum of pharmacological benefits. In addition to health benefits such as improved bone health and reduced postmenopausal complications owing to its phytoestrogen properties, it has been widely evaluated for its anti-cancer potential. Several studies have established the potential for its usage in the management of breast, lung, and prostate cancers, and its usage has significantly evolved from early applications in traditional systems of medicine. This review offers an insight into its current status of usage, the chemistry, and pharmacokinetics of the molecule, an exploration of its apoptotic mechanisms in cancer management, and opportunities for synergism to improve therapeutic outcomes. In addition to this, the authors have presented an overview of recent clinical trials, to offer an understanding of contemporary studies and explore prospects for a greater number of focused trials, moving forward. Advancements in the application of nanotechnology as a strategy to improve safety and efficacy have also been highlighted, with a brief discussion of results from safety and toxicology studies.

Therapeutic potential of flavonoids in the management of obesity-induced Alzheimer's disease: an overview of preclinical and clinical studies.

Obesity is a global epidemic that affects people of all ages, genders, and backgrounds. It can lead to a plethora of disorders, including diabetes mellitus, renal dysfunction, musculoskeletal problems, metabolic syndrome, cardiovascular, and neurodegenerative abnormalities. Obesity has also been linked to neurological diseases such as cognitive decline, dementia, and Alzheimer's disease (AD), caused by oxidative stress, pro-inflammatory cytokines, and the production of reactive oxygen free radicals (ROS). Secretion of insulin hormone is impaired in obese people, leading to hyperglycaemia and increased accumulation of amyloid-ß in the brain. Acetylcholine, a key neurotransmitter necessary for forming new neuronal connections in the brain, decreases in AD patients. To alleviate acetylcholine deficiency, researchers have proposed dietary interventions and adjuvant therapies that enhance the production of acetylcholine and assist in the management of AD patients. Such measures include dietary intervention with antioxidant and anti-inflammatory flavonoid-rich diets, which have been found to bind to tau receptors, reduce gliosis, and reduce neuroinflammatory markers in animal models. Furthermore, flavonoids like curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, and oleocanthal have shown to cause significant reductions in interleukin-1ß, increase BDNF levels, stimulate hippocampal neurogenesis and synapse formation, and ultimately prevent the loss of neurons in the brain. Thus, flavonoid-rich nutraceuticals can be a potential cost-effective therapeutic option for treating obesity-induced AD, but further well-designed, randomized, and placebo-controlled clinical studies are needed to assess their optimal dosages, efficacy, and long-term safety of flavonoids in humans. The main objectives of this review are to underscore the therapeutic potential of different nutraceuticals containing flavonoids that can be added in the daily diet of AD patients to enhance acetylcholine and reduce neuronal inflammation in the brain.

Role of polyphenolic compounds and their nanoformulations: a comprehensive review on cross-talk between chronic kidney and cardiovascular diseases.

Chronic kidney disease (CKD) affects a huge portion of the world's population and frequently leads to cardiovascular diseases (CVDs). It might be because of common risk factors between chronic kidney disease and cardiovascular diseases. Renal dysfunction caused by chronic kidney disease creates oxidative stress which in turn leads to cardiovascular diseases. Oxidative stress causes endothelial dysfunction and inflammation in heart which results in atherosclerosis. It ends in clogging of veins and arteries that causes cardiac stroke and myocardial infarction. To develop an innovative therapeutic approach and new drugs to treat these diseases, it is important to understand the pathophysiological mechanism behind the CKD and CVDs and their interrelationship. Natural phytoconstituents of plants such as polyphenolic compounds are well known for their medicinal value. Polyphenols are plant secondary metabolites with immense antioxidant properties, which can protect from free radical damage. Nowadays, polyphenols are generating a lot of buzz in the scientific community because of their potential health benefits especially in the case of heart and kidney diseases. This review provides a detailed account of the pathophysiological link between CKD and CVDs and the pharmacological potential of polyphenols and their nanoformulations in promoting cardiovascular and renal health.

Resveratrol and Its Role in the Management of B-Cell Malignancies-A Recent Update.

The growing incidence of B cell malignancies globally has prompted research on the pharmacological properties of phytoconstituents in cancer management. Resveratrol, a polyphenolic stilbenoid widely found in nature, has been explored for its anti-inflammatory and antioxidant properties, and promising results from different pre-clinical studies have indicated its potential for management of B cell malignancies. However, these claims must be substantiated by a greater number of clinical trials in diverse populations, in order to establish its safety and efficacy profile. In addition to this, there is a need to explore nanodelivery of this agent, owing to its poor solubility, which in turn may impact its bioavailability. This review aims to offer an overview of the occurrence and pathogenesis of B cell malignancies with a special focus on the inflammatory pathways involved, the mechanism of actions of resveratrol and its pharmacokinetic profile, results from pre-clinical and clinical studies, as well as an overview of the marketed formulations. The authors have also presented their opinion on the various challenges associated with the clinical development of resveratrol and future perspectives regarding therapeutic applications of this agent.

Anticancer potential of oroxylin A: from mechanistic insight to synergistic perspectives.

Oroxylin A (OA), a well-known constituent of the root of Scutellariae plants, has been used in ethnomedicine already for centuries in treating various neoplastic disorders. However, only recent molecular studies have revealed the different mechanisms behind its action, demonstrating antiproliferative, anti-inflammatory, and proapoptotic effects, restricting also the spread of cancer cells to distant organs. A variety of cellular targets and modulated signal transduction pathways regulated by OA have been determined in diverse cells derived from different malignant tissues. In this review article, these anticancer activities are thoroughly described, representing OA as a potential lead structure for the design of novel more potent anticancer medicines. In addition, co-effects of this natural compound with conventional anticancer agents are analyzed and the advantages provided by nanotechnological methods for more efficient application of OA are discussed. In this way, OA might represent an excellent example of using ethnopharmacological knowledge for designing modern medicines.

Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects.

Cancer is a highly lethal disease, and its incidence has rapidly increased worldwide over the past few decades. Although chemotherapeutics and surgery are widely used in clinical settings, they are often insufficient to provide the cure for cancer patients. Hence, more effective treatment options are highly needed. Although licorice has been used as a medicinal herb since ancient times, the knowledge about molecular mechanisms behind its diverse bioactivities is still rather new. In this review article, different anticancer properties (antiproliferative, antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory effects) of various bioactive constituents of licorice (Glycyrrhiza glabra L.) are thoroughly described. Multiple licorice constituents have been shown to bind to and inhibit the activities of various cellular targets, including B-cell lymphoma 2, cyclin-dependent kinase 2, phosphatidylinositol 3-kinase, c-Jun N-terminal kinases, mammalian target of rapamycin, nuclear factor-κB, signal transducer and activator of transcription 3, vascular endothelial growth factor, and matrix metalloproteinase-3, resulting in reduced carcinogenesis in several in vitro and in vivo models with no evident toxicity. Emerging evidence is bringing forth licorice as an anticancer agent as well as bottlenecks in its potential clinical application. It is expected that overcoming toxicity-related obstacles by using novel nanotechnological methods might importantly facilitate the use of anticancer properties of licorice-derived phytochemicals in the future. Therefore, anticancer studies with licorice components must be continued. Overall, licorice could be a natural alternative to the present medication for eradicating new emergent illnesses while having just minor side effects.

Onosma L. as a source of anticancer agents: phytochemistry to mechanistic insight.

Onosma (O.) is a genus of perennial flowering plants in the family Boraginaceae with approximately 250 species widely dispersed in temperate, tropical, and subtropical areas. It is traditionally used to treat rheumatism, fever, asthma, stomach irritation, and inflammatory ailments. The bioactive constituents present in the genus O. include benzoquinones, naphthazarins, alkaloids, phenolic, naphthoquinones, and flavonoids whereas shikonins and onosmins are the most significant. The review compiled contemporary research on O. L., including its distribution, morphology, traditional applications, phytochemistry, ethnopharmacology, and toxicology. This review also highlights a few critical challenges and possible future directions for O. L. research. Modern research has demonstrated a wide range of pharmacological effects of different species of O. L., including anti-diabetic, anticancer, anti-inflammatory, and cardiovascular protective. However, the studies on the O. genus are still not fully explored, therefore, researchers need to discover novel products with their toxicity studies, molecular mechanism, and associated side effects. Future exploration of potent constituents from this genus and clinical trials are required to explore its pharmacological importance.

The effect of metal-containing nanoparticles on the health, performance and production of livestock animals and poultry.

The application of high doses of mineral feed additives in the form of inorganic salts increases the growth performance of animals, but at the same, due to their low bioavailability, can contaminate the environment. Therefore, there is a need to find a replacement of administering high doses of minerals with an equally effective alternative. The application of lower doses of metal-containing nanoparticles with the same effect on animal production could be a potential solution. In the present review, zinc, silver, copper, gold, selenium, and calcium nanoparticles are discussed as potential feed additives for animals. Production of nanoparticles under laboratory conditions using traditional chemical and physical methods as well as green and sustainable methods - biosynthesis has been described. Special attention has been paid to the biological properties of nanoparticles, as well as their effect on animal health and performance. Nano-minerals supplemented to animal feed (poultry, pigs, ruminants, rabbits) acting as growth-promoting, immune-stimulating and antimicrobial agents have been highlighted. Metal nanoparticles are known to exert a positive effect on animal performance, productivity, carcass traits through blood homeostasis maintenance, intestinal microflora, oxidative damage prevention, enhancement of immune responses, etc. Metal-containing nanoparticles can also be a solution for nutrient deficiencies in animals (higher bioavailability and absorption) and can enrich animal products with microelements like meat, milk, or eggs. Metal-containing nanoparticles are proposed to partially replace inorganic salts as feed additives. However, issues related to their potential toxicity and safety to livestock animals, poultry, humans, and the environment should be carefully investigated.

Natural product-based nanoformulations for cancer therapy: Opportunities and challenges.

Application of natural product-based nanoformulations for the treatment of different human diseases, such as cancer, is an emerging field. The conventional cancer therapeutic modalities, including surgery, chemotherapy, immunotherapy, radiotherapy has limited achievements. A larger number of drawbacks are associated with these therapies, including damage to proliferating healthy tissues, structural deformities, systemic toxicity, long-term side effects, resistance to the drug by tumor cells, and psychological problems. The advent of nanotechnology in cancer therapeutics is recent; however, it has progressed and transformed the field of cancer treatment at a rapid rate. Nanotherapeutics have promisingly overcome the limitations of conventional drug delivery system, i.e., low aqueous solubility, low bioavailability, multidrug resistance, and non-specificity. Specifically, natural product-based nanoformulations are being intentionally studied in different model systems. Where it is found that these nanoformulations has more proximity and reduced side effects. The nanoparticles can specifically target tumor cells, enhancing the specificity and efficacy of cancer therapeutic modalities which in turn improves patient response and survival. The integration of phytotherapy and nanotechnology in the clinical setting may improve pharmacological response and better clinical outcome of patients.

Therapeutic Applications of Human and Bovine Colostrum in the Treatment of Gastrointestinal Diseases and Distinctive Cancer Types: The Current Evidence.

The incidence of gastrointestinal disorders (GID) and cancers is escalating all over the world. Limited consumption of colostrum by newborns not only weakens the immune system but also predisposes infants to microbial infections. Colostrum is nature's perfect food, sometimes referred to as the 'elixir of life'. Breast-fed infants have a lower incidence of GI tract infections than infants fed formula or cow's milk. As per WHO statistics, cancer is the most prevalent disease globally and causes 9.6 million deaths worldwide. The current strategies for treating cancer include chemotherapy, radiation, and surgery. However, chemotherapy and radiation exposure are usually associated with serious long-term side effects and deterioration in the quality of life (QOL) of patients. Furthermore, the hospitalization and medication costs for treating cancers are exorbitant and impose high economic burden on healthcare systems. People are desperately looking for cost-effective and affordable alternative therapies for treating GID and cancers. Therefore, there is an urgent need for clinically evaluating the anticancer compounds isolated from plants and animals. Such therapies would not only be economical and have fewer side effects, but also help to improve the QOL of cancer patients. Recently, bovine colostrum (BC) has caught the attention of many investigators to explore its anticancer potential in humans. BC impregnated dressings are highly effective in treating chronic wounds and diabetic foot ulcer. BC is rich in lactoferrin, a glycoprotein with strong antioxidant, anti-inflammatory, anti-cancer, and anti-microbial properties. Intravaginal application of BC tablets is effective in causing the regression of low-grade cervical intraepithelial neoplasia. The underlying mechanisms of BC at cellular, genetic, and molecular levels remain to be ascertained. Oral BC supplement is well-tolerated, but some people may experience problems such as flatulence and nausea. Well-designed, randomized, placebo-controlled, clinical trials are needed to access the therapeutic potential, long-term safety, and optimal doses of BC products. This review is aimed to highlight the anticancer potential of BC and its components, and the therapeutic applications of BC supplements in treating gastrointestinal diseases in children and adults. We also discuss the health promotion benefits and therapeutic potential of BC nutraceuticals in reducing the incidence of non-communicable diseases.

Ayurveda and Allopathic Therapeutic Strategies in Coronavirus Pandemic Treatment 2020.

Purpose of Review: In the last month of 2019, i.e., December, COVID-19 hit Wuhan city in China. Since then, it has infected more than 210 countries and nearly about 33.4 million people with one million deaths globally. It is a viral disease with flu-like symptoms; hence, prevention and management is the best option to be adopted for its cure. Recent Findings: Many healthcare systems, scientists, and researchers are fighting for the cure of this pandemic. Ayurvedic and allopathic treatments have been studied extensively and approached for the cure of COVID-19. In addition to ayurvedic treatments, the Ministry of Ayush, India, has also recommended many remedies to boost up immunity. Allopathic studies involved several antiviral drugs which were used in different combinations for the treatment of COVID-19. Summary: Comparative analysis of Ayurveda and allopathic treatment strategies were carried out in the present study. Depending upon the patient's conditions and symptoms, Ayurveda is useful for the treatment of COVID-19. Allopathic treatments inhibit viral infection by targeting majorly endocytosis, and angiotensin-converting enzyme (Ace) receptor signaling. In this article, we summarize different ayurvedic and allopathic medicines and treatment strategies which have been used for the treatment of COVID-19, a global pandemic.

Antioxidant Phytoconstituents From Onosma bracteata Wall. (Boraginaceae) Ameliorate the CCl4 Induced Hepatic Damage: In Vivo Study in Male Wistar Rats.

Onosma bracteata Wall. (Boraginaceae) is a highly valuable medicinal herb that is used for the treatment of fever, bronchitis, asthma, rheumatism, stomach irritation, and other inflammatory disorders. The present study aims to explore the hepatoprotective potential of ethanolic extract (Obeth) from O. bracteata aerial parts against carbon tetrachloride (CCl4) which causes hepatic damage in the male Wistar rats. Obeth showed effective radical quenching activity with an EC50 of 115.14 and 199.33 µg/mL in superoxide radical scavenging and lipid peroxidation analyses respectively along with plasmid DNA protective potential in plasmid nicking assay. The Obeth modulated mutagenicity of 2 Aminofluorine (2AF) in the pre-incubation mode of investigation (EC50 10.48 µg/0.1 mL/plate) in TA100 strain of Salmonella typhimurium. In in vivo studies, pretreatment of Obeth (50, 100, and 200 mg/kg) had the potential to normalize the biochemical markers aggravated by CCl4 (1mL/kg b.wt.) including liver antioxidative enzymes. Histopathological analysis also revealed the restoration of CCl4-induced liver histopathological alterations. Immunohistochemical studies showed that the treatment of Obeth downregulated the expression levels of p53 and cyclin D in hepatocytes. and downregulation in the Western blotting analysis revealed the downregulation of p-NF-kB, COX-2, and p53. HPLC data analysis showed the supremacy of major compounds namely, catechin, kaempferol, epicatechin, and Onosmin A in Obeth. The present investigation establishes the hepatoprotective and chemopreventive potential of O. bracteata against CCl4-induced hepatotoxicity via antioxidant defense system and modulation of the expression of proteins associated with the process of carcinogenesis in hepatic cells.

Molecular Mechanisms of Action of Tocotrienols in Cancer: Recent Trends and Advancements.

Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only because of continual aging and growth in global population, but also due to the adaptation of Western lifestyle behaviours, including intake of high fat diets and low physical activity. Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas. These findings, together with the reported safety profile of tocotrienols in healthy human volunteers, encourage further studies on the potential application of these compounds in cancer prevention and treatment. In the current article, detailed information about the potential molecular mechanisms of actions of tocotrienols in different cancer models has been presented and the possible effects of these vitamin E analogues on various important cancer hallmarks, i.e., cellular proliferation, apoptosis, angiogenesis, metastasis, and inflammation have been briefly analyzed.

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy.

A wide variety of chronic diseases, such as neurodegenerative and cardiovascular disorders, diabetes mellitus, osteoarthtitis, obesity and various cancers, are now being treated with cost effective phytomedicines. Since synthetic medicines are very expensive, concerted efforts are being made in developing and poor countries to discover cost effective medicines for the treatment of non-communicable diseases (NCDs). Understanding the underlying mechanisms of bioactive medicines from natural sources would not only open incipient avenues for the scientific community and pharmaceutical industry to discover new drug molecules for the therapy of NCDs, but also help to garner knowledge for alternative therapeutic approaches for the management of chronic diseases. Fisetin is a polyphenolic molecule of flavonoids class, and belongs to the bioactive phytochemicals that have potential to block multiple signaling pathways associated with NCDs such as cell division, angiogenesis, metastasis, oxidative stress, and inflammation. The emerging evidence suggests that fisetin may be useful for the prevention and management of several types of human malignancies. Efforts are being made to enhance the bioavailability of fisetin after oral administration to prevent and/or treat cancer of the liver, breast, ovary and other organs. The intent of this review is to highlight the in vitro and in vivo activities of fisetin and to provide up-to-date information about the molecular interactions of fisetin with its cellular targets involved in cancer initiation, promotion and progression as well as to focus on strategies underway to increase the bioavailability and reduce the risk of deleterious effects, if any, associated with fisetin administration.

Molecular targets of gambogic acid in cancer: recent trends and advancements.

Natural compounds have been known as biosafety agents for their significant clinical and biological activity against dreadful diseases, including cancer, cardiovascular, and neurodegenerative disorders. Gambogic acid (GA), a naturally occurring xanthone-based moiety, reported from Garcinia hanburyi tree, is known to perform numerous intracellular and extracellular actions, including programmed cell death, autophagy, cell cycle arrest, antiangiogenesis, antimetastatic, and anti-inflammatory activities. In addition, GA-based synergistic approaches have been proven to enhance the healing strength of existing chemotherapeutic agents along with lesser side effects. The present review uncovers the bio-therapeutic potential of gambogic acid along with the possible mechanistic interactions of GA with its recognized cellular targets.

Molecular mechanisms underlying chemopreventive potential of curcumin: Current challenges and future perspectives.

In recent years, natural compounds have received considerable attention in preventing and curing most dreadful diseases including cancer. The reason behind the use of natural compounds in chemoprevention is associated with fewer numbers of side effects than conventional chemotherapeutics. Curcumin (diferuloylmethane, PubMed CID: 969516), a naturally occurring polyphenol, is derived from turmeric, which is used as a common Indian spice. It governs numerous intracellular targets, including proteins involved in antioxidant response, immune response, apoptosis, cell cycle regulation and tumor progression. A huge mass of available studies strongly supports the use of Curcumin as a chemopreventive drug. However, the main challenge encountered is the low bioavailability of Curcumin. This extensive review covers various therapeutic interactions of Curcumin with its recognized cellular targets involved in cancer treatment, strategies to overcome the bioavailability issue and adverse effects associated with Curcumin consumption.