PX-12 synergistically enhances the therapeutic efficacy of vorinostat under hypoxic tumor microenvironment in oral squamous cell carcinoma in vitro.

Hypoxia is a characteristic feature of solid tumors, including oral squamous cell carcinoma (OSCC), which causes therapeutic resistance. The hypoxia-inducible factor 1-alpha (HIF-1α) is a key regulator of hypoxic tumor microenvironment (TME) and a promising therapeutic target against solid tumors. Among other HIF-1α inhibitors, vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor (HDACi) targeting the stability of HIF-1α, and PX-12 (1-methylpropyl 2-imidazolyl disulfide) is a thioredoxin-1 (Trx-1) inhibitor preventing accumulation of HIF-1α. HDACis are effective against cancers; however, they are accompanied by several side effects along with an emerging resistance against it. This can be overcome by using HDACi in a combination regimen with Trx-1 inhibitor, as their inhibitory mechanisms are interconnected. HDACis inhibit Trx-1, leading to an increase in the production of reactive oxygen species (ROS) and inducing apoptosis in cancer cells; thus, the efficacy of HDACi can be elevated by using a Trx-1 inhibitor. In this study, we have tested the EC50 (half maximal effective concentration) doses of vorinostat and PX-12 on CAL-27 (an OSCC cell line) under both normoxic and hypoxic conditions. The combined EC50 dose of vorinostat and PX-12 is significantly reduced under hypoxia, and the interaction of PX-12 with vorinostat was evaluated by combination index (CI). An additive interaction between vorinostat and PX-12 was observed in normoxia, while a synergistic interaction was observed under hypoxia. This study provides the first evidence for vorinostat and PX-12 synergism under hypoxic TME, at the same time highlighting the therapeutically effective combination of vorinostat and PX-12 against OSCC in vitro.

Arctium lappa (Burdock): Insights from ethnopharmacology potential, chemical constituents, clinical studies, pharmacological utility and nanomedicine.

Arctium lappa L. is a medicinal edible homologous plant, commonly known as burdock or bardana, which belongs to the Asteraceae family. It is widely distributed throughout Northern Asia, Europe, and North America and has been utilized for hundreds of years. The roots, fruits, seeds, and leaves of A. lappa have been extensively used in traditional Chinese Medicine (TCM). A. lappa has attracted a great deal of attention due to its possession of highly recognized bioactive metabolites with significant therapeutic potential. Numerous pharmacological effects have been demonstrated in vitro and in vivo by A. lappa and its bioactive metabolites, including antimicrobial, anti-obesity, antioxidant, anticancer, anti-inflammatory, anti-diabetic, anti-allergic, antiviral, gastroprotective, hepatoprotective, and neuroprotective activities. Additionally, A. lappa has demonstrated considerable clinical efficacies and valuable applications in nanomedicine. Collectively, this review covers the properties of A. lappa and its bioactive metabolites, ethnopharmacology aspects, pharmacological effects, clinical trials, and applications in the field of nanomedicine. Hence, a significant attention should be paid to clinical trials and industrial applications of this plant with particular emphasis, on drug discovery and nanotechnology.

Saudi Arabian Plants: A Powerful Weapon against a Plethora of Diseases.

The kingdom of Saudi Arabia (SA) ranks fifth in Asia in terms of area. It features broad biodiversity, including interesting flora, and was the historical origin of Islam. It is endowed with a large variety of plants, including many herbs, shrubs, and trees. Many of these plants have a long history of use in traditional medicine. The aim of this review is to evaluate the present knowledge on the plants growing in SA regarding their pharmacological and biological activities and the identification of their bioactive compounds to determine which plants could be of interest for further studies. A systematic summary of the plants' history, distribution, various pharmacological activities, bioactive compounds, and clinical trials are presented in this paper to facilitate future exploration of their therapeutic potential. The literature was obtained from several scientific search engines, including Sci-Finder, PubMed, Web of Science, Google Scholar, Scopus, MDPI, Wiley publications, and Springer Link. Plant names and their synonyms were validated by 'The Plant List' on 1 October 2021. SA is home to approximately 2247 plant species, including native and introduced plants that belong to 142 families and 837 genera. It shares the flora of three continents, with many unique features due to its extreme climate and geographical and geological conditions. As plants remain the leading supplier of new therapeutic agents to treat various ailments, Saudi Arabian plants may play a significant role in the fight against cancer, inflammation, and antibiotic-resistant bacteria. To date, 102 active compounds have been identified in plants from different sites in SA. Plants from the western and southwestern regions have been evaluated for various biological activities, including antioxidant, anti-cancer, antimicrobial, antimalarial, anti-inflammatory, anti-glycation, and cytotoxic activities. The aerial parts of the plants, especially the leaves, have yielded most of the bioactive compounds. Most bioactivity tests involve in vitro assessments for the inhibition of the growth of tumour cell lines, and several compounds with in vitro antitumour activity have been reported. More in-depth studies to evaluate the mode of action of the compounds are necessary to pave the way for clinical trials. Ecological and taxonomical studies are needed to evaluate the flora of SA, and a plan for the conservation of wild plants should be implemented, including the management of the protection of endemic plants.

Insights into the Role of Natural Products in the Control of the Honey Bee Gut Parasite (Nosema spp.).

The honey bee is an important economic insect due to its role in pollinating many agricultural plants. Unfortunately, bees are susceptible to many pathogens, including pests, parasites, bacteria, and viruses, most of which exert a destructive impact on thousands of colonies. The occurrence of resistance to the therapeutic substances used against these organisms is rising, and the residue from these chemicals may accumulate in honey bee products, subsequently affecting the human health. There is current advice to avoid the use of antibiotics, antifungals, antivirals, and other drugs in bees, and therefore, it is necessary to develop alternative strategies for the treatment of bee diseases. In this context, the impact of nosema diseases (nosemosis) on bee health and the negative insults of existing drugs are discussed. Moreover, attempts to combat nosema through the use of alternative compounds, including essential oils, plant extracts, and microbes in vitro and in vivo, are documented.

Chemistry and the Potential Antiviral, Anticancer, and Anti-Inflammatory Activities of Cardiotonic Steroids Derived from Toads.

Cardiotonic steroids (CTS) were first documented by ancient Egyptians more than 3000 years ago. Cardiotonic steroids are a group of steroid hormones that circulate in the blood of amphibians and toads and can also be extracted from natural products such as plants, herbs, and marines. It is well known that cardiotonic steroids reveal effects against congestive heart failure and atrial fibrillation; therefore, the term "cardiotonic" has been coined. Cardiotonic steroids are divided into two distinct groups: cardenolides (plant-derived) and bufadienolides (mainly of animal origin). Cardenolides have an unsaturated five-membered lactone ring attached to the steroid nucleus at position 17; bufadienolides have a doubly unsaturated six-membered lactone ring. Cancer is a leading cause of mortality in humans all over the world. In 2040, the global cancer load is expected to be 28.4 million cases, which would be a 47% increase from 2020. Moreover, viruses and inflammations also have a very nebative impact on human health and lead to mortality. In the current review, we focus on the chemistry, antiviral and anti-cancer activities of cardiotonic steroids from the naturally derived (toads) venom to combat these chronic devastating health problems. The databases of different research engines (Google Scholar, PubMed, Science Direct, and Sci-Finder) were screened using different combinations of the following terms: "cardiotonic steroids", "anti-inflammatory", "antiviral", "anticancer", "toad venom", "bufadienolides", and "poison chemical composition". Various cardiotonic steroids were isolated from diverse toad species and exhibited superior anti-inflammatory, anticancer, and antiviral activities in in vivo and in vitro models such as marinobufagenin, gammabufotalin, resibufogenin, and bufalin. These steroids are especially difficult to identify. However, several compounds and their bioactivities were identified by using different molecular and biotechnological techniques. Biotechnology is a new tool to fully or partially generate upscaled quantities of natural products, which are otherwise only available at trace amounts in organisms.

Bee Stressors from an Immunological Perspective and Strategies to Improve Bee Health.

Honeybees are the most prevalent insect pollinator species; they pollinate a wide range of crops. Colony collapse disorder (CCD), which is caused by a variety of biotic and abiotic factors, incurs high economic/ecological loss. Despite extensive research to identify and study the various ecological stressors such as microbial infections, exposure to pesticides, loss of habitat, and improper beekeeping practices that are claimed to cause these declines, the deep understanding of the observed losses of these important insects is still missing. Honeybees have an innate immune system, which includes physical barriers and cellular and humeral responses to defend against pathogens and parasites. Exposure to various stressors may affect this system and the health of individual bees and colonies. This review summarizes and discusses the composition of the honeybee immune system and the consequences of exposure to stressors, individually or in combinations, on honeybee immune competence. In addition, we discuss the relationship between bee nutrition and immunity. Nutrition and phytochemicals were highlighted as the factors with a high impact on honeybee immunity.

Cosmetic Applications of Bee Venom.

Bee venom (BV) is a typical toxin secreted by stingers of honeybee workers. BV and BV therapy have long been attractive to different cultures, with extensive studies during recent decades. Nowadays, BV is applied to combat several skin diseases, such as atopic dermatitis, acne vulgaris, alopecia, vitiligo, and psoriasis. BV is used extensively in topical preparations as cosmetics and used as dressing for wound healing, as well as in facemasks. Nevertheless, the safety of BV as a therapeutic choice has always been a concern due to the immune system reaction in some people due to BV use. The documented unfavorable impact is explained by the fact that the skin reactions to BV might expand to excessive immunological responses, including anaphylaxis, that typically resolve over numerous days. This review aims to address bee venom therapeutic uses in skin cosmetics.

Overview of Bee Pollination and Its Economic Value for Crop Production.

Pollination plays a significant role in the agriculture sector and serves as a basic pillar for crop production. Plants depend on vectors to move pollen, which can include water, wind, and animal pollinators like bats, moths, hoverflies, birds, bees, butterflies, wasps, thrips, and beetles. Cultivated plants are typically pollinated by animals. Animal-based pollination contributes to 30% of global food production, and bee-pollinated crops contribute to approximately one-third of the total human dietary supply. Bees are considered significant pollinators due to their effectiveness and wide availability. Bee pollination provides excellent value to crop quality and quantity, improving global economic and dietary outcomes. This review highlights the role played by bee pollination, which influences the economy, and enlists the different types of bees and other insects associated with pollination.

Bee Pollen: Current Status and Therapeutic Potential.

Bee pollen is a combination of plant pollen and honeybee secretions and nectar. The Bible and ancient Egyptian texts are documented proof of its use in public health. It is considered a gold mine of nutrition due to its active components that have significant health and medicinal properties. Bee pollen contains bioactive compounds including proteins, amino acids, lipids, carbohydrates, minerals, vitamins, and polyphenols. The vital components of bee pollen enhance different bodily functions and offer protection against many diseases. It is generally marketed as a functional food with affordable and inexpensive prices with promising future industrial potentials. This review highlights the dietary properties of bee pollen and its influence on human health, and its applications in the food industry.

Marine Natural Products: A Source of Novel Anticancer Drugs.

Cancer remains one of the most lethal diseases worldwide. There is an urgent need for new drugs with novel modes of action and thus considerable research has been conducted for new anticancer drugs from natural sources, especially plants, microbes and marine organisms. Marine populations represent reservoirs of novel bioactive metabolites with diverse groups of chemical structures. This review highlights the impact of marine organisms, with particular emphasis on marine plants, algae, bacteria, actinomycetes, fungi, sponges and soft corals. Anti-cancer effects of marine natural products in in vitro and in vivo studies were first introduced; their activity in the prevention of tumor formation and the related compound-induced apoptosis and cytotoxicities were tackled. The possible molecular mechanisms behind the biological effects are also presented. The review highlights the diversity of marine organisms, novel chemical structures, and chemical property space. Finally, therapeutic strategies and the present use of marine-derived components, its future direction and limitations are discussed.