Naturally-Occurring Bioactives in Oral Cancer: Preclinical and Clinical Studies, Bottlenecks and Future Directions.

Oral cancer (OC) is the eighth most common cancer, particularly prevalent in developing countries. Current treatment includes a multidisciplinary approach, involving chemo, radio, and immunotherapy and surgery, which depends on cancer stage and location. As a result of the side effects of currently available drugs, there has been an increasing interest in the search for naturally-occurring bioactives for treating all types of cancer, including OC. Thus, this comprehensive review aims to give a holistic view on OC incidence and impact, while highlights the preclinical and clinical studies related to the use of medicinal plants for OC prevention and the recent developments in bioactive synthetic analogs towards OC management. Chemoprophylactic therapies connect the use of natural and/or synthetic molecules to suppress, inhibit or revert the transformation of oral epithelial dysplasia (DOK) into oral squamous cell carcinoma (OSCC). Novel searches have underlined the promising role of plant extracts and phytochemical compounds, such as curcumin, green tea extract, resveratrol, isothiocyanates, lycopene or genistein against this malignancy. However, poor bioavailability and lack of in vivo and clinical studies and complex pharmacokinetic profiles limit their huge potential of application. However, recent nanotechnological and related advances have shown to be promising in improving the bioavailability, absorption and efficacy of such compounds.

An Updated Review on The Properties of Melissa officinalis L.: Not Exclusively Anti-anxiety.

Melissa officinalis L. is a plant of the Lamiaceae family known in numerous countries for its medicinal activities. This plant has been used since ancient times to treat different disorders, including gastrointestinal, cardiovascular, neurological, psychological conditions. M. officinalis contains several phytochemicals such as phenolic acids, flavonoids, terpenoids, and many others at the basis of its pharmacological activities. Indeed, the plant can have antioxidant, anti-inflammatory, antispasmodic, antimicrobial, neuroprotective, nephroprotective, antinociceptive effects. Given its consolidated use, M. officinalis has also been experimented with clinical settings, demonstrating interesting properties against different human diseases, such as anxiety, sleeping difficulties, palpitation, hypertension, depression, dementia, infantile colic, bruxism, metabolic problems, Alzheimer's disease, and sexual disorders. As for any natural compound, drug, or plant extract, also M. officinalis can have adverse effects, even though the reported events are very rare and the plant can be considered substantially safe. This review has been prepared with a specific research strategy, interrogating different databases with the keyword M. officinalis. Moreover, this work analyzes the properties of this plant updating currently available literature, with a special emphasis on human studies.

Common bean (Phaseolus vulgaris L.) α-amylase inhibitors as safe nutraceutical strategy against diabetes and obesity: An update review.

Overweight and obesity are constantly increasing, not only in Western countries but also in low-middle-income ones. The decrease of both the intake of carbohydrates and their assimilation are among the main dietary strategies to counter these conditions. α-Amylase, a key enzyme involved in the digestion of carbohydrates, is the target enzyme to reduce the absorption rate of carbohydrates. α-Amylase inhibitors (α-AIs) can be found in plants. The common bean, Phaseolus vulgaris is of particular interest due to the presence of protein-based α-AIs which, through a protein-protein interaction, reduce the activity of this enzyme. Here we describe the nature of the various types of common bean seed extracts, the type of protein inhibitors they contain, reviewing the recent Literature about their molecular structure and mechanism of action. We also explore the existing evidence (clinical trials conducted on both animals and humans) supporting the potential benefits of this protein inhibitors from P. vulgaris, also highlighting the urgent need of further studies to confirm the clinical efficacy of the commercial products. This work could contribute to summarize the knowledge and application of P. vulgaris extract as a nutraceutical strategy for controlling unwanted weight gains, also highlighting the current limitations.

Plant Natural Compounds in the Treatment of Adrenocortical Tumors.

Plant natural products are a plethora of diverse and complex molecules produced by the plant secondary metabolism. Among these, many can reserve beneficial or curative properties when employed to treat human diseases. Even in cancer, they can be successfully used and indeed numerous phytochemicals exert antineoplastic activity. The most common molecules derived from plants and used in the fight against cancer are polyphenols, i.e., quercetin, genistein, resveratrol, curcumin, etc. Despite valuable data especially in preclinical models on such compounds, few of them are currently used in the medical practice. Also, in adrenocortical tumors (ACT), phytochemicals are scarcely or not at all used. This work summarizes the available research on phytochemicals used against ACT and adrenocortical cancer, a very rare disease with poor prognosis and high metastatic potential, and wants to contribute to stimulate preclinical and clinical research to find new therapeutic strategies among the overabundance of biomolecules produced by the plant kingdom.

Phenolic Bioactives as Antiplatelet Aggregation Factors: The Pivotal Ingredients in Maintaining Cardiovascular Health.

Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. The development of these diseases has a specific factor-alteration in blood platelet activation. It has been shown that phenolic compounds have antiplatelet aggregation abilities and a positive impact in the management of CVD, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects. Thus, this review is intended to address the antiplatelet activity of phenolic compounds with special emphasis in preventing CVD, along with the mechanisms of action through which they are able to prevent and treat CVD. In vitro and in vivo studies have shown beneficial effects of phenolic compound-rich plant extracts and isolated compounds against CVD, despite that the scientific literature available on the antiplatelet aggregation ability of phenolic compounds in vivo is scarce. Thus, despite the current advances, further studies are needed to confirm the cardioprotective potential of phenolic compounds towards their use alone or in combination with conventional drugs for effective therapeutic interventions.

Antioxidant potential of family Cucurbitaceae with special emphasis on Cucurbita genus: A key to alleviate oxidative stress-mediated disorders.

Oxidative stress is the imbalance between reactive oxygen species (ROS) production, and accumulation and the ability of a biological system to clear these reactive products. This imbalance leads to cell and tissue damage causing several disorders in human body, such as neurodegeneration, metabolic problems, cardiovascular diseases, and cancer. Cucurbitaceae family consists of about 100 genera and 1,000 species of plants including mostly tropical, annual or perennial, monoecious, and dioecious herbs. The plants from Cucurbita species are rich sources of phytochemicals and act as a rich source of antioxidants. The most important phytochemicals present in the cucurbits are cucurbitacins, saponins, carotenoids, phytosterols, and polyphenols. These bioactive phyto-constituents are responsible for the pharmacological effects including antioxidant, antitumor, antidiabetic, hepatoprotective, antimicrobial, anti-obesity, diuretic, anti-ulcer activity, and antigenotoxic. A wide number of in vitro and in vivo studies have ascribed these health-promoting effects of Cucurbita genus. Results of clinical trials suggest that Cucurbita provides health benefits for diabetic patients, patients with benign prostate hyperplasia, infertile women, postmenopausal women, and stress urinary incontinence in women. The intend of the present review is to focus on the protective role of Cucurbita spp. phytochemicals on oxidative stress-related disorders on the basis of preclinical and human studies. The review will also give insights on the in vitro and in vivo antioxidant potential of the Cucurbitaceae family as a whole.

Ginkgolic Acids Confer Potential Anticancer Effects by Targeting Pro- Inflammatory and Oncogenic Signaling Molecules.

BACKGROUND: Medicinal plants and herbal preparations in the form of traditional medicines have been used in healthcare worldwide. The extracts of Ginkgo biloba L. seeds and leaves contain a complex mixture of numerous components, such as flavonol glycosides, terpene lactones, and a group of alkylphenols (anacardic or ginkgolic acids, cardanols and cardols) that have been a part of traditional Chinese medicine. These extracts are also sold as dietary supplements worldwide. G. biloba extract (EGb 761 and LI 1370) represent the standard form of G. biloba extract. Six different 6-alkylsalicylic acids (syn. ginkgolic acids) with alkyl substituents (C13:0, C15:0, C15:1, C17:0, C17:1, and C17:2) have been identified. OBJECTIVE: The aim of this review is to unravel scientific evidence on anti-inflammatory and anticancer activities of ginkgolic acids to understand its therapeutic potential against inflammatory and oncologic diseases. METHODS: A structured literature search was independently performed by the authors on PubMed, ScienceDirect, Scopus, and Web of Science. Accordingly, this review article critically analyses available scientific evidence on anti-inflammatory and anticancer activities of ginkgolic acids. Moreover, the review only included articles written in the English language. RESULTS: Several forms of ginkgolic acids, especially C13:0, C15:0 and C17:1, isolated from the leaves of G. biloba exhibited cytotoxic activity against a variety of human cancers by suppressing various pro-inflammatory signaling cascades and oncogenic transcription factors through multiple modes of action in various in vitro and in vivo preclinical models. Ginkgolic acids have also been reported to be potent post-translational small ubiquitin-related modifiers (SUMO)ylation inhibitors. CONCLUSION: In this review, we present updated information on the anti-inflammatory and anticancer properties of ginkgolic acids both in vitro and in vivo. Although ginkgolic acids show significant therapeutic potential in inflammatory and oncologic diseases, more investigations regarding the safety and efficacy of these natural agents are warranted before the clinical transition.

Gut Microbiota as a Prospective Therapeutic Target for Curcumin: A Review of Mutual Influence.

BACKGROUND: Turmeric is a spice that has recently received much interest and has been widely used in Ayurvedic medicine. Turmeric products are diarylheptanoids and have been characterized as safe. They are termed as curcuminoids that consists essentially of three major compounds: curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcumin is a lipophilic polyphenol that has poor systemic bioavailability and suffers from biotransformation by human intestinal microflora to yield different metabolites that are easily conjugated to glucuronides and sulfate O-conjugated derivatives. Recently, an increasing number of studies have indicated that dysbiosis is linked with many metabolic diseases, though gut microbiota could be a novel potential therapeutic target. SCOPE AND APPROACH: Thus, it is suspected that curcumin and its derivatives exert direct regulative effects on the gut microbiota which could explain the paradox between curcumin's poor systemic bioavailability and its widely reported pharmacological activities. KEY FINDINGS AND CONCLUSIONS: This article summarizes a range of studies that highlight the interaction between curcumin and gut microbiota and considers opportunities for microbiome-targeting therapies using turmeric extract.

Impact of Phytochemicals and Dietary Patterns on Epigenome and Cancer.

Cancer remains one of the leading causes of death around the world. Initially it is recognized as a genetic disease, but now it is known to involve epigenetic abnormalities along with genetic alterations. Epigenetics refers to heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression. It includes changes in DNA methylation, histone modifications, and RNA interference. Although it is heritable, environmental factors such as diet could directly influence epigenetic mechanisms in humans. This article will focus on the role of dietary patterns and phytochemicals that have been demonstrated to influence the epigenome and more precisely histone and non-histone proteins modulation by acetylation that helps to induce apoptosis and phosphorylation inhibition, which counteracts with cells proliferation. Recent developments discussed here enhance our understanding of how dietary intervention could be beneficial in preventing or treating cancer and improving health outcomes.

Alginate-pomegranate peels' polyphenols beads: effects of formulation parameters on loading efficiency

Calcium alginate beads containing pomegranate peels' polyphenol extract were encapsulated by ionic gelation method. The effects of various formulation factors (sodium alginate concentration, calcium chloride concentration, calcium chloride exposure time, gelling bath time maintaining, and extract concentration) on the efficiency of extract loading were investigated. The formulation containing an extract of 1 g pomegranate peels in 100 mL distilled water encapsulated with 3 % of sodium alginate cured in 0.05 M calcium chloride for 20 minutes and kept in a gelling bath for 15 minutes was chosen as the best formula regarding the loading efficiency. These optimized conditions allowed the encapsulation of 43.90% of total extracted polyphenols and 46.34 % of total extracted proanthocyanidins. Microencapsulation of pomegranate peels' extract in calcium alginate beads is a promising technique for pharmaceutical and food supplementation with natural antioxidants.

Pérolas de alginato de cálcio, contendo polifenóis de extrato de casca de romã, foram encapsuladas pelo método de gelificação iônica. Os efeitos de vários fatores de formulação (concentração de alginato de sódio, concentração de cloreto de cálcio, cloreto de cálcio, o tempo de exposição, o tempo de manutenção do banho de gelificação e a concentração do extrato) sobre a eficiência de carga do extrato foram investigados. A formulação que contém 1 g extrato de casca de romã em 100 mL de água destilada, encapsulado com 3% de alginato de sódio curada em 0,05 M de cloreto de cálcio durante 20 minutos e mantido em banho de gelificação por 15 min foi escolhida como a melhor em relação à eficiência de carga. Estas condições otimizadas permitem o encapsulamento de 43,90% do total de polifenóis extraídos e de 46,34% do total de proantocianidinas extraídas. A microencapsulação de extrato de cascas de romã em esferas de alginato de cálcio é uma técnica promissora para a suplementação farmacêutica e de alimentos com antioxidantes naturais.