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.

Anticancer properties of bromelain: State-of-the-art and recent trends.

Bromelain is a key enzyme found in pineapple (Ananas comosus (L.) Merr.); a proteolytic substance with multiple beneficial effects for human health such as anti-inflammatory, immunomodulatory, antioxidant and anticarcinogenic, traditionally used in many countries for its potential therapeutic value. The aim of this updated and comprehensive review focuses on the potential anticancer benefits of bromelain, analyzing the cytotoxic, apoptotic, necrotic, autophagic, immunomodulating, and anti-inflammatory effects in cancer cells and animal models. Detailed information about Bromelain and its anticancer effects at the cellular, molecular and signaling levels were collected from online databases such as PubMed/MedLine, TRIP database, GeenMedical, Scopus, Web of Science and Google Scholar. The results of the analyzed studies showed that Bromelain possesses corroborated pharmacological activities, such as anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair. Nonetheless, bromelain clinical studies are scarce and still more research is needed to validate the scientific value of this enzyme in human cancer diseases.

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.

Antiproliferative and antiviral activity of methanolic extracts from Sardinian Maltese Mushroom (Cynomorium coccineum L.).

Cynomorium coccineum is a non-photosynthetic plant that grows in Mediterranean countries and that is amply used in the traditional medicine. The aim of this study was to extend previous studies on the chemical and biological properties of C. coccineum, evaluating the potential antiviral and antiproliferative activity of the methanolic extract. The MTT assay was used for the in vitro cytotoxic studies against human cancer-derived cell lines, while both MTT and plaque reduction (PRT) methods were used to evaluate the potential inhibitory effect of the extract against a panel of mammal viruses. The results obtained showed no selective activity against any DNA and RNA virus but revealed an interesting antiproliferative activity against human leukaemia-derived cell lines.

Absence of Polyphenol Oxidase in Cynomorium coccineum, a Widespread Holoparasitic Plant.

Polyphenol oxidase (PPO, E.C. 1.14.18.1) is a nearly ubiquitous enzyme that is widely distributed among organisms. Despite its widespread distribution, the role of PPO in plants has not been thoroughly elucidated. In this study, we report for the absence of PPO in Cynomorium coccineum, a holoparasitic plant adapted to withstand unfavorable climatic conditions, growing in Mediterranean countries and amply used in traditional medicine. The lack of PPO has been demonstrated by the absence of enzymatic activity with various substrates, by the lack of immunohistochemical detection of the enzyme, and by the absence of the PPO gene and, consequently, its expression. The results obtained in our work allow us to exclude the presence of the PPO activity (both latent and mature forms of the enzyme), as well as of one or more genes coding for PPO in C. coccineum. Finally, we discuss the possible significance of PPO deficiency in parasitic plants adapted to abiotic stress.

Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases.

Oxidative stress plays an essential role in the pathogenesis of chronic diseases such as cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. Long term exposure to increased levels of pro-oxidant factors can cause structural defects at a mitochondrial DNA level, as well as functional alteration of several enzymes and cellular structures leading to aberrations in gene expression. The modern lifestyle associated with processed food, exposure to a wide range of chemicals and lack of exercise plays an important role in oxidative stress induction. However, the use of medicinal plants with antioxidant properties has been exploited for their ability to treat or prevent several human pathologies in which oxidative stress seems to be one of the causes. In this review we discuss the diseases in which oxidative stress is one of the triggers and the plant-derived antioxidant compounds with their mechanisms of antioxidant defenses that can help in the prevention of these diseases. Finally, both the beneficial and detrimental effects of antioxidant molecules that are used to reduce oxidative stress in several human conditions are discussed.

Sisymbrium officinale, the Plant of Singers: A Review of Its Properties and Uses.

Sisymbrium officinale (hedge mustard and formerly called Erysimum officinale) is a common plant in wild lands of Europe and Africa. It is also cultivated for its seeds and leaves to be used in salad or mustard. Sisymbrium officinale is useful not only in culinary preparations, but it also seems to possess interesting therapeutic properties, especially for throat diseases such as aphonia and hoarseness. For this reason, it is commonly called "herb of singers" (in Italian, "Erba dei cantanti"). Indeed a cup of Sisymbrium officinale infusion is frequently consumed by singers before artistic performance, even if its beneficial ability still needs to be scientifically demonstrated. Some preliminary data can be analyzed, but new efforts and resources should be devoted to study and investigate a plant with valuable therapeutic potential. This review summarizes the data available for Sisymbrium officinale.

Astringent drugs for bleedings and diarrhoea: The history of Cynomorium coccineum (Maltese Mushroom).

ETHNOPHARMACOLOGICAL RELEVANCE: The botanical identity of the ancient vernacular cynomorium does not correspond to the modern scientific genus while it is not clear how many species of hipocistis (Cytinus sp.) were differentiated by the ancient physicians and whether Cynomorium coccineum was subsumed. The early history of therapeutic uses related to the herbal drugs derived from these parasitic taxa is therefore not easily accessible. Cynomorium coccineum became an important pharmaceutical commodity after the Siege of Malta but its importance decreased in the 18th century and now is considered obsolete. MATERIAL AND METHODS: We compare the morphological, ecological and therapeutic information of Cynomorium and other parasitizing plant taxa across the past 2000 years and contextualize their uses with the pharmacological properties of their principal metabolites focusing on the raise and fall of C. coccineum as a medicine. RESULTS: The therapeutic uses of C. coccineum, the Maltese mushroom, seem to become clearly traceable since the Canon of Medicine by Avicenna. Styptic and astringent drugs such as Cynomorium, Cytinus but also gall apples and many others have been selected for their protein-linking capacity leading to the formation of a protective layer on the mucous membranes, which can be used to reduce the secretion of water and electrolytes in case of diarrhoea, dysentery and external bleedings. Whether C. coccineum is effective as a systemically applied anti-haemorrhagic drug is questionable. CONCLUSION: It appears that the vernacular cynomorium of the ancients corresponds to an edible Orobanche sp. while it remains doubtful whether the vernacular hipocistis was next to Cytinus sp. also applied to C. coccineum as evidence of C. coccineum parasitizing Cistus sp. is scarce. The isolation of gallic acid used as a styptic and the increasing availability of chemical styptics in the 18th century together with the availability of effective alternative anti-diarrhoeic drugs with a more reliable supply very probably led to the decline of the importance of the Maltese mushroom in pharmacy during the 18th century. The effectiveness of gallic acid as a systemic anti-haemorrhagic remains uncertain.

The Modern Use of an Ancient Plant: Exploring the Antioxidant and Nutraceutical Potential of the Maltese Mushroom (Cynomorium Coccineum L.).

In the continuous scientific search for new safe and effective drugs, there has recently been a rediscovery of natural substances as a potential reservoir of innovative therapeutic solutions for human health, with the prospect of integrating with and sometimes replacing conventional drugs. Cynomorium coccineum subsp. coccineum is a holoparasitic plant well known in ethnopharmacology, although its current use as a curative remedy is reported only in some ethnic groups of North Africa and the Arabian Peninsula. Often known as 'Maltese mushroom' due to its unique appearance and the absence of chlorophyll, C. coccineum is present in almost all of the Mediterranean Basin. It is only recently that a few research groups have begun to look for confirmation of some of its traditional uses to highlight previously unknown biological activities. Here, we review the recent scientific findings on the plant's phytochemistry and the most significant descriptions of some of its antioxidant and biological activities (antimicrobial, anticancer, pro-erectile, and anti-tyrosinase enzyme) both in vivo and in vitro. Some of these may be promising from the perspective of food and cosmetic formulations. The purpose of this review is to provide an initial impetus to those who, in the foreseeable future, will want to increase the knowledge and possible applications of this plant full of history, charm, and mystery.

Tannin profile, antioxidant properties, and antimicrobial activity of extracts from two Mediterranean species of parasitic plant Cytinus.

BACKGROUND: Cytinus is small genus of endophytic parasitic plants distributed in South Africa, Madagascar, and in the Mediterranean region. In the latter area, two species occur, Cytinus hypocistis and C. ruber, distinguished by both morphological characters and ecological traits. We characterized the ethanolic and aqueous extracts obtained from the inflorescences of C. hypocistis and C. ruber collected in Sardinia, Italy, and explored their tannin content, antioxidant properties and antimicrobial activities. METHODS: Total phenolic contents were determined by Folin-Ciocalteu spectrophotometric method. Tannin content was determined by HPLC. Antioxidant activity of the extracts was tested with both electron transfer-based (FRAP, TEAC, DPPH) and spectrophotometric HAT methods (ORAC-PYR). The antimicrobial activities of extracts/compounds were evaluated using the broth microdilution method. The bactericidal activity was evaluated using the time-kill method. Biofilm formation was evaluated by crystal violet (CV) staining assay. RESULTS: Characterization of the tannin profile of C. hypocistis and C. ruber revealed a significant amount of gallotannins, in particular 1-O-galloyl-ß-D-glucose. In addition, pentagalloyl-O-ß-D-glucose was present in all extracts, reaching the concentration of 0.117 g/kg in the ethanolic extract of C. hypocistis. C. hypocistis extracts displayed a strongest antioxidant activity than C. ruber extracts. Three Gram-positive bacterial species tested (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium) resulted sensitive to both Cytinus extracts, with MICs ranging from 125 to 500 µg/ml for aqueous extracts and from 31.25 to 250 µg/ml for ethanolic extracts; on the contrary, Gram-negative strains (Pseudomonas aeruginosa and Klebsiella pneumoniae) were not affected by Cytinus extracts. Intriguingly, we observed the suppressive activity of ethanolic extracts of C. hypocistis and C. ruber on biofilm formation of S. epidermidis. Experiments performed with synthetic compounds indicated that pentagalloyl-O-ß-D-glucose is likely to be one of the active antimicrobial components of Cytinus extracts. CONCLUSIONS: These findings show that Cytinus extracts have antimicrobial and antioxidant activities, suggesting a possible application of Cytinus as sources of natural antimicrobials and antioxidants.

Epithelial-mesenchymal transition as a target for botanicals in cancer metastasis.

BACKGROUND: The plant kingdom represents an unlimited source of phytotherapeutics with promising perspectives in the field of anticancer drug discovery. PURPOSE: In this view, epithelial-mesenchymal transition (EMT) represents a novel and major target in anticancer therapy. Therefore, this narrative review aims to provide an updated overview on the bioactive phytochemicals with anti-EMT activity. CONCLUSION: Among the plant products reviewed, phenylpropanoids were the most investigated at preclinical phase, thus exhibiting a promising potential as anticancer drugs, though an evidence-based clinical efficacy is still lacking.

The Therapeutic Potential of Naringenin: A Review of Clinical Trials.

Naringenin is a flavonoid belonging to flavanones subclass. It is widely distributed in several Citrus fruits, bergamot, tomatoes and other fruits, being also found in its glycosides form (mainly naringin). Several biological activities have been ascribed to this phytochemical, among them antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic and cardioprotective effects. Nonetheless, most of the data reported have been obtained from in vitro or in vivo studies. Although some clinical studies have also been performed, the main focus is on naringenin bioavailability and cardioprotective action. In addition, these studies were done in compromised patients (i.e., hypercholesterolemic and overweight), with a dosage ranging between 600 and 800 µM/day, whereas the effect on healthy volunteers is still debatable. In fact, naringenin ability to improve endothelial function has been well-established. Indeed, the currently available data are very promising, but further research on pharmacokinetic and pharmacodynamic aspects is encouraged to improve both available production and delivery methods and to achieve feasible naringenin-based clinical formulations.

Phytotherapeutics in cancer invasion and metastasis.

Cancer is a multifactorial disease, and therefore, a multitarget approach is needed to face the complex cancer biology, based on the combined use of different natural and synthetic anticancer agents able to target synergistically multiple signaling pathways involved in carcinogenesis, including angiogenesis and metastasis. In this view, the plant kingdom represents an unlimited source of phytotherapeutics with promising perspectives in the field of anticancer drug discovery. This narrative review aims to provide an updated overview on the bioactive phytochemicals exhibiting a promising potential as adjuvants in conventional anticancer therapies, with emphasis on antiangiogenic and antimetastatic activities.

Antimicrobial, antioxidant and anti-tyrosinase properties of extracts of the Mediterranean parasitic plant Cytinus hypocistis.

BACKGROUND: Cytinus is an endophytic parasitic plant occurring in South Africa, Madagascar, and in the Mediterranean region. We have extracted the inflorescences (the only visible part of the plant, emerging from the host roots at the time of blossom) of Cytinus hypocistis collected in Sardinia, Italy, and explored the antimicrobial, antioxidant, anti-tyrosinase, and cytotoxic activities of the extracts. METHODS: Extracts from C. hypocistis were prepared using increasing polarity solvents: cyclohexane, ethanol, and water. Phenolic composition were determined through spectrophotometric assays, and antioxidant activity with both electron-transfer and hydrogen-atom assays. Nine different bacterial strains, including clinical isolate methicillin-resistant Staphylococcus aureus, were used in agar diffusion method. Cytotoxicity was tested using against the B16F10 melanoma cell line. RESULTS: While cyclohexane extracts where biologically inactive, ethanolic and aqueous extracts displayed an intriguing activity against several Gram-positive bacterial strains, including methicillin-resistant S. aureus, and against the Gram-negative Acinetobacter baumanii. Compared to the conventional antibiotics like cloxacillin, ampicillin, and oxytetracycline, C. hypocistis extracts were less active in absolute terms, but displayed a wider spectrum (notably, cloxacillin and ampicillin were inactive against methicillin-resistant S. aureus). The ethanolic extract of C. hypocistis was found to be particularly rich in polyphenols, in most part hydrolysable tannins. The antioxidant activity of extracts, tested with several methodologies, resulted to be particularly high in the case of ethanolic extracts, in accordance with the composition in phenolics. In detail, ethanol extracts presented about a twofold higher activity than the water sample when tested through the oxygen radical absorbance capacity-pyrogallol red (ORAC-PYR) assay. Cytotoxicity analysis against the B16F10 melanoma cell line showed that both extracts have not significant cytotoxic effect, even at the highest dose (1000 µg/mL). Tests showed that ethanolic extracts also had the greatest tyrosinase inhibition activity, indicating that C. hypocistis-derived substances could find application in food formulations as anti-browning agents. CONCLUSIONS: Overall, these results point to the need of further studies on C. hypocistis extracts, aimed at isolating and fully characterizing its biologically active compounds.

Isolation and characterization of polyphenol oxidase from Sardinian poisonous and non-poisonous chemotypes of Ferula communis (L.).

Ferula communis (L.), a plant belonging to Apiaceae, is widely present in Sardinia, Italy. Currently, interest in F. communis focuses on the presence of two chemotypes in the wild. One chemotype is poisonous to animals, whereas the other chemotype is non-poisonous. Polyphenol oxidase (PPO) has been extracted and partially purified from the two chemotypes of F. communis. The biochemical characterization of the enzymes showed significant differences. In particular, while the two PPOs were not able to use 6- and 7-hydroxycoumarin as substrates, they showed distinct specificity for 6,7- and 7,8-dihydroxycoumarin. Significant differences in the enzyme behavior towards common PPO inhibitors were also observed. In addition, activation energy and activation energy for denaturation were determined, showing significant differences between FP-PPO and FNP-PPO, particularly for denaturation kinetics. The possible roles of the two PPOs in determining differences in composition and toxicity of the two F. communis chemotypes are also discussed.

Evaluation of antioxidant potential of "maltese mushroom" (Cynomorium coccineum) by means of multiple chemical and biological assays.

Cynomorium coccineum is an edible, non-photosynthetic plant widespread along the coasts of the Mediterranean Sea. The medicinal properties of Maltese mushroom - one of the oldest vernacular names used to identify this species - have been kept in high regard since ancient times to the present day. We evaluated the antioxidant potential of fresh specimens of C. coccineum picked in Sardinia, Italy. Both aqueous and methanolic extracts were tested by using multiple assay systems (DPPH, FRAP, TEAC, ORAC-PYR). Total phenolics and flavonoids were also determined. Gallic acid and cyanidin 3-O-glucoside were identified as the main constituents and measured. Both extracts showed antioxidant capacities; ORAC-PYR assay gave the highest antioxidant value in both cases. The methanolic extract was further investigated with in vitro biological models of lipid oxidation; it showed a significant activity in preventing cholesterol degradation and exerted protection against Cu2+-mediated degradation of the liposomal unsaturated fatty acids. Results of the present study demonstrate that the extracts of C. coccineum show a significant total antioxidant power and also exert an in vitro protective effect in different bio-assays of oxidative stress. Therefore, Maltese mushroom can be considered a valuable source of antioxidants and phytochemicals useful in the preparation of nutraceuticals and functional foods.

Chemical composition and effect on intestinal Caco-2 cell viability and lipid profile of fixed oil from Cynomorium coccineum L.

Cynomorium coccineum L. is a non-photosynthetic plant, spread over Mediterranean countries, amply used in traditional medicine. We investigated the composition and effect on intestinal Caco-2 cell viability and lipid profile of fixed oil obtained from dried stems of the plant. Oil isolation has been performed by supercritical fractioned extraction with CO2. 13C NMR spectroscopy has been used to study the molecular composition of oil lipids; fatty acid composition was identified using GC and HPLC techniques. The fixed oil was composed mainly by triacylglycerols and derivates. The main fatty acids were 18:1 n-9 (38%), 18:2 n-6 (20%), 16:0 (15%), and 18:3 n-3 (10.8%). The oil showed a significant in vitro inhibitory effect on the growth of colon cancer undifferentiated Caco-2 cells. Moreover, cell viability, lipid composition, and lipid peroxidation were measured in intestinal epithelial cells (differentiated Caco-2 cells) after 24 h incubation with fixed oil. The oil did not show a toxic effect on colon epithelial cell viability but induced a significant change in fatty acid composition, with a significant accumulation of the essential fatty acids 18:3 n-3 and 18:2 n-6. The results showed remarkable biological activity of Maltese mushroom oil, and qualify it as a potential resource for food/pharmaceutical applications.

Umbelliferone and esculetin: inhibitors or substrates for polyphenol oxidases?

Recently, an interesting debate arose about the nature (substrate versus inhibitor) of esculetin, a coumarin derivative, for mushroom polyphenol oxidase (PPO). The present study examined the behavior of PPOs preparations from fungal and plant origin towards esculetin as a substrate. Both enzymes were able to oxidize esculetin though at a slow rate. A higher sensitivity was reached when the assay was performed in the presence of 3-methyl-2-benzothiazolinone hydrazone (MBTH) even with a lower amount of PPO. These observations unambiguously confirmed that esculetin has to be considered a substrate for mushroom polyphenol oxidase. The oxidation of esculetin was also demonstrated for the first time by a fungal laccase. This should be taken into account because some mushroom PPO preparations could exert contaminant laccase activity. In addition, a PPO preparation from Ferula communis was demonstrated to use esculetin as a substrate. Umbelliferone, the monophenolic precursor of esculetin along the phenylpropanoid pathway, behaved as a competitive inhibitor for the monophenolase activity of mushroom PPO with a K(i) value=0.014 mM. This is worth a mention because only a few couples of mono- and corresponding o-diphenol show such opposite behavior towards PPO. A possible role of PPO in the esculetin fate along biosynthesis pathway of coumarin derivatives is also discussed.

Supercritical CO2 extract of Cinnamomum zeylanicum: chemical characterization and antityrosinase activity.

The volatile oil of the bark of Cinnamomum zeylanicum was extracted by means of supercritical CO2 fluid extraction in different conditions of pressure and temperature. Its chemical composition was characterized by GC-MS analysis. Nineteen compounds, which in the supercritical extract represented >95% of the oil, were identified. (E)-Cinnamaldehyde (77.1%), (E)-beta-caryophyllene (6.0%), alpha-terpineol (4.4%), and eugenol (3.0%) were found to be the major constituents. The SFE oil of cinnamon was screened for its biological activity about the formation of melanin in vitro. The extract showed antityrosinase activity and was able to reduce the formation of insoluble flakes of melanin from tyrosine. The oil also delayed the browning effect in apple homogenate. (E)-Cinnamaldehyde and eugenol were found to be mainly responsible of this inhibition effect.