Anticancer and chemopreventive potential of Morinda citrifolia L. bioactive compounds: A comprehensive update.

Morinda citrifolia L., commonly known as Noni, has a longstanding history in traditional medicine for treating various diseases. Recently, there has been an increased focus on exploring Noni extracts and phytoconstituents, particularly for their effectiveness against cancers such as lung, esophageal, liver, and breast cancer, and their potential in cancer chemoprevention. This study aims to provide a comprehensive review of in vitro and in vivo studies assessing Noni's impact on cancer, alongside an exploration of its bioactive compounds. A systematic review was conducted, encompassing a wide range of scientific databases to gather pertinent literature. This review focused on in vitro and in vivo studies, as well as clinical trials that explore the effects of Noni fruit and its phytoconstituents-including anthraquinones, flavonoids, sugar derivatives, and neolignans-on cancer. The search was meticulously structured around specific keywords and criteria to ensure a thorough analysis. The compiled studies highlight Noni's multifaceted role in cancer therapy, showcasing its various bioactive components and their modes of action. This includes mechanisms such as apoptosis induction, cell cycle arrest, antiangiogenesis, and immune system modulation, demonstrating significant anticancer and chemopreventive potential. The findings reinforce Noni's potential as a safe and effective option in cancer prevention and treatment. This review underscores the need for further research into Noni's anticancer properties, with the hope of stimulating additional studies and clinical trials to validate and expand upon these promising findings.

Spasmolytic Activity of Gentiana lutea L. Root Extracts on the Rat Ileum: Underlying Mechanisms of Action.

The roots of Gentiana lutea L. are utilized in the preparation of various beverages and herbal remedies, serving as a traditional remedy for gastrointestinal ailments. The spasmolytic activity that could substantiate the traditional use of G. lutea root had not been investigated. The main objective goal of the study was to determine the validity of its use as a traditional remedy. The extraction of G. lutea root was performed using a 50% hydroethanolic solvent with three different extraction techniques: ultrasound-assisted extraction (UAE), heat-assisted extraction, and percolation. The spasmolytic activity was tested on isolated rat ileum. The mechanism of action was monitored using the models of spontaneous contractions and acetylcholine-, histamine-, CaCl2-, Bay K8644-, L-NAME-, ODQ-, apamin-, BaCl2-, charybdotoxin-, glibenclamide-, TRAM-34-, and quinine-modified contractions. UAE, having the best bioactivity, was further subjected to a liquid-liquid extraction fractionation. HPLC phytochemical analysis was performed for all tested extracts and fractions. Gentian root extracts were rich in secoiridoids, xanthones, and flavonoids. The UAE has shown better results on spontaneous contractions in comparison to its fractions, leading to the more detailed testing of its spasmolytic mechanism of activity. The extract's activity is primarily mediated through intermediate conductance Ca2+-activated K+ channels, ATP-sensitive K+ channels, voltage-sensitive K+ channels, and mechanisms that activate Ca2+ channels. Overall, the G. lutea root shows great potential in the treatment of spasmodic gastrointestinal ailments.

An In Vitro and In Silico Characterization of Salvia sclarea L. Methanolic Extracts as Spasmolytic Agents.

The use of medicinal plant species and their products is widespread in the field of gastrointestinal and respiratory diseases. This study aimed to evaluate the traditional use of Salvia sclarea L., clary sage, finding the possible mechanisms of its spasmolytic and bronchodilator actions in in vitro conditions supported by molecular docking analysis, along with the antimicrobial effects. Four dry extracts were prepared from the aerial parts of S. sclarea, using absolute or 80% (v/v) methanol by the method of a single-stage maceration or an ultrasound-assisted extraction. Characterization of the bioactive compounds by high-performance liquid chromatography indicated the presence of significant amounts of polyphenolics, with rosmarinic acid as the prevalent one. The spontaneous ileal contractions were best inhibited by the extract prepared with 80% methanol and maceration. The same extract was superior in the carbachol- and KCl-induced tracheal smooth muscle contractions, being the strongest bronchodilator agent. The most powerful relaxation of KCl-induced ileal contractions was achieved with the extract made of absolute methanol by maceration, while the 80% methanolic extract made with the ultrasound method generated the best spasmolytic effects in the acetylcholine-induced ileal contractions. Docking analysis suggested that apigenin-7-O-glucoside and luteolin-7-O-glucoside exhibited the highest binding affinity to voltage-gated calcium channels. Gram (+) bacteria were more susceptible to the effects of the extracts, particularly Staphylococcus aureus, in contrast to Gram (-) bacteria and Candida albicans. This is the first study to point out the influence of S. sclarea methanolic extracts on the gastrointestinal and respiratory spasm reduction, paving the way for their potential place in complementary medicine.

Delphinidin-3-rutinoside from Blackcurrant Berries (Ribes nigrum): In Vitro Antiproliferative Activity and Interactions with Other Phenolic Compounds.

Blackcurrant berries (Rigrum L.) are of great interest for food scientists/technologists as a source of delphinidin-3-rutinoside (D3R). This is an uncommon phenolic compound in diets that unveils potent antiproliferative activity besides its colour. Other phenolic compounds, such as chlorogenic acid (CA) and epicatechin (EC), also known by their antiproliferative effects, are abundant in foods and beverages. To design smart food/supplements combinations containing blackcurrant and improved anticancer properties at the gastrointestinal level, there is the need for more data concerning the combined effects of those molecules. In this work, synergistic, additive, or antagonistic effects against gastric and intestinal cancers of D3R, CA, and EC were assessed in vitro. The antiproliferative activity of D3R, CA, and EC, alone and in binary combinations (D3R+CA, D3R+EC, and CA+EC) on NCI-N87 (gastric) and Caco-2 (intestinal) cells, was assessed following the Chou-Talalay theorem at equipotent contributions (i.e., (IC50)1/(IC50)2). D3R presented the strongest antiproliferative activity of the single molecules tested, with IC50 values of 24.9 µM and 102.5 µM on NCI-N87 and Caco-2 cells, respectively. The combinations D3R+CA and CA+EC were synergic against NCI-N87 until IC50 and IC75, respectively, while D3R+EC shifted from slight antagonism to synergism at higher doses. On Caco-2 cells, antagonism at low doses and synergism at high doses was observed. Therefore, the synergisms observed on the gastric cancer model at low doses occurred on the colon model only at high doses. Data herein described is vital to the targeted smart design of foods and supplements, as it is foreseen that the same combination of phenolic compounds causes different interactions/effects depending on the dose and gastrointestinal compartment.

Anticancer Potential and Other Pharmacological Properties of Prunus armeniaca L.: An Updated Overview.

Prunus armeniaca L. (Rosaceae)-syn. Amygdalus armeniaca (L.) Dumort., Armeniaca armeniaca (L.) Huth, Armeniaca vulgaris Lam is commonly known as the apricot tree. The plant is thought to originate from the northern, north-western, and north-eastern provinces of China, although some data show that it may also come from Korea or Japan. The apricot fruit is used medicinally to treat a variety of ailments, including use as an antipyretic, antiseptic, anti-inflammatory, emetic, and ophthalmic remedy. The Chinese and Korean pharmacopeias describe the apricot seed as an herbal medicinal product. Various parts of the apricot plant are used worldwide for their anticancer properties, either as a primary remedy in traditional medicine or as a complementary or alternative medicine. The purpose of this review was to provide comprehensive and up-to-date information on ethnobotanical data, bioactive phytochemicals, anticancer potential, pharmacological applications, and toxicology of the genus Prunus armeniaca, thus providing new perspectives on future research directions. Included data were obtained from online databases such as PubMed/Medline, Google Scholar, Science direct, and Wiley Online Library. Multiple anticancer mechanisms have been identified in in vitro and in vivo studies, the most important mechanisms being apoptosis, antiproliferation, and cytotoxicity. The anticancer properties are probably mediated by the contained bioactive compounds, which can activate various anticancer mechanisms and signaling pathways such as tumor suppressor proteins that reduce the proliferation of tumor cells. Other pharmacological properties resulting from the analysis of experimental studies include neuroprotective, cardioprotective, antioxidant, immunostimulatory, antihyperlipidemic, antibacterial, and antifungal effects. In addition, data were provided on the toxicity of amygdalin, a compound found in apricot kernel seeds, which limits the long-term use of complementary/alternative products derived from P. armeniaca. This updated review showed that bioactive compounds derived from P. armeniaca are promising compounds for future research due to their important pharmacological properties, especially anticancer. A detailed analysis of the chemical structure of these compounds and their cytotoxicity should be carried out in future research. In addition, translational pharmacological studies are required for the correct determination of pharmacologically active doses in humans.

Can the chokeberry juice be used as additional therapy for burning mouth syndrome in menopausal women?

The researchers' aims were to evaluate the effects of chokeberry juice in the treatment of burning mouth syndrome (BMS) and oral discomfort in menopausal women. The following validated scales and questionnaires were used before and after treatment: questionnaire used for selection of research participants with xerostomia, the xerostomia inventory, Visual Analogue Scale (VAS), localization of pain before and after treatment, short-form McGill pain questionnaire. There was statistically significant decrease in number of research participants who felt pain after therapeutic procedure (p < 0.05). Chokeberry juice, as additional therapy for BMS, reduced intensity of characteristic types of pain sensations and oral dryness feeling.

Cytotoxicity screening of Thymus vulgaris L. essential oil in brine shrimp nauplii and cancer cell lines.

Among natural products, essential oils from aromatic plants have been reported to possess potent anticancer properties. In this work, we aimed to perform the cytotoxic concentration range screening and antiproliferative activity screening of chemically characterized Thymus vulgaris L. essential oil. In vivo bioassay was conducted using the brine shrimp lethality test (BSLT). In vitro evaluation of antiproliferative activity was carried out on three human tumor cell lines: breast adenocarcinoma MCF-7, lung carcinoma H460 and acute lymphoblastic leukemia MOLT-4 using MTT assay. Essential oil components thymol (36.7%), p-cymene (30.0%), γ-terpinene (9.0%) and carvacrol (3.6%) were identified by gas chromatography/mass spectrometry. Analyzed essential oil should be considered as toxic/highly toxic with LC50 60.38 µg/mL in BSLT and moderate/weakly cytotoxic with IC50 range 52.65-228.78 µg/mL in vitro, according to evaluated cytotoxic criteria. Essential oil induced a dose-dependent inhibition of cell proliferation in all tested tumor cell lines and showed different sensitivity. Dose dependent toxicity observed in bioassay as well as the in vitro assay confirmed that brine shrimp lethality test is an adequate method for preliminary toxicity testing of Thymus vulgaris L. essential oil in tumor cell lines.

Transport of mycotoxins across human gastric NCI-N87 and intestinal Caco-2 cell models.

Aflatoxin B1 (AFB1), deoxynivalenol (DON), fumonisin B1 (FB1), and ochratoxin A (OTA) are prevalent mycotoxins co-occurring in food, and their oral intake is conceivable to occur in the gastrointestinal epithelium. The intestinal absorption of some mycotoxins has been studied but only considering their isolated intake, while their gastric absorption in humans has not been explored. This study evaluated the bidirectional in vitro transport of four mycotoxins, isolated and in mixture, across gastric NCI-N87 and intestinal Caco-2 monolayers. AFB1 and DON were bidirectionally transported, more rapidly for AFB1; whereas OTA and FB1 were only transported in the absorptive direction, the first in both monolayers, and the second only in the gastric epithelium. The mixture of four mycotoxins exhibited some differences in cell uptake/excretion ratios. AFB1 presented the highest fraction absorbed (>96%) isolated and in mixture, followed by DON (72.8 and 82.9%); and OTA (11 and 66%) when transported isolated and in mixture, respectively. Different absorptive patterns on both epithelia were found when mycotoxins are transported isolated or in mixture. Further investigation on combined ingestion of toxins and their mixed transport should be considered for the proper evaluation of human absorption and toxicity of those mycotoxins considering their frequent co-occurrence and consequent co-exposure.

Chokeberry juice supplementation in type 2 diabetic patients - impact on health status.

Recent literature evidence indicates the potential use of chokeberry preparations in the prevention and treatment of some chronic noncommunicable diseases. The aim of the present study was to evaluate the effects of the three months oral chokeberry juice supplementation in type 2 diabetic patients, as well as its influence on hematological parameters and certain parameters of the renal dysfunction. The study was designed as an open-label trial, which included 35 patients who have received the herbal supplement, polyphenol-rich chokeberry juice (150 ml/day, three times a day for 50 ml), in addition to their standard therapy. Chokeberry juice as a rich source of polyphenol compounds could be an effective preventive and therapeutic agent in diabetes mellitus type 2. Hematological and biochemical parameters were measured at baseline, after 3 months with the chokeberry juice supplementation and after the next 3 months without the chokeberry juice supplementation (follow-up period). Significant difference was noticed in the levels of LDL-cholesterol, glycated hemoglobin and serum creatinine (p < 0.05), as well as in the levels of some hematological parameters, such as white blood cell and lymphocyte count (p < 0.01), hematocrit, blood hemoglobin, mean corpuscular volume, hemoglobin and hemoglobin concentration and red blood cell count (p < 0.05). The daily consumption of the chokeberry juice could improve the health status in patients with type 2 diabetes mellitus, in combination with their standard therapy.

Antispasmodic Effect of Blackcurrant (Ribes nigrum L.) Juice and Its Potential Use as Functional Food in Gastrointestinal Disorders.

OBJECTIVE: The purpose of this study was to investigate the relaxative effects of blackcurrant juice on the gastrointestinal smooth muscle in vitro. MATERIALS AND METHODS: Berries of the blackcurrant cultivar Ometa were used for the preparation of the juice used. The spasmolytic activity of blackcurrant juice was tested on rat ileum isolated from male Wistar rats by monitoring its influence on spontaneous contractions, as well as contractions induced by potassium chloride (KCl), barium chloride (BaCl2), calcium chloride (CaCl2), and acetylcholine (Ach). The results are expressed as the mean ± standard deviation obtained in 6 measurements and statistical significance was determined by the Student t test, with p < 0.05 taken as significant. RESULTS: The blackcurrant cultivar Ometa significantly reduced the frequency and the amplitude of spontaneous contractions (57.94 ± 3.44%) and Ach-induced contractions (42.74 ± 5.36%; p < 0.05) of the isolated rat ileum. Cumulative concentrations (0.01-3 mg/mL) of the Ometa juice also reduced contractions of the isolated rat ileum stimulated by KCl (51.46 ± 6.87%), CaCl2 (57.54 ± 6.47%), and BaCl2 (58.54 ± 10.55%). The inhibitory effects of the juice were proportional to the applied concentration. CONCLUSION: The antispasmodic effect of Ometa cultivar shows that common gastrointestinal disorders could be treated by the functional food.

Hypotensive, cardiodepressant, and vasorelaxant activities of black currant (Ribes nigrum 'Ben Sarek') juice.

The aim of this study was to evaluate the effects of black currant (Ribes nigrum L. 'Ben Sarek') juice on the blood pressure and frequency of cardiac contractions, as well as vasomotor responses of rat aortic rings. Arterial blood pressure was measured directly from the carotid artery in the anaesthetized rabbits. The aortic rings were pre-contracted with KCl (80 mmol·L-1), after which black currant juice was added. An intravenous injection of black currant juice (0.33-166.5 mg·kg-1) induced a significant and dose-dependent decrease of rabbit arterial blood pressure and heart rate. The black currant juice decreased arterial blood pressure of rabbit by 22.33% ± 3.76% (p < 0.05) and heart rate by 17.18% ± 2.93% (p < 0.05). Cumulative addition of the black currant juice (0.01-3 mg·mL-1) inhibited concentration-dependent KCl induced contractions of the isolated rat aorta. The black currant juice, at the concentration of 3 mg·mL-1, caused a maximum relaxation of 21.75% ± 3.15% (p < 0.05). These results demonstrate that black currant juice can induce hypotension. The hypotensive effect of the black currant may occur as the consequence of its inhibitory activity on the rate of heart contraction and vasorelaxant effects.

Chemical profile and antioxidative and antimicrobial activity of juices and extracts of 4 black currants varieties (Ribes nigrum L.).

UNLABELLED: The aim of this article was to determine the chemical composition (anthocyanin and ascorbic acid contents, total phenols, and tannins), and the antioxidative, and antimicrobial activities of the juices and methanol extracts of 4 varieties-Tenah, Triton, Ben Sarek, and Ometa. The juices were made during 2008, 2009, and 2010 from the berries grown on the same location. Statistically significant differences were found in all the tested parameters of each variety for every year. Ometa variety exhibited the best antioxidative activity. The highest ascorbic acid value had Tenah juice from 2010 (211 mg/100 g) and Ben Sarek methanol extract (656 mg/100 g). Delphinidin-3-ruthenoside was the dominant anthocyanin in Triton, Tenah, and Ben Sarek variety during all 3 y and Ometa in 2010 where Ometa in 2008 and 2009 had slightly higher content of cyanidin-3-ruthenoside. The minimum inhibitory and microbicidal concentrations ranged from MIC/MBC(MFC) = 62.5 to 500 mg/mL for juices and 0.4 to 500 mg/mL for extracts. There was no significant difference in the effect of the juices against Gram(+) and Gram(-) bacteria. All the extracts acted in lower concentrations than juices. PRACTICAL APPLICATION: Data contained in this article provide an insight into the effects the weather condition has on the content of the bioactive compounds in genetically different types of black currants, during the 3-y observation period. This article is relevant to the commercial application of black currants-based dietary supplements.

Effects of extracts of ginkgo, onion, and celery on the contractility of isolated rat atria.

The acute negative inotropic and chronotropic effects of the commercial extract of ginkgo leaf (Gingium(®)) and ethanolic extracts of onion bulbs and celery root on spontaneous and noradrenalin-stimulated contractions of the Wistar rat atria were investigated. All analyzed extracts exerted negative inotropic effects on the isolated rat atria. Among the tested extracts, the extract of ginkgo showed the strongest negative inotropic effects on rat atria, either in spontaneous or noradrenalin-induced contractions, being more potent than the onion and celery extracts, respectively.

Comparison of the hypotensive and bradycardic activity of ginkgo, garlic, and onion extracts.

The acute effect of ethanol extracts ginkgo (Ginkgo biloba L.), garlic (Allium sativum L.), and onion (Allium cepa L.) on arterial blood pressure (BP), and heart rate (HR) in anesthetized normotensive rats was examined and compared. Arterial BP was registered in the left carotid artery. The data showed that intravenous administration of the extracts produced dose-dependent and reversible hypotensive and bradycardic effects. The most effective in reducing arterial BP and HR is extract of garlic. There were statistically significant differences in bradycardic and hypotensive effects of the garlic and ginkgo extracts.

Inhibitory effect of aqueous and ethanolic garlic (Allium sativum L., Lilliaceae) extracts on the rat atria.

The acute negative inotropic and chronotrophic effects of aqueous and alcoholic garlic extracts (Allium sativum L.) on spontaneous and adrenalin-stimulated contractions of the Wistar rat atria were investigated. The addition of garlic extracts to isolated rat atria evoked negative inotropic and chronotropic effects. Ethanolic garlic extract exerts much stronger negative inotropic (58.33 +/- 14.76%) effects than aqueous extract (43.66 +/- 16.32%). The difference in frequency reduction is especially conspicuous. Aqueous garlic extract very slightly affects the frequency, while ethanolic extract reduces it by more than 40%. In addition to these effects, the positive inotropism and chronotropism induced by the addition of noradrenaline, were much more antagonized by ethanolic garlic extract than by aqueous extract. Moreover, ethanolic garlic extract establishes sinus rhythm in the atria with extrasystoles induced by noradrenaline.