Molecular Mechanisms of Anti-Inflammatory Phytochemicals 2.0.

Inflammation is currently the most investigated cell response, not only for the frequency with which it occurs but essentially due to the growing incidence of inflammatory diseases, increasingly labeled as characteristics of modern society [...].

Non-edible fruit seeds: nutritional profile, clinical aspects, and enrichment in functional foods and feeds.

Nowadays, fruits are gaining high demand due to their promising advantages on human health. Astonishingly, their by-products, that is, seeds and peels, account for 10-35% of fruit weight and are usually thrown as waste after consumption or processing. But it is neglected that fruit seeds also have functional properties and nutritional value, and thus could be utilized for dietary and therapeutic purposes, ultimately reducing the waste burden on the environment. Owing to these benefits, researchers have started to assess the nutritional value of different fruits seeds, in addition to the chemical composition in various bioactive constituents, like carotenoids (lycopene), flavonoids, proteins (bioactive peptides), vitamins, etc., that have substantial health benefits and can be used in formulating different types of food products with noteworthy functional and nutraceutical potential. The current review aims to comprehend the known information of nutritional and phytochemical profiling of non-edible fruits seeds, viz. apple, apricot, avocado, cherry, date, jamun, litchi, longan, mango, and papaya. Additionally, clinical studies conducted on these selected non-edible fruit seed extracts, their safety issues and their enrichment in food products as well as animal feed has also been discussed. This review aims to highlight the potential applications of the non-edible fruit seeds in developing new food products and also provide a viable alternative to reduce the waste disposal issue faced by agro-based industries.

Medicinal Plant-Derived Phytochemicals in Detoxification.

The average worldwide human life expectancy is 70 years, with a significantly higher value in Western societies. Many modern diseases are not associated with premature mortality but with a decreased quality of life in aged patients and an excessive accumulation of various toxic compounds in the human body during life. Today, scientists are especially interested in finding compounds that can help increase a healthy lifespan by detoxifying the body. Phytotherapy with specific approaches is used in alternative medicine to remove toxins from the body. Worldwide, research is conducted to identify medicinal plant-derived molecules that, with few or no side effects, may protect the liver and other organs. This review provides updated information about the detoxification process, the traditional and modern use of the most effective medicinal plants, their active metabolites as detoxifying agents, and the mechanisms and pathways involved in the detoxification process. Among medicinal plants with substantial detoxifying properties, a major part belongs to the Asteraceae family (Silybum marianum, Cynara scolymus, Arctium lappa, Helichrysum spp, Inula helenium, and Taraxacum officinale). The most widely used hepatoprotective phytocomponent is silymarin, a standardized extract from the Silybum marianum seeds containing a mixture of flavonolignans. Many polysaccharides, polyphenols, and terpenoids have a detoxifying effect. Overall, scientific data on medicinal plants used in phytotherapeutic practice worldwide provides an understanding and awareness of their efficacy in detoxification.

Advances in Plants-Derived Bioactives for Cancer Treatment.

Cancer, while a multifactorial chronic disease with an increasing prevalence, has been the subject of intense investigation, not only because of the growing need to find the main triggers that motivate its onset but essentially because of the need to discover increasingly safer and effective therapeutic options that have fewer adverse effects and associated toxicity [...].

Anticancer activity of broccoli, its organosulfur and polyphenolic compounds.

The use of natural bioactive constituents from various food sources for anticancer purposes has become increasingly popular worldwide. Broccoli (Brassica oleracea var. italica) is on the top of the consumed vegetables by the masses. Its raw matrix contains a plethora of phytochemicals, such as glucosinolates and phenolic compounds, along with rich amounts of vitamins, and minerals. Consumption of broccoli-derived phytochemicals provides strong antioxidant effects, particularly due to its sulforaphane content, while modulating numerous molecules involved in cell cycle regulation, control of apoptosis, and tuning enzyme activity. Thus, the inclusion of broccoli in the daily diet lowers the susceptibility to developing cancers. Numerous studies have underlined the undisputable role of broccoli in the diet as a chemopreventive raw food, owing to the content in sulforaphane, an isothiocyanate produced as a result of hydrolysis of precursor glucosinolates called glucoraphanin. This review will provide evidence supporting the specific role of fresh florets and sprouts of broccoli and its key bioactive constituents in the prevention and treatment of different cancers; a number of studies carried out in the in vitro and in vivo conditions as well as clinical trials were analyzed.

Riparin-B as a Potential Inhibitor of AdeABC Efflux System from Acinetobacter baumannii.

Acinetobacter baumannii is an important opportunistic pathogen that causes serious health-related infections, especially in intensive care units. The present study aimed to investigate the antimicrobial activity of Riparin-B (Rip-B) alone and in association with norfloxacin against multidrug-resistant clinical isolates of A. baumannii. For this, the minimum inhibitory concentrations were determined by the microdilution method. For the evaluation of resistance-modulating activity, MIC values for antibiotics were determined in the presence or absence of subinhibitory concentrations of Rip-B or chlorpromazine (CPZ). The AdeABC-AdeRS efflux system genes from these isolates were detected by PCR. Docking studies were also carried out to evaluate the interaction of Riparin-B and the AdeABC-AdeRS efflux system. The study was conducted from 2017 to 2019. The results showed that Rip-B showed weak intrinsic activity against the strains tested. On the other hand, Rip-B was able to modulate norfloxacin's response against A. baumannii strains that express efflux pump-mediated resistance. Docking studies provided projections of the interaction between Rip-B and EtBr with the AdeB protein, suggesting that Rip-B acts by competitive inhibition with the drug. Results found by in vitro and in silico assays suggest that Rip-B, in combination with norfloxacin, has the potential to treat infections caused by multidrug-resistant A. baumanni with efflux pump resistance.

An approach on detection, quantification, technological properties, and trends market of A2 cow milk.

The genetic variant A2 ß-casein integrates the casein protein group in milk and has been often associated with positive health outcomes. Therefore, this review explores the present understanding of A2 ß-casein, including detection methods and the market trends for dairy from A2 milk. Also, the interaction of A2 ß-casein with αs1-casein and κ-casein genotypes was examined in terms of technological impacts on A2 milk. A limited number of preliminary studies has aimed to investigate the sensorial and technological impacts of ß-casein variants in milk matrices, for instance, in yogurt and other derivatives. Nevertheless, considering studies carried out so far, it is concluded that the manufacture of dairy products from A2 milk is perfectly feasible, as the products presented slight differences when compared to those derived from traditional milk. In one of the works, sensitive drops in rennet coagulation time and curd firmness values were observed in cheese traits. However, it is relevant to point out that variant A of κ-casein plays a negative role in the coagulation features of milk. Therefore, alterations in the pattern of cheese-making properties are not uniquely related to ß-casein variants. Attempts to produce A2 ß-casein in laboratory (non-natural source), through biosynthesis, for example, have not been found so far. This knowledge gap offers a promising area for future studies concerning proteins and bioactive peptide production.

Incidence of Bloodstream Infection in Patients with Pulmonary Hypertension under Intravenous Epoprostenol or Iloprost-A Multicentre, Retrospective Study.

Intravenous synthetic prostacyclin analogs (iPCAs), such as epoprostenol, treprostinil and iloprost have been widely used for the treatment of pulmonary arterial hypertension (PAH). Despite having good outcomes, continuous infusion of iPCAs has been associated with some adverse effects. Bloodstream infection (BSI) is one of the most severe complications, although poorly recognized, especially under iloprost administration, which few studies have addressed. This study aimed to compare the BSI incidence rates between intravenous iloprost and epoprostenol administration. Patients with pulmonary hypertension (PH) functional class III or IV receiving intravenous iloprost or epoprostenol through Hickman catheter, between 2004 and 2019, were retrospectively selected from two PH treatment centers. From a total of 36 patients (13 for iloprost and 23 for epoprostenol), 75% (n = 27) fulfilled the PAH criteria, mainly belonging to the idiopathic group. Overall BSI rate was 1.5/1000 days of treatment (3.38 and 0.09/1000 days for iloprost and epoprostenol, respectively). Patients receiving iloprost were at a higher risk of developing BSI than those receiving epoprostenol (HR: 12.5; 95% CI: 1.569-99.092). A higher mortality rate from BSI was also identified in the iloprost group (p = 0.04). Twenty-seven patients developed BSI, with 92% of them requiring hospitalization. A total of 29 agents were found, 10 Gram-positive (mainly Staphylococcus aureus; n = 5) and 19 Gram-negative (mainly Pseudomonas aeruginosa; n = 6) bacteria. Iloprost administration was linked to a significantly higher incidence of BSI, worse prognosis, and more BSI-related deaths than epoprostenol. BSI due to Gram-negative, commensal, low-virulence bacteria was also higher in the iloprost group. In short, physicians should be aware when prescribing iPCA to guarantee their patients' safety and best medical care.

Plant-food-derived Bioactives in Managing Hypertension: From Current Findings to Upcoming Effective Pharmacotherapies.

A sedentary lifestyle has evoked a high risk of cardiovascular (CV) disease, diabetes, and obesity, all of them with high morbimortality rates and with a common denominator, hypertension. Numerous pharmacological drugs have been used for the treatment of hypertension. However, the side effects associated with the use of existing pharmacological therapies have triggered a demand for plant-based medications. In this connection, the aim of this review was to provide an in-depth analysis of the use of plant-derived bioactives for the effective management of hypertension. Phytoconstituents from leaves, bark, stem, roots, seeds, and fruits of medicinal plants grown in our different regions of the globe have been highly searched. Among them, polyphenols (e.g., flavonoids as quercetin, anthocyanins as cyanidin, tannins as ellagic acid, stilbenes as resveratrol, lignans as honokiol and others as hydroxytyrosol or curcumin), organosulfur compounds (e.g. s-allyl cysteine and allicin), fatty acids (e.g. α-lipoic acid, DHA and oleic acid), alkaloids (e.g. berberine or tetrandrine) and some terpenes have been intensively investigated for the management of hypertension, with effective ability being stated in controlling high blood pressure and related health problems both in vivo and in vitro studies. Some of the activities presented by these bioactive compounds are reducing oxidative stress, renin-angiotensin system control, SIRT1 activation, regulating platelet aggregation and COX activity, anti-atherogenic effects, anti-inflammatory properties, vasorelaxation and other results that translate into the prevention or control of hypertension. The knowledge of these bioactive compounds is important in developing countries where traditional medicine is the majority, but it can also give rise to new approaches in hypertension therapy.

Promising Molecular Targets in Pharmacological Therapy for Neuronal Damage in Brain Injury.

The complex etiopathogenesis of brain injury associated with neurodegeneration has sparked a lot of studies in the last century. These clinical situations are incurable, and the currently available therapies merely act on symptoms or slow down the course of the diseases. Effective methods are being sought with an intent to modify the disease, directly acting on the properly studied targets, as well as to contribute to the development of effective therapeutic strategies, opening the possibility of refocusing on drug development for disease management. In this sense, this review discusses the available evidence for mitochondrial dysfunction induced by Ca2+ miscommunication in neurons, as well as how targeting phosphorylation events may be used to modulate protein phosphatase 2A (PP2A) activity in the treatment of neuronal damage. Ca2+ tends to be the catalyst for mitochondrial dysfunction, contributing to the synaptic deficiency seen in brain injury. Additionally, emerging data have shown that PP2A-activating drugs (PADs) suppress inflammatory responses by inhibiting different signaling pathways, indicating that PADs may be beneficial for the management of neuronal damage. In addition, a few bioactive compounds have also triggered the activation of PP2A-targeted drugs for this treatment, and clinical studies will help in the authentication of these compounds. If the safety profiles of PADs are proven to be satisfactory, there is a case to be made for starting clinical studies in the setting of neurological diseases as quickly as possible.

NMDA Inhibitors: A Potential Contrivance to Assist in Management of Alzheimer's Disease.

Alzheimer's disease (AD) is an increasingly common neurodegenerative disease that attracts the attention of researchers and medical community in order to develop new, safe and more effective drugs. Currently available drugs could only slow the AD progression and relieve the symptoms, in addition to being linked to moderate-to-severe side effects. N-methyl D-aspartate (NMDA) receptors antagonists were reported to have the ability to block the glutamate-mediated excitotoxic activity being good therapeutic targets for several neurodegenerative diseases, including AD. Based on data obtained so far, this review provides an overview over the use of NMDA antagonists for AD treatment, starting with a key emphasis on present features and future aspects regarding the use of NMDA antagonists for AD, and lastly a key focus is also given on its use in precision medicine.

Current insights into epigenetics, noncoding RNA interactome and clinical pharmacokinetics of dietary polyphenols in cancer chemoprevention.

Several studies have reported the health-beneficial effects of dietary phytochemicals, namely polyphenols, to prevent various diseases, including cancer. Polyphenols, like (-)-epigallocatechin-3-gallate (EGCG) from green tea, curcumin from turmeric, and ellagic acid from pomegranate are known to act by modulating antioxidant, anti-inflammatory and apoptotic signal transduction pathways in the tumor milieu. The evolving literature underscores the role of epigenetic regulation of genes associated with cancer by these polyphenols, primarily via non-coding RNAs (ncRNAs), such as microRNAs (miRNA) and long noncoding RNA (lncRNA). However, there is little clarity on the exact role(s) played by these ncRNAs and their interactions with other ncRNAs, or with their protein targets, in response to modulation by these dietary polyphenols. Here, we review ncRNA interactions and functional networks of the complex ncRNA interactome with their targets in preclinical studies along with the role of epigenetics as well as key aspects of pharmacokinetics and phytochemistry of dietary polyphenols. We also summarize the current state of clinical trials with these dietary polyphenols. Taken together, this synthetic review provides insights into the molecular aspects underlying the anticancer chemopreventive effects of dietary polyphenols as well as summarizes data on novel biomarkers modulated by these polyphenols for preventive or therapeutic purposes in various types of cancer.

Recent advances in the concept of paraprobiotics: Nutraceutical/functional properties for promoting children health.

Probiotics consumption has been associated with various health promoting benefits, including disease prevention and even treatment by modulating gut microbiota. Contrary to this, probiotics may also overstimulate the immune system, trigger systemic infections, harmful metabolic activities, and promote gene transfer. In children, the fragile immune system and impaired intestinal barrier may boost the occurrence of adverse effects following probiotics' consumption. To overcome these health challenges, the key focus has been shifted toward non-viable probiotics, also called paraprobiotics. Cell wall polysaccharides, peptidoglycans, surface proteins and teichoic acid present on cell's surface are involved in the interaction of paraprobiotics with the host, ultimately providing health benefits. Among other benefits, paraprobiotics possess the ability to regulate innate and adaptive immunity, exert anti-adhesion, anti-biofilm, anti-hypertensive, anti-inflammatory, antioxidant, anti-proliferative, and antagonistic effects against pathogens, while also enhance clinical impact and general safety when administered in children in comparison to probiotics. Clinical evidence have underlined the paraprobiotics impact in children and young infants against atopic dermatitis, respiratory and gastrointestinal infections, in addition to be useful for immunocompromised individuals. Therefore, this review focuses on probiotics-related issues in children's health and also discusses the Lactobacillus and Bifidobacterium spp. qualities for qualifying as paraprobiotics and their role in promoting the children's health.

Genome shuffling for phenotypic improvement of industrial strains through recursive protoplast fusion technology.

Strains' improvement technology plays an essential role in enhancing the quality of industrial strains. Several traditional methods and modern techniques have been used to further improve strain engineering programs. The advances stated in strain engineering and the increasing demand for microbial metabolites leads to the invention of the genome shuffling technique, which ensures a specific phenotype improvement through inducing mutation and recursive protoplast fusion. In such technique, the selection of multi-parental strains with distinct phenotypic traits is crucial. In addition, as this evolutionary strain improvement technique involves combinative approaches, it does not require any gene sequence data for genome alteration and, therefore, strains developed by this elite technique will not be considered as genetically modified organisms. In this review, the different stages involved in the genome shuffling technique and its wide applications in various phenotype improvements will be addressed. Taken together, data discussed here highlight that the use of genome shuffling for strain improvement will be a plus for solving complex phenotypic traits and in promoting the rapid development of other industrially important strains.

Pharmacological screening of species from the Lippia genus, content in terpenes and phenylpropanoids, and their vasorelaxing effects on human umbilical artery.

BACKGROUND: Naturally occurring bioactive compounds have a plethora of biological effects. OBJECTIVE: In this study, we examined a pharmacological screening of natural products on the human umbilical artery (HUA). METHODS: HUA preparations were used to follow contractions by KCl (60 mM) and tested at different concentrations (1-5000 µg/mL and µM) of the Lippia alba (EOLa) and Lippia origanoides (EOLo) essential oils, terpenes (citral, limonene perilic alcohol) and phenylpropanoids (eugenol, methyl eugenol). Discussion/Results: The reduction corresponded to approximately 100%, except for limonene (80±1.2 %). When evaluating the concentration of the natural product that promotes 50 % relaxation of the HUA contracted by KCL, EC50 values were: 424.3 µg/mL (EOLa); 468.7±6.7 µg/mL (EOLo); 264.2 ± 8.2 µM (citral); 677.8±5.4 µM (limonene); 186.3±6.4 µM (peryl alcohol); 986.4±7.9 µM (eugenol); and 279.1±4.4 µM (methyl-eugenol). Perillyl alcohol had a lower EC50 (consequently it has a higher pharmacological potency). CONCLUSION: The plant extracts have a promising vasorelaxing effect in HUAs, paving the way for future investigations: as applications in diseases related to these vessels, such as preeclampsia.

Chemical Composition and Bioinsecticidal Effects of Thymus zygis L., Salvia officinalis L. and Mentha suaveolens Ehrh. Essential Oils on Medfly Ceratitis capitata and Tomato Leaf Miner Tuta absoluta.

The present work was aimed to study the toxicity of the essential oils of three aromatic and medicinal plants on the tomato leaf miner Tuta absoluta and the Medfly Ceratitis capitata as an alternative to conventional pesticides. We carried out a phytochemical and insecticide study of T. zygis L., S. officinalis L. and M. suaveolens Ehrh. essential oils (EOs) through the study of their chemical composition and their toxicity on C. capitata adults and T. absoluta larvae. The extraction of the EOs by hydrodistillation showed yields of 3.87 ± 0.03, 4.09 ± 0.23 and 4.35 ± 0.11 for T. zygis, S. officinalis L. and M. suaveolens Ehrh., respectively. The identification of the chemical composition of the EOs by GC/MS showed that oxygenated monoterpenes constituted the most abundant group for all the extracted EOs. The major compounds were rather diversified depending on plant species. In fact, the S. officinalis L. EO mainly contained trans-thujone (21.80 %), the M. suaveolens Ehrh. EO mainly contained piperitenone oxide (71.19%), and carvacrol (61.60%) was the main component of the T. zygis L. EO. An insecticidal effect was observed for the three studied EOs on C. capitata adults and T. absoluta larvae. The observed LD50 values were 0.80 µL/mL and 11.04 µL/mL for M. suaveolens and S. officinalis, respectively, on T. absoluta larvae. For C. capitata adults, the obtained LD50 values were 0.9 µL/mL and 11.78 µL/mL for M. suaveolens and T. zygis, respectively. The presented findings could contribute to the development of biopesticides for plants as a component of integrated pest management strategies in citrus and tomato crops.

Revisiting the Nutritional, Chemical and Biological Potential of Cajanus cajan (L.) Millsp.

The genus Cajanus (Family: Fabaceae) consists of approximately 37 species, and Cajanus cajan (C. cajan) is a significant member of the genus. It is a commercial legume crop widely grown in sub-tropical and semi-arid tropical areas of the world. C. cajan is well known for its folk medicinal uses to treat various disorders, such as toothache, dizziness, diabetes, stomachache, female ailments and chronic infections. These properties have been linked to the presence of several value-added nutritional and bioactive components. Different solvent extracts from C.cajan (leaves, root, stem and seeds) have been evaluated for their phytochemical and biological activities, namely antioxidant, antimicrobial, antidiabetic, neuroprotective, and anti-inflammatory effects. Taken together, and considering the prominent nutraceutical and therapeutic properties of C. cajan, this review article focuses on the important details including ethnomedicinal uses, chemical composition, biological applications and some other medicinal aspects related to C.cajan nutraceutical and pharmacological applications.

Molecular Mechanisms of Anti-Inflammatory Phytochemicals.

Naturally occurring bioactives, also known as phytochemicals, have been widely recognized and researched owing to their multiple potentialities [...].

Extraction Kinetics and Reaction Rates of Sacred Lotus Stamen Tea Infusion-Derived Flavonoids in Relation with Its Antioxidant Capacity.

Stamen tea from Nelumbo nucifera Gaertn. (or the so-called sacred lotus) is widely consumed, and its flavonoids provide various human health benefits. The method used for tea preparation for consumption, namely the infusion time, may affect the levels of extractable flavonoids, ultimately affecting their biological effects. To date, there is no report on this critical information. Thus, this study aims to determine the kinetics of solid liquid extraction of flavonoid from sacred lotus stamen using the traditional method of preparing sacred lotus stamen tea. Phytochemical composition was also analyzed using high-performance liquid chromatography (HPLC). The antioxidant potential of stamen tea was also determined. The results indicated that the infusion time critically affects the concentrations of flavonoids and the antioxidant capacity of sacred lotus stamen tea, with a minimum infusion time of 5-12 min being required to release the different flavonoids from the tea. The extraction was modeled using second order kinetics. The rate of release was investigated by the glycosylation pattern, with flavonoid diglycosides, e.g., rutin and Kae-3-Rob, being released faster than flavonoid monoglycosides. The antioxidant activity was also highly correlated with flavonoid levels during infusion. Taken together, data obtained here underline that, among others, the infusion time should be considered for the experimental design of future epidemiological studies and/or clinical trials to reach the highest health benefits.

In vivo and in silico anti-inflammatory properties of the sesquiterpene valencene.

Valencene (VLN) is a sesquiterpene found in juices and essential oils of citrus species such as Cyperus rotundus. Considering the evidence that this species has anti-inflammatory effects, the present study aims to evaluate the anti-inflammatory activity of VLN in vivo and in silico. Swiss mice (n = 6) were orally treated according to their treatment groups as follows: VLN (10, 100 or 300 mg/kg), negative control (0.9% saline), and positive controls (indomethacin 25 mg/kg or promethazine 6 mg/kg). The anti-inflammatory activity was evaluated in murine models of acute and chronic inflammation. The inhibition of acute inflammation was evaluated in models of paw edema induced by different inflammatory agents (carrageenan, dextran, histamine, and arachidonic acid (AA)) and carrageenan-induced pleurisy and peritonitis. The modulation of chronic inflammation was evaluated in a granuloma model induced cotton pellets implantation. The interaction with inflammatory targets was evaluated in silico using molecular docking analysis. The administration of VLN to challenged mice significantly inhibited paw edema formation with no significant difference between the administered doses. The compound also reduced albumin extravasation, leukocyte recruitment, and the production of myeloperoxidase (MPO), IL-1ß, and TNF-α in both pleural and peritoneal lavages. According to the mathematical-statistical model observed in silico analysis, this compound has favorable energy to interact with the cyclooxygenase enzyme (COX-2) and the histamine 1 (H1) receptor. Finally, animals treated with the sesquiterpene showed a reduction in both granuloma weight and concentration of total proteins in a chronic inflammation model. Given these findings, it is concluded that NLV presents promising pharmacological activity in murine models of acute and chronic inflammation.