Plant Polyphenolic Compounds Research Articles

The signaling pathway through which Procyanidin B2 increases the activity of the Na+/K+ ATPase in Caco-2 cells

Procyanidins are plant polyphenolic compounds reported to play a beneficial role in inflammatory bowel disease which is usually accompanied with a reduced activity of the Na+/K+ ATPase. Thus, a correlation between procyanidins and the ATPase was suspected and was examined in this work. The activity of the ATPase was assayed by measuring the amount of inorganic phosphate liberated in presence and absence of ouabain. Caco-2 cells treated with Procyanidin B2 exerted a stimulatory effect on the Na+/K+ ATPase which disappeared in the presence of inhibitors of PI3K, PKC, PKA, and COX enzymes. Exogenous PGE2 stimulated the ATPase via EP4 receptors and PKA. PKC was found to be downstream PI3K and upstream PGE2 while p38MAPK had a modulatory role but was not along the signaling pathway. It was concluded that procyanidin B2 acts via PI3K, activating PKC and leading to PGE2 release. PGE2 then stimulates the ATPase via EP4 and PKA.

Medicinal Properties of Plant Polyphenolic Compounds

Medicinal Properties of Plant Polyphenolic Compounds

Cardiovascular risk of dietary trimethylamine oxide precursors and the therapeutic potential of resveratrol and its derivatives.

Overall diet, lifestyle choices, genetic predisposition, and other underlying health conditions may contribute to higher trimethylamine N-oxide (TMAO) levels and increased cardiovascular risk. This review explores the potential therapeutic ability of RSV to protect against cardiovascular diseases (CVD) and affect TMAO levels. This review considers recent studies on the association of TMAO with CVD. It also examines the sources, mechanisms, and metabolism of TMAO along with TMAO-induced cardiovascular events. Plant polyphenolic compounds, including resveratrol (RSV), and their cardioprotective mechanism of regulating TMAO levels and modifying gut microbiota are also discussed here. RSV's salient features and bioactive properties in reducing CVD have been evaluated. The close relationship between TMAO and CVD is clearly understood from currently available data, making it a potent biomarker for CVD. Precise investigation, including clinical trials, must be performed to understand RSV's mechanism, dose, effects, and derivatives as a cardioprotectant agent.

Study of an inhibitory effect of plant polyphenolic compounds against digestive enzymes using bench-working experimental evidence predicted by molecular docking and dynamics

The substantial nutritional content and diversified biological activity of plant-based nutraceuticals are due to polyphenolic chemicals. These chemicals are important and well-studied plant secondary metabolites. Their protein interactions are extensively studied. This relationship is crucial for the logical development of functional food and for enhancing the availability and usefulness of polyphenols. This study highlights the influence of protein types and polyphenols on the interaction, where the chemical bindings predominantly consist of hydrophobic interactions and hydrogen bonds. The interaction between polyphenolic compounds (PCs) and digestive enzymes concerning their inhibitory activity has not been fully studied. Therefore, we have examined the interaction of four digestive enzymes (α-amylase, pepsin, trypsin, and α-chymotrypsin) with four PCs (curcumin, diosmin, morin, and 2′,3′,4′-trihydroxychalcone) through in silico and in vitro approaches. In vitro plate assays, enzyme kinetics, spectroscopic assays, molecular docking, and simulations were performed. We observed all these PCs have significant docking scores and preferable interaction with the active site of the digestive enzymes, resulting in the reduction of enzyme activity. The enzyme-substrate binding mechanism was determined using the Lineweaver Burk plot, indicating that the inhibition occurred competitively. Among four PCs diosmin and morin has the highest interaction energy over digestive enzymes with IC50 value of 1.13 ± 0.0047 and 1.086 ± 0.0131 μM. Kinetic studies show that selected PCs inhibited pepsin, trypsin, and chymotrypsin competitively and inhibited amylase in a non-competitive manner, especially by 2′,3′,4′-trihydroxychalcone. This study offers insights into the mechanisms by which the selected PCs inhibit the enzymes and has the potential to enhance the application of curcumin, diosmin, morin, and 2′,3′,4′-trihydroxychalcone as natural inhibitors of digestive enzymes.

Resveratrol can improve spinal cord injury by activating Nrf2/HO-1 signaling pathway

Spinal cord injury (SCI) often induces severe sensory and motor dysfunction. Oxidative stress is an important pathophysiological process of secondary SCI, and its inhibition could facilitate the alleviation of the injury. Resveratrol is a natural plant polyphenol compound that has significant antioxidant and anti-inflammatory effects. It can inhibit oxidative stress by activating the Nrf2/HO-1 signal pathway. In this report, we analyze the antioxidant effect of resveratrol in SCI, clarify the specific mechanism of action and provide a theoretical basis for the clinical employment of resveratrol for SCI.

Production of (hydroxy)benzoate-derived polyketides by engineered Pseudomonas with in situ extraction

Polyketides from (hydroxy)benzoates are an interesting group of plant polyphenolic compounds, whose biotechnological production is so far underrepresented due to their challenging heterologous biosynthesis. Efficient heterologous production of 2,4,6-tri- and 2,3′,4,6-tetrahydroxybenzophenone, 3,5-dihydroxybiphenyl, and 4-hydroxycoumarin by whole-cell biocatalysis in combination with in situ product extraction with an organic solvent was demonstrated. Production was highly dependent on the used CoA ligase and polyketide synthase type III. Therefore, different combinations of polyketide synthases and benzoate-CoA ligases were evaluated for their biosynthesis performance in the solvent-tolerant Pseudomonas taiwanensis VLB120. A solvent screening yielded 2-undecanone as biocompatible, extraction-efficient solvent with good phase separation. In aqueous-organic two-phase cultivations, this solvent extraction circumvents product instability in the aqueous cultivation medium, and it increases yields by reducing inhibitory effects. Complete de novo synthesis from glucose of all (hydroxy)benzoate-derived polyketides was achieved in two-phase cultivations with metabolically engineered strains. Additionally, mutasynthesis was applied to obtain fluorinated benzophenone derivatives.

Phytochemical profile and in vitro protoscolicidal effects of Juniperus phoenicea L., Calotropis procera (Aiton) Dryand, and Artemisia judaica L. against Echinococcus granulosus cysts

Context: Echinococcus granulosus (E. granulosus) is a significant zoonotic agent in veterinary and medicinal fields. Surgery and benzimidazole drugs are used as treatments but have significant drawbacks. Therefore, there is growing interest in ethnomedical approaches to investigating the scolicidal properties of plants traditionally as anthelmintics. Calotropis procera, Juniperus phoenicea, and Artemisia judaica are three plants traditionally used as anthelmintics. Aims: To examine the phytochemical composition and scolicidal capability against E. granulosus cysts of C. procera, J. phoenicea, and A. judaica methanolic extracts. Methods: Fresh E. granulosus cysts were isolated from livestock in southern Jordan and tested to determine the scolicidal potential of C. procera, J. phoenicea, and A. judaica aerial parts methanolic extracts, and their chemical compositions were examined using LC-MS. Results: Although all treatments were protoscolicidal, that of J. phoenicea exhibited higher protoscolices mortality rates at lower concentrations and treatment times than the other extracts. The LC-MS analysis revealed several components with biologically active properties were present in the plant extracts, including terpenes and polyphenolic compounds. Only C. procera contained the steroid uzarin and the flavonoid isoquercitrin. Conclusions: This study demonstrated the potent effects of A. judaica, J. phoenicea, and C. procera methanolic extracts against E. granulosus protoscoleces in vitro, indicating that these plants and/or their phytochemical components may be attractive sources of novel scolicidal medications.

Assessment of sperm quality in Plasmodium berghei NK65 infected mice treated with brimstone (Morinda lucida Benth) tree plant

Malaria fever is a common infection in Nigeria while the uncontrolled usage of synthesized anti-malarial drugs might have contributed to the ineffectiveness of the male reproductive hormones and the sperm quality in humans. Brimstone plant called “Oruwo” by Yoruba tribe in Nigeria has been used locally for the treatment of symptomatic malaria with no information of its effect on sperm quality. This study sought to evaluate the anti-plasmodial activity, reproductive hormones and sperm quality of the aqueous extracts on mice infected with Plasmodium berghei NK65. Adult male mice were infected with Plasmodium berghei NK65 while infection was confirmed after 72 h.The mice were divided into 5 groups [group A control, group B infected and treated with 2.5mgkg/bwt chloroquine (standard drug), group C infected without treatment while groups D and E were given 200 and 400mg/kg btw of the extracts respectively]. The treatment was orally administered daily for 7 days and the parasitemia level was checked after which the mice were sacrificed and the semen collected for sperm characteristics [sperm count, sperm viability, sperm morphology and sperm motility] while the right testis was used for the in-vivo antioxidant assays The blood serum was used to assess reproductive hormones such as [serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH)] using standardized methods. The results reveal that treatment of Morinda lucida caused a significant (p < 0.05) increase in serum testosterone and a decrease in LH, FSH levels in a dose-dependent manner as well as an increase in sperm count, motility and viability with a significant restoration of sperm morphology as seen in the histopathology plate. This observation might be due to the properties of the plant polyphenolic compounds identified. In conclusion, this study was able to prove that Morinda lucida used in folk-lore medicine to treat symptomatic malaria also improves sperm functions better than synthetic drugs and could be further explored as a natural product in the pharma industry.

Flavonoid Production: Current Trends in Plant Metabolic Engineering and De Novo Microbial Production.

Flavonoids are secondary metabolites that represent a heterogeneous family of plant polyphenolic compounds. Recent research has determined that the health benefits of fruits and vegetables, as well as the therapeutic potential of medicinal plants, are based on the presence of various bioactive natural products, including a high proportion of flavonoids. With current trends in plant metabolite research, flavonoids have become the center of attention due to their significant bioactivity associated with anti-cancer, antioxidant, anti-inflammatory, and anti-microbial activities. However, the use of traditional approaches, widely associated with the production of flavonoids, including plant extraction and chemical synthesis, has not been able to establish a scalable route for large-scale production on an industrial level. The renovation of biosynthetic pathways in plants and industrially significant microbes using advanced genetic engineering tools offers substantial promise for the exploration and scalable production of flavonoids. Recently, the co-culture engineering approach has emerged to prevail over the constraints and limitations of the conventional monoculture approach by harnessing the power of two or more strains of engineered microbes to reconstruct the target biosynthetic pathway. In this review, current perspectives on the biosynthesis and metabolic engineering of flavonoids in plants have been summarized. Special emphasis is placed on the most recent developments in the microbial production of major classes of flavonoids. Finally, we describe the recent achievements in genetic engineering for the combinatorial biosynthesis of flavonoids by reconstructing synthesis pathways in microorganisms via a co-culture strategy to obtain high amounts of specific bioactive compounds.

The Effect Of Gallic Acid As A Plant Polyphenol Compound On Oxidative Stress Induced In Alzheimer’s Neurodegenerative Disease.

Abstract Alzheimer’s disease as a neurodegenerative disorder is the most common reason of dementia. This disease is associated with many problems, including the inability to perform daily life activities and mood changes. The disease is defined by neuropathological signs including intracellular neurofibrillary tangles and extracellular amyloid beta plaques. Oxidative stress plays an important role in neurological diseases such as Alzheimer’s, which can change the signaling pathways and change the function of the tau protein. Since there are many sources of reactive oxygen species in neurons, these cells create a system of antioxidant defense to protect themselves from free radical damage. Disruption of this antioxidant defense can make nerve cells vulnerable to oxidative damage. Natural compounds that have antioxidant properties can largely protect cells against these oxidative damages. One of these compounds is gallic acid, which is a phenolic compound and has a very strong antioxidant activity. This compound is found in plants such as oak bark, tea leaves, sumac, grapes, coriander, honey, berries, pomegranate, mango, and other fruits and vegetables. Gallic acid inhibits the accumulation of beta-amyloid plaques and reduces neurotoxicity, which prevents neurotoxicity and oxidative damage. The aim of this study is to review the effect of gallic acid as a plant polyphenol compound on oxidative stress induced in Alzheimer’s neurodegenerative disease.

DNA Repair Activation and Cell Death Suppression by Plant Polyphenols in Keratinocytes Exposed to Ultraviolet Irradiation.

This work investigated effects of plant polyphenolic compounds (PPs) on responses of cultured human HaCaT keratinocytes to ultraviolet radiation in the C range (UV-C). The experimental data obtained indicate a cytoprotective effect of PPs added immediately after UV-C exposure. The efficiency of PPs was lowered in the following order: acacetin ≥ silybin > quercetin. The influence of PPs on phosphorylation of histone H2AX and the number of single-strand DNA breaks in the nuclei of keratinocytes were also studied. Using the comet assay and γH2AX staining, followed by fluorescence microscopy, it has been established that PPs can reduce DNA damage in the nuclei of keratinocytes exposed to UV-C. It is concluded that PPs can diminish the destructive effect of UV radiation on skin cells, activating the process of repairing genetic damage.

Pterostilbene Ameliorates Fumonisin B1-Induced Cytotoxic Effect by Interfering in the Activation of JAK/STAT Pathway.

Fumonisin B1 (FB1) is a mycotoxin that poses a great threat to agricultural production and the health of humans and animals. Pterostilbene (PTE) is a natural plant polyphenolic compound with good anti-inflammatory, antioxidant and cell regeneration effects, yet its effectiveness in treating FB1-induced cytotoxicity remains to be explored. In this study, we used porcine alveolar macrophages (3D4/21) as a model to characterize the cytotoxicity induced by FB1, and to investigate the potential alleviating effect of PTE on FB1-induced cytotoxicity. We demonstrate that FB1 induces cytotoxicity, apoptosis, pro-inflammatory cytokine production and mitochondrial damage, which can be largely recovered by PTE treatment, suggesting the promising application of PTE to treat FB1-induced damage. Mechanistically, FB1 activates the JAK/STAT signaling pathway, while PTE attenuates FB1-induced cytotoxicity through the inhibition of key JAK/STAT genes such as JAK2 and STAT3. Overall, our study characterized the molecular mechanism for FB1-induced cytotoxicity and found PTE to be a promising component which can alleviate FB1-induced cytotoxicity by interfering in the activation of JAK/STAT pathway.

Polyphenols and Their Nanoformulations: Protective Effects against Human Diseases.

Polyphenols are the secondary metabolites synthesized by the plants as a part of defense machinery. Owing to their antioxidant, anti-inflammatory, anticancerous, antineoplastic, and immunomodulatory effects, natural polyphenols have been used for a long time to prevent and treat a variety of diseases. As a result, these phytochemicals may be able to act as therapeutic agents in treating cancer and cardiovascular and neurological disorders. The limited bioavailability of polyphenolic molecules is one issue with their utilization. For the purpose of increasing the bioavailability of these chemicals, many formulation forms have been developed, with nanonization standing out among them. The present review outlines the biological potential of nanoformulated plant polyphenolic compounds. It also summarizes the employability of various polyphenols as nanoformulations for cancer and neurological and cardiovascular disease treatment. Nanoencapsulated polyphenols, singular or in combinations, effective both in vitro and in vivo, need more investigation.

The Beneficial Effects of Natural Extracts and Bioactive Compounds on the Gut-Liver Axis: A Promising Intervention for Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. It can cause fatty liver (steatosis), steatohepatitis, fibrosis, cirrhosis, and liver cancer. Alcohol consumption can also disturb the composition of gut microbiota, increasing the composition of harmful microbes and decreasing beneficial ones. Restoring eubiosis or preventing dysbiosis after alcohol consumption is an important strategy in treating ALD. Plant natural products and polyphenolic compounds exert beneficial effects on several metabolic disorders associated with ALD. Natural products and related phytochemicals act through multiple pathways, such as modulating gut microbiota, improving redox stress, and anti-inflammation. In the present review article, we gather information on natural extract and bioactive compounds on the gut-liver axis for the possible treatment of ALD. Supplementation with natural extracts and bioactive compounds promoted the intestinal tight junction, protected against the alcohol-induced gut leakiness and inflammation, and reduced endotoxemia in alcohol-exposed animals. Taken together, natural extracts and bioactive compounds have strong potential against ALD; however, further clinical studies are still needed.

In vitro release mechanism and cytotoxic behavior of curcumin loaded casein nanoparticles

In the recent past, drug delivery through nanoparticles is considered an effective tool to treat various diseases. Biopolymeric nanoparticles such as protein based nanoparticles have vital role as drug carrier as it is non-antigenic, and easily biodegradable. Curcumin, plant polyphenolic anticancerous compound was loaded into the casein nanoparticles by coacervation method. Particle size and surface charge of spherical casein nanoparticles as observed to be 201.4 nm and -86.9 mV. The loading efficiency of curcumin loaded casein nanoparticles was found to 85.05 %. In vitro drug release was performed at different pH (7.4 and 3.0), and the cumulative release was observed to be 24.8 and 20.13% and at different temperatures (25°C and 37°C), the cumulative release was observed to be 24.8 and 28.60 % respectively in 48 h. Curcumin release from casein nanoparticles was shown to be in a steady, and prolonged rate. The nanoparticles were observed to have an effective antimocrobial activity than curcumin in free form. The drug loaded casein nanoparticles were found to be potent particles to protect cells from hydrogen peroxide and UV light damage. The cytotoxic activity of nanoparticles on MCF7 and A549 cells were assayed and was observed to have an IC50 value of 609 and 825.2µg/ml. Cell death was observed to be through apoptosis, accompanied by DNA fragmentation.

Cytotoxicity and anti-small cell lung cancer potential of 3-methoxy-5-nitrosalicylaldehyde: an analog for treatment of diabetes mellitus with considerable binding affinity to α-amylase enzyme

Introductionα-Amylase inhibitors are present in plants and are thought to be produced by plants to strengthen their defenses against predators. They include plant components, polyphenolic compounds and glycoproteins with enzymatic inhibitory activity.Material and methodsIn this study, the inhibitory effect of metabolic enzyme was obtained, IC50: 95.14 µM. The molecular docking investigation was performed as a versatile method for the evaluation of the biological activities of 3-methoxy-5-nitrosalicylaldehyde in the presence of α-amylase. The compound exhibited a considerable binding affinity to the enzyme with a docking score of –7.676 kcal/mol.ResultsThe results of the molecular docking revealed that 3-methoxy-5-nitrosalicylaldehyde is able to construct hydrophobic contacts with crucial residues of the catalytic domain of the enzyme. According to these findings, the compound has the potential to be an inhibitor of α-amylase. The MTT test was used on normal (human umbilical vein endothelial cells (HUVECs)) and small cell lung cancer (SBC-3, DMS273, and DMS114) cell lines. 3-Methoxy-5-nitrosalicylaldehyde had high cell death and anti-small cell lung cancer effects against SBC-3, DMS273, and DMS114 cell lines. Among the above cell lines, the best result of anti-small cell lung cancer properties of the molecule was obtained in the cell line DMS273.ConclusionsThe results of this study indicated the excellent anti-small cell lung cancer potential of 3-methoxy-5-nitrosalicylaldehyde in in vitro conditions. After confirming the above results in the clinical trial research, this formulation may be administrated for the treatment of several types of small cell lung cancer in humans.

Assessment of Antioxidant and Antimutagenic Properties of Red and White Wine Extracts In Vitro.

Wine is an alcoholic beverage of complex composition obtained through the fermentation of grape must. The consumption of wine has already been associated with a multitude of beneficial effects due to its high polyphenolic content. In this study, four Greek emblematic wines from two red (i.e., Xinomavro and Agiorgitiko) and two white (i.e., Assyrtiko and Malagouzia) varieties were analyzed for the estimation of their antioxidant profiles. To address this question, we assessed their ability to scavenge both synthetic and endogenous free radicals, such as DPPH•, ABTS+•, OH•, O2−, their potential reducing power, and their antimutagenic and antigenotoxic properties. All varieties exhibited potent antioxidant activity, as indicated by the results of methods above, with the red wines appearing more effective than the white ones regarding antioxidant capacity. Our small-scale study is the first to reveal that these wine varieties may have the ability to scavenge the most reactive endogenous radicals. In the future, this finding must be accompanied by larger studies to fill a knowledge gap in the scientific literature concerning a holistic approach of the in vitro antioxidant action of plant polyphenolic compounds. Conclusively, we believe that wines possess high bioactivity that allow them to settle in the industry of food additives and medicinal products.

Antiviral Effects of Polyphenols from Marine Algae.

The disease-preventive and medicinal properties of plant polyphenolic compounds have long been known. As active ingredients, they are used to prevent and treat many noncommunicable diseases. In recent decades, marine macroalgae have attracted the attention of biotechnologists and pharmacologists as a promising and almost inexhaustible source of polyphenols. This heterogeneous group of compounds contains many biopolymers with unique structure and biological properties that exhibit high anti-infective activity. In the present review, the authors focus on the antiviral potential of polyphenolic compounds (phlorotannins) from marine algae and consider the mechanisms of their action as well as other biological properties of these compounds that have effects on the progress and outcome of viral infections. Effective nutraceuticals, to be potentially developed on the basis of algal polyphenols, can also be used in the complex therapy of viral diseases. It is necessary to extend in vivo studies on laboratory animals, which subsequently will allow proceeding to clinical tests. Polyphenolic compounds have a great potential as active ingredients to be used for the creation of new antiviral pharmaceutical substances.

24 Condensed tannins: structure, activity and characterization

Abstract As a class of plant polyphenolic compounds contained in some forages [i.e., sainfoin (Onobrychis viciifolia Scop.), big trefoil (Lotus pedunculatus Cav.), birdsfoot trefoil (Lotus corniculatus L.)], condensed tannins (CTs) exhibit a variety of biological effects on ruminants. The potential positive impact of CTs on the agricultural industry stems from their ability to modulate proteolysis during forage conservation and ruminal digestion, to prevent bloat, to reduce intestinal parasite burdens, and to abate methane and ammonia emissions from ruminants. How CTs exert these effects on ruminants focuses on the interaction of CTs with proteins. The structure-activity relationship in CT–protein interaction is not well understood but is known to be dependent on the structure and properties of both the CT and the protein. The objectives of this presentation are fivefold. First, examples of the structural diversity of CTs will be provided to enable the audience members to appreciate that not all CTs are the same. Second, examples of how CTs structural diversity affects their interaction with the protein, which in turn, dictates the biological response from the animal will be discussed. Third, the presentation will outline hurdles in obtaining highly pure and well-characterized CTs from natural sources for use in CT structural analysis and in vitro experiments. This will be followed by brief descriptions of improved and emerging techniques for CT analysis and, finally, the presentation concludes with questions to address in future investigations and a list of recommendations for CT researchers to follow.

RADIOPROTECTIVE PROPERTIES OF POLYPHENOLIC COMPOUNDS OF EDIBLE AND AROMATIC PLANTS

The proliferation of nuclear technologies threatens by the negative impact of ionizing radiation on the human body and requires the search of new effective means for prevention from radiation damage. Informational search in scientific editions and search databases on radioprotective effects of food and aromatic plants, radiation nephropathy and promising herbal drugs for its prevention has been carried out. Methods of analysis, systematization, comparison, generalization of information data have been applied. An overview of the results of experimental phytochemical and clinical studies of domestic and foreign scientists on radioprotective effects of biologically active substances of food and aromatic herbs has been carried out. It is revealed that plant polyphenolic compounds, due to their antioxidant properties, are able to neutralize free radicals and thus leading to a stop of radio-induced chain oxidation reactions in cells, to scavenge and neutralize of lipoperoxyl radicals, chelate ions of metals, as well as to exhibit antimutagenic activity. Radiotherapy might cause several radiation-induced kidney injuries, including radiation nephropathy. Search of promising herbal substances for prevention and alleviation of radiation nephropathy is under active investigation in recent years. Preventive inclusion of radioprotective agents, containing polyphenolic compounds, before irradiation seems to be an obvious renoprotective strategy. The prospect for further phytochemical, pharmacodynamic and toxicological studies of properties of polyphenolic compounds in food and aromatic plants with an objective to create new effective remedies for the prevention and treatment of radiation damage is shown.