Major Polyphenol Research Articles

Inhibitory activities of grape bioactive compounds against enzymes linked with human diseases.

A quest for identification of novel, safe and efficient natural compounds, as additives in the modern food and cosmetic industries, has been prompted by concerns about toxicity and side effects of synthetic products. Plant phenolic compounds are one of the most documented natural products due to their multifarious biological applications. Grape (Vitis vinifera) is an important source of phenolic compounds such as phenolic acids, tannins, quinones, coumarins and, most importantly, flavonoids/flavones. This review crisply encapsulates enzyme inhibitory activities of various grape polyphenols towards different key human-ailment-associated enzymes: xanthine oxidase (gout), tyrosinase (hyperpigmentation), α-amylase and α-glucosidase (diabetes mellitus), pancreatic lipase (obesity), cholinesterase (Alzheimer's disease), angiotensin i-converting enzymes (hypertension), α-synuclein (Parkinson's disease) and histone deacetylase (various diseases). The review also depicts the enzyme inhibitory mechanism of various grape polyphenols and briefly discusses their stature as potential therapeutic and drug development candidates. KEY POINTS: • Nineteen major bioactive polyphenols from the grape/grape products and their disease targets are presented • Sixty-two important polyphenols as enzyme inhibitors from grape/grape products are presented • A thorough description and graphical presentation of biological significance of polyphenols against various diseases.

Hyperoside and Quercitrin in Houttuynia cordata Extract Attenuate UVB-Induced Human Keratinocyte Cell Damage and Oxidative Stress via Modulation of MAPKs and Akt Signaling Pathway.

Ultraviolet radiation is a major environmental harmful factor on human skin. In this paper, we investigate the potential mechanism of Houttuynia cordata extract on UVB-induced HaCaT keratinocyte cell death and inflammation. We found that Houttuynia cordata ethyl acetate extract fraction (HC-EA) protected against UVB-induced cell damage. The HPLC results indicate that quercitrin and hyperoside are the major polyphenolics in HC-EA and are responsible for providing protection against UVB-induced cell death. These responses were associated with the regulation of caspase-9 and caspase-3 activation, which rescued HaCaT cells from UVB-induced apoptosis. In addition, HC-EA, quercitrin, and hyperoside attenuated UVB-induced inflammatory mediators, including IL-6, IL-8, COX-2, and iNOS. Furthermore, the treatment of cells with HC-EA and its active compounds abolished intracellular ROS and increased levels of heme oxygenase-1 and superoxide dismutase. UVB-induced ROS production mediated Akt and mitogen activated protein kinases (MAPKs) pathways, including p38, ERK, and JNK. Our results show HC-EA, quercitrin, and hyperoside decreased UVB-induced p38 and JNK phosphorylation, while increasing ERK and Akt phosphorylation. MAPKs and Akt mediated cell survival and death were confirmed by specific inhibitors to Akt and MAPKs. Thus, HC-EA, which contains quercitrin and hyperoside, protected keratinocyte from UVB-induced oxidative damage and inflammation through the modulation of MAPKs and Akt signaling.

Effects of luteolin-rich chrysanthemum flower extract on purine base absorption and blood uric acid in Japanese subjects

Background and objective: Chrysanthemum flowers are consumed as fresh condiments, herbal teas, and processed foods in Japan and Taiwan. They contain luteolin as a major polyphenol and are traditionally used for eye care. We previously demonstrated that the ingestion of Chrysanthemum flower extract (CFE) for 1 month reduced serum uric acid levels. However, the findings obtained were considered to be biased because the study was performed by a CFE manufacturer. Therefore, we herein conducted a clinical trial on CFE on a larger scale and examined its effects on purine base absorption from the intestines, which represents an effective approach for reducing serum uric acid levels. Methods: Both studies were performed as randomized, double-blind, placebo-controlled trials and CFE (100 mg) containing 1 mg of luteolin was used as the active sample. We enrolled 44 healthy Japanese men and women with 6.0 to 7.9 mg/dL serum uric acid. All subjects were randomly allocated to an active group (n=22) or placebo group (n=22) using a computerized random number generator. In the purine base absorption study, CFE was ingested with a purine base-rich diet and serum uric acid levels were measured chronologically. In the 12-week consecutive ingestion study, CFE or placebo was administered between January and April 2021. Serum uric acid levels after 12 weeks were assessed as the primary outcome, and uric acid were measured before and after 4 weeks of the intervention as secondary outcomes. Blood, urine and body parameters were examined to evaluate the safety of CFE. Results: Thirty-nine subjects completed the trial, and the per protocol set comprised 18 and 21 subjects in the active and placebo groups, respectively. In the single dosing study of CFE on subjects loaded by the purine base-rich diet, no significant changes were observed between the CFE and placebo groups. On the other hand, in the 12-week ingestion study, serum uric acid levels were significantly lower in the CFE group than in the placebo group. Laboratory tests revealed no abnormalities to suggest any side effects of CFE.Conclusions: CFE (100 mg/day) containing 1 mg of luteolin reduced serum uric acid levels. CFE may be beneficial for improving hyperurichemia. Trial Registration: UMIN-CTR: UMIN000042327Foundation: The present study was funded by Oryza Oil & Fat Chemical Co., Ltd. Keywords: Chrysanthemum, luteolin, uric acid, purine base

Evaluation of Phytochemical, Antimicrobial, and Antioxidant Properties of Wild versus Cultivated Olive Leaves

The relation between Olea europaea subspecies cuspidata and subspecies europaea in Saudi Arabia were investigated for determination of the bioactive compounds in olive leaves. The antioxidant and total phenolic content were demonstrated by HPLC/MS. Also, the antimicrobial agar gel well diffusion activity was done for ethanolic extracts. The study identified a great number of phenolic compounds out of which some anticancer compounds were identified. The content of olive leaves extract differs according to habitat (either wild or cultivated). The ethanolic extract of both types has high phenolic content (21.3 to 22.6 mg GA/gdw) and antioxidant activity (71% to 57%) for wild and cultivated leaf extracts, respectively. The phenolic profiles revealed the presence of plenty of flavonoids and phenolic compounds. The major polyphenol in the extracts is naringenin, which appears at peaks 8 with concentrations of 21.93 and 17.35 μg/mL for cultivated and wild leave respectively, which retention times 14.99 and 14.98. The antimicrobial activity showed that the leaves extract have strong antimicrobial activity against Bacillus subtilis, with the highest inhibition zones (28 and 26 mm) for wild and cultivated leaf extracts, respectively. This is considered as valuable data about the potential for industrial mass production of polyphenol.

Structure-based design and synthesis of a novel long-chain 4''-alkyl ether derivative of EGCG as potent EGFR inhibitor: in vitro and in silico studies.

Herein, we report the discovery of a novel long-chain ether derivative of (−)-epigallocatechin-3-gallate (EGCG), a major green tea polyphenol as a potent EGFR inhibitor. A series of 4′′-alkyl EGCG derivatives have been synthesized via regio-selectively alkylating the 4′′ hydroxyl group in the D-ring of EGCG and tested for their antiproliferative activities against high (A431), moderate (HeLa), and low (MCF-7) EGFR-expressing cancer cell lines. The most potent compound, 4′′-C14 EGCG showed the lowest IC50 values across all the tested cell lines. 4′′-C14 EGCG was also found to be significantly more stable than EGCG under physiological conditions (PBS at pH 7.4). Further western blot analysis and imaging data revealed that 4′′-C14 EGCG induced cell death in A431 cells with shrunken nuclei, nuclear fragmentation, membrane blebbing, and increased population of apoptotic cells where BAX upregulation and BCLXL downregulation were observed. In addition, autophosphorylation of EGFR and its downstream signalling proteins Akt and ERK were markedly inhibited by 4′′-C14 EGCG. MD simulation and the MM/PBSA analysis disclosed the binding mode of 4′′-C14 EGCG in the ATP-binding site of EGFR kinase domain. Taken together, our findings demonstrate that 4′′-C14 EGCG can act as a promising potent EGFR inhibitor with enhanced stability.

Study of Epilobium angustifolium L. amino acids content by HPLC method

The use of plant raw materials is one of the areas of modern pharmaceutical science in the production of herbal drugs. The genus Epilobium counts more than 200 species, many species of which are used in traditional medicine. Among the Epilobium species, Epilobium angustifolium is one of the well-known medicinal plants which have been used worldwide in habitual medicine. There is insufficient information in the literature on the biologically active substances of Epilobium angustifolium L. The presence of three major polyphenol groups: phenolic acids, flavonoids, and ellagitannins were identified in E. angustifolium extracts. Traditionally, the infusion of leaves of this plant could be useful for headaches, cold and gastrointestinal disorder. The Epilobium angustifolium L. as an insufficiently studied plant is a promising object of study, including amino acids composition. To assess the relationship between the production of primary metabolites and their possible therapeutic properties, we analyzed the amino acid profile of the plant Epilobium angustifolium used in traditional medicine. The study of compounds generated by plants as a result of defense mechanisms permits an understanding of the molecular mechanism involved in their medicinal properties.
 The aim. Thus, the aim of the study was to conduct an HPLC analysis of the amino acids of E. angustifolium to establish the prospects for the use of the raw materials in medical and pharmaceutical practice. The results of the current study will be used in further breeding programs aimed to obtain an industrial form of E. angustifolium suitable for pharmaceutical and food applications.
 Materials and methods. The determination of amino acids composition of Epilobium angustifolium was conducted using Agilent 1200 (Agilent Technologies, USA).
 Results. The HPLC method identified sixteen free amino acids and seventeen bound amino acids in the Epilobium angustifolium herb. The studies have shown that Epilobium angustifolium L. herb is mainly composed of free amino acids such as L-phenylalanine (1.65 µg/mg), L-glutamic acid (1.51 µg/mg), L-arginine (1.24 µg/mg), L-alanine (0.98 µg/mg) and L-aspartic acid (0.57 µg/mg), which were presents in the greatest amount. The dominant bound amino acids in the studied raw material were L-glutamic acid, L-aspartic acid, L-leucine, and L-alanine, the content of which was 32.37 µg/mg, 10.59 µg/mg, 8.70 µg/mg, and 6.22 µg/mg respectively.
 Conclusions. Using the HPLC method determined the amino acids in the herb of Epilobium angustifolium L. The concentrations of L-aspartic acid, L-glutamic acid, L-arginine, L-alanine and L-phenylalanine are predominate among free and bound amino acids in the Epilobium angustifolium L. herb. The result shows that Epilobium angustifolium L. is the source of amino acids, so the use of this plant raw material for new remedies is possible in the future

A comparative study of HPLC-DAD and UPLC-UV methods for simultaneous determination of 11 polyphenols in Moringa oleifera leaves

Purpose: To develop, validate and compare two chromatographic methods - high performance liquid chromatography with diode array detector ((HPLC-DAD) and high performance liquid chromatography with ultraviolet detection (UPLC-UV) for the effective analysis of polyphenols in Moringa oleifera leaves.Methods: HPLC-DAD and UPLC-UV methods were applied for the accurate determination of eleven major polyphenols in Moringa oleifera leaves. The chromatographic conditions of the eleven polyphenols was determined on two C18 column by gradient elution with 0.5 % phosphoric acid solution -acetonitrile as the eluate, and at a flow rate of 1.0 and 0.5 mL/min for HPLC-DAD and UPLC-UV methods, respectively. Detector parameter of UPLC-UV was fixed at 203 nm. The assay methods were validated systematically.Results: The instrumental methods (HPLC-DAD and UPLC-UV) had good linearity, precision,repeatability and recovery. For both methods, quantification limits of UPLC-UV (0.057 - 0.363 μg/mL) were lower than those of UPLC-UV (0.094 - 1.532 μg/mL). The UPLC method with a shorter running time and more sensitive detection was applied in comparing to the HPLC method. After optimization and evaluation, the baseline of 11 compounds was separated effectively within 68 and 34 min, respectively.Conclusion: The developed HPLC-DAD and UPLC-UV assays were successfully utilized for thesimultaneous analysis of eleven major polyphenols and can readily be utilized as quality control tools for Moringa oleifera leaves in China, with UPLC-UV method showing better separation, lower organic solvent usage and shorter analytical period.

Magnolol and Honokiol Inhibited the Function and Expression of BCRP with Mechanism Exploration.

Breast cancer resistance protein (BCRP), one of the ATP-binding cassette (ABC) transporters, was associated with the multidrug resistance (MDR) of chemotherapy. Magnolol (MN) and honokiol (HK) are major bioactive polyphenols of Magnolia officinalis. This study investigated the effects of MN and HK on the function and expression of BCRP for the purpose of developing BCRP inhibitor to overcome MDR. Cell lines including MDCKII-BCRP and MDCKII-WT were used for evaluating the function and expression of BCRP. The results showed that MN (100–12.5 µM) and HK (100–12.5 µM) significantly decreased the function of BCRP by 80~12% and 67~14%, respectively. In addition, MN and HK were verified as substrates of BCRP. Furthermore, MN and HK reduced the protein expression of BCRP, and inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K). In conclusion, both MN and HK decreased the function and expression of BCRP via EGFR/PI3K signaling pathway. Therefore, both compounds were promising candidates for reversing the MDR of chemotherapy.

Effects of isomerisation and oxidation on the immunomodulatory activity of chlorogenic acid in RAW264.7 macrophages

SummaryChlorogenic acid (CA) is one of the major polyphenols in fruit that contributes to most bioactivities. However, it is susceptible to isomerisation and oxidation in processing and thus displays varied bioactivity. This study aimed to evaluate the isomerisation and oxidation effects of CA on the potential immunomodulatory activity in RAW264.7 macrophages through the NF‐E2‐related factor‐2 (Nrf2) and nuclear factor‐kappa B (NF‐κB) signalling pathways. The results showed that isomerisation significantly affected the immunomodulation of CA by reducing Nrf2 and increasing NF‐κB nuclear translocation. The oxidation of CA weakened the effect of immune regulation in macrophages through impacts on the nucleic translocation of Nrf2 and NF‐κB, cellular reactive oxygen species (ROS) accumulation, antioxidant enzyme (superoxide dismutase, SOD) activity and cytokine expression. Consequently, isomerisation and oxidation remarkably affect the immunomodulation of CA via the Nrf2 and NF‐κB pathways.

HPTLC and FTIR Fingerprinting of Olive Leaves Extracts and ATR-FTIR Characterisation of Major Flavonoids and Polyphenolics.

The aim of this study was to analyse the effect of spontaneous microbial maceration on the release and extraction of the flavonoids and phenolics from olive leaves. Bioprofiling based on thin-layer chromatography effect-directed detection followed by ATR-FTIR spectroscopy proved to be a reliable and convenient method for simultaneous comparison of the extracts. Results show that fermentation significantly enhances the extraction of phenolic compounds and flavonoids. The polyphenolic content was increased from 6.7 µg GAE (gallic acid equivalents) to 25.5 µg GAE, antioxidants from 10.3 µg GAE to 25.3 µg GAE, and flavonoid content from 42 µg RE (rutin equivalents) to 238 µg RE per 20 µL of extract. Increased antioxidant activity of fermented ethyl acetate extracts was attributed to the higher concentration of extracted flavonoids and phenolic terpenoids, while increased antioxidant activity in fermented ethanol extract was due to increased extraction of flavonoids as extraction of phenolic compounds was not improved. Lactic acid that is released during fermentation and glycine present in the olive leaves form a natural deep eutectic solvent (NADES) with significantly increased solubility for flavonoids.

Phenolic Profiles and Biological Activities of Extracts from Edible Wild Fruits Ehretia tinifolia and Sideroxylon lanuginosum.

Ehretia tinifolia Linnaeus (Boraginacea) and Sideroxylon lanuginosum Michaux (Sapotaceae) are wild fruits consumed in North America and are appreciated for their pleasant flavor and sweet taste. However, details regarding their composition and biological properties in the available literature are scarce. This study reports the phenolic composition, antioxidant, antiproliferative activities, and digestive enzymatic inhibition of amberlite-retained methanolic extracts from both fruits. Results revealed that these wild fruit extracts are rich in antioxidants. S. lanuginosum had lower phenolic but higher flavonoid contents (21.4 ± 1.5 mg GAE/100 g FW and 6.42 ± 0.9 mg CE/100 g FW) than E. tinifolia (64.7 ± 2.6 mg GAE/100 g FW and 5.1 ± 0.4 mg CE/100 g FW). HPLC-DAD-MS/MS analysis showed rosmarinic acid as a major polyphenol in E. tinifolia and quercetin glucoside in S. lanuginosum. Polyphenols content in E. tinifolia was related to a significant free radical scavenging ability: DPPH (EC50 = 0.32 ± 0.03 mg/mL), TEAC (4134 ± 9.7 μM TE/g dry extract), and hemolysis inhibition (IC50 = 58.55 ± 2.4 μg/mL). Both extracts were capable of inhibiting α-glucosidase, partially inhibiting α-amylase, and showed no inhibition against lipase, while showing antiproliferative activity against HeLa, HT-29 and MCF-7 cancer cell lines. Our study revealed that these wild fruit extracts are rich in health-beneficial phytochemicals and hold significant potential for elaborating functional foods.

Impact of an Olive Leaf Polyphenol 3,4-DHPEA-EDA on Physical Properties of Food Protein Gels.

A cold-water extract of olive leaves (Olea europaea L.) is useful as a texture-improving agent for food protein gels. In this work, the compound contributing to the improvement of gel properties was investigated by using the egg white gel (EWG) as a model for food protein gels. Adding 1.0% (w/v) cold-water extract (OLEx) greatly improved the elasticity (2.1 times), viscosity (4.5 times), and breaking stress (1.4 times) of the EWG. Chemical analyses of the protein revealed that the enhancement of physical properties by OLEx was attributed to protein cross-linking activity of polyphenols. LC/MS and NMR analyses indicated that a major protein cross-linker is the dialdehydic form of demethoxycarbonylelenolic acid linked to hydroxytyrosol (3,4-DHPEA-EDA), which is an aglycone derived from oleuropein, a major polyphenol of olive leaves. These results suggest that 3,4-DHPEA-EDA generated by cold-water extraction from the leaf improves the physical properties, that is, texture, of protein gels.

Dietary and bioactive properties of the berries and leaves from the underutilized Hippophae salicifolia D. Don grown in Northeast India.

The online version contains supplementary material available at 10.1007/s10068-021-00988-8.

Inhibitory effects of hyperoside and quercitrin from Zanthoxylum bungeanum Maxim. leaf on 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine formation by trapping phenylacetaldehyde

2-amino-1-methyl-6-phenylimidazole[4,5-b]pyridine (PhIP) is one of the most abundant Heterocyclic amines (HAs) in meat products. Zanthoxylum bungeanum Maxim. leaf (ZML) extract has been shown to be rich in polyphenols, which are gaining increasing interest as efficient tools for inhibiting the formation of HAs. In the present work, the effects of ZML extract, major polyphenols, chlorogenic acid, hyperoside and quercitrin on the formation of PhIP in both roast beef patties and chemical model systems were investigated. UPLC-MS showed that ZML extract and those three polyphenols effectively inhibited PhIP formation. Additionally, GC-MS analysis showed that those three polyphenols significantly reduced the content of phenylacetaldehyde in the model systems, a key intermediate involved in PhIP formation. The subsequent UPLC-MS and TOF-MS/MS analysis found that hyperoside and quercitrin reacted with phenyacetaldehyde to form those four adducts, 8-C-(E-Phenylethenyl)hyperoside, 6-C-(E-Phenylethenyl)hyperoside, 8-C-(E-Phenylethenyl)quercitrin and 6-C-(E-Phenylethenyl)quercitrin, respectively. The results revealed that hyperoside and quercitrin could trap phenylacetaldehyde to form adducts, thereby, retarding the reaction of phenylacetaldehyde and creatinine, blocking the generation of PhIP.

Anthocyanins from Aristotelia chilensis Prevent Olanzapine-Induced Hepatic-Lipid Accumulation but Not Insulin Resistance in Skeletal Muscle Cells.

Type 2 diabetes and obesity are major problems worldwide and dietary polyphenols have shown efficacy to ameliorate signs of these diseases. Anthocyanins from berries display potent antioxidants and protect against weight gain and insulin resistance in different models of diet-induced metabolic syndrome. Olanzapine is known to induce an accelerated form of metabolic syndrome. Due to the aforementioned, we evaluated whether delphinidin-3,5-O-diglucoside (DG) and delphinidin-3-O-sambubioside-5-O-glucoside (DS), two potent antidiabetic anthocyanins isolated from Aristotelia chilensis fruit, could prevent olanzapine-induced steatosis and insulin resistance in liver and skeletal muscle cells, respectively. HepG2 liver cells and L6 skeletal muscle cells were co-incubated with DG 50 μg/mL or DS 50 μg/mL plus olanzapine 50 μg/mL. Lipid accumulation was determined in HepG2 cells while the expression of p-Akt as a key regulator of the insulin-activated signaling pathways, mitochondrial function, and glucose uptake was assessed in L6 cells. DS and DG prevented olanzapine-induced lipid accumulation in liver cells. However, insulin signaling impairment induced by olanzapine in L6 cells was not rescued by DS and DG. Thus, anthocyanins modulate lipid metabolism, which is a relevant factor in hepatic tissue, but do not significantly influence skeletal muscle, where a potent antioxidant effect of olanzapine was found.

Cryo-Ground Mango Kernel Powder: Characterization, LC-MS/MS Profiling, Purification of Antioxidant-Rich Gallic Acid, and Molecular Docking Study of Its Major Polyphenols as Potential Inhibitors against SARS-CoV-2 Mpro.

Mango processing waste (MPW) is an inexpensive and rich source of valuable substances. Hence, the mango kernel powder (MKP) from four cultivars (Chausa, Neelum, Barahmasi, and Dashehari) was characterized for the selection of the best cultivar. The MKP of the best cultivar (Dashehari) was analyzed for the profiling of polyphenols using LC-MS/MS in both modes of ionization (positive and negative) and indicated the presence of 50 compounds with specific retention times. After identification, gallic acid (GA), an important industrial compound, was targeted and purified followed by its confirmation using NMR (600 MHz) and HRMS. The antioxidant activity (IC50: 1.96 μg/mL) of extracted GA proposes its use as a natural antioxidant in novel food formulations. Additionally, SARS-CoV-2 main protease (Mpro) was selected for molecular docking based virtual screening of seven major polyphenols (MKP), and the results were compared with hydroxychloroquine. The docking scores of targeted polyphenols revealed that three compounds (epicatechin, mangiferin, and quercetin) exhibited appreciable proteolytic activity against Mpro. In this way, it is a favorable approach toward environmental safety on the standpoint of green chemistry owing to the use of food processing waste and elimination of the waste dumping/composting problems.

Prenatal EGCG exposure-induced heart mass reduction in adult male mice and underlying mechanisms

Epigallocatechin-3-gallate (EGCG), which is a major polyphenol in tea, has an unclear effect on cardiac development. In the present study, mice (C57BL/6) were exposed in utero to EGCG dissolved in drinking water (3 μg/ml) for 16 days. A significant decrease in the heart/body weight ratio was observed in adult males but not in adult females. The protein expression levels of TGF-β1 and its downstream transcription factors SMAD3 and SMAD4 were significantly decreased in male hearts. The PI3K/AKT signaling pathway was inhibited, the expression of proapoptotic proteins, such as BAX, Cleaved Caspase3 and Cleaved Caspase9, was elevated, and the level of antiapoptotic proteins, such as BCL-2, was decreased. A reduced heart/body weight ratio may be associated with the loss of cardiac fibers and an increase in myocardial apoptosis. The cardiac levels of aromatic hydrocarbon receptor and androgen receptor were elevated only in males, which may explain the sexual dimorphism in the effects. The promoter methylation levels of pik3r1, tgf-β, smad4 were elevated, and those of ahr were reduced, explaining the mechanism underlying the cardiac histological alteration caused by prenatal exposure to EGCG. The results suggest that ingestion of EGCG during pregnancy may be a risk factor for cardiac development in offspring.

Pomegranate, fruit of the desert, a functional food, and a healthy diet

Traditional medicinal plants contain various ranges of chemical contents and they have become popular because of effectiveness, frequently inadequate provision of modern medicine, preferences and cultural beliefs. Pomegranate belongs to the family of Punicaceae, and its various pharmacological activities are due to presence of wide range of bioactive compounds. The current searching was done by the keywords in main indexing systems including PubMed/MEDLINE, Scopus, and Institute for Scientific Web of Science as well as the search engine of Google Scholar. The keywords were traditional medicine, health benefits, pharmaceutical science, pomegranate, punicalin, punicalagin, and ellagitannins. Major polyphenols in peel and juice of pomegranate are flavonoids such as flavonols (catechin, epicatechin, gallocatechin), condensed tannins, phenolic acids such as gallic, ellagic and caffeic, hyrolysable tannins such as ellagitannins and gallotannins. The main organic acids in pomegranate juice are malic and citric, and in seed is fatty acids (punicic). The major alkaloids and lignans in peel are punigratane and isolariciresinol, respectively. Pomegranate fruit has been proven to act against various diseases like cancer, cardiovascular disorders, diabetes, AIDS, Alzheimer’s disease, male infertility, inflammation, coronary heart disease, and aging. The review summarizes the beneficial impacts of pomegranate which is recommended for consumption. Pomegranate is a high potential natural functional food due to its high pharmacological activities as an ancient efficacious natural drug.

Pharmacokinetic characterization of carnosol from rosemary (Salvia Rosmarinus) in male C57BL/6 mice and inhibition profile in human cytochrome P450 enzymes

Rosemary (Salvia Rosmarinus) is a rich source of dietary diterpenes with carnosol as one of the major polyphenols used to standardize rosemary extracts approved as a food preservative, however, at present there is not any information on the murine pharmacokinetic profile of carnosol or its potential for drug interactions. The present study utilizes cell-free, cell-based, and animal-based experiments to define the pharmacokinetic profile of the food based phytochemical carnosol. Mice were administered carnosol (100 mg/kg body weight) by oral gavage and plasma levels were analyzed by LC-MS/MS to establish a detailed pharmacokinetic profile. The maximum plasma concentration exceeded 1 μM after a single administration. The results are significant as they offer insights on the potential for food-drug interactions between carnosol from rosemary and active pharmaceutical ingredients. Carnosol was observed to inhibit selected CYP450 enzymes and modulate metabolic enzymes and transporters in in vitro assays.

Pomegranate peel polyphenols prophylaxis against SARS-CoV-2 main protease by in-silico docking and molecular dynamics study

Pomegranate peel, the waste product generated from pomegranate fruit, has prophylactic properties, such as antimicrobial, anti-malarial, and controls respiratory infections and influenza. Based on the previous literature and need of the hour, molecular docking was performed to evaluate the inhibitory effects of major pomegranate peel polyphenols against COVID-19. Among the 44 studied compounds, 37 polyphenols show interaction with the catalytic dyad of the Mpro protease and 18 polyphenols have a higher binding affinity than that of the Mpro protease inhibitor (N3), indicating their high probability of binding at ACE2: SARS-CoV-2 interface. Furthermore, several polyphenols studied in this work are found to have higher binding affinity as compared to those of hydroxychloroquine, lopinavir, nelfinavir, and curcumin, some of which have been earlier tested against COVID-19. Further, molecular dynamics simulations (200 ns) for Mpro–polyphenols including pelargonidin3-glucoside, quercetin3-O-rhamnoside, cyanidin3-glucoside and punicalin revealed highly stable complexes with less conformational fluctuations and similar degree of compactness. Estimation of total number of intermolecular hydrogen bonds and binding free energy confirmed the stability of these Mpro–polyphenol complexes over Mpro–curcumin complex. Based on the greater binding affinity of polyphenols of pomegranate peel towards Mpro as compared to that of curcumin, pomegranate peel may be considered in any herbal medicinal formulation or may be incorporated into daily diets for prevention of COVID-19. Communicated by Ramaswamy H. Sarma