Polyphenols Research Articles

A Supramolecular Assembly of EGCG for Long-Term Treatment of Allergic Rhinitis.

Allergic rhinitis (AR) is a type-I hypersensitivity disease mediated by immunoglobulin E (IgE). Although antihistamines, glucocorticoids, leukotriene receptor antagonists, and other drugs are widely used to treat AR, the various adverse side effects of long-term use of these drugs should not be ignored. Therefore, more effective and safe natural alternative strategies are urgently needed. To this end, this study designed a nanosupramolecular delivery system composed of β-cyclodextrin supramolecular polymer (PCD), thiolated chitosan (TCS), and natural polyphenol epigallocatechin gallate (EGCG) for intranasal topical continuous treatment of AR. The TCS/PCD@EGCG nanocarriers exhibited an excellent performance in terms of retention and permeability in the nasal mucosa and released the vast majority of EGCG responsively in the nasal microenvironment, thus resulting in the significantly high antibacterial and antioxidant capacities. According to the in vitro model, compared with free EGCG, TCS/PCD@EGCG inhibited mast cell activity and abnormal histamine secretion in a more long-term and sustained manner. According to the in vivo model, whether in the presence of continuous or intermittent administration, TCS/PCD@EGCG substantially inhibited the secretion of allergenic factors and inflammatory factors, mitigated the pathological changes of nasal mucosa, alleviated the symptoms of rhinitis in mice, and produced a satisfactory therapeutic effect on AR. In particular, the therapeutic effect of TCS/PCD@EGCG systems were even superior to that of budesonide during intermittent treatment. Therefore, the TCS/PCD@EGCG nanocarrier is a potential long-lasting antiallergic medicine for the treatment of AR.

Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.

The Modulatory Effects of Curcumin on the Gut Microbiota: A Potential Strategy for Disease Treatment and Health Promotion.

Curcumin (CUR) is a lipophilic natural polyphenol that can be isolated from the rhizome of turmeric. Studies have proposed that CUR possesses a variety of biological activities. Due to its anti-inflammatory and antioxidant properties, CUR shows promise in the treatment of inflammatory bowel disease, while its anti-obesity effects make it a potential therapeutic agent in the management of obesity. In addition, curcumin's ability to prevent atherosclerosis and its cardiovascular benefits further expand its potential application in the treatment of cardiovascular disease. Nevertheless, owing to the limited bioavailability of CUR, it is difficult to validate its specific mechanism of action in the treatment of diseases. However, the restricted bioavailability of CUR makes it challenging to confirm its precise mode of action in disease treatment. Recent research indicates that the oral intake of curcumin may lead to elevated levels of residual curcumin in the gastrointestinal system, hinting at curcumin's potential to directly influence gut microbiota. Furthermore, the ecological dysregulation of the gut microbiota has been shown to be critical in the pathogenesis of human diseases. This review summarizes the impact of gut dysbiosis on host health and the various ways in which curcumin modulates dysbiosis and ameliorates various diseases caused by it through the administration of curcumin.

Abstract 1830: Bergenin inhibits growth of human cervical cancer cells by decreasing galectin-3 and MMP-9 expression

Abstract Cervical cancer is still the leading of cancer mortality worldwide, even after introducing a vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for more targeted therapy and lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus. Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties. Still, its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent -angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells at cellular level as shown by western blotting assay. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for Bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of Bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer. Citation Format: Mayank Singh, Ravi Chauhan, Lakshay Malhotra, Ashna Gupta, Gunjan Dagar, Dayasagar Das, Shahab Uddin, Ethayathulla Abdul Samath, Muzafar A. Macha, Ammira Al shabeeb Akil, Ajaz A. Bhat. Bergenin inhibits growth of human cervical cancer cells by decreasing galectin-3 and MMP-9 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1830.

Solvent and low temperature resistant natural polyphenolic adhesives

The development of robust and bioinspired adhesives with excellent performances including fast gel time, low cost, good adhesion strength and stability, and excellent solvent and temperature resistance against harsh environment is urgent for practical applications. In this paper, kinds of natural polyphenolic adhesives have been successfully fabricated via the multiple polyphenol-diisocyanate cross-linking (PDC) reactions between natural polyphenols (extracts) and diisocyanate molecules. Under heating, as-prepared adhesives could effectively adhere onto a wide range of substrates (i.e. PTFE, PET, PMMA, Al, Cu, paper, glass, wood) through hierarchical interactions. Moreover, these adhesives exhibited great adhesion stability against complex solvents and low-temperature environments, whose adhesion strength could remain unchanged after soaking solvents after 30 days, which was conducive to their potential applications in industry and chemical fields, including petroleum, wood, metal, glass, plastics, and rubber adhesion. We believed that this work would provide new strategies towards the preparation of robust adhesives with excellent resistant against various solvents and low temperature for many fields by using naturally occurring building blocks.

Review on the Effective Implications of Plant-generated Polyphenols as Novel Therapeutic Agents against Neurodegenerative Diseases

Abstract: Various neurodegenerative diseases have become a serious threat to human health all around the world. The progressive loss of functionality of active neurons causes neurodegenerative disease. Current research suggests that plant-derived foods, such as fruits and vegetables, are a good source of natural polyphenols, which can be effective in reducing the risk factors of neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), etc. These polyphenols exhibit cognitive repair and can reduce the production of reactive oxygen species (ROS) to establish neuroprotection. Various animal models were developed to understand the neuromodulatory and therapeutic activities of polyphenols for the treatment of AD, PD, HD, etc. Moreover, polyphenols indirectly modulate the gut microbiome to generate neuroprotection. Although there is a disadvantage to the low oral bioavailability of these polyphenols, the conjugation can enhance the efficiency of these compounds with nanoparticles. The present review gives an outline of plant-generated polyphenols and highlights their effects in the treatment of various neurodegenerative diseases. As a result, the prevention of aging-related disorders through natural products certainly shows excellent therapeutic efficiency soon. For this study, various reviews as well as original research articles from PubMed describing the possible therapeutic effects of dietary polyphenols to cure neurodegenerative diseases are used.

Effect of the combined binding of topotecan and catechin/protocatechuic acid to a pH-sensitive DNA tetrahedron on release and cytotoxicity: Spectroscopic and calorimetric studies

The therapeutic efficacy of chemotherapy drugs can be effectively improved through the dual effects of their combination with natural polyphenols and the delivery of targeted DNA nanostructures. In this work, the interactions of topotecan (TPT), (+)-catechin (CAT), or protocatechuic acid (PCA) with a pH-sensitive DNA tetrahedron (MUC1-TD) in the binary and ternary systems at pHs 5.0 and 7.4 were investigated by fluorescence spectroscopy and calorimetry. The intercalative binding mode of TPT/CAT/PC to MUC1-TD was confirmed, and their affinity was ranked in the order of PCA > CAT > TPT. The effects of the pH-sensitivity of MUC1-TD and different molecular structures of CAT and PCA on the loading, release, and cytotoxicity of TPT were discussed. The weakened interaction under acidic conditions and the co-loading of CAT/PCA, especially PCA, improved the release of TPT loaded by MUC1-TD. The targeting of MUC1-TD and the synergistic effect with CAT/PCA, especially CAT, enhanced the cytotoxicity of TPT on A549 cells. For L02 cells, the protective effect of CAT/PCA reduced the damage caused by TPT. The single or combined TPT loaded by MUC1-TD was mainly concentrated in the nucleus of A549 cells. This work will provide key information for the combined application of TPT and CAT/PCA loaded by DNA nanostructures to improve chemotherapy efficacy and reduce side effects.

Syrah Grape Polyphenol Extracts Protect Human Skeletal Muscle Cells from Oxidative and Metabolic Stress Induced by Excess of Palmitic Acid: Effect of Skin/Seed Ripening Stage.

Metabolic skeletal muscle (SM) dysfunction, triggered by increased oxidative stress and mitochondrial impairment, is a pivotal contributor to obesity-associated insulin resistance (IR). Addressing obesity and SM IR demands substantial lifestyle changes including regular exercise and dietary adjustments that are difficult to follow over time. This prompted exploration of alternative approaches. Grape polyphenols (GPPs) have demonstrated a positive impact on metabolism, although few studies have focused on SM. Since grape polyphenolic content and composition depend on tissue and ripening, we explored the antioxidant potential of GPPs from skin (Sk) and seeds (Sd) extracted before veraison (Bv) and at mature (M) stages, on palmitate-induced IR in primary human SM cells. Despite their important difference in polyphenol (PP) content: Sd-BvPP > Sd-MPP/Sk-BvPP > Sk-MPP, all extracts reduced lipid peroxidation by 44-60%, up-regulated the heme-oxygenase 1 protein level by 75-132% and mitochondrial activity by 47-68%. Contrary to the other extracts, which improved insulin response by 50%, Sd-BvPP did not. Our findings suggest that compounds other than stilbenoids or anthocyanin-type molecules, present only in grape Sk, could play an active role in regulating SM oxidative and metabolic stress and insulin sensitivity, paving the way for further exploration of novel bioactive compounds.

Resveratrol evokes neuroprotective effects and improves foot stance following kainate-induced excitotoxic damage to the mouse spinal cord

Excitotoxicity, characterized by over-activation of glutamate receptors, is a major contributor to spinal cord injury (SCI) pathophysiology, resulting in neuronal death and loss of locomotor function. In our previous in vitro studies, we showed that excitotoxicity induced by the glutamate analogue kainate (KA) leads to a significant reduction in the number of neurons, providing a model for SCI. Our current objective was to assess the neuroprotective role of resveratrol (RESV), a natural polyphenol, following KA-induced SCI. In vivo excitotoxicity was induced by intraspinal injection of KA immediately followed by RESV administration to Balb/C adult male mice. In neonatal mouse spinal cord preparations, excitotoxicity was transiently induced by bath-applied KA, either with or without RESV. KA administration resulted in a significant deterioration in hindlimb motor coordination and balance during locomotion, which was partially reverted by RESV. Additionally, RESV preserved neurons in both dorsal and ventral regions. Sirtuin 2 (SIRT2) immunoreactive signal was increased by RESV, while the selective SIRT1 inhibitor 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide (EX-527) attenuated RESV neuroprotective effects. These findings suggest that RESV attenuation of excitotoxic-induced neuronal loss and locomotor deficits is mediated, at least in part, through the activation of SIRT1, potentially involving SIRT2 as well. Indeed, our results highlight the potential use of RESV to enhance neuroprotective strategies for SCI.

Chicoric Acid Alleviates Colitis via Targeting the Gut Microbiota Accompanied by Maintaining Intestinal Barrier Integrity and Inhibiting Inflammatory Responses.

Polyphenols have shown great potential to prevent ulcerative colitis. As a natural plant polyphenol, chicoric acid (CA) has antioxidant and anti-inflammatory properties. This study explored the intervention effects and potential mechanism of CA on dextran sodium sulfate (DSS)-induced colitis mice. The results showed that CA alleviated the symptoms of colitis and maintained the intestinal barrier integrity. CA significantly downregulated the mRNA expression levels of inflammatory factors including IL-6, IL-1β, TNF-α, IFN-γ, COX-2, and iNOS. In addition, CA modulated the gut microbiota by improving the microbial diversity, reducing the abundance of Gammaproteobacteriaand Clostridium_XI and increasing the abundance ofBarnesiellaandLachnospiraceae. Further fecal microbiota transplantation experiments showed that FM from CA donor mice significantly alleviated the symptoms of colitis, verifying the key role of gut microbiota. These results indicate that CA effectively relieves DSS-induced colitis via targeting gut microbiota along with preserving intestinal barrier function and suppressing inflammatory responses.

Adsorption equilibrium, kinetics and dynamic process of polyphenols from orange peel extract on mixed‐mode adsorption resin HD‐1

AbstractBACKGROUNDThe extraction and separation of natural polyphenols are attractive. Many researchers used high‐speed counter‐current chromatography to separate and purify polyphenols. However, it requires a long operating time, a large amount of organic solvent consumption, and high operating costs. In this work, the adsorption behaviors of polyphenols from orange peel extract on mixed‐mode resins were studied. The adsorption capacities and selectivities of different resins to the main polyphenols in the extract including gallic acid, p‐coumaric acid and ferulic acid were compared. The adsorption mechanism was analyzed by adsorption equilibrium and kinetics studies as well as molecular docking. The fixed‐bed adsorption was studied experimentally and theoretically.RESULTSHD‐1 resin has excellent adsorption selectivities among the resins. The yield of polyphenols from orange peel by integrated extraction‐adsorption increased by 82.94% compared with that of extraction without adsorption. The adsorption isotherms agreed with the Freundlich model. Dubinin–Radushkevich model results indicated that the adsorption of gallic acid mainly depends on nonelectrostatic interaction. The adsorption of the other two polyphenols involves electrostatic and nonelectrostatic interaction. The adsorption kinetics curves accorded with the pseudo‐second‐order model, and the adsorption rate of gallic acid was the highest among the polyphenols. Adsorption of polyphenols involves both physical and chemical adsorption. The breakthrough curves could be closely simulated by Yoon–Nelson and Thoms models. Significant differences existed in times for 50% breakthrough.CONCLUSIONMixed‐mode chromatography with HD‐1 resin as stationary phase is applicable to the separation of polyphenols. © 2024 Society of Chemical Industry (SCI).

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis.

Keratoconus (KC) is a multifactorial disorder. This study aimed to conduct a systematic meta-analysis to exclusively explore the candidate proteins associated with KC pathogenesis. Relevant literature published in the last ten years in Pubmed, Web of Science, Cochrane, and Embase databases were searched. Protein expression data were presented as the standard mean difference (SMD) and 95% confidence intervals (CI). The meta-analysis is registered on PROSPERO, registration number CRD42022332442 and was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA). GO and KEGG enrichment analysis were performed, as well as the miRNAs and chemicals targeting the candidate proteins were predicted. PPI was analyzed to screen the hub proteins, and their expression was verified by RT-qPCR. A total of 21 studies were included in the meta-analysis, involving 346 normal eyes and 493 KC eyes. 18 deregulated proteins with significant SMD values were subjected to further analysis. In which, 7 proteins were up-regulated in KC compared with normal controls, including IL6 (SMD 1.54, 95%CI [0.85, 2.24]), IL1B (SMD 2.07, 95%CI [0.98, 3.16]), TNF (SMD 2.1, 95%CI [0.24, 3.96]), and MMP9 (SMD 1.96, 95%CI [0.68, 3.24]). While 11 proteins were down-regulated in KC including LOX (SMD 2.54, 95%CI [-4.51, -0.57]). GO and KEGG analysis showed that the deregulated proteins were involved in inflammation, extracellular matrix (ECM) remodeling, and apoptosis. MMP9, IL6, LOX, TNF, and IL1B were regarded as hub proteins according to the PPI analysis, and their transcription changes in stromal fibroblasts of KC were consistent with the results of the meta-analysis. Moreover, 10 miRNAs and two natural polyphenols interacting with hub proteins were identified. This study obtained 18 candidate proteins and demonstrated altered cytokine profiles, ECM remodeling, and apoptosis in KC patients through meta-analysis and bioinformatic analysis. It will provide biomarkers for further understanding of KC pathogenesis, and potential therapeutic targets for the drug treatment of KC.

Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR study

The Nociceptin/orphanin FQ peptide (NOP) receptor is considered a member of the opioid receptor subfamily of G-protein coupled receptors (GPCRs) which has been shown to be present in many parts of the central nervous system (CNS). It plays biologically diverse roles in pain modulation, immune response and in neurodegenerative diseases. In this work, phytochemical conjugates of two known neuropeptides, melanocyte inhibition factor (MiF-1) and mammalian amidated neuropeptide NPFF with pain modulating ability were developed. The binding interactions of those conjugates with NOP receptor was examined as an approach to develop novel natural compounds that can modulate NOP receptor activity. The selected phytochemicals are well-known for their antioxidant abilities and are derived either from natural alkaloids (betanin), polyphenols (gallic acid and sinapic acid) or terpenes (pomolic acid). Each of the phytochemicals selected are antioxidants which may play a role in mitigating diseases. Three conjugates of betanin were designed with each peptide by conjugating each of the three carboxylic acid groups of betanin with the peptides, while all others were mono-conjugates. Our results indicated that the betanin conjugates with both peptides showed strong binding interactions while the pomolate-peptide conjugates showed moderate binding. In general, NPFF and its conjugates showed stronger binding with the receptor. Docking and molecular dynamics studies revealed that binding interactions occurred at the binding pocket encompassing the transmembrane helices TM1, TM3 and TM7 in most cases, with the ligands binding deep within the hydrophobic core. The binding interactions were further confirmed experimentally through SPR analysis, which also showed higher binding with the betanin conjugates. MMGBSA studies indicated that the binding energies of MiF-1 conjugates were higher compared to neat MiF-1. However, in the case of NPFF, while the betanin conjugates showed enhancement, in some cases the binding energies were found to be slightly reduced compared to neat NPFF. Overall our studies reveal that such natural phytochemical derivatives that can bind to the NOP receptor when conjugated to the mammalian amidated neuropeptide NPFF and the short sequence of melanocyte inhibiting factor MiF-1 may be potentially developed for further laboratory studies for potential pharmaceutical applications.

Utilization of composite particles with customizable cross-linked lignin patches for dental cleansing

Lignin, a natural polyphenol polymer, is a biocompatible, cost-effective and accessible material. To fully utilize the benefits of lignin, it is crucial to transform its complex macromolecules into nanoscale particles in a single solvent. In this research, an assembly-mediated internal cross-linking method in single solvent was proposed to manufacture cross-linked lignin colloidal particles with nanoscale particle size controlled to be around 50 nm. Then, cross-linked lignin composite particles with a unique “patchy” structure for dental cleansing were obtained by rapidly grafting the cross-linked lignin colloidal particles onto the surface of silica microspheres through the bridging effect of silane coupling agent. The resulting composite particles have rivets with adjustable hardness, significantly lower than traditional abrasives like silica in both hardness and modulus. Through the group cleansing behavior of soft interlocking, a breakthrough has been achieved in the high solid content agglomeration friction mode of traditional abrasives, which effectively reduces tooth wear and exhibits an excellent plaque removal effect.

Brazilin-7-2-butenoate inhibits amyloid β-protein aggregation, alleviates cytotoxicity, and protects Caenorhabditis elegans

The fibrillogenesis of amyloid β-protein (Aβ) gradually accumulates to form neurotoxic Aβ aggregates in the human brain, which is the direct cause of Alzheimer's disease (AD) related symptoms. There are currently no effective therapies for AD. Brazilin, a natural polyphenol, inhibits Aβ fibrillogenesis, disrupts the mature fibrils and alleviates the corresponding cytotoxicity, but it also has the high toxic. Therefore, brazilin-7-2-butenoate (B-7-2-B), a brazilin derivative, was designed and synthesized. B-7-2-B exhibited lower toxicity and stronger inhibitory effect on Aβ aggregation than brazilin. B-7-2-B could prevent the formation of Aβ fibrils and oligomers, and depolymerize pre-formed aggregates in a dose-dependent manner. Furthermore, B-7-2-B prominently alleviated the cytotoxicity and the oxidative stress induced by Aβ aggregates in PC12 cells. The protective impacts of B-7-2-B were further demonstrated by using the Caenorhabditis elegans model, including decreasing the extent of Aβ aggregation, improving the motility and sensation disorders. Eventually, B-7-2-B was proven to be no apparent damage to worms. In summarize, it can be concluded that B-7-2-B has the potential as a drug for treating AD.

Adjuvant Anti-tumor Therapy with Polyphenolic Compounds: A Review

Abstract: The search for effective methods of treatment and prevention of oncological diseases, despite the successes achieved in recent decades, remains one of the most urgent issues in modern medicine. It is known that chemotherapy and radiation therapy are based on the induction of cell death by increasing the intracellular concentration of reactive oxygen species (ROS). To increase the effectiveness of chemo- and radiotherapy, inducing and increasing oxidative stress in tumor cells has been proposed. A new class of promising adjuvants in combination with anticancer therapy, which has already been shown to be effective in preclinical and clinical studies, includes natural and synthetic polyphenols. Polyphenolic compounds not only exhibit antitumor activity but also significantly reduce the resistance of tumor cells to chemo- and radiotherapy. However, almost all chemotherapeutic drugs and regimens of radiation treatment have a damaging toxic effect on normal tissues, which significantly affects the quality of life of patients, and treatment options for managing these side effects are limited. In this regard, some of the most promising agents for the management of toxic side effects are natural polyphenols. This study discusses the possible molecular mechanisms and prospects for the clinical use of natural and synthetic polyphenolic compounds in chemo- and radiotherapy. In addition, the protective role/effect of polyphenols on the effects of chemoand radiotherapy in tumor patients is discussed.

Effect of liposomal complexes of quercetin-rich flavonoids from French Marigold (Tagetes patula L.) on Jurkat cell viability

Background: Natural polyphenols are naturally used in traditional medicine to treat various diseases. Despite their healthful properties, ingesting phenolic compounds in food form does not provide a sufficient concentration for systemic therapeutic effects due to their low solubility in water, poor absorption, and fast metabolism. This problem has been solved by creating various composite pharmaceuticals from phenolic compounds using different methods to stabilize polyphenols. Objective: The purpose of this study was to assess the effects of the DPPA (1,2-palmitoyl phosphatidic acid) and DPPC (dipalmitoyl phosphatidylcholine) liposomes on the protective effects of a quercetin-rich flavonoid fraction extracted from French Marigold (Tagetes patula L.) on the viability of Jurkat cells. The study will examine both intact cells and cells that have been incubated under oxidative stress conditions. Materials and Methods: Quercetin-rich flavonoid fraction was extracted from a French Marigold (Tagetes patula L.) by thin-layer chromatography (TLC), High-pressure liquid chromatography (HPLC), and Liquid Chromatography-Mass Spectrometry (LC-MS) methods. Extract alone and in complex with dipalmitoyl phosphatidylcholine (DPPC) and 1,2- dipalmitoyl phosphatidic acid (DPPA) liposomes were added to the Jurkat cells culture at a rate of 2 mg/mL−1.The 3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium bromide (MTT) test assayed Cell viability by evaluating cellular dehydrogenase activity. Results: Flavonoids were separated and identified in the marigold extracts by TLC, HPLC, and LC-MS methods. The spectrophotometric absorption spectrum of the quercetin-rich flavonoid fraction extracted from French Marigold (Tagetes patula L.) shows two peaks corresponding to benzoyl (254nm) and cinnamyl (375nm) aromatic rings. In the complex of quercetin-rich flavonoid fraction with DPPC and DPPA liposomes, the spectrophotometric absorption peak at 254nm was not detected, while the absorption intensity of the peak at 375nm was sharply reduced. The quercetin-rich flavonoid fraction alone and in combination with DPPC liposome increased intact and incubated under low- and high-intensity oxidative stress conditions Jurkat cells’ viability but did not reveal effect in combination with DPPA liposome. Conclusions: The quercetin-rich flavonoid fraction extracted from French Marigold (Tagetes patula L.) forms stable complexes with DPPC and DPPA liposomes that allow the storage of high content of phenolic compounds in lipid nanocapsules. The use of the liposomal system in the pharmaceutical and food industry allows for carried and controlled bioactive-compound release, which is considered one of the main strategies to improve and enhance the quality of food, providing preventative healthcare for the population and decreasing the risk of disease. Keywords: bioactive-compound, polyphenols, Quercetin, Liposomes, Jurkat cells, therapeutic effects, pharmaceuticals

(206) Strategies of Nitric Oxide Augmentation for PDE5 Inhibitors

Abstract Introduction Erectile function and endothelial functions are closely related entities. Nitric oxide NO regulates circulation and microcirculation involved in erection.NO concentration is reduced with aging, diabetes, environment pollution smoking, obesity, inflammation, high prolactin, low testosterone oxidative stress and atherosclerosis. Many of erectile dysfunction patients are PDE5 inhibitor resistant. Strategies to enhance NO expression, can be employed to convert treatment resistant patient into responder. Objective Employ every possible mechanism to augment nitric oxide expression. Greater base line nitric oxide better would be PDE5 inhibitor respose. Methods Internet search was made on various website including pub med, science direct, google scholars using key words like erection, erectile dysfunction, nitric oxide, l arginine, oxidative stress, antioxidant, NOS, endothelial dysfunction, atherosclerosis and etc. This was followed by literature study on given topic. Results Efficacy of PDE 5 inhibitor in ED treatment is 70%. NO concentration decline to 50% by age of 40 and is only 15% at age 60. Humming can increase nasal NO level up to 15 time. Conclusions NO regulates endothelial function, vasodilatation, platelet aggregation inhibition, free radical scavenging, testosterone synthesis and neuronal protection. Study of mechanism of NO production provides, strategies for its enhancement. L arginine, L citrulline, serve as substrate and vitamin C, tetrahydrobiopterin (BH4) act as co factors in production of NO. Endothelial nitric oxide synthase e NOS, neuronal nitric oxide synthase n NOS are major enzymes act involved in synthesis. Oxygen is required for NO synthesis process. Supplementation of substrate and cofactors help increase NO levels. Oxygen availability can be increased through exercise and raising hemoglobin level. Reactive oxygen species ROS convert NO into bioinactive peroxynitrite which itself is ROS. Oxidative stress can cause endothelial nitric oxide synthase uncoupling. Consequently eNOS start producing ROS. This causes oxidation of NOS and as well as of cofactor like BH4 and vitamin C. ROS also increase level of methylarginines. Antioxidant used to neutralize ROS include Co Q10, alpha lipoic acid, flavonoids, bioflavonoids poly phenols, pycnogenol, resveterol, fulvic acid and etc. Second mechanism NO production is from dietary nitrates. Nutritional nitrates are converted into nitrite by oral anaerobic bacteria’s. Nitrate rich foods like beet root or spinach are added to enhance nitrate based NO. Nitric oxide thus produced is used for vasodilatation of penile vessels as well sinuses of corpus cavernousm. Apart from that it inhibits uncoupling of NOS. This support L arginine based mechanism of NO production. Nitroglycerin or minoxidal act as NO donors. These agents can be used locally at glans penis to augment NO availability. Bee breathing is maneuver in which humming sound vibrates nasal sinus increasing NO production up to 15 folds. Inhaled NO act as bronchodilator which increase lung capacity leading to higher blood oxygen concentration. Various NO enhancement strategies thus applied, may convert non responder PDE5 inhibitor to responders. Disclosure No.

Dual-ROS Sensitive Moieties Conjugate Inhibits Curcumin Oxidative Degradation for Colitis Precise Therapy.

Curcumin, a natural bioactive polyphenol with diverse molecular targets, is well known for its anti-oxidation and anti-inflammatory potential. However, curcumin exhibits low solubility (<1µgmL-1), poor tissue-targeting ability, and rapid oxidative degradation, resulting in poor bioavailability and stability for inflammatory therapy. Here, poly(diselenide-oxalate-curcumin) nanoparticle (SeOC-NP) with dual-reactive oxygen species (ROS) sensitive chemical moieties (diselenide and peroxalate ester bonds) is fabricated by a one-step synthetic strategy. The results confirmed that dual-ROS sensitive chemical moieties endowed SeOC-NP with the ability of targeted delivery of curcumin and significantly suppress oxidative degradation of curcumin for high-efficiency inflammatory therapy. In detail, the degradation amount of curcumin for SeOC is about 4-fold lower than that of free curcumin in an oxidative microenvironment. As a result, SeOC-NP significantly enhanced the antioxidant activity and anti-inflammatory efficacy of curcumin in vitro analysis by scavenging intracellular ROS and suppressing the secretion of nitric oxide and pro-inflammatory cytokines. In mouse colitis models, orally administered SeOC-NP can remarkably alleviate the symptoms of IBD and maintain the homeostasis of gut microbiota. This work provided a simple and effective strategy to fabricate ROS-responsive micellar and enhance the oxidation stability of medicine for precise therapeutic inflammation.

MiRNAs: Emerging Agents for Therapeutic Effects of Polyphenols on Ovarian Cancer.

In terms of female reproductive tract cancers, ovarian cancer remains the principal reason for mortality globally and is notably difficult to identify in its early stages. This fact highlights the critical need to establish prevention strategies for patients with ovarian cancer, look for new robust diagnostic and prognostic markers, and identify potential targets of response to treatment. MicroRNAs (miRNAs) are one of the novel treatment targets in cancer treatment. Thus, understanding the part of miRNAs in the pathogenesis and metastasis of ovarian cancer is at the center of researchers' attention. MiRNAs are suggested to play a role in modulating many essential cancer processes, like cell proliferation, apoptosis, differentiation, adhesion, epithelial-mesenchymal transition (EMT), and invasion. In two recent decades, natural polyphenols' anti-cancer features have been a focal point of research. Meanwhile, polyphenols are good research subjects for developing new cancer treatments. Polyphenols can modify miRNA expression and impact the function of transcription factors when used as dietary supplements. Multiple works have indicated the impact of polyphenols, including quercetin, genistein, curcumin, and resveratrol, on miRNA expression in vitro and in vivo. Here, we provide an in-depth description of four polyphenols used as dietary supplements: quercetin, genistein, curcumin, and resveratrol, and we summarize what is currently known about their regulatory abilities on influencing the miRNA functions in ovarian tumors to achieve therapeutic approaches.