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Naringin, a bioflavonoid compound from grapefruit or citrus, exerts anticancer activities on cervical, thyroid, colon, brain, liver, lung, thyroid, and breast cancers. The present investigation addressed exploring the anticancer effects of naringin on nasopharyngeal carcinoma (NPC) cells. Naringin exhibits a cytotoxic effect on NPC‐TW 039 and NPC‐TW 076 cells with IC50 372/328 and 394/307 μM for 24 or 48 h, respectively, while causing little toxicity toward normal gingival epithelial (SG) cells (>500/500 μM). We established that naringin triggered G1 arrest is achieved by suppressing cyclin D1, cyclin A, and CDK2, and upregulating p21 protein in NPC cells. Exposure of NPC cells to naringin caused a series of events leading to apoptosis including morphology change (cell shrinkage and membrane blebbing) and chromatin condensation. Annexin V and PI staining indicated that naringin treatment promotes necrosis and late apoptosis in NPC cells. DiOC6 staining showed a decline in the mitochondrial membrane potential by naringin treatment, which was followed with cytochrome c release, Apaf‐1/caspase‐9/‐3 activation, PARP cleavage, and EndoG expression in NPC cells. Naringin upregulated proapoptotic Bax and decreased antiapoptotic Bcl‐xL expression, and dysregulated Bax/Bcl‐xL ratio in NPC cells. Notably, naringin enhanced death receptor‐related t‐Bid expression. Furthermore, an increased Ca2+ release by naringin treatment which instigated endoplasmic reticulum stress‐associated apoptosis through increased IRE1, ATF‐6, GRP78, GADD153, and caspase‐12 expression in NPC cells. In addition, naringin triggers ROS production, and inhibition of naringin‐induced ROS generation by antioxidant N‐acetylcysteine resulted in the prevention of G1 arrest and apoptosis in NPC cells. Naringin‐induced ROS‐mediated G1 arrest and mitochondrial‐, death receptor‐, and endoplasmic reticulum stress–mediated apoptosis may be a promising strategy for treating NPC. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases. Topical treatments are recommended for all patients regardless of severity, making it essential to develop an effective topical AD treatment with minimal side effects; We investigated the efficacy of topical application of naringin in AD and explored the possible mechanisms using an AD mouse model induced by 1-chloro-2,4-dinitrobenzene (DNCB). Clinical, histological, and immunological changes related to AD and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling proteins in the skin tissues were measured as outcomes; Naringin treatment resulted in a significant improvement in dermatitis severity score and reduced epidermal thickness and mast cell count in the skin (p < 0.05). Naringin also demonstrated the ability to inhibit DNCB-induced changes in interleukin (IL) 4, chemokine (C-C motif) ligand (CCL) 17, CCL22, IL1β, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) levels by quantitative real-time polymerase chain reaction (qRT-PCR) and IL13 by enzyme-linked immunosorbent assay (ELISA) (p < 0.05). Western blot results exhibited the decreased JAK1, JAK2, STAT1, STAT3, phospho-STAT3, and STAT6 expression in the naringin-treated groups (p < 0.05); The findings of this study suggest that topical naringin may effectively improve the symptoms of AD and could be used as a therapeutic agent for AD. [ABSTRACT FROM AUTHOR]

The widespread presence of microplastics in the environment has raised significant concerns regarding their potential impact on human and animal health. Among various microplastic types, polyethylene microplastics (PE-MPs) are particularly prevalent due to the extensive use in packaging and consumer products. Exploring the uncharted therapeutic potentials of naringin, this study delves into its mitigating effects on disruptions in kallikrein-3 levels, steroidal-thyroidal hormone balance, and antioxidant defense triggered by PE-MPs exposure, paving the way for novel interventions in environmental toxin-induced endocrine and oxidative stress disorders. Male Wistar rats (n = 24) were randomly grouped into four: Control, PE-MPs (1.5 mg/kg), PE-MPs + NAR (1.5 mg/kg PE-MPs + 100 mg/kg NAR), and NAR (100 mg/kg). Hormonal and antioxidant parameters were assessed after 28 days of exposure. PE-MPs exposure caused a significant increase(p < 0.005) in the level of kallikrein-3 (KLK-3) while it significantly reduces the levels of testosterone (TST), luteinizing hormone, thyroid stimulating hormone (TSH) and Free-triiodothyronine (fT3) and Total cholesterol (TChol) concentration. PE-MPs exposure also disrupted significantly (p < 0.005) antioxidant profile by down-regulating the activities of glutathione-S-transferase, catalase (CAT), superoxide dismutase (SOD) and reducing levels of glutathione (GSH) and ascorbic acid (AA) while concentration of malondialdehyde (MDA) levels were increased relative to control. However, the mitigating potentials of naringin on disruptions in hormonal and antioxidant profiles caused by PE-MPs exposure were demonstrated, as NAR normalized KLK-3, steroid, and thyroid hormone levels, cholesterol concentration, and enhanced antioxidant defense. This suggests that NAR is a promising protective agent against endocrine and oxidative damage induced by environmental contaminants such as microplastics. [ABSTRACT FROM AUTHOR]

In the present work, phytoconstituents from Citrus limon are computationally tested against SARS‐CoV‐2 target protein such as Mpro ‐ (5R82.pdb), Spike ‐ (6YZ5.pdb) &RdRp ‐ (7BTF.pdb) for COVID‐19. Docking was done by glide model, QikProp was performed by in silico ADMET screening & Prime MM‐GB/SA modules were used to define binding energy. When compared with approved COVID‐19 drugs such as Remdesivir, Ritonavir, Lopinavir, and Hydroxychloroquine, plant‐based constituents such as Quercetin, Rutoside, Naringin, Eriocitrin, and Hesperidin. bind with significant G‐scores to the active SARS‐CoV‐2 place. The constituents Rutoside and Eriocitrin were studied in each MD simulation in 100 ns against 3 proteins 5R82.pdb, 6YZ5.pdb and 7BTF.pdb.We performed an assay with significant natural compounds from contacts and in silico results (Rutin, Eriocitrin, Naringin, Hesperidin) using 3CL protease assay kit (B.11529 Omicron variant). This kit contained 3CL inhibitor GC376 as Control. The IC50 value of the test compound was found to be Rutin −17.50 μM, Eriocitrin−37.91 μM, Naringin−39.58 μM, Hesperidine−140.20 μM, the standard inhibitory concentration of GC376 was 38.64 μM. The phytoconstituents showed important interactions with SARS‐CoV‐2 targets, and potential modifications could be beneficial for future development. [ABSTRACT FROM AUTHOR]

Objective(s): Gefitinib (GEF) is a targeted medicine used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). However, GEF’s hepatotoxicity limits its clinical use. This study aims to investigate the protective effect of naringin (NG) against GEF-induced hepatotoxicity. Materials and Methods: Fifty female ICR mice were randomly divided into 5 groups: Control, GEF (200 mg/kg), NG (50 mg/kg) + GEF (200 mg/kg), NG (100 mg/kg) +GEF (200 mg/kg), NG (200 mg/kg) +GEF (200 mg/kg). After 4 weeks of continuous administration, the mice were euthanized. The blood and liver tissue samples were collected. Results: The results indicated that the GEF group showed increased liver index, liver enzyme activities, and decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Some hepatocytes showed hydropic degeneration and focal necrosis. Cell apoptosis, Cleaved-caspase3, and Poly (ADP-ribose) polymerase 1 (PARP1) increased. Transmission electron microscopy revealed the presence of numerous autophagic lysosomes or autophagosomes around the cell nucleus. Compared to the GEF group, NG can reverse these changes. Conclusion: In summary, NG alleviates GEF-induced hepatotoxicity by anti-oxidation, inhibiting cell apoptosis, and autophagy. Therefore, this study suggests the use of NG to mitigate GEF’s toxicity to the liver. [ABSTRACT FROM AUTHOR]

The conjugates of gluten and polyphenols (naringin, hesperetin or curcumin) were produced by alkaline method and the effects of conjugation on physicochemical properties of gluten were investigated in this study. The results show that the conjugates possess lower content of free amino and sulfhydryl groups, and higher molecular mass, which indicate the covalent binding occurred. As compared with corresponding mixtures, the conjugates show lower intensity of the amide A, surface hydrophobicity, intermolecular β-sheets, interfacial and surface tension, as well as higher fluorescence intensity, antiparallel β-sheets and particle size (in the range of 130–150 μm). Furthermore, the conjugates also exhibit better emulsifying and foaming properties, higher storage modulus and lower degradation temperature than native gluten. However, the changes in physicochemical properties of conjugates depend on the type of polyphenols and curcumin-gluten conjugates possess the improved emulsifying, foaming and gelation properties among conjugates, due to their more flexible structure. [ABSTRACT FROM AUTHOR]

In order to solve the problems of flesh loss in the process of navel orange juice extraction and poor suspension stability of navel orange juice, this study used an industrial-scale microfluidizer system (ISMS) to prepare whole-flesh Gannan navel orange pulp, achieving ultra-fine pulp of Gannan navel orange. The effects of different ISMS processing pressures (0, 60, 90, and 120 MPa) on the physicochemical properties (particle size distribution, rheological properties, micro morphology, suspension stability, color, pH) and nutritional qualities (soluble solids, VC, carotenoids, limonin, naringin content) of Gannan navel orange pulp was investigated. The results showed that the particle size of whole-flesh Gannan navel orange pulp gradually decreased, and D[3,2] decreased from 59.77 μm to 26.47 μm when the ISMS pressure increased from 0 MPa to 120 MPa. The pulp particles were refined and dispersed more evenly. In addition, the apparent viscosity of orange pulp gradually increased, and the consistency coefficient K increased from 0.126 to 0.165. Compared with whole-flesh Gannan navel orange pulp without ISMS processing, when the ISMS processing pressure was 90 MPa, the instability index of navel orange pulp was the smallest, decreasing from 0.504 to 0.374, and the precipitation weight ratio was the highest, increasing from 40.80% to 59.48%, indicating that the suspension stability of the whole-flesh Gannan navel orange pulp was the best at this time. In addition, after ISMS processing, the C* of the whole flesh Gannan navel orange pulp gradually increased, and the overall color of the navel orange pulp became more saturated. Moreover, ISMS processing did not affect its pH and total soluble solid content. With the increase of ISMS processing pressure, the VC content in navel orange pulp increased by 11%, the total carotenoid content increased by 15%, and the limonin content increased by 10% after ISMS processing, but the naringin content remained was not changed. In summary, in order to preserve as much nutrients as possible, 120 MPa was chosen as the optimal pressure. This study shows that ISMS can produce whole-flesh Gannan navel orange pulp with good suspension stability and nutritional quality at the industrial level, providing a new pulping route for the navel orange industry. [ABSTRACT FROM AUTHOR]

An oral colon-targeted drug delivery system holds great potential in preventing systemic toxicity and preserving the therapeutic benefits of ulcerative colitis (UC) treatment. In this study, we developed a negatively charged PLGA-PEG nanoparticle system for encapsulating naringin (Nar). Additionally, chitosan and mannose were coated on the surface of these nanoparticles to enhance their mucosal adsorption and macrophage targeting abilities. The resulting nanoparticles, termed MC@Nar-NPs, exhibited excellent resistance against decomposition in the strong acidic gastrointestinal environment and specifically accumulated at inflammatory sites. Upon payload release, MC@Nar-NPs demonstrated remarkable efficacy in alleviating colon inflammation as evidenced by reduced levels of pro-inflammatory cytokines in both blood and colon tissues, as well as the scavenging of reactive oxygen species (ROS) in the colon. This oral nanoparticle delivery system represents a novel approach to treating UC by utilizing Chinese herbal ingredient-based oral delivery and provides a theoretical foundation for local and precise intervention in specific UC treatment. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is a major pathological basis of coronary heart disease. However, the currently available medications are unable to effectively reduce the incidence of cardiovascular events in the majority of patients with AS. Therefore, naringin has been attracting considerable attention owing to its anti-AS effects. Naringin can inhibit the growth, proliferation, invasion, and migration of vascular smooth muscle cells, ameliorate endothelial cell inflammation and apoptosis, lower blood pressure, halt the cell cycle at the G1 phase, and impede growth via its antioxidant and free radical scavenging effects. These activities suggest the potential anti-AS effects of naringin. In this review article, we comprehensively summarized the latest findings on the anti-AS effects of naringin and their underlying mechanisms, providing a crucial reference for future research on the anti-AS potential of this agent. [ABSTRACT FROM AUTHOR]

Naringin, a flavonoid, exhibits diverse therapeutic properties and has been proven to exert cytotoxic effects on cancer cells. Nevertheless, the precise mechanism of naringin maintaining its cytotoxic effect on glioblastoma (GBM) remains unknown. Thus, the current study aimed to establish a plausible cellular mechanism for Naringin's inhibition of GBM. We employed various system biology techniques to forecast the primary targets, including gene ontology and cluster analysis, KEGG enrichment pathway estimation, molecular docking, MD (molecular dynamic) simulation and MMPBSA analysis. Glioblastoma target sequences were obtained via DisGeNet and Therapeutic Target Prediction, aligned with naringin targets, and analyzed for gene enrichment and ontology. Gene enrichment analysis identified the top ten hub genes. Further, molecular docking was conducted on all identified targets. For molecular dynamics modelling, we selected the two complexes that exhibited the most docking affinity and the two most prominent genes of the hub identified through analysis of the enrichment of genes. The PARP1 and ALB1 signalling pathways were found to be the main regulated routes. Naringin exhibited the highest binding potential of − 12.90 kcal/mol with PARP1 (4ZZZ), followed by ABL1 (2ABL), with naringin showing a − 8.4 kcal/mol binding score, as determined by molecular docking. The molecular dynamic approach and MM-PBSA investigation along with PCA study revealed that the complex of Naringin, with 4ZZZ (PARP1) and, 2ABL (ABL1), are highly stable compared to that of imatinib and talazoparib. Analyses of the signalling pathway suggested that naringin may have anticancer effects against GBM by influencing the protein PARP and ALB1 levels. Cytotoxicity assay was performed on two different glioblastoma cell lines C6 and U87MG cells. Naringin demonstrates a higher cytotoxic potency against U87MG human glioblastoma cells compared to C6 rat glioma cells. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsDiscussionAlzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. This situation imposes a great burden on individuals, both economically and socially. Today, an effective method for treating the disease and protective approach to tau accumulation has not been developed yet. Studies have been conducted on the effects of hesperidin and naringin flavonoids found in citrus fruits on many diseases.In this review, the pathophysiology of AD is defined, and the effects of hesperidin and naringin on these factors are summarized.Studies have shown that both components may potentially affect AD due to their antioxidative and anti-inflammatory properties. Based on these effects of the components, it has been shown that they may have ameliorative effects on Aβ, α-synuclein aggregation, tau pathology, and cognitive functions in the pathophysiology of AD.There are studies suggesting that hesperidin and naringin may be effective in the prevention/treatment of AD. When these studies are examined, it is seen that more studies should be conducted on the subject. [ABSTRACT FROM AUTHOR]

Background: Endometritis seriously affects maternal reproductive health and fertility. Natural compounds have the characteristics of high efficiency and low residue in disease treatment. We aimed to discover and reveal the pharmacological effects of naringin, which is widely present in food and plants, on endometritis. Methods: Based on network pharmacology, the potential targets and pathways of naringin's actions on endometritis were predicted. Animal in vivo experiments were conducted to examine the inflammatory response of lipopolysaccharides (LPSs) in uterine tissue and the therapeutic effect of naringin. An in vitro primary bovine endometrial epithelial cell inflammation and drug treatment model was constructed. The production of reactive oxygen species (ROS) was measured using DCFH-DA, and the effect of naringin on LPS-induced endometritis was evaluated using HE staining, real-time quantitative PCR, Western blot, and immunofluorescence staining methods. Results: Naringin alleviated LPS-induced inflammatory injury and oxidative stress in the endometrium of mice and bovine endometrial epithelial cells (bEECs). Furthermore, in vitro studies were carried out to reveal the potential anti- inflammatory mechanisms of naringin based on network pharmacology. We found that naringin significantly inhibited LPS-stimulated endoplasmic reticulum stress (ERS)-related gene and protein expression, thus reducing the unfolded protein response (UPR). Furthermore, treatment of naringin attenuated the autophagic flux induced by ERS. In a further study, we observed that PI3K/AKT pathway inhibitors or ERS inducers partially reverse naringin's inhibition of autophagy and cell apoptosis. Conclusion: It is demonstrated that naringin suppresses autophagy by directly inhibiting the ERS-PI3K/AKT axis and exerting anti-inflammatory and antioxidant effects in endometritis. These findings provide novel insights into the pathogenesis of endometritis, highlighting potential therapeutic targets of traditional herbs and compounds. [ABSTRACT FROM AUTHOR]

Introduction: Bisphenol-A is categorized as an endocrine disruptor. A biological thiol antioxidant that lowers oxidative damage is alpha-lipoic acid. Flavone naringin has antioxidant properties. Aim of the Work: To evaluate the ability of α-Lipoic Acid and Naringin to ameliorate disruptive effects of BPA on the prostate gland in adult rats. Materials and Methods: Seventy-two adult rats were divided randomly into nine groups. Group I: (IA, IB and group IC). Group II: BPA, group III: BPA+α-LA, group IV: BPA+N, group V: BPA+α-LA+N, group VI: α-LA group, and group VII: N. After 30 days, the rats were sacrificed and evaluation of blood T, E2, weight gain, prostate volume, weight, index, and ventral lobe weight were done. The ventral lobes of Prostate were handled for the histological, immunohistochemical and morphometric analyses. Results: Bisphenol-A significantly reduced serum T and E2 levels, decreased the weight gain, increased the prostatic volume, prostatic weight, and the prostatic index. It induced histopathological alterations of the ventral lobe of the prostate by histological and immunohistochemical studies. These changes were also confirmed by the morphometric assessment of the prostate tissue. Alpha-lipoic acid exhibited mild improvement in all parameters. Naringin had a moderate improvement in the parameters disrupted by the BPA. The combination of the α-LA and the N showed synergistic effects compared to the BPA+α-LA and the BPA+N groups. It showed marked improvement in all parameters to be near to normal. Conclusion: Both Naringin and Alpha-lipoic acid have the potential to be effective protective agents against reproductive toxicity caused by endocrine disruptors. [ABSTRACT FROM AUTHOR]

A novel and facile surface molecularly imprinted polymer coated on magnetic chitosan (Fe3O4@CS@MIP) was fabricated for the selective recognition and enrichment of naringin (NRG). The Fe3O4@CS@MIP was prepared based on covalent–noncovalent synergistic imprinting strategies, utilizing 4‐vinyl phenyl boric acid as covalent functional monomer, deep eutectic solvent (choline chloride/methacrylic acid [ChCl/MAA]) as non‐covalent functional monomer and Fe3O4@CS nanoparticles as the magnetic support. The obtained Fe3O4@CS@MIP exhibited a uniform morphology, excellent crystallinity, outstanding magnetic properties, and high surface area. Owing to the double recognition abilities, the resultant polymer showed exceptional binding performance and rapid mass transfer in phosphate buffer (pH 7.0). The maximum binding amount of Fe3O4@CS@MIP was found to be 15.08 mg g−1, and the equilibrium adsorption could be achieved within 180 min. Moreover, they also exhibited stronger selectivity for NRG and satisfactory reusability, with only 11.0% loss after five adsorption‐desorption cycles. Additionally, the Fe3O4@CS@MIP, serving as an adsorbent, presented practical application potential in the separation and enrichment of NRG from pummelo peel, with extraction efficiency in the range of 79.53% to 84.63%. This work provided a new strategy for improving the performance of MIP and contributed an attractive option for the extraction of NRG in complex samples. [ABSTRACT FROM AUTHOR]

This study assessed the impact of sweetened alcohol and naringin on cardiac function in Sprague‐Dawley rats. Male (n = 40) and female (n = 40) rats were allocated to control, sweetened alcohol (SOH), naringin (NA), and sweetened alcohol with naringin (SOH + NA) groups. SOH and SOH + NA rats received 10% alcohol + 20% fructose in gelatine; SOH + NA and NA rats received 50 mg/kg naringin in gelatine daily for 10 weeks. Echocardiography was performed to assess left ventricular (LV) function. LV cardiomyocyte diameters and collagen area fraction were determined by H&E and picrosirius‐red staining, respectively. In males, sweetened alcohol and naringin did not affect cardiac function. Female SOH rats had increased LV end‐diastolic posterior wall (p = 0.04), relative wall thicknesses (p = 0.01), and LV cardiomyocyte diameters (p = 0.005) compared with control. Female SOH and SOH + NA had reduced lateral e' and e'/a' and increased E/e' (p < 0.0001). Female SOH (p = 0.01) and SOH + NA (p = 0.04) rats had increased LV collagen area fraction compared with controls. In males, neither sweetened alcohol nor naringin affected cardiac geometry or diastolic function. In females, sweetened alcohol induced concentric remodelling, impaired LV relaxation, and elevated filling pressures. Naringin may have the potential to improve the sweetened alcohol‐induced concentric remodelling; however, it did not ameliorate diastolic dysfunction in females. [ABSTRACT FROM AUTHOR]

Cisplatin nephrotoxicity is a well-known emergency clinical condition caused by oxidative stress and inflammation. Naringin (NAR) is considered an antioxidant agent with renoprotective effects capable of removing reactive oxygen species. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) are reported to have anti-inflammatory and antioxidant properties. The present research examined the renoprotective effect of the combination of NAR and AD-MSCs as opposed to each one alone on cisplatin-induced nephrotoxicity through SIRT-1/Nrf-2/HO-1 pathway. This study included five groups (n = 8 each) of male Sprague-Dawley rats (200 − 220 g): sham, cisplatin: rats receiving cisplatin (6.5 mg/kg, i.p.) on the 4th day; NAR+cisplatin: rats pretreated with NAR (1 week, i.p.) + cisplatin on the 4th day; AD-MSCs: rats receiving AD-MSCs (1 × 106) by injection through the tail vein on the 5th day + cisplatin on the 4th day; and NAR+AD-MSCs+cisplatin. On the 8th day, the animals were anesthetized to obtain tissue and blood samples. Biochemical factors, inflammation, oxidative stress, and gene expression were explored. Cisplatin increased blood urea nitrogen, creatinine, inflammation, and oxidative stress. Moreover, mRNA expression of Sirtuin1, nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (HO-1) remarkably reduced. Furthermore, cisplatin led to a disturbance in kidney structure (glomerular atrophy, cell infiltrations, and tubular dysfunction) as confirmed by histology findings. However, NAR pretreatment, AD-MSC administration, or a combination of both significantly reversed these changes. Overall, when used together, NAR and AD-MSCs had stronger cisplatin-induced effects on kidney dysfunction by inhibiting inflammation, reducing oxidative stress, and increasing the Sirtuin1/Nrf-2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

Objective: To explore the potential of metanephric mesenchymal cells (MMCs) for osteogenesis and naringin's ability to enhance this process and its molecular mechanism. Methods: Porcine MMCs at 70 days of gestation were used as tool cells, cultured in osteogenic induction medium, identified by immunocytochemistry staining. Osteogenic potential of porcine MMCs and naringin's ability to enhance this process was tested by detecting changes in cell viability, alkaline phosphatase (ALP) activity, the expression of runt-related transcription factor 2 (Runx2), osteopontin (OPN) and osteocalcin (OCN), and the formation of mineralized nodules, and the application of the p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin. Results: Immunocytochemical staining showed that the cells were Vimentin and Six2(+), E-cadherin and CK-18(−). Naringin can activate the p38 signaling pathway to enhance the osteogenesis of porcine MMCs by increasing cell viability, ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). The application of p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin, manifested by decreased ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). Conclusion: Naringin, the active ingredient of Chinese herbal medicine Rhizoma Drynariae for nourishing Shen (Kidney) and strengthening bone, enhances the osteogenic differentiation of renal MMCs through the p38 signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract The widespread presence of microplastics in the environment has raised significant concerns regarding their potential impact on human and animal health. Among various microplastic types, polyethylene microplastics (PE-MPs) are particularly prevalent due to the extensive use in packaging and consumer products. Exploring the uncharted therapeutic potentials of naringin, this study delves into its mitigating effects on disruptions in kallikrein-3 levels, steroidal-thyroidal hormone balance, and antioxidant defense triggered by PE-MPs exposure, paving the way for novel interventions in environmental toxin-induced endocrine and oxidative stress disorders. Male Wistar rats (n = 24) were randomly grouped into four: Control, PE-MPs (1.5 mg/kg), PE-MPs + NAR (1.5 mg/kg PE-MPs + 100 mg/kg NAR), and NAR (100 mg/kg). Hormonal and antioxidant parameters were assessed after 28 days of exposure. PE-MPs exposure caused a significant increase(p

Abstract An oral colon-targeted drug delivery system holds great potential in preventing systemic toxicity and preserving the therapeutic benefits of ulcerative colitis (UC) treatment. In this study, we developed a negatively charged PLGA-PEG nanoparticle system for encapsulating naringin (Nar). Additionally, chitosan and mannose were coated on the surface of these nanoparticles to enhance their mucosal adsorption and macrophage targeting abilities. The resulting nanoparticles, termed MC@Nar-NPs, exhibited excellent resistance against decomposition in the strong acidic gastrointestinal environment and specifically accumulated at inflammatory sites. Upon payload release, MC@Nar-NPs demonstrated remarkable efficacy in alleviating colon inflammation as evidenced by reduced levels of pro-inflammatory cytokines in both blood and colon tissues, as well as the scavenging of reactive oxygen species (ROS) in the colon. This oral nanoparticle delivery system represents a novel approach to treating UC by utilizing Chinese herbal ingredient-based oral delivery and provides a theoretical foundation for local and precise intervention in specific UC treatment.

Abstract Naringin, a flavonoid, exhibits diverse therapeutic properties and has been proven to exert cytotoxic effects on cancer cells. Nevertheless, the precise mechanism of naringin maintaining its cytotoxic effect on glioblastoma (GBM) remains unknown. Thus, the current study aimed to establish a plausible cellular mechanism for Naringin’s inhibition of GBM. We employed various system biology techniques to forecast the primary targets, including gene ontology and cluster analysis, KEGG enrichment pathway estimation, molecular docking, MD (molecular dynamic) simulation and MMPBSA analysis. Glioblastoma target sequences were obtained via DisGeNet and Therapeutic Target Prediction, aligned with naringin targets, and analyzed for gene enrichment and ontology. Gene enrichment analysis identified the top ten hub genes. Further, molecular docking was conducted on all identified targets. For molecular dynamics modelling, we selected the two complexes that exhibited the most docking affinity and the two most prominent genes of the hub identified through analysis of the enrichment of genes. The PARP1 and ALB1 signalling pathways were found to be the main regulated routes. Naringin exhibited the highest binding potential of − 12.90 kcal/mol with PARP1 (4ZZZ), followed by ABL1 (2ABL), with naringin showing a − 8.4 kcal/mol binding score, as determined by molecular docking. The molecular dynamic approach and MM-PBSA investigation along with PCA study revealed that the complex of Naringin, with 4ZZZ (PARP1) and, 2ABL (ABL1), are highly stable compared to that of imatinib and talazoparib. Analyses of the signalling pathway suggested that naringin may have anticancer effects against GBM by influencing the protein PARP and ALB1 levels. Cytotoxicity assay was performed on two different glioblastoma cell lines C6 and U87MG cells. Naringin demonstrates a higher cytotoxic potency against U87MG human glioblastoma cells compared to C6 rat glioma cells.

BACKGROUND: It has been found that abnormal apoptosis of bone tissue cells induced by abnormal iron metabolism plays an important role in the progression of osteoporosis. OBJECTIVE: To investigate the effect of naringin on iron metabolism and cell apoptosis in bone tissue of rats with osteoporosis. METHODS: Fifty 2-month-old female Sprague-Dawley rats were randomly divided into five groups with 10 rats in each group: sham group, osteoporosis group, naringin low-dose group, naringin high-dose group, and naringin high-dose+DKK-1 group. Except for the sham group, rat models of osteoporosis were established by removing bilateral ovarian tissues in the other groups. At 8 weeks after modeling, rats in the naringin low- and high-dose groups were given 100 and 400 mg/kg/d naringenin by gavage, respectively, and rats in the naringenin high dose+DKK-1 group were given 400 mg/kg/d naringin by gavage and subcutaneous injection of 25 mg/kg/d DKK-1, an inhibitor of the Wnt1 signaling pathway, for 7 consecutive days. Relevant indexes were detected after administration. RESULTS AND CONCLUSION: Compared with the osteoporosis group, naringin could enhance the bone mineral density and serum calcium and superoxide dismutase levels in rats (P < 0.05), and reduce the serum levels of osteocalcin, malondialdehyde, and phosphorus (P < 0.05), while DKK-1 could partially inhibit the interventional effect of naringin (P < 0.05). Results from Micro-CT scanning, hematoxylin-eosin and TUNEL staining showed that compared with the osteoporosis group, naringin significantly improved bone microstructure and reduced the rate of cell apoptosis, while DKK-1 partially inhibited the interventional effect of naringin. Immunofluorescence staining results showed that compared with the osteoporosis group, naringin could reduce the oxygen content, anti-tartaric acid phosphatase expression, and elevate the expression of alkaline phosphatase in active tibia tissues (P < 0.05), while DKK-1 could partially inhibit the interventional effect of naringin (P < 0.05). Results from Prussian blue staining and immunohistochemical staining showed that compared with the osteoporosis group, naringin reduced iron deposition in bone and liver tissues as well as the expression of transferrin receptor 1 (P < 0.05), and elevated the protein expression of ferroportin 1 (P < 0.05) in bone tissue, and DKK-1 partially inhibited the intervention of naringin (P < 0.05). PCR and western blot assay of tibia specimens showed that compared with the osteoporosis group, naringin decreased the expression of anti-tartrate acid phosphatase, transferrin receptor 1 and Bax (P < 0.05), and elevated the expression of alkaline phosphatase, ferroportin 1, Bcl-2, Wnt1 and β-catenin (P < 0.05), while DKK- 1 partially inhibited the interfering effect of naringin (P < 0.05). To conclude, naringin inhibits the progression of osteoporosis by reducing iron deposition and apoptosis rate in bone tissue, which may be related to the activation of the Wnt1 signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent studies have shown that research on naringin anti-osteoporosis mostly stays in in vitro and in vivo experiments. Understanding the mechanism of related signaling pathways and the expression of related proteins and some specific genes is an important way to deeply understand naringin anti-osteoporosis. At present, traditional Chinese medicine has been confirmed to have a significant role in anti-osteoporosis. Naringin is one of the main active ingredients in Rhizoma Drynariae. Its effectiveness and mechanism of action against osteoporosis have been gradually recognized by scholars, and its clinical and basic research has been gradually emphasized. OBJECTIVE: To analyze and summarize the research progress of naringin in anti-osteoporosis in vitro and in vivo, thereby providing some ideas for the next step to study its related mechanism of action. METHODS: The relevant literatures included in CNKI and PubMed database were searched with the Chinese search terms of “naringin, osteoporosis, traditional Chinese medicine compound, pathogenesis, signaling pathway, bone marrow mesenchymal stem cells, osteoblasts, osteoclasts” in Chinese and English, respectively. The corresponding criteria were established according to the research needs, and finally 69 articles were included for review. RESULTS AND CONCLUSION: Naringin blocks the increase in the number of osteoclasts and adipocytes, the decrease in the number of osteocytes and osteocalcin (+) cells induced by fructose-rich diet, and promotes the secretion of Sema3A from osteoblasts and osteocytes, thereby enhancing local bone formation and inhibiting osteoclast production by activating the Wnt/β-catenin pathway. Naringin is an important way to induce autophagy of osteoblasts, but autophagy-related proteins participate in osteoblast differentiation and bone formation. Lack of autophagy in osteoblasts reduces mineralization and leads to an imbalance in the number of osteoblasts and osteoclasts, which results in bone loss and decreased bone density. The composite scaffold loaded with naringin can be used as a necessary carrier for bone defect repair and has excellent bone repair properties. Naringin can also accelerate the growth of new bone tissue by increasing the local contents of bone morphogenetic protein 2 and vascular endothelial growth factor. Naringin can regulate bone metabolism and inhibit oxidative stress via ERK, PI3K/Akt and Wnt signaling pathways to improve osteoporosis, which can play a good role in preventing and controlling the disease. However, the depth and breadth of the relevant research is insufficient. Based on the mechanism of the current study, we should investigate the specific mechanisms by which naringin regulates different pathways and inter-pathway interactions in the future, which will be beneficial to the multifaceted development of naringin used in the treatment of osteoporosis.. [ABSTRACT FROM AUTHOR]

The function of mitochondria as a regulator of myocyte calcium homeostasis has been extensively discussed. The aim of the present work was further clarification of the details of modulation of the functional activity of rat cardiac mitochondria by exogenous Ca2+ ions either in the absence or in the presence of the plant flavonoid naringin. Low free Ca2+ concentrations (40–250 nM) effectively inhibited the respiratory activity of heart mitochondria, remaining unaffected the efficacy of oxygen consumption. In the presence of high exogenous Ca2+ ion concentrations (Ca2+ free was 550 µM), we observed a dramatic increase in mitochondrial heterogeneity in size and electron density, which was related to calcium-induced opening of the mitochondrial permeability transition pores (MPTP) and membrane depolarization (Ca2+free ions were from 150 to 750 µM). Naringin partially prevented Ca2+-induced cardiac mitochondrial morphological transformations (200 µM) and dose-dependently inhibited the respiratory activity of mitochondria (10–75 µM) in the absence or in the presence of calcium ions. Our data suggest that naringin (75 µM) promoted membrane potential dissipation, diminishing the potential-dependent accumulation of calcium ions by mitochondria and inhibiting calcium-induced MPTP formation. The modulating effect of the flavonoid on Ca2+-induced mitochondria alterations may be attributed to the weak-acidic nature of the flavonoid and its protonophoric/ionophoric properties. Our results show that the sensitivity of rat heart mitochondria to Ca2+ ions was much lower in the case of MPTP opening and much higher in the case of respiration inhibition as compared to liver mitochondria. [ABSTRACT FROM AUTHOR]

Bitterness in citrus juice is a common quality issue in the fruit-based beverage industry. Naringin, the dominant flavonoid responsible for bitterness in citrus fruit juice, can be mitigated by the enzyme naringinase. This study focuses on the isolation of novel naringinase-producing bacterium from mandarin orange peel, followed by the production and partial purification of naringinase. The bacterial strain exhibiting the highest enzyme production potential was identified as Bacillus megaterium AULS 1. The effects of carbon source (naringin) concentration, inducer (naringenin), pH, and temperature on naringinase production were investigated. Optimized conditions yielded a maximum naringinase production of 386.43 U mL–1. The produced enzyme was partially purified using ammonium sulfate precipitation and dialysis. The effects of pH, temperature, and metal ion concentration on the activity of the partially purified enzyme were evaluated, resulting in a highest activity of naringinase of 539.25 U mL–1 under optimized conditions. The debittering activity of the partially purified enzyme was 45.78 %. These findings demonstrate that Bacillus megaterium AULS 1 has the potential for naringinase production, and can be utilized for debittering citrus juices.

Çanakkale Ezine İlçesine bağlı olan Geyikli beldesi Çanakkale’nin batısında bulunmaktadır. Yörede, doğadan toplanarak tüketilen pek çok bitkiden birisi olan Deniz Börülcesi (Salicornia europaea); Türkiye’de farklı bölgelerde de toplanıp sebze olarak kullanılmaktadır. Türkiye’de aktif olarak kültüre alınmamış olmakla birlikte bazı bilimsel denemelerde yer almıştır ve önemli bir halofittir. Deniz börülcesi pek çok besleyici özelliği olduğuna inanıldığından dolayı sık olarak tüketilmekte ve ticarete konu olmaktadır. Bu bitkinin yöreden toplanıp önemli özelliklerinin değerlendirilmesi bölgenin tarımsal anlamda gelişimi ve bitki ile yapılabilecek diğer tarımsal çalışmalara yol göstermesi açılarından önemli bir konudur. Çalışmanın amacı Çanakkale Ezine İlçesi, Geyikli beldesinde doğal ortamından toplanan S. europaea bitkisini askorbik asit, toplam karotenoid, suda çözünen kuru madde, pH, titre edilebilir asitlik parametreleri ve luteolin, apigenin, naringin, kateşin flavonoidleri açısından incelemektir. Böylece bölge tarımına katkıda bulunmak ve bu bitki ile yapılabilecek çeşitli çalışmalara yol göstermektir. Çalışma sonucunda değerlendirilen S. europaea popülasyonunun flavonoid içeriklerinin çoktan aza sırasıyla apigenin (649,461 mg/kg), naringin (117,51 mg/kg), kateşin (13,574 mg/kg) ve luteolin (0,984 mg/kg) olarak sıralandığı belirlenmiştir. Bunun yanı sıra yüksek bir suda çözünen kuru madde (°Briks) içeriğine (%11,7) sahip olduğu belirlenmiştir.

Abstract This work examines the capacity of Naringin and Rutin to influence the DNA damage response (DDR) pathway by investigating their interactions with key DDR proteins, including PARP-1, ATM, ATR, CHK1, and WEE1. Through a combination of in silico molecular docking and in vitro evaluations, we investigated the cytotoxic and genotoxic effects of these compounds on MDA-MB-231 cells, comparing them to normal human fibroblast cells (2DD) and quiescent fibroblast cells (QFC). The research found that Naringin and Rutin had strong affinities for DDR pathway proteins, indicating their capacity to specifically regulate DDR pathways in cancer cells. Both compounds exhibited preferential cytotoxicity towards cancer cells while preserving the vitality of normal 2DD fibroblast cells, as demonstrated by cytotoxicity experiments conducted at a dose of 10 µM. The comet experiments performed particularly on QFC cells provide valuable information on the genotoxic impact of Naringin and Rutin, highlighting the targeted initiation of DNA damage in cancer cells. The need to use precise cell models to appropriately evaluate toxicity and genotoxicity is emphasized by this discrepancy. In addition, ADMET and drug-likeness investigations have emphasized the pharmacological potential of these compounds; however, they have also pointed out the necessity for optimization to improve their therapeutic profiles. The antioxidant capabilities of Naringin and Rutin were assessed using DPPH and free radical scavenging assays at a concentration of 10 µM. The results confirmed that both compounds have a role in reducing oxidative stress, hence enhancing their anticancer effects. Overall, Naringin and Rutin show potential as medicines for modulating the DDR in cancer treatment. They exhibit selective toxicity towards cancer cells while sparing normal cells and possess strong antioxidant properties. This analysis enhances our understanding of the therapeutic uses of natural chemicals in cancer treatment, supporting the need for more research on their mechanisms of action and clinical effectiveness.

Shuwei Gong,1,&ast; Shuang Lang,2,&ast; Yan Wang,3,&ast; Xiongfeng Li,1,&ast; Aixian Tian,3 Jianxiong Ma,3 Xinlong Ma3 1Department of Orthopedics, Huzhou Central Hospital, Zhejiang University Huzhou Hospital, Huzhou, Zhejiang, 313000, People’s Republic of China; 2Department of Traditional Chinese Medicine, Huzhou Central Hospital, Zhejiang University Huzhou Hospital, Huzhou, Zhejiang, 313000, People’s Republic of China; 3Tianjin Key Laboratory of Orthopedic Biomechanics and Medical Engineering, Orthopedic Research Institute, Tianjin Hospital, Tianjin, 300050, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianxiong Ma; Xinlong Ma, Tianjin Key Laboratory of Orthopedic Biomechanics and Medical Engineering, Orthopedic Research Institute, Tianjin Hospital, 155 Munan Road, Heping District, Tianjin, 300050, People’s Republic of China, Email mjxtianjin@foxmail.com; maxinlong8686@126.comBackground: It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research.Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo.Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤ 120 μg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent.Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect. Keywords: pH-sensitive gated nano-drug delivery system, mesoporous silica nanoparticles, naringin, chitosan, osteoclast

Abstract This study aimed to explore naringin’s potential to promote the osteogenic differentiation of MC3T3-E1 under oxidative stress. It delved into Nar’s connection with the Wnt/β-catenin and PI3K/Akt signaling pathways. Initially, 2911 OP-related genes were analyzed, revealing close ties with the PI3K/Akt and Wnt pathways alongside oxidative stress. Nar’s potential targets—ESR1, HSP90AA1, and ESR2—were identified through various databases and molecular docking studies confirmed Nar’s affinity with ESR1 and HSP90AA1. Experiments established optimal concentrations for Nar and H2O2. H2O2 at 0.3 mmol/L damaged MC3T3-E1 cells, alleviated by 0.1 µmol/L Nar. Successful establishment of oxidative stress models was confirmed by DCFH-DA probe and NO detection. Nar exhibited the ability to enhance osteogenic differentiation, counteracting oxidative damage. It notably increased osteoblast-related protein expression in MC3T3-E1 cells under oxidative stress. The study found Nar’s positive influence on GSK-3β phosphorylation, β-catenin accumulation, and pathway-related protein expression, all critical in promoting osteogenic differentiation. The research concluded that Nar effectively promotes osteogenic differentiation in MC3T3-E1 cells under oxidative stress. It achieved this by activating the Wnt/β-catenin and PI3K/Akt pathways, facilitating GSK-3β phosphorylation, and enhancing β-catenin accumulation, pivotal in osteogenesis.

In this work, we demonstrated a novel, sensitive and effective fluorescent naringin (NRG) and naringenin (NRGe) detection method using polymethionine nanoparticles (PMNPs) as a fluorescent nanoprobe. The PMNPs were first synthesized by autopolymerization of methionine at 90 °C when trace copper ions existed. The as-prepared PMNPs were thoroughly characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), gel permeation chromatograph (GPC), nuclear magnetic resonance spectroscopy (NMR), transient and steady-state fluorescence and UV–Vis absorption spectroscopy. The quenching mechanism was attributed to the inner filter effect (IFE). Moreover, the developed assay was used successfully to detect NRG and NRGe in real samples of citrus fruits, illustrating that this detection method has great potential application in the field of citrus fruits analysis. [ABSTRACT FROM AUTHOR]

Introduction: Glioblastoma, which affects a large number of patients every year and has an average overall lifespan of around 14.6 months following diagnosis stands out as the most lethal primary invasive brain tumor. Currently, surgery, radiation, and chemotherapy with temozolomide (TMZ) are the three major clinical treatment approaches. However, the ability to treat patients effectively is usually limited by TMZ resistance. Naringin, a bioflavonoid with anti-cancer, antioxidant, metal-chelating, and lipid-lowering effects, has emerged as a promising therapeutic option. Methods: To explore the targets and pathways of naringin and TMZ in glioblastoma network pharmacology, cell line-based ELISA, flow cytometry, immunocytochemistry, western blotting, and LC-HRMS based metabolomics study were used. Results: The findings through the network pharmacology suggested that the key targets of naringin in the chemosensitization of glioblastoma would be Poly [ADP-ribose] polymerase 1 (PARP-1), O-6-Methylguanine-DNA Methyltransferase (MGMT), and caspases. The functional enrichment analysis revealed that these targets were significantly enriched in important pathways such as p53 signaling, apoptosis, and DNA sensing. Further, the results of the in-vitro study in U87-MG and T98-G glioblastoma cells demonstrated that TMZ and naringin together significantly reduced the percentage of viability and inhibited the DNA repair enzymes PARP-1 and MGMT, and PI3K/AKT which led to chemosensitization and, in turn, induced apoptosis, which was indicated by increased p53, caspase-3 expression and decreased Bcl2 expression. Additionally, a metabolomics study in T98-G glioblastoma cells using liquid chromatography high-resolution mass spectrometry (LC-HRMS) revealed downregulation of C8-Carnitine (-2.79), L-Hexanoylcarnitine (-4.46), DLCarnitine (-2.46), Acetyl-L-carnitine (-3.12), Adenine (-1.3), Choline (-2.07), Propionylcarnitine (-1.69), Creatine (-1.33), Adenosine (-0.84), Spermine (-1.42), and upregulation of Palmitic Acid (+1.03) and Sphingosine (+0.89) in the naringin and TMZ treatment groups. Discussion: In conclusion, it can be said that naringin in combination with TMZ chemosensitized TMZ antiglioma response and induced apoptosis in tumor cells. [ABSTRACT FROM AUTHOR]

This study aimed to provide scientific data on the anti-Alzheimer's disease (AD) effects of phenolic compounds from Drynariae Rhizoma (DR) extract using a multi-component approach. Screening of DR extracts, fractions, and the ten phenolic compounds isolated from DR against the key AD-related enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and monoamine oxidase-B (MAO-B) confirmed their significant inhibitory activities. The DR extract was confirmed to have BACE1-inhibitory activity, and the ethyl acetate and butanol fractions were found to inhibit all AD-related enzymes, including BACE1, AChE, BChE, and MAO-B. Among the isolated phenolic compounds, compounds (2) caffeic acid 4-O-β-D-glucopyranoside, (6) kaempferol 3-O-rhamnoside 7-O-glucoside, (7) kaempferol 3-o-b-d-glucopyranoside-7-o-a-L-arabinofuranoside, (8) neoeriocitrin, (9) naringin, and (10) hesperidin significantly suppressed AD-related enzymes. Notably, compounds 2 and 8 reduced soluble Amyloid Precursor Protein β (sAPPβ) and β-secretase expression by over 45% at a concentration of 1.0 μM. In the thioflavin T assay, compounds 6 and 7 decreased Aβ aggregation by approximately 40% and 80%, respectively, and degraded preformed Aβ aggregates. This study provides robust evidence regarding the potential of DR as a natural therapeutic agent for AD, highlighting specific compounds that may contribute to its efficacy. [ABSTRACT FROM AUTHOR]

Xylitol candies offer numerous health benefits such as preventing cavities and obesity. However, a preference for them tends to be low due to their distinctive flavor. In this study, we developed xylitol candies containing mature yuja peel (MYP-C), immature yuja peel (IYP-C), and yuja pulp (YP-C). To determine the optimal yuja added to xylitol candy, we compared and analyzed its physicochemical properties, sensory characteristics, and antioxidant activities. IYP-C and MYP-C significantly increased the naringin and hesperidin contents compared to the control and the YP-C. In particular, the IYP-C exhibited the highest content of flavonoids and polyphenols, which contributed to enhancing antioxidant activity such as ferric reducing antioxidant power (FRAP), 1,1 diphenyl-2-picrylhydrazyl (DPPH), and 2,2′-azino-di-2 ethyl-benzothiazoline sulfonate (ABTS+) radical scavenging activities. The IYP-C had the highest crude ash content. The L*, a*, and b* values of MYP-C and IYP-C showed dark red and yellow colors compared to the CON and YP-C groups. The sensory analysis conducted using electronic tongue equipment revealed that IYP-C exhibited high levels of umami, sweetness, and bitterness, while YP-C showed the highest intensity of sourness. In conclusion, these results suggest that IYP-C rather than MYP-C and YP-C provide xylitol candy with good qualities in terms of antioxidant activities and physicochemical characteristics. [ABSTRACT FROM AUTHOR]

Palbociclib and ribociclib an orally bioavailable, potent cyclin-dependent kinase 4/6 inhibitors, with low oral bioavailability due to substrate specificity towards CYP3A and P-glycoprotein. Thus, current research aims to examine the effect of a bioenhancer (naringin), on oral pharmacokinetics of palbociclib and ribociclib. Naringin’s affinity for CYP3A4 and P-glycoprotein was studied using molecular docking; its impact on palbociclib/ribociclib CYP3A metabolism and P-glycoprotein-mediated efflux was examined using in vitro preclinical models; and its oral pharmacokinetics in rats were assessed following oral administration of palbociclib/ribociclib in presence of naringin (50 and 100 mg/kg). Naringin binds optimally to both proteins with the highest net binding energy of − 1477.23 and − 1607.47 kcal/mol, respectively. The microsomal intrinsic clearance of palbociclib and ribociclib was noticeably reduced by naringin (5–100 µM), by 3.0 and 2.46-folds, respectively. Similarly, naringin had considerable impact on the intestinal transport and efflux of both drugs. The pre-treatment with 100 mg/kg naringin increased significantly (p < 0.05) the oral exposure of palbociclib (2.0-fold) and ribociclib (1.95-fold). Naringin's concurrent administration of palbociclib and ribociclib increased their oral bioavailability due to its dual inhibitory effect on CYP3A4 and P-glycoprotein; thus, concurrent naringin administration may represent an innovative strategy for enhancing bioavailability of cyclin-dependent kinase inhibitors. [ABSTRACT FROM AUTHOR]

Diabetes mellitus remains a significant global health concern, necessitating the exploration of novel therapeutic strategies. In this study, we investigated the in vivo antidiabetic potential of Niosome Naringin Nanoconjugate, a nanoformulation designed to enhance the bioavailability and therapeutic efficacy of naringin, a naturally occurring flavonoid with reported antidiabetic properties. Male Wistar rats were induced with diabetes mellitus using streptozotocin and treated with Niosome Naringin Nanoconjugate orally for a specified duration. The effects of the nanoconjugate on glucose tolerance, fasting blood glucose levels, insulin resistance, and lipid profile were evaluated. Our results demonstrate that Niosome Naringin Nanoconjugate significantly improved glucose tolerance, reduced fasting blood glucose levels, and ameliorated insulin resistance compared to diabetic control groups. Additionally, the nanoconjugate exhibited enhanced bioavailability and prolonged circulation time, suggesting potential for sustained therapeutic effects. These findings highlight the promising antidiabetic efficacy of Niosome Naringin Nanoconjugate and underscore its potential as a novel therapeutic agent for the management of diabetes mellitus. Further investigations, including long-term safety assessments and clinical trials, are warranted to fully elucidate its clinical applicability. Overall, this study contributes valuable insights into the development of innovative nanomedicine approaches for diabetes management, with Niosome Naringin Nanoconjugate emerging as a promising candidate for future therapeutic interventions. [ABSTRACT FROM AUTHOR]

Currently, several studies have demonstrated the benefits of medicinal plants in managing type 2 diabetes. In this work, we evaluated the beneficial effects of the polyphenolic extract (PESB) from Salvia blancoana subsp. mesatlantica in the management of hypercaloric-feeding and small-dose alloxan-brought type 2 diabetes in rats. We analyzed the chemical constituents of the extract, including flavones and flavonols content, to understand its biological action. The antioxidant activities were evaluated by total antioxidant action, scavenging effect of the free radical DPPH, and reducing power. The obtained results showed that the value of TFC was estimated at 31.90 ± 0.34 mgEQ/g in the PESB extract. The total antioxidant capacity was estimated at 593.51 ± 4.09 mg (EAA)/g, the value of DPPH IC50 was 7.3 ± 0.00 μg/mL, and the value of EC50 of reducing power was estimated at 6.43 ± 0.01 μg/mL. In total, 14 phenolic compounds were identified and the naringin was the most dominant (63.19%) while the vanillin was the less recorded (0.10%). Serum glucose decreased significantly (p < 0.05) in rats given PESB (100 mg/kg) after four weeks. Glibenclamide (GLB) and PESB reduced HbA1c and increased plasma insulin in diabetic rats, restoring HOMA-β and HOMA-IR levels to near-normal. Additionally, diabetic rats treated with GLB or PESB showed statistically equivalent results to those of non-diabetic rats regarding hepatic enzymes, renal and lipid markers, as well as cardiovascular indices. The weight loss was significantly lower in diabetic rats receiving a dose of PESB (100 mg/kg), and GLB compared to corresponding untreated diabetic rats (p < 0.01). PESB and GLB showed a prominent protective function in the pancreas, liver, and kidney tissues. This investigation demonstrates the capacity of extracts from leaves of S. blancoana subsp. mesatlantica to manage diabetes mellitus due to their richness in a wide range of bioactive compounds. Therefore, more investigations are required to estimate the safety of the plant use. [ABSTRACT FROM AUTHOR]

Type-II transmembrane serine proteases are effective pharmacological targets for host defence against viral entry and in certain cancer cell progressions. These serine proteases cleave viral spike proteins to expose the fusion peptide for cell entry, which is essential to the life cycle of the virus. TMPRSS2 inhibitors can also fight against respiratory viruses that employ them for cell entry. Our study combining virtual screening, all-atom molecular dynamics, and well-tempered metadynamics simulation identifies vicenin-2, neohesperidin, naringin, and rhoifolin as promising TMPRSS2 antagonists. The binding energies obtained are − 16.3, − 15.4, − 13.6, and − 13.8 kcal/mol for vicenin-2, neohesperidin, naringin, and rhoifolin respectively. The RMSD, RMSF, PCA, DCCM, and binding free energy profiles also correlate with the stable binding of these ligands at the active site of TMPRSS2. The study reveals that these molecules could be promising lead molecules for combating future outbreaks of coronavirus and other respiratory viruses. [ABSTRACT FROM AUTHOR]

This work examines the capacity of Naringin and Rutin to influence the DNA damage response (DDR) pathway by investigating their interactions with key DDR proteins, including PARP-1, ATM, ATR, CHK1, and WEE1. Through a combination of in silico molecular docking and in vitro evaluations, we investigated the cytotoxic and genotoxic effects of these compounds on MDA-MB-231 cells, comparing them to normal human fibroblast cells (2DD) and quiescent fibroblast cells (QFC). The research found that Naringin and Rutin had strong affinities for DDR pathway proteins, indicating their capacity to specifically regulate DDR pathways in cancer cells. Both compounds exhibited preferential cytotoxicity towards cancer cells while preserving the vitality of normal 2DD fibroblast cells, as demonstrated by cytotoxicity experiments conducted at a dose of 10 µM. The comet experiments performed particularly on QFC cells provide valuable information on the genotoxic impact of Naringin and Rutin, highlighting the targeted initiation of DNA damage in cancer cells. The need to use precise cell models to appropriately evaluate toxicity and genotoxicity is emphasized by this discrepancy. In addition, ADMET and drug-likeness investigations have emphasized the pharmacological potential of these compounds; however, they have also pointed out the necessity for optimization to improve their therapeutic profiles. The antioxidant capabilities of Naringin and Rutin were assessed using DPPH and free radical scavenging assays at a concentration of 10 µM. The results confirmed that both compounds have a role in reducing oxidative stress, hence enhancing their anticancer effects. Overall, Naringin and Rutin show potential as medicines for modulating the DDR in cancer treatment. They exhibit selective toxicity towards cancer cells while sparing normal cells and possess strong antioxidant properties. This analysis enhances our understanding of the therapeutic uses of natural chemicals in cancer treatment, supporting the need for more research on their mechanisms of action and clinical effectiveness. [ABSTRACT FROM AUTHOR]

The study investigates the impact of different drying methods on the selection of thin-layer drying kinetic models, parameters, and quality for Exocarpium Citreic Grandis. This study investigates the drying characteristics, index constituents content, and microscopic structures of Exocarpium Citreic Grandis slices, subjected to three drying techniques: HAD (at 50, 60, 70 ∘ C), VD (at 50, 60, 70 ∘ C), and MVD (at 1000, 1500, 2000W). A thin-layer drying kinetic model was established. The findings demonstrated that the drying process was primarily dominated by the falling rate phase. When the drying temperature was 70 ∘ C and the microwave power was 2000W, the HAD VD, and MVD took 120, 360, and 20 minutes respectively. By fitting six commonly used thin-layer drying models, it was discovered that the optimal mathematical models for HAD, VD, and MVD were the Page model, the Logarithmic model, and the Page model, respectively. The highest average R 2 values were 0.9963, 0.9965, and 0.9964, and the lowest average RMSE values were 0.01782, 0.01704, and 0.0174 respectively. The effective diffusion coefficient increased with the drying temperature and microwave power, with MVD having the maximum coefficient. As the temperature and microwave power increased, the contents of naringin and rhoifolin decreased. However, the naringin content in MVD was 23.05% and 45.71% higher compared to hot air and VD respectively. The cross-section of Exocarpium Citreic Grandis dried via microwave vacuum exhibited a porous honeycomb structure with uniformly distributed spaces and larger pores, reflecting an expansion effect. The HAD process also resulted in a honeycomb-like structure, but with smaller pores. The VD process resulted in a layered structure with significant cell collapse. Microwave vacuum drying demonstrates superior energy efficiency and product quality compared to hot air and vacuum drying methods. The study finds that microwave drying does not have a destructive impact on the active compounds of Exocarpium Citreic Grandis. To facilitate large-scale, continuous production, microwave drying can be practically applied in industrial processing. [ABSTRACT FROM AUTHOR]

To elucidate the characteristic taste distinctions between Shitougan and other citrus species, the primary taste-contributing substances in the juice sac, segment membrane, albedo and epicarp of 9 citrus varieties, including Shitougan citrus, were analyzed. Our findings revealed that the distribution patterns and concentrations of sugars, organic acids, flavonoids and triterpenoids in different tissues determined the taste profiles of various citrus species. The outer tissues of citrus fruits were identified as the principal sites for accumulation of sugars, organic acids, flavonoids, and triterpenes. Notably, amino acids, such as arginine (Arg), glutamate (Glu), histidine (His), alanine (Ala), aspartic acid (Asp), and proline (Pro), played a pivotal role in shaping the overall taste characteristics of these citrus species. In particular reference to Shitougan fruit - its main edible components comprising juice sacs and segment membranes exhibited relatively lower levels of sugars and organic acids; however higher contents of naringin and neohesperidin were detected in four other tissues within Shitougan fruit. Furthermore, principal component analysis (PCA) indicated that naringin and neohesperidin were primarily responsible for conferring a unique bitter taste to Shitougan fruit. These comprehensive results effectively bridge existing knowledge gaps pertaining to taste-contributing substances specific to Shitougan fruit while simultaneously providing a solid theoretical foundation for further exploration into molecular mechanisms underlying important flavor-imparting constituents within this variety. [ABSTRACT FROM AUTHOR]

Osteomyelitis is an invasive bone infection that can lead to severe pain and even disability, posing a challenge for orthopedic surgery. Naringin can reduce bone‐related inflammatory conditions. This study aimed to elucidate the function and mechanism of naringin in a Staphylococcus aureus–induced mouse model of osteomyelitis. Femurs of S. aureus–infected mice were collected after naringin administration and subjected to microcomputed tomography to analyze cortical bone destruction and bone loss. Bacterial growth in femurs was also assessed. Proinflammatory cytokine levels in mouse femurs were measured using enzyme‐linked immunosorbent assays. Pathological changes and bone resorption were analyzed using hematoxylin and eosin staining and tartrate‐resistant acid phosphatase staining, respectively. Quantitative reverse transcription polymerase chain reaction and western blot analysis were used to quantify the messenger RNA and protein expression of osteogenic differentiation–associated genes in the femurs. The viability of human bone marrow–derived stem cells (hBMSCs) was determined using cell counting kit‐8. Alizarin Red S staining and alkaline phosphatase staining were performed to assess the formation of mineralization nodules and bone formation in vitro. Notch signaling–related protein levels in femur tissues and hBMSCs were assessed using western blot analysis. Experimental results revealed that naringin alleviated S. aureus–induced cortical bone destruction and bone loss in mice by increasing the bone volume/total volume ratio. Naringin suppressed S. aureus–induced bacterial growth and inflammation in femurs. Moreover, it alleviated histopathological changes, inhibited bone resorption, and increased the expression of osteogenic markers in osteomyelitic mice. It increased the viability of hBMSCs and promoted their differentiation and bone mineralization in vitro. Furthermore, naringin activated Notch signaling by upregulating the protein levels of Notch1, Jagged1, and Hes1 in the femurs of model mice and S. aureus–stimulated hBMSCs. In conclusion, naringin reduces bacterial growth, inflammation, and bone resorption while upregulating the expression of osteogenic markers in S. aureus–infected mice and hBMSCs by activating Notch signaling. [ABSTRACT FROM AUTHOR]

Paclitaxel (PTX), which is actively used in the treatment of many types of cancer, has a toxic effect by causing increased oxidative stress in testicular tissues. Naringin (NRG) is a natural flavonoid found in plants, and its antioxidant properties are at the forefront. This study aims to investigate the protective feature of NRG in PTX‐induced testicular toxicity. Thirty‐five male Sprague rats were divided into five groups: control, NRG, PTX, PTX + NRG50, and PTX + NRG100. Rats were administered PTX (2 mg/kg, BW) intraperitoneally once daily for the first 5 days. Then, between the 6th and 14th days, NRG (50 and 100 mg/kg) was administered orally once a day. NRG reduced PTX‐induced lipid peroxidation and increased testicular tissue antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). While NRG reduces the mRNA expression levels of nuclear factor kappa B, tumor necrosis factor‐alpha, interleukin‐1 beta, cyclooxygenase‐2, interleukin‐6, inducible‐nitric oxide synthase, mitogen‐activated protein kinase 14 (MAPK)14, MAPK15, c‐Jun N‐terminal kinase, P53, Apaf1, Caspase3, Caspase6, Caspase9, and Bax in testicular tissues; it caused an increase in Nrf2, HO‐1, NQO1 and Bcl‐2 levels. NRG also improved the structural and functional integrity of testicular tissue disrupted by PTX. PTX‐induced sperm damage was alleviated by NRG. NRG showed a protective effect by alleviating the PTX‐induced testicular toxicity by increasing oxidative stress, inflammation, apoptosis, and autophagy. [ABSTRACT FROM AUTHOR]

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Objective: The present study aims to investigate the specific protective effects and underlying mechanisms of Ganshuang granule (GSG) on dimethylnitrosamine (DMN)-induced hepatic fibrosis in rat models. Methods: Hepatic fibrosis was experimentally evoked in rats by DMN administration, and varying dosages of GSG were employed as an intervention. Hepatocellular damage was assessed by measuring serum levels of aminotransferase and bilirubin, accompanied by histopathological examinations of hepatic tissue. The hepatic concentrations of platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) were quantitated via enzyme-linked immunosorbent assay (ELISA). The expression of α-smooth muscle actin (α-SMA) within hepatic tissue was evaluated using immunohistochemical techniques. The levels of hepatic interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and a spectrum of interleukins (IL-2, IL-4, IL-6, IL-10) were quantified by quantitative real-time PCR (qRT-PCR). Additionally, hepatic stellate cells (HSCs) were cultured in vitro and exposed to TNF-α in the presence of naringin, a principal component of GSG. The gene expression levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase-1 (MMP-1) in these cells were also quantified by qRT-PCR. Proliferative activity of HSCs was evaluated by the Cell Counting Kit-8 assay. Finally, alterations in Smad protein expression were analyzed through Western blotting. Results: Administration of GSG in rats with fibrosis resulted in reduced levels of serum aminotransferases and bilirubin, along with alleviation of histopathological liver injury. Furthermore, the fibrosis rats treated with GSG exhibited significant downregulation of hepatic TGF-β1, PDGF, and TNF-α levels. Additionally, GSG treatment led to increased mRNA levels of IFN-γ, IL-2, and IL-4, as well as decreased expression of α-SMA in the liver. Furthermore, treatment with naringin, a pivotal extract of GSG, resulted in elevated expression of MMP-1 and decreased levels of TIMP-1 in TNF-α-stimulated HSCs when compared to the control group. Additionally, naringin administration led to a reduction in Smad expression within the HSCs. Conclusion: GSG has the potential to mitigate fibrosis induced by DMN in rat models through the regulation of inflammatory and fibrosis factors. Notably, naringin, the primary extract of GSG, may exert a pivotal role in modulating the TGF-β-Smad signaling pathway. [ABSTRACT FROM AUTHOR]

Huyou (Citrus changshanensis) is a significant citrus species that originated in Zhejiang Province, China, where it is also primarily cultivated. It is valued for its distinctive flavor and notable health benefits, owing to its high content of bioactive compounds like naringin and limonin. However, the absence of a high quality reference genome has limited the exploration of these health-promoting compounds in Huyou and hindered research into the mechanisms behind its medicinal properties. In this study, we present a phased chromosome-level genome assembly of Huyou. By combining PacBio and Hi-C sequencing, we generated a primary genome assembly and two haplotypes, comprising nine pseudo-chromosomes, with sizes of 339.91 Mb, 323.51 Mb, and 311.89 Mb, respectively. By integrating transcriptome data and annotations of homologous species, we identified a total of 29,775 protein-coding genes in the genome of Huyou. Additionally, we detected lots of structural variants between the two haplotypes. This represents the first reference genome of Huyou, providing a valuable resource for future studies on its agricultural characteristics and medicinal applications. [ABSTRACT FROM AUTHOR]

The primary objective of this investigation is to uncover notable interactions between dietary supplements and the pharmaceutical agent Binimetinib with the CYP3A4 receptor, employing the HEX 8.0 docking program. Binding energy is utilized as a critical measure to assess the strength and stability of these interactions. Our analysis reveals a robust binding affinity between Binimetinib and CYP3A4. However, when associated with Naringin and Naringenin, an increase in binding energy is observed, indicating a slightly lower drug metabolism in the presence of these supplements. These findings underscore the critical importance of understanding food-drug interactions and the potential alterations in systemic bioavailability and drug pharmacokinetics that may result. Interactions with CYP3A4 significantly affect treatment efficacy and safety. Dietary habits and supplement intake can influence these interactions. Therefore, a thorough understanding and vigilant monitoring of these dynamics are imperative to ensure the appropriateness and safety of therapeutic regimens. [ABSTRACT FROM AUTHOR]

Citrus amblycarpa possesses various pharmacological activities, such as antioxidant, anticancer, antitumor, hepatoprotective, anti-inflammatory, antidiabetic, antiviral, antibacterial, and antifungal. The main active compounds in C. amblycarpa (including gamma (γ)-aminobutyric acid [GABA], hesperidin, naringin, neoeriocitrin, poncirin, quercetin, and rutin) show potential to interact with the inflammatory proteins in hepatic steatosis (such as nuclear factor kappa beta [NF-κB], tumor necrosis alpha [TNF-alpha], interleukin-6 [IL-6], c-Jun NH2-terminal kinase [JNK], and adiponectin). Molecular docking simulations were performed using Swiss Dock (http://www.swissdock.ch/), and analysis and visualization were conducted using Discovery Studio 4.1. Rutin, poncirin, hesperidin, and neoeriocitrin exhibit high affinities to NF-κB, TNF-alpha, IL-6, and adiponectin proteins, respectively. Similar to curcumin--adiponectin complex interaction, neoeriocitrin--adiponectin interaction involves GLY 223, PRO41, and VAL93 residues. Thus, the most potent inhibitor of hepatic sterosis marker was neoeriocitrin. [ABSTRACT FROM AUTHOR]

The present research work was planned to explore the nutraceutical composition of sweet orange varieties during different developmental stages for fresh fruit consumption and industrial purposes. Five sweet orangeswere analysed for total phenolic content (TPC), total flavonoid content (TFC) along with the antioxidant capacity by four different assays viz. DPPH radical scavenging activity, hydroxyl ion (OH–) activity, ferric reducing antioxidant power (FRAP) and total reducing power (TRP), some major flavanone like hesperidin and other like naringin. The outcomes of the research work revealed more pronounced antioxidant readings in Early Gold peel (90 days after fruit set, DAFS), while the phenolics were found maximum in the Ruby Nucellar peel; TPC at 90 DAFS (15.4 mg GAE g–1 dry wt) and TFC at 150 DAFS (2.23 mg RE g–1 dry wt). Whereas greater concentrations of hesperidin (7.25 mg g–1 dry wt) and naringin (4.52 mg g–1 dry wt) were detected in Itaborai at 90 DAFS. [ABSTRACT FROM AUTHOR]

Hua‐ju‐hong (HJH) is a Chinese medicinal material obtained from Citrus grandis 'Tomentosa' (CGT) and Citrus grandis (L.) Osbeck (CG) with various commercial specifications. It is known for relieving cough and dispelling phlegm. To reveal the quality marker for distinguishing the various HJH, 215 batches of commercial HJH were studied systematically using multidimensional chemical analysis. Ten major components were identified by high‐performance liquid chromatography coupled with quadrupole‐time‐of‐flight mass spectrometry and quantified via high‐performance liquid chromatography coupled with diode array detection. In this study, a rapid, efficient, and low‐cost chromatographic method was established. Total coumarin‐hemiterpene and total coumarin‐monoterpene were first classified and analyzed in HJH. The result indicated that the main component, naringin, was not the quality marker for differentiating CGT from CG. For reflecting the unique medicinal and food value of HJH, coumarins should be the more potential quality markers. Flavonoids were the possible quality markers for distinguishing two growth stages of fruit‐exocarp and young fruit. For the first time, two chemotypes of HJH were identified in CG. This study provides a convenient yet reliant chromatographic method and novel yet systematic strategies for overall quality control of commercial HJH. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the protective potential of naringin (NG) against di-n-butyl phthalate (DBP)- induced testicular damage and impairment of spermatogenesis in rats. Forty-two male Wistar albino rats were divided into six equal groups, and treated orally, 3 times weekly for 8 successive weeks. Control vehicle group was administrated olive oil, naringin-treated group was administered NG (80 mg/kg), DBP 250- and DBP 500- intoxicated groups received DBP (250 mg/kg) and (500 mg/kg), respectively, NG + DBP 250 and NG + DBP 500 groups received NG, an hour prior to DBP 250 and 500 administration. The results revealed that DBP induced dose-dependent male reproductive dysfunctions, included a significant decrease in the serum testosterone level concomitantly with significant decreases in the sperm count, viability, and total motility. Meanwhile, DBP significantly increased the testicular malondialdehyde level with significant reductions of glutathione content and catalase activity. Histopathologically, DBP provoked absence of spermatozoa, degenerative changes in the cell layers of seminiferous tubules and a significant decrease in the thickness of the seminiferous tubules epithelium. Conversely, the concomitant treatment with NG, one hour before DBP 250 or 500- intoxication mitigated the dose-dependent reproductive dysfunctions induced by DBP, evidenced by significant increases of serum testosterone level, sperm motility, count and viability along with marked improvement of the oxidant/antioxidant status and testicular histoarchitecture. In conclusion, the findings recorded herein proved that NG could mitigate DBP-induced testicular damage and impairment of spermatogenesis, suggesting the perspective of using NG as a natural protective and therapeutic agent for alleviating the reproductive dysfunctions and improving reproductive performance, mainly via its potent antioxidant activity. [ABSTRACT FROM AUTHOR]