Naringin Research Articles

Protective effect of naringin against oxaliplatin-induced peripheral neuropathy in rats: A behavioral and molecular study.

Oxaliplatin (OXL) is a chemotherapeutic drug used for metastatic and other types of cancer, but it causes peripheral neuropathy as a dose-limiting side effect. Herein, we used the rat model of OXL-induced peripheral neuropathy to demonstrate the protective effects of naringin (NRG) in this neuropathy. In this study, rats were injected with OXL (4 mg/kg, body weight, i.p.) in 5% glucose solution 30 min after oral administration of NRG (50 and 100 mg/kg, body weight) on the 1st, 2nd, 5th, and 6th days. OXL caused sensory and motor neuropathy (as revealed by the hot plate, tail flick, rota-rod, and cold hyperalgesia tests) in the sciatic nerve of rats. Coadministration of oral NRG alleviated OXL-induced sensory and motor neuropathy. Levels of superoxide dismutase, catalase, glutathione peroxidase, nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, nuclear factor-κ B, tumor necrosis factor-α, interleukin-1β, Bax, Bcl-2, caspase-3, paraoxonase, mitogen-activated protein kinase 14, neuronal nitric oxide synthase(nNOS), acetylcholinesterase, and arginase 2 in the sciatic nerve tissues were assessed by real-time polymerase chain reaction. Moreover, the protein levels of caspase-3, Bax, Bcl-2, intercellular adhesion molecules-1, glial fibrillary acidic protein, and nNOS were examined by Western blot analysis. NRG treatment significantly improved all the above-mentioned parameters and reduced OXL-induced oxidative stress, inflammation, and apoptosis in the sciatic nerve tissue. In conclusion, this study demonstrated that NRG significantly attenuated OXL-induced peripheral neuropathy and might be considered as a new protective agent to prevent the OXL-induced peripheral neuropathy.

Naringin Inhibits Multiple Myeloma Cells Proliferation by Altering Mitochondrial Function

This study was conducted to evaluate the effect of Naringin (NAR) on multiple myeloma cells through assessment of cell proliferation and mitochondrial function. Methods: Human myeloma cell line (KMS-20) was subjected to normal (control) and treatment conditions. The viability, toxicity, cardiolipin content and mitochondrial membrane potential of KMS-20 cells in all groups were analyzed by using suitable kits. Results: The obtained data showed that NAR is toxic and inhibits the growth of KMS-20 cells. Similar to Doxorubicin (DOX)-treated cell group, the KMS-20 cell group supplemented with NAR had a sharp decrease in cardiolipin content compared to those in control group. The cardiolipin contents of KMS-20 cells in the DOX- and NAR-treated groups were 38.78±3.74 and 47.23±4.65 (% of control, p<0.05), respectively. In contrast to DOX, NAR strongly elevated the mitochondrial membrane potential of the KMS-20 cells. Conclusion: This study shows that NAR has the ability to inhibit the growth of KMS-20 multiple myeloma celline by altering their mitochondrial structure and function.

Evaluation of the combined effect of naringin and imatinib in philadelphia positive chronic myeloid leukemia

The combined effect of Naringin (NAR) and Imatinib mesylate (IMT) in Philadelphia positive chronic myeloid leukaemia was studied in vitro and in silico in this study. The chronic myeloid leukemia (CML) is a myeloproliferative hematopoietic cancer caused by a chromosomal translocation t (9;22). (q34; q11). IMT, a Tyrosine Kinase inhibitor that targets the BCR-ABL oncoprotein, is a first-line treatment for CML. IMT is related with the development of resistance due to mutation of Abl kinase domain. Natural compounds generated from plants have been linked to enhanced therapeutic efficacy and fewer adverse effects in cancer patients. Flavonoids, for example, are physiologically active substances with anti-cancer capabilities that influence a number of cellular signalling pathways suppressing a variety of malignancies. The primary goal of combining synthetic medications with phytochemicals is to achieve a therapeutic activity with the greatest pharmacological efficacy. Targeting AKT with flavonoid (NAR) compounds in conjunction with IMT treatment could be extremely beneficial in CML through additive processes. The combined effect of IMT and NAR in the treatment of CML was assessed using a silico molecular docking and long-term in vitro cytotoxicity assay on K562 cells.

Naringin Regulates Microglia BV-2 Activation and Inflammation via the JAK/STAT3 Pathway.

Objective Microglial BV-2 cells are activated in the brain following insomnia. Naringin (NAR) is a polymethoxylated flavonoid that is also commonly found in citrus fruits and is known for its antioxidant potential. However, the effect of NAR on microglial cells has rarely been studied in the brain of an organism after insomnia. This study aimed to investigate the effects and potential mechanisms of action of NAR on microglial cell activation and inflammation. Methods BV-2 cells were obtained from the China Center for Type Culture Collection and randomly divided into five treatment groups: control, model, NAR (10 μM), WP1066 (5 μM), and NAR + WP1066. With the exception of the control group, all groups were stimulated with LPS (1 μg/mL) for 6 h. CCK8 was used to quantify cell viability and a scratch test was performed to detect cell migration. The expression levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), nterleukin 10 (IL-10), and insulin like growth factor (1IGF-1) were measured by ELISA. Western blotting was performed to determine the levels of p-STAT3 and p-JAK. The Focalcheck™ Thin-Ring Fluorescent Microspheres kit was used to detect cell phagocytosis. Immunofluorescence was used to observe the expression of iNOS and arginase1 in BV-2 cells. Results Compared with the control group, cell migration, cell viability, and the expression of IL-1β, IL-6, TNF-α, and iNOS were significantly increased in the model group, whereas the expression levels of IL-10, IGF-1, and arginase 1, as well as cell phagocytosis were reduced. With the increase in NAR concentration, cell migration, cell viability, the expression levels of IL-1β, IL-6, TNF-α, and iNOS decreased, while the expression of IL-10, IGF-1, and arginase 1 increased. Compared with the control group, p-STAT3, and p-JAK expression in the model group were significantly increased (P<0.05). Compared with the model group, the expression of p-STAT3 and p-JAK in the NAR, NAR + WP1066, and WP1066 groups was significantly decreased (P < 0.05). Conclusion NAR treatment inhibited the proliferation, migration, and inflammation of BV-2 cells as well as the activation of microglia to the M1 phenotype. Conversely, NAR treatment promoted the activation of microglia to the M2 phenotype and enhanced the phagocytic function of BV-2 cells by regulating the activity of the JAK/STAT3 pathway.

The antifibrotic effects of naringin in a hypochlorous acid (HOCl)-induced mouse model of skin fibrosis

Objectives Fibrosis is a chronic inflammation caused by the loss of innate compensational mechanisms. Naringin (NR) is a flavonoid with antineoplastic and anti-inflammatory effects. Here, we aimed to investigate the antifibrotic effects of NR and underlying mechanisms in a Hypochlorous acid (HOCl)-induced mouse model of skin fibrosis. Materials and methods A total of 24 six-week-old female BALB/c mice were randomly allocated into five groups: HOCl, Sham, PBS, HOCl + NR and DMSO and selected skin regions were treated for 6 weeks, until sacrifice. The histopathologic and collagenesis of skin resections were analyzed using H&E and PR staining. The mRNA levels of COL1, COL3 and αSMA genes were quantified. Serum samples were also used to evaluate TGF-β levels and LDH activity. Results HOCl could increase the relative collagen content, while NR administration on HOCl-treated biopsies decreased collagenesis. COL1, COL3 and αSMA mRNA levels were significantly increased among HOCl-treated skin samples, while NR treatment could decrease these mRNA levels of genes to the extent equal to the levels in the Sham group. Similarly, Naringin-treated samples could decrease TGF-β levels. Conclusions We demonstrated that Naringin could exert protective effects against fibrotic complications of HOCL in skin tissue in vivo, by reducing the collagenesis and decreasing the levels of fibrosis-associated genes.

Naringin Alleviates H2O2-Inhibited Osteogenic Differentiation of Human Adipose-Derived Stromal Cells via Wnt/β-Catenin Signaling.

Osteoporosis is an age-related systemic bone disease that places a heavy burden on patients and society. In this study, we aimed to investigate the effects of naringin (NAR) on the osteogenic differentiation of human adipose-derived stromal cells (ADSCs). The results demonstrated that NAR pretreatment effectively abated H2O2-induced cell death and ROS accumulation in ADSCs undergoing osteogenic differentiation (ADSCs-OD). In addition, we also observed that the impaired extracellular matrix mineralization and ALP activity in H2O2-stimulated ADSCs-OD were notably rescued by NAR pretreatment. Moreover, the effects of H2O2 exposure on Wnt/β-catenin signaling in ADSCs-OD were largely reversed by NAR pretreatment. Collectively, our findings indicated that NAR could protect ADSCs-OD against H2O2-inhibited osteogenic differentiation.

Protective effect of naringin ameliorates TNBS‐induced colitis in rats via improving antioxidant status and pro-inflammatory cytokines

Aim: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that disturbs the colon mucosal lining and is characterized by oxido-nitrosative stress and the release of pro-inflammatory cytokines. Naringin (NG) belongs to a group of chemicals called bioflavonoids derived from grapefruit and related citrus species. NG has been widely used as folk medicine in many countries, due to its several health benefits. Method: This study examined the effect of NG on 2,4,6 trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Forty-two male Wistar rats were divided into seven groups like Normal Control (NC), Ethanol Control (EC), Disease Control (DC), NG 20 (20 mg/kg, p.o.), NG 40 (40 mg/kg, p.o.), NG 80 (80 mg/kg, p.o.), and Dexamethasone (DEX) (2 mg/kg, p.o.). Colitis was induced in Wistar albino rats by administering TNBS intra-rectally (in 50% ethanol). The rats were then given 14 days of NG (20, 40, and 80 mg/kg) and DEX (2 mg/kg) treatment. Several behavioral, biochemical, molecular, and histological analyses were performed. Result: The treatment of rats with NG significantly increased the body weight (p < .05, p < .01), hematological parameters like hemoglobin (p < .05, p < .01, p < .001), red blood cells (p < .01, p < .001), and platelets count (p < .01, p < .001) and decreased in spleen weight (p < .01, p < .001), colon weight (p < .01, p < .001), colon weight to length ratio (p < .05, p < .01, p < .001), macroscopic score (p < .01, p < .001), adhesion score (p < .01, p < .001), diarrhea score (p < .05, p < .001), stool consistency (p < .01, p < .001), rectal bleeding score (p < .05, p < .01, p < .001), white blood cells count (p < .01, p < .001). NG significantly (p < .01, p < .001) increased colonic superoxide, glutathione, and catalase levels and decreased malondialdehyde and myeloperoxidase levels. It also significantly (p < .01, p < .001) decreased the biochemical parameters, proinflammatory cytokines and reduced the histological damage in the colon tissue caused by TNBS. Conclusion: Our results demonstrated that NG treatment attenuated pathologic changes of TNBS-induced colitis in rats through restoring colonic damage and reducing inflammatory response in the colon tissue. Thus, NG might be considered as an effective candidate for the treatment of UC patients.

Zein enhanced the digestive stability of five citrus flavonoids via different binding interaction.

Zein is commonly used to construct food flavonoid delivery systems. This study investigated the effect and mechanism of zein on the digestive stability of five citrus flavonoids, namely hesperetin (HET), hesperidin (HED), neohesperidin (NHD), naringenin (NEN), and naringin (NIN). Zein enhanced the digestive stability of the five citrus flavonoids, especially that of HET and NEN, during digestion in the stomach and small intestine. Fluorescence spectroscopy results suggested that citrus flavonoids spontaneously quenched the endogenous fluorescence of zein in static quenching mode. The binding of HET, HED and NHD to zein was driven respectively by electrostatic, hydrophobic and electrostatic interaction. However, Van der Waals' force and hydrogen (H)-bond interaction represented the primary driving force for binding NEN, and NIN to zein to form complexes. The binding of the five citrus flavonoids to zein also caused a diverse bathochromic shift in ultraviolet absorbance. Analysis using Fourier-transform infrared and Raman spectroscopy revealed that the binding behavior of the five citrus flavonoids had different effects on changes in the secondary structures, disulfide bonds, and tyrosine exposure of zein. The results were also partially verified by molecular dynamic simulation. Zein enhanced the digestive stability of the five citrus flavonoids via different binding interactions that was due to the difference in molecular structure of citrus flavonoids. © 2022 Society of Chemical Industry.

Citrus flavonoids against Fusarium verticillioides in post-harvest maize: Minimization of fumonisins and alteration of fungal ultrastructure.

To minimize fumonisins (FBs) accumulation by Fusarium verticillioides in post-harvest maize, using flavonoids obtained from citrus residues: naringin (NAR), neohesperidin (NEO), quercetin (QUER), and its mixtures. Response surface methodology with Box-Behnken design was applied in maize at 0.98 and 0.95 aw . The optimal mixture found, composed of 0.40mmolkg-1 NAR, 0.16mmolkg-1 NEO and 0.37mmolkg-1 QUER, reduced the accumulation of FBs B1, B2, and B3 by 88±6%, 90±6% and 85±5%, respectively, when applied to maize at 0.98 aw . The mentioned mixture led to a 54±9% reduction of fumonisin B1 accumulation in maize adjusted to 0.95 aw . These flavonoids applied individually and as a mixture, affected the structure of both the cell wall and the cytoplasm of F. verticillioides. The cell wall lost rigidity and the cells appeared highly deformed, with ruptured plasmalemma and disrupted endomembranes. It was possible to diminish the accumulation of FBs in maize by a highly toxigenic Fusarium strain, producing severe damage to its ultrastructure. The results indicate the possible use of flavonoids from citrus industry residues as natural and environmentally friendly antifungal agents to restrain the accumulation of FBs in stored maize.

Liquid chromatography-mass spectrometry method for discovering the metabolic markers to reveal the potential therapeutic effects of naringin on osteoporosis

The pharmacological effects and therapeutic targets of naringin (NG) against osteoporosis (OP) is still unclear. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) based non-targeted metabonomics has been used to explore the differentiated metabolites and potential biological pathways of NG in the pathological process of OP. Using network pharmacology analysis, the key protein targets of NG against OP were also screened. By the metabonomics analysis, a total of 33 differentiated metabolites in serum were discovered, of which 21 were significantly regulated by NG treatment. These metabolites majorly associated with to amino acid metabolism,polyunsaturated fatty acid metabolism, pyruvate metabolism and glycerophospholipidmetabolism. Using the network pharmacology prediction analysis, NG was related to the expression changes of 13 important protein targets. It showed that high-throughput metabonomics strategy integrated with network pharmacology could insight into molecular mechanisms of natural products.

Strategy to counteract the pyrazinamide induced hepatotoxicity by developing naringin based Co-amorphous system with supplementary benefits

Pyrazinamide (PZA) is one of the first-line drugs used in the multi-drug regimen treatment for tuberculosis (TB). Hepatotoxicity and liver damage was found to be the major adverse event associated with the PZA containing anti-tubercular treatment. The success rate of the anti-TB treatment is getting highly affected due to the hepatotoxic effects of PZA, which needs to be solved with new drug development ideas. In the present study, a new co-amorphous system (CAM) of PZA was developed using naringin (NGN) as a co-former. Chemically, NGN is a flavonoid of herbal origin with antioxidant and hepatoprotective effects. Three CAMs were prepared by taking PZA and NGN in different ratios like 1:1, 1:2, and 2:1 successively. Further, the amorphous nature of the developed CAM products was confirmed by using DSC, PXRD, and FT-IR. The CAM 1:1 was found to be the most superior in terms of solubility, dissolution rate as well as permeability. Solubility of the drug enhanced up to 25-fold. In the dissolution study, about 97.2% release at 30 min and100% release at 1 h was observed. The apparent permeability of the CAM 1:1 was found to be 3.41 times that of the pure drug. Apart from these supplementary benefits, evaluation of the pharmacodynamic hepatoprotective effect of the developed CAM demonstrated that the developed formulation could be a better alternative for currently available formulations of PZA concerning for to hepatotoxicity.

The Inhibitory Effects of Naringin in a Rat Model of Postoperative Intraperitoneal Adhesion Formation.

Background Many attempts have been made to inhibit the formation of postoperative intraperitoneal adhesions, but the results have been discouraging. Therefore, the identification of effective preventative measures or treatments is of great importance. In this study, the substantial potential of naringin (NG) to reduce peritoneal adhesions was validated in a rat model. Materials and Methods A rat peritoneal adhesion model was established by abrasion of the cecum and its opposite intraperitoneal region under aseptic surgical conditions. After the operation, three groups of NG-treated rats were given 2 mL of NG by gavage at different concentrations (40, 60, or 80 mg/kg/d). The sham, control, and hyaluronan (HA) groups were given equal volumes of normal saline daily. On the 8th day, all rats were sacrificed 30 min after the administration of an activated carbon solution (10 mL/kg) by oral gavage. Intraperitoneal adhesion formation was adequately evaluated by necropsy, hematoxylin and eosin (HE) staining, Sirius red staining, immunofluorescence staining, enzyme-linked immunosorbent assays, and reactive oxygen species (ROS) probes. The gastrointestinal dynamics of the rats were assessed on the basis of a small intestinal charcoal powder propulsion test and the detection of motilin and gastrin levels in serum. Results Intraperitoneal adhesions were markedly reduced in the group of rats receiving high-dose NG. Compared with the control group, the high-dose NG group showed clear reductions in inflammatory reactions, oxidative stress, collagen deposition, and fibroblast formation in the adhesion tissue and enhanced gastrointestinal dynamics (P < 0.05). Conclusion NG alleviated the severity of intraperitoneal adhesions in a rat model by reducing inflammation, oxidative stress, collagen deposition, and fibroblast formation, highlighting the potential of NG as a drug candidate to prevent postoperative peritoneal adhesion formation.

A new combination of naringin and trimetazidine protect kidney Mitochondria dysfunction induced by renal Ischemia / Reperfusion injury in rat

Ischemia/reperfusion (IR) injury leads to overproduction of Reactive Oxygen Species (ROS), and disrupts membrane potential that contributes to cell death. The aim of this study was to determine if naringin (NAR), trimetazidine (TMZ) or their combination, protect the kidney mitochondrial from IR injury. Forty rats were randomly allocated into five groups, harboring eight rats each: Sham, IR, NAR (100 mg/kg), TMZ (5 mg/kg) and NAR plus TMZ. Ischemia was induced by obstructing both renal pedicles for 45 min, followed by reperfusion for 4 hours. The mitochondria were isolated to examine the ROS, Malondialdehyde (MDA), Glutathione (GSH), mitochondrial membrane potential (MMP) and mitochondrial viability (MTT). Our findings indicated that IR injury resulted in excessive ROS production, increased MDA levels and decreased GSH, MMP and MMT levels. However, NAR, TMZ or their combination reversed these changes. Interestingly, a higher protection was noted with the combination of both, compared to each drug alone. We speculate that this combination demonstrates a promising process for controlling renal failure, especially with the poor clinical outcome, acquired with NAR alone. This study revealed that pretreatment their combination serves as a promising compound against oxidative stress, leading to suppression of mitochondrial stress pathway and elevation of GSH level.

Local delivery of naringin in beta-cyclodextrin modified mesoporous bioactive glass promotes bone regeneration: from anti-inflammatory to synergistic osteogenesis and osteoclastogenesis.

The bone immune response dominated by macrophages plays an indispensable role in the osteogenesis of bone defects. Moreover, moderate polarization of macrophages against inflammatory M2 has been proved to promote osteogenesis. Therefore, the addition of anti-inflammatory agents to bioactive bone repair materials facilitates efficient bone regeneration by regulating the polarization of macrophages. Bioactive glass (BG) has been widely used for bone defect repair. However, BG alone cannot effectively inhibit the inflammatory response caused by in vivo biomaterial implantation, and finally cannot achieve satisfactory bone repair effect. Herein, the design of mesoporous bioactive glass nanoparticles (MBG) modified with β-cyclodextrin (CD-MBG) is reported. Our research shows that the anti-inflammatory drug naringin (NG) is loaded into CD-MBG (NG@CD-MBG), which achieves a sustained release within 6 days. In vitro studies reveal that NG@CD-MBG promotes better transformation of macrophages to the M2 phenotype than MBG inhibiting macrophage inflammatory responses, while the induced local immune microenvironment synergistically facilitates osteogenesis and inhibits osteoclastogenesis. Furthermore, in vivo high expression of osteogenesis-related genes in the microenvironment stimulated by NG@CD-MBG significantly promotes new bone formation in the femoral defect model of rats. The results indicate that the combination of MBG and NG has a synergistic effect on immunomodulating osteogenesis and osteoclastogenesis, providing a novel idea for the development of bone biomaterials with favorable bone immunomodulatory properties.

Naringin prevents bone damage in the experimental metabolic syndrome induced by a fructose-rich diet.

We analyzed the effect of naringin (NAR), a flavonoid from citric fruits, on bone quality and biomechanical properties, as well as the redox state of bone marrow in rats fed a fructose-rich diet (FRD), an experimental model to mimic human metabolic syndrome. NAR blocked the increase in the number of osteoclasts and adipocytes and the decrease in the number of osteocytes and osteocalcin (+) cells caused by FRD. Trabecular number was significantly higher in the FRD+NAR group. FRD induced a decrease in the femoral trabecular and cortical bone mineral density, which was blocked by NAR. The fracture and ultimate loads were also decreased in the FRD and FRD+NAR groups. NAR increased the number of nodes to terminal trabecula, the number of nodes to node trabecula, the number of nodes, and the number of nodes with 2 terminals and decreased the Dist (mean size of branches) value. FRD decreased bone marrow catalase activity, an effect that was prevented by NAR. In conclusion, FRD has detrimental effects on the long bones, which are associated with oxidative stress in the bone marrow. Most of these changes are prevented by NAR through its antioxidant properties and promotion of bone formation. Novelty: Fructose-rich diets have detrimental effects on long bones, which are associated with oxidative stress in the bone marrow. Most of these changes are prevented by naringin through its antioxidant properties and promotion of bone formation.

Formation of boronate-based macroporous copolymer via emulsion-assisted interface self-assembly method for specific enrichment of Naringin

In this paper, the boronate affinity (BA) copolymer sorbents with crosslinked hydrogen bond networks were successfully synthesized by emulsion-induced interface self-assembly and applied in high-performance copolymer materials (BCDPs-CPs-2) for the specific separation and purification of separate cis-diol containing naringin (NRG). A novel solid particle β-cyclodextrins (CDs) based on microporous organic polymers (MOPs) with high surface area were fabricated. As the main solid emulsifier, β-CDs-based MOPs (CDPs) can effectively improve the emulsifying performance of the emulsion droplet, whilst reducing the amounts of surfactant. At the same time, CDPs can effective combined with boronate affinity functioned adamantane (Ad) inclusion derivative were by self-assembly at the two phase interface, which realizes the surface boronic acid functionalities of copolymer materials conveniently. Furthermore, the copolymer materials with crosslinked hydrogen bond networks were obtained via a interface copolymerization between water phase monomer N-(methoxymethyl)-2-methyl-2-propenamide (MMP) and the oil phase monomer methoxyethyl acrylate (MEA). The obtained copolymer materials exhibited stable macroporous structure and shape memory abilities, which effectively improve the regeneration property in practical extract conditions. The combination of excellent performance, BCDPs-CPs-2 showed rapid binding rate (360 min) and high adsorption capacity (3.14 μmol g−1) at 298 K. Moreover, outstanding reusability of 5.34% loss in enrichment performance after five times repeatedly. The NRG component content of the purified samples (approximately 96.67%) was superior to original crude extract (about 75.0%). Additionally, the adsorption mechanism is discussed in detail with the effect of pH, different copolymer materials, and thermodynamics.

Pharmacoinformatics-based investigation of bioactive compounds of Rasam (South Indian recipe) against human cancer

Spice-rich recipes are referred to as “functional foods” because they include a variety of bioactive chemicals that have health-promoting properties, in addition to their nutritional value. Using pharmacoinformatics-based analysis, we explored the relevance of bioactive chemicals found in Rasam (a South Indian cuisine) against oxidative stress-induced human malignancies. The Rasam is composed of twelve main ingredients, each of which contains a variety of bioactive chemicals. Sixty-six bioactive compounds were found from these ingredients, and their structures were downloaded from Pubchem. To find the right target via graph theoretical analysis (mitogen-activated protein kinase 6 (MAPK6)) and decipher their signaling route, a network was built. Sixty-six bioactive compounds were used for in silico molecular docking study against MAPK6 and compared with known MAPK6 inhibitor drug (PD-173955). The top four compounds were chosen for further study based on their docking scores and binding energies. In silico analysis predicted ADMET and physicochemical properties of the selected compounds and were used to assess their drug-likeness. Molecular dynamics (MD) simulation modelling methodology was also used to analyse the effectiveness and safety profile of selected bioactive chemicals based on the docking score, as well as to assess the stability of the MAPK6-ligand complex. Surprisingly, the discovered docking scores against MAPK6 revealed that the selected bioactive chemicals exhibit varying binding ability ranges between − 3.5 and − 10.6 kcal mol−1. MD simulation validated the stability of four chemicals at the MAPK6 binding pockets, including Assafoetidinol A (ASA), Naringin (NAR), Rutin (RUT), and Tomatine (TOM). According to the results obtained, fifty of the sixty-six compounds showed higher binding energy (− 6.1 to − 10.6 kcal mol−1), and four of these compounds may be used as lead compounds to protect cells against oxidative stress-induced human malignancies.

A Naringin-loaded gelatin-microsphere/nano-hydroxyapatite/silk fibroin composite scaffold promoted healing of critical-size vertebral defects in ovariectomised rat

In this study, we investigated the effect of three-dimensional of naringin/gelatin microspheres/nano-hydroxyapatite/silk fibroin (NG/GMs/nHA/SF) scaffolds on repair of a critical-size bone defect of lumbar 6 in osteoporotic rats. In this work, a cell-free scaffold for bone-tissue engineering based on a silk fibroin (SF)/nano-hydroxyapatite (nHA) scaffold was developed. The scaffold was fabricated by lyophilization. Naringin (NG) was loaded into gelatin microspheres (GMs), which were encapsulated in the nHA/SF scaffolds. The materials were characterized using x ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. Moreover, the biomechanics, degradation, and drug-release profile of the scaffold were also evaluated. In vitro, the effect of the scaffold on the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) was evaluated. In vivo, at 3 months after ovariectomy, a critical-size lumbar defect was indued in the rats to evaluate scaffold therapeutic potential. A 3-mm defect in L6 developed in 60 SD rats, which were randomly divided into SF scaffold, nHA/SF scaffold, NG/nHA/SF scaffold, NG/GMs/nHA/SF scaffold, and blank groups (n = 12 each). At 4, 8, 12, and 16 weeks postoperatively, osteogenesis was evaluated by X-ray, micro-computed tomography, hematoxylin-eosin staining, and fast green staining, and by analysis of BMP-2, Runx2, and Ocn protein levels at 16 weeks. In our results, NG/GM/nHA/SF scaffolds exhibited good biocompatibility, biomechanical strength, and promoted BMSC adhesion, proliferation, and calcium nodule formation in vitro. Moreover, NG/GMs/nHA/SF scaffolds showed greater osteogenic differentiation potential than the other scaffolds in vitro. In vivo, gradual new bone formation was observed, and bone defects recovered by 16 weeks in the experimental group. In the blank group, limited bone formation was observed, and the bone defect was obvious. In conclusion, NG/GMs/nHA/SF scaffolds promoted repair of a lumbar 6 defect in osteoporotic rats. Therefore, the NG/GMs/nHA/SF biocomposite scaffold has potential as a bone-defect-filling biomaterial for bone regeneration.

Naringin as Sustained Delivery Nanoparticles Ameliorates the Anti-inflammatory Activity in a Freund's Complete Adjuvant-Induced Arthritis Model.

Naringin (NAR), a naturally occurring essential flavonoid, present in grapefruit and Chinese herbal medicines, creates great interest in researchers due to its diverse biological and pharmacological activities. However, further development of NAR is hindered due to its poor water solubility and dissolution rates in GIT. To address these limitations, in this study, we report polymeric nanoparticles (NPs) of NAR (NAR-PLGA-NPs) for enhancing the oral NAR efficiency, with a biodegradable polymer (PLGA) to improve its absorption and bioavailability. NAR-PLGA-NPs were fabricated by a modified solvent emulsification–evaporation technique. Physicochemical properties were evaluated by SEM, particle size distribution, entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). In vitro drug release and ex vivo permeation studies were carried out in phosphate buffer (pH 6.8) for 24 h. Furthermore, in vivo anti-arthritic studies were performed on a mouse model, and the results were compared with free NAR. The modulation of inflammatory mediators was also evidently supported by docking studies. Optimized nanoformulation FN4 (NAR-PLGA-NPs) prepared with acetone–ethanol (2:1) as a solvent system in a combination of stabilizers, i.e., poloxamer-188 and sodium deoxylate (1:1), along with 2% PVA solution, was prepared. From size characterization studies, it was observed that nanoformulations possessed a low particle size (179.7 ± 2.05 nm), a low polydispersity index (0.206 ± 0.001), and a negative zeta potential (−9.18 ± 0.78 mV) with a maximum entrapment efficiency (74 ± 3.61%). The drug release followed a Korsmeyer–Peppas release kinetic model (anomalous non-Fickian diffusion), providing greater NAR release after lyophilization (82.11 ± 3.65%) drug release in pH 6.8 phosphate buffer for 24 h. Ex vivo permeation analysis through an isolated goat intestinal membrane revealed 80.02 ± 3.69% drug release in 24 h. Encapsulation of a drug into PLGA is well described by the results of FTIR, DSC, and XRD. Finally, the therapeutic efficacy of optimized FN4 (NAR-PLGA-NPs) and its possible application on RA were further confirmed in a Freund’s complete adjuvant-induced rat arthritic model as against free NAR at a dose of 20 mg/kg body wt. Our findings demonstrate that sustained action of NAR from optimized FN4 NPs with a rate-controlling polymeric carrier system exhibited prolonged circulation time and reduced arthritic inflammation, hence indicating the possibility as a novel strategy to secure the unpropitious biological interactions of hydrophobic NAR in a gastric environment.

Naringin Effectively Protects Cardiomyocytes Against Hypoxia/Reoxygenation Injury

This study was conducted to evaluate the protective effect of Naringin (NAR) on H9C2 cardiomyocytes in hypoxia/reoxygenation (HR) injury in vitro induced by the hypoxia chamber. Methods: H9C2 cells were grown under normal (control) and HR conditions. The viability, cardiolipin content and mitochondrial membrane potential of H9C2 cells in experimental groups were analyzed by using suitable kits. Results: The obtained results showed that the addition of Naringin (16÷160 µM) significantly increased the survival rate of H9C2 cells under HR conditions. In particular, NAR had the highest efficiency in preserving mitochondrial function at concentrations of 80 µM and 160 µM. In HR-exposed H9C2 cell group, the cardiolipin content and mitochondrial membrane potential values of H9C2 cells were decreased sharply with that of control (71,64±1,37% and 68,12±2,78%, p&lt;0,05). Interestingly, mitochondrial cardiolipin contents were signigicantly increased in H9C2 cells post-hypoxic treated wtih NAR at dose of 80 µM 160 µM to 87,76±1,89% and 81,09±1,21%. Additionally, post-hypoxic supplementation of NAR at concentration of 80 µM and 160 µM effectively increased mitochondrial membrane potential values. Conclusion: The obtained results are preliminary data on the effects of NAR in protecting mitochondrial-targeted cardiomyocytes against HR injury.