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Zhenzhen Yuan,* Zhao Yang* Orthopaedics, Tianjin Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhao Yang, Email anny.allan@126.comObjective: The aim of this study was to explore the naringin suppressive effect on human degenerative nucleus pulposus cells (D-NPCs) apoptosis and its mechanism.Methods: The degenerative NPCs were divided into 5 groups: the blank control (0μg/mL naringin), 10μg/mL, 20μg/mL, 40μg/mL and 100μg/mL naringin group. Flow cytometry and CCK-8 assay were used to determine the influence on the cell apoptosis and viability in the presence of naringin among groups. The expressions of genes and proteins related to apoptosis and ECM were detected, respectively. Finally, the inhibitors or agonist of apoptotic pathways were used for experiments.Results: In this study, we found naringin treatment led to a decrease of the D-NPCs apoptosis at an optimal concentration of 20μg/mL. After naringin treatment, the expressions of Wnt1 and β-catenin; Fas and Fasl; ATF-4 and CHOP; cleaved caspase-3 and caspase-8; P53 and P16INK4a; pro-apoptotic protein Bax were down‐regulated, while the expressions of anti-apoptotic protein Bcl-2, aggrecan and collagen II were up‐regulated in human D-NPCs. The inhibitors or agonist of pathways could promote or reverse the decrease of apoptosis of degenerative NPCs induced by naringin.Conclusion: Our data indicated that naringin had an antiapoptotic effect via inhibiting P53, P16INK4a, Wnt/β-catenin, and related apoptosis pathway, while the expression of ECM was increased in degenerative NPCs.Keywords: apoptosis, naringin, nucleus pulposus cells

This review describes the various innovative approaches implemented for naringin extraction as well as the recent developments in the field. Naringin was assessed in terms of its structure, chemical composition, and potential food sources. How naringin works pharmacologically was discussed, including its potential as an anti-diabetic, anti-inflammatory, and hepatoprotective substance. Citrus flavonoids are crucial herbal additives that have a huge spectrum of organic activities. Naringin is a nutritional flavanone glycoside that has been shown to be effective in the treatment of a few chronic disorders associated with ageing. Citrus fruits contain a common flavone glycoside that has specific pharmacological and biological properties. Naringin, a flavone glycoside with a range of intriguing characteristics, is abundant in citrus fruits. Naringin has been shown to have a variety of biological, medicinal, and pharmacological effects. Naringin is hydrolyzed into rhamnose and prunin by the naringinase, which also possesses l-rhamnosidase activity. D-glucosidase subsequently catalyzes the hydrolysis of prunin into glucose and naringenin. Naringin is known for having anti-inflammatory, antioxidant, and tumor-fighting effects. Numerous test animals and cell lines have been used to correlate naringin exposure to asthma, hyperlipidemia, diabetes, cancer, hyperthyroidism, and osteoporosis. This study focused on the many documented actions of naringin in in-vitro and in-vivo experimental and preclinical investigations, as well as its prospective therapeutic advantages, utilizing the information that is presently accessible in the literature. In addition to its pharmacokinetic characteristics, naringin’s structure, distribution, different extraction methods, and potential use in the cosmetic, food, pharmaceutical, and animal feed sectors were discussed.

Abnormal regulation of glucose and impaired carbohydrate utilization that result from a defective or deficient insulin are the key pathogenic events in type 2 diabetes mellitus (T2DM). The present study was hypothesized to investigate the beneficial effects of hesperidin and naringin on hyperglycemia-induced oxidative damage in HFD/STZ-induced diabetic rats. Diabetes was induced by feeding rats with an HFD for 2weeks followed by an intraperitoneal injection of STZ (35mg/kg body weight). An oral dose of 50mg/kg hesperidin or naringin was daily given for 4weeks after diabetes induction. At the end of the experimental period, blood was obtained from jugular vein and livers were rapidly excised and homogenized for biochemical assays. In the diabetic control group, levels of glucose, glycosylated hemoglobin (HbA1c%), MDA, NO, TNF-α and IL-6 were significantly increased, while serum insulin, GSH, vitamin C, and vitamin E levels were decreased. Both hesperidin and naringin administration significantly reversed these alterations. Moreover, supplementation with either compound significantly ameliorated serum and liver MDA, NO and glutathione, and liver antioxidant enzymes. Although detailed studies are required for the evaluation of the exact mechanism of the ameliorative effects of hesperidin and naringin against diabetic complications, these preliminary experimental findings demonstrate that both hesperidin and naringin exhibit antidiabetic effects in a rat model of T2DM by potentiating the antioxidant defense system and suppressing proinflammatory cytokine production.

Use of by-product waste from farm products to prepare clinical dressings is a resource-saving and eco-friendly approach. In this research, a series of pH-sensitive hydrogels constructed with oxidized microcrystalline cellulose from pineapple peel, quaternized chitosan from hericium erinaceus residue and gelatin were prepared based on Schiff-base reaction.The structures of the prepared hydrogels were characterized by FT-IR, XRD and SEM. Absorption peak at around 1656 cm −1 (due to –C = N–) appeared and peak at 1726 cm −1 disappeared of the hydrogel confirmed occurrence of Schiff-base reaction. XRD and SEM results showed the composite hydrogels are compatible and well cross-linked. A series of experiments were performed to investigate the blood clotting activity and physicochemical property. It was found that the composite hydrogels show shrink and expansion behaviors under different pH environments, and exhibited adjustable in swelling ability (up to 4383%), water evaporation rate, gel time and mechanical property as change of gelatin content. Oxidized microcrystalline cellulose/quaternized chitosan/gelatin (OMQCS-G) hydrogel showed well coagulation effect and controlled release of the loaded naringin. Naringin release of OMQCS-G5 reached more than 70% within initial 6 h, suggesting the potential of the prepared hydrogels used as wound dressing. Graphical abstract The brief preparation processes of OMQCS-G hydrogel and used as wound dressing. The oxidized microcrystalline cellulose (OMCC) and quaternized chitosan (QCS) is obtained from pineapple peel residues and hericium erinaceus residues after extraction and modification, the gelatin is from pig skin. Then the OMCC/QCS-G hydrogel is formed via Schiff-base reaction, applied for drug delivery and blood clotting.

Among natural substances widespread in fruits, vegetables, spices, and medicinal plants, flavonoids and organic acids belong to the promising groups of bioactive compounds with strong antioxidant and anti-inflammatory properties. The aim of the present work was to evaluate the antibacterial activity of 13 common flavonoids (flavones, flavonols, flavanones) and 6 organic acids (aliphatic and aromatic acids). The minimal inhibitory concentrations (MICs) of selected plant substances were determined by the micro-dilution method using clinical strains of four species of pathogenic bacteria. All tested compounds showed antimicrobial properties, but their biological activity was moderate or relatively low. Bacterial growth was most strongly inhibited by salicylic acid (MIC = 250–500 μg/mL). These compounds were generally more active against Gram-negative bacteria: Escherichia coli and Pseudomonas aeruginosa than Gram-positive ones: Enterococcus faecalis and Staphylococcus aureus. An analysis of the antibacterial effect of flavone, chrysin, apigenin, and luteolin showed that the presence of hydroxyl groups in the phenyl rings A and B usually did not influence on the level of their activity. A significant increase in the activity of the hydroxy derivatives of flavone was observed only for S. aureus. Similarly, the presence and position of the sugar group in the flavone glycosides generally had no effect on the MIC values.

The consumption of plant-based food is important for health promotion, especially concerning the prevention and management of chronic diseases. Flavonoids are the main bioactive compounds in citrus fruits, with multiple beneficial effects, especially antidiabetic effects. We systematically review the potential antidiabetic action and molecular mechanisms of citrus flavonoids based on in vitro and in vivo studies. A search of the PubMed, EMBASE, Scopus, and Web of Science Core Collection databases for articles published since 2010 was carried out using the keywords citrus, flavonoid, and diabetes. All articles identified were analyzed, and data were extracted using a standardized form. The search identified 38 articles, which reported that 19 citrus flavonoids, including 8-prenylnaringenin, cosmosiin, didymin, diosmin, hesperetin, hesperidin, isosiennsetin, naringenin, naringin, neohesperidin, nobiletin, poncirin, quercetin, rhoifolin, rutin, sineesytin, sudachitin, tangeretin, and xanthohumol, have antidiabetic potential. These flavonoids regulated biomarkers of glycemic control, lipid profiles, renal function, hepatic enzymes, and antioxidant enzymes, and modulated signaling pathways related to glucose uptake and insulin sensitivity that are involved in the pathogenesis of diabetes and its related complications. Citrus flavonoids, therefore, are promising antidiabetic candidates, while their antidiabetic effects remain to be verified in forthcoming human studies.

Response surface methodology (RSM) was used to optimize the extraction process of naringin. The central component design included three parameters of extraction, namely temperature (X1), solid–liquid ratio (X2), and extraction time (X3). The optimum extraction temperature was 67 °C; the ratio of feed to solvent was 54:1 mL/g, and the extraction time was 2.8 h. According to the best extraction conditions, naringin was processed to verify the accuracy of the model. Five parallel experiments were set up, and a yield of 3.248% naringin was obtained, which was equivalent to the predicted yield of 3.256%. Naringin was purified to obtain naringin-refined products using DM101 macroporous adsorption resin. Naringin dihydrochalcone was synthesized following catalytic hydrogenation of purified naringin. The structures of naringin and naringin dihydrochalcone were determined via Fourier infrared spectrometer and nuclear magnetic resonance spectrometry. In vitro determination of the lipid-lowering activity of naringin dihydrochalcone was also conducted. Further focusing on HepG2 cells, a high cholesterol-induced high-fat HepG2 cell model was established. We measured the effects of different concentrations of naringin dihydrochalcone on intracellular lipids in denatured HepG2 cells and further validated the lipid-lowering effect of naringin at the cellular level. The results showed that naringin dihydrochalcone has a potential application in functional foods for lowering blood lipids.

1. Diabetic chronic wounds, mainly foot ulcers, constitute one of the most common complications of poorly managed diabetes mellitus. The most typical reasons are insufficient glycemic management, latent neuropathy, peripheral vascular disease, and neglected foot care. In addition, it is a common cause of foot osteomyelitis and amputation of the lower extremities. Patients are admitted in larger numbers attributable to chronic wounds compared to any other diabetic disease. In the United States, diabetes is currently the most common cause of non-traumatic amputations. Approximately five percent of diabetics develop foot ulcers, and one percent require amputation. Therefore, it is necessary to identify sources of lead with wound-healing properties. Redox imbalance due to excessive oxidative stress is one of the causes for the development of diabetic wounds. Antioxidants have been shown to decrease the progression of diabetic neuropathy by scavenging ROS, regenerating endogenous and exogenous antioxidants, and reversing redox imbalance. Matrix metalloproteinases (MMPs) play vital roles in numerous phases of the wound healing process. Antioxidant and fibroblast cell migration activity of Marantodes pumilum (MP) crude extract has previously been reported. Through their antioxidant, epithelialization, collagen synthesis, and fibroblast migration activities, the authors hypothesise that naringin, eicosane and octacosane identified in the MP extract may have wound-healing properties. 2. The present study aims to identify the bioactive components present in the dichloromethane (DCM) extract of M. pumilum and evaluate their antioxidant and wound healing activity. Bioactive components were identified using LCMS, HPTLC and GCMS. Excision wound on STZ-induced diabetic rat model, human dermal fibroblast (HDF) cell line and colorimetric antioxidant assays were used to evaluate wound healing and antioxidant activities, respectively. Molecular docking and pkCMS software would be utilised to predict binding energy and affinity, as well as ADME parameters. 3. Naringin (NAR), eicosane (EIC), and octacosane (OCT) present in MP displayed antioxidant action and wound excision closure. Histological examination HDF cell line demonstrates epithelialization, collagen production, fibroblast migration, polymorphonuclear leukocyte migration (PNML), and fibroblast movement. The results of molecular docking indicate a substantial attraction and contact between MMPs. pkCMS prediction indicates inadequate blood-brain barrier permeability, low toxicity, and absence of hepatotoxicity. 4. Wound healing properties of (NEO) naringin, eicosane and octacosane may be the result of their antioxidant properties and possible interactions with MMP.

Naringin and naringenin are the main bioactive polyphenols in citrus fruits, the consumption of which is beneficial for human health and has been practiced since ancient times. Numerous studies have reported these substances’ antioxidant and antiandrogenic properties, as well as their ability to protect from inflammation and cancer, in various in vitro and in vivo experimental models in animals and humans. Naringin and naringenin can suppress cancer development in various body parts, alleviating the conditions of cancer patients by acting as effective alternative supplementary remedies. Their anticancer activities are pleiotropic, and they can modulate different cellular signaling pathways, suppress cytokine and growth factor production and arrest the cell cycle. In this narrative review, we discuss the effects of naringin and naringenin on inflammation, apoptosis, proliferation, angiogenesis, metastasis and invasion processes and their potential to become innovative and safe anticancer drugs.

Osteoporosis is considered an age-related disorder of the skeletal system, characterized primarily by decreased bone mineral density (BMD), microstructural quality and an elevated risk of fragility fractures. This silent disease is increasingly becoming a global epidemic due to an aging population and longer life expectancy. It is known that nutrition and physical activity play an important role in skeletal health, both in achieving the highest BMD and in maintaining bone health. In this review, the role of macronutrients (proteins, lipids, carbohydrates), micronutrients (minerals—calcium, phosphorus, magnesium, as well as vitamins—D, C, K) and flavonoid polyphenols (quercetin, rutin, luteolin, kaempferol, naringin) which appear to be essential for the prevention and treatment of osteoporosis, are characterized. Moreover, the importance of various naturally available nutrients, whether in the diet or in food supplements, is emphasized. In addition to pharmacotherapy, the basis of osteoporosis prevention is a healthy diet rich mainly in fruits, vegetables, seafood and fish oil supplements, specific dairy products, containing a sufficient amount of all aforementioned nutritional substances along with regular physical activity. The effect of diet alone in this context may depend on an individual’s genotype, gene-diet interactions or the composition and function of the gut microbiota.