Protective Effects Of Naringin Research Articles

Protective effects of naringin on fipronil-induced cardiovascular and renal dysfunctions in rats

BackgroundNaringin as a bioflavanone glycoside is abundant in citrus fruits, which since ancient times have been utilized as natural herbal treatments in traditional medicine. Naringin has potent antioxidant effect that may mitigate oxidative stress mediated cardiovascular and renal dysfunctions in mammalian systems. ObjectiveTo explore probable modulatory actions of naringin on fipronil-induced cardio-renal dysfunctions. MethodsTwenty-four Wistar rats weighing 140±3.0 g were divided into four groups including normal control (saline), 10 mg/kg Fipronil (FIP), FIP+100 mg/kg naringin, and 100 mg/kg naringin.. Administration of naringin and fipronil was by oral gavage for 28 consecutive days. Urinalysis, blood pressure monitoring, biochemical assays, histology, and immunohistochemical evaluations were performed. ResultsNaringin significantly (P <0.001) lessened blood pressure parameters, oxidative stress markers but significantly (P <0.001) heightened the systemic antioxidants. Likewise, naringin prevented fipronil-induced histopathological lesions such as congestion and cellular infiltration in cardiac and renal tissues. Moreover, naringin attenuated the immunohistochemical expression of troponin 1 and matrix metalloperoxidase-2 in cardiac tissues, but heightened angiotensin converting enzyme 2 expression in contrast to fipronil group. ConclusionThe observation in this study shows potent attenuation of fipronil-induced toxicity by naringin, through inhibiting processes related to oxidation and inflammation.

Protective effects of naringin on colistin-induced damage in rat testicular tissue: Modulating the levels of Nrf-2/HO-1, AKT-2/FOXO1A, Bax/Bcl2/Caspase-3, and Beclin-1/LC3A/LC3B signaling pathways.

Antimicrobial agent resistance has become a growing health issue across the world. Colistin (COL) is one of the drugs used in the treatment of multidrug-resistant bacteria resulting in toxic effects. Naringin (NRG), a natural flavonoid, has come to the fore as its antioxidant, anti-inflammatory, and antiapoptotic activities. The aim of the present study was to determine whether NRG has protective effects on COL-induced toxicity in testicular tissue. Thirty-five male Spraque rats were randomly divided into five groups (n = 7 per group): Control, COL, NRG, COL + NRG 50, COL + NRG 100. COL (15 mg/kg b.w., i.p., once per/day), and NRG (50or 100 mg/kg, oral, b.w./once per/day) were administered for 7 days. The parameters of oxidative stress, inflammation, apoptosis, and autophagic damage were evaluated by using biochemical, molecular, western blot, and histological methods in testicular issues. NRG treatment reversed the increased malondialdehyde level and reduced antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione) levels due to COL administration (p < 0.001), and oxidative stress damage was mitigated. Nuclear factor erythroid 2-related factor-2 pathway, one of the antioxidant defence systems, was stimulated by NRG (p < 0.001). NRG treatment reduced the levels of markers for the pathways of apoptotic (p < 0.001) and autophagic (p < 0.001) damages induced by COL. Sperm viability and the live/dead ratio were reduced by COL but enhanced by NRG treatment. Testicular tissue integrity was damaged by COL but showed a tendency to improve by NRG. In conclusion, COL exhibited toxic effect on testicular tissue by elevating the levels of oxidative stress, apoptosis, autophagy, inflammation, and tissue damage. NRG demonstrated a protective effect by alleviating toxic damage.

Protective effects of naringin against oxaliplatin-induced testicular damage in rats: Involvement of oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and histopathology.

Oxaliplatin (OXL) is a platinum-based chemotherapeutic agent widely used in the treatment of colorectal cancer. Unfortunately, this important drug also causes unwanted side effects such as neuropathy, ototoxicity, and testicular toxicity. This study aimed to investigate the possible protective effects of naringin (NRG) against OXL-induced testicular toxicity in rats. In the present study, rats were injected with OXL (4 mg/kg, b.w./day, IP) in 5% dextrose solution 30 min after oral administration of NRG (50 and 100 mg/kg, b.w./day) on the 1st, 2nd, 5th, and 6th days. Then, the rats were sacrificed on the 7th day and the testicular tissues were removed. The results showed that NRG decreased (P<0.001) lipid peroxidation, increased (P<0.001) the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and the levels of glutathione (GSH), and also maintained the testis histological architecture and integrity. NRG decreased the levels of apoptosis-related markers such as caspase-3, Bax, and Apaf-1 and increased Bcl2 in the OXL-induced testicular toxicity (P<0.001). In addition, NRG reversed the changes in mRNA transcript levels of oxidative stress, inflammation, and endoplasmic reticulum stress parameters such as Nrf2, HO-1, NQO1, RAGE, NLRP3, MAPK-14, STAT3, NF-κB, IL-1β, TNF-α, PERK, IRE1, ATF6, and GRP78 in OXL-induced testicular toxicity (P<0.001). Our results demonstrated that NRG can protect against OXL-induced testicular toxicity by enhancing the anti-oxidant defense system and suppressing apoptosis, inflammation, and endoplasmic reticulum stress.

Biochemical and Histopathological effects of Acetaminophen and Protective Effects of Naringin on Liver Rats

This study was conducted to find out liver protective activity of naringin (NRG) 40-80 mg/kg body weight(b.w.) against acetaminophen (ACN) 2g/kg induced liver damage in rats. Thirty two male rats were dividedinto four groups : group1: negative control, (1 ml/kg Saline orally) group II: positive control ACN (2g/kg), orally as single dose at first day, group III: ACN (2g/kg), orally as single dose at first day , plus NRG(40 mg//kg) orally for (8) consecutive days, group IV: ACN (2g/kg), orally as single dose at first day , plusNRG (80 mg//kg) orally for (8) consecutive days. All the rats were anesthetized to collect blood then killedon the (9) day of the experiment to take the liver samples. ACN induced liver damage was proved by asignificant (P&lt;0.01) reduction in the body weight , total protein (TP) , albumin (AB) , superoxide dismutase(SOD) and catalase (CAT) enzymes and a significant (P&lt;0.01) increased in liver weight, serum aspartatetransaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), directbilirubin (DB) , malondialdehyde enzyme (MAD) and histopathological changes. Protective liver toxicityeffect and oxidative damage caused by ACN significantly (P&lt;0.01) increasing in body weight, TP, AB ,SODand CAT and significantly (P&lt;0.01) decreasing in liver weight , AST, ALT, ALP, TB, DB and MAD andimproving tissue morphology by a meliorative in NRG 40 , 80 mg/kg b.w. These results confirm that NRGantioxidant effects can protect ACN induced hepatic toxicity in rats.

Protective effects of naringin on valproic acid-induced hepatotoxicity in rats

Valproic acid (VPA) is mainly prescribed to treat epilepsy. VPA has been reported to be associated with many adverse effects, including hepatotoxicity. Naringin (NRG) is a natural, therapeutically active flavanone glycoside with anti-inflammatory, anti-apoptotic, and antioxidant. The current study was therefore designed to investigate the protective effect of NRG against the VPA-induced experimental hepatotoxicity model. For this purpose, 24 Wistar albino rats were randomly divided into three groups as control (Vehicle), VPA (500 mg/kg), and NRG + VPA (100 mg/kg NRG + 500 mg/kg VPA) groups. The agents were administered via oral gavage for 14 days. Blood and liver tissue samples were taken on the end of the experiment. Biochemical analyzes were performed on the blood and liver samples. Also, malondialdehyde (MDA), superoxide dismutase (SOD) enzyme, glutathione (GSH) content, catalase (CAT) enzyme levels were examined in the liver tissue samples. Histopathological changes (hydropic degeneration and congestion) in the VPA group were increased significantly when compared to the control group (p < 0.05). We also found a decrease in enzymes of serum liver function in the VPA group. However, NRG has been shown not to prevent histopathological changes in the VPA group. According to our results with this experiment protocol, NRG could not exert sufficient protection against VPA-induced hepatotoxicity.

Siklofosfamidle İndüklenmiş Ratlarda Serbest Radikaller ve Antioksidanlar Üzerine Naringinin Protektif Etkileri

Bu calismada siklofosfamid (CYP) ile uygulanan ratlarda kan ve serum orneklerinde Naringin (NA)’in antioksidanlar ve serbest radikaller uzerine protektif etkilerinin arastirilmasi amaclandi. Arastirmamizda yaklasik 200-250 g agirliginda, 40 adet erkek eriskin Sprague Dawley rat kullanildi ve her bir grupta 8 ratin bulundugu 5 grup olusturuldu. Kontrol grubuna 10 gun boyunca intra gastrik (i.g.) serum fizyolojik (1 ml) verildi. CYP grubuna 10 gun boyunca i.g. serum fizyolojik verildi ve 10. gun tek doz intra peritonal (i.p.) CYP (200 mg/kg) enjekte edildi. NA50+CYP ve NA100+CYP gruplarina 10 gun boyunca sirasiyla serum fizyolojikte cozdurulmus 50 ve 100 mg/kg dozunda i.g. NA uygulandi ve NA’nin son enjeksiyondan sonra tek doz CYP (200 mg/kg, i.p.) enjekte edildi. NA100 grubuna ise 10 gun boyunca 100 mg/kg dozunda i.g. NA uygulandi. Deneyin 12. gununde ratlar tiopental sodyum (20 mg/kg) ile anestezi altina alinarak intra kardiyak kan ornekleri alindi ve dekapite edildiler. Ratlardan elde edilen kan ve serum orneklerinde Total Antioksidan Durumu (TAS), Total Oksidan Durumu (TOS), Oksidatif stres indeksi (OSI) ve 8-Hydroxydeoxyguanosine (8-OHdG) parametreleri analiz edildi. CYP’nin ratlarda oksidatif stresi artirdigi, antioksidanlari baskiladigi ve DNA hasarina yol actigi tespit edildi. NA’nin farkli dozlarinin, CYP’nin sebep oldugu oksidatif stresi baskiladigi, antioksidan miktarini artirdigi ve DNA hasarini onledigi belirlendi.

Protective Effects of Naringin on Lung Toxicity Induced by 5-Fluorouracil in Rats

Mevcut çalışmanın amacı; kemoterapötik olarak kullanılan 5-FU’nun akciğerlerde oluşturduğu hasara karşı doğal flavonoidlerden olan naringinin koruyucu etkilerini araştırmaktır. Çalışmada 200-250 g ağırlığında, 30 adet Sprague Dawley cinsi erkek rat kullanıldı. Ratlar rastgele seçilerek Kontrol grubu, 5-FU grubu ve NA+5-FU grubu olarak ayrıldı. 5-Fluorouracilin akciğer dokularında interstisyel fibrozis ve konjesyona, alveoller arası septumda yangısal hücre infiltrasyonuna bağlı kalınlaşma, peribronşiyal lenfoid doku hiperplazisi ile birlikte bronşiyollerde epitelyal hücre dökülmelerine neden olduğu gözlendi. Naringin uygulamasının ise akciğerdeki histopatolojik bulguları hafiflettiği ve normal akciğer doku histolojisine yaklaştırdığı gözlendi. 5-Fluorouracil uygulamasının akciğerlerdeki Bax immünpozitifliğini artırırken, Bcl-2 immünpozitifliğini azalttığı, naringin uygulamasının ise kontrol grubuna benzer şekilde Bax immünpozitifliğini azaltıp, Bcl-2 immünpozitifliğini artırdığı belirlendi. Akciğer dokularında kontrole kıyasla TBARS ve NO düzeylerinin 5-FU uygulaması ile anlamlı şekilde arttığı, GSH düzeyinin ise anlamlı şekilde azaldığı, naringin uygulanan grupta ise bu parametrelerin kontrol grubundaki düzeylere yaklaştığı tespit edildi. Tüm bu bulgular naringin uygulamasının, 5-FU kaynaklı akciğer hasarında faydalı etkiler gösterebileceğini düşündürmektedir.

Protective effects of naringin against drugs and chemical toxins induced hepatotoxicity: A review.

The liver is a vital metabolic organ for drug and xenobiotic metabolism which is influenced by chemical and natural toxins. Liver injury is associated with systemic oxidative stress, which leads to cellular necrosis, fibrosis, tissue lipid peroxidation, and depletion in glutathione levels. Considering the lack of reliable hepato-protective drugs in modern medicine, plant-derived phytoconstituents seem to be a noteworthy option. Naringin is an abundant flavonoid found in citrus fruits with various pharmacological benefits such as antioxidant, anti-inflammatory, and antiapoptotic, activities. In this review, we summarize available data from recent studies about the hepatoprotective effects of naringin against chemical toxicants and discuss the possible mechanisms of actions.

Protective Effects of Naringin in Cerebral Infarction and Its Molecular Mechanism.

BackgroundCerebral infarction is a cardiovascular disease with high morbidity and mortality. At present, many studies have reported the treatment of cerebral infarction by traditional Chinese medicine. Naringin, a flavonoid, is a major traditional Chinese medicine. However, the effect and mechanism of naringin on cerebral infarction is unclear.Material/MethodsIn our study, we established a rat model of cerebral infarction through middle cerebral artery occlusion (MCAO) to study the influence of naringin on cerebral infarction in vivo. After treatment with naringin, brain water content was detected to assess brain edema. Cerebral infarction volume and neurological deficits were also measured. Production of the inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6) was measured using enzyme-linked immunosorbent assay (ELISA). Besides, the effect of naringin on cerebral infarction was investigated in vitro by establishing an oxygen-glucose deprivation (OGD) model in neuronal cells. Cell apoptosis and cell viability was determined using flow cytometry and MTT assay.ResultsWe found that naringin pretreatment significantly decreased the brain water content, cerebral infarction volume, and neurological deficit scores of MCAO subjected rats. And naringin treatment reduced apoptosis of nerve cells in rat hippocampus and the secretion of inflammatory factor such as TNF-α and IL-6. Besides, we found that naringin increased cell viability and inhibited apoptosis in OGD induced neuronal cells. Finally, we found that naringin promoted the expression of p-AKT protein in a concentration-dependent manner and activated the PI3K/AKT pathway in OGD induced neurons.ConclusionsNaringin played a protective role in cerebral infarction via suppressing neuronal apoptosis and inflammation.

Protective effects of naringin in indomethacin-induced gastric ulcer in rats

Protective effects of naringin in indomethacin-induced gastric ulcer in rats

Protective effects of naringin and trimetazidine on remote effect of acute renal injury on oxidative stress and myocardial injury through Nrf-2 regulation.

Ischemia/reperfusion (I/R) is the predominant cause of acute renal failure (ARF), which damages the remote organs, especially the heart, and subsequently leads to death. The aim of the current study was to examine the effects of naringin (NAR), trimetazidine (TMZ), or their combination on the Nrf-2 expression in the kidney tissue, and myocardial injury in the renal IR injury in rats. Forty male Sprague-Dawley rats were randomly separated into five groups as follows: sham, IR injury, TMZ (5 mg/kg, intravenously), NAR (100 mg/kg), and their combination. Renal I/R injury and ischemia were induced by using clamps for 45 min, and after 4 h reperfusion, respectively. Then, the Nrf-2 expression in the kidney, antioxidant activity (CAT, SOD, and GPx), total antioxidant capacity (TAC), oxidative stress, electrocardiogram (ECG) parameters, and biochemical markers were examined. Renal IR injury significantly reduced the Nrf-2 expression, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) enzymes' activities and TAC. Moreover, Malondialdehyde (MDA) level in kidney and heart tissues, plasma creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH) activity were increased, and ECG parameters were significantly distributed; however, NAR, TMZ, or their combination improved these changes, in comparison with the renal IR injury in rats. NAR, TMZ, or their combination could attenuate the Nrf-2 expression in the kidney tissue, following the renal IR injury through inhibition of lipid peroxidase, and enhancement of antioxidant activity.

Naringin abrogates HIV-1 protease inhibitors-induced atherogenic dyslipidemia and oxidative stress in vivo

Protective effects of naringin against HIV-1 protease inhibitors (PIs)-induced dyslipidemia and oxidative stress were investigated in vivo. Male Wistar rats were orally treated daily with atazanavir {ATV; 133 mg/kg body weight (BW)}, saquinavir (SQV; 333 mg/kg BW), distilled water (3.0 ml/kg BW) and with or without naringin (NAR; 50 mg/kg BW) for 56 days, respectively. ATV or SQV significantly reduced body weights and plasma HDL cholesterol concentrations but increased total cholesterol, triglycerides, LDL-cholesterol, VLDL-cholesterol concentrations and calculated atherogenic index ratio, respectively. Furthermore, ATV or SQV treatment significantly increased lipid peroxidation and carbonyl proteins concentrations in plasma, liver and pancreas tissues but significantly reduced antioxidant activities in the liver and pancreas compared to the controls, respectively. However, naringin treatment significantly improved weight loss, dyslipidemia and oxidative stress in ATV- or SQV-treated rats, respectively. Naringin prevents HIV PIs-induced dyslipidemia and oxidative stress and may therefore mitigate PI-associated metabolic complications in HIV patients.

Protective effects of Naringin in a rat model of spinal cord ischemia–reperfusion injury

Purpose : To evaluate the activity of naringin (NAR) in a rat model of spinal cord ischemic injury (SCII). Methods: Forty female rats were randomized into four groups: saline without  occlusion (control; group I), SCII (group II), 50 mg/kg NAR (group III), or 100 mg/kg NAR (group IV) for 7 days prior to SCI insult (pre-treatment). Neurological and locomotor functions, antioxidant activity, edema and inflammatory markers were determined. Results: Pre-treatment with NAR considerably lowered the incidence of spinal edema, lipid peroxidation products, and inflammatory markers (TNF-α, NF-p65, IL-1β, and IL-6). It also successfully reverted the antioxidative activity to near-normal levels and improved locomotor function by protecting spinal tissue from oxidative damage and inflammatory insults. NAR administration effectively downregulated the protein expression of TNF-α and NF-κB p65 subunit in spinal tissue, thus confirming its antiinflammatory activity. Conclusion : The results suggests that NAR exhibits neuroprotective effects by inhibiting free radical generation and downregulating inflammatory markers in an SCI rat model. Keywords : Naringin, Spinal cord injury, Locomotor function, Edema, Oxidative  stress, Inflammation

Protective effect of naringin against ankylosing spondylitis via ossification, inflammation and oxidative stress in mice.

Naringin is an abundant flavanone in pomelo, grapefruit as well as lime and its variants, has been shown to exhibit certain antioxidative, anti-inflammatory, anti-cancer and hypoglycemic effects. The aim of the current study was to evaluate the protective effects of naringin against ankylosing spondylitis (AS) and to elucidate the potential underlying mechanism. Firstly, a mouse model of ankylosing spondylitis (AS) was established. Next, osteocalcin (OC), alkaline phosphatase (ALP) and triglyceride (TG) activity values, inflammatory factor and oxidative stress were evaluated in the AS mice. Then, the Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) protein expression levels in the AS mice were investigated using western blot analysis. The results showed that naringin increased OC, ALP and TG activity values in the AS mouse model. Furthermore, inflammatory factor and oxidative stress levels in the AS mice were restrained by treatment with naringin. Furthermore, JAK2 and STAT3 protein expression levels were reduced by treatment with naringin. In conclusion, the present results indicated that the protective effects of naringin against AS are exerted via the induction of ossification, suppression of inflammation and oxidative stress and the downregulation of JAK2/STAT3 in mice.

Protective effects of naringin against gp120-induced injury mediated by P2X7 receptors in BV2 microglial cells.

This study was aimed at exploring the effects of P2X7 receptors on gp120-induced injury and naringin's protective effects against gp120-induced injury in BV2 microglia. BV2 microglia injury model was established by gp120 treatment and MTS assay was used to verify whether naringin has a cell-protective effect against gp120-induced injury. Changes in P2X7 receptor expression were assayed using RT-PCR, qPCR, and western blot. Results showed that the ODs of the Ctrl, gp120, gp120+naringin, and gp120+BBG groups were 0.91 ± 0.10, 0.71 ± 0.09, 0.83 ± 0.10, and 0.83 ± 0.10, respectively. Compared to the control group, the gp120 group showed a significantly decreased cell survival rate. Cell survival rates of the gp120+naringin group increased significantly compared to those of the gp120 group, while no difference was observed when compared to the gp120+BBG group. The relative P2X7 mRNA expression levels in the Ctrl, gp120, gp120+naringin, and gp120+BBG groups were 0.73 ± 0.06, 1.05 ± 0.06, 0.78 ± 0.05, and 0.81 ± 0.04, respectively. The corresponding P2X7 protein expression levels were 0.46 ± 0.04, 0.79 ± 0.04, 0.38 ± 0.07, and 0.42 ± 0.06. P2X7 mRNA and protein expression in the gp120 group increased significantly compared to those in the control group, and declined in the gp120+naringin group compared to those in the gp120 group. Therefore, P2X7 receptors might be involved in gp120-induced injury in BV2 microglia, and naringin might play a protective role by inhibiting the up-regulated expression of P2X7 receptors.

GW26-e4786 Protective effects of naringin on diabetic cardiomyopathy in rats through inhibiting p38MAPK pathway

GW26-e4786 Protective effects of naringin on diabetic cardiomyopathy in rats through inhibiting p38MAPK pathway

Naringin mitigate okadaic acid-induced cognitive impairment in an experimental paradigm of Alzheimer's disease

Okadaic acid (OKA), a selective and potent inhibitor of serine/threonine phosphatases 1 and 2A, induces hyper-phosphorylation of tau and thus has emerged as an effective tool to develop AD like pathology in animals. In the present study, we investigated the effect of naringin, against ICV-OKA-induced cognitive impairment as assessed by Morris water maze task which was accompanied by significantly enhanced oxidative-nitrosative stress, TNF-α, TGF-β, NF-κB, caspase-3 and IL-1β levels as well as increased acetylcholinesterase and mitochondrial enzyme activities in hippocampus and cerebral cortex of rats. Treatment with naringin significantly and dose dependently improved ICV-OKA-induced cognitive deficits. The protective effects of naringin were targeted on downregulation of cortical and hippocampal cholinesterase as well as NF-κB along with downstream mediators. The protective effects of naringin (200 mg/kg) were similar to these of rivastigmine (2 mg/kg) in ICV-OKA-induced rats implicating that naringin has a potential to be explored as a novel strategy for treatment of dementias.

Anti-genotoxic effect of naringin against bleomycin-induced genomic damage in human lymphocytes in vitro

Naringin is a flavonoid found in grapefruit and other citrus fruits that shows antioxidant activity. The aim of the present study was to determine the anti-genotoxic and protective effects of naringin on the chemotherapeutic/radiomimetic agent bleomycin (BLM) in human blood lymphocyte cultures in vitro using micronucleus test and chromosomal aberrations (CA) assay. We tested the three doses of naringin (1, 2, 3 µg/mL) and a single dose of BLM (20 µg/mL). BLM significantly increased the total CAs and micronucleus frequency at a concentration of 20 µg/mL. Naringin did not show any toxicity in doses of 1, 2, and 3 µg/mL. Combined treatments of BLM and naringin (2 and 3 µg/mL) significantly reduced micronucleus formation. Naringin dose-dependently decreased the total chromosome aberrations frequency induced by BLM. These results indicate that naringin could prevent BLM (20 µg/mL)-induced genotoxicity.