Protective Effect Of Zingerone Research Articles

Protective effects of zingerone against sodium arsenite-induced lung toxicity: A multi-biomarker approach.

Sodium arsenite (SA) exposure is toxic to the body. Zingerone (ZNG) is a flavonoid with many biological properties found naturally in honey and plants. This study aimed to determine the effects of ZNG on SA-induced rat lung toxicity. Thirty-five male Sprague rats were divided into Control, SA, ZNG, SA+ZNG25, and SA+ZNG50 groups (n=7). SA 10 mg/kg and ZNG were administered at two doses (25 and 50 mg/kg) (orally, 14 days). Analysis of oxidative stress, inflammation damage, apoptosis damage, and autophagic damage markers in lung tissue were determined by biochemical and histological methods. The administration of ZNG reduced oxidative stress by increasing SA-induced decreased antioxidant enzyme activities, increasing Nrf-2, HO-1, and NQO1, and decreasing MDA level. ZNG administration reduced inflammation marker levels. Anti-apoptotic Bcl-2 increased and apoptotic Bax and Caspase-3 decreased with ZNG. ZNG promoted the regression of autophagy by reducing Beclin-1, LC3A, and LC3B levels. Evaluating all data showed that SA caused toxic damage to lung tissue by increasing inflammation, apoptosis, autophagy, and oxidant levels, whereas ZNG had a protective effect by reducing this damage.

Zingerone Alleviate Toxicity Induced by Cisplatin or Gamma Radiation in Rats by Modulating Pro-Inflammatory Mediators

Background: Zingerone is one of the active components of ginger that possesses multiple biological activities and anti-inflammatory properties against either radiation effect or cisplatin toxicity. Purpose: to examine the protective effect of zingerone against gamma radiation (IR) or cisplatin-induced immunotoxicity. Material and Methods: 48 rats were divided into six groups as follows: (group-1); normal control group received distilled water; (group-2); rats received Zingerone orally at a dose of 25 mg/kg b.wt. Once / day for 14 consecutive days (Zing.). (group-3); Rats were given a single injection of Cisplatin at a dose of 7.5 mg/kg b.wt. intraperitoneally (Cispl.). (group-4); Rats exposed to a single dose of 6 Gy whole-body gamma irradiation using 137Cesium source in a Gamma cell 40 (Rad.). (group-5); rats received same dose of Zingerone then they were exposed to gamma radiation as in group 4 (Zing+Rad.). (group-6); rats received Zingerone followed by single injection of Cisplatin at the dose of 7.5 mg/kg b.wt. Intraperitoneally (Zing+Cisp.). Results: Exhibited a significant increase in expression of NF-κB, IL-10, caspase-3, and gene expression of TNF-α as well as oxidative stress biomarkers (MDA and NO) levels accompanied with a reduced level of SOD in either whole body-irradiated or cisplatin-received group. Conversely, pro-inflammatory cytokines levels were significantly decreased with an improvement of oxidative stress in groups that received zingerone. Conclusion: It could be concluded that zingerone exerts its antioxidative activity and immunomodulatory effects through inhibition of pro-inflammatory mediators induced by whole body-gamma irradiation or cisplatin administration at two time interval early and late stage of radiation exposure (after 2 h and one week).Therefore, further studies are required to elucidate the molecular signaling pathway concerning zingerone.

Protective effects of zingerone on high cholesterol diet-induced atherosclerosis through lipid regulatory signaling pathway.

A high cholesterol diet (HCD) is known to cause metabolic dysregulation, oxidative stress, cardiovascular diseases and atherogenesis. Zingerone is a pharmacologically active component of dry ginger. Zingerone has been shown to have a wide range of pharmacological properties, including scavenging free radicals, high antioxidant activity, suppressing lipid peroxidation and anti-inflammatory. This study aimed to investigate the effects of Zingerone on HCD-induced atherosclerosis in rats. Animals were divided into four categories (n = 6). Group I: normal control, Group II: zingerone control (20 mg/kg b.wt.), group III: HCD-induced atherosclerosis, Group IV: HCD + zingerone, respectively, for 8 weeks. The HCD-fed rats resulted in a significant increase in an atherosclerotic lesion, lipid peroxidation, lipid profile, high-density lipoprotein concentration, cardiac markers, body weight, reduced antioxidant status, and displayed atherosclerosis. These findings were conventional by up-regulated expression of lipid regulatory genes like sterol-regulatory-element-binding protein-c (SREBP-c), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), acetyl-CoA synthetase (ACS), liver X receptor-alpha (LXR-α), and down-regulated expression of acetyl-CoA oxidase (ACO), peroxisome proliferator-activated receptor-alpha (PPAR-α) and carnitine palmitoyl transferase-1 (CPT-1) in HCD-fed rats. These significant changes were observed in the zingerone-treated rats for the last 4 weeks. These findings suggest that zingerone reduced atherosclerosis by modulated the atherosclerotic lesion, lipid profile, antioxidant status and lipid regulatory gene expression in HCD-fed rats.

Zingerone [4-(3-Methoxy-4-hydroxyphenyl)-butan-2] Attenuates Lipopolysaccharide-Induced Inflammation and Protects Rats from Sepsis Associated Multi Organ Damage.

The present investigation aimed to evaluate the protective effect of Zingerone (ZIN) against lipopolysaccharide-induced oxidative stress, DNA damage, and cytokine storm in rats. For survival study the rats were divided into four groups (n = 10). The control group was treated with normal saline; Group II received an intraperitoneal (i.p) injection (10 mg/kg) of LPS as disease control. Rats in Group III were treated with ZIN 150 mg/kg (p.o) 2 h before LPS challenge and rats in Group IV were given ZIN only. Survival of the rats was monitored up to 96 h post LPS treatment. In another set, the animals were divided into four groups of six rats. Animals in Group I served as normal control and were treated with normal saline. Animals in Group II were treated with lipopolysaccharide (LPS) and served as disease control. Group III animals were treated with ZIN 2 h before LPS challenge. Group IV served as positive control and were treated with ZIN (150 mg/kg orally). The blood samples were collected and used for the analysis of biochemical parameters like alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), blood urea nitrogen (BUN), Cr, Urea, lactate dehydrogenase (LDH), albumin, bilirubin (BIL), and total protein. Oxidative stress markers malondialdehyde (MDA), glutathione peroxidase (GSH), myeloperoxidase (MPO), and (DNA damage marker) 8-OHdG levels were measured in different organs. Level of nitric oxide (NO) and inflammatory markers like TNF-α, IL-1ß, IL-1α, IL-2, IL-6, and IL-10 were also quantified in plasma. Procalcitonin (PCT), a sepsis biomarker, was also measured. ZIN treatment had shown significant (p < 0.5) restoration of plasma enzymes, antioxidant markers and attenuated plasma proinflammatory cytokines and sepsis biomarker (PCT), thereby preventing the multi-organ and tissue damage in LPS-induced rats also confirmed by histopathological studies of different organs. The protective effect of ZIN may be due to its potent antioxidant potential. Thus ZIN can prevent LPS-induced oxidative stress as well as inflammatory and multi-organ damage in rats when administered to the LPS treated animals.

Zingerone protects liver and kidney tissues by preventing oxidative stress, inflammation, and apoptosis in methotrexate-treated rats

The clinical use of drugs used in the treatment of diseases is limited due to the toxic side effects, and many studies have been conducted to benefit from herbal adjuvant therapies recently to eliminate these effects. In this study, the protective effect of zingerone against liver and kidney damage generated in rats through methotrexate (MTX). Histopathological investigations were performed to determine tissue damage caused by MTX and the healing effect of zingone and liver function markers such as serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and renal function markers such as urea, creatine, and aquaporin-1 (AQP-1) were measured. The effects of MTX and protective properties of zingerone on oxidative stress were investigated through the measurement of malondialdehyde and reduced glutathione (GSH) levels, catalase (CAT), and glutathione peroxidase (GPx) enzyme activities. The anti-inflammatory effect of zingerone was determined by measuring the cytokine levels causing inflammation such as nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), and its effects on apoptosis were determined by immunohistochemical analysis of caspase-3 and B-cell lymphoma-2 (Bcl-2) expression levels. According to the results obtained within the scope of the study, it was determined that zingerone treatment prevented the increase in MTX-induced liver and kidney function markers, showed healing effects on antioxidant parameters degraded in both tissues, and decreased the inflammation parameters. It was determined that it also prevented apoptosis and possessed a protective effect on disrupted tissue architecture by decreasing the increased caspase-3 expression and increasing the decreased Bcl-2 level.

The Possible Protective Role of Zingerone on Ethanol Induced Entrotoxicity of Jejunum in Adult Albino Rats: Light and Scanning Electron Microscopic Study.

Introduction:Zingerone is a nontoxic important extract of dry ginger plant. It is reported that zingerone has an anticancer property, strong anti-inflammatory and antimicrobial properties.Aim of the Work:is to evaluate the possible protective effects of zingerone on ethanol-induced lesions on the jejunum of adult male albino rats.Materials and Methods:twenty four adult male albino rats were used, divided into 3 groups; A control group (I); consisted of 8 rats, ethanol group (II); contained 8 rats and each rat given 50% v/v alcohol at a dose of 4 g/kg.bw orally for 15 days. Ethanol zingerone group (III); consisted of 8 rats, each received zingerone at a dose of 50 mg/kg and alcohol at the same previous dose daily and orally for 15 days. At the appropriate time, the specimens were taken and prepared for light and electron microscope study.Results:Histological examination of jejunum sections of ethanol group (II) showed massive jejunal villi ulcerations with shedding of their surface epithelium, loss of the villous architecture and loss of the microvilli covering some enterocytes. Examination of ethanol zingerone group (III) showed evidence of improvement in the form of nearly normal architecture of the jejunal villi with few areas of ulcerations on the top of some villi and increased cells with mitotic activity.Conclusion:Accordingly, we can conclude that zingerone administration can remarkably ameliorate ethanol-induced enterotoxiciy and jejunal ulcerations in rats by its anti-inflammatory properties and by suppressing oxidative stress.

Protective effect of Zingerone against mouse testicular damage induced by zinc oxide nanoparticles.

The purpose of the present study was to evaluate the effect of Zingerone (Zing) on zinc oxide nanoparticle (ZNP)-induced spermatogenesis defects in mice. To this end, 50mg/kg of ZNP was prescribed to the mice as an intoxicated group for 35days. In protection groups, Zing (10, 20, and 40mg/kg) was given prior to ZNP treatment for seven days and then co-administration of ZNP for 35days. Epididymal sperm parameters, testicular histology, Johnsen's scoring, morphometric parameters, TUNEL staining, oxidative stress, and serum testosterone level were evaluated for determining ZNP and Zing effects on the mouse testicles. Effects of Zing and ZNP on the viability of mouse Leydig (TM3) and mouse Sertoli (TM4) cell lines were also done. Testicular weights, testosterone levels, sperm quality, morphometric parameters, Johnsen's score, and superoxide dismutase (SOD) and catalase (CAT) activities were significantly decreased in ZNP-intoxicated mice, while apoptotic index, Malondialdehyde (MDA) content, and histological features, including epithelial vacuolization, sloughing, and germ cell detachment, were improved significantly in ZNP-intoxicated mice. Pretreatment with 20 or 40mg/kg Zing significantly reduced the histological criteria, increased morphometric parameters, enhanced testosterone levels, attenuated apoptotic index, improved sperm quality, and reversed oxidative stress by reducing the level of MDA and incrementing the activity level of SOD and CAT enzymes. Zing dose-dependently enhanced the viability of ZNP-treated TM3 and TM4 cells in comparison with only ZNP-exposed cells. According to the results of our study, Zing effectively prevented the defects in spermatogenesis among mice treated by ZNP.

Protective effects of zingerone on cisplatin-induced nephrotoxicity in female rats.

Zingerone (ZO), one of the active components of ginger (Zingiber officinale), is a phenolic alkanone with antioxidant, antiapoptotic, and anti-inflammatory properties. Cisplatin (CP) is a widely used chemotherapeutic drug for solid tumors, but its therapeutic use is limited due to dose-dependent nephrotoxicity. In the present study, we investigated the ameliorative effect of ZO against CP-induced nephrotoxicity. Intraperitoneal administration of single-dose CP (7mg/kg body weight) on the first day enhanced kidney lipid peroxidation and reduced antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH). CP increased serum urea and creatinine levels and disrupted histological integrity while causing a decrease aquaporin 1 (AQP1) level in the kidney tissues. CP induced inflammatory responses by elevating the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-33 (IL-33) and nuclear factor kappa B (NF-κB), and activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it also caused oxidative DNA damage and activation of apoptotic pathway by increasing of 8-hydroxy-2'-deoxyguanosine (8-OHdG), p53, cysteine aspartate-specific protease-3 (caspase-3), and Bcl-2-associated x protein (bax) while decreasing B cell lymphoma-2 (Bcl-2). However, treatment with ZO at a dose of 25 and 50mg/kg b.wt. for 7days significantly decreased oxidative stress, apoptosis, inflammation, and histopathological alterations while increased AQP1 levels in the kidney tissue. The results of the current study suggested that ZO as an effective natural product attenuates CP-induced nephrotoxicity.

Protective effects of zingerone on oxidative stress and inflammation in cisplatin-induced rat nephrotoxicity.

Cisplatin is one of the most commonly used and highly effective cancer chemotherapeutic agents. Use of cisplatin is limited due to persistence of severe side effects such as nephrotoxicity, neurotoxicity, and hearing loss. Nephrotoxicity is the most common limiting side effect of cisplatin use. Zingerone is one of the active ingredients present in ginger plant that has anti-inflammatory and antioxidant effects. In this study, Wistar rats were assigned randomly to 6 groups with 5 animals in each group. The control group; cisplatin group which received 7.5 mg/kg of cisplatin intraperitoneally (i.p.) at the 4th day; zingerone group received 50 mg/kg of zingerone orally for 7 days. Three other groups were pretreated with 10, 20, and 50 mg/kg of zingerone orally for 7 days and cisplatin administered 7.5 mg/kg i.p. at the 4th day, respectively. The animals were sacrificed 72 h after cisplatin injection and blood samples were taken to evaluate the serum factors. Right kidneys were collected for histopathological studies and left kidneys were considered to measure the oxidative stress parameters and TNF-α cytokine. Co-administration of zingerone along with cisplatin resulted a statistically significant reduction in lactate dehydrogenase (LDH) activity, creatinine and BUN levels of serum in comparison with cisplatin alone group (P < 0.01). Zingerone significantly decreased the tissue levels of malondialdehyde (MDA) (P < 0.05) and significantly retained the enzyme activity of catalase (CAT) (P < 0.05) and glutathione peroxidase (GPX) (P < 0.05) in kidney tissue compared to cisplatin. Zingerone did not permit the reduction of glutathione (GSH) levels (P < 0.001) in kidney tissue and by reducing the level of tumor necrosis factor (TNF)-α (P < 0.05) suppressed the inflammation produced by cisplatin. Furthermore, zingerone improved histopathological changes such as vacuolation (fat deposit), brush border loss, infiltration of leukocytes, glomerular diameters and congestion of RBCs. However, our findings suggest that zingerone has nephroprotective effects in cisplatin rat model of nephrotoxicity mostly through suppression of oxidative stress and inflammation.

Nephroprotective Effect of Zingerone against CCl4-Induced Renal Toxicity in Swiss Albino Mice: Molecular Mechanism.

The protective effects of Zingerone against CCl4 induced nephrotoxicity in Swiss albino mice via modulation of metabolizing enzyme, oxidative stress, inflammatory cytokines, and apoptosis. The biochemical estimation indicated that the BUN and creatinine were significantly increased in group 2 (CCl4) compared to group 1 (normal) which was significantly reduced after treatment with Zingerone in group 3 when compared with group 2. The CCl4 treatment has significantly increased TBARS levels and reduced the antioxidant enzyme such as GSH, GPx, GR, GST, CAT, and SOD in group 2 compared to group 1, while the Zingerone treatment showed significant reduction in TBARS levels and increased the antioxidant enzymes in group 3 (CCl4 + Zingerone) as compared to group 2. Similarly, it was observed that CCl4 significantly increased the cytokines such as IL-1β, IL-2, and TNFα levels in group 2 as compared to group 1. The treatment with Zingerone significantly attenuated the levels of IL-1β, IL-2, and TNFα in group 3 compared to group 2. Caspase 3 and caspase 9 were also significantly increased in CCl4-treated group 2, whereas Zingerone treatment significantly reduced the elevated levels of caspases 3 and 9 in group 3 compared to group 2.

Protective effects of zingerone on lipopolysaccharide-induced hepatic failure through the modulation of inflammatory pathways

The aim of this study was to investigate the effects of zingerone (ZGR) on lipopolysaccharide (LPS)-induced liver failure in mice, and to elucidate underlying mechanisms. ZGR is a phenolic alkanone isolated from ginger, and has potential health benefits. Mice were treated intravenously with ZGR at 12 h after LPS treatment. LPS significantly increased mortality, serum levels of alanine transaminase, aspartate transaminase, and inflammatory cytokines, and toll-like receptor 4 (TLR4) protein expression; these effects of LPS were inhibited by ZGR. It also attenuated the LPS-induced activation of myeloid differentiation primary response gene 88 and TLR-associated activator of interferon-dependent signaling pathways of the TLR system. Our results suggest that ZGR protects against LPS-induced liver damage by inhibiting the TLR-mediated inflammatory pathway, indicating its potential to treat liver diseases.

Protective effect of zingerone on increased vascular contractility in diabetic rat aorta

The aim of the present study was to investigate the effect and possible mechanism of action of zingerone, the main constituent of ginger, on vascular reactivity in isolated aorta from diabetic rats. The results show that incubation of aortae with zingerone alleviates the exaggerated vasoconstriction of diabetic aortae to phenylephrine, as well as the impaired relaxatory response to acetylcholine in a concentration-dependent manner. Furthermore, Zingerone directly relax phenylephrine-precontracted aortae. The vasorelaxatory response is significantly attenuated by the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride and the guanylate cyclase inhibitor methylene blue but no effect of either the potassium channels blocker tetraethylammonium chloride, or the cyclooxygenase inhibitor indomethacin was observed. Zingerone had no effect on advanced glycation end product formation as well. In conclusion, zingerone ameliorates enhanced vascular contraction in diabetic aortae which may be mediated by its vasodilator effect through NO– and guanylate cyclase stimulation.