Administration Of Rutin Research Articles

Rutin prevents EqHV-8 induced infection and oxidative stress via Nrf2/HO-1 signaling pathway.

The Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway has been extensively studied for its role in regulating antioxidant and antiviral responses. The Equid herpesvirus type 8 (EqHV-8) poses a significant threat to the equine industry, primarily manifesting as respiratory disease, abortions, and neurological disorders in horses and donkeys. Oxidative stress is considered a key factor associated with pathogenesis of EqHV-8 infection. Unfortunately, there is currently a dearth of therapeutic interventions available for the effective control of EqHV-8. Rutin has been well documented for its antioxidant and antiviral potential. In current study we focused on the evaluation of Rutin as a potential therapeutic agent against EqHV-8 infection. For this purpose, we encompassed both in-vitro and in-vivo investigations to assess the effectiveness of Rutin in combatting EqHV-8 infection. The results obtained from in vitro experiments demonstrated that Rutin exerted a pronounced inhibitory effect on EqHV-8 at multiple stages of the viral life cycle. Through meticulous experimentation, we elucidated that Rutin's antiviral action against EqHV-8 is intricately linked to the Nrf2/HO-1 signaling pathway-mediated antioxidant response. Activation of this pathway by Rutin was found to significantly impede EqHV-8 replication, thereby diminishing the viral load. This mechanistic insight not only enhances our understanding of the antiviral potential of Rutin but also highlights the significance of antioxidant stress responses in combating EqHV-8 infection. To complement our in vitro findings, we conducted in vivo studies employing a mouse model. These experiments revealed that Rutin administration resulted in a substantial reduction in EqHV-8 infection within the lungs of the mice, underscoring the compound's therapeutic promise in vivo. In summation, our finding showed that Rutin holds promise as a novel and effective therapeutic agent for the prevention and control of EqHV-8 infections.

Impact of the Rutin on Diabetic Complications

Abstract: Diabetes is spread all over the world and frequently causes side effects, such as neuropathy, eye disease, kidney disease, and cardiovascular disease. The patient's life span is shortened by these problems. Numerous fruits and vegetables contain the naturally active flavonoid rutin. It has several medicinal benefits, including anti-inflammatory, antioxidant, and anticancer properties. Different researches suggest that rutin may be useful in treating these problems. The purpose of this study was to investigate the connection between the administration of rutin and the complications of diabetes. According to this study, rutin has both preventive and therapeutic effects on the side effects of diabetes as it lowers oxidative stress, inflammation., and apoptosis in animal models. To completely comprehend the preventive and therapeutic benefits of rutin in diabetic patients, more clinical study is necessary.

Oral administration of phytochemicals protects honey bees against cognitive and motor impairments induced by the insecticide fipronil.

Pollution produced by exposure to pesticides is a major concern for food security because the negative impacts on pollinators. Fipronil, an insecticide broadly used around the globe has been associated with the ongoing decline of bees. With a characteristic neuroactive toxicodynamic, fipronil leads to cognitive and motor impairments at sublethal dosages. Despite of regional bans, multilevel strategies are necessary for the protection of pollinators. Recent evidence suggests that specific nutrients in the diets of bees may induce protection against insecticides. Here, we evaluated whether the administration of three phytochemicals, namely rutin, kaempferol and p-coumaric acid provide protection to the Africanized honey bee Apis mellifera against oral administration of realistic dosages of fipronil. We tested the potential impairment produced by fipronil and the protection induced by the phytochemicals in learning, 24h memory, sucrose sensitivity and motor control. We found that the administration of fipronil induced a concentration-dependent impairment in learning and motor control, but not 24h memory or sucrose sensitivity across a 24h window. We also found that the administration of rutin, p-coumaric acid, kaempferol and the mixture was innocuous and generally offered protection against the impairments induced by fipronil. Overall, our results indicate that bees can be prophylactically protected against insecticides via nutrition, providing an alternative to the ongoing conflict between the use of insecticides and the decline of pollinators. As the studied phytochemicals are broadly present in nectar and pollen, our results suggest that the nutritional composition, and not only its production, should be considered when implementing strategies of conservation via gardens and co-cropping.

Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin.

Radiation triggers salivary gland damage and excess iron accumulates in tissues induces cell injury. Flavonoids are found in some fruits and are utilized as potent antioxidants and radioprotective agents. This study aimed to evaluate the antioxidant and anti-inflammatory effects of hesperidin and rutin on gamma radiation and iron overload induced submandibular gland (SMG) damage and to evaluate their possible impact on mitigating the alteration in mTOR signaling pathway and angiogenesis. Forty-eight adult male Wistar albino rats were randomly assigned to six groups: group C received a standard diet and distilled water; group H received hesperidin at a dose of 100mg/kg; four times a week for four weeks; group U received rutin at a dose of 50mg/kg; three times a week for three weeks; group RF received a single dose (5Gy) of gamma radiation followed by iron at a dose of 100mg/kg; five times a week for four weeks; group RFH received radiation and iron as group RF and hesperidin as group H; group RFU received radiation and iron as group RF and rutin as group U. SMG specimens from all groups were removed at the end of the experiment; and some were used for biochemical analysis, while others were fixed for histological and immunohistochemical examination. In the RF group, several genes related to antioxidants (Nrf-2 and SOD) and DNA damage (BRCA1) were significantly downregulated, while several genes related to inflammation and angiogenesis (TNFα, IL-1β and VEGF) and the mTOR signaling pathway (PIK3ca, AKT and mTOR) were significantly upregulated. Acinar cytoplasmic vacuolation, nuclear pyknosis, and interacinar hemorrhage with distinct interacinar spaces were observed as histopathological changes in SMGs. The duct system suffered significant damage, eventually degenerating entirely as the cells were shed into the lumina. VEGF and NF-κB were also significantly overexpressed. Hesperidin and rutin cotreatment generated partial recovery as indicated by significant upregulation of Nrf-2, SOD and BRCA1 and considerable downregulation of TNF-α, IL-1β, VEGF, PIK3ca, AKT, and mTOR. Although some acini and ducts continued to deteriorate, most of them had a normal appearance. There was a notable decrease in the expression of VEGF and NF-κB. In γ-irradiated rats with iron overload, the administration of hesperidin and rutin may mitigate salivary gland damage.

Benefits of rutin on mitochondrial function and inflammation in an aluminum-induced neurotoxicity rat model: Potential interest for the prevention of neurodegeneration

Rutin, a phenolic compound, exhibits a diverse range of biological properties, including antioxidant, anti-inflammatory, and antimicrobial effects. In this study, we aimed to investigate the potential of rutin, a naturally occurring plant bioactive molecule, to mitigate the neurotoxic effects induced by aluminum chloride (AlCl3). Over a period of 6 weeks, rats were intraperitoneally injected with AlCl3 at a weekly dose of 60 mg/kg, while rutin treatment was administered orally via gavage at a daily dose of 30 mg/kg. AlCl3 exposure resulted in a significant increase lipid peroxidation (LPO) by 316.24%, nitrate levels by 504.14%, and tumor necrosis factor-alpha (TNF-α) levels by 93.82% in brain mitochondria. Additionally, AlCl3 exposure led to a reduction in glutathione levels and the activity of antioxidant enzymes, including superoxide dismutase (SOD) by 19.74%, glutathione peroxidase (GPx) by 44.76%, and catalase by 50.50%. There was also a significant decline in the activity of mitochondrial complex enzymes. In contrast, rutin treatment significantly enhanced the activity of antioxidant enzymes while concurrently reducing lipid peroxidation levels in rats. Specifically, rutin administration exerted a modulatory effect on the inflammatory response triggered by aluminum exposure, effectively suppressing the excessive production of nitrate and TNF-α. These findings highlight the potential of rutin as an effective therapeutic strategy in mitigating and combating neuro-inflammation and oxidative stress associated with aluminum-induced toxicity, thereby effectively restoring mitochondrial function.

Influence of rutin and its combination with metformin on vascular functions in type 1 diabetes

The present work examined the effect of oral administration of rutin and its combination with metformin, an antidiabetic drug on blood glucose, total cholesterol and triglycerides level and vascular function in streptozotocin (STZ) -induced diabetic rats. Male Sprague Dawley rats were rendered diabetic by a single intraperitoneal injection of STZ (50 mg/kg). Rutin and metformin were orally administered to diabetic rats at a dose of 100 mg/kg and 300 mg/kg body weight/day, respectively, for 4 weeks. Plasma analysis was conducted to determine changes in the plasma glucose and lipid levels. Rat aortic ring reactivity in response to endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) relaxants, and to the α1-adrenergic agonist phenylephrine (PE) were recorded. Histology of pancreas, liver and kidney were evaluated. In results, rutin and metformin alone and in combination has led to significant improvements in blood glucose, cholesterol and triglyceride levels compared to diabetic group. Diabetic aortic rings showed significantly greater contraction in response to PE, and less relaxation in response to ACh and SNP. Treatment with rutin and metformin in combination significantly reduced PE-induced contraction and increased ACh-induced and SNP-induced relaxation in diabetes when compared to rutin or metformin alone. Significant histological improvements were seen with combination therapy. In conclusion, rutin and metformin combination therapy has the most potentiality for restoring blood glucose and lipid level as well as vascular function.

Mitigation potential of zingerone and rutin on toxicity mechanisms of nickel to zebrafish based on morphological, DNA damage and apoptosis outcome analysis

Although nickel (Ni) is an important cofactor for various enzymes in biological systems, it can cause serious problems when insufficient or excessive in an organism. Therefore, it is very important to investigate Ni in biological systems, especially in cells with its related pathogenic mechanism. This study was carried out to demonstrate the effects of zingerone (ZO) and rutin (RN) administration against nickel chloride (NiCl2) toxicity on neurobehavioral performance and brain oxidative status in zebrafish (Danio rerio) embryos/larvae on histological perspective. The experimental design of the study, which included twenty groups of fish, each containing 10 embryos, was prepared as semi-static and the trial continued for 96 hpf. In the obtained findings, it was determined that ZO and RN had a mitigating effect in this toxicity table where Ni caused oxidative stress in zebrafish larvae, induced DNA damage and apoptosis. A similar picture is valid for malformation processes as well as survival and hatching rates. These results showed that nickel is toxic to developing embryos via acting different mechanisms. In conclusion, we observed that ZO and RN have a greater effect on physiology, DNA damage and apoptosis than gross morphology, with a significant ameliorative effect.

Reduced graphene oxide for selective administration of rutin toward the cancer cell therapy

Reduced graphene oxide for selective administration of rutin toward the cancer cell therapy

Protective Effect of Rutin and Vitamin E on Cobalt Chloride Induced Neurotoxicity

Toxic exposures to cobalt chloride could occur from dietary, occupational, and medical sources. This study evaluated the ameliorative effect of oral administration of rutin and vitamin E on cobalt chloride (CoCl2)-induced oxidative stress in the brain of rats following exposure to cobalt chloride (CoCl2) toxicity. Wistar rats were randomly divided into five groups. Group 1 received only water, while group 2 received cobalt chloride (300 ppm) in drinking water. Groups 3, 4 and 5 also received cobalt chloride, but were treated with rutin (100 mg/kg body weight), rutin (200 mg/kg BW) and vitamin E (50 mg/kg BW) respectively for seven consecutive days. The rats were euthanized 24 hours after the last treatment. The brain was collected for biochemical and histopathological evaluations. The study demonstrated that cobalt chloride caused a significant (P<0.05) decrease in the activities of superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione level, whereas the levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) increased significantly (P<0.05). However, rutin and vitamin E treatment attenuated CoCl2-induced oxidative stress. Histopathological findings also revealed the ameliorative effect of rutin and Vitamin E on the neuronal damage caused by CoCl2 treatment.

Rutin alleviates EndMT by restoring autophagy through inhibiting HDAC1 via PI3K/AKT/mTOR pathway in diabetic kidney disease

BackgroundDiabetic kidney disease (DKD) is a primary microvascular complication of diabetes. However, a complete cure for DKD has not yet been found. Although there is evidence that Rutin can delay the onset of DKD, the underlying mechanism remains unclear. PurposeTo investigate the renoprotective effect of Rutin in the process of DKD and to explore its potential molecular mechanisms. MethodsDb/db mice and high glucose (HG)-induced human renal glomerular endothelial cells (GEnCs) were used as in vivo and in vitro models, respectively. Western blot (WB), Immunohistochemistry (IHC)and Immunofluorescence (IF) staining were used to identify the expression level of proteins associated with endothelial-to-mesenchymal transition (EndMT) and autophagy. Tandem Mass Tag (TMT)-based proteomics analysis was utilized to reveal the mechanism of Rutin in DKD. Transfection with small interfering RNA (siRNA) to reveal the role of histone deacetylase 1 (HDAC1) in HG-induced GEnCs. ResultsFollowing 8 weeks of Rutin administration, db/db mice's kidney function and structure significantly improved. In HG-induced GEnCs, activation of autophagy attenuates cellular EndMT. Rutin could alleviate EndMT and restore autophagy in vivo and in vitro models. Proteomics analysis results showed that HDAC1 significantly downregulated in the 200 mg/kg/d Rutin group compared with the db/db group. Transfection with si-HDAC1 in GEnCs partially blocked HG-induced EndMT and restored autophagy. Furthermore, Rutin inhibits the phosphorylation of the PI3K / AKT/ mTOR pathway. HDAC1 overexpression was suppressed in HG-induced GEnCs after using Rapamycin, a specific mTOR inhibitor, verifying the correlation between mTOR and HDAC1. ConclusionRutin alleviates EndMT by restoring autophagy through inhibiting HDAC1 via the PI3K/AKT/mTOR pathway in DKD.

Ameliorative Effect of Rutin Supplement on Chronic Unpredictable Mild Stress-Induced Depressive Phenotypes in Mice

Depression is a severe disorder that results in poor quality of life and affects hundreds of millions worldwide. Research on the relationship between depression and oxidative stress has shown important biochemical aspects in disease development. Flavonoids are a class of natural products that exhibit several pharmacological properties, including antidepressant-like activity and hence, suggested by studies to be exciting prototypes for new antidepressant drugs. Rutin is a flavonoid glycoside abundantly found in plants. The study evaluated the effect of rutin supplementation on depression using the chronic unpredictable mild stress depression mice models. Twenty-five mice were grouped into 5 (n = 5) and subjected to chronic unpredictable mild stressors. Groups 1-5 were orally served distilled water (no treatment), Rutin 30 mg/kg, 60 mg/kg, 120 mg/kg, and fluoxetine 20 mg/kg respectively. The study was conducted in the span of 30 days. Administration of rutin produced a reduction in immobility time at a dose of 120 mg/kg, a significant (p<0.05) decrease in the concentration of serum superoxide dismutase at doses of 30 and 60 mg/kg, and showed no significant difference on catalase and malondialdehyde levels. Rutin supplementation showed the potential of positively reversing behavioural despair. Thus, may be considered a possible treatment option for depressive symptoms in view of it attaining lesser side effects compared to orthodox treatments

Topical Application Using Non-ionic Surfactant for Formulation and Evaluation of Flavonoid Proniosomes

It is the goal of this research to examine the topical use of non-ionic surfactant for the Formulation and Evaluation of Flavonoid Proniosomes developed for the transdermal delivery of Rutin. The Proniosomal topical gel was prepared using the slurry technique involved with a non-ionic surfactant, Maltodextrin, Cholestrol and Glycerin. A robust design of experiments was used to optimize the various formulation variables. The optimized PG4 formulation was evaluated for entrapment efficiency, SEM, ATR –FTIR, Viscosity, Spreadability, Drug content, in-vitro diffusion study, and stability studies. PG4 formulation showed the highest entrapment efficiency and the higher percent of drug content. Evaluated for viscosity and spreadability which indicated the ratio of span 80: cholesterol demonstrated presenting some fluctuation. The SEM exhibited spherical vesicles and the optimal particle size for proniosome. In vitro drug release was better drug release throughout the process. After 3 months of storage at refrigerator temperatures, the stability in the presence of the percentage drug content of Rutin proniosomal gel formulation 4. There are several benefits to using Span 80 as the nonionic surfactant in these Proniosomal gel formulations, including increased drug accumulation in the different skin layers and increased carrier potential for the topical administration of rutin for the treatment of rheumatoid arthritis.

The flavonoid rutin protects the bumble bee Bombus impatiens against cognitive impairment by imidacloprid and fipronil.

ABSTRACTThe ongoing decline of bee populations and its impact on food security demands integrating multiple strategies. Sublethal impairments associated with exposure to insecticides, affecting the individual and the colony levels, have led to insecticide moratoria and bans. However, legislation alone is not sufficient and remains a temporary solution to an evolving market of insecticides. Here, we asked whether bees can be prophylactically protected against sublethal cognitive effects of two major neurotoxic insecticides, imidacloprid and fipronil, with different mechanisms of action. We evaluated the protective effect of the prophylactic administration of the flavonoid rutin, a secondary plant metabolite, present in nectar and pollen, and known for its neuroprotective properties. Following controlled or ad libitum administration of rutin, foragers of the North American bumble bee Bombus impatiens received oral administration of the insecticides at sublethal realistic dosages. Learning acquisition, memory retention and decision speed were evaluated using olfactory absolute conditioning of the proboscis extension response. We show that the insecticides primarily impair acquisition but not retention or speed of the conditioned proboscis extension response. We further show that the administration of the flavonoid rutin successfully protects the bees against impairments produced by acute and chronic administration of insecticides. Our results suggest a new avenue for the protection of bees against sublethal cognitive effects of insecticides.

Rutin Suppresses DMBA Carcinogenesis in the Breast Through Modulating IL-6/NF-κB, SRC1/HSP90 and ER-α

Rutin dietary supplements may offer pharmacological benefits as anticancer and antiinflammatory properties. This study aimed to investigate the inhibitory and protective effect of rutin on signaling pathways of mammary gland carcinogenesis expermintally induced in female rats by 7,12-di-methyl benz (a) anthracene (DMBA). Results showed that rutin administration ameliorated DMBA toxicity and carcinogic effect on kidney and liver revealed by a significant decrease of urea and creatinine levels, and the activity of the liver enzymes alanine aminotransferase (ALT) and alkaline phosphatase (ALP). The antioxidant state indicated by the total antioxidant capacity (TAC) was significantly increased accompanied by a reduction in the inflammatory markers of interleukin-1β (IL-1B), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) with induction of apoptosis indicated by a significant increase in caspase-3 level. Rutin significantly reduced the levels of the tumor markers carcinoma antigen 15-3 (CA 15-3) and proto-oncogene tyrosine-protein kinase Src1 (Src1). along with downregulation of nuclear factor-kB (NF-κB), heat shock protein 90 (HSP 90), and inducible nitric oxide synthase (iNOS) gene expression. The present study demonstrated the beneficial anticancer activity of rutin as a protective and therapeutic agent. Rutin induces its antitumor activity through elevation of the antioxidant state, inhibition of inflammatory cytokines, downregulation of oncogenes expression, and stimulation of apoptosis.

Formation and metabolism of 6-(1-acetol)-8-(1-acetol)-rutin in foods and in vivo, and their cytotoxicity.

Methylglyoxal (MGO) is a highly reactive precursor which forms advanced glycation end-products (AGEs) in vivo, which lead to metabolic syndrome and chronic diseases. It is also a precursor of various carcinogens, including acrylamide and methylimidazole, in thermally processed foods. Rutin could efficiently scavenge MGO by the formation of various adducts. However, the metabolism and safety concerns of the derived adducts were paid less attention to. In this study, the optical isomers of di-MGO adducts of rutin, namely 6-(1-acetol)-8-(1-acetol)-rutin, were identified in foods and in vivo. After oral administration of rutin (100 mg/kg BW), these compounds reached the maximum level of 15.80 μg/L in plasma at 15 min, and decreased sharply under the quantitative level in 30 min. They were detected only in trace levels in kidney and fecal samples, while their corresponding oxidized adducts with dione structures presented as the predominant adducts in kidney, heart, and brain tissues, as well as in urine and feces. These results indicated that the unoxidized rutin-MGO adducts formed immediately after rutin ingestion might easily underwent oxidation, and finally deposited in tissues and excreted from the body in the oxidized forms. The formation of 6-(1-acetol)-8-(1-acetol)-rutin significantly mitigated the cytotoxicity of MGO against human gastric epithelial (GES-1), human colon carcinoma (Caco-2), and human umbilical vein endothelial (HUVEC) cells, which indicated that rutin has the potential to be applied as a safe and effective MGO scavenger and detoxifier, and AGEs inhibitor.

The effect of rutin on pulmonary contusion induced by blunt trauma in rats: Biochemical and histopathological evaluation.

Background This study aims to investigate the possible protective effects of rutin, also called vitamin P1, against pulmonary contusion induced by blunt chest trauma in a rat model. Methods Thirty male albino Wistar rats were separated into three equal groups as healthy group, trauma group, and trauma+rutin group. After anesthesia provided by intraperitoneal administration of 60 mg/kg ketamine and xylazine by inhalation at appropriate intervals, 200 g weight was dropped from 1 m height to the anterior chest wall of the animals in the trauma group (n=10) and trauma+rutin group (n=10) and pulmonary contusion was created. Thirty min after the trauma, 50 mg/kg of rutin was administered into the stomach of trauma+rutin group animals orally with gavage. The rats received rutin once daily for two days and were sacrificed 48 h later. Their lung tissues were removed and examined biochemically and histopathologically. Results Nuclear factor-kappa B, cyclooxygenase-2, and malondialdehyde levels increased in the trauma group compared to the healthy group, and rutin administration prevented this increase. Total glutathione levels decreased in the trauma group, and rutin administration also prevented this decrease. The histopathological findings were compatible with the biochemical findings. Conclusion Our study results suggest that rutin has a protective effect on contused lung tissue in rats.

Use of flavonoids with antioxidant potential to prevent morphophysiological intestinal damage induced by the antineoplastic fluorouracil

Intestinal mucositis is a common complication associated with 5‐Fluorouracil (5‐FU) treatment, a chemotherapeutic agent widely used for cancer treatment. Characterized by inflammatory and/or ulcerative processes, intestinal mucositis is pathophysiologically based on the promotion of direct damage to the epithelium resulting from oxidative stress from the generation of reactive oxygen species (ROS). Flavonoids such as rutin, troxerutin and isoquercitrin, obtained from D. Gardnerian, have been reported with antioxidant and anti‐inflammatory properties. The present study aimed to evaluate the effect of flavonoids obtained from D. Gardnerian on 5‐fluorouracil‐induced intestinal mucositis in Swiss mice and identification of possible interactions of flavonoids in pro‐ inflammatory proteins. The mice (25‐30g) were divided into 4 groups (n=6): Saline group (NaCl 0.9%), 5‐FU group, Troxerutin group (150mg/kg troxerutin, orally) and Rutin group (300mg/kg rutin, orally). All animals except the Saline group received 5‐ FU at a concentration of 450 mg/kg in the first experimental protocol. To investigate morphological changes, periodic acid Schiff (PAS), toluidine blue, hematoxylin and eosin staining were performed. For the oxidative damage evaluation, the levels of the reduced antioxidant glutathione and the lipid peroxidation product, malondylaldehyde, of duodenal segments were determined. In silico molecular docking assays of the complexes formed between flavonoids (rutin, troxerutin and isoquercitrin) and the COX‐2, TNF‐α and NF‐kB enzymes were performed. The results showed that the antineoplastic 5‐FU promoted oxidative stress, evidenced by a decrease in reduced glutathione (GSH) and an increase in malondialdehyde (MDA) when compared to the saline group (p <0.05). Furthermore, the administration of flavonoids rutin and troxerutin promotes a decrease in MDA levels and an increase in GSH reserves (p <0.05), which culminate in attenuation of the oxidative stress promoted by the antineoplastic agent. The antioxidant effect of flavonoids corroborates the histopathological results, which show that both flavonoids have a significant reversal of antineoplastic‐induced morphological changes (p <0.05), such as reduction of villus height, deepening of the crypts, decrease in goblet cells and increase in mast cells and inflammatory infiltrate. Finally, molecular docking showed that the flavonoids rutin, troxerutin and isoquercitrin show stable binding to the target sites of COX‐2, NF‐kB, TNF‐α, important pro‐inflammatory proteins in inflammatory and ulcerative processes such as intestinal mucositis. It was concluded that the antioxidant effect promoted by flavonoids is one of the protective mechanisms of these natural products of the D. Gardnerian tree to prevent the morphophysiological damage of 5‐FU induced intestinal mucositis.

Comprehensive chemical profiling of the flowers of Citrus aurantium L. var. amara Engl. and uncovering the active ingredients of lipid lowering

The flowers of Citrus aurantium L. var. amara Engl. (FCAVA) is popularly consumed as an edible tea for anti-hyperlipidemia. But the active ingredients are not fully clear. In this study, ultra-high performance liquid chromatography coupled to quadrupole time of flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) with diagnostic product ions and neutral loss filtering strategy were successfully used for comprehensive characterization of chemical components in FCAVA. A total of 228 constituents, including 46 organic acids, 12 coumarins and 170 flavonoids, were tentatively characterized (30 confirmed with reference standards). Among them, nineteen flavonoids in 70 batches of FCAVA from different geographical origins were quantified by UHPLC tandem triple quadrupole mass spectrometry (QQQ-MS), which displayed satisfactory linearity, sensitivity, precision, accuracy, and stability. According to analytical results, the distribution of nineteen flavonoids in different geographical origins of FCAVA was clarified. In addition, the effect on LDL uptake of twenty-five flavonoids was investigated in HepG2 cell. It was found that the acacetin, diosmetin and rutin dose-dependently enhanced LDL uptake in HepG2 cells comparing to control. Furthermore, in a hyperlipidemia C57BL/6J mice model, administration of acacetin, diosmetin and rutin (30 mg/kg/d, intragastric, for three weeks) significantly decreased the levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) in plasma, respectively. Overall, these findings indicated the potential of FCAVA in the development of functional food or medicine for the prevention and treatment of hyperlipidemia, which could be considered for the improvement of quality standardization of FCAVA.

Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat's Heart.

BackgroundCisplatin is a common anticancer drug with potential cardiac and renal toxicities. Rutin, a natural compound present in various medicinal plants, has been shown to protect against chemotherapy-induced toxicities. In this study, we explored the protective effect of rutin against the dose-dependent cardiotoxic effects of cisplatin such as perfusion pressure, histopathologic effect on the myocardium, and oxidative stress in isolated perfused rat hearts.MethodologyThe cardiotoxic effects of cisplatin were studied at three dosages (1, 7, and 14 mg/L) in isolated perfused rat hearts. The dose-dependent, cisplatin-induced toxic effects on left ventricular pressure (LVP), heart rate (HR), dp/dt (maximum), dp/dt (minimum), perfusion pressure, pressure-time index, contractility index, and duration of diastole were assessed. The effects of cisplatin were measured one minute before perfusion of cisplatin and 60 minutes after perfusion of the isolated rat hearts.ResultsCisplatin (1-14 mg/L) caused a significant (p < 0.05) dose-dependent reduction in LVP. The percentage LVP values reduced from 94 ± 9 (control untreated hearts) to 70 ± 6, 69 ± 5, and 65 ± 4 in hearts treated with 1, 7, and 14 mg/L of cisplatin, respectively. Similarly, cisplatin at similar doses caused a marked reduction in the values of dp/dt (maximum), dp/dt (minimum), and pressure-time index in isolated rat hearts. The respective percentage values of these parameters compared to those of untreated hearts were significantly reduced from 101 ± 7 to 72 ± 5, 92 ± 8 to 69 ± 4, and 92 ± 12 to 57 ± 7 in hearts treated with 14 mg/L of cisplatin. Perfusion of hearts with rutin trihydrate (1 µM/L) 10 minutes before administration of cisplatin and throughout the experiment attenuated the detrimental effects of cisplatin on cardiac functions in isolated rat hearts (p < 0.05). In addition, cisplatin-induced degeneration and necrosis of cardiac muscle cells reduced with the concurrent administration of rutin and restored normal heart histology. Moreover, cisplatin-induced reduction in glutathione and increased level of malondialdehyde in the myocardium was reversed by concurrent administration of rutin in isolated rat hearts.ConclusionsCisplatin produced a dose-dependent impairment of several parameters of cardiac function such as LVP, contractility index, and pressure-time index. It caused histopathological alterations in isolated rat hearts. These harmful effects of cisplatin were suppressed by rutin trihydrate, suggesting the potential protective effects of rutin against cisplatin-induced cardiotoxicity. Rutin trihydrate also improved the reduced glutathione contents and suppressed the malondialdehyde contents in the cardiac tissue of isolated rat hearts, suggesting that the observed beneficial effects of rutin trihydrate in this study could be related to its antioxidant properties.

Rutin prevents seizures in kainic acid-treated rats: evidence of glutamate levels, inflammation and neuronal loss modulation.

Rutin, a naturally derived flavonoid molecule with known neuroprotective properties, has been demonstrated to have anticonvulsive potential, but the mechanism of this effect is still unclear. The current study aimed to investigate the probable antiseizure mechanisms of rutin in rats using the kainic acid (KA) seizure model. Rutin (50 and 100 mg kg-1) and carbamazepine (100 mg kg-1) were administered daily by oral gavage for 7 days before KA (15 mg kg-1) intraperitoneal (i.p.) injection. Seizure behavior, neuronal cell death, glutamate concentration, excitatory amino acid transporters (EAATs), glutamine synthetase (GS), glutaminase, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluA1 and GluA2, N-methyl-D-aspartate (NMDA) receptor subunits GluN2A and GluN2B, activated astrocytes, and inflammatory and anti-inflammatory molecules in the hippocampus were evaluated. Supplementation with rutin attenuated seizure severity in KA-treated rats and reversed KA-induced neuronal loss and glutamate elevation in the hippocampus. Decreased glutaminase and GluN2B, and increased EAATs, GS, GluA1, GluA2 and GluN2A were observed with rutin administration. Rutin pretreatment also suppressed activated astrocytes, downregulated the protein levels of inflammatory molecules [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high mobility group Box 1 (HMGB1), interleukin-1 receptor 1 (IL-1R1), and Toll-like receptor-4 (TLR-4)] and upregulated anti-inflammatory molecule interleukin-10 (IL-10) protein expression. Taken together, the results indicate that the preventive treatment of rats with rutin attenuated KA-induced seizures and neuronal loss by decreasing glutamatergic hyperactivity and suppressing the IL-1R1/TLR4-related neuroinflammatory cascade.