Effects of hesperidin on the histological structure, oxidative stress, and apoptosis in the liver and kidney induced by NiCl2.

The aim of this study was to investigate the effect of hesperidin on the liver and kidney dysfunctions induced by nickel. The mice were divided into six groups: nickel treatment with 80 mg/kg, 160 mg/kg, 320 mg/kg hesperidin groups, 0.5% CMC-Na group, nickel group, and blank control group. Histopathological techniques, biochemistry, immunohistochemistry, and the TUNEL method were used to study the changes in structure, functions, oxidative injuries, and apoptosis of the liver and kidney. The results showed that hesperidin could alleviate the weight loss and histological injuries of the liver and kidney induced by nickel, and increase the levels of lactate dehydrogenase (LDH), alanine aminotransferase (GPT), glutamic oxaloacetic transaminase (GOT) in liver and blood urea nitrogen (BUN), creatinine (Cr) and N-acetylglucosidase (NAG) in kidney. In addition, hesperidin could increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) in the liver and kidney, decrease the content of malondialdehyde (MDA) and inhibit cell apoptosis. It is suggested that hesperidin could help inhibit the toxic effect of nickel on the liver and kidney.

Phytochemical analysis and biological evaluation of essential oils and extracts from Heracleum pastinacifolium subsp. incanum (Boiss. & A.Huet) P.H.Davis, an endemic plant from Turkey.

Essential oil content of and phenolic compounds flower-fruit, root, and aerial parts of Heracleum pastinacifolium subsp. incanum were analysed by GC/MS and LC/MS methods, respectively. Antidiabetic, anticholinesterase, and antioxidant activities of flower-fruit, root, aerial parts methanol extracts were evaluated. Apiole (35.0%), myristicine (72.2%), and myristicine (15.1%) were found as major compounds of fruit-flower mixture, root, aerial part essential oils, respectively. Hesperidin was found the highest amount in aerial part and flower-fruit extracts with 8904.2621 ng/mL and 11558.3634 ng/mL values, respectively. Fruit-flower extract showed the highest activity against α-glucosidase (24%). Root extract demonstrating the highest activity (18%) against AChE enzyme. Flowers-fruits mixture methanol extract had a higher % inhibition value on ABTS·+ and DPPH•. Flowers-fruits mixture methanol extract was rich in total phenol, total tannin, and protein content. All the extracts were determined as genetoxically safe according to the results of Ames/Salmonella, Escherichia coli WP2 and Allium cepa assays.

Data-driven dentistry: Computational revelations redefining pulp capping.

Introduction: Pulpal and periradicular diseases stem from immune reactions to microbiota, causing inflammation. Limited blood supply hampers dental pulp self-healing. Managing inflammation involves eliminating bacteria and reducing pro-inflammatory mediators especially MMP-9, which has a significant correlation with pulpitis. s. Flavonoids like Hesperidin, Baicalein, Epigallocatechin gallate, Genistein, Icariin, and Quercetin show potential for pulp capping. Aim: This in-silico study compares various Flavonoids for their anti-inflammatory effects on MMP-9, with Chlorhexidine as a control, a known MMP-9 inhibitor. Materials and Methods: Protein and Ligand Preparation: The human MMP-9 catalytic domain (PDB ID: 4XCT) structure was retrieved, and necessary modifications were made. Flavonoids from PubChem database were prepared for docking using AutoDock Vina. A grid for docking was created, and molecular dynamics simulations were conducted using Gromacs-2019.4 with GROMOS96 force field. Trajectory analysis was performed, and MM-PBSA calculation determined binding free energies. Results: Analysis of MMP-9 and ligand interactions revealed Hesperidin's high binding affinity, forming numerous hydrogen bonds with specific amino acids. Molecular dynamics simulations confirmed stability, with RMSD, RMSF, Rg, and SASA indicating consistent complex behaviour over 100 ns. MM-PBSA calculation affirmed favourable energy contributions in MMP-9-Hesperidin interactions. Conclusion: MMP-9 plays a crucial role in prognosis of pulpitis. Incorporating MMP-9 inhibitors into pulp capping agents may enhance therapeutic efficacy. Hesperidin emerges as a potent MMP-9 inhibitor, warranting further in vivo validation against other agents.

Hesperidin Alleviated Intestinal Barrier Injury, Mitochondrial Dysfunction, and Disorder of Endoplasmic Reticulum Mitochondria Contact Sites under Oxidative Stress.

As primary flavonoids extracted from citrus fruits, hesperidin has been attracting attention widely for its capacity to act as antioxidants that are able to scavenge free radicals and reactive oxygen species (ROS). Many factors have made oxidative stress a risk factor for the occurrence of intestinal barrier injury, which is a serious health threat to human beings. However, little data are available regarding the underlying mechanism of hesperidin alleviating intestinal injury under oxidative stress. Recently, endoplasmic reticulum (ER) mitochondria contact sites (ERMCSs) have aroused increasing concerns among scholars, which participate in mitochondrial dynamics and Ca2+ transport. In our experiment, 24 piglets were randomly divided into 4 groups. Piglets in the diquat group and hesperidin + diquat group received an intraperitoneal injection of diquat (10 mg/kg), while piglets in the hesperidin group and hesperidin + diquat group received hesperidin (300 mg/kg) with feed. The results indicated that hesperidin alleviated growth restriction and intestinal barrier injury in piglets compared with the diquat group. Hesperidin ameliorated oxidative stress and restored antioxidant capacity under diquat exposure. The mitochondrial dysfunction was markedly alleviated via hesperidin versus diquat group. Meanwhile, hesperidin alleviated ER stress and downregulated the PERK pathway. Furthermore, hesperidin prevented the disorder of ERMCSs by downregulating the level of ERMCS proteins, decreasing the percentage of mitochondria with ERMCSs/total mitochondria and the ratio of ERMCSs length/mitochondrial perimeter. These results suggested hesperidin could alleviate ERMCS disorder and prevent mitochondrial dysfunction, which subsequently decreased ROS production and alleviated intestinal barrier injury of piglets under oxidative stress.

In Vitro Biological Activities of Hesperidin-Related Compounds with Different Solubility.

The biological activities of hesperidin-related compounds, such as hesperetin laurate (HTL), hesperetin (HT), hesperidin (HD), and hesperidin glucoside (HDG), were investigated in vitro. The compounds showed different hydrophobicities, and the octanol-water partition coefficient log P were 7.28 ± 0.06 for HTL, 2.59 ± 0.04 for HT, 2.13 ± 0.03 for HD, and -3.45 ± 0.06 for HDG, respectively. In the DPPH assay and ß-carotene bleaching assay to determine antioxidant capacity, all compounds tested showed antioxidant activity in a concentration-dependent manner, although to varying degrees. HTL and HT showed similarly high activities compared to HD or HDG. HD and HDG did not show a significant difference despite the difference in solubility between the two. Cytotoxicity was high; in the order of hydrophobicity-HTL > HT > HD > HDL in keratinocyte HaCaT cells. All compounds tested showed reducing effects on cellular inflammatory mediators and cytokines induced by UV irradiation. However, HTL and HT effectively reduced nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) levels compared to HD and HDG. The inhibitory effects of hesperidin-related compounds on skin-resident microorganisms were evaluated by measuring minimum inhibitory concentration (MIC). HTL showed the highest inhibitory effects against Staphylococcus aureus, Cutibacterium acnes, Candida albicans, and Malassezia furfur, followed by HT, while HD and HDF showed little effect. In conclusion, the hydrophobicity of hesperidin-related compounds was estimated to be important for biological activity in vitro, as was the presence or absence of the sugar moiety.

Enhancement of aqueous solubility of hesperidin and naringenin utilizing hydrotropic solubilization technique: characterization and in vitro evaluation.

The therapeutic potential of two important flavonoids, i.e. hesperidin and naringenin, remains unutilized due to pharmacokinetics issues, especially poor aqueous solubility. Hydrotropic solid dispersions with different agents like sodium salicylate, niacinamide, benzoic acid, and urea etc. can change the solubility profile of poorly soluble drugs. The current study investigated the potential of different hydrotropic agents in improving the solubility of both natural bioactives. The hydrotropic solid dispersion in 1:3 w/w drug: sodium salicylate ratio showed maximum solubility and dissolution amongst all the tested hydrotropes. This novel and economical approach could be explored for other poorly soluble pharmaceuticals.

Hesperidin/Salinomycin Combination; a Natural Product for Deactivation of the PI3K/Akt Signaling Pathway and Anti-Apoptotic Factors in KG1a Cells.

AML is a highly aggressive malignant clonal disease of hematopoietic origin. Hesperidin as a polyphenol glycoside, Activates the apoptotic pathway and salinomycin as a k + selective ionophore. We examined how hesperidin and salinomycin induce pro-apoptotic effects in KG1a cells. Cells were divided into four groups; 1) control cells (CRTL), 2) cells treated with hesperidin 85 µM, 3) cells treated with 2 µM salinomycin, 4) cells treated with combination of salinomycin and hesperidin. The MTT assay was implemented to determine the IC50 of hesperidin and salinomycin in KG1a cell lines. Propidium iodide staining and flow cytometry were used to analyze the distribution of the cell cycle. The level of ROS was evaluated by fluorescent microscopy and spectrophotometry. Additionally, Akt, XIAP, Bad, and FOXO1 gene expression was analyzed by real-time PCR. Hesperidin/Salinomycin decreased the viability of KG1a leukemic cells more than Hesperidin and Salinomycin separately. Changes in the shape of apoptotic cells and rise in ROS levels were detected after Hesperidin/Salinomycin treatment. Our findings showed that following Hesperidin/Salinomycin treatment, the expression of PI3K/AKT signaling pathway related genes (AKT, PTEN and FOXO1), were in line with the destruction of KG-1a cells. Furthermore, XIAP and BAD mRNA were regulated to trigger apoptosis in cancer cells. The study discovered that hesperidin and salinomycin, could effectively hinder the PI3K/Akt signaling pathway in leukemia cancer cells. Also, the combination of hesperidin and salinomycin has the potential to be a treatment option for acute myeloid leukemia.

Reduced Insulin Resistance and Oxidative Stress in a Mouse Model of Metabolic Syndrome following Twelve Weeks of Citrus Bioflavonoid Hesperidin Supplementation: A Dose-Response Study.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg/kg/day), mid- (140 mg/kg/day), or high-dose (280 mg/kg/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice (p < 0.0001). Fasting blood glucose (FBG) increased by 40% (p < 0.0001), plasma insulin by 100% (p < 0.05), and HOMA-IR by 150% (p < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day (p < 0.0001) and 50% at 280 mg/kg/day (p < 0.005). HOMA-IR decreased by 45% at both doses (p < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups (p < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice (p < 0.001) and reduced by 20% with all hesperidin doses (p < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS.

Hesperidin, a Potential Antiviral Agent against SARS-CoV-2: The Influence of Citrus Consumption on COVID-19 Incidence and Severity in China.

This review examines hesperidin, a citrus bioflavonoid, as a potential antiviral agent against SARS-CoV-2. The COVID-19 pandemic has demanded an urgent need to search for effective antiviral compounds, including those of natural origin, such as hesperidin. The review provides a comprehensive analysis of the chemical properties, bioavailability and antiviral mechanisms of hesperidin, particularly its potential efficacy against SARS-CoV-2. A review of databases, including PubMedPico, Scopus and Web of Science, was conducted using specific keywords and search criteria in accordance with PRISMA (Re-porting Items for Systematic Reviews and Meta-Analysis) guidelines between 2020 and 2024. Of the 207 articles, 37 were selected for the review. A key aspect is the correlation of in vitro, in silico and clinical studies on the antiviral effects of hesperidin with epidemiological data on citrus consumption in China during 2020-2024. The importance of integrating laboratory findings with actual consumption patterns to better understand the role of hesperidin in mitigating COVID-19 was highlighted, and an attempt was made to analyze epidemiological studies to examine the association between citrus juice consumption as a source of hesperidin and the incidence and severity of COVID-19 using China as an example. The review identifies consistencies and discrepancies between experimental and epidemiological data, highlighting the need to correlate the two fields to better understand the potential of hesperidin as an agent against SARS-CoV-2. Challenges and limitations in interpreting the results and future research perspectives in this area are discussed. The aim of this comprehensive review is to bridge the gap between experimental studies and epidemiological evidence and to contribute to the understanding of their correlation.

Hesperidin Alleviates Hepatic Injury Caused by Deoxynivalenol Exposure through Activation of mTOR and AKT/GSK3ß/TFEB Pathways.

Deoxynivalenol (DON) is a common agricultural mycotoxin that is chemically stable and not easily removed from cereal foods. When organisms consume food made from contaminated crops, it can be hazardous to their health. Numerous studies in recent years have found that hesperidin (HDN) has hepatoprotective effects on a wide range of toxins. However, few scholars have explored the potential of HDN in attenuating DON-induced liver injury. In this study, we established a low-dose DON exposure model and intervened with three doses of HDN, acting on male C57 BL/6 mice and AML12 cells, which served as in vivo and in vitro models, respectively, to investigate the protective mechanism of HDN against DON exposure-induced liver injury. The results suggested that DON disrupted hepatic autophagic fluxes, thereby impairing liver structure and function, and HDN significantly attenuated these changes. Further studies revealed that HDN alleviated DON-induced excessive autophagy through the mTOR pathway and DON-induced lysosomal dysfunction through the AKT/GSK3ß/TFEB pathway. Overall, our study suggested that HDN could ameliorate DON-induced autophagy flux disorders via the mTOR pathway and the AKT/GSK3ß/TFEB pathway, thereby reducing liver injury.

Mitigating cyclophosphamide-associated gonadotoxicity in male Wistar rats: exploring the therapeutic potential of hesperidin.

Hesperidin, a bioactive flavanone glycoside prevalent in citrus fruits, with remarkable therapeutic properties stands out as a formidable defender against the debilitating reproductive toxicity associated with Cyclophosphamide (CYP) chemotherapy. This study explores the protective potential of hesperidin (HSP@100 mg/kg b.wt PO daily) against CYP-induced (@ 40 mg/kg b.wt IP once in a week) reproductive toxicity in male Wistar rats as several studies were documented on single dose toxicity of CYP. In this experiment, we chose multidosage drug effects, which are more relevant in chemotherapy. Twenty-four rats were divided into four groups: Group 1 (Control), group 2 (CYP-treated), group 3 (HSP-treated), and group 4 (CYP + HSP-treated) for 28 days. The experimental design included assessments of relative testicular weight, semen analysis, testosterone levels, oxidative stress markers, inflammatory cytokines, gross and histopathological changes, and immunohistochemical evaluation. The results revealed that the administration of CYP led to a significant reduction in testicular weight, sperm count, motility, and testosterone levels, accompanied by increased oxidative stress and inflammatory response. Hesperidin co-administration demonstrated a protective effect by restoring these parameters to near-normal levels. Histopathological analysis revealed improved testicular architecture in the group 4 compared with the group 2. Oxidative stress indices indicated that hesperidin attenuated CYP-induced damage by reducing malondialdehyde levels, enhancing superoxide dismutase activity and maintaining glutathione levels. Similarly, inflammatory cytokine analysis demonstrated anti-inflammatory effects of hesperidin by reducing tumor necrosis factor-alpha (TNF-α) and elevating interleukin-10 (IL-10) levels in the group 4. Immunohistochemical evaluation of nuclear factor-kappa B (NF-κB) revealed increased inflammation in the CYP group, while hesperidin significantly reduced NF-κB expression, suggesting its anti-inflammatory properties.

Ameliorative potentials of diosmin and hesperidin fractions on chlorpyriphos-induced changes in reproductive hormones, sperm characteristics, and testicular glycogen in male Wistar rats.

Reproductive deficiency is a major outcome of pesticide exposure sequel to cellular oxidative damage to sex organs. Flavonoid possess potent antioxidant capacities to mitigate pesticide related cellular injury. The present investigation examined the mitigative effect of micronized purified fractions of diosmin and hesperidin on reproductive hormones, sperm parameters, and testicular glycogen in male Wistar rats after sub-chronic Chlorpyriphos (CPF) exposure. Twenty-five male Wistar rats (120-145 g) were randomly allocated five rats per group. Group I (DW) received distilled water (2 ml/kg), Group II (S/oil) received soya oil (2 ml/kg), Group III (DAF) received Daflon at 1000 mg/kg, Group IV (CPF) received Chlorpyriphos (7.74 mg/kg), and Group V (DAF + CPF) received Daflon (1000 mg/kg) followed by CPF (7.74 mg/kg) after 30 min of Daflon. This regimen was administered daily for 60 days. After cervical venesection under light chloroform anesthesia, blood samples were examined for levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Each rat's testicular tissue was quickly cut, collected, and glycogen evaluated. Sperm concentration, motility, morphology, and viability were measured in the right caudal epididymis. Results revealed that the untreated CPF group had significantly lower FSH, LH, testosterone, testicular glycogen, and sperm concentration. Additionally, CPF group sperm characteristics were abnormal compared to other groups. These reproductive hormones, testicular glycogen, and sperm parameters improved in the Daflon-treated groups. Hence, pre-treatment with flavonoid fractions of diosmin and hesperidin mitigated CPF-induced reproductive toxicity.

Hesperidin reduces systolic blood pressure in diabetic patients and has no effect on blood pressure in healthy individuals: A systematic review and meta-analysis.

In recent years, there have been a number of studies where hesperidin was administered to modify arterial blood pressure, but the conclusions of each study are contradictory. In order to investigate the effect of hesperidin on blood pressure, we searched the CNKI, Wanfang Database, the VIP database, Sinomed database, Pubmed, Embase and The Cochrane Library databases, and searched the literature on hesperidin and blood pressure published in Chinese and English journals, mainly focusing on patients' systolic blood pressure and diastolic blood pressure. The search time frame was from the inception of the databases until December 2023. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the overall quality and used Cohen's kappa coefficient (κ) to measure agreement. We did preliminary screening of the retrieved literature through Notexpress, 14 articles with a total of 656 patients were included. Cochrance data conversion tool was used for data conversion, and RevMan 5.3 was used for meta-analysis, and finally Stata was used to make the Egger's test for the included study. The results of total population blood pressure showed that hesperidin had no antihypertensive effect on the population, but the conclusions changed when the population was divided into groups. The results of different populations showed that hesperidin had no effect on systolic blood pressure (weighted mean difference [WMD] = -0.50, 95% CI: -3.25 ~ 2.26, Z = 0.35, p = 0.72) and diastolic blood pressure (WMD = -0.51, 95% CI: -2.53 ~ 1.51, Z = 0.50, p = 0.62) in healthy individuals. However, hesperidin reduced systolic blood pressure in patients with type 2 diabetes (WMD = -4.32, 95% CI: - 7.77 ~ - 0.87, Z = 2.45, p = 0.01), and had a tendency to reduce diastolic blood pressure in diabetic patients (WMD = -3.72, 95% CI: -7.63 ~ 0.18, Z = 1.87, p = 0.06). The results in patients with type 2 diabetes needed to be further supported by future research focusing on individuals with diabetes.

Evaluating the Nutritional Composition of Unripe Citrus and Its Effect on Inhibiting Adipogenesis and Adipocyte Differentiation.

Citrus fruits offer a range of health benefits due to their rich nutritional profile, including vitamin C, flavonoids, carotenoids, and fiber. It is known that unripe citrus has higher levels of vitamin C, dietary fiber, polyphenols, and flavonoids compared to mature fruits. In this study, we assessed the nutritional components of unripe citrus peel and pressed juices, as well as their anti-obesity potential through the modulation of adipocyte differentiation and the expression of adipogenesis-related genes, specifically PPARγ and C/EBPα, in 3T3-L1 preadipocytes. Our analysis revealed that unripe citrus peel exhibited elevated levels of fiber and protein compared to pressed juice, with markedly low levels of free sugar, particularly sucrose. The content of hesperidin, a representative flavonoid in citrus fruits, was 3,157.6 mg/kg in unripe citrus peel and 455.5 mg/kg in pressed juice, indicating that it was approximately seven times higher in unripe citrus peel compared to pressed juice. Moreover, we observed that the peel had a dose-dependently inhibitory effect on adipocyte differentiation, which was linked to a significant downregulation of adipogenesis-related gene expression. Thus, our findings suggest that unripe citrus possesses anti-obesity effects by impeding adipogenesis and adipocyte differentiation, with the peel demonstrating a more pronounced effect compared to pressed juice.

Hesperidin neuroprotective effects against carbon monoxide-induced toxicity in male rats.

Carbon monoxide (CO) is produced via incomplete combustion of fossil fuels and it may cause long-term neurological sequel upon exposure. Hesperidin (HES), a flavanone glycoside found in citrus plants, exerts diverse beneficial health effects. The present study mechanistically examined the neuroprotective effects of HES in CO-poisoned rats. Thirty male Wistar rats (five groups of six animals) were exposed to 3000 ppm CO for 1 h. Immediately after the exposure and on the next 4 consecutive days (totally five doses), rats intraperitoneally received either normal saline (the control group) or different doses of HES (25, 50, and 100 mg/kg). A sham group that was not exposed to CO was also considered. After evaluation of spatial learning and memory using a Morris water maze (MWM), animals were sacrificed and oxidative stress status in blood samples, and Akt, Bax, Bcl2, and brain-derived neurotrophic factor (BDNF) expression in brain samples were assessed. Western blot analysis indicated increased Akt but decreased Bax/Bcl2 levels in the HES 100 mg/kg, and induced BDNF levels in all HES-treated groups. MWM results showed that HES significantly decreased memory loss. The current findings indicate that HES could alleviate neurological impairments induced by CO in rats.

Immature mandarin orange extract increases the amount of hyaluronic acid in human skin fibroblast and keratinocytes.

Immature mandarin orange is thinned in order to maturation of orange. To use immature mandarin orange as a cosmetic functional material, we investigated the seasonal fluctuation changes in hesperidin and narirutin levels of immature mandarin oranges, and the effects on human skin cells. The contents of hesperidin from Aoshima, Otsu, and Shonan gold, is higher at about a month after flowering. Shonan gold has higher content of narirutin to compere that of Aoshima and Otsu. We found the addition of immature mandarin orange extracts to the human skin fibroblasts and keratinocytes, gene expression level of hyaluronic acid synthase and the hyaluronic acid contents in the medium are higher than that of the control. It was suggested that hesperidin in immature mandarin orange enhances the ability of skin cells to produce hyaluronic acid. Our findings indicate that the immature mandarin orange is a characteristic material on cosmetics and functional foods.

Drug repurposing: identification of SARS-CoV-2 potential inhibitors by virtual screening and pharmacokinetics strategies.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused global health, economic, and population loss. Variants of the coronavirus contributed to the severity of the disease and persistent rise in infections. This study aimed to identify potential drug candidates from fifteen approved antiviral drugs against SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike protein (6M0J) using virtual screening and pharmacokinetics to gain insights into COVID-19 therapeutics. METHODOLOGY: We employed drug repurposing approach to analyze binding performance of fifteen clinically approved antiviral drugs against the main protease of SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike proteins bound to ACE-2 receptor (6M0J), to provide an insight into the therapeutics of COVID-19. AutoDock Vina was used for docking studies. The binding affinities were calculated, and 2-3D structures of protein-ligand interactions were drawn. RESULTS: Rutin, hesperidin, and nelfinavir are clinically approved antiviral drugs with high binding affinity to proteins 6LU7, 5B6O, and 6M0J. These ligands have excellent pharmacokinetics, ensuring efficient absorption, metabolism, excretion, and digestibility. Hesperidin showed the most potent interaction with spike protein 6M0J, forming four H-bonds. Nelfinavir had a high human intestinal absorption (HIA) score of 0.93, indicating maximum absorption in the body and promising interactions with 6LU7. CONCLUSIONS: Our results indicated that rutin, hesperidin, and nelfinavir had the highest binding results against the proposed drug targets. The computational approach effectively identified SARS-CoV-2 inhibitors. COVID-19 is still a recurrent threat globally and predictive analysis using natural compounds might serve as a starting point for new drug development against SARS-CoV-2 and related viruses.

Eltroxin and Hesperidin mitigate testicular and renal damage in hypothyroid rats: amelioration of oxidative stress through PPARγ and Nrf2/HO-1 signaling pathway.

BACKGROUND: Thyroid hormones (THs) regulate growth, development and function of different tissues. Hypothyroidism is a common clinical disorder characterized by deficiency in THs and adversely affects the development and functions of several organs. This work aimed to investigate the ameliorative effect of eltroxin (ELT), a hypothyroidism medication, and hesperidin (HSP), a flavonoid, against testicular and renal toxicity in hypothyroid rats. Twenty-four rats were divided into four groups and treated orally for 12 weeks. Group I (control), group II (hypothyroidism) received 20 mg/kg carbimazole (CBZ), group III received CBZ and 0.045 mg/kg ELT, and group IV received CBZ and 200 mg/kg HSP. RESULTS: CBZ administration induced biochemical and histopathological changes in testis and kidney. Co-administration of ELT or HSP significantly (P < 0.05) ameliorated THs, reduced urea and creatinine while raised follicle stimulating hormone (FSH), Luteinizing hormone (LH), and testosterone in serum. Testicular and renal malondialdehyde level as a lipid peroxidation indicator, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly (P < 0.05) decreased while glutathione content, glutathione peroxidase, and glutathione-s-transferase activities were significantly (P < 0.05) increased. The histopathological changes were also diminished. Decreased mRNA and protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and peroxisome proliferator-activated receptor gamma(PPARγ) in hypothyroid rats were up-regulated after ELT or HSP treatment. CONCLUSIONS: ELT and HSP showed antioxidant and anti-inflammatory effects against CBZ-induced testicular and renal toxicity, and these effects may be promoted via activating Nrf2/HO-1 and PPARγ signaling pathways.

Evaluation of the Effect of Loratadine versus Diosmin/Hesperidin Combination on Vinca Alkaloids-Induced Neuropathy: A Randomized Controlled Clinical Trial.

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group-neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response.

Testicular protective effects of hesperidin against chemical and biological toxicants.

Toxic agents can adversely impact the male reproductive system mainly via activating oxidative stress affecting the seminiferous epithelia, spermatogenesis, sperms, and the testis. Toxic agents lead to the excessive generation of reactive oxygen species (ROS), such as hydroxyl radicals, hydrogen peroxide, and superoxide anions. ROS exert a cytotoxic effect and oxidative damage to nucleic acids, proteins, and membrane lipids. Hesperidin is a pharmacologically active phytoflavone abundantly occurring in citrus fruits, such as oranges and lemons. It has shown various pharmacological properties such as antioxidant, anti-inflammatory, anti-carcinogenic, analgesic, antiviral, anti-coagulant, hypolipidemic, and hypoglycemic effects. Hesperidin has been found to exert protective effects against natural and chemical toxins-induced organ toxicity. Considerable evidence has implicated the testicular protective effects of hesperidin against the toxicological properties of pharmaceutical drugs as well as biological and chemical agents, and in the present review, we discussed, for the first time, the reported studies. The resultant data indicate that hesperidin can exert testicular protective effects through antioxidant properties.