Octanal enhances disease resistance in postharvest citrus fruit by the biosynthesis and metabolism of aromatic amino acids.

Octanal was found to be able to reduce green mold incidence in citrus fruit by a defense response mechanism. However, the underlying mechanism remains largely unclear. Herein, the metabolomics, RNA-seq and biochemical analyses were integrated to explore the effect of octanal on disease resistance in harvested citrus fruit. Results showed that octanal fumigation at 40 µL L-1 was effective in controlling citrus green mold. Metabolomics analysis showed that octanal mainly led to the accumulation of some plant hormones including methyl jasmonate, abscisic acid, indole-3-butyric acid, indoleacetic acid (IAA), salicylic acid, and gibberellic acid and many phenylpropanoid metabolites including cinnamyl alcohol, hesperidin, dihydrokaempferol, vanillin, quercetin-3-O-malonylglucoside, curcumin, naringin, chrysin, coniferin, calycosin-7-O-ß-D-glucoside, trans-cinnamaldehyde, and 4',5,7-trihydroxy-3,6-dimethoxyflavone. Particularly, IAA and hesperidin were dramatically accumulated in the peel, which might be the contributors to the resistance response. Additionally, transcriptome analysis showed that octanal greatly activated the biosynthesis and metabolism of aromatic amino acids. This was further verified by the accumulation of some metabolites (shikimic acid, tryptophan, tyrosine, phenylalanine, IAA, total phenolics, flavonoids and lignin), increase in some enzyme activities (phenylalanine ammonia-lyase, tyrosine ammonia-lyase, 4-coumarate CoA ligase, cinnamic acid 4-hydroxylase, polyphenol oxidase, and peroxidase), up-regulation of some genes (tryptophan pyruvate aminotransferase, aldehyde dehydrogenase, shikimate kinase and shikimate dehydrogenase) expressions and molecular docking results. Thus, these results indicate that octanal is an efficient strategy for the control of postharvest green mold by triggering the defense response in citrus fruit.

Formation of Hesperetin-Methylglyoxal Adducts in Food and In Vivo, and Their Metabolism In Vivo and Potential Health Impacts.

Polyphenols with a typical meta-phenol structure have been intensively investigated for scavenging of methylglyoxal (MGO) to reduce harmful substances in food. However, less attention has been paid to the formation level of polyphenol-MGO adducts in foods and in vivo and their absorption, metabolism, and health impacts. In this study, hesperitin (HPT) was found to scavenge MGO by forming two adducts, namely, 8-(1-hydroxyacetone)-hesperetin (HPT-mono-MGO) and 6-(1-hydroxyacetone)-8-(1-hydroxyacetone)-hesperetin (HPT-di-MGO). These two adducts were detected (1.6-15.9 mg/kg in total) in cookies incorporated with 0.01%-0.5% HPT. HPT-di-MGO was the main adduct detected in rat plasma after HPT consumption. The adducts were absorbed 8-30 times faster than HPT, and they underwent glucuronidation and sulfation in vivo. HPT-mono-MGO would continue to react with endogenous MGO in vivo to produce HPT-di-MGO, which effectively reduced the cytotoxicity of HPT and HPT-mono-MGO. This study provided data on the safety of employing HPT as a dietary supplement to scavenge MGO in foods.

Pervasive influence of heavy metals on metabolic pathways is potentially relieved by hesperidin to enhance the phytoremediation efficiency of Bassia scoparia.

Hesperidin (HSP), a flavonoid, is a potent antioxidant, metal chelator, mediator of signaling pathways, and regulator of metal uptake in plants. The study examined the ameliorative effects of HSP (100 µM) on Bassia scoparia grown under excessive levels of heavy metals (zinc (500 mg kg-1), copper (400 mg kg-1), cadmium (100 mg kg-1), and chromium (100 mg kg-1)). The study clarifies the underlying mechanisms by which HSP lessens metabolic mayhem to enhance metal stress tolerance and phytoremediation efficiency of Bassia scoparia. Plants manifested diminished growth because of a drop in chlorophyll content and nutrient acquisition, along with exacerbated deterioration of cellular membranes reflected in elevated reactive oxygen species (ROS) production, lipid peroxidation, and relative membrane permeability. Besides the colossal production of cytotoxic methylglyoxal, the activity of lipoxygenase was also higher in plants under metal toxicity. Conversely, hesperidin suppressed the production of cytotoxic ROS and methylglyoxal. Hesperidin improved oxidative defense that protected membrane integrity. Hesperidin caused a more significant accumulation of osmolytes, non-protein thiols, and phytochelatins, thereby rendering metal ions non-toxic. Hydrogen sulfide and nitric oxide endogenous levels were intricately maintained higher in plants treated with HSP. Hesperidin increased metal accumulation in Bassia scoparia and thereby had the potential to promote the reclamation of metal-contaminated soils.

Citrate synthase lysine K215 hypoacetylation contributes to microglial citrate accumulation and pro-inflammatory functions after traumatic brain injury.

AIMS: This study aimed to investigate the relationship between microglial metabolism and neuroinflammation by examining the impact of citrate accumulation in microglia and its potential regulation through Cs K215 hypoacetylation. METHODS: Experimental approaches included assessing Cs enzyme activity through Cs K215Q mutation and investigating the inhibitory effects of hesperidin, a natural flavanone glycoside, on citrate synthase. Microglial phagocytosis and expression of pro-inflammatory cytokines were also examined in relation to Cs K215Q mutation and hesperidin treatment. RESULTS: Cs K215Q mutation and hesperidin exhibited significant inhibitory effects on Cs enzyme activity, microglial citrate accumulation, phagocytosis, and pro-inflammatory cytokine expression. Interestingly, Sirt3 knockdown aggravated microglial pro-inflammatory functions during neuroinflammation, despite its proven role in Cs deacetylation. CONCLUSION: Cs K215Q mutation and hesperidin effectively inhibited microglial pro-inflammatory functions without reversing the metabolic reprogramming. These findings suggest that targeting Cs K215 hypoacetylation and utilizing hesperidin may hold promise for modulating neuroinflammation in microglia.

Hesperidin and chlorogenic acid mitigate arsenic-induced oxidative stress via redox regulation, photosystems-related gene expression, and antioxidant efficiency in the chloroplasts of Zea mays.

The ubiquitous metalloid arsenic (As), which is not essential, can be found extensively in the soil and subterranean water of numerous nations, raising substantial apprehensions due to its impact on both agricultural productivity and sustainability. Plants exposed to As often display morphological, physiological, and growth-related abnormalities, collectively leading to reduced productivity. Polyphenols, operating as secondary messengers within the intricate signaling networks of plants, assume integral functions in the acquisition of resistance to diverse environmental stressors, including but not limited to drought, salinity, and exposure to heavy metals. The pivotal roles played by polyphenols in these adaptive processes underscore their profound significance in plant biology. This study aims to elucidate the impact of hesperidin (HP) and chlorogenic acid (CA), recognized as potent bioactive compounds, on maize plants exposed to As. To achieve this objective, the study examined the physiological and biochemical impacts, including growth parameters, photosynthesis, and chloroplastic antioxidants, of HP (100 µM) and CA (50 µM) on Zea mays plants exposed to arsenate stress (AsV, 100 µM - Na2HAsO4⋅7H2O). As toxicity led to reductions in fresh weight (FW) and dry weight (DW) by 33% and 26%, respectively. However, the application of As+HP and As + CA increased FW by 22% and 40% and DW by 14% and 17%, respectively, alleviating the effects of As stress. As toxicity resulted in the up-regulation of PSII genes (psbA and psbD) and PSI genes (psaA and psaB), indicating a potential response to the re-formation of degraded regions, likely driven by the heightened demand for photosynthesis. Exogenous HP or/and CA treatments effectively counteracted the adverse effects of As toxicity on the photochemical quantum efficiency of PSII (Fv/Fm). H2O2 content showed a 23% increase under As stress, and this increase was evident in guard cells when examining confocal microscopy images. In the presence of As toxicity, the chloroplastic antioxidant capacity can exhibit varying trends, with either a decrease or increase observed. After the application of CA and/or HP, a significant increase was observed in the activity of GR, APX, GST, and GPX enzymes, resulting in decreased levels of H2O2 and MDA. Additionally, the enhanced functions of MDHAR and DHAR have modulated the redox status of ascorbic acid (AsA) and glutathione (GSH). The HP or CA-mediated elevated levels of AsA and GSH content further contributed to the preservation of redox homeostasis in chloroplasts facing stress induced by As. In summary, the inclusion of HP and CA in the growth medium sustained plant performance in the presence of As toxicity by regulating physiological and biochemical characteristics, chloroplastic antioxidant enzymes, the AsA-GSH cycle and photosynthesis processes, thereby demonstrating their significant potential to confer resistance to maize through the mitigation of As-induced oxidative damage and the safeguarding of photosynthetic mechanisms.

The promotion of fatty acid ß-oxidation by hesperidin via activating SIRT1/PGC1α to improve NAFLD induced by a high-fat diet.

Reducing fat deposits in hepatocytes is a direct treatment for nonalcoholic fatty liver disease (NAFLD) and the fatty acid metabolic processes mediated by fatty acid ß-oxidation are important for the prevention of NAFLD. In this study, we established high-fat-diet models in vitro and in vivo to investigate the mechanism by which hesperidin (HDN) prevents NAFLD by modulating fatty acid ß oxidation. Based on LC-MS screening of differential metabolites, many metabolites involved in phospholipid and lipid metabolism were found to be significantly altered and closely associated with fatty acid ß-oxidation. The results from COIP experiments indicated that HDN increased the deacetylation of PGC1α by SIRT1. In addition, the results of CETSA and molecular docking experiments suggest that HDN targeting of SIRT1 plays an important role in their stable binding. Meanwhile, it was found that HDN reduced fatty acid uptake and synthesis and promoted the expression of SIRT1/PGC1α and fatty acid ß-oxidation, and the latter process was inhibited after transfection to knockdown SIRT1. The results suggest that HDN improves NAFLD by promoting fatty acid ß-oxidation through activating SIRT1/PGC1α. Thus, the findings indicate that HDN may be a potential drug for the treatment of NAFLD.

Protective role of hesperidin in finasteride-induced testicular toxicity in adult male Wistar rats: Insights into oxidative stress, apoptosis, and ultrastructure of seminiferous tubules.

A negative impact of finasteride on fertility has been reported, in which over production of reactive oxygen species and apoptosis were implicated. Hesperidin, a plant-derived bioflavonoid with antioxidant and anti-apoptotic effects, may mitigate these adverse effects. In order to investigate the possible protective role of hesperidin against finasteride-induced seminiferous tubules toxicity in adult male Wistar rats, 60 rats were randomized into five groups (I-V) receiving distilled water, 0.5% sodium carboxymethylcellulose solution, hesperidin, finasteride, and combined hesperidin and finasteride respectively. Testicular weight, sperm count and motility were determined. Testicular tissue homogenates were prepared to measure the level of malondialdehyde (MDA), total antioxidant capacity (TAC), reduced glutathione (GSH) and the gene expression of caspase-3 and B-cell lymphoma 2 (Bcl2). Testes were processed for light and electron microscopic evaluation. Johnsen score was calculated. Administration of finasteride resulted in significantly decreased testicular weights, sperm count and motility, Johnsen score, tissue levels of TAC and GSH together with significant increase in tissue MDA. Gene expression revealed significantly increased caspase-3 and decreased Bcl2. Furthermore, finasteride disrupted the seminiferous tubules, causing degenerative changes affecting Sertoli cells and spermatogenic cells. Co-administration of hesperidin with finasteride resulted in improvement in testicular weights, TAC, GSH, Bcl2, Johnsen score, sperm count and motility as well as preservation of the structure of the seminiferous tubules. To conclude, hesperidin was found to have a protective potential on finasteride-induced oxidative stress, apoptosis and testicular structural damage.

Antioxidant responses driven by Hesperetin and Hesperidin counteract Parkinson's disease-like phenotypes in Drosophila melanogaster.

The study investigated the protective effects of Hesperetin (HSP) and Hesperidin (HSD) on 1 methyl, 4 phenyl, 1,2,3,6 tetrahydropyridine hydrochloride (MPTP)-induced Parkinsonism in Drosophila melanogaster (D. melanogaster). After a lifespan study to select exposure time and concentrations, flies were co-exposed to MPTP (0.4 mg/g diet), Hesperetin (0.2 and 0.4 mg/g diet), and Hesperidin (0.1 and 0.4 mg/g) for 7 days. In addition to in vivo parameters, we assayed some markers of oxidative stress and antioxidant status (lipid peroxidation, protein carbonylation, thiol content, hydrogen peroxide, and nitrate/nitrite levels, mRNA expression of Keap-1 (Kelch-like ECH associated protein 1), /Nrf2 (Nuclear factor erythroid 2 related factor 2), catalase, and glutathione-S-transferase (GST) activities), and cholinergic (acetyl cholinesterase activity (AChE) and dopaminergic signaling content and the mRNA expression of tyrosine hydroxylase (TH), monoamine oxidase (MAO-like) activity). In addition to increasing the lifespan of flies, we found that both flavonoids counteracted the adverse effects of MPTP on survival, offspring emergence, and climbing ability of flies. Both flavonoids also reduced the oxidative damage on lipids and proteins and reestablished the basal levels of pro-oxidant species and activities of antioxidant enzymes in MPTP-exposed flies. These responses were accompanied by the normalization of the mRNA expression of Keap1/Nrf2 disrupted in flies exposed to MPTP. MPTP exposure also elicited changes in mRNA expression and content of TH as well as in MAO and AChE activity, which were reversed by HST and HSD. By efficiently hindering the oxidative stress in MPTP-exposed flies, our findings support the promising role of Hesperetin and Hesperidin as adjuvant therapy to manage Parkinsonism induced by chemicals such as MPTP.