Natural compounds are proper tools for inhibiting cancer cell proliferation. Hence, the search for these ligands of overexpressed receptors in breast cancer has been a competitive challenge recently ...and opens new avenues for drug discovery. In this research, we have investigated molecular interactions between natural products and overexpressed receptors in breast cancer using molecular docking and dynamic simulation approaches followed by extraction of the best ligand from Citrus limetta and developing for nanoscale encapsulation composed of soy lecithin using a sonicator machine. The encapsulation process was confirmed by DLS and TEM analyses. Anticancer activity was also examined using MTT method. Among the investigated natural compounds, hesperidin was found to bind to specific targets with stronger binding energy. The molecular dynamics results indicated that the hesperidin-MCL-1 complex is very stable at 310.15 K for 200 ns. The RP-HPLC analysis revealed that the purity of extracted hesperidin was 98.8% with a yield of 1.72%. The results of DLS and TEM showed a strong interaction between hesperidin and lecithin with an entrapped efficiency of 92.02 ± 1.08%. Finally, the cytotoxicity effect of hesperidin was increased against the MDA-MB-231 cell line with an IC50 value of 62.93 μg/mL after encapsulation, whereas no significant effect against the MCF10A cell line. We showed for the first time that hesperidin is a flexible and strong ligand for the MCL-1 receptor. Also, it has the in vitro ability to kill the MDA-MB-231 cell lines without having a significant effect on the MCF10A cell lines. Therefore, hesperidin could be used as a food ingredient to generate functional foods.
Background
Hesperidin, a flavanone commonly found in citrus fruits and herbal formulations, has emerged as a potential new therapeutic agent for modulating several diseases. Since pre‐eclampsia is a ...growing public health threat, it may negatively impact the economy and increase the disease burden of South Africa. Phytocompounds are easily accessible, demonstrate minimal side effects, and may confer novel medicinal options as a treatment and preventive preference.
Objective
To investigate the physiological, biochemical, and hematological outcomes of hesperidin in an arginine vasopressin (AVP)‐induced rodent model of pre‐eclampsia.
Methods
Female Sprague–Dawley rats were surgically implanted with mini‐osmotic pumps to deliver AVP (200 ng/h) subcutaneously. Animals were treated with hesperidin at 200 mg/kg.b.w via oral gavage for 14 days. Systolic and diastolic blood pressures were measured on GD 7, 14, and 18 using a non‐invasive tail‐cuff method and were euthanized on GD 21.
Results
The findings showed that hesperidin administration significantly decreased blood pressure (P < 0.05) and urinary protein levels in pregnant rats (P < 0.001). Placental and individual pup weight also increased significantly in the pregnant hesperidin‐treated groups compared to AVP untreated groups (P < 0.001). Biochemical and hematological markers such as white blood cell count and lymphocyte levels differed significantly (P < 0.05) in AVP groups treated with and without hesperidin.
Conclusion
Our results suggest that hesperidin is an antihypertensive agent with modes of action associated with its diuretic and blood pressure lowering effects and reduction of proteinuria in AVP‐induced pre‐eclamptic rats.
Hepatic encephalopathy (HE) is a serious neurological disorder which might occur in both acute and chronic liver injury. Aims: This study was carried out to explore the protective effects of ...hesperidin against experimentally induced HE. Main methods: Rats were sorted into four groups each of six; Normal group, TAA group: rats were administered 350 mg/kg of TAA i.p. from day 5 to day 7. TAA+ Hesp 100 group: rats were administered hesperidin 100 mg/kg/day orally for 7 days along with i.p TAA injection 350 mg/kg from day 5 to 7. TAA+ Hesp 200 group: rats were administered hesperidin 200 mg/kg/day orally for 7 days along with i.p TAA injection 350 mg/kg from day 5 to 7. Liver function, oxidative stress biomarkers, behavioral tests in addition to histopathological examination were assessed. Key findings: Hesperidin efficiently mitigated TAA-induced HE as evidenced by significant reduction in liver enzymes, bile and ammonia levels in serum. Moreover, hesperidin restored oxidant/antioxidant balance as manifested by reduction in MDA content in both cerebral and hepatic tissues. Additionally, hesperidin improved motor and cognitive abilities besides tissues' architecture as demonstrated by behavioral tests and histopathology results, respectively. Hesperidin also decreased levels of NLRP3 and increased levels of Sirt1 and FOXO in both cerebral and hepatic tissues. Finally, hesperidin markedly decreased the expression of IL-1β and caspase-1 as shown by immunohistochemical results. Significance: Taken together, the hepatoprotective impact of hesperidin and its ameliorative effect on the progression of HE appear to be mediated by its modulatory influence on NLRP3/Sirt1/FOXO signaling.
•Hesperidin possessed antioxidant properties by restoring antioxidant/oxidant balance.•Hesperidin inhibited NLRP3 inflammasome pathway.•Hesperidin downregulated both hepatic and cerebral Sirt1/FOXO1.•Hesperidin exerted both hepatoprotective and cognitive enhancing effects against hepatic encephalopathy.
Introduction
In the present study, a green and efficient extraction method using deep eutectic solvents as extraction solvent was developed for extracting the four major active compounds narirutin, ...naringin, hesperidin and neohesperidin from Aurantii Fructus.
Methodology
A series of tunable deep eutectic solvents were prepared and investigated by mixing choline chloride or betaine to different hydrogen‐bond donors, and betaine/ethanediol was found to be the most suitable extraction solvent. To achieve the best extraction yield, the primary factors affecting the extraction efficiency, such as hydrogen‐bond acceptor/hydrogen‐bond donor ratio, water content in deep eutectic solvents, extraction temperature, solid/liquid ratio and extraction time, were investigated.
Results
The optimal extraction conditions were 40% of water in betaine/ethanediol (1:4) at 60°C for heated extraction of 30 min and solid/liquid ratio 1:100 g/mL. Under the optimum extraction condition, the extraction yields of narirutin, naringin, hesperidin, and neohesperidin were 8.39 ± 0.61, 83.98 ± 1.92, 3.03 ± 0.35 and 35.94 ± 0.63 mg/g, respectively, which were much higher than those of methanol as extraction solvent (5.5 ± 0.48, 64.23 ± 1.51, 2.16 ± 0.15 and 30.14 ± 0.62 mg/g).
Conclusion
The present results showed that deep eutectic solvents could be promising green and efficient solvents for extraction of the bioactive ingredients from traditional Chinese medicine.
A green and efficient extraction method using deep eutectic solvents as extraction solvent was developed for extracting the bioactive compounds from Aurantii Fructus.
Prenatal exposure to valproic acid (VPA) induces behavioral disorders and enhancement of oxido-inflammatory stress in Autism Spectrum Disorders (ASDs). The aim of this study was to investigate the ...comparative effects of hesperetin (Hst) and nano-hesperetin on social behavior deficits and oxido-inflammatory indexes in prenatally valproic acid-exposed rat offspring. Pregnant Wistar rats on embryonic day 0 (E0) were segregated into six groups; Group-1 served as vehicle, received distillated water orally (PO) from E1 until the end of lactation and saline intraperitoneally (i.p) on E12.5. Group-2 received sodium valproate (500 mg/kg in 0.9% saline, i.p) on E12.5 was considered as VPA-exposed group, Group-3 to 6 were VPA-exposed which received hesperetin and nano-hesperetin (10 and 20 mg/kg/day, PO) from E0 until the end of lactation respectively. Social interaction and open field tests were conducted on postnatal day 28 (PND 28) and PND 30, cerebral antioxidant enzymes activity and biochemical indexes, the level of inflammatory factors in plasma and histopathology of cerebellum were estimated on PND 28 and PND 30. Prenatal valproic acid-exposed rat exhibited poor sociability and high level of anxiety-like behaviors (P < 0.05). In addition, increased level of oxidative stress and inflammation were found by determining different oxido-inflammatory markers. Hesperetin and nano-hesperetin treatment improved the behavioral disorder and reduced the oxidative stress in brain and significantly (p < 0.05) plasma's inflammation indexes. In conclusion, it can be state that nano-hesperetin exerts neuroprotective action in comparison with hesperetin and could be efficacious for treatment of VPA animal model of autism during pregnancy and lactation.
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•Isolation of hesperidin from orange peel and characterization by UV–visible spectroscopy, FTIR and NMR.•Synthesis and characterization of Hesperidin gold nanoparticles by UV–visible ...spectroscopy, FTIR, TEM and SAED.•Photocatalytic degradation study of environmental organic pollutants.•Antioxidant activity assessment by scavenging of DPPH, ABTS and hydroxyl free radical of hydrogen peroxide.
The unique properties of nanomaterials have the potential application in different fields of biomedical application along with the management of environmental pollutants. This research work involved the isolation of hesperidin from the orange peel and the preparation of hesperidin gold nanoparticles by the chemical reduction method. The high substrate specificity and lower band gap enable the excitation of gold nanoparticles in visible light. Hence gold nanoparticles are chosen nowadays for the management and removal of organic pollutants. The efficacy of hesperidin gold nanoparticles was evaluated by the photocatalytic activity on organic dyes and pollutants like methyl orange, methylene blue, bromocresol green, and 4 – nitro phenol with sodium borohydride as reducing agent and the antioxidant study by scavenging of free radicals of DPPH, ABTS, and hydroxyl free radicals of hydrogen peroxide. The kinetics of photocatalytic degradation of organic dyes and 4 – nitro phenol was found to follow the first order with rate constants of 10 × 10−3, 37 × 10−3, 23 × 10−3 and 49 × 10−3 min−1 for methyl orange, methylene blue, bromocresol green and 4 – nitro phenol respectively. The hesperidin gold nanoparticles showed significant antioxidant activity as compared to ascorbic acid as standard. The flavonoid conjugated gold nanoparticles can be an efficient antioxidant and photocatalyst for the management of different diseases and wastewater treatment respectively.
In recent years much attention has been focused on the pharmaceutical relevance of bioflavonoids, especially hesperidin and its aglycon hesperetin in terms of their antioxidant and anti-inflammatory ...actions. However, the bioactivity of their metabolites, the real molecules in vivo hesperetin glucuronides/sulfates produced after ingestion, has been poorly understood. Thus, the study using an ex vivo approach is aimed to compare the antioxidant and anti-inflammatory activities of hesperidin/hesperetin or hesperetin metabolites derived from hesperetin-administered rat serum. We found that hesperetin metabolites (2.5–20 μM) showed higher antioxidant activity against various oxidative systems, including superoxide anion scavenging, reducing power, and metal chelating effects, than that of hesperidin or hesperetin. The data also showed that pretreatment of hesperetin metabolites (1–10 μM) within the range of physiological concentrations, compared to hesperetin, significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production, as evidenced by the inhibition of their precursors, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels without appreciable cytotoxicity on LPS-activated RAW264.7 macrophages or A7r5 smooth muscle cells. Concomitantly, hesperetin metabolites dose-dependently inhibited LPS-induced intracellular reactive oxygen species (ROS). Furthermore, hesperetin metabolites significantly downregulate LPS-induced nuclear factor-κB (NF-κB) activation followed by the suppression of inhibitor-κB (I-κB) degradation and phosphorylation of c-Jun N-terminal kinase1/2 (JNK1/2) and p38 MAPKs after challenge with LPS. Hesperetin metabolites ex vivo showed potent antioxidant and anti-inflammatory activity in comparison with hesperidin/hesperetin.
Major depressive disorder (MDD) is a debilitating psychiatric disorder which is common and endangers human physical and mental health. Studies have shown that hesperidin could improve the symptoms of ...depression with unclear mechanisms.
In this study, hesperidin was administered to chronic unpredictable mild stress (CUMS) depressed mice before behavioral test, network pharmacology analysis, RNA expression microarray analysis, pathway validation and molecular docking experiments.
we found that hesperidin intervention could significantly improve the depressive symptoms and downregulate the expression level of pyroptosis pathway including caspase 1 (Casp1), interleukin 18 (IL18), interleukin-1β (IL-1β) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). In addition, we found that hesperidin could possibly bind to NLRP3.
Our study demonstrated that hesperidin had huge potential as anti-depressive neuroprotectant, and may play a role in treating MDD by regulating NLRP3-mediated pyroptosis.
Hesperetin is a class of natural products with a wide range of sources and remarkable biological activities. In this study, we described the synthesis of a series of novel hesperetin derivatives and ...evaluated the in vitro antioxidant and antitumor activity of these compounds. Eleven novel compounds were synthesized in moderate yields. The compounds synthesized in this work exhibited antioxidant activities against DPPH and ABTS free radicals in a dose-dependent manner. Among them, compound
had the best antioxidant activity, with IC
of 1.2 μM and 24 μM for DPPH and ABTS, respectively. The antitumor activity of the compounds against human cancer cell lines, such as breast MCF-7, liver HepG2, and cervical Hela, was determined by a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-
-tetrazolium bromide (MTT) assay. Three compounds had moderate IC
values. Interestingly, compound
had better biological activity than hesperetin, which matches the prediction by Maestro from Schrödinger. Therefore, the new hesperidin derivative is a promising drug for the treatment of cancer due to its effective antitumor activity. The results also suggested that the antitumor activities of hesperetin derivatives may be related to their antioxidant activities.
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.
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