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Green tea, a widely consumed beverage in Asia, contains green tea catechins effective against obesity, especially epigallocatechin-3- O -gallate (EGCG), but must be consumed in an impractically huge amount daily to elicit its biological effect. Meanwhile, citrus polyphenols have various physiological effects that could enhance EGCG functionality. Here we investigated the antiobesity effect of a combination of EGCG and α-glucosyl hesperidin, a citrus polyphenol, at doses that have not been previously reported to exert antiobesity effects by themselves in any clinical trial. In a randomized, placebo-controlled, double-blinded, and parallel-group-designed clinical trial, 60 healthy Japanese males and females aged 30–75 years consumed green tea combined with α-glucosyl hesperidin (GT-gH), which contained 178 mg α-glucosyl hesperidin and 146 mg EGCG, for 12 weeks. Physical, hematological, blood biochemical, and urine examinations showed that GT-gH is safe to use. At week 12, GT-gH prevented weight gain and reduced body mass index (BMI) compared with the placebo. Especially in those aged < 50 years, triglyceride and body fat percentage decreased at week 6, visceral fat level and body fat percentage decreased at week 12; body weight, BMI, and blood LDL/HDL ratio also decreased. In conclusion, taking GT-gH prevents weight gain, and the antiobesity effect of GT-gH was more pronounced in people aged < 50 years.

Hesperidin, a secondary orange (Citrus sinensis) metabolite, was extracted from orange bagasse. No organic solvents or additional energy consumption were used in the clean and sustainable process. Hesperidin purity was approximately 98% and had a yield of 1%. Hesperidin is a known supplement due to antioxidant, chelating, and anti-ageing properties. Herein, hesperidin application to eliminate dark eye circles, which are sensitive and thin skin regions, was studied. In addition, the proposed method for its aqueous extraction was especially important for human consumption. Further, the most effective methods for hesperidin nanonization were explored, after which the nanoemulsions were incorporated into a cream formulation that was formulated for a tropical climate. Silky cream formulations (oil in water) were tested in vitro on artificial 3D skin from cultured cells extracted from skin residues after plastic surgery. The proposed in vitro assay avoided tests of the different formulations in human volunteers and animals. It was shown that one of the nanonized hesperidin formulations was the most skin-friendly and might be used in cosmetics.

Alzheimer’s disease is a neurodegenerative disorder that impairs neurocognitive functions. Acetylcholinesterase, Butyrylcholinesterase, Monoamine Oxidase B, Beta-Secretase, and Glycogen Synthase Kinase Beta play central roles in its pathogenesis. Current medications primarily inhibit AChE but fail to halt or reverse disease progression due to the multifactorial nature of Alzheimer’s. This underscores the necessity of developing multi-target ligands for effective treatment. This study investigates the potential of phytochemical compounds from Moroccan medicinal plants as multi-target agents against Alzheimer’s disease, employing computational approaches. A virtual screening of 386 phytochemical compounds, followed by an assessment of pharmacokinetic properties and ADMET profiles, led to the identification of two promising compounds, naringenin (C23) and hesperetin (C24), derived from Anabasis aretioides . These compounds exhibit favourable pharmacokinetic profiles and strong binding affinities for the five key targets associated with the disease. Density functional theory, molecular dynamics simulations, and MM-GBSA calculations further confirmed their structural stability, with a slight preference for C24, exhibiting superior intermolecular interactions and overall stability. These findings provide a strong basis for further experimental research, including in vitro and in vivo studies, to substantiate their potential efficacy in Alzheimer’s disease.

Herein, we report green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids Hesperidin (HDN) and Naringin (NRG) as novel antimicrobial agents against brain-eating amoebae and multi-drug resistant bacteria. Nanoparticles were thoroughly characterized by using zetasizer, zeta potential, atomic force microscopy, ultravoilet-visible and Fourier transform-infrared spectroscopic techniques. The size of these spherical nanoparticles was found to be in the range of 100–225 nm. The antiamoebic effects of these green synthesized Silver and Gold nanoparticles loaded with HDN and NRG were tested against Acanthamoeba castellanii and Naegleria fowleri , while antibacterial effects were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Amoebicidal assays revealed that HDN loaded Silver nanoparticles stabilized by gum acacia (GA-AgNPs-HDN) quantitatively abolished amoeba viability by 100%, while NRG loaded Gold nanoparticles stabilized by gum tragacanth (GT-AuNPs-NRG) significantly reduced the viability of A. castellanii and N. fowleri at 50 µg per mL. Furthermore, these nanoparticles inhibited the encystation and excystation by more than 85%, as well as GA-AgNPs-HDN only completely obliterated amoeba-mediated host cells cytopathogenicity. Whereas, GA-AgNPs-HDN exhibited significant bactericidal effects against MRSA and E. coli K1 and reduced bacterial-mediated host cells cytotoxicity. Notably, when tested against human cells, these nanoparticles showed minimal (23%) cytotoxicity at even higher concentration of 100 µg per mL as compared to 50 µg per mL used for antimicrobial assays. Hence, these novel nanoparticles formulations hold potential as therapeutic agents against infections caused by brain-eating amoebae, as well as multi-drug resistant bacteria, and recommend a step forward in drug development.

Neuroprotection is the preservation of function and networks of neural tissues from damages caused by various agents, as well as neurodegenerative diseases such as Parkinson’s, Alzheimer’s, Huntington’s diseases, and multiple sclerosis. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against development of neurodegenerative diseases. Our review discusses neuropharmacological mechanisms for preventive and therapeutic effects of hesperidin in neurodegenerative diseases. In addition, the review examines clinical evidence confirming its neuroprotective function. Various cellular and animal models specific to neurodegenerative diseases have been conducted to evaluate the underlying neuropharmacological mechanisms of hesperidin. Neuroprotective potential of this flavonoid is mediated by improvement of neural growth factors and endogenous antioxidant defense functions, diminishing neuro-inflammatory and apoptotic pathways. Despite the various preclinical studies on the role of hesperidin in the neurodegenerative diseases, less is known about its definite effect on humans. A limited number of clinical trials showed that hesperidin-enriched dietary supplements can significantly improve cerebral blood flow, cognition, and memory performance. Further clinical trials are also required for confirming neuroprotective efficacy of this natural flavonoid and evaluating its safety profile.

Flavonoids are natural phytochemicals that have therapeutic effects and act in the prevention of several pathologies. These phytochemicals can be found in seeds, grains, tea, coffee, wine, chocolate, cocoa, vegetables and, mainly, in citrus fruits. Neohesperidin, hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory and antioxidant potential. Neohesperidin, in the form of neohesperidin dihydrochalcone (NHDC), also has dietary properties as a sweetener. In general, these flavanones have been investigated as a strategy to control bone diseases, such as osteoporosis and osteoarthritis. In this literature review, we compiled studies that investigated the effects of neohesperidin, hesperidin and its aglycone, hesperetin, on bone health. In vitro studies showed that these flavanones exerted an antiosteoclastic and anti- inflammatory effects, inhibiting the expression of osteoclastic markers and reducing the levels of reactive oxygen species, proinflammatory cytokines and matrix metalloproteinase levels. Similarly, such studies favored the osteogenic potential of preosteoblastic cells and induced the overexpression of osteogenic markers. In vivo, these flavanones favored the regeneration of bone defects and minimized inflammation in arthritis- and periodontitis-induced models. Additionally, they exerted a significant anticatabolic effect in ovariectomy models, reducing trabecular bone loss and increasing bone mineral density. Although research should advance to the clinical field, these flavanones may have therapeutic potential for controlling the progression of metabolic, autoimmune or inflammatory bone diseases.

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 IC 50 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.

Hesperidin is a flavonoid glycoside with proven therapeutic activities for various diseases, including cancer. However, its poor solubility and bioavailability render it only slightly absorbed, requiring a delivery system to reach its therapeutic target. Hesperidin loaded on gold nanoparticles (Hsp-AuNPs) was prepared by a chemical synthesis method. Various characterization techniques such as UV-VIS spectroscopy, FTIR, XRD, FESEM, TEM and EDX, Zeta potential analysis, particle size analysis, were used to confirm the synthesis of Hsp-AuNPs. The cytotoxic effect of Hsp-AuNPs on human breast cancer cell line (MDA-MB-231) was assessed using MTT and crystal violet assays. The results revealed significant decrease in proliferation and inhibition of growth of the treated cells when compared with human normal breast epithelial cell line (HBL-100). Determination of apoptosis by fluorescence microscope was also performed using acridine orange-propidium iodide dual staining assay. The in vivo study was designed to evaluate the toxicity of Hsp-AuNPs in mice. The levels of hepatic and kidney functionality markers were assessed. No significant statistical differences were found for the tested indicators. Histological images of liver, spleen, lung and kidney showed no apparent damages and histopathological abnormalities after treatment with Hsp-AuNPs. Hsp-AuNPs ameliorated the functional activity of macrophages against Ehrlich ascites tumor cells-bearing mice. The production of the pro-inflammatory cytokines was also assessed in bone marrow–derived macrophage cells treated with Hsp-AuNPs. The results obviously demonstrated that Hsp-AuNPs treatment significantly inhibited the secretion of IL-1β, IL-6 and TNF.

Cancer represents one of the most frequent causes of death in the world. The current therapeutic options, including radiation therapy and chemotherapy, have various adverse effects on patients’ health. In this vista, the bioactive ingredient of natural products plays a vital role in disease management via the inhibition and activation of biological processes such as oxidative stress, inflammation, and cell signaling molecules. Although natural products are not a substitute for medicine, they can be effective adjuvants or a type of supporting therapy. Hesperidin, a flavonoid commonly found in citrus fruits, with its potential antioxidant, anti-inflammatory, and hepatoprotective properties, and cardio-preventive factor for disease prevention, is well-known. Furthermore, its anticancer potential has been suggested to be a promising alternative in cancer treatment or management through the modulation of signal transduction pathways, which includes apoptosis, cell cycle, angiogenesis, ERK/MAPK, signal transducer, and the activator of transcription and other cell signaling molecules. Moreover, its role in the synergistic effects with anticancer drugs and other natural compounds has been described properly. The present article describes how hesperidin affects various cancers by modulating the various cell signaling pathways.

Recently, hesperidin, a flavonone mainly present in citrus fruits, has emerged as a new potential therapeutic agent able to modulate several cardiovascular diseases (CVDs) risk factors. Animal and in vitro studies demonstrate beneficial effects of hesperidin and its derived compounds on CVD risk factors. Thus, hesperidin has shown glucose-lowering and anti-inflammatory properties in diabetic models, dyslipidemia-, atherosclerosis-, and obesity-preventing effects in CVDs and obese models, and antihypertensive and antioxidant effects in hypertensive models. However, there is still controversy about whether hesperidin could contribute to ameliorate glucose homeostasis, lipid profile, adiposity, and blood pressure in humans, as evidenced by several clinical trials reporting no effects of treatments with this flavanone or with orange juice on these cardiovascular parameters. In this review, we focus on hesperidin’s beneficial effects on CVD risk factors, paying special attention to the high interindividual variability in response to hesperidin-based acute and chronic interventions, which can be partly attributed to differences in gut microbiota. Based on the current evidence, we suggest that some of hesperidin’s contradictory effects in human trials are partly due to the interindividual hesperidin variability in its bioavailability, which in turn is highly dependent on the α-rhamnosidase activity and gut microbiota composition.