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The Tyndall effect of (a) rutin in water, (b) prenanoemulsion of rutin in water, and (c) pure water.
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![The chemical structure of rutin [26].](publication/347785170/figure/fig1/AS:1083903829909527@1635434219311/The-chemical-structure-of-rutin-26_Q320.jpg)
In this work, prenanoemulsion of rutin was prepared using PEG and Tween as emulsifiers via homogenization and evaporation techniques. The particle size of rutin was investigated with high-resolution transmission electron microscopy (HR-TEM); particle size distribution and its chemical structure were analysed by nuclear magnetic resonance (NMR) and...
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Citations
... They have been tested for their anticancer potential against breast and pancreatic cancer, 41,42 management of cerebral ischemia 43 with anti-inflammatory, 44 antibacterial, antioxidant, and photocatalytic activities 45 and had been suggested for possible use in cosmetics and wound healing. 46,47 Although there are very limited reports on the use of rutin-loaded CNPs for cancer therapy, rutin has been successfully loaded on several other nanoparticles including mineral-, lipid-, ionic-liquid, silica-, PEGylated nanoliposome-, solid lipid-, nanoemulsion-, nanocrystal-, keratin-, PLGA-, platinum and palladium-based nanomaterials and on phyto-sterosomes for the treatment of breast, [48][49][50] lung, 51,52 renal, 53 head and neck, 54 colorectal, 31,55 cervical, 56 brain 57 and liver 58,59 cancers at the preclinical level. Other than cytotoxic effects on cancer cells, rutin conjugated with mesoporous silica, nanolipids, nanomagnesia, selenium, PLGA nanoparticles and prepared in the form of nanocrystals have been proven effective for antibacterial, 60,61 antioxidant, 62 photoprotective, 63 anti-epilectic 64 and anti-parasitic 65 activities. ...
Background
Liver cancer remains to be one of the leading causes of cancer worldwide. The treatment options face several challenges and nanomaterials have proven to improve the bioavailability of several drug candidates and their applications in nanomedicine. Specifically, chitosan nanoparticles (CNPs) are extremely biodegradable, pose enhanced biocompatibility and are considered safe for use in medicine.
Methods
CNPs were synthesized by ionic gelation, loaded with rutin (rCNPs) and characterized by ultraviolet–visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and transmission electron microscopy (TEM). The rCNPs were tested for their cytotoxic effects on human hepatoma Hep3B cells, and experiments were conducted to determine the mechanism of such effects. Further, the biocompatibility of the rCNPs was tested on L929 fibroblasts, and their hemocompatibility was determined.
Results
Initially, UV–vis and FTIR analyses indicated the possible loading of rutin on rCNPs. Further, the rutin load was quantitatively measured using Ultra-Performance Liquid Chromatography (UPLC) and the concentration was 88 µg/mL for 0.22 micron filtered rCNPs. The drug loading capacity (LC%) of the rCNPs was observed to be 13.29 ± 0.68%, and encapsulation efficiency (EE%) was 19.55 ± 1.01%. The drug release was pH-responsive as 88.58% of the drug was released after 24 hrs at the lysosomal pH 5.5, whereas 91.44% of the drug was released at physiological pH 7.4 after 102 hrs. The cytotoxic effects were prominent in 0.22 micron filtered samples of 5 mg/mL rutin precursor. The particle size for the rCNPs at this concentration was 144.1 nm and the polydispersity index (PDI) was 0.244, which is deemed to be ideal for tumor targeting. A zeta potential (ζ-potential) value of 16.4 mV indicated rCNPs with good stability. The IC50 value for the cytotoxic effects of rCNPs on human hepatoma Hep3B cells was 9.7 ± 0.19 μg/mL of rutin load. In addition, the increased production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential (MMP) were observed. Gene expression studies indicated that the mechanism for cytotoxic effects of rCNPs on Hep3B cells was due to the activation of Unc-51-like autophagy-activating kinase (ULK1) mediated autophagy and nuclear factor kappa B (NF-κB) signaling besides inhibiting the epithelial–mesenchymal Transition (EMT). In addition, the rCNPs were less toxic on NCTC clone 929 (L929) fibroblasts in comparison to the Hep3B cells and possessed excellent hemocompatibility (less than 2% of hemolysis).
Conclusion
The synthesized rCNPs were pH-responsive and possessed the physicochemical properties suitable for tumor targeting. The particles were effectively cytotoxic on Hep3B cells in comparison to normal cells and possessed excellent hemocompatibility. The very low hemolytic profile of rCNPs indicates that the drug could be administered intravenously for cancer therapy.
... Previous research studies addressed the exploration of RUT as a potential strategy in LC treatment. Such an example would be the study conducted by Hoai and collaborators showing that RUT at concentrations of 150 and 300 µM caused cell death rates of 4.65% and 4.4% in A549 cells, while exerting a stronger effect when incorporated in a nanoemulsion [31]. Sghaier et al. showed that RUT efficiently inhibited the viability, adhesion, and migration of A549 cells that expressed higher resistance to the flavonoid treatment (IC 50 = 559.83 ...
Lung cancer (LC) represents one of the most prevalent health issues globally and is a leading cause of tumor-related mortality. Despite being one the most attractive compounds of plant origin due to its numerous biological properties, the therapeutic applications of rutin (RUT) are limited by its disadvantageous pharmacokinetics. Thus, the present study aimed to evaluate in vitro the application of two RUT fatty acids bioconjugates, rutin oleate (RUT-O) and rutin linoleate (RUT-L), as potential improved RUT-based chemotherapeutics in non-small cell lung cancer (NSCLC) treatment. The results indicate that both compounds lacked cytotoxic potential in EpiAirway™ tissues at concentrations up to 125 µM. However, only RUT-L exerted anti-tumorigenic activity in NCI-H23 NSCLC cells after 24 h of treatment by reducing cell viability (up to 47%), proliferation, and neutral red uptake, causing cell membrane damage and lactate dehydrogenase (LDH) leakage, affecting cytoskeletal distribution, inducing cytoplasmic vacuolation, and increasing oxidative stress. The cytopathic effects triggered by RUT-L at 100 and 125 µM are indicators of a non-apoptotic cell death pathway that resembles the characteristics of paraptosis. The novel findings of this study stand as a basis for further investigations on the anti-cancer properties of RUT-L and their underlying mechanisms.
... Additionally, it has low toxicity and thereby is a good candidate for possible clinical uses. [13][14][15] Currently, numerous studies examine the biological impact of nanoparticles. [16] Wistar mice exposed to ZrO 2 NPs demonstrated that this nanoparticle could boost the production of Reactive Oxygen Species (ROS) within the cell. ...
... Rutin is a bioflavonoid that can be found in vegetables, fruits, medicinal herbs, and plant-based beverages [74]. In vitro studies have shown its anti-cancer potential against a wide variety of human cancers such as those found in the colon [75][76][77], lungs [75][76][77], prostate, cervical, pancreas and others [75][76][77]. This phytochemical counteracts cancer through several mechanisms such as induction of apoptosis, cell cycle arrest, modulation of angiogenesis, regulation of inflammation and oxidative stress, and inhibition of malignant cell growth [74]. ...
... Rutin is a bioflavonoid that can be found in vegetables, fruits, medicinal herbs, and plant-based beverages [74]. In vitro studies have shown its anti-cancer potential against a wide variety of human cancers such as those found in the colon [75][76][77], lungs [75][76][77], prostate, cervical, pancreas and others [75][76][77]. This phytochemical counteracts cancer through several mechanisms such as induction of apoptosis, cell cycle arrest, modulation of angiogenesis, regulation of inflammation and oxidative stress, and inhibition of malignant cell growth [74]. ...
... Rutin is a bioflavonoid that can be found in vegetables, fruits, medicinal herbs, and plant-based beverages [74]. In vitro studies have shown its anti-cancer potential against a wide variety of human cancers such as those found in the colon [75][76][77], lungs [75][76][77], prostate, cervical, pancreas and others [75][76][77]. This phytochemical counteracts cancer through several mechanisms such as induction of apoptosis, cell cycle arrest, modulation of angiogenesis, regulation of inflammation and oxidative stress, and inhibition of malignant cell growth [74]. ...
Osmanthus fragrans (Thunb.) Lour. flowers (OF-F) have been traditionally consumed as a functional food and utilized as folk medicine. This study evaluated the antioxidant, anti-inflammatory and cytotoxic effects of OF-F extracts on prostate cancer cells (DU-145) and determined possible protein-ligand interactions of its compounds in silico. The crude OF-F extracts—water (W) and ethanol (E) were tested for phytochemical screening, antioxidant, anti-inflammatory, and anti-cancer. Network and molecular docking analyses of chemical markers were executed to establish their application for anticancer drug development. OF-F-E possessed higher total polyphenols (233.360 ± 3.613 g/kg) and tannin (93.350 ± 1.003 g/kg) contents than OF-F-W. In addition, OF-F-E extract demonstrated effective DPPH scavenging activity (IC50 = 0.173 ± 0.004 kg/L) and contained a high FRAP value (830.620 ± 6.843 g Trolox/kg). In cell culture experiments, OF-F-E significantly reduced NO levels and inhibited cell proliferation of RAW-264.7 and DU-145 cell lines, respectively. Network analysis revealed O. fragrans (Thunb.) Lour. metabolites could affect thirteen molecular functions and thirteen biological processes in four cellular components. These metabolites inhibited key proteins of DU-145 prostate cancer using molecular docking with rutin owning the highest binding affinity with PIKR31 and AR. Hence, this study offered a new rationale for O. fragrans (Thunb.) Lour. metabolites as a medicinal herb for anticancer drug development.
... There are several validated studies emphasizing the in vitro anticancer properties of rutin against numerous human cancers including colorectal cancer, lung cancer, glioblastoma, ovarian cancer, melanoma, prostate cancer, lung cancer, leukemia, cancer cervical cancer by induction of apoptosis pathway, enhancement of immunity, angiogenesis modulation and hinder cell migration which consequently results to a considerable motility rate of cancerous cells [201][202][203][204]. ...
Colorectal cancer is among the frequently diagnosed cancers with high mortality rates around the world. Polyphenolic compounds such as flavonoids are secondary plant metabolites which exhibit anti-cancer activities along with anti-inflammatory effects. However, due to their hydrophobicity, sensitivity to degradation and low bioavailability, therapeutic effects have shown poor therapeutic effect. Nano delivery systems such as nanoliposomes, nanomicelles, silica nanoparticles have been investigated to overcome these difficulties. This review provides a summary of the efficiency of certain flavonoids and polyphenols (apigenin, genistein, resveratrol, quercetin, silymarin, catechins, luteolin, fisetin, gallic acid, rutin, and curcumin) on colorectal cancer models. It comprehensively discusses the influence of nano-formulation of flavonoids on their biological functions, including cellular uptake rate, bioavailability, solubility, and cytotoxicity, as well as their potential for reducing colorectal cancer tumor size under in vivo situations.
... The bioavailability and solubility of Rutin are improved by premixing with Tween-80 and PEG-600, which form nanoemulsions under biological conditions. The pre-nanoemulsion of Rutin (spherical, 15 nm) has shown anticancer properties in lung and colon cancer cells [95]. Rutin-loaded Poly(ε-caprolactone)-poly(ethylene glycol) and PLGA nanoparticles have shown anticancer properties against ovarian cancer and HCC cells, respectively. ...
Redox homeostasis, a dynamic process ensuring a balance between cellular oxidizing and reducing reactions, is crucial for maintaining healthy cellular physiology and regulating many biological processes, requiring continuous monitoring and fine-tuning. Reactive species play a critical role in intra/intercellular signaling, and each cell has a specific system guarding cellular redox homeostasis. ROS signaling and oxidative stress are involved in cancer initiation and progression. However, the generation of reactive species beyond the threshold level inside the tumor microenvironment is considered one of the therapeutic approaches. Various studies have shown that some phytochemicals can target the redox homeostasis of the tumor microenvironment. Recent advances have focused on developing and introducing phytochemical interventions as favorable therapeutic options against cancer. However, studies have also suggested the "virtuous" and "evil" impacts of phytochemicals. Some phytochemicals enhance therapeutic efficacy by promoting intracellular oxidant accumulation. However, under certain conditions, some phytochemicals may harm the cellular microenvironment to promote cancer and tend to target different pathways for cancer initiation and development instead of targeting redox homeostasis. In this context, this review is focused on providing an overall understanding of redox homeostasis and intends to highlight the potential positive and negative impacts of phytochemicals in redox homeostasis and disease development. We also discuss the recent nanotechnology-based advancements in combating cancer development.
... Another compound detected in rice bran extract was rutin, which is a flavone, and inhibits A549 lung cancer cells and colon cancer cells effectively [49]. Additionally, Maeda et al. reported that rutin inhibited poly(ADP-ribose) polymerase, and induce DNA damage in BRCA mutant cells [50]. ...
Emerging evidence supports the role of rice bran in cancer prevention. Studies were conducted on multiple rice cultivars. However, limited studies were conducted on rice cultivars in the Middle East. In this study, rice bran growing in Iraq (O. sativa ssp. Japonica, cultivars: Amber Barka) was evaluated for its effect on preventing cancer and stimulating the immune system. Rice bran was collected from local mills in Al-Najaf (south of Iraq). Several solvent extracts (ethanol, methanol, n-hexane, and water) were prepared by maceration. MTT assay was used to measure the antiproliferative effects of extracts against a panel of cancer cell lines. The ability of each extract to induce apoptosis and inhibit angiogenesis was measured using standard ELISA kits. The effect of extracts on the immune system was evaluated using a lymphocyte proliferation assay, a pinocytic activity assay, a phagocytic activity assay, and a Th1/Th2 cytokine detection kit. A microbroth dilution method was used to detect the antimicrobial activity of each extract against different microbial strains. LC–MS analysis was used to detect the phytochemical composition of extracts, while DPPH assay was used to determine the antioxidant activity. For the in vivo study, rice bran was added to mouse fodder at 10% and 20 %. Mice were treated for two weeks using mouse fodder supplemented with rice bran. In the third week of the experiment, EMT6/P breast cancer cells (1 × 10⁶ cells/mL) were injected subcutaneously into the abdominal area of each mouse. The dimensions of the grown tumors were measured after 14 days of tumor inoculation. A microbroth dilution method was used to evaluate the antimicrobial activity of rice bran extracts against three bacterial strains. The highest antiproliferative activity was observed in ethanol and n-hexane extracts. Ethanol and methanol extract showed the highest activity to induce apoptosis and inhibit angiogenesis. Both extracts were also effective to enhance immunity by activating lymphocytes and phagocytes proliferation with modulations of cytokine levels. The incorporation of rice bran in mice food caused a 20% regression in tumor development and growth compared with the negative control. All extracts exhibited limited antimicrobial activity against tested microorganisms. Methanol extract showed antioxidant activity with an IC₅₀ value of 114 µg/mL. LC–MS analysis revealed the presence of multiple phytochemicals in rice bran including apiin, ferulic acid, and succinic acid. Rice bran is a rich source of active phytochemicals that may inhibit cancer and stimulate the immune system. Rice bran's biological activities could be due to the presence of multiple synergistically active phytochemicals. Further studies are needed to understand the exact mechanisms of action of rice bran.
... The high solubility of nanoparticles declines the energy barrier and so improves the rate of intermembrane transmission. Then, the absorption of nanoformulation rutin into the cell was more than free rutin [62]. Hoai and coworkers also showed this clarification for rutin-loaded polymeric nanoparticles [62]. ...
... Then, the absorption of nanoformulation rutin into the cell was more than free rutin [62]. Hoai and coworkers also showed this clarification for rutin-loaded polymeric nanoparticles [62]. Moreover, it has been revealed that the shape and size of particles have a critical role in the uptake of nanoparticles into cells and initial internalization into cells [63]. ...
Background
The studies have shown that rutin has great potential as an anticancer and antimicrobial plant base agent; nevertheless, poor bioavailability and low aqueous solubility of rutin limit its application. One of the beneficial routes to increase the solubility and bioavailability of rutin is the development of nanoparticulate material. This study aimed to assess the anticancer and antibacterial effects of rutin-loaded mesoporous silica nanoparticles (RUT-MSNs).
Methods
RUT-MSNs were prepared and physicochemically characterized. The cytotoxicity of RUT-MSNs on the HN5 cells as head and neck cancer cells was evaluated. The expression level of apoptosis-related genes such as Bcl-2 and Bax genes were evaluated. In addition, ROS production of RUT-MSNs treated cells was assessed. In addition, minimum inhibitory concentration (MIC), biofilm, and attachment inhibitory effects of RUT-MSNs compared with free rutin were assessed against different bacterial strains.
Results
Transmission electron microscopy (TEM) showed mesoporous rod-shaped nanoparticles with an average particle size of less than 100 nm. RUT-MSNs displayed the cytotoxic effect with IC50 of 20.23 µM in 48 h of incubation time (p < 0.05). The elevation in the ratio of Bax/Bcl-2 was displayed within the IC50 concentration of RUT-MSNs in 48 h (p < 0.05). The antibacterial action of rutin was improved by loading rutin in MSNs to the nano-sized range in the MIC test.
Conclusion
The anticancer and antibacterial effects of RUT-MSNs were considerably more than rutin. RUT-MSNs inhibited the growth of HN5 cells by inducing apoptosis and producing ROS. These results suggest that RUT-MSNs may be useful in the treatment of cancers and infections.
... The HPLC analysis showed that the methanol extract of the different parts of C. aeruginosa contain seven active substances: gallic acid, kaempferol, quercetin, caffeic acid, coumaric acid, naringin, rutin (Fig. 3a-3c). These compounds are recognized as apoptosis inducers in human lung and cervical cancer cells evidenced by their ability to induce the activation of caspase-involved apoptotic pathway [82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101]. ...
The aim of the current study was to examine the efficacy of the leaf, stem and rhizome of Curcuma aeruginosa Roxb. for their phytochemical content, antioxidant and anti-cancer activities. The different parts of C. aeruginosa were subjected to sequential extraction to give three fractions viz., hexane, ethyl acetate and methanol extract. The cytotoxic effect and the mode of action against A-549 human lung adenocarcinoma and HeLa cell lines were examined. C. aeruginosa presented no significant toxic effect in normal human lung cells (L-132). The methanol extracts were found to be the most cytotoxic and further investigation was carried out to understand the effects. The methanol extracts induced DNA damage after 24 h with significant increase in tail DNA and tail moment when compared to untreated control. Up-regulation in the expression of the caspase − 8 and − 3 activity was observed after 48 h of treatment. The mechanism of cell death and apoptosis induced by the methanol extracts on A549 and HeLa cells were studied using fluorescent staining. Bioactive compounds detected from the HPLC revealed phenol and flavonoid compounds: Gallic acid, quercetin, caffeic acid, kaempferol, rutin, coumaric acid and naringenin. GC-MS results identified the presence of sesquiterpenoids: α-curcumene, curzerene curcumenol, curzerenone epicurzerenone, caryophyllene oxide and diterpenoid, andrographolide. These compounds are known for inducing apoptosis in human cancer cells through caspase - dependent pathways. Therefore, C. aeruginosa and its potential to induce apoptosis in cancer cells suggest that they have potential in medical applications.
... Rutin is a naturally occurring bioflavonoid abundantly reported in medicinal herbs, fruits, vegetables, and plant-based beverages. Research has further presented the in vitro potential of rutin in the suppression of numerous human cancers such as lung cancer, prostate cancer, colorectal cancer, breast cancer, liver cancer, glioblastoma, melanoma, osteosarcoma, ovarian cancer, leukemia, cervical cancer, and pancreatic cancer via apoptosis induction, immunity enhancement, or cell migration knockdown, which leads to a significant reduction in the motility rate of cancerous cells [20][21][22][23][24]. ...
Cancer is a complex ailment orchestrated by numerous intrinsic and extrinsic pathways. Recent research has displayed a deep interest in developing plant-based cancer therapeutics for better management of the disease and limited side effects. A wide range of plant-derived compounds have been reported for their anticancer potential in the quest of finding an effective therapeutic approach. Rutin (vitamin P) is a low-molecular weight flavonoid glycoside (polyphenolic compound), abundantly present in various vegetables, fruits (especially berries and citrus fruits), and medicinal herbs. Numerous studies have delineated several pharmacological properties of rutin such as its antiprotozoal, antibacterial, anti-inflammatory, antitumor, antiviral, antiallergic, vasoactive, cytoprotective, antispasmodic, hypolipidemic, antihypertensive, and antiplatelet properties. Specifically, rutin-mediated anticancerous activities have been reported in several cancerous cell lines, but the most common scientific evidence, encompassing several molecular processes and interactions, including apoptosis pathway regulation, aberrant cell signaling pathways, and oncogenic genes, has not been thoroughly studied. In this direction, we attempted to project rutin-mediated oncogenic pathway regulation in various carcinomas. Additionally, we also incorporated advanced research that has uncovered the notable potential of rutin in the modulation of several key cellular functions via interaction with mRNAs, with major emphasis on elucidating direct miRNA targets of rutin as well as the process needed to transform these approaches for developing novel therapeutic interventions for the treatment of several cancers.
