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Ganguly SC, Maity R, Manna P, Sardar A, Mukherjee S, Karati D. Amplifying therapeutic potential through optimization of bioavailability of poorly soluble flavonols via albumin-based nanoparticles. Drug Dev Ind Pharm 2025; 51:534-545. [PMID: 40186858 DOI: 10.1080/03639045.2025.2490281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 03/25/2025] [Accepted: 04/02/2025] [Indexed: 04/07/2025]
Abstract
OBJECTIVE Flavonols have different pharmacological actions that render them highly promising therapeutic targets. However, their water solubility and bioavailability are low, which restricts their therapeutic potential. ABNPs, albumin-based nanoparticles, are potential nanocarriers that enhance flavonol solubility, stability, and targeted delivery. By utilizing ABNPs, in this work we provide a detailed overview of strategies employed to attain maximum bioavailability of poorly water-soluble flavonols. The review critically evaluates ABNP-mediated delivery's pharmacokinetic advantage, physicochemical properties, and formulation principles. We also highlight existing gaps in research, such as the need for stringent in vivo validity tests, standardized formulation procedures, and in-depth mechanistic understanding of flavonol-albumin interactions. SIGNIFICANCE Despite having potential therapeutic activities, the utilization of flavonoids in the form of medication is limited. Some recent studies have shown that flavonoids exhibit low solubility, low permeability and chemical instability, thereby limiting their bioavailability and therapeutic responses. METHODS To overcome these drawbacks, multiple novel drug delivery approaches have emerged in the pharmaceutical research. RESULTS These novel approaches seem to offer a viable foundation for improving the bioavailability of the flavonoids and positioning them as viable therapeutic options. Out of all the polymers implemented in enhancing the solubility and bioavailability of the flavonoids, albumin-based nanomaterials have been the most efficacious one. CONCLUSION Compared to all other polymeric nano-carriers, albumin nano-carriers offer a greater scale of drug entrapment and drug loading because of their capacity for surface modification, crosslinking, conjugation, coupling, and characteristics including biodegradability and biocompatibility.
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Affiliation(s)
| | - Ritam Maity
- Department of Pharmaceutical Technology, Brainware University, Kolkata, India
| | - Priya Manna
- Department of Pharmaceutical Technology, Brainware University, Kolkata, India
| | - Avisek Sardar
- Department of Pharmaceutical Technology, Brainware University, Kolkata, India
| | - Swarupananda Mukherjee
- NSHM College of Pharmacy and Technology, NSHM Knowledge Campus, Kolkata - Group of Institutions, Kolkata, India
| | - Dipanjan Karati
- Department of Pharmaceutical Technology, School of Pharmacy, Techno India University, West Bengal, Kolkata, India
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2
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Ye LS, Mu HF, Wang BL. Advances in flavonoid bioactivity in chronic diseases and bioavailability: transporters and enzymes. JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 2025:1-29. [PMID: 40279202 DOI: 10.1080/10286020.2025.2493925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 04/09/2025] [Accepted: 04/10/2025] [Indexed: 04/27/2025]
Abstract
Flavonoids, abundant in the human diet, have been extensively studied for their therapeutic bioactivities. Recent research has made significantly advances in our understanding of the biological activities of flavonoids, demonstrating their therapeutic effects for various chronic diseases. However, the generally low bioavailability of flavonoids limits their effectiveness. Therefore, it is essential to explore the pharmacokinetics of flavonoids, paying particular attention to the roles of transporters and metabolizing enzymes. This paper reviews recent studies on the bioactivity of flavonoids, highlighting the importance of transporters and metabolic enzymes in their pharmacokinetics.
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Affiliation(s)
- Li-Sha Ye
- Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100050, China
| | - Hong-Fei Mu
- Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100050, China
| | - Bao-Lian Wang
- Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100050, China
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Ding Y, Yu Y. Therapeutic potential of flavonoids in gastrointestinal cancer: Focus on signaling pathways and improvement strategies (Review). Mol Med Rep 2025; 31:109. [PMID: 40017144 PMCID: PMC11884236 DOI: 10.3892/mmr.2025.13474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 01/30/2025] [Indexed: 03/01/2025] Open
Abstract
Flavonoids are a group of polyphenolic compounds distributed in vegetables, fruits and other plants, which have considerable antioxidant, anti‑tumor and anti‑inflammatory activities. Several types of gastrointestinal (GI) cancer are the most common malignant tumors in the world. A large number of studies have shown that flavonoids have inhibitory effects on cancer, and they are recognized as a class of potential anti‑tumor drugs. Therefore, the present review investigated the molecular mechanisms of flavonoids in the treatment of different types of GI cancer and summarized the drug delivery systems commonly used to improve their bioavailability. First, the classification of flavonoids and the therapeutic effects of various flavonoids on human diseases were briefly introduced. Then, to clarify the mechanism of action of flavonoids on different types of GI cancer in the human body, the metabolic process of flavonoids in the human body and the associated signaling pathways causing five common types of GI cancer were discussed, as well as the corresponding therapeutic targets of flavonoids. Finally, in clinical settings, flavonoids have poor water solubility, low permeability and inferior stability, which lead to low absorption efficiency in vivo. Therefore, the three most widely used drug delivery systems were summarized. Suggestions for improving the bioavailability of flavonoids and the focus of the next stage of research were also put forward.
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Affiliation(s)
- Ye Ding
- Henan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Yong Yu
- Henan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
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An Y, Zou H, Zhou Q, Deng T, Tian J, Qiu Y, Xue W. Design, Synthesis, and Biological Activity Studies of Myricetin Derivatives Containing a Diisopropanolamine Structure. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:25034-25044. [PMID: 39498550 DOI: 10.1021/acs.jafc.4c08663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/14/2024]
Abstract
A series of myricetin derivatives containing diisopropanolamine were designed and synthesized. The in vitro inhibitory effects of the target compounds on 9 fungal pathogens and 3 bacterial pathogens were also evaluated. A12 had the best inhibitory effect against Xanthomonas oryzae pv. oryzae (Xoo), with an EC50 value of 4.9 μg/mL, which was better than zinc-thiazole (ZT: EC50 = 7.3 μg/mL) and thiodiazole-copper (TC: EC50 = 65.5 μg/mL); A25 had the best inhibitory effect against Phomopsis sp. (Ps), with an EC50 value of 17.2 μg/mL, which was better than azoxystrobin (Az: EC50 = 22.3 μg/mL). In vivo inhibition tests were performed on kiwifruit for A25 and rice leaves for A12. At 200 μg/mL, the curative activity of A12 against rice leaf blight was 40.7%, which was better than that of ZT (37.2%) and TC (32.9%), and the protective activity of A12 was 44.8%, which was better than that of ZT (39.5%) and TC (34.6%). The curative activity of A25 against kiwi soft rot disease was 70.1%, which was better than that of Az (62.8%). Preliminary elucidation of the possible mechanisms of action was carried out by experiments on fluorescence microscopy, scanning electron microscopy, formation of biofilms, density functional theory calculations, and so on.
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Affiliation(s)
- Youshan An
- State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals, Guizhou University, Guiyang 550025, P. R. China
| | - Hongqian Zou
- State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals, Guizhou University, Guiyang 550025, P. R. China
| | - Qing Zhou
- State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals, Guizhou University, Guiyang 550025, P. R. China
| | - Tianyu Deng
- State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals, Guizhou University, Guiyang 550025, P. R. China
| | - Jiao Tian
- State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals, Guizhou University, Guiyang 550025, P. R. China
| | - Yujiao Qiu
- State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals, Guizhou University, Guiyang 550025, P. R. China
| | - Wei Xue
- State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals, Guizhou University, Guiyang 550025, P. R. China
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Wang W, Wu YR, Li J, Zhou Q, Yu ZY, Liu YN, Zheng MM, Zhou YB, Liu K. Comparison of Alternative Protein Hydrogels for Delivering Myricetin: Interaction Mechanism and Stability Evaluation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:8784-8797. [PMID: 38566473 DOI: 10.1021/acs.jafc.3c09896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
Food protein carriers from different sources might have distinct stabilizing and enhancing effects on the same small molecule. To elucidate the molecular mechanism, five different sourced proteins including soy protein isolates (SPIs), whey protein isolates (WPIs), edible dock protein (EDP), Tenebrio molitor protein (TMP), and yeast protein (YP) were used to prepare protein hydrogels for delivering myricetin (Myr). The results suggested that the loading capacity order of Myr in different protein hydrogels was EDP (11.5%) > WPI (9.3%) > TMP (8.9%) > YP (8.0%) > SPI (7.6%), which was consistent with the sequence of binding affinity between Myr and different proteins. Among five protein hydrogels, EDP had an optimum loading ability since it possessed the highest hydrophobic amino acid content (45.52%) and thus provided a broad hydrophobic cavity for loading Myr. In addition, these protein-Myr composite hydrogels displayed the core-shell structure, wherein hydrogen bonding and hydrophobic interaction were the primary binding forces between proteins and Myr. Moreover, the thermal stability, storage stability, and sustained-release properties of Myr were significantly enhanced via these protein delivery systems. These findings can provide scientific guidance for deeper utilization of food alternative protein sources.
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Affiliation(s)
- Wei Wang
- Key Laboratory of Jianghuai Agricultural Product Fine Processing and Resource Utilization, Ministry of Agriculture and Rural Affairs, Anhui Engineering Research Center for High Value Utilization of Characteristic Agricultural Products, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Yu-Ru Wu
- Key Laboratory of Jianghuai Agricultural Product Fine Processing and Resource Utilization, Ministry of Agriculture and Rural Affairs, Anhui Engineering Research Center for High Value Utilization of Characteristic Agricultural Products, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Jing Li
- Key Laboratory of Jianghuai Agricultural Product Fine Processing and Resource Utilization, Ministry of Agriculture and Rural Affairs, Anhui Engineering Research Center for High Value Utilization of Characteristic Agricultural Products, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Qian Zhou
- Key Laboratory of Jianghuai Agricultural Product Fine Processing and Resource Utilization, Ministry of Agriculture and Rural Affairs, Anhui Engineering Research Center for High Value Utilization of Characteristic Agricultural Products, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Zhen-Yu Yu
- Key Laboratory of Jianghuai Agricultural Product Fine Processing and Resource Utilization, Ministry of Agriculture and Rural Affairs, Anhui Engineering Research Center for High Value Utilization of Characteristic Agricultural Products, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Ying-Nan Liu
- Key Laboratory of Jianghuai Agricultural Product Fine Processing and Resource Utilization, Ministry of Agriculture and Rural Affairs, Anhui Engineering Research Center for High Value Utilization of Characteristic Agricultural Products, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Ming-Ming Zheng
- Key Laboratory of Jianghuai Agricultural Product Fine Processing and Resource Utilization, Ministry of Agriculture and Rural Affairs, Anhui Engineering Research Center for High Value Utilization of Characteristic Agricultural Products, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Yi-Bin Zhou
- Key Laboratory of Jianghuai Agricultural Product Fine Processing and Resource Utilization, Ministry of Agriculture and Rural Affairs, Anhui Engineering Research Center for High Value Utilization of Characteristic Agricultural Products, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Kang Liu
- Key Laboratory of Jianghuai Agricultural Product Fine Processing and Resource Utilization, Ministry of Agriculture and Rural Affairs, Anhui Engineering Research Center for High Value Utilization of Characteristic Agricultural Products, College of Tea & Food Science and Technology, Anhui Agricultural University, Hefei 230036, China
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Nasser N, Hathout RM, Abd-Allah H, Sammour OA. Simplex Lattice Design and Machine Learning Methods for the Optimization of Novel Microemulsion Systems to Enhance p-Coumaric Acid Oral Bioavailability: In Vitro and In Vivo Studies. AAPS PharmSciTech 2024; 25:56. [PMID: 38448576 DOI: 10.1208/s12249-024-02766-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 02/10/2024] [Indexed: 03/08/2024] Open
Abstract
Novel p-coumaric acid microemulsion systems were developed to circumvent its absorption and bioavailability challenges. Simplex-lattice mixture design and machine learning methods were employed for optimization. Two optimized formulations were characterized using in vitro re-dispersibility and cytotoxicity on various tumor cell lines (MCF-7, CaCO2, and HepG2). The in vivo bioavailability profiles of the drug loaded in the two microemulsion systems and in the suspension form were compared. The optimized microemulsions composed of Labrafil M1944 CS (5.67%)/Tween 80 (38.71%)/Labrasol (38.71%)/water (16.92%) and Capryol 90 (0.50%)/Transcutol P (26.67%)/Tween 80 (26.67%)/Labrasol (26.67%)/water (19.50%), respectively. They revealed uniform and stable p-coumaric acid-loaded microemulsion systems with a droplet size diameter of about 10 nm. The loaded microemulsion formulations enhanced the drug re-dispersibility in contrast to the drug suspension which exhibited 5 min lag time. The loaded formulae were significantly more cytotoxic on all cell lines by 11.98-16.56 folds on MCF-7 and CaCo2 cells and 47.82-98.79 folds on HepG2 cells higher than the pure drug. The optimized microemulsions were 1.5-1.8 times more bioavailable than the drug suspension. The developed p-coumaric acid microemulsion systems could be considered a successful remedy for diverse types of cancer.
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Affiliation(s)
- Nayera Nasser
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, African Union Organization St., Cairo, 11566, Egypt
| | - Rania M Hathout
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, African Union Organization St., Cairo, 11566, Egypt.
| | - Hend Abd-Allah
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, African Union Organization St., Cairo, 11566, Egypt
| | - Omaima A Sammour
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, African Union Organization St., Cairo, 11566, Egypt
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7
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Sharma P, Chaturvedi S, Khan MA, Rai Y, Bhatt AN, Najmi AK, Akhtar M, Mishra AK. Nanoemulsion potentiates the anti-cancer activity of Myricetin by effective inhibition of PI3K/AKT/mTOR pathway in triple-negative breast cancer cells. Med Oncol 2024; 41:56. [PMID: 38218749 DOI: 10.1007/s12032-023-02274-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 11/28/2023] [Indexed: 01/15/2024]
Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous tumor with a poor prognosis and high metastatic potential, resulting in poor clinical outcomes, necessitating investigation to devise effective therapeutic strategies. Multiple studies have substantiated the anti-cancer properties of the naturally occurring flavonoid "Myricetin" in various malignancies. However, the therapeutic application of Myricetin is impeded by its poor water solubility and low oral bioavailability. To overcome this limitation, we aimed to develop nanoemulsion of Myricetin (Myr-NE) and evaluate its advantage over Myricetin alone in TNBC cells. The nanoemulsion was formulated using Capryol 90 (oil), Tween 20 (surfactant), and Transcutol HP (co-surfactant). The optimized nano-formulation underwent an evaluation to determine its size, zeta potential, morphology, stability, drug encapsulation efficiency, and in vitro release properties. The anti-cancer activity of Myr-NE was further studied to examine its distinct impact on intracellular drug uptake, cell-viability, anti-tumor signaling, oxidative stress, clonogenicity, and cell death, compared with Myricetin alone in MDA-MB-231 (TNBC) cells. The in vitro drug release and intracellular drug uptake of Myricetin was significantly increased in Myr-NE formulation as compared to Myricetin alone. Moreover, Myr-NE exhibited significant inhibition of cell proliferation, clonogenicity, and increased apoptosis with ~ 2.5-fold lower IC50 as compared to Myricetin. Mechanistic investigation revealed that nanoemulsion augmented the anti-cancer efficacy of Myricetin, most likely by inhibiting the PI3K/AKT/mTOR pathway, eventually leading to enhanced cell death in TNBC cells. The study provides substantial experimental evidence to support the notion that the Myr-NE formulation has the potential to be an effective therapeutic drug for TNBC treatment.
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Affiliation(s)
- Preeti Sharma
- Department of Pharmacology, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard (Hamdard University), New Delhi, 110062, India
- Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Timarpur, Delhi, 110054, India
| | - Shubhra Chaturvedi
- Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Timarpur, Delhi, 110054, India
| | - Mohammad Ahmed Khan
- Department of Pharmacology, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard (Hamdard University), New Delhi, 110062, India
| | - Yogesh Rai
- Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Timarpur, Delhi, 110054, India
| | - Anant Narayan Bhatt
- Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Timarpur, Delhi, 110054, India
| | - Abul Kalam Najmi
- Department of Pharmacology, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard (Hamdard University), New Delhi, 110062, India
| | - Mohd Akhtar
- Department of Pharmacology, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
| | - Anil Kumar Mishra
- Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Timarpur, Delhi, 110054, India.
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8
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Yuan D, Guo Y, Pu F, Yang C, Xiao X, Du H, He J, Lu S. Opportunities and challenges in enhancing the bioavailability and bioactivity of dietary flavonoids: A novel delivery system perspective. Food Chem 2024; 430:137115. [PMID: 37566979 DOI: 10.1016/j.foodchem.2023.137115] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 07/31/2023] [Accepted: 08/05/2023] [Indexed: 08/13/2023]
Abstract
Flavonoids have multiple favorable bioactivities including antioxidant, anti-inflammatory, and antitumor. Currently, flavonoid-containing dietary supplements are widely tested in clinical trials for the prevention and/or treatment of multiple diseases. However, the clinical application of flavonoids is largely compromised by their low bioavailability and bioactivity, probably due to their poor aqueous solubility, intensive metabolism, and low systemic absorption. Therefore, formulating flavonoids into novel delivery systems is a promising approach for overcoming these drawbacks. In this review, we highlight the opportunities and challenges in the clinical use of dietary flavonoids from the perspective of novel delivery systems. First, the classification, sources, and bioactivity of dietary flavonoids are described. Second, the progress of clinical research on flavonoid-based dietary supplements is systematically summarized. Finally, novel delivery systems developed to improve the bioavailability and bioactivity of flavonoids are discussed in detail to broaden the clinical application of dietary flavonoids.
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Affiliation(s)
- Dan Yuan
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, PR China; Research Center for Pharmaceutical Preparations, Hubei University of Chinese Medicine, Wuhan 430065, PR China
| | - Yujie Guo
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, PR China; Research Center for Pharmaceutical Preparations, Hubei University of Chinese Medicine, Wuhan 430065, PR China
| | - Feiyan Pu
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, PR China; Research Center for Pharmaceutical Preparations, Hubei University of Chinese Medicine, Wuhan 430065, PR China
| | - Can Yang
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, PR China; Research Center for Pharmaceutical Preparations, Hubei University of Chinese Medicine, Wuhan 430065, PR China
| | - Xuecheng Xiao
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, PR China; Research Center for Pharmaceutical Preparations, Hubei University of Chinese Medicine, Wuhan 430065, PR China
| | - Hongzhi Du
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, PR China; Research Center for Pharmaceutical Preparations, Hubei University of Chinese Medicine, Wuhan 430065, PR China.
| | - Jianhua He
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, PR China; Research Center for Pharmaceutical Preparations, Hubei University of Chinese Medicine, Wuhan 430065, PR China.
| | - Shan Lu
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, PR China; Research Center for Pharmaceutical Preparations, Hubei University of Chinese Medicine, Wuhan 430065, PR China.
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9
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Kumar S, Swamy N, Tuli HS, Rani S, Garg A, Mishra D, Abdulabbas HS, Sandhu SS. Myricetin: a potential plant-derived anticancer bioactive compound-an updated overview. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:2179-2196. [PMID: 37083713 DOI: 10.1007/s00210-023-02479-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/28/2023] [Indexed: 04/22/2023]
Abstract
The globe is currently confronting a global fight against the deadliest cancer sickness. Chemotherapy, hormonal therapy, surgery, and radiation therapy are among cancer treatment options. Still, these treatments can induce patient side effects, including recurrence, multidrug resistance, fever, and weakness. As a result, the scientific community is always working on natural phytochemical substances. Numerous phytochemical compounds, including taxol analogues, vinca alkaloids such as vincristine and vinblastine, and podophyllotoxin analogues, are currently undergoing testing and have shown promising results against a number of the deadliest diseases, as well as considerable advantages due to their safety and low cost. According to research, secondary plant metabolites such as myricetin, a flavonoid in berries, herbs, and walnuts, have emerged as valuable bio-agents for cancer prevention. Myricetin and its derivatives have antiinflammatory, anticancer, apoptosis-inducing, and anticarcinogenic properties and can prevent cancer cell proliferation. Multiple studies have found that myricetin has anticancer characteristics in various malignancies, including colon, breast, prostate, bladder, and pancreatic cancers. Current knowledge of the anticancer effects of myricetin reveals its promise as a potentially bioactive chemical produced from plants for the prevention and treatment of cancer. This review aimed to study the numerous bioactivities, mode of action, and modification of several cellular processes that myricetin possesses to impede the spread of cancer cells. This review also addresses the challenges and future prospects of using myricetin as a anticancer drug.
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Affiliation(s)
- Suneel Kumar
- Department of Botany, Government Girls College Khargone, 451001, Khargone, Madhya Pradesh, India
| | - Nitin Swamy
- Fungal Biotechnology and Invertebrate Pathology Laboratory, Department of Biological Sciences, Rani Durgavati University, Jabalpur, 482001, Madhya Pradesh, India
| | - Hardeep Singh Tuli
- Department of Biotechnology, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala, 133207, Haryana, India
| | - Seema Rani
- Department of Chemistry, Government M. H. College of Home Science & Science for Women, Autonomous, Jabalpur, 482002, Madhya Pradesh, India
| | - Abhijeet Garg
- Fungal Biotechnology and Invertebrate Pathology Laboratory, Department of Biological Sciences, Rani Durgavati University, Jabalpur, 482001, Madhya Pradesh, India
| | - Deepa Mishra
- Department of Biotechnology, Mata Gujri Mahila Mahavidyalaya Jabalpur, 482001, Jabalpur, Madhya Pradesh, India
| | - Hadi Sajid Abdulabbas
- Continuous Education Department, Faculty of Dentistry, University of Al-Ameed, Karbala, 56001, Iraq
| | - Sardul Singh Sandhu
- Bio-Design Innovation Centre, Rani Durgavati University, Jabalpur, 482001, Madhya Pradesh, India.
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Luo J, Yang B, Yang X, Ji S, Guo Z, Liu Y, Chen Q, Zhao T, Wang Y, Lu B. Sophorolipid-based microemulsion delivery system: Multifaceted enhancement of physicochemical properties of xanthohumol. Food Chem 2023; 413:135631. [PMID: 36804741 DOI: 10.1016/j.foodchem.2023.135631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 01/19/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023]
Abstract
Xanthohumol (XN) has numerous compelling physiological activities, but the poor solubility and stability severely limit its utilization. Therefore, a microemulsion (ME) delivery system based on biosurfactant sophorolipids (SLs) was established and its improvement on physicochemical properties of XN was investigated. The results showed that the systems increased the solubility of XN by about 4000 times, and its half-life during storage was extended to over 150 days. Partial replacement of Tween 80 with SL did not greatly affect their ability to form O/W subregions (in the high aqueous phase), but further improved the solubilization efficiency, storage stability, and antioxidant properties of XN. In vitro models revealed the release profile of XN from the systems followed non-Fickian diffusion, and the ME structure markedly strengthened its digestive stability and bioaccessibility. These results indicated that SL-based ME systems had great potential as a green solubilization and delivery method for XN and other hydrophobic drugs.
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Affiliation(s)
- Jingyang Luo
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro-Products Storage and Preservation of Ministry of Agriculture and Rural Affairs, Zhejiang University, Hangzhou 310058, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, China
| | - Bowen Yang
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro-Products Storage and Preservation of Ministry of Agriculture and Rural Affairs, Zhejiang University, Hangzhou 310058, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, China
| | - Xiaoling Yang
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro-Products Storage and Preservation of Ministry of Agriculture and Rural Affairs, Zhejiang University, Hangzhou 310058, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, China
| | - Shengyang Ji
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro-Products Storage and Preservation of Ministry of Agriculture and Rural Affairs, Zhejiang University, Hangzhou 310058, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, China
| | - Zefeng Guo
- Hangzhou Qiandao Lake Beer Company Limited, Hangzhou 311700, China
| | - Yan Liu
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro-Products Storage and Preservation of Ministry of Agriculture and Rural Affairs, Zhejiang University, Hangzhou 310058, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, China
| | - Qi Chen
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro-Products Storage and Preservation of Ministry of Agriculture and Rural Affairs, Zhejiang University, Hangzhou 310058, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, China
| | - Tian Zhao
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro-Products Storage and Preservation of Ministry of Agriculture and Rural Affairs, Zhejiang University, Hangzhou 310058, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, China
| | - Yixuan Wang
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro-Products Storage and Preservation of Ministry of Agriculture and Rural Affairs, Zhejiang University, Hangzhou 310058, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, China
| | - Baiyi Lu
- College of Biosystems Engineering and Food Science, Key Laboratory for Quality Evaluation and Health Benefit of Agro-Products of Ministry of Agriculture and Rural Affairs, Key Laboratory for Quality and Safety Risk Assessment of Agro-Products Storage and Preservation of Ministry of Agriculture and Rural Affairs, Zhejiang University, Hangzhou 310058, China; Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, China.
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11
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Topical Delivery of Diacetyl Boldine in a Microemulsion Formulation for Chemoprotection against Melanoma. Pharmaceutics 2023; 15:pharmaceutics15030901. [PMID: 36986762 PMCID: PMC10054442 DOI: 10.3390/pharmaceutics15030901] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 03/06/2023] [Accepted: 03/08/2023] [Indexed: 03/12/2023] Open
Abstract
This study aimed to develop a microemulsion formulation for topical delivery of Diacetyl Boldine (DAB) and to evaluate its cytotoxicity against melanoma cell line (B16BL6) in vitro. Using a pseudo-ternary phase diagram, the optimal microemulsion formulation region was identified, and its particle size, viscosity, pH, and in vitro release characteristics were determined. Permeation studies were performed on excised human skin using Franz diffusion cell assembly. The cytotoxicity of the formulations on B16BL6 melanoma cell lines was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Two formulation compositions were selected based on the higher microemulsion area of the pseudo-ternary phase diagrams. The formulations showed a mean globule size of around 50 nm and a polydispersity index of <0.2. The ex vivo skin permeation study demonstrated that the microemulsion formulation exhibited significantly higher skin retention levels than the DAB solution in MCT oil (Control, DAB-MCT). Furthermore, the formulations showed substantially higher cytotoxicity toward B16BL6 cell lines than the control formulation (p < 0.001). The half-maximal inhibitory concentrations (IC50) of F1, F2, and DAB-MCT formulations against B16BL6 cells were calculated to be 1 µg/mL, 10 µg/mL, and 50 µg/mL, respectively. By comparison, the IC50 of F1 was 50-fold lower than that of the DAB-MCT formulation. The results of the present study suggest that microemulsion could be a promising formulation for the topical administration of DAB.
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12
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Singh AK, Singh SV, Kumar R, Kumar S, Senapati S, Pandey AK. Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise. World J Hepatol 2023; 15:1-18. [PMID: 36744169 PMCID: PMC9896505 DOI: 10.4254/wjh.v15.i1.1] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 07/02/2022] [Accepted: 12/21/2022] [Indexed: 01/16/2023] Open
Abstract
Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year, with an estimated 5-year survival rate of 30%-35% after diagnosis. Hepatocellular carcinoma (HCC) constitutes a significant subtype of liver cancer (approximate75%) and is considered primary liver cancer. Treatment for liver cancer mainly depends on the stage of its progression, where surgery including, hepatectomy and liver transplantation, and ablation and radiotherapy are the prime choice. For advanced liver cancer, various drugs and immunotherapy are used as first-line treatment, whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins. Sorafenib and lenvatinib are first-line therapies, while regorafenib and ramucirumab are second-line therapy. Various metabolic and signaling pathways such as Notch, JAK/ STAT, Hippo, TGF-β, and Wnt have played a critical role during HCC progression. Dysbiosis has also been implicated in liver cancer. Drug-induced toxicity is a key obstacle in the treatment of liver cancer, necessitating the development of effective and safe medications, with natural compounds such as resveratrol, curcumin, diallyl sulfide, and others emerging as promising anticancer agents. This review highlights the current status of liver cancer research, signaling pathways, therapeutic targets, current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.
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Affiliation(s)
- Amit Kumar Singh
- Department of Botany, Government Naveen Girls College, Balod (Hemchand Yadav University), Durg, Chattisgarh, India
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India
| | - Shiv Vardan Singh
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India
- Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Shashank Kumar
- Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Sabyasachi Senapati
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India.
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13
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Bai HJ, Qi DY, Li HW, Wu Y. Assembly-Induced Emission Enhancement in Glutathione-Capped Bimetallic Gold and Copper Nanoclusters by Al 3+ Ions and Further Application in Myricetin Determination. Molecules 2023; 28:758. [PMID: 36677816 PMCID: PMC9864343 DOI: 10.3390/molecules28020758] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/31/2022] [Accepted: 01/07/2023] [Indexed: 01/15/2023] Open
Abstract
A significant emission enhancement (>100-fold) of glutathione-capped bimetallic gold and copper nanoclusters (AuCuNC@GSH) was achieved by assembling with Al3+ ions and by assembly-induced emission enhancement (AIEE). Further chelation of myricetin to Al3+ resulted in emission quenching of AuCuNC-Al3+, which was applied to specifically detect myricetin. Two linear responses were shown in the range of 0−1.5 μM and 1.5−50 μM, separately, leading to a low limit of detection at 8.7 nM. The method was successfully and accurately applied to myricetin determination in grape juice, which showed good application for real samples. Finally, the in-depth mechanism revealed that both the chelation of myricetin and Al3+ and the inner filter effect (IFE) between myricetin-Al3+ and AuCuNC-Al3+ greatly contributed to the quenching response of myricetin. Therefore, the present study provides an easy way to improve the fluorescence property of metal nanoclusters. Additionally, it supplies a cost-effective and easily performed approach to detect myricetin with high selectivity and sensitivity.
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Affiliation(s)
- Hao-Jie Bai
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
- Institute of Theoretical Chemistry, College of Chemistry, Jilin University, 2 Liutiao Road, Changchun 130023, China
| | - De-Yan Qi
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
- Institute of Theoretical Chemistry, College of Chemistry, Jilin University, 2 Liutiao Road, Changchun 130023, China
| | - Hong-Wei Li
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
- Institute of Theoretical Chemistry, College of Chemistry, Jilin University, 2 Liutiao Road, Changchun 130023, China
| | - Yuqing Wu
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
- Institute of Theoretical Chemistry, College of Chemistry, Jilin University, 2 Liutiao Road, Changchun 130023, China
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14
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Zhang R, Zhang H, Shi H, Zhang D, Zhang Z, Liu H. Strategic developments in the drug delivery of natural product dihydromyricetin: applications, prospects, and challenges. Drug Deliv 2022; 29:3052-3070. [PMID: 36146939 PMCID: PMC9518266 DOI: 10.1080/10717544.2022.2125601] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Dihydromyricetin (DHM) is an important natural flavonoid that has attracted much attention because of its various functions such as protecting the cardiovascular system and liver, treating cancer and neurodegenerative diseases, and anti-inflammation effect, etc. Despite its great development potential in pharmacy, DHM has some problems in pharmaceutical applications such as low solubility, permeability, and stability. To settle these issues, extensive research has been carried out on its physicochemical properties and dosage forms to produce all kinds of DHM preparations in the past ten years. In addition, the combined use of DHM with other drugs is a promising strategy to expand the application of DHM. However, although invention patents for DHM preparations have been issued in several countries, the current transformation of DHM research results into market products is insufficient. To date, there is still a lack of deep research into the pharmacokinetics, pharmacodynamics, toxicology, and action mechanism of DHM preparations. Besides, preparations for combined therapy of DHM with other drugs are scarcely reported, which necessitates the development of dosage forms for this application. Apart from medicine, the development of DHM in the food industry is also of great potential. Due to its multiple effects and excellent safety, DHM preparations can be developed for functional drinks and foods. Through this review, we hope to draw more attention to the development potential of DHM and the above challenges and provide valuable references for the research and development of other natural products with a similar structure-activity relationship to this drug.
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Affiliation(s)
- Ruirui Zhang
- School of Pharmacy, Southwest Medical University, Luzhou City, Sichuan, People's Republic of China
| | - Hao Zhang
- School of Pharmacy, Southwest Medical University, Luzhou City, Sichuan, People's Republic of China
| | - Houyin Shi
- Department of Orthopedics, Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou City, Sichuan, People's Republic of China
| | - Dan Zhang
- School of Pharmacy, Southwest Medical University, Luzhou City, Sichuan, People's Republic of China
| | - Zhuo Zhang
- School of Pharmacy, Southwest Medical University, Luzhou City, Sichuan, People's Republic of China
| | - Hao Liu
- School of Pharmacy, Southwest Medical University, Luzhou City, Sichuan, People's Republic of China
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15
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Ahmad G, Khan SU, Mir SA, Iqbal MJ, Pottoo FH, Dhiman N, Malik F, Ali A. Myrica esculenta Buch.-Ham. (ex D. Don): A Review on its Phytochemistry, Pharmacology and Nutritional Potential. Comb Chem High Throughput Screen 2022; 25:2372-2386. [PMID: 36330658 DOI: 10.2174/1386207325666220428105255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 02/24/2022] [Accepted: 03/12/2022] [Indexed: 01/27/2023]
Abstract
Myrica esculenta is an important ethnomedicinal plant used in the traditional system of medicine and as an important nutraceutical. Several studies on the plant justify its use in alternative systems of medicine and establish a scientific rationale for its possible therapeutic application. The plant contains a range of biologically active classes of compounds, particularly diarylheptanoids, flavonoids, terpenes, tannins, and glycosides. The nutraceutical potential of the plant can be particularly attributed to its fruit, and several studies have demonstrated the presence of carbohydrates, proteins, fats, fiber content, and minerals like sodium, potassium, calcium, manganese, iron, copper, and zinc, in it. The current review aims to provide complete insight into the phytochemistry, pharmacological potential, and nutritional potential of the plant, which would not only serve as a comprehensive source of information but also will highlight the scope of isolation and evaluation of these molecules for various disease conditions.
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Affiliation(s)
- Gazanfar Ahmad
- Amity Institute of Pharmacy, Amity University, Noida, UP 201301 India
| | - Sameer Ullah Khan
- Cancer Pharmacology Division, CSIR-IIIM, Sanatnagar, Srinagar, J&K 190005, India.,Academy of Scientific and Innovative Research (AcSIR), New Delhi, India
| | - Sameer Ahmad Mir
- Cancer Pharmacology Division, CSIR-IIIM, Sanatnagar, Srinagar, J&K 190005, India.,Academy of Scientific and Innovative Research (AcSIR), New Delhi, India
| | - Mir Javid Iqbal
- Department of Pharmacy, Northeastern University, 360 Huntington Avenue-140TF, Boston, Massachusetts MA, 02115, USA
| | - Faheem Hyder Pottoo
- Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Neerupma Dhiman
- Amity Institute of Pharmacy, Amity University, Noida, UP 201301 India
| | - Fayaz Malik
- Cancer Pharmacology Division, CSIR-IIIM, Sanatnagar, Srinagar, J&K 190005, India.,Academy of Scientific and Innovative Research (AcSIR), New Delhi, India
| | - Asif Ali
- Natural Product Laboratory, CSIR-IIIM, Jammu, J&K 180001, India
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Kanike S, Sarolia J, Toor J, Ray D, Aswal VK, Tiwari S. Loading of alpha-tocopherol in a nonionic microemulsion: phase behaviour and structural characteristics. Colloids Surf A Physicochem Eng Asp 2022. [DOI: 10.1016/j.colsurfa.2022.130785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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17
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Preparation of myricetin nanoliposomes using film-ultrasonic dispersion method and characterization. APPLIED NANOSCIENCE 2022. [DOI: 10.1007/s13204-022-02648-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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18
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Supramolecular aggregates of myricetin improve its bioavailability and its role in counteracting alcoholism. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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19
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Shimada Y, Sato Y, Kumazoe M, Kitamura R, Fujimura Y, Tachibana H. Myricetin improves cognitive function in SAMP8 mice and upregulates brain-derived neurotrophic factor and nerve growth factor. Biochem Biophys Res Commun 2022; 616:33-40. [DOI: 10.1016/j.bbrc.2022.05.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 05/11/2022] [Indexed: 11/02/2022]
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20
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Javed Z, Khan K, Herrera-Bravo J, Naeem S, Iqbal MJ, Raza Q, Sadia H, Raza S, Bhinder M, Calina D, Sharifi-Rad J, Cho WC. Myricetin: targeting signaling networks in cancer and its implication in chemotherapy. Cancer Cell Int 2022; 22:239. [PMID: 35902860 PMCID: PMC9336020 DOI: 10.1186/s12935-022-02663-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
The gaps between the complex nature of cancer and therapeutics have been narrowed down due to extensive research in molecular oncology. Despite gathering massive insight into the mysteries of tumor heterogeneity and the molecular framework of tumor cells, therapy resistance and adverse side effects of current therapeutic remain the major challenge. This has shifted the attention towards therapeutics with less toxicity and high efficacy. Myricetin a natural flavonoid has been under the spotlight for its anti-cancer, anti-oxidant, and anti-inflammatory properties. The cutting-edge molecular techniques have shed light on the interplay between myricetin and dysregulated signaling cascades in cancer progression, invasion, and metastasis. However, there are limited data available regarding the nano-delivery platforms composed of myricetin in cancer. In this review, we have provided a comprehensive detail of myricetin-mediated regulation of different cellular pathways, its implications in cancer prevention, preclinical and clinical trials, and its current available nano-formulations for the treatment of various cancers.
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Affiliation(s)
- Zeeshan Javed
- Office of Research Innovation and Commercialization, Lahore Garrison University, Lahore, Pakistan
| | - Khushbukhat Khan
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000 Pakistan
| | - Jesús Herrera-Bravo
- Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad Santo Tomas, Santiago, Chile
- Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, 4811230 Temuco, Chile
| | - Sajid Naeem
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, 730000 China
| | - Muhammad Javed Iqbal
- Department of Biotechnology, Faculty of Sciences, University of Sialkot, Sialkot, Pakistan
| | - Qamar Raza
- Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Punjab Pakistan
| | - Haleema Sadia
- Department of Biotechnology, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta, 87100 Pakistan
| | - Shahid Raza
- Office of Research Innovation and Commercialization, Lahore Garrison University, Lahore, Pakistan
| | - Munir Bhinder
- Department of Human Genetics & Molecular Biology, University of Health Sciences, Lahore, 54600 Pakistan
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | | | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong China
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21
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Banik S, Yamada K, Sato H, Onoue S. Development of Poly(lipoic acid) Nanoparticles with Improved Oral Bioavailability and Hepatoprotective Effects of Quercetin. Mol Pharm 2022; 19:1468-1476. [PMID: 35353535 DOI: 10.1021/acs.molpharmaceut.2c00009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Quercetin (QUE)-loaded poly(lipoic acid) nanoparticles (QUE/pLA) were developed to improve chemical stability in the gastrointestinal (GI) tract, oral bioavailability (BA), and pharmacological properties of QUE. QUE/pLA was prepared by emulsion solvent evaporation with ultrasonication followed by freeze-drying. Its mean particle size was 185 nm, with a high encapsulation efficiency of QUE (84.8%). QUE/pLA exhibited sustained release of QUE with improved dissolution compared with crystalline QUE and significantly enhanced chemical stability under physiological pH in the GI tract. Orally dosed QUE/pLA (50 mg QUE/kg) in rats exhibited significantly prolonged systemic exposure, possibly due to the sustained release of QUE. The oral BAs of QUE in QUE/pLA and crystalline QUE groups were 29 and 0.19%, respectively, suggesting significant enhancement of oral absorbability, likely due to the improved stability and dissolution property of QUE in the GI tracts. In hepatic injury model rats, QUE/pLA (50 mg QUE/kg) led to marked reductions in the plasma biomarker levels of alanine aminotransferase and aspartate aminotransferase by 70 and 46%, respectively, compared with the vehicle group. QUE/pLA also showed improved antioxidant potential as evidenced by the enhanced activities of hepatic glutathione, superoxide dismutase, and a decrease in the level of malondialdehyde, a marker of lipid peroxidation. Based on these findings, QUE/pLA might be a promising option to improve both the nutraceutical and pharmaceutical properties of QUE.
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Affiliation(s)
- Sujan Banik
- Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
| | - Kohei Yamada
- Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
| | - Hideyuki Sato
- Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
| | - Satomi Onoue
- Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
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22
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Xi Y, Wang W, Xu N, Shi C, Xu G, Sun J, He H, Jiang T. Myricetin loaded nano-micelles delivery system reduces bone loss induced by ovariectomy in rats through inhibition of osteoclast formation. J Pharm Sci 2022; 111:2341-2352. [PMID: 35341721 DOI: 10.1016/j.xphs.2022.03.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 03/20/2022] [Accepted: 03/21/2022] [Indexed: 11/24/2022]
Abstract
In recent years, much attention has been paid to the therapeutic effects of phytochemicals on osteoporosis. Other studies have shown that myricetin (MY) could promote osteogenic activity and inhibit osteoclastic effect, albeit little is known about effect of MY micellar system on osteoporosis. Therefore, we sought to discuss the therapeutic effect and mechanism of MY-loaded bone-targeting micelles on osteoporosis induced by ovariectomy (OVA) in rats. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles were prepared via ethanol injection method, while in vitro release study, bone targeting, pharmacokinetic studies, and the effect on proliferation of osteoblasts were investigated. Further, the therapeutic effect on osteoporosis was studied through ovariectomized rats. Compared with free MY, oral bioavailability of AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles in rats was increased by 3.54 times. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles exhibited bone targeting potential, and could significantly increase the activity of alkaline phosphatase and promote the proliferation of osteoblasts. Importantly, AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles mainly regulated bone metabolism by inhibiting bone resorption, thereby improving the symptoms of osteoporosis in OVA rats. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles substantially enhanced the oral bioavailability of MY and demonstrated good bone targeting capability, thereby suggesting its prospect as carrier for osteoporotic improvement in OVA rats.
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Affiliation(s)
- Yanhai Xi
- Department of Orthopedics, Spine Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China.
| | - Weiheng Wang
- Department of Orthopedics, Spine Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China
| | - Ning Xu
- Department of Orthopedics, Spine Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China
| | - Changgui Shi
- Department of Orthopedics, Spine Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China
| | - Guohua Xu
- Department of Orthopedics, Spine Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China
| | - Jinxing Sun
- Department of Spine Surgery, Shandong Wendeng Osteopathic Hospital, Weihai 264200, China
| | - Hailong He
- Department of Orthopedics, Spine Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China
| | - Tingwang Jiang
- Department of Key Laboratory, The Affiliated Changshu Hospital of Xuzhou Medical School, The Second People's Hospital of Changshu, Changshu 215500, China.
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23
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Nanoencapsulated Myricetin to Improve Antioxidant Activity and Bioavailability: A Study on Zebrafish Embryos. CHEMISTRY 2021. [DOI: 10.3390/chemistry4010001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Flavonoids are natural polyphenolic compounds that mainly possess antioxidant properties due to more hydroxyl groups in their structure and play an important role in combatting many diseases. Myricetin is a flavonoid found in grapes, green tea, fruits, and vegetables and is not only an antioxidant but also is a pro-oxidant. Myricetin is sparingly soluble in water and restricts its properties due to low bioavailability. The present study reports the liposomal nanoformulations of myricetin to improve its bioavailability with reduced pro-oxidant activity. The nanoformulated myricetin was characterized using different photophysical tools, such as dynamic light scattering (DLS), zeta potential, and scanning electron microscopy (SEM). The effect of nanoencapsulated myricetin on the developing zebrafish embryo was studied in terms of microscopic observations, cumulative hatchability, and antioxidant activities, such as catalase, glutathione peroxidase, and superoxide dismutase, after treating the zebrafish embryo with standard oxidant hydrogen peroxide. The results obtained from the cumulative hatchability, developmental studies, and antioxidant assays indicated that the liposomal nanoformulation of myricetin had enhanced antioxidant activity, leading to defense against oxidative stress. The formulation was highly biocompatible, as evidenced by the cumulative hatching studies as well as microscopic observations. The positive effects of liposomal nanoformulation on zebrafish embryos can open an avenue for other researchers to carry out further related research and to check its activities in clinical studies and developmental studies.
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Tan OJ, Loo HL, Thiagarajah G, Palanisamy UD, Sundralingam U. Improving oral bioavailability of medicinal herbal compounds through lipid-based formulations - A Scoping Review. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 90:153651. [PMID: 34340903 DOI: 10.1016/j.phymed.2021.153651] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 06/28/2021] [Accepted: 07/01/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Although numerous medicinal herbal compounds demonstrate promising therapeutic potential, their clinical application is often limited by their poor oral bioavailability. To circumvent this barrier, various lipid-based herbal formulations have been developed and trialled with promising experimental results. PURPOSE This scoping review aims to describe the effect of lipid-based formulations on the oral bioavailability of herbal compounds. METHODS A systematic search was conducted across three electronic databases (Medline, Embase and Cochrane Library) between January 2010 and January 2021 to identify relevant studies. The articles were rigorously screened for eligibility. Data from eligible studies were then extracted and collated for synthesis and descriptive analysis using Covidence. RESULTS A total of 109 studies were included in the present review: 105 animal studies and four clinical trials. Among the formulations investigated, 50% were emulsions, 34% lipid particulate systems, 12% vesicular systems, and 4% were other types of lipid-based formulations. Within the emulsion system classification, self-emulsifying drug delivery systems were observed to produce the best improvements in oral bioavailability, followed by mixed micellar formulations. The introduction of composite lipid-based formulations and the use of uncommon surfactants such as sodium oleate in emulsion preparation was shown to consistently enhance the bioavailability of herbal compounds with poor oral absorption. Interestingly, the lipid-based formulations of magnesium lithospermate B and Pulsatilla chinensis produced an absolute bioavailability greater than 100% indicating the possibility of prolonged systemic circulation. With respect to chemical conjugation, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was the most frequently used and significantly improved the bioavailability of its phytoconstituents. CONCLUSION Our findings suggest that there is no distinct lipid-based formulation superior to the other. Bioavailability improvements were largely dependent on the nature of the phytoconstituents. This scoping review, however, provided a detailed summary of the most up-to-date evidence on phytoconstituents formulated into lipid preparations and their oral bioavailability. We conclude that a systematic review and meta-analysis between bioavailability improvements of individual phytoconstituents (such as kaempferol, morin and myricetin) in various lipid-based formulations will provide a more detailed association. Such a review will be highly beneficial for both researchers and herbal manufacturers.
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Affiliation(s)
- Oi Jin Tan
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Malaysia.
| | - Hooi Leong Loo
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Malaysia.
| | - Gayathiri Thiagarajah
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya, Malaysia.
| | - Uma Devi Palanisamy
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya, Malaysia.
| | - Usha Sundralingam
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Malaysia.
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de Oliveira WQ, Neri-Numa IA, Arruda HS, Lopes AT, Pelissari FM, Barros FFC, Pastore GM. Special emphasis on the therapeutic potential of microparticles with antidiabetic effect: Trends and possible applications. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.02.043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Plaza-Oliver M, Santander-Ortega MJ, Lozano MV. Current approaches in lipid-based nanocarriers for oral drug delivery. Drug Deliv Transl Res 2021; 11:471-497. [PMID: 33528830 PMCID: PMC7852471 DOI: 10.1007/s13346-021-00908-7] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2021] [Indexed: 02/06/2023]
Abstract
Lipid-based nanocarriers have gained much interest as carriers of drugs with poor oral bioavailability because of their remarkable advantages like low toxicity, affordable scale-up manufacture, strong biocompatibility or high drug loading efficiency. The potential of these nanocarriers lies in their ability to improve the gastrointestinal stability, solubility and permeability of their cargo drugs. However, achieving efficient oral drug delivery through lipid-based nanocarriers is a challenging task, since they encounter multiple physicochemical barriers along the gastrointestinal tract, e.g. the gastric acidic content, the intestinal mucus layer or the enzymatic degradation, that they must surmount to reach their target. These limitations may be turned into opportunities through a rational design of lipid-based nanocarriers. For that purpose, this review focuses on the main challenges of the oral route indicating the strategies undertaken for lipid-based nanocarriers in order to overcome them. Understanding their shortcomings and identifying their strengths will determine the future clinical success of lipid-based nanocarriers.
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Affiliation(s)
- María Plaza-Oliver
- Faculty of Pharmacy, Cellular Neurobiology and Molecular Chemistry of the Central Nervous System Group, 02008, Albacete, Spain
- Regional Centre of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 02008, Albacete, Spain
| | - Manuel Jesús Santander-Ortega
- Faculty of Pharmacy, Cellular Neurobiology and Molecular Chemistry of the Central Nervous System Group, 02008, Albacete, Spain
- Regional Centre of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 02008, Albacete, Spain
| | - María Victoria Lozano
- Faculty of Pharmacy, Cellular Neurobiology and Molecular Chemistry of the Central Nervous System Group, 02008, Albacete, Spain.
- Regional Centre of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 02008, Albacete, Spain.
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Vazhappilly CG, Amararathna M, Cyril AC, Linger R, Matar R, Merheb M, Ramadan WS, Radhakrishnan R, Rupasinghe HPV. Current methodologies to refine bioavailability, delivery, and therapeutic efficacy of plant flavonoids in cancer treatment. J Nutr Biochem 2021; 94:108623. [PMID: 33705948 DOI: 10.1016/j.jnutbio.2021.108623] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 01/21/2021] [Accepted: 02/28/2021] [Indexed: 02/06/2023]
Abstract
Over the last two decades, several advancements have been made to improve the therapeutic efficacy of plant flavonoids, especially in cancer treatment. Factors such as low bioavailability, poor flavonoid stability and solubility, ineffective targeted delivery, and chemo-resistance hinder the application of flavonoids in anti-cancer therapy. Many anti-cancer compounds failed in the clinical trials because of unexpected altered clearance of flavonoids, poor absorption after administration, low efficacy, and/or adverse effects. Hence, the current research strategies are focused on improving the therapeutic efficacy of plant flavonoids, especially by enhancing their bioavailability through combination therapy, engineering gut microbiota, regulating flavonoids interaction with adenosine triphosphate binding cassette efflux transporters, and efficient delivery using nanocrystal and encapsulation technologies. This review aims to discuss different methodologies with examples from reported dietary flavonoids that showed an enhanced anti-cancer efficacy in both in vitro and in vivo models. Further, the review discusses the recent progress in biochemical modifications of flavonoids to improve bioavailability, solubility, and therapeutic efficacy.
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Affiliation(s)
| | - Madumani Amararathna
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia, Canada
| | - Asha Caroline Cyril
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Rebecca Linger
- Department of Pharmaceutical and Administrative Sciences, University of Charleston, Charleston, West Virginia, USA
| | - Rachel Matar
- Department of Biotechnology, American University of Ras Al Khaimah, Ras Al Khaimah, UAE
| | - Maxime Merheb
- Department of Biotechnology, American University of Ras Al Khaimah, Ras Al Khaimah, UAE
| | - Wafaa S Ramadan
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE; College of Medicine, University of Sharjah, Sharjah, UAE
| | - Rajan Radhakrishnan
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - H P Vasantha Rupasinghe
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia, Canada; Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
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Krzyżek P, Migdał P, Paluch E, Karwańska M, Wieliczko A, Gościniak G. Myricetin as an Antivirulence Compound Interfering with a Morphological Transformation into Coccoid Forms and Potentiating Activity of Antibiotics against Helicobacter pylori. Int J Mol Sci 2021; 22:ijms22052695. [PMID: 33800082 PMCID: PMC7962197 DOI: 10.3390/ijms22052695] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 02/28/2021] [Accepted: 03/04/2021] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori, a gastric pathogen associated with a broad range of stomach diseases, has a high tendency to become resistant to antibiotics. One of the most important factors related to therapeutic failures is its ability to change from a spiral to a coccoid form. Therefore, the main aim of our original article was to determine the influence of myricetin, a natural compound with an antivirulence action, on the morphological transformation of H. pylori and check the potential of myricetin to increase the activity of antibiotics against this pathogen. We observed that sub-minimal inhibitory concentrations (sub-MICs) of this compound have the ability to slow down the process of transformation into coccoid forms and reduce biofilm formation of this bacterium. Using checkerboard assays, we noticed that the exposure of H. pylori to sub-MICs of myricetin enabled a 4–16-fold reduction in MICs of all classically used antibiotics (amoxicillin, clarithromycin, tetracycline, metronidazole, and levofloxacin). Additionally, RT-qPCR studies of genes related to the H. pylori morphogenesis showed a decrease in their expression during exposure to myricetin. This inhibitory effect was more strongly seen for genes involved in the muropeptide monomers shortening (csd3, csd6, csd4, and amiA), suggesting their significant participation in the spiral-to-coccoid transition. To our knowledge, this is the first research showing the ability of any compound to synergistically interact with all five antibiotics against H. pylori and the first one showing the capacity of a natural substance to interfere with the morphological transition of H. pylori from spiral to coccoid forms.
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Affiliation(s)
- Paweł Krzyżek
- Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland; (E.P.); (G.G.)
- Correspondence:
| | - Paweł Migdał
- Department of Environment, Hygiene and Animal Welfare, Wroclaw University of Environmental and Life Sciences, 51-630 Wroclaw, Poland;
| | - Emil Paluch
- Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland; (E.P.); (G.G.)
| | - Magdalena Karwańska
- Department of Epizootiology and Veterinary Administration with Clinic of Infectious Diseases, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, 50-366 Wroclaw, Poland; (M.K.); (A.W.)
| | - Alina Wieliczko
- Department of Epizootiology and Veterinary Administration with Clinic of Infectious Diseases, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, 50-366 Wroclaw, Poland; (M.K.); (A.W.)
| | - Grażyna Gościniak
- Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland; (E.P.); (G.G.)
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29
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Guo H, Chen YF, Tang Y, Qian JQ. Method for enhancing bioavailability of myricetin based on self-assembly of casein-myricetin nanomicelles. IET Nanobiotechnol 2021; 14:239-244. [PMID: 32338633 DOI: 10.1049/iet-nbt.2018.5431] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
In order to expand the application in the medical field and enhance pharmacological effects, casein-myricetin nanomicelles were prepared by the self-assembly method and characterised by ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy. The parameters in self-assembly were optimised according to the factors of particle size, encapsulation yield, and drug loading. The result showed a pH of 5.5, a casein concentration of 2 mg/ml, a mass ratio of casein to myricetin of 8:1, ultrasonic power of 300 W, ultrasonic time of 5 min and ethanol volume of 7 ml were the optimal conditions. The situ cycle intestinal perfusion methods indicated that casein-myricetin nanomicelles can be more easily absorbed by small intestine than myricetin standard sample. Therefore, casein micelles are effective for improving the water solubility of myricetin.
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Affiliation(s)
- Hui Guo
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.
| | - Yun Fei Chen
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
| | - Yi Tang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
| | - Jun Qing Qian
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
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30
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Wang M, Kang X, Deng L, Wang M, Xia Z, Gao D. Deep eutectic solvent assisted synthesis of carbon dots using Sophora flavescens Aiton modified with polyethyleneimine: Application in myricetin sensing and cell imaging. Food Chem 2020; 345:128817. [PMID: 33307432 DOI: 10.1016/j.foodchem.2020.128817] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 12/01/2020] [Accepted: 12/02/2020] [Indexed: 02/06/2023]
Abstract
Here, an efficient method for synthesizing carbon dots (CDs) using a deep eutectic solvent (DES) was developed. To investigate the influence of different DESs on the quantum yield of CDs, different hydrogen-bonding acceptors (HBAs) and hydrogen-bonding donors (HBDs) were used to synthesize the DES and prepare CDs. Using Sophora flavescens Aiton as precursor, CDs were prepared using choline chloride (ChCl)/urea based DES as reaction media and doping agent in the presence of water. The CDs showed strong blue fluorescence and were further modified with polyethyleneimine (CDs@PEI). The fluorescence intensity of CDs@PEI was selectively quenched by myricetin with a limit of detection (LOD) of 10 nM. Furthermore, CDs@PEI was used to analyze myricetin in the extracts that were fluorescent by DES with satisfactory performance of Abelmoschus manihot (Linn.) Medicus flowers, vine teas and blueberries. Finally, the bio-imaging application of CDs@PEI was tested and the results confirmed its potential application in bio-imaging.
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Affiliation(s)
- Min Wang
- School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China
| | - Xun Kang
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Linlin Deng
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Min Wang
- School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China
| | - Zhining Xia
- School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China.
| | - Die Gao
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
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31
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Nasser N, Hathout RM, Abd-Allah H, Sammour OA. Enhancement of oral bioavailability of drugs using lipid-based carriers: a meta-analysis study. Drug Dev Ind Pharm 2020; 46:2105-2110. [PMID: 33185482 DOI: 10.1080/03639045.2020.1851245] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Cancer is the disease of this era. Its therapy is moving through ups and downs not only due to poor effectiveness of many treating drugs, but also due to the serious side effects always evolving. In an attempt to overcome this problem, many systems, including lipid-based carriers, have been exploited for their oral delivery. Throughout this study, the meta-analysis tool was used to combine data from different studies and extract evidences that lipid-based carriers enhance the oral bioavailability. Consequently, increasing the efficiency and the reduction in side effects of drugs would follow. Accordingly, the usual parameter to indicate the bioavailability; the area under effect curve (AUC) was used where the lipid carriers have proven their superiority over conventional formulations. Interestingly, by comparing microemulsion/self-microemulsifying system (SMEDDS) versus liposomes/pro-liposomes as subgroups of the meta-analysis study, insignificant differences were recorded between them.
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Affiliation(s)
- Nayera Nasser
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Rania M Hathout
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Hend Abd-Allah
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Omaima A Sammour
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
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32
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Maroufi NF, Vahedian V, Mazrakhondi SAM, Kooti W, Khiavy HA, Bazzaz R, Ramezani F, Pirouzpanah SM, Ghorbani M, Akbarzadeh M, Hajipour H, Ghanbarzadeh S, Sabzichi M. Sensitization of MDA-MBA231 breast cancer cell to docetaxel by myricetin loaded into biocompatible lipid nanoparticles via sub-G1 cell cycle arrest mechanism. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2020; 393:1-11. [PMID: 31372697 DOI: 10.1007/s00210-019-01692-5] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 07/05/2019] [Indexed: 12/20/2022]
Abstract
The harmful dose-dependent side effects of chemotherapy drugs have caused the discovery of novel perspective to evaluate chemotherapy protocols. In this study, the potential application of Compritol was investigated as a major scaffold into nanostructured lipid careers to highlight myricetin efficiency in treatment of breast cancer cells along with codelivery of docetaxel (DXT). Characterization of myricetin-loaded NLCs was carried out by measuring the particle size and zeta potential, using the scanning electron microscopy. MTT, DAPI staining, flow cytometric, and RT-PCR (real-time) assays were used to recognize novel formulation behavior on cell cytotoxicity as well as recognizing molecular mechanism of formulation concerning apoptosis phenomenon. Myricetin-loaded NLCs reduced the cell viability from 50 ± 2.3 to 40 ± 1.3% (p < 0.05). Percentage of apoptosis improved with combination treatment of myricetin-loaded NLCs and DXT in the MDA-MBA231 breast cancer cells. Expression of antiapoptotic genes (survivin, Cyclin B1, and Mcl1) indicated a significant reduction in factor along with increment in proapoptotic factor Bax and Bid mRNA rates. Overall, our results represented that the NLC delivery system could be a promising strategy to enhance the effect of anticancer agents such as DXT on breast cancer.
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Affiliation(s)
- Nazila Fathi Maroufi
- Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vahid Vahedian
- Department of Medical Laboratory Sciences, Faculty of Medicine, Islamic Azad University (IAU), Sari, Iran
| | | | - Wesam Kooti
- Lung Diseases and Allergy Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Hosein Ajami Khiavy
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roya Bazzaz
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Ramezani
- Department of Molecular Medicine, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Marjan Ghorbani
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Akbarzadeh
- Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamed Hajipour
- Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saeed Ghanbarzadeh
- Cancer Gene Therapy Research Center, Zanjan University of Medical Science, Zanjan, Iran.
| | - Mehdi Sabzichi
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
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Ibrahim MM, Maria DN, Mishra SR, Guragain D, Wang X, Jablonski MM. Once Daily Pregabalin Eye Drops for Management of Glaucoma. ACS NANO 2019; 13:13728-13744. [PMID: 31714057 PMCID: PMC7785203 DOI: 10.1021/acsnano.9b07214] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Elevated intraocular pressure (IOP) is the most significant risk factor contributing to visual field loss in glaucoma. Unfortunately, the deficiencies associated with current therapies have resulted in reduced efficacy, several daily dosings, and poor patient compliance. Previously, we identified the calcium voltage-gated channel auxiliary subunit alpha2delta 1 gene (Cacna2d1) as a modulator of IOP and demonstrated that pregabalin, a drug with high affinity and selectivity for CACNA2D1, lowered IOP in a dose-dependent manner. Unfortunately, IOP returned to baseline at 6 h after dosing. In the current study, we develop a once daily topical pregabalin-loaded multiple water-in-oil-in-water microemulsion formulation to improve drug efficacy. We characterize our formulations using multiple in vitro and in vivo evaluations. Our lead formulation provides continuous release of pregabalin for up to 24 h. Because of its miniscule droplet size (<20 nm), our microemulsion has a transparent appearance and should not blur vision. It is also stable at one month of storage at temperatures ranging from 5 to 40 °C. Our formulation is nontoxic, as illustrated by a cell toxicity study and slit-lamp biomicroscopic exams. CACNA2D1 is highly expressed in both the ciliary body and the trabecular meshwork, where it functions to modulate IOP. A single drop of our lead pregabalin formulation reduces IOP by greater than 40%, which does not return to baseline until >30 h post-application. Although there were no significant differences in the amplitude of IOP reduction between the formulations we tested, a significant difference was clearly observed in their duration of action. Our multilayered microemulsion is a promising carrier that sustains the release and prolongs the duration of action of pregabalin, a proposed glaucoma therapeutic.
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Affiliation(s)
- Mohamed Moustafa Ibrahim
- Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States
- Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Doaa Nabih Maria
- Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States
- Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Sanjay R. Mishra
- Department of Physics and Materials Science, The University of Memphis, Memphis, Tennessee 38152, United States
| | - Deepa Guragain
- Department of Physics and Materials Science, The University of Memphis, Memphis, Tennessee 38152, United States
| | - XiangDi Wang
- Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States
| | - Monica M. Jablonski
- Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States
- Corresponding Author:
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Guo Y, Mao X, Zhang J, Sun P, Wang H, Zhang Y, Ma Y, Xu S, Lv R, Liu X. Oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution. Drug Deliv 2019; 26:1191-1205. [PMID: 31738085 PMCID: PMC6882477 DOI: 10.1080/10717544.2019.1689312] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 10/30/2019] [Accepted: 11/01/2019] [Indexed: 12/11/2022] Open
Abstract
Lycopene is considered as a promising neuroprotector with multiple bioactivities, while its therapeutic use in neurological disorders is restricted due to low solubility, instability and limited bioavailability. Our work aimed to develop lycopene-loaded microemulsion (LME) and investigate its potentials in improving bioavailability and brain-targeting efficiency following oral administration. The blank microemulsion (ME) excipients were selected based on orthogonal design and pseudo-ternary phase diagrams, and LME was prepared using the water titration method and characterized in terms of stability, droplet size distribution, zeta potential, shape and lycopene content. The optimized LME encompassed lycopene, (R)-(+)-limonene, Tween 80, Transcutol HP and water and lycopene content was 463.03 ± 8.96 µg/mL. This novel formulation displayed transparent appearance and satisfactory physical and chemical stabilities. It was spherical and uniform in morphology with an average droplet size of 12.61 ± 0.46 nm and a polydispersity index (PDI) of 0.086 ± 0.028. The pharmacokinetics and tissue distributions of optimized LME were evaluated in rats and mice, respectively. The pharmacokinetic study revealed a dramatic 2.10-fold enhancement of relative bioavailability with LME against the control lycopene dissolved in olive oil (LOO) dosage form in rats. Moreover, LME showed a preferential targeting distribution of lycopene toward brain in mice, with the value of drug targeting index (DTI) up to 3.45. In conclusion, the optimized LME system demonstrated excellent physicochemical properties, enhanced oral bioavailability and superior brain-targeting capability. These findings provide a basis for the applications of ME-based strategy in brain-targeted delivery via oral route, especially for poorly water-soluble drugs.
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Affiliation(s)
- Yunliang Guo
- Department of Geriatrics, Shandong Provincial
Hospital Affiliated to Shandong University, Jinan, PR
China
- Department of Geriatric Neurology, Shandong
Provincial Hospital Affiliated to Shandong University, Jinan, PR
China
- Anti-Aging Monitoring Laboratory, Shandong
Provincial Hospital Affiliated to Shandong University, Jinan, PR
China
| | - Xuyan Mao
- Bio-nano & Medical Engineering Institute,
Jining Medical University, Jining, PR China
| | - Jing Zhang
- Department of Cell and Neurobiology, School of
Basic Medical Sciences, Shandong University, Jinan, PR
China
| | - Peng Sun
- Institute of Materia Medica, Shandong Academy
of Medical Sciences, Jinan, PR China
| | - Haiyang Wang
- Institute of Materia Medica, Shandong Academy
of Medical Sciences, Jinan, PR China
| | - Yue Zhang
- Department of Geriatrics, Shandong Provincial
Hospital Affiliated to Shandong University, Jinan, PR
China
- Department of Geriatric Neurology, Shandong
Provincial Hospital Affiliated to Shandong University, Jinan, PR
China
- Anti-Aging Monitoring Laboratory, Shandong
Provincial Hospital Affiliated to Shandong University, Jinan, PR
China
| | - Yingjuan Ma
- Department of Geriatrics, Shandong Provincial
Hospital Affiliated to Shandong University, Jinan, PR
China
- Department of Geriatric Neurology, Shandong
Provincial Hospital Affiliated to Shandong University, Jinan, PR
China
- Anti-Aging Monitoring Laboratory, Shandong
Provincial Hospital Affiliated to Shandong University, Jinan, PR
China
| | - Song Xu
- Department of Geriatrics, Shandong Provincial
Hospital Affiliated to Shandong University, Jinan, PR
China
- Department of Geriatric Neurology, Shandong
Provincial Hospital Affiliated to Shandong University, Jinan, PR
China
- Anti-Aging Monitoring Laboratory, Shandong
Provincial Hospital Affiliated to Shandong University, Jinan, PR
China
| | - Renjun Lv
- Shandong Provincial Hospital, Shandong First
Medical University & Shandong Academy of Medical Sciences, Jinan,
PR China
| | - Xueping Liu
- Department of Geriatrics, Shandong Provincial
Hospital Affiliated to Shandong University, Jinan, PR
China
- Department of Geriatric Neurology, Shandong
Provincial Hospital Affiliated to Shandong University, Jinan, PR
China
- Anti-Aging Monitoring Laboratory, Shandong
Provincial Hospital Affiliated to Shandong University, Jinan, PR
China
- Department of Anti-Aging, Shandong Provincial
Hospital Affiliated to Shandong University, Jinan, PR
China
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Subramaniam S, Selvaduray KR, Radhakrishnan AK. Bioactive Compounds: Natural Defense Against Cancer? Biomolecules 2019; 9:biom9120758. [PMID: 31766399 PMCID: PMC6995630 DOI: 10.3390/biom9120758] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 11/14/2019] [Accepted: 11/15/2019] [Indexed: 12/24/2022] Open
Abstract
Cancer is a devastating disease that has claimed many lives. Natural bioactive agents from plants are gaining wide attention for their anticancer activities. Several studies have found that natural plant-based bioactive compounds can enhance the efficacy of chemotherapy, and in some cases ameliorate some of the side-effects of drugs used as chemotherapeutic agents. In this paper, we have reviewed the literature on the anticancer effects of four plant-based bioactive compounds namely, curcumin, myricetin, geraniin and tocotrienols (T3) to provide an overview on some of the key findings that are related to this effect. The molecular mechanisms through which the active compounds may exert their anticancer properties in cell and animal-based studies also discussed.
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Affiliation(s)
- Shonia Subramaniam
- Pathology Division, School of Medicine, International Medical University, Bukit Jalil, Kuala Lumpur 50050, Malaysia;
- Product Development and Advisory Services, Malaysian Palm Oil Board, Kajang, Selangor 43000, Malaysia;
| | - Kanga Rani Selvaduray
- Product Development and Advisory Services, Malaysian Palm Oil Board, Kajang, Selangor 43000, Malaysia;
| | - Ammu Kutty Radhakrishnan
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor 47500, Malaysia
- Correspondence: ; Tel.: +60-355-144-902
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Hosny KM. Development Of Saquinavir Mesylate Nanoemulsion-Loaded Transdermal Films: Two-Step Optimization Of Permeation Parameters, Characterization, And Ex Vivo And In Vivo Evaluation. Int J Nanomedicine 2019; 14:8589-8601. [PMID: 31802871 PMCID: PMC6830379 DOI: 10.2147/ijn.s230747] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 10/12/2019] [Indexed: 12/12/2022] Open
Abstract
Background Saquinavir mesylate (SQR) tablets are widely used against human immunodeficiency virus. SQR has bioavailability issues owing to its poor aqueous solubility, extensive first-pass metabolism, and even low gastrointestinal tract permeability and absorption. Objective An in-depth optimization process was carried out using factorial design to improve the permeation parameters and thereby the bioavailability of SQR by formulating self-nanoemulsifying drug delivery system (SNEDDS)-loaded polymeric transdermal films. Methods The solubility of SQR in different nanoemulsion components was examined. Various combinations of selected components were prepared in an extreme vertices mixture design to identify the useful nanoemulsion zone and to develop SNEDDS with minimum globule size. The optimized SQR-SNEDDS was loaded in polyvinyl alcohol (PVA)-based transdermal films. The Box-Behnken design was used to optimize and evaluate SQR permeability. The prepared films were characterized for thickness, tensile strength, elongation, folding endurance, and accelerated stability studies. The optimized film was examined for ex vivo skin permeation and in vivo pharmacokinetic parameters. Results The optimized SQR-SNEDDS was prepared in proportions of 0.1, 0.55, and 0.35 of clove oil, labrasol, and Transcutol, respectively. The implemented Box-Behnken design indicated the optimized film consisted of 1.0% PVA, 0.25% propylene glycol, and clove oil as the oil phase. The tensile strength, thickness, percent elongation, and folding endurance of the optimized SQR-SNEDDS film were 0.93 ± 0.013 kg/cm2, 0.22 ± 0.006 mm, 43.1 ± 0.022%, and >200 times, respectively. A higher Cmax and double the AUC were observed for SQR-SNEDDS–loaded film in comparison to pure SQR-loaded films. Conclusion Implementation of a two-step design to optimize and control experimental factors in the preparation of SQR-SNEDDS and its loading onto PVA-based transdermal films was achieved. The films indicated improved ex vivo skin permeation, enhanced bioavailability, and overcame the limitations of the oral dosage form.
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Affiliation(s)
- Khaled M Hosny
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
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Alpha-tocopherol-based microemulsion improving the stability of carnosic acid and its electrochemical analysis of antioxidant activity. Colloids Surf A Physicochem Eng Asp 2019. [DOI: 10.1016/j.colsurfa.2019.123708] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Zhao J, Yang J, Xie Y. Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: An overview. Int J Pharm 2019; 570:118642. [DOI: 10.1016/j.ijpharm.2019.118642] [Citation(s) in RCA: 135] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/20/2019] [Accepted: 08/21/2019] [Indexed: 01/29/2023]
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Zhu S, Yang C, Zhang L, Wang S, Ma M, Zhao J, Song Z, Wang F, Qu X, Li F, Li W. Development of M10, myricetin-3-O-β-d-lactose sodium salt, a derivative of myricetin as a potent agent of anti-chronic colonic inflammation. Eur J Med Chem 2019; 174:9-15. [DOI: 10.1016/j.ejmech.2019.04.031] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 04/08/2019] [Accepted: 04/13/2019] [Indexed: 12/18/2022]
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Hou Y, Zhang F, Lan J, Sun F, Li J, Li M, Song K, Wu X. Ultra-small micelles based on polyoxyl 15 hydroxystearate for ocular delivery of myricetin: optimization, in vitro, and in vivo evaluation. Drug Deliv 2019; 26:158-167. [PMID: 30822157 PMCID: PMC6407586 DOI: 10.1080/10717544.2019.1568624] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The aim was to develop a nanocarrier based on polyoxyl 15 hydroxystearate (Kolliphor® HS15, HS15) micelles for the solubility, stability, and ocular delivery of myricetin (Myr). An optimized ratio of HS15 and Myr was prepared to fabricate HS15-Myr micelle ophthalmic solution. Myr-encapsulating HS15 micelles (HS15-Myr micelles) were subjected to physicochemical characterizations. The chemical stability of Myr in HS15 micelles and storage stability of HS15-Myr micelle ophthalmic solutions were evaluated. In vitro parallel artificial membrane permeability assay and antioxidant activity of Myr in HS15 micelles were also measured. In vivo ocular tolerance, corneal permeation, and anti-inflammatory efficacy studies were conducted following ocular topical administration. HS15-Myr micelles were successfully prepared and presented transparent appearance with high encapsulation (96.12 ± 0.31%), ultra-small micelle size (a mean diameter of 12.17 ± 0.73 nm), uniform size distribution (polydispersity index [PDI] = 0.137 ± 0.013), and negative surface charge (- [4.28 ± 0.42] mV). Myr in HS15 micelle solution demonstrated higher aqueous stability than the free Myr solution among the accepted pH range for eyedrops. HS15-Myr micelle ophthalmic solution demonstrated high storage stability at 4 °C and 25 °C. HS15 micelles could significantly improve in vitro antioxidant activity and faster membrane permeation of Myr. No irritations or corneal damage were revealed in rabbit eyes after ocular administration of HS15-Myr micelle solution. In vivo corneal permeation study demonstrated that HS15-Myr micelles could penetrate the cornea efficiently in mouse eyes. Further, HS15-Myr micelles also demonstrated significant in vivo anti-inflammatory activity. It can be concluded that HS15 micelles are a potential ophthalmic delivery nanocarrier for poorly soluble drugs such as Myr.
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Affiliation(s)
- Yuzhen Hou
- a Department of Pharmacy, College of Chemical Engineering , Qingdao University of Science and Technology , Qingdao , China
| | - Fan Zhang
- a Department of Pharmacy, College of Chemical Engineering , Qingdao University of Science and Technology , Qingdao , China
| | - Jie Lan
- b Qingdao Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences , Qingdao , China
| | - Fengyuan Sun
- a Department of Pharmacy, College of Chemical Engineering , Qingdao University of Science and Technology , Qingdao , China
| | - Jun Li
- b Qingdao Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences , Qingdao , China
| | - Mengshuang Li
- a Department of Pharmacy, College of Chemical Engineering , Qingdao University of Science and Technology , Qingdao , China.,c Qingdao Women and Children's Hospital, Pharmacy Intravenous Admixture Services , Qingdao , China
| | - Kaichao Song
- a Department of Pharmacy, College of Chemical Engineering , Qingdao University of Science and Technology , Qingdao , China
| | - Xianggen Wu
- a Department of Pharmacy, College of Chemical Engineering , Qingdao University of Science and Technology , Qingdao , China
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Fan J, Zhang H, Yi M, Liu F, Wang Z. Temperature induced phase transformation and in vitro release kinetic study of dihydromyricetin-encapsulated lyotropic liquid crystal. J Mol Liq 2019. [DOI: 10.1016/j.molliq.2018.11.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Caffeic Acid Phenethyl Ester Loaded in Microemulsions: Enhanced In Vitro Activity against Colon and Breast Cancer Cells and Possible Cellular Mechanisms. FOOD BIOPHYS 2018. [DOI: 10.1007/s11483-018-9559-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Tao J, Zheng ZP, Guo F, Chen J. Formulation of a 7,2′,4′-trihydroxyflavanone oil-in-water microemulsion using aqua coconut oil: Characterization, stability, and antibrowning effects on fresh apple juice. Lebensm Wiss Technol 2018. [DOI: 10.1016/j.lwt.2018.03.039] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Zhao X, Wang Z, Yuan S, Lu J, Wang Z. MesoDyn prediction of a pharmaceutical microemulsion self-assembly consistent with experimental measurements. RSC Adv 2017. [DOI: 10.1039/c7ra01541k] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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