|
1
|
Chauhan D, Yadav PK, Sultana N, Agarwal A, Verma S, Chourasia MK, Gayen JR. Advancements in nanotechnology for the delivery of phytochemicals. JOURNAL OF INTEGRATIVE MEDICINE 2024; 22:385-398. [PMID: 38693014 DOI: 10.1016/j.joim.2024.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 04/08/2024] [Indexed: 05/03/2024]
Abstract
Phytosomes (phytophospholipid complex) are dosage forms that have recently been introduced to increase the stability and therapeutic effect of herbal medicine. Currently, bioactive herbs and the phytochemicals they contain are considered to be the best remedies for chronic diseases. One promising approach to increase the efficacy of plant-based therapies is to improve the stability and bioavailability of their bio-active ingredients. Phytosomes employ phospholipids as their active ingredients, and use their amphiphilic properties to solubilize and protect herbal extracts. The unique properties of phospholipids in drug delivery and their use in herbal medicines to improve bioavailability results in significantly enhanced health benefits. The introduction of phytosome nanotechnology can alter and revolutionize the current state of drug delivery. The goal of this review is to explain the application of phytosomes, their future prospects in drug delivery, and their advantages over conventional formulations. Please cite this article as: Chauhan D, Yadav PK, Sultana N, Agarwal A, Verma S, Chourasia MK, Gayen JR. Advancements in nanotechnology for the delivery of phytochemicals. J Integr Med. 2024; 22(4): 385-398.
Collapse
Affiliation(s)
- Divya Chauhan
- Division of Pharmaceutics and Pharmacokinetics, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research, Ghaziabad 201002, Uttar Pradesh, India
| | - Pavan K Yadav
- Division of Pharmaceutics and Pharmacokinetics, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research, Ghaziabad 201002, Uttar Pradesh, India
| | - Nazneen Sultana
- Division of Pharmaceutics and Pharmacokinetics, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, Uttar Pradesh, India
| | - Arun Agarwal
- Division of Pharmaceutics and Pharmacokinetics, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research, Ghaziabad 201002, Uttar Pradesh, India
| | - Saurabh Verma
- Division of Pharmaceutics and Pharmacokinetics, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research, Ghaziabad 201002, Uttar Pradesh, India
| | - Manish K Chourasia
- Division of Pharmaceutics and Pharmacokinetics, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research, Ghaziabad 201002, Uttar Pradesh, India
| | - Jiaur R Gayen
- Division of Pharmaceutics and Pharmacokinetics, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research, Ghaziabad 201002, Uttar Pradesh, India.
| |
Collapse
|
|
2
|
Liu L, Lv L, Dai W, Nie J. The effect of naringenin-phospholipid complex on thermal oxidative stability of soybean oil under heating condition. Food Chem 2024; 444:138631. [PMID: 38325079 DOI: 10.1016/j.foodchem.2024.138631] [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: 10/28/2023] [Revised: 01/15/2024] [Accepted: 01/28/2024] [Indexed: 02/09/2024]
Abstract
Naringenin (NGE), a typical flavanone abundant in citrus fruits, exhibits remarkable antioxidant activities. However, its low solubility in oil restricts its widespread use in inhibiting lipid oxidation. In this study, we present a novel and effective approach to address this limitation by developing a naringenin-phospholipid complex (NGE-PC COM). Comprehensive analytical techniques including Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were employed to confirm the formation of the NGE-PC COM and elucidate the interaction mechanism between NGE and phospholipids molecules. Notably, the oil-solubility of NGE was significantly enhanced by approximately 2700-fold when formulated as a phospholipid complex in soybean oil. The improved oil-solubility of NGE-PC COM enabled effective inhibition of oil thermal oxidation under high temperature conditions. Generally, this investigation proposed a novel and promising strategy for employing flavanones with strong antioxidant activities to enhance the thermal oxidative stability of edible oil during heating processes.
Collapse
Affiliation(s)
- Liyao Liu
- College of Basic Science, Tianjin Agriculture University, Tianjin 300392, PR China
| | - Lifei Lv
- College of Basic Science, Tianjin Agriculture University, Tianjin 300392, PR China
| | - Wenjie Dai
- College of Basic Science, Tianjin Agriculture University, Tianjin 300392, PR China
| | - Jinju Nie
- Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Shandong 264000, PR China.
| |
Collapse
|
|
3
|
Toma L, Deleanu M, Sanda GM, Barbălată T, Niculescu LŞ, Sima AV, Stancu CS. Bioactive Compounds Formulated in Phytosomes Administered as Complementary Therapy for Metabolic Disorders. Int J Mol Sci 2024; 25:4162. [PMID: 38673748 PMCID: PMC11049841 DOI: 10.3390/ijms25084162] [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: 03/10/2024] [Revised: 04/02/2024] [Accepted: 04/05/2024] [Indexed: 04/28/2024] Open
Abstract
Metabolic disorders (MDs), including dyslipidemia, non-alcoholic fatty liver disease, diabetes mellitus, obesity and cardiovascular diseases are a significant threat to human health, despite the many therapies developed for their treatment. Different classes of bioactive compounds, such as polyphenols, flavonoids, alkaloids, and triterpenes have shown therapeutic potential in ameliorating various disorders. Most of these compounds present low bioavailability when administered orally, being rapidly metabolized in the digestive tract and liver which makes their metabolites less effective. Moreover, some of the bioactive compounds cannot fully exert their beneficial properties due to the low solubility and complex chemical structure which impede the passive diffusion through the intestinal cell membranes. To overcome these limitations, an innovative delivery system of phytosomes was developed. This review aims to highlight the scientific evidence proving the enhanced therapeutic benefits of the bioactive compounds formulated in phytosomes compared to the free compounds. The existing knowledge concerning the phytosomes' preparation, their characterization and bioavailability as well as the commercially available phytosomes with therapeutic potential to alleviate MDs are concisely depicted. This review brings arguments to encourage the use of phytosome formulation to diminish risk factors inducing MDs, or to treat the already installed diseases as complementary therapy to allopathic medication.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Camelia Sorina Stancu
- Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8 B.P. Haşdeu Street, 050568 Bucharest, Romania; (L.T.); (M.D.); (G.M.S.); (T.B.); (L.Ş.N.); (A.V.S.)
| |
Collapse
|
|
4
|
He YQ, Zhou CC, Jiang SG, Lan WQ, Zhang F, Tao X, Chen WS. Natural products for the treatment of chemotherapy-related cognitive impairment and prospects of nose-to-brain drug delivery. Front Pharmacol 2024; 15:1292807. [PMID: 38348396 PMCID: PMC10859466 DOI: 10.3389/fphar.2024.1292807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 01/15/2024] [Indexed: 02/15/2024] Open
Abstract
Chemotherapy-related cognitive deficits (CRCI) as one of the common adverse drug reactions during chemotherapy that manifest as memory, attention, and executive function impairments. However, there are still no effective pharmacological therapies for the treatment of CRCI. Natural compounds have always inspired drug development and numerous natural products have shown potential therapeutic effects on CRCI. Nevertheless, improving the brain targeting of natural compounds in the treatment of CRCI is still a problem to be overcome at present and in the future. Accumulated evidence shows that nose-to-brain drug delivery may be an excellent carrier for natural compounds. Therefore, we reviewed natural products with potential anti-CRCI, focusing on the signaling pathway of these drugs' anti-CRCI effects, as well as the possibility and prospect of treating CRCI with natural compounds based on nose-to-brain drug delivery in the future. In conclusion, this review provides new insights to further explore natural products in the treatment of CRCI.
Collapse
Affiliation(s)
- Yu-Qiong He
- Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Can-Can Zhou
- Department of Pharmacy, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Sheng-Gui Jiang
- Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wen-Qian Lan
- Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Feng Zhang
- Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Xia Tao
- Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wan-Sheng Chen
- Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China
| |
Collapse
|
|
5
|
Dutt Y, Pandey RP, Dutt M, Gupta A, Vibhuti A, Raj VS, Chang CM, Priyadarshini A. Liposomes and phytosomes: Nanocarrier systems and their applications for the delivery of phytoconstituents. Coord Chem Rev 2023; 491:215251. [DOI: 10.1016/j.ccr.2023.215251] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2025]
|
|
6
|
Fernandes G, Pusuluri SLA, Nikam AN, Birangal S, Shenoy GG, Mutalik S. Solvent Free Twin Screw Processed Silybin Nanophytophospholipid: In Silico, In Vitro and In Vivo Insights. Pharmaceutics 2022; 14:pharmaceutics14122729. [PMID: 36559222 PMCID: PMC9782009 DOI: 10.3390/pharmaceutics14122729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/21/2022] [Accepted: 11/25/2022] [Indexed: 12/12/2022] Open
Abstract
Silybin (SIL) is a polyphenolic phytoconstituent that is commonly used to treat liver disorders. It is difficult to fabricate an orally delivered SIL product due to its low oral bioavailability (0.95%). Therefore, the current research focusses on the development of a novel composition of a phospholipid complex, termed as nanophytophospholipid, of SIL by employing a unique, solvent-free Twin Screw Process (TSP), with the goal of augmenting the solubility and bioavailability of SIL. The optimised SIL-nanophytophospholipid (H6-SNP) was subjected to physicochemical interactions by spectrometry, thermal, X-ray and electron microscopy. The mechanism of drug and phospholipid interaction was confirmed by molecular docking and dynamics studies. Saturation solubility, in vitro dissolution, ex vivo permeation and preclinical pharmacokinetic studies were also conducted. H6-SNP showed good complexation efficiency, with a high practical yield (80%). The low particle size (334.7 ± 3.0 nm) and positively charged zeta potential (30.21 ± 0.3 mV) indicated the immediate dispersive nature of H6-SNP into nanometric dimensions, with good physical stability. Further high solubility and high drug release from the H6-SNP was also observed. The superiority of the H6-SNP was demonstrated in the ex vivo and preclinical pharmacokinetic studies, displaying enhanced apparent permeability (2.45-fold) and enhanced bioavailability (1.28-fold). Overall, these findings indicate that not only can phospholipid complexes be formed using solvent-free TSP, but also that nanophytophospholipids can be formed by using a specific quantity of lipid, drug, surfactant, superdisintegrant and diluent. This amalgamation of technology and unique composition can improve the oral bioavailability of poorly soluble and permeable phytoconstituents or drugs.
Collapse
Affiliation(s)
- Gasper Fernandes
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Sai Lalitha Alekhya Pusuluri
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Ajinkya Nitin Nikam
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Sumit Birangal
- Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Gautham G. Shenoy
- Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Srinivas Mutalik
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
- Scires Technologies Private Limited, Manipal-Government of Karnataka Bioincubator, Advanced Research Centre, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
- Correspondence:
| |
Collapse
|
|
7
|
Kumar M, Kumar D, Kumar S, Kumar A, Mandal UK. A Recent Review on Bio-availability Enhancement of Poorly Water-soluble Drugs by using Bioenhancer and Nanoparticulate Drug Delivery System. Curr Pharm Des 2022; 28:3212-3224. [PMID: 36281868 DOI: 10.2174/1381612829666221021152354] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 08/17/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND Intravenous route of drug administration has maximum bioavailability, which shows 100% of the drug reaches blood circulation, whereas the oral administration of drugs, are readily undergoing pre-systemic metabolism, which means the poor bioavailability of the drug and limited amount of drug reaches the target site. INTRODUCTION Bioenhancers are substances having medicinal entities which enhance the bioavailability and efficacy of the active constituents of drugs. The enhanced bioavailability of drugs may lead to dose reduction, which may further reduce the cost and undesired side effects associated with the drugs. METHODS The solid lipid nanoparticles (SLNs) loaded with ketoprofen made from carnauba wax and beeswax. It was discovered that when the drug-loaded SLNs were mixed with egg-lecithin and Tween-80, as well as when the total surfactant concentration was increased, the average particle size of the drug-loaded SLNs decreased. RESULTS The drug-loaded nanoparticles, when given in combination with bio-enhancers such as piperine and quercetin, enhanced the drug's effectiveness. The Area Under Curve (AUC) was increased when the drug was coupled with bio-enhancers. Based on the findings, it can be concluded that piperine and quercetin when used with drug-loaded nanoparticles improve their therapeutic effectiveness. CONCLUSION Bioenhancers are crucial to amplifying the bioavailability of many synthetic drugs. These attributes are useful to reduce the dose of drugs and increase the therapeutic efficacy of drugs with poor bioavailability.
Collapse
Affiliation(s)
- Mohit Kumar
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India
| | - Devesh Kumar
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India
| | - Sumant Kumar
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India
| | - Akshay Kumar
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India
| | - Uttam Kumar Mandal
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India
| |
Collapse
|
|
8
|
Sarma H, Kashyap P, Zothantluanga JH, Devi R. Nanotherapeutics of Phytoantioxidants for Cardiovascular Diseases. PHYTOANTIOXIDANTS AND NANOTHERAPEUTICS 2022:405-431. [DOI: 10.1002/9781119811794.ch18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
9
|
Flavonoids: Food associations, therapeutic mechanisms, metabolism and nanoformulations. Food Res Int 2022; 157:111442. [PMID: 35761682 DOI: 10.1016/j.foodres.2022.111442] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 01/09/2023]
Abstract
Flavonoids possess an impressive therapeutic potential, thereby imparting them a nutraceutical character. As it becomes increasingly common to consume foods associated with healing properties, it is imperative to understand the associations of different foods with different classes of nutraceutic compounds, and their mechanisms of therapeutic action. At the same time, it is important to address the limitations thereof so that plausible future directions may be drawn. This review summarizes the food associations of flavonoids, and discusses the mechanisms responsible for imparting them their nutraceutic properties, detailing the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway, inhibition of inflammatory signaling pathways such as toll-like receptor (TLR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), cyclooxygenase 2 (COX-2) and lipoxygenase-2 (LOX-2) mediators. Further on, the review explains the mechanism of flavonoids metabolism, reasons for low bioavailability and thereafter recapitulates the role of technological interventions to overcome the limitations, with a particular focus on nanoformulations that utilize the synergy between flavonoids and biocompatible materials used as nanocarriers, as reported in works spanning over a decade. It is the Generally Recognized as Safe (GRAS) classified carriers that will become the basis for developing functional formulations. It is promisingly noteworthy that some flavonoid formulations have been commercialized and mentioned therein. Such commercially viable and safe for consumption technological applications pave way for bringing science to the table, and add value to the innate properties of flavonoids.
Collapse
|
|
10
|
Rathor S, Bhatt DC. Formulation, Characterization, and Pharmacokinetic Evaluation of Novel Glipizide-Phospholipid Nano-complexes with Improved Solubility and Bioavailability. Pharm Nanotechnol 2022; 10:125-136. [PMID: 35346004 DOI: 10.2174/2211738510666220328151512] [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: 12/15/2021] [Revised: 02/01/2022] [Accepted: 02/09/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND The proposed study was aimed to formulate and evaluate the Glipizide-Phospholipid Nano-complex. Since Glipizide is a poorly soluble drug, its complexation with phospholipids is an ideal approach to improving solubility. METHOD To improve the oral potency of Glipizide, its phospholipid complex was prepared by employing the solvent evaporation method. The formulations were characterized using DSC, FT-IR, PXRD, SEM, TEM, and hot stage microscopy (HSM). Solubility tests of the Glipizide-Phospholipid Nano-complex revealed a significant increase in aqueous solubility compared to Glipizide's physical combination. The oral bioavailability of the Glipizide-Phospholipid Nano-complex was measured by using HPLC in Wistar rats' plasma. FTIR and PXRD results revealed no significant interaction between the drug and the phospholipid in the formulation. SEM and TEM studies confirmed the morphology of the formulation assuring the conversion of crystalline form into an amorphous structure. RESULTS The Glipizide-Phospholipid Nano-complex had a greater peak plasma concentration (5.2 vs 3.8 g/mL), a larger AUC (26.31 vs 19.55 μgh/L), and a longer T1/2 (2.1 vs 4.1 h) than free Glipizide, indicating that it improved drug dissolution rate. CONCLUSION The outcomes suggested that a phospholipid complexation is a potential approach to increasing water-insoluble drugs' oral bioavailability.n.
Collapse
Affiliation(s)
- Sandeep Rathor
- Department of Pharmaceutical Sciences, Guru Jambheswar University of Sciences & Technology, Hisar, Haryana-125001, India
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab-142001, India
| | - D C Bhatt
- Department of Pharmaceutical Sciences, Guru Jambheswar University of Sciences & Technology, Hisar, Haryana-125001, India
| |
Collapse
|
|
11
|
Teja PK, Mithiya J, Kate AS, Bairwa K, Chauthe SK. Herbal nanomedicines: Recent advancements, challenges, opportunities and regulatory overview. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 96:153890. [PMID: 35026510 DOI: 10.1016/j.phymed.2021.153890] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 11/14/2021] [Accepted: 12/11/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND Herbal Nano Medicines (HNMs) are nano-sized medicine containing herbal drugs as extracts, enriched fractions or biomarker constituents. HNMs have certain advantages because of their increased bioavailability and reduced toxicities. There are very few literature reports that address the common challenges of herbal nanoformulations, such as selecting the type/class of nanoformulation for an extract or a phytochemical, selection and optimisation of preparation method and physicochemical parameters. Although researchers have shown more interest in this field in the last decade, there is still an urgent need for systematic analysis of HNMs. PURPOSE This review aims to provide the recent advancement in various herbal nanomedicines like polymeric herbal nanoparticles, solid lipid nanoparticles, phytosomes, nano-micelles, self-nano emulsifying drug delivery system, nanofibers, liposomes, dendrimers, ethosomes, nanoemulsion, nanosuspension, and carbon nanotube; their evaluation parameters, challenges, and opportunities. Additionally, regulatory aspects and future perspectives of herbal nanomedicines are also being covered to some extent. METHODS The scientific data provided in this review article are retrieved by a thorough analysis of numerous research and review articles, textbooks, and patents searched using the electronic search tools like Sci-Finder, ScienceDirect, PubMed, Elsevier, Google Scholar, ACS, Medline Plus and Web of Science. RESULTS In this review, the authors suggested the suitability of nanoformulation for a particular type of extracts or enriched fraction of phytoconstituents based on their solubility and permeability profile (similar to the BCS class of drugs). This review focuses on different strategies for optimising preparation methods for various HNMs to ensure reproducibility in context with all the physicochemical parameters like particle size, surface area, zeta potential, polydispersity index, entrapment efficiency, drug loading, and drug release, along with the consistent therapeutic index. CONCLUSION A combination of herbal medicine with nanotechnology can be an essential tool for the advancement of herbal medicine research with enhanced bioavailability and fewer toxicities. Despite the challenges related to traditional medicine's safe and effective use, there is huge scope for nanotechnology-based herbal medicines. Overall, it is well stabilized that herbal nanomedicines are safer, have higher bioavailability, and have enhanced therapeutic value than conventional herbal and synthetic drugs.
Collapse
Affiliation(s)
- Parusu Kavya Teja
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India
| | - Jinal Mithiya
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India
| | - Abhijeet S Kate
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India
| | - Khemraj Bairwa
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India..
| | - Siddheshwar K Chauthe
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India..
| |
Collapse
|
|
12
|
Gupta MK, Sansare V, Shrivastava B, Jadhav S, Gurav P. Comprehensive review on use of phospholipid based vesicles for phytoactive delivery. J Liposome Res 2021; 32:211-223. [PMID: 34727833 DOI: 10.1080/08982104.2021.1968430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Plant-derived phytoconstituents are well known for their therapeutic potential. It has been experimentally demonstrated that whole-plant extract or isolated phytoconstituents reveal various therapeutic potentials like hepatoprotective, antimicrobial, neuroprotective, antitumor, antioxidant, skin protectives, etc. Although these phytoconstituents have potential therapeutic benefits, their use is limited due to their poor bioavailability, stability in biological fluids, and authentication issues. These continue to be an open problem that affects the application of these valuable ancient herbal herbs in the effective treatment and management of various disease conditions. A potential solution to these difficult problems could be the loading of phytoactives in phospholipid-based vesicular systems. Phospholipid-based vesicles like liposomes, phytosomes, ethosomes as well as transfersomes were effectively utilized recently to solve drawbacks and for effective delivery of phytoactives. Several landmark studies observed better therapeutic efficacy of phytoactive loaded vesicles compared to conventional drug delivery. Thus phospholipid-based vesicles mediated phytoactive delivery is a recently developed promising and attractive strategy for better therapeutic control on disease conditions. The present short review highlights recent advances in herbal bioactive loaded phospholipid-based vesicles.
Collapse
Affiliation(s)
- Manish Kumar Gupta
- School of Pharmaceutical Sciences, Jaipur National University, Jaipur, India
| | - Vipul Sansare
- School of Pharmaceutical Sciences, Jaipur National University, Jaipur, India
| | | | - Santosh Jadhav
- Department of Pharmaceutical Chemistry, SVPM'S College of Pharmacy, Malegaon, India
| | - Prashant Gurav
- Department of Pharmaceutics, Indira Institute of Pharmacy, Sadavali, India
| |
Collapse
|
|
13
|
Khosh manzar M, Mohammadi M, Hamishehkar H, Piruzifard MK. Nanophytosome as a promising carrier for improving cumin essential oil properties. FOOD BIOSCI 2021. [DOI: 10.1016/j.fbio.2021.101079] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
|
|
14
|
Pandey R, Bhairam M, Shukla SS, Gidwani B. Colloidal and vesicular delivery system for herbal bioactive constituents. ACTA ACUST UNITED AC 2021; 29:415-438. [PMID: 34327650 DOI: 10.1007/s40199-021-00403-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 06/16/2021] [Indexed: 12/18/2022]
Abstract
OBJECTIVES The main objective of the present review is to explore and examine the effectiveness of currently developed novel techniques to resolve the issues which are associated with the herbal constituents/extract. METHODS A systematic thorough search and collection of reviewed information from Science direct, PubMed and Google Scholar databases based on various sets of key phrases have been performed. All the findings from these data have been studied and briefed based on their relevant and irrelevant information. RESULT Herbal drugs are gaining more popularity in the modern world due to their applications in curing various ailments with minimum toxic effects, side effect or adverse effect. However, various challenges exist with herbal extracts/plant actives such as poor solubility (water/lipid), poor permeation, lack of targeting specificity, instability in highly acidic pH, and liver metabolism, etc. Nowadays with the expansion in the technology, novel drug delivery system provides avenues and newer opportunity towards the delivery of herbal drugs with improved physical chemical properties, pharmacokinetic and pharmacodynamic. Developing nano-strategies like Polymeric nanoparticles, Liposomes, Niosomes, Microspheres, Phytosomes, Nanoemulsion and Self Nano Emulsifying Drug Delivery System, etc. imparts benefits for delivery of phyto formulation and herbal bioactives. Nano formulation of phytoconstituents/ herbal extract could lead to enhancement of aqueous solubility, dissolution, bioavailability, stability, reduce toxicity, permeation, sustained delivery, protection from enzymatic degradation, etc. CONCLUSION: Based on the above findings, the conclusion can be drawn that the nano sized novel drug delivery systems of herbal and herbal bioactives have a potential future for upgrading the pharmacological action and defeating or overcoming the issues related with these constituents. The aims of the present review was to summarize and critically analyze the recent development of nano sized strategies for promising phytochemicals delivery systems along with their therapeutic applications supported by experimental evidence and discussing the opportunities for further aspects.
Collapse
Affiliation(s)
- Ravindra Pandey
- Columbia Institute of Pharmacy Raipur, Raipur, Chhattisgarh, India.
| | - Monika Bhairam
- Columbia Institute of Pharmacy Raipur, Raipur, Chhattisgarh, India
| | | | - Bina Gidwani
- Columbia Institute of Pharmacy Raipur, Raipur, Chhattisgarh, India
| |
Collapse
|
|
15
|
Enhanced permeability and photoprotective potential of optimized p-coumaric acid-phospholipid complex loaded gel against UVA mediated oxidative stress. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2021; 221:112246. [PMID: 34243023 DOI: 10.1016/j.jphotobiol.2021.112246] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 06/11/2021] [Accepted: 06/17/2021] [Indexed: 01/14/2023]
Abstract
Photo-oxidative skin damage is mainly caused by the UV-A radiation of the sun. Synthetic sunscreens used to counter this acts mostly on the superficial skin layer and possess serious side effects. P-coumaric acid (PCA) is a UV-A protective plant phenolic having quick diffusion and distribution in superficial skin layers limiting its application as herbal sunscreen. The present study was designed to formulate an optimized phospholipid complex of PCA (PCAPC) through response surface methodology to enhance its skin permeation to deeper skin layers providing protection against photo-oxidative stress. PCAPC was characterized by FT-IR, DTA, PXRD, TEM, zeta potential etc. PCAPC was then incorporated into a gel formulation (PCAPC-GE) to facilitate its transdermal delivery. Physicochemical properties of the gel were assessed by pH, homogeneity, rheology, spreadability etc. In-vitro SPF and UVA-PF of the gel was evaluated and compared with conventional gel (PCA-GE). Ex-vivo skin permeation flux, permeability coefficient, skin deposition and dermatokinetic analysis were carried out to measure the rate and level of skin permeation. This was accompanied by in-vivo evaluation of PCAPC-GE and PCA-GE in the experimental rat model by measuring the various oxidative stress markers such as superoxide dismutase, catalase etc. PCAPC-GE provided high SPF and UVA-PF value compared to PCA-GE. The physicochemical parameters were suitable for transdermal application. PCAPC-GE enhanced the permeation rate of PCA by almost 6 fold compared to PCA-GE. Besides, a significant reduction of UV-A induced oxidative stress biomarkers were observed for PCAPC-GE. Thus, the PCAPC-GE may be an effective alternative of synthetic sunscreens due to its enhanced permeation and protection against UVA-induced oxidative stress.
Collapse
|
|
16
|
Luo X, Wang D, Wang M, Deng S, Huang Y, Xia Z. Development of phospholipid complex loaded self-microemulsifying drug delivery system to improve the oral bioavailability of resveratrol. Nanomedicine (Lond) 2021; 16:721-739. [PMID: 33860675 DOI: 10.2217/nnm-2020-0422] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: The aim of this study was to develop a formulation that combines a phospholipid complex (PC) and self-microemulsifying drug delivery system (SMEDDS) to improve the bioavailability of poorly water-soluble resveratrol (RES), called RPC-SMEDDS. Methods: RES-PC (RPC) and RPC-SMEDDS were optimized by orthogonal experiment and central composite design, respectively. The characteristics and mechanism of intestinal absorption were studied by Ussing chamber model. The pharmacokinetics was evaluated in rats. Results: RES was the substrate of MRP2 and breast cancer resistance protein (BCRP) rather than P-gp. The prepared RPC-SMEDDS prevented the efflux mediated by MRP2 and BCRP and improved the bioavailability of RES. Conclusion: These results suggested that the combination system of PC and SMEDDS was a promising method to improve the oral bioavailability of RES.
Collapse
Affiliation(s)
- Xinxin Luo
- School of Chemistry & Chemical Engineering, Chongqing University, Chongqing, 401331, China
| | - Dandan Wang
- School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, China
| | - Min Wang
- School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, China
| | - Suya Deng
- School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, China
| | - Yike Huang
- College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China
| | - Zhining Xia
- School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, China
| |
Collapse
|
|
17
|
Zhang M, Zhu S, Yang W, Huang Q, Ho CT. The biological fate and bioefficacy of citrus flavonoids: bioavailability, biotransformation, and delivery systems. Food Funct 2021; 12:3307-3323. [PMID: 33735339 DOI: 10.1039/d0fo03403g] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Citrus fruits are among the most popularly consumed fruits worldwide, including oranges, grapefruits, pomelos and lemons. Citrus flavonoids such as hesperidin, naringin and nobiletin have shown an array of health benefits in cell, animal and clinical studies, including antioxidative, anti-inflammatory, neuroprotective, anticancer, and anti-obesity activities. Citrus flavonoids have limited bioavailability after oral administration, leaving the major part unabsorbed and persisted in the colon. Recent studies have highlighted the important role of the gut microbiota and in vivo biotransformation on the bioactivity of citrus flavonoids. This article discusses the biological fate of citrus flavonoids from the viewpoint of their absorption, distribution, metabolism and excretion in vivo. Many delivery systems have been designed to enhance the oral bioavailability of citrus flavonoids, such as emulsions, self-emulsifying systems, nanoparticles and solid dispersions. The ultimate goal of these delivery systems is to enhance the bioefficacy of citrus flavonoids. Several studies have found that the increased bioavailability leads to enhanced bioefficacy of citrus flavonoids in specific animal models. Regarding the complex dynamics of citrus flavonoids and gut microbiota, the bioavailability-bioactivity relationship is an interesting but under-discussed area. Comprehensively understanding the biological fate and bioefficacy of citrus flavonoids would be helpful to develop functional foods with better health benefits.
Collapse
Affiliation(s)
- Man Zhang
- Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick 08901, New Jersey, USA.
| | | | | | | | | |
Collapse
|
|
18
|
|
|
19
|
Mangrulkar S, Shah P, Navnage S, Mazumdar P, Chaple D. Phytophospholipid Complex of Caffeic Acid: Development, In vitro Characterization, and In Vivo Investigation of Antihyperlipidemic and Hepatoprotective Action in Rats. AAPS PharmSciTech 2021; 22:28. [PMID: 33404939 DOI: 10.1208/s12249-020-01887-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 11/23/2020] [Indexed: 11/30/2022] Open
Abstract
Caffeic acid (CA), a hydroxycinnamic acid possessing a variety of pharmacological activities, has caused a growing interest for the treatment of hyperlipidemia and associated conditions. This work endeavored to develop a novel formulation of CA-Phospholipon® 90H complex (CA-PC) using a solvent evaporation method. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectrophotometry (FTIR), and powder X-ray powder diffraction (PXRD) was carried to confirm the formation of CA-PC. The CA-PC was functionally evaluated in terms of solubility, in vitro and ex vivo drug release, and in vivo bioavailability and efficacy studies. SEM, DSC, FTIR, and XRD studies indicated the physical interaction of CA with Phospholipon® 90H to form a complex. Dynamic light scattering (DLS) studies described particle size of 168 ± 3.9 nm with a monodisperse distribution (PDI 0.17) and a negative zeta-potential of - 16.6 ± 2.1 mV. The phospholipid complex significantly improved (4.2-fold) the solubility of CA. In vitro and ex vivo dissolution studies of the formulated CA-PC revealed a significantly higher release compared with the pure CA. The pharmacokinetic study of CA-PC in rats demonstrated a significant increase (4.79-fold) in oral bioavailability when compared with pure CA as well. Additionally, a significant improvement in serum lipid profile, serum liver biomarker enzyme levels and, restoration of hepatic tissue architecture to normal, in high-fat diet (HFD) induced hyperlipidemic model was obtained upon CA-PC administration when compared with pure CA. These findings indicated that CA-PC would serve as an effective and promising formulation for CA delivery with improved antihyperlipidemic and hepatoprotective activity.Graphical abstract.
Collapse
|
|
20
|
Verma VK, Zaman MK, Verma S, Verma SK, Sarwa KK. Role of semi-purified andrographolide from Andrographis paniculata extract as nano-phytovesicular carrier for enhancing oral absorption and hypoglycemic activity. CHINESE HERBAL MEDICINES 2020; 12:142-155. [PMID: 36119803 PMCID: PMC9476388 DOI: 10.1016/j.chmed.2019.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 09/23/2019] [Accepted: 10/10/2019] [Indexed: 11/17/2022] Open
Abstract
Objective Andrographis paniculata is a well-known medicinal plant in Southeast Asia, India and China. The plant contains andrographolide (AN), a very important phytochemical used in various health problems. However, AN is low in oral absorption bioavailability of AN due to the rapid clearance and high protein binding capacity. Methods The present study was aimed to develop a nano-phytovesicular formulation of semi-purified AN extracts from a naturally occurring phospholipid (soya phosphatidylcholine) in order to increase the oral absorption and antihyperglycemic activity in rats. Results The nano-phyto vesicle of semi-purified AN extracts equivalent to 25 mg /kg AN significantly protected the hyperglycemic condition of rats. The in vitro and in vivo experiments results proved that the nano- phytovesicular system of plant extracts containing AN produced better oral absorption, bioavailability and improved antihyperglycemic activity compared with that of free AN at dose of 50 mg/kg. Conclusion Hence, the prepared semi-purified extract nano-phytovesicular system is helpful in solving the problem of rapid clearance of AN.
Collapse
|
|
21
|
Ustuner D, Kolac UK, Ustuner MC, Tanrikut C, Ozdemir Koroglu Z, Burukoglu Donmez D, Ozen H, Ozden H. Naringenin Ameliorate Carbon Tetrachloride-Induced Hepatic Damage Through Inhibition of Endoplasmic Reticulum Stress and Autophagy in Rats. J Med Food 2020; 23:1192-1200. [PMID: 32125927 DOI: 10.1089/jmf.2019.0265] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Hepatic fibrosis emerges upon exposure of liver to various chemicals and if not treated, it develops various diseases such as cirrhosis and cancer. Carbon tetrachloride (CCl4) is a widely used toxin in animal models to develop hepatic fibrosis. Accumulation of unfolded proteins in cells causes stress in the endoplasmic reticulum (ER) and various mechanisms are involved in the cell to reduce the damage caused by these unfolding proteins. The most well known of these is the unfolded protein response. Further, autophagy works to remove these proteins if the damage cannot be repaired and is permanent. In our study, we investigated the effects of naringenin (NRG), a flavanon abundant in citrus fruits, on ER stress and autophagy in CCl4-injured rat liver. The animals were given 0.2 mL/kg of CCl4 for 10 days and treatment group was administered 100 mg/kg of NRG for 14 days. Histopathological examination was performed to show liver damage and to determine the therapeutic properties of the active substance. Transmission electron microscopy (TEM) analysis was carried out to establish cell level damage and effect of treatment. In addition, levels of ER stress and autophagy markers of liver were measured. According to our findings, TEM demonstrated positive effect of NRG and histological examinations reported ameliorative effects. In addition, NRG reduced levels of ER stress markers and inhibited autophagy significantly compared to CCl4-treated group. As a result, NRG significantly reduced damage in hepatocytes and provided a significant amelioration.
Collapse
Affiliation(s)
- Derya Ustuner
- Department of Medical Laboratory, Vocational School of Health Services Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Umut Kerem Kolac
- Department of Medical Biology, Faculty of Medicine, Aydın Adnan Menderes University, Efeler, Turkey
| | - Mehmet Cengiz Ustuner
- Department of Medical Biology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Cihan Tanrikut
- Department of Medical Biology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Zeynep Ozdemir Koroglu
- Department of Medical Laboratory, Vocational School of Health Services Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Dilek Burukoglu Donmez
- Department of Histology and Embryology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Hulya Ozen
- Department of Biostatistics and Medical Informatics, and Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Hilmi Ozden
- Department of Anatomy, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
| |
Collapse
|
|
22
|
Malayeri A, Badparva R, Mombeini MA, Khorsandi L, Goudarzi M. Naringenin: a potential natural remedy against methotrexate-induced hepatotoxicity in rats. Drug Chem Toxicol 2020; 45:491-498. [DOI: 10.1080/01480545.2020.1719132] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Alireza Malayeri
- Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Reza Badparva
- Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Amin Mombeini
- Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Layasadat Khorsandi
- Department of Anatomical Sciences, Faculty of Medicine, Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mehdi Goudarzi
- Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| |
Collapse
|
|
23
|
Kalita B, Patwary BN. Formulation and in vitro Evaluation of Hesperidin-Phospholipid Complex and its Antioxidant Potential. CURRENT DRUG THERAPY 2020. [DOI: 10.2174/1574885514666190226155933] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background:
The recent trend of herbal drug delivery has been focused on developing
novel drug delivery carriers to address problems related to solubility, oral bioavailability, skin permeation
and stability. The phyto-phospholipid complex (phytosomes®) technology has been used to
overcome the problems associated with many conventional herbal extracts.
Aim:
The present work aimed to formulate phospholipid-complex of the flavanoid Hesperidin to
enhance its dissolution leading to enhanced oral bioavailability.
Method:
The complex was prepared by refluxing various molar ratios of hesperidin and PC followed
by solvent evaporation. The prepared complexes were evaluated for saturation solubility,
partition co-efficient and drug content. The free drug and phospholipid complexes were analyzed in
DSC. Surface morphology of the prepared complexes was viewed using SEM images. Selected
formulations were subjected to in vitro drug release study. Antioxidant effect was examined by free
radical scavenging method.
Results:
Solubility and partition coefficient of the prepared complexes were improved in comparison
to free drug. Based on the results of solubility, partition coefficient and drug content, formulation
F2 was selected as an optimized batch. DSC thermograms confirmed the formation of phospholipid
complex. Free Hesperidin and Hesperidin-phospholipid complex (F2) showed 46.9 % and
78.20 % of drug release, respectively, at seven hours phosphate buffer (pH 7.4). The optimized
formulation showed concentration-dependent anti-oxidant property.
Conclusion:
Results of the present study suggested that the phospholipid complex of Hesperidin
possesses the antioxidant potential and may be of potential use for improving the dissolution of
hesperidin and hence oral bioavailability.
Collapse
Affiliation(s)
- Bhupen Kalita
- Girijananda Chowdhury Institute of Pharmaceutical Science, Guwahati-781017, Assam, India
| | - Bhargab Nath Patwary
- Girijananda Chowdhury Institute of Pharmaceutical Science, Guwahati-781017, Assam, India
| |
Collapse
|
|
24
|
Wang J, Ding Y, Zhou W. Albumin self-modified liposomes for hepatic fibrosis therapy via SPARC-dependent pathways. Int J Pharm 2019; 574:118940. [PMID: 31830578 DOI: 10.1016/j.ijpharm.2019.118940] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 11/17/2019] [Accepted: 12/06/2019] [Indexed: 12/16/2022]
Abstract
Activated hepatic stellate cells (HSCs) have a central role in the progression of liver fibrosis and express a large amount of secreted protein, acidic and rich in cysteine (SPARC), a specific protein-binding protein. In this study, we reported the preparation and evaluation of naringenin (Nar) -loaded albumin self-modified liposomes (NaAlLs), which delivered Nar, a specific Smad3 inhibitor that blocked the TGF-β/Smad3 signaling pathway and played an anti-fibrosis role. After a series of characterization, it was found that NaAlLs had favorable dispersion (PDI < 0.15) with an average particle size of about 120 nm and high entrapment efficiency (>85%), albumin coated the surface of liposomes or embedded in phospholipid bilayer by interaction with the encapsulated naringenin and phospholipid molecules during the preparation of liposomes. The amount of albumin modified to the surface of NaAlLs by this method is not only more than that of the physical adsorption method, but also the binding force between albumin and liposomes is stronger. The albumin modified to the surface of NaAlLs greatly reduced the aggregation of liposomes and drug leakage and increased the stability of liposomes. More importantly, the uptake of NaAlLs by activated HSCs was 1.5 times higher than that of Nar-loaded liposomes (NaLs), suggesting that NaAlLs specifically increased targeting of activated HSCs via albumin and SPARC-dependent pathways. As expected, NaAlLs was more effective in improving liver fibrosis than the NaLs or the inclusion complex solution of Nar and Hydroxypropyl-β-cyclodextrin (NaICS). The results suggested that NaAlLs was a promising drug delivery system, which could target drug delivery to activated HSC for the treatment of liver fibrosis.
Collapse
Affiliation(s)
- Jianzhu Wang
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu 210009, China; School of Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong 271016, China
| | - Yu Ding
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu 210009, China
| | - Wei Zhou
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
| |
Collapse
|
|
25
|
A Solid Dispersion of Quercetin Shows Enhanced Nrf2 Activation and Protective Effects against Oxidative Injury in a Mouse Model of Dry Age-Related Macular Degeneration. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:1479571. [PMID: 31781321 PMCID: PMC6875405 DOI: 10.1155/2019/1479571] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 09/17/2019] [Indexed: 12/15/2022]
Abstract
Age-related macular degeneration (AMD) represents a major reason for blindness in the elderly population. Oxidative stress is a predominant factor in the pathology of AMD. We previously evaluated the effects of phospholipid complex of quercetin (Q-PC) on oxidative injury in ARPE-19 cells, but the underlying mechanisms are not fully understood. Herein, the solid dispersion of quercetin-PC (Q-SD) was prepared with solubility being 235.54 μg/mL in water and 2.3×104 μg/mL in chloroform, which were significantly higher than that of quercetin (QT) and Q-PC. Q-SD also exhibited a considerably higher dissolution rate than QT and Q-PC. Additionally, Q-SD had Cmax of 4.143 μg/mL and AUC of 12.015 μg·h/mL in rats, suggesting better bioavailability than QT and Q-PC. Then, a mouse model of dry AMD (Nrf2 wild-type (WT) and Nrf2 knockout (KO)) was established for evaluating the effects of Q-SD in vivo. Q-SD more potently reduced retinal pigment epithelium sediments and Bruch's membrane thickness than QT and Q-PC at 200 mg/kg in Nrf2 WT mice and did not work in Nrf2 KO mice at the same dosage. Additionally, Q-SD significantly decreased ROS and MDA contents and restored SOD, GSH-PX, and CAT activities of serum and retinal tissues in Nrf2 WT mice, but not in Nrf2 KO mice. Furthermore, Q-SD more potently increased Nrf2 mRNA expression and stimulated its nuclear translocation in retinal tissues of Nrf2 WT mice. Q-SD significantly increased the expression of Nrf2 target genes HO-1, HQO-1, and GCL of retinal tissues in Nrf2 WT mice, not in Nrf2 KO mice. Altogether, Q-SD had improved physicochemical and pharmacokinetic properties compared to QT and Q-PC and exhibited more potent protective effects on retina oxidative injury in vivo. These effects were associated with activation of Nrf2 signaling and upregulation of antioxidant enzymes.
Collapse
|
|
26
|
Rashid M, Malik MY, Singh SK, Chaturvedi S, Gayen JR, Wahajuddin M. Bioavailability Enhancement of Poorly Soluble Drugs: The Holy Grail in Pharma Industry. Curr Pharm Des 2019; 25:987-1020. [DOI: 10.2174/1381612825666190130110653] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Accepted: 01/24/2019] [Indexed: 02/07/2023]
Abstract
Background:
Bioavailability, one of the prime pharmacokinetic properties of a drug, is defined as the
fraction of an administered dose of unchanged drug that reaches the systemic circulation and is used to describe
the systemic availability of a drug. Bioavailability assessment is imperative in order to demonstrate whether the
drug attains the desirable systemic exposure for effective therapy. In recent years, bioavailability has become
the subject of importance in drug discovery and development studies.
Methods:
A systematic literature review in the field of bioavailability and the approaches towards its enhancement
have been comprehensively done, purely focusing upon recent papers. The data mining was performed
using databases like PubMed, Science Direct and general Google searches and the collected data was exhaustively
studied and summarized in a generalized manner.
Results:
The main prospect of this review was to generate a comprehensive one-stop summary of the numerous
available approaches and their pharmaceutical applications in improving the stability concerns, physicochemical
and mechanical properties of the poorly water-soluble drugs which directly or indirectly augment their bioavailability.
Conclusion:
The use of novel methods, including but not limited to, nano-based formulations, bio-enhancers,
solid dispersions, lipid-and polymer-based formulations which provide a wide range of applications not only
increases the solubility and permeability of the poorly bioavailable drugs but also improves their stability, and
targeting efficacy. Although, these methods have drastically changed the pharmaceutical industry demand for the
newer potential methods with better outcomes in the field of pharmaceutical science to formulate various dosage
forms with adequate systemic availability and improved patient compliance, further research is required.
Collapse
Affiliation(s)
- Mamunur Rashid
- Pharmaceutics and Pharmacokinetics Division, CSIR-CDRI, Lucknow, India
| | - Mohd Yaseen Malik
- Pharmaceutics and Pharmacokinetics Division, CSIR-CDRI, Lucknow, India
| | - Sandeep K. Singh
- Pharmaceutics and Pharmacokinetics Division, CSIR-CDRI, Lucknow, India
| | - Swati Chaturvedi
- Pharmaceutics and Pharmacokinetics Division, CSIR-CDRI, Lucknow, India
| | - Jiaur R Gayen
- Pharmaceutics and Pharmacokinetics Division, CSIR-CDRI, Lucknow, India
| | | |
Collapse
|
|
27
|
Therapeutic potential of naringin in neurological disorders. Food Chem Toxicol 2019; 132:110646. [PMID: 31252025 DOI: 10.1016/j.fct.2019.110646] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 05/26/2019] [Accepted: 06/23/2019] [Indexed: 12/23/2022]
Abstract
Neurological illnesses are multifactorial incurable debilitating disorders that may cause neurodegeneration. These diseases influence approximately 30 million people around the world. Despite several therapies, effective management of such disorders remains a global challenge. Thus, natural products might offer an alternative therapy for the treatment of various neurological disorders. Polyphenols, such as curcumin, resveratrol, myricetin, mangiferin and naringin (NRG) have been shown to possess promising potential in the treatment of neurogenerative illness. In this review, we have targeted the therapeutic potential of naringin as a neuroprotective agent. The overall neuroprotective effects and different possible underlying mechanisms related to NRG are discussed. In light of the strong evidence for the neuropharmacological efficacy of NRG in various experimental paradigms, it is concluded that this molecule should be further considered and studied as a potential candidate for neurotherapeutics, focusing on mechanistic and clinical trials to ascertain its efficacy.
Collapse
|
|
28
|
Keophiphath M, Courbière C, Manzato L, Lamour I, Gaillard E. "Miliacin encapsulated by polar lipids stimulates cell proliferation in hair bulb and improves telogen effluvium in women". J Cosmet Dermatol 2019; 19:485-493. [PMID: 31135099 DOI: 10.1111/jocd.12998] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 02/26/2019] [Accepted: 04/22/2019] [Indexed: 11/26/2022]
Abstract
BACKGROUND Miliacin, the main triterpenoid from millet, is known to stimulate keratinocyte metabolism and proliferation. Polar lipids are able to form vesicles with active compounds and to improve their bioavailability. OBJECTIVES We aimed to demonstrate potential benefits of a solution of miliacin encapsulated within polar lipids (MePL) on telogen effluvium prevention and hair condition in women. METHODS After preliminary cell proliferation studies, a placebo-controlled, multicentric, randomized, double-blind trial was performed on sixty-five nonmenopausal women affected by telogen effluvium, to assess the efficacy of a 12-week oral supplementation with MePL. Telogen and anagen densities were determined by phototrichogram analysis. Scalp dryness and hair brightness were clinically evaluated using a Likert scale. RESULTS MePL further enhanced cell proliferation in hair bulb from human scalp than miliacin alone. Compared to the placebo treatment, MePL supplementation significantly reduced telogen density after 12 weeks of treatment. An increase of anagen density was observed in both groups, although there was no significant difference between the two treatments. Scalp dryness was more decreased in the MePL group than in the placebo group. A better improvement of hair brightness was also observed after 12 weeks of supplementation with MePL. CONCLUSION Twelve weeks of MePL supplementation significantly reduced the hair density in the telogen phase and, in parallel, improved scalp dryness and hair condition. These effects could be linked to MePL activity on cell proliferation in hair bulb. MePL is an original association of plant extract that could help to prevent and/or limit hair loss in women.
Collapse
|
|
29
|
Boisnic S, Keophiphath M, Serandour AL, Branchet MC, Le Breton S, Lamour I, Gaillard E. Polar lipids from wheat extract oil improve skin damages induced by aging: Evidence from a randomized, placebo-controlled clinical trial in women and an ex vivo study on human skin explant. J Cosmet Dermatol 2019; 18:2027-2036. [PMID: 31033133 DOI: 10.1111/jocd.12967] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 03/08/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Polar lipids from wheat (Triticum vulgare/aestivum) extract oil (WEO) are known to improve skin hydration. AIMS These studies aimed to assess WEO benefits on the skin appearance of middle-aged women. METHODS A double-blind, randomized, placebo-controlled clinical study was carried out on 64 healthy women, aged from 45 to 60 years, to investigate antiaging effects and benefits for the skin. The study lasted 20 weeks including 12 weeks of oral supplementation with WEO or placebo and 8 weeks of follow-up. Wrinkles in the "crow's-feet" area were evaluated by the Lemperle score. Skin hydration was measured using a corneometer, while roughness and radiance were determined by clinical scoring. Collagen content was quantified in human skin explants exposed to ultraviolet (UV) irradiations and treated with WEO or vehicle control. RESULTS Compared to the placebo group, the Lemperle score was significantly reduced in the WEO group between W0 and W8 to reach a clinically significant 1 grade at W12. Facial hydration was significantly improved in the WEO group from W0 to W12, whereas leg hydration was significantly increased after 4 weeks and lasted throughout the supplementation period. Skin roughness and radiance were also significantly improved from W0 to W8 in the WEO group compared to placebo group. A higher collagen content was measured in the UV-irradiated skin explants treated with WEO compared to the untreated ones. CONCLUSION These results confirmed the moisturizing effect of WEO and, for the first time, revealed its potential antiaging properties.
Collapse
|
|
30
|
Mishra M, Kumar P, Rajawat JS, Malik R, Sharma G, Modgil A. Nanotechnology: Revolutionizing the Science of Drug Delivery. Curr Pharm Des 2019; 24:5086-5107. [PMID: 30727873 DOI: 10.2174/1381612825666190206222415] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Accepted: 02/02/2019] [Indexed: 12/12/2022]
Abstract
Growing interest in the field of nanotechnology has led to its emergence in the field of medicine too.
Nanomedicines encompass the various medical tools, diagnostic agents and the drug delivery vehicles being
evolved with the advancements in the aura of nanotechnology. This review emphasizes on providing a cursory
literature on the past events that led to the procession of nanomedicines, various novel drug delivery systems
describing their structural features along with the pros and cons associated with them and the nanodrugs that
made a move to the clinical practice. It also focuses on the need of the novel drug delivery systems and the challenges
faced by the conventional drug delivery systems.
Collapse
Affiliation(s)
- Mohini Mishra
- Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, NH-8, Bandarsindri, Ajmer, Rajasthan, India
| | - Pramod Kumar
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Guwahati, Assam, India
| | | | - Ruchi Malik
- Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, NH-8, Bandarsindri, Ajmer, Rajasthan, India
| | - Gitanjali Sharma
- Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, United States
| | - Amit Modgil
- Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, United States
| |
Collapse
|
|
31
|
Enhancing Curcumin Oral Bioavailability Through Nanoformulations. Eur J Drug Metab Pharmacokinet 2019; 44:459-480. [DOI: 10.1007/s13318-019-00545-z] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
|
|
32
|
Ravi GS, Charyulu RN, Dubey A, Prabhu P, Hebbar S, Mathias AC. Nano-lipid Complex of Rutin: Development, Characterisation and In Vivo Investigation of Hepatoprotective, Antioxidant Activity and Bioavailability Study in Rats. AAPS PharmSciTech 2018; 19:3631-3649. [PMID: 30280357 DOI: 10.1208/s12249-018-1195-9] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 09/21/2018] [Indexed: 01/25/2023] Open
Abstract
The current study was aimed to develop an amphiphilic drug-lipid nano-complex of rutin:egg phosphatidylcholine (EPC) to enhance its poor absorption and bioavailability, and investigated the impact of the complex on hepatoprotective and antioxidant activity. Rutin nano-complexes were prepared by solvent evaporation, salting out and lyophilisation methods and compared for the complex formation. For the selected lyophilisation method, principal solvent DMSO, co-solvent (t-butyl alcohol) and rutin:EPC ratios (1:1, 1:2 and 1:3) were selected after optimisation. The properties of the nano-complexes such as complexation, thermal behaviour, surface morphology, molecular crystallinity, particle size, zeta potential, drug content, solubility, in vitro stability study, in vitro drug release, in vitro and in vivo antioxidant study, in vivo hepatoprotective activity and oral bioavailability/pharmacokinetic studies were investigated. Rutin nano-complexes were developed successfully via the lyophilisation method and found to be in nanometric range. Rutin nano-complexes significantly improved the solubility and in vitro drug release, and kinetic studies confirmed the diffusion-controlled release of the drug from the formulation. The nano-complex showed better antioxidant activity in vitro and exhibited well in vitro stability in different pH media. The in vivo study showed better hepatoprotective activity of the formulation compared to pure rutin at the same dose levels with improved oral bioavailability. Carbon tetrachloride (CCl4)-treated animals (group II) failed to restore the normal levels of serum hepatic marker enzymes and liver antioxidant enzyme compared to the nano-complex-treated animals. The results obtained from solubility, hepatoprotective activity and oral bioavailability studies proved the better efficacy of the nano-complex compared to the pure drug.
Collapse
|
|
33
|
Ge L, He X, Zhang Y, Zhang Y, Chai F, Jiang L, Webster TJ, Zheng C. A dabigatran etexilate phospholipid complex nanoemulsion system for further oral bioavailability by reducing drug-leakage in the gastrointestinal tract. NANOMEDICINE : NANOTECHNOLOGY, BIOLOGY, AND MEDICINE 2017; 14:S1549-9634(17)30156-9. [PMID: 28842377 DOI: 10.1016/j.nano.2017.08.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Revised: 08/07/2017] [Accepted: 08/11/2017] [Indexed: 02/06/2023]
Abstract
Dabigatran etexilate (DE) is insoluble at neutral pH values but soluble at low pH values due to protonation, which is the major cause for the poor bioavailability of commercial DE products. Here, we first developed a DE nanoemulsion system and improved dissolution in simulated intestinal fluids by encapsulating DE into an oil phase, but 35.8% of the drug still leaked out. Further, we prepared a DE-phospholipid complex (DE-PC) to enhance lipophilicity and solubility of DE. The resulting DE-PC nanoemulsions significantly (P<0.05) reduced drug leakage and subsequent precipitation. As a result, the relative bioavailability of DE-PC nanoemulsions increased to 147.3% and 606.6% compared to DE nanoemulsions and commercial DE products, respectively. Thus, the presently developed drug-phospholipid complex nanoemulsion system is a promising drug delivery system for improving the oral bioavailability of pH-dependent soluble drugs.
Collapse
Affiliation(s)
- Liang Ge
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China
| | - Xinyi He
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China
| | - Yajie Zhang
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China
| | - Yuan Zhang
- Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Fujuan Chai
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China
| | - Liqun Jiang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Thomas J Webster
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA.
| | - Chunli Zheng
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
| |
Collapse
|
|
34
|
Hernández-Aquino E, Zarco N, Casas-Grajales S, Ramos-Tovar E, Flores-Beltrán RE, Arauz J, Shibayama M, Favari L, Tsutsumi V, Segovia J, Muriel P. Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways. World J Gastroenterol 2017; 23:4354-4368. [PMID: 28706418 PMCID: PMC5487499 DOI: 10.3748/wjg.v23.i24.4354] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Revised: 03/22/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To study the molecular mechanisms involved in the hepatoprotective effects of naringenin (NAR) on carbon tetrachloride (CCl4)-induced liver fibrosis.
METHODS Thirty-two male Wistar rats (120-150 g) were randomly divided into four groups: (1) a control group (n = 8) that received 0.7% carboxy methyl-cellulose (NAR vehicle) 1 mL/daily p.o.; (2) a CCl4 group (n = 8) that received 400 mg of CCl4/kg body weight i.p. 3 times a week for 8 wk; (3) a CCl4 + NAR (n = 8) group that received 400 mg of CCl4/kg body weight i.p. 3 times a week for 8 wk and 100 mg of NAR/kg body weight daily for 8 wk p.o.; and (4) an NAR group (n = 8) that received 100 mg of NAR/kg body weight daily for 8 wk p.o. After the experimental period, animals were sacrificed under ketamine and xylazine anesthesia. Liver damage markers such as alanine aminotransferase (ALT), alkaline phosphatase (AP), γ-glutamyl transpeptidase (γ-GTP), reduced glutathione (GSH), glycogen content, lipid peroxidation (LPO) and collagen content were measured. The enzymatic activity of glutathione peroxidase (GPx) was assessed. Liver histopathology was performed utilizing Masson’s trichrome and hematoxylin-eosin stains. Zymography assays for MMP-9 and MMP-2 were carried out. Hepatic TGF-β, α-SMA, CTGF, Col-I, MMP-13, NF-κB, IL-1, IL-10, Smad7, Smad3, pSmad3 and pJNK proteins were detected via western blot.
RESULTS NAR administration prevented increases in ALT, AP, γ-GTP, and GPx enzymatic activity; depletion of GSH and glycogen; and increases in LPO and collagen produced by chronic CCl4 intoxication (P < 0.05). Liver histopathology showed a decrease in collagen deposition when rats received NAR in addition to CCl4. Although zymography assays showed that CCl4 produced an increase in MMP-9 and MMP-2 gelatinase activity; interestingly, NAR administration was associated with normal MMP-9 and MMP-2 activity (P < 0.05). The anti-inflammatory, antinecrotic and antifibrotic effects of NAR may be attributed to its ability to prevent NF-κB activation and the subsequent production of IL-1 and IL-10 (P < 0.05). NAR completely prevented the increase in TGF-β, α-SMA, CTGF, Col-1, and MMP-13 proteins compared with the CCl4-treated group (P < 0.05). NAR prevented Smad3 phosphorylation in the linker region by JNK since this flavonoid blocked this kinase (P < 0.05).
CONCLUSION NAR prevents CCl4 induced liver inflammation, necrosis and fibrosis, due to its antioxidant capacity as a free radical inhibitor and by inhibiting the NF-κB, TGF-β-Smad3 and JNK-Smad3 pathways.
Collapse
|
|
35
|
Badea G, Badea N, Brasoveanu LI, Mihaila M, Stan R, Istrati D, Balaci T, Lacatusu I. Naringenin improves the sunscreen performance of vegetable nanocarriers. NEW J CHEM 2017. [DOI: 10.1039/c6nj02318e] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Naringenin enhances the UV protection, photostability and cell viability of lipid based vegetable nanocarriers.
Collapse
Affiliation(s)
- Gabriela Badea
- Faculty of Applied Chemistry and Material Science
- University POLITEHNICA of Bucharest
- 011061 Bucharest
- Romania
| | - Nicoleta Badea
- Faculty of Applied Chemistry and Material Science
- University POLITEHNICA of Bucharest
- 011061 Bucharest
- Romania
| | | | - Mirela Mihaila
- Romanian Academy
- Stefan S. Nicolau Institute of Virology
- 030304 Bucharest
- Romania
| | - Raluca Stan
- Faculty of Applied Chemistry and Material Science
- University POLITEHNICA of Bucharest
- 011061 Bucharest
- Romania
| | - Daniela Istrati
- Faculty of Applied Chemistry and Material Science
- University POLITEHNICA of Bucharest
- 011061 Bucharest
- Romania
| | - Teodora Balaci
- University of Medicine and Pharmacy Carol Davila
- 70183 Bucharest
- Romania
| | - Ioana Lacatusu
- Faculty of Applied Chemistry and Material Science
- University POLITEHNICA of Bucharest
- 011061 Bucharest
- Romania
| |
Collapse
|
|
36
|
Zhang X, Zhang Y, Guo S, Bai F, Wu T, Zhao Y. Improved oral bioavailability of 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol using nanoemulsion based on phospholipid complex: design, characterization, and in vivo pharmacokinetics in rats. Drug Des Devel Ther 2016; 10:3707-3716. [PMID: 27877020 PMCID: PMC5108498 DOI: 10.2147/dddt.s114374] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
The aim of the study was to improve the oral absorption of the compound 25-OCH3-PPD with poor hydrophilicity and lipophilicity. 25-OCH3-PPD-phospholipid complex was prepared by solvent evaporation, then characterized by differential scanning calorimetry, scanning electron microscopy, and infrared absorption spectroscopy. The aqueous solubility and oil-water partition coefficient were compared with the free compound. A nanoemulsion loaded with 25-OCH3-PPD-phospholipid complex was developed by dissolving the complex in water in the presence of hydrophilic surfactant under sonication. After oral administration of the nanoemulsion and the suspension of 25-OCH3-PPD in rats, the concentrations of 25-OCH3-PPD in plasma were determined by high-performance liquid chromatography-tandem mass spectrometry method. The results showed that the solubility of the complex in water and n-octanol was enhanced. The oil-water partition coefficient improved 1.7 times. Peak plasma concentration and area under the curve(0-24 h) of the nanoemulsion of 25-OCH3-PPD-phospholipid complex were higher than that of free compound by 3.9- and 3.5-folds.
Collapse
Affiliation(s)
- Xiangrong Zhang
- Department of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education
- Department of Pharmaceutics, School of Pharmacy
| | - Yi Zhang
- Department of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education
| | - Shuang Guo
- Department of Biomedical Science, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China
| | - Feifei Bai
- Department of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education
| | - Tong Wu
- Department of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education
| | - Yuqing Zhao
- Department of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education
| |
Collapse
|
|
37
|
Recent expansion of pharmaceutical nanotechnologies and targeting strategies in the field of phytopharmaceuticals for the delivery of herbal extracts and bioactives. J Control Release 2016; 241:110-124. [DOI: 10.1016/j.jconrel.2016.09.017] [Citation(s) in RCA: 86] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2016] [Revised: 09/18/2016] [Accepted: 09/19/2016] [Indexed: 12/18/2022]
|
|
38
|
|
|
39
|
Saoji SD, Dave VS, Dhore PW, Bobde YS, Mack C, Gupta D, Raut NA. The role of phospholipid as a solubility- and permeability-enhancing excipient for the improved delivery of the bioactive phytoconstituents of Bacopa monnieri. Eur J Pharm Sci 2016; 108:23-35. [PMID: 27590125 DOI: 10.1016/j.ejps.2016.08.056] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Revised: 06/30/2016] [Accepted: 08/29/2016] [Indexed: 10/21/2022]
Abstract
In an attempt to improve the solubility and permeability of Standardized Bacopa Extract (SBE), a complexation approach based on phospholipid was employed. A solvent evaporation method was used to prepare the SBE-phospholipid complex (Bacopa Naturosome, BN). The formulation and process variables were optimized using a central-composite design. The formation of BN was confirmed by photomicroscopy, Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD). The saturation solubility, the in-vitro dissolution, and the ex-vivo permeability studies were used for the functional evaluation of the prepared complex. BN exhibited a significantly higher aqueous solubility compared to the pure SBE (20-fold), or the physical mixture of SBE and the phospholipid (13-fold). Similarly, the in-vitro dissolution revealed a significantly higher efficiency of the prepared complex (BN) in releasing the SBE (>97%) in comparison to the pure SCE (~42%), or the physical mixture (~47%). The ex-vivo permeation studies showed that the prepared BN significantly improved the permeation of SBE (>90%), compared to the pure SBE (~21%), or the physical mixture (~24%). Drug-phospholipid complexation may thus be a promising strategy for solubility enhancement of bioactive phytoconstituents.
Collapse
Affiliation(s)
- Suprit D Saoji
- Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur, India
| | - Vivek S Dave
- St. John Fisher College, Wegmans School of Pharmacy, Rochester, NY, USA
| | - Pradip W Dhore
- Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur, India
| | - Yamini S Bobde
- Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur, India
| | - Connor Mack
- St. John Fisher College, Wegmans School of Pharmacy, Rochester, NY, USA
| | - Deepak Gupta
- Lake Erie College of Osteopathic Medicine, School of Pharmacy, Bradenton, FL, USA
| | - Nishikant A Raut
- Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur, India.
| |
Collapse
|
|
40
|
Kumar RP, Abraham A. PVP- coated naringenin nanoparticles for biomedical applications - In vivo toxicological evaluations. Chem Biol Interact 2016; 257:110-8. [PMID: 27417253 DOI: 10.1016/j.cbi.2016.07.012] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2016] [Revised: 07/08/2016] [Accepted: 07/10/2016] [Indexed: 12/18/2022]
Abstract
Naringenin (NAR) is one of the naturally occurring flavonoids found in citrus fruits and exerts a wide variety of pharmacological activities. The clinical relevance of naringenin is limited by its low solubility and minimal bioavailability, owing to its largely hydrophobic ring structure. The aim of the present study is to develop a novel naringenin nanoparticle system (NAR NP) using simple nanoprecipitation technique with polyvinylpyrrolidone (PVP) as the hydrophilic carrier. The synthesized nanoparticles were characterized using XRD, FTIR, SEM and EDX. The characterization study revealed the nanoscale properties and the interactions between NAR and PVP. In vivo toxicological evaluations were carried out at various doses (1, 5, 10 & 50 mg/kg body wt) in male Sprague-Dawley rats in comparison with silver nanoparticle (AgNP) at toxic concentration (50 mg/kg body wt). The altered hepatotoxicity markers, hematology parameters and antioxidant defense system were observed in AgNP- treated rats. But NAR NP - treated rats did not show any biochemical alterations and improved the antioxidant defense indices when compared to control group, by virtue of the pharmacological properties exerted by NAR. The modulatory effect of NAR NP over inflammatory and stress signaling cascades were confirmed by the normalized mRNA expressions of NF-κB, TNF-α and IL-6. The histopathological analysis of liver, kidney and heart reinforce our findings. These studies provide preliminary answers to some of the key biological issues raised over the use and safety of nanoparticles for diagnostic and therapeutic applications. Consequently, we suggest that the safe NAR NP can be used to reduce the dosage of NAR, improve its bioavailability and merits further investigation for therapeutic applications.
Collapse
Affiliation(s)
- R Pradeep Kumar
- Centre for Nanoscience and Nanotechnology, Kariavattom Campus, University of Kerala, Thiruvananthapuram, Kerala, India.
| | - Annie Abraham
- Department of Biochemistry, Kariavattom Campus, University of Kerala, Thiruvananthapuram, Kerala, India.
| |
Collapse
|
|
41
|
Djekic L, Krajisnik D, Micic Z. Polyphenolics-Phospholipid Complexes as Natural Cosmetic Ingredients: Properties and Application. TENSIDE SURFACT DET 2015. [DOI: 10.3139/113.110364] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Abstract
Phospholipids and polyphenolic phytoconstituents may form specific molecular complexes (polyphenolics-phospholipid complexes, phyto-phospholipid complexes) with definite chemical structure, solubility, thermal and spectroscopic characteristics. Furthermore, such specific molecular entities may self-associate into spherical unilamellar vesicles (phyto-vesicles, herbosomes) with size at nano- or microscale. Phyto-phospholipid complexation was recognised as a promising strategy to improve formulation performances and enhance efficiency of herbal polyphenolics with cosmetic relevance in comparison with pure phytoconstituents. This concise review summarizes the current knowledge on preparation methods, physico-chemical properties and aspects of application of the selected phyto-complexes as cosmetic active ingredients.
Collapse
Affiliation(s)
- Ljiljana Djekic
- University of Belgrade – Faculty of Pharmacy , Department of Pharmaceutical technology and Cosmetology, Belgrade , Serbia
| | - Danina Krajisnik
- University of Belgrade – Faculty of Pharmacy , Department of Pharmaceutical technology and Cosmetology, Belgrade , Serbia
| | - Zorica Micic
- Evropa lek d.o.o./GlaxoSmithKline Export Ltd. Representative Office , Belgrade , Serbia
| |
Collapse
|
|
42
|
Vora AK, Londhe VY, Pandita NS. Preparation and characterization of standardized pomegranate extract-phospholipid complex as an effective drug delivery tool. J Adv Pharm Technol Res 2015; 6:75-80. [PMID: 25878977 PMCID: PMC4397622 DOI: 10.4103/2231-4040.154542] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Punicalagins, a pair of anomeric ellagitannins, present in Punica granatum (Pomegranates) are known to possess excellent antioxidant activity in vitro, but poor oral bioavailability. The reasons cited for poor bioavailability are their large molecular size, poor lipophilicity, and degradation by colonic microflora into less active metabolites. The objective of the present research work was to complex the standardized pomegranate extract (SPE) with phospholipid to formulate standardized pomegranate extract-phospholipid complex (SPEPC), characterize it and check its permeability through an ex vivo everted gut sac experiment. SPEPC was prepared by mixing SPE (30% punicalagins) and soya phosphatidylcholine (PC) in 1:1 v/v mixture of methanol and dioxane and spray-drying the mixture. The complex was characterized by infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy. It was evaluated for its octanol solubility, dissolution, and permeability by everted the gut sac technique. The characterization methods confirmed the formation of complex. Increased n-octanol solubility of the complex proved its increased lipophilicity. Dissolution studies revealed that the phospholipid covering may prevent the punicalagins to be released in gastro-intestinal tract, thus preventing their colonic microbial degradation. SPEPC showed better apparent permeability than SPE in an everted gut sac technique. Hence, it could be concluded that phospholipid complex of SPE may be of potential use in increasing the permeability and hence the bioavailability of punicalagins.
Collapse
Affiliation(s)
- Amisha Kamlesh Vora
- Department of Pharmaceutical Chemistry, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai, Maharashtra, India
| | - Vaishali Y Londhe
- Quality Assurance, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai, Maharashtra, India
| | | |
Collapse
|
|
43
|
Vora A, Londhe V, Pandita N. Herbosomes enhance the in vivo antioxidant activity and bioavailability of punicalagins from standardized pomegranate extract. J Funct Foods 2015. [DOI: 10.1016/j.jff.2014.12.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
|
|
44
|
Sethiya NK, Shah P, Rajpara A, Nagar PA, Mishra SH. Antioxidant and hepatoprotective effects of mixed micellar lipid formulation of phyllanthin and piperine in carbon tetrachloride-induced liver injury in rodents. Food Funct 2015; 6:3593-603. [DOI: 10.1039/c5fo00947b] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Phyllanthin, a sparingly water-soluble hepatoprotective lignin obtained from Phyllanthus amarus Schum. et Thonn. (Euphorbiaceae) possesses low bioavailability.
Collapse
Affiliation(s)
- Neeraj K. Sethiya
- Pharmacy Department
- Faculty of Technology and Engineering
- Kalabhavan
- The M. S. University of Baroda
- Vadodara 390002 (Gujarat)
| | - Pankaj Shah
- Pharmacy Department
- Faculty of Technology and Engineering
- Kalabhavan
- The M. S. University of Baroda
- Vadodara 390002 (Gujarat)
| | - Aruna Rajpara
- Pharmacy Department
- Faculty of Technology and Engineering
- Kalabhavan
- The M. S. University of Baroda
- Vadodara 390002 (Gujarat)
| | - P. A. Nagar
- Pharmacy Department
- Faculty of Technology and Engineering
- Kalabhavan
- The M. S. University of Baroda
- Vadodara 390002 (Gujarat)
| | - S. H. Mishra
- Pharmacy Department
- Faculty of Technology and Engineering
- Kalabhavan
- The M. S. University of Baroda
- Vadodara 390002 (Gujarat)
| |
Collapse
|
|
45
|
Mir IA, Tiku AB. Chemopreventive and therapeutic potential of "naringenin," a flavanone present in citrus fruits. Nutr Cancer 2014; 67:27-42. [PMID: 25514618 DOI: 10.1080/01635581.2015.976320] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Cancer is one of the major causes of deaths in developed countries and is emerging as a major public health burden in developing countries too. Changes in cancer prevalence patterns have been noticed due to rapid urbanization and changing lifestyles. One of the major concerns is an influence of dietary habits on cancer rates. Approaches to prevent cancer are many and chemoprevention or dietary cancer prevention is one of them. Therefore, nutritional practices are looked at as effective types of dietary cancer prevention strategies. Attention has been given to identifying plant-derived dietary agents, which could be developed as a promising chemotherapeutic with minimal toxic side effects. Naringenin, a phytochemical mainly present in citrus fruits and tomatoes, is a frequent component of the human diet and has gained increasing interest because of its positive health effects not only in cancer prevention but also in noncancer diseases. In the last few years, significant progress has been made in studying the biological effects of naringenin at cellular and molecular levels. This review examines the cancer chemopreventive/therapeutic effects of naringenin in an organ-specific format, evaluating its limitations, and its considerable potential for development as a cancer chemopreventive/therapeutic agent.
Collapse
Affiliation(s)
- Irfan Ahmad Mir
- a Department of Clinical Biochemistry , University of Kashmir , Kashmir , India
| | | |
Collapse
|
|
46
|
Wang H, Cui Y, Fu Q, Deng B, Li G, Yang J, Wu T, Xie Y. A phospholipid complex to improve the oral bioavailability of flavonoids. Drug Dev Ind Pharm 2014; 41:1693-703. [DOI: 10.3109/03639045.2014.991402] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
|
|
47
|
Khatik R, Dwivedi P, Shukla A, Srivastava P, Rath SK, Paliwal SK, Dwivedi AK. Development, characterization and toxicological evaluations of phospholipids complexes of curcumin for effective drug delivery in cancer chemotherapy. Drug Deliv 2014; 23:1067-78. [DOI: 10.3109/10717544.2014.936988] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
| | | | | | - Pallavi Srivastava
- Toxicology Division, CSIR – Central Drug Research Institute, Lucknow, Uttar Pradesh, India, and
| | - Srikanta Kumar Rath
- Toxicology Division, CSIR – Central Drug Research Institute, Lucknow, Uttar Pradesh, India, and
| | - Sarvesh Kumar Paliwal
- Department of Pharmaceutical Sciences, Banasthali VidyaPeeth, Banasthali, Rajasthan, India
| | | |
Collapse
|
|
48
|
Bhattacharyya S, Ahmmed SM, Saha BP, Mukherjee PK. Soya phospholipid complex of mangiferin enhances its hepatoprotectivity by improving its bioavailability and pharmacokinetics. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2014; 94:1380-8. [PMID: 24114670 DOI: 10.1002/jsfa.6422] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Revised: 09/06/2013] [Accepted: 10/01/2013] [Indexed: 06/02/2023]
Abstract
BACKGROUND Mangiferin is a xanthonoid present in Mangifera indica. It has been reported for a variety of pharmacological activities, including hepatoprotection. However, the major disadvantage of mangiferin is its reduced biological activity due to poor absorption, low bioavailability and rapid elimination from the body after administration. The aim of this study was to prepare a phospholipid complex of mangiferin to overcome these limitations and to investigate the impact of the complex on hepatoprotective activity and bioavailability. RESULTS The results showed that the complex has an enhanced hepatoprotective and in vivo antioxidant activity as compared to pure mangiferin at the same dose level (30 and 60 mg kg⁻¹). The complex restored the levels of serum hepatic marker enzymes and liver antioxidant enzymes with respect to carbon tetrachloride-treated animals. The complex also increased the bioavailability of mangiferin in rat serum by 9.75-fold compared to pure mangiferin at the same dose level and enhanced the elimination half-life (t(1/2 el)) from 1.71 ± 0.12 h⁻¹ to 3.52 ± 0.27 h⁻¹. CONCLUSION The results suggested that the complexation of mangiferin with soya phospholipid enhanced the hepatoprotection and in vivo antioxidant activity, which may be due to the improved bioavailability and pharmacokinetics of mangiferin in rat serum.
Collapse
Affiliation(s)
- Sauvik Bhattacharyya
- Department of Pharmaceutical Technology, School of Natural Product Studies, Jadavpur University, Kolkata, 700032, India
| | | | | | | |
Collapse
|
|
49
|
Hermenean A, Ardelean A, Stan M, Hadaruga N, Mihali CV, Costache M, Dinischiotu A. Antioxidant and hepatoprotective effects of naringenin and its β-cyclodextrin formulation in mice intoxicated with carbon tetrachloride: a comparative study. J Med Food 2014; 17:670-7. [PMID: 24611872 DOI: 10.1089/jmf.2013.0007] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The present study evaluated the antioxidant and hepatoprotective effects of the flavonoid naringenin (NGN) and its β-cyclodextrin formulation at a dose of 50 mg/kg b.w. The assessment was done by the investigation of serum-enzymatic and liver antioxidant activity, histopathological and ultrastructural changes in male Swiss mice, which were subjected to acute experimental intoxication with CCl4. Formulated and free flavonoid were orally given to mice for 7 days and then were intraperitoneally injected with 1.0 mL/kg CCl4 on the 8th day. After 24 h of CCl4 administration, an increase in the levels of transaminases aspartate aminotransferase and alanine aminotransferase activities and malondialdehyde concentration occurred and a significant decrease in superoxide dismutase, catalase glutathione-peroxidase activities, and glutathione levels was detected as well. These were accompanied by extended centrilobular necrosis, steatosis, fibrosis, and an altered ultrastructure of hepatocytes. Pretreatment with formulated or free flavonoid retained the biochemical markers to control values. Histopathological and electron-microscopic examination confirmed the biochemical results. In conclusion, both NGN and NGN/β-cyclodextrin complex showed antioxidant and hepatoprotective effects against injuries induced by CCl4.
Collapse
Affiliation(s)
- Anca Hermenean
- 1 Department of Histology, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad , Arad, Romania
| | | | | | | | | | | | | |
Collapse
|
|
50
|
Ramprasath T, Senthamizharasi M, Vasudevan V, Sasikumar S, Yuvaraj S, Selvam GS. Naringenin confers protection against oxidative stress through upregulation of Nrf2 target genes in cardiomyoblast cells. J Physiol Biochem 2014; 70:407-15. [PMID: 24526395 DOI: 10.1007/s13105-014-0318-3] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Accepted: 01/29/2014] [Indexed: 12/22/2022]
Abstract
Cardiovascular diseases are the major health concern and the leading cause of death. Numerous studies have shown that oxidative stress stimuli have been incriminated in the pathogenesis of both acute and chronic heart disease. Though it is well known that bioflavonoids protect cells against reactive oxygen species (ROS)-induced damage, the molecular mechanisms involved are uncertain. Understanding the possible intracellular signaling pathways triggered by flavonoids will help to overcome the cardiac diseases resulting from oxidative stress. In the present study, we investigated whether naringenin (NGN) supplementation would improve the antioxidant defence under oxidative stress through the activation of Nrf2 signaling in cultured cardiomyoblast. NGN pretreatment significantly reduced stress-mediated apoptotic cell death and lipid peroxidation and showed increased level of reduced glutathione in H2O2-treated cardiomyoblast. In addition, NGN inhibited the production of NO and trigged the synthesis of antioxidant marker enzymes. Gene expression studies revealed that NGN upregulated the transcription of Akt and downregulated NF-κB and Caspase 3 genes. Notably, transcription of Nrf2 and its target genes was also upregulated. Taken together, the present study revealed that NGN elicits potent cytoprotective effect against oxidative stress by regulating Nrf2 and its target genes. In conclusion, the present work suggests that improving Nrf2 signaling by NGN supplementation would be a rational approach to facilitate ROS detoxification by augmenting both expression and activity of phase II detoxification enzymes for the alleviation of cardiac complications.
Collapse
Affiliation(s)
- Tharmarajan Ramprasath
- Molecular Cardiology Unit, Department of Biochemistry (Center for Excellence in Genomic Sciences), School of Biological Sciences, Madurai Kamaraj University, Madurai, 625 021, Tamilnadu, India
| | | | | | | | | | | |
Collapse
|