Naringin and naringeninin as anticancer agents and adjuvants in cancer combination therapy; efficacy and molecular mechanisms of action, a comprehensive narrative review

Published on Sep 1, 2021in Pharmacological Research5.893
· DOI :10.1016/J.PHRS.2020.105264
Zahra Memariani9
Estimated H-index: 9
(Babol University of Medical Sciences),
Syed Qamar Abbas1
Estimated H-index: 1
(Sarhad University of Science & IT, Ring Road (Hayatabad Link) Peshawar)
+ 2 AuthorsAroona Chabra11
Estimated H-index: 11
(Mazandaran University of Medical Sciences)
Although the rates of many cancers are controlled in Western countries, those of some cancers, such as lung, breast, and colorectal cancer are currently increasing in many low- and middle-income countries due to increases in risk factors caused by development and societal problems. Additionally, endogenous factors, such as inherited mutations, steroid hormones, insulin, and insulin-like growth factor systems, inflammation, oxidative stress, and exogenous factors (including tobacco, alcohol, infectious agents, and radiation), are believed to compromise cell functions and lead to carcinogenesis. Chemotherapy, surgery, radiation therapy, hormone therapy, and targeted therapies are some examples of the approaches used for cancer treatment. However, various short- and long-term side effects can also considerably impact patient prognosis based on clinical factors associated with treatments. Recently, increasing numbers of studies have been conducted to identify novel therapeutic agents from natural products, among which plant-derived bioactive compounds have been increasingly studied. Naringin (NG) and its aglycone naringenin (NGE) are abundantly present in citrus fruits, such as grapefruits and oranges. Their anti-carcinogenic activities have been shown to be exerted through several cell signal transduction pathways. Recently, different pharmacological strategies based on combination therapy, involving NG and NGE with the current anti-cancer agents have shown prodigious synergistic effects when compared to monotherapy. Besides, NG and NGE have been reported to overcome multidrug resistance, resulting from different defensive mechanisms in cancer, which is one of the major obstacles of clinical treatment. Thus, we comprehensively reviewed the inhibitory effects of NG and NGE on several types of cancers through different signal transduction pathways, the roles on sensitizing with the current anticancer medicines, and the efficacy of the cancer combination therapy.
#1Cord Naujokat (University Hospital Heidelberg)H-Index: 2
#2Dwight L. McKeeH-Index: 3
Cancer stem cells (CSCs) constitute a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity, and the ability to give rise to the heterogeneous lineages of cancer cells that comprise the tumor. CSCs exhibit intrinsic mechanisms of resistance to virtually all conventional cancer therapeutics, allowing them to survive current cancer therapies and to initiate tumor recurrence and metastasis. Different pathways and mechanisms that confer resistance and survival of CSCs,...
15 CitationsSource
#1Emran Habibi (Mazandaran University of Medical Sciences)H-Index: 9
#2Mohammad Shokrzadeh (Mazandaran University of Medical Sciences)H-Index: 20
Last. Fatemeh Salehi (Mazandaran University of Medical Sciences)H-Index: 4
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Objective To evaluate the protective effect of Zataria multiflora extract, an antioxidative medicinal plant, against cyclophosphamide (CP)-induced oxidative lung damage in mice.
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Naringin and naringenin are major flavonoids in citrus fruits. This study investigated the pharmacokinetics of naringin and naringenin in rats. Single dose of naringenin was administered to rats via intravenous bolus and oral route, whereas naringin was given orally as single dose and multiple doses (twice daily for 9 days). The serum concentrations of naringenin were assayed by HPLC method prior to and after hydrolysis with β-glucuronidase and sulfatase, respectively. After intravenous bolus of...
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#1Ruyin Lin (Fujian Medical University)H-Index: 2
#2Xinxin Hu (Fujian Medical University)H-Index: 1
Last. Huiqing Chen (Fujian Medical University)H-Index: 2
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Naringin is a promising anticancer bioflavonoid phytochemical, mainly extracted from citrus fruits. This study evaluates the antiproliferative effect and the cell death mechanism induced by naringin on cervical cancer (CC) cells. Our results demonstrated that naringin exerts significant inhibition in cell viability and exhibits IC50 value 745, 764, 793 microM against C33A, SiHa, and HeLa cells respectively. Annexin V FITC and immunoblotting analysis reveal significant apoptosis induction in cell...
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#1Peibo Li (SYSU: Sun Yat-sen University)H-Index: 19
#2Hao Wu (SYSU: Sun Yat-sen University)H-Index: 5
Last. Weiwei Su (SYSU: Sun Yat-sen University)H-Index: 28
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Abstract Naringin is a type of bioflavonoid widely found in a lot of dietary products. Our previous studies revealed that naringin was practically non-toxic for SD rats in an oral acute toxicity study and the no-observed-adverse-effect-level (NOAEL) in SD rats was greater than 1250 mg/kg/day when administered by oral gavage for 13 consecutive weeks or 6 consecutive months. Herein we assessed the safety of naringin in Beagle dogs. Acute oral administration of naringin was done as a single bolus d...
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#1Melaine Priscila Fidelix (UNESP: Sao Paulo State University)H-Index: 3
#2Dragan Milenkovic (UC Davis: University of California, Davis)H-Index: 32
Last. Thais Borges Cesar (UNESP: Sao Paulo State University)H-Index: 17
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The impact of habitual orange juice consumption on microbiota, lipid and glycides metabolism was investigated in a controlled clinical trial. Ten women who had a regular diet without orange juice for 30 days (OJ-free diet), followed by a regular diet plus 300 ml/d orange juice for 60 days (OJ-Diet), and 30 days with regular diet without orange juice (Washout). It was monitoring biochemical and dietary parameters, and blood, urine and stool samples were collected every 30 days until the end of th...
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#1Mahshid Moballegh Nasery (KMU: Kerman Medical University)H-Index: 1
#2Banafshe Abadi (KMU: Kerman Medical University)H-Index: 2
Last. Gautam Sethi (NUS: National University of Singapore)H-Index: 111
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Todays, nano-pharmaceutics is emerging as an important field of science to develop and improve efficacy of different drugs. Although nutraceuticals are currently being utilized in the prevention and treatment of various chronic diseases such as cancers, a number of them have displayed issues associated with their solubility, bioavailability, and bio-degradability. In the present review, we focus on curcumin, an important and widely used polyphenol, with diverse pharmacological activities such as...
58 CitationsSource
#1Teodora Costea (UMFCD: Carol Davila University of Medicine and Pharmacy)H-Index: 4
#2Oana Cezara Vlad (UMFCD: Carol Davila University of Medicine and Pharmacy)H-Index: 1
Last. Maria-Magdalena Mocanu (UMFCD: Carol Davila University of Medicine and Pharmacy)H-Index: 9
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The aim of the manuscript is to discuss the influence of plant polyphenols in overcoming multidrug resistance in four types of solid cancers (breast, colorectal, lung and prostate cancer). Effective treatment requires the use of multiple toxic chemotherapeutic drugs with different properties and targets. However, a major cause of cancer treatment failure and metastasis is the development of multidrug resistance. Potential mechanisms of multidrug resistance include increase of drug efflux, drug i...
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#1Candida J. RebelloH-Index: 14
#2Robbie A. BeylH-Index: 15
Last. Leanne M. RedmanH-Index: 57
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AIMS: To evaluate the safety and pharmacokinetics of naringenin in healthy adults consuming whole-orange (Citrus sinensis) extract. METHODS AND METHODS: In a single-ascending-dose randomized crossover trial, 18 adults ingested doses of 150 mg (NAR150), 300 mg (NAR300), 600 mg (NAR600) and 900 mg (NAR900) naringenin or placebo. Each dose or placebo was followed by a wash-out period of at least 1 week. Blood safety markers were evaluated pre-dose and 24 hours post-dose. Adverse events (AEs) were r...
25 CitationsSource
#1Muhammad Fiaz Qamar (BZU: Bahauddin Zakariya University)H-Index: 6
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Naringin, a natural flavonoid mainly found in citrus fruit, has been reported to exert a positive effect on improving skeletal muscle health. However, the effects and potential mechanisms of naringin on skeletal muscle fiber switching is still unclear. Here, we discovered that oral administration of naringin increased the low-speed running time, four-limb hanging time, body oxygen consumption in mice, enhanced aerobic enzyme activity, MyHC I expression, and slow-twitch fiber percentage in mice s...
#1Pratibha Pandey (Noida Institute of Engineering and Technology)H-Index: 6
#2Fahad Khan (Noida Institute of Engineering and Technology)H-Index: 7
Abstract null null Hesperidin, a phytoactive compound, is an abundant and economical dietary bioflavonoid possessing numerous biological and medicinal benefits. Several studies have strongly proven the significant chemotherapeutic potential of hesperidin. Therefore this review is an effort to bring together the existing studies demonstrating hesperidin as a potential anticancer agent with its mode of action reported in the therapeutic strategies for numerous cancer types. Hesperidin acts via mod...
#1Karolina Chairez-Cantu (Tec: Monterrey Institute of Technology and Higher Education)H-Index: 1
#2Alonso Ornelas-González (Tec: Monterrey Institute of Technology and Higher Education)H-Index: 1
Lung cancer is the third most common cause of death and the main factor of cancer-related deaths in both males and females in the United States to the rest of the world. Diagnosis at an important level is associated with high mortality in the population of cases. Herein, we present a very easy and cost-effective method that incorporates drugs reconstruction, tumor-specific targeting supramolecular nanoassembly, and therapeutically to overcome the different challenges raised by the distribution o...
#1Maryam Ghanbari-Movahed (Kermanshah University of Medical Sciences)H-Index: 1
#2Gloria JacksonH-Index: 1
Last. Anupam Bishayee (Lake Erie College of Osteopathic Medicine)H-Index: 64
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Background: Natural product-based cancer preventive and therapeutic entities, such as flavonoids and their derivatives, are shown to have a noticeable capability to suppress tumor formation and cancer cell growth. Naringin, a natural flavanone glycoside present in various plant species, has been indicated to modulate different signaling pathways and interact with numerous cell signaling molecules, which allows for an extensive variety of pharmacological actions, such as amelioration of inflammat...
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