Safety evaluation of tangeretin and the effect of using emulsion-based delivery system: Oral acute and 28-day sub-acute toxicity study using mice

Ting, Yuwen; Chiou, Yi‐Shiou; Jiang, Yike; Pan, Min‐Hsiung; Lin, Zhong‐Zhe; Huang, Qingrong

doi:10.1016/j.foodres.2015.04.031

Cited by 22 publications

(20 citation statements)

References 29 publications

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“…However, daily use of low dose tangeretin displayed a U-shaped dose-response curve including hepatic changes. It was concluded that PMF available as a beneficial ingredient in the human diet could be applied safely at different conditions [70]. Consistent with the previous study, Vanhoecke et al proved the safety of Tangeretin when administrated orally to experimental mice.…”

Section: Safety and Toxicity Of Tangeretinsupporting

confidence: 70%

“…In order to investigate the possibility of oral toxicity, tangeretin was used as a typical compound for safety assessment as it is considered one of the most common PMF that originated from natural sources [70]. In a study carried out by Ting et al to examine the acute oral toxicity in mice genders, tangeretin was administrated in 1000, 2000, and 3000 mg/kg from a single gavage in an oil suspension.…”

Section: Safety and Toxicity Of Tangeretinmentioning

confidence: 99%

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Therapeutic Implications of a Polymethoxylated Flavone, Tangeretin, in the Management of Cancer via Modulation of Different Molecular Pathways

Arafa

Shurrab

Buabeid

2021

Advances in Pharmacological and Pharmaceutical Sciences

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Chemotherapeutics can induce oxidative stress, inflammation, apoptosis, mitochondrial dysfunction, and abnormalities in neurotransmitter metabolism leading to toxicity. Because there have been no therapeutic strategies developed to target inflammation and oxidative stress, there is a continuing need for new and improved therapy. As a result, there has been increasing interest in complementary and alternative medicine with anticancer potential. Studies have shown that the antioxidant activities and anti-inflammatory effects of citrus fruits are promising natural phytochemicals in the development of new anticancer agents. Tangeretin is a naturally polymethoxylated flavone compound extracted from the citrus peel that has shown significant intestinal absorption and adequate bioavailability, with the added benefit of promoting longevity. In addition, tangeretin is known to exhibit considerable selective toxicity to many types of cancer cell proliferation such as ovarian, brain, blood, and skin cancer. Evidence indicates that tangeretin acts through several mechanisms including growth inhibition, induction of apoptosis, autophagy, antiangiogenesis, and estrogenic-like effects. Furthermore, tangeretin works through mitigating levels of inflammatory mediators in the immune system. Using tangeretin in combination with clinically applied anticancer drugs could be a good strategy for increasing the efficiency of these agents and protecting noncancerous cells from damage caused by chemotherapy. The purpose of this review is to highlight the protective effects of a novel natural product, tangeretin against chemotherapeutic-induced toxicity. The development of chemoprevention strategies can lead to significant health care improvement in cancer survivors. Thus, study outcomes may attract more investigators to conduct tangeretin-related research and find out potentially significant impacts on health care of cancer patients and decreased health problems associated with chemotherapeutics-induced toxicity.

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Section: Safety and Toxicity Of Tangeretinsupporting

confidence: 70%

Section: Safety and Toxicity Of Tangeretinmentioning

confidence: 99%

Therapeutic Implications of a Polymethoxylated Flavone, Tangeretin, in the Management of Cancer via Modulation of Different Molecular Pathways

Arafa

Shurrab

Buabeid

2021

Advances in Pharmacological and Pharmaceutical Sciences

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“…However, to date, information on the toxicology profile for PMFs is still limited. Ting et al (2015) [ 41 ] reported that rats administered tangeretin up to 1000 to 3000 mg/kg bw showed no evidence of death nor significant change of clinical chemistry in oral acute and sub-acute study. Alterations of the hepatic cell and lipid profile increased dose-dependently and exhibited a distinct injury recovery pattern.…”

Section: Discussionmentioning

confidence: 99%

Polymethoxyflavones: Novel β-Secretase (BACE1) Inhibitors from Citrus Peels

Youn

Lee

et al. 2017

Nutrients

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Beta-site amyloid precursor protein (APP) cleaving enzyme1 (BACE1) catalyzes the rate-limiting step of amyloid-β protein (Aβ) generation, and is considered as a prime target for Alzheimer’s disease (AD). In search of a candidate for AD prevention, our efforts exploring the natural BACE1 inhibitor have led to the finding of nobiletin, tangeretin, and sinensetin—representative compounds of polymethoxyflavones (PMFs). Tangeretin exhibited the strongest BACE1 inhibition (IC50, 4.9 × 10−5 M), followed by nobiletin and sinensetin with IC50 values of 5.9 × 10−5 M and 6.3 × 10−5 M, respectively. In addition, all compounds reacted in a non-competitive manner with the substrate. Docking analysis results for complexes with BACE1 indicated that SER10 and THR232 residues of BACE1 hydrogen bonded with two oxygen atoms of tangeretin, while three additional BACE1 residues (ALA157, VAL336 and THR232) interacted with three oxygen atoms of nobiletin. Furthermore, sinensetin formed four hydrogen bonds through nitrogen atoms of TYR71, LYS75, and TRP76, and an oxygen atom of TYR198. Furthermore, the lowest-energy conformations of the most proposed complexes of sinensetin, nobiletin, and tangeretin with BACE1 were −7.2, −7.0, and −6.8 kcal/mol, respectively. Taken together, our results suggest that these polymethoxyflavones (PMFs) might be considered as promising BACE1 inhibitory agents that could lower Aβ production in AD.

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“…leucemia, resistencia a los quimioterapéuticos (6) ; la demanda de estos productos ha llevado a la necesidad de evaluar no solo la eicacia, sino también los problemas de seguridad (24) . Se ha realizado la investigación con el objetivo determinar la seguridad de la asociación del extracto atomizado del rizoma de Curcuma longa, lores de Cordia lutea, y hojas de Annona muricata, administrado a ratas por vía oral una vez al día durante 28 días.…”

Section: Resultsunclassified

Estudio de toxicidad a 28 días del extracto atomizado de rizoma de Curcuma longa (A4R), lores de Cordia lutea (A4F) y hojas de Annona muricata (A4L) en un modelo murino

Arroyo-Acevedo

Franco-Quino

Figueroa

et al. 2016

Rev. per. med. integr.

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La asociación de las tres plantas ha sido aprobada por la Institución de Salud en Canadá bajo la forma de extracto liofilizado, la cual ha demostrado poseer efectos terapéuticos. Objetivo: Determinar la seguridad de la asociación del extracto atomizado del rizoma de Curcuma longa (A4R), flores de Cordia lutea (A4F) y hojas de Annona muricata (A4L) a una dosis repetida durante 28 días por vía oral en ratas. Materiales y Métodos: Diseño experimental, se utilizaron 40 ratas Holtzman (20 machos – 20 hembras); se siguió las directrices o normas de la Organisation for Economic Cooperation and Development (OECD) Norma 407; se administró el extracto atomizado durante 28 días por vía oral, se realizaron las observaciones, registro de signos y evolución semanal del peso corporal de los animales, al final se extrajo muestra de sangre para estudio hematológico y bioquímico, posteriormente fueron sacrificados para estudio anatomopatológico de hígado, riñón, corazón, médula, cerebro, páncreas, bazo; se aplicó el ANOVA, considerando el valor p<0.05 para la significancia. Resultados: Al administrar la asociación en forma de extracto atomizado, se observó una evolución temporal homogénea del peso corporal. No hubo variación significativa en los niveles de glucemia, urea, colesterol, triglicéridos, bilirrubina indirecta, transaminasas (GPT–GOT), fosfatasa alcalina ni hemoglobina (p>0,05); Conclusión: Los hallazgos demuestran que el extracto atomizado del rizoma de Curcuma longa (A4R), flores de Cordia lutea (A4F) y hojas de Annona muricata (A4L) no es toxico al ser administrado por un periodo de 28 días en ratas.

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Safety evaluation of tangeretin and the effect of using emulsion-based delivery system: Oral acute and 28-day sub-acute toxicity study using mice

Cited by 22 publications

References 29 publications

Therapeutic Implications of a Polymethoxylated Flavone, Tangeretin, in the Management of Cancer via Modulation of Different Molecular Pathways

Therapeutic Implications of a Polymethoxylated Flavone, Tangeretin, in the Management of Cancer via Modulation of Different Molecular Pathways

Polymethoxyflavones: Novel β-Secretase (BACE1) Inhibitors from Citrus Peels

Estudio de toxicidad a 28 días del extracto atomizado de rizoma de Curcuma longa (A4R), lores de Cordia lutea (A4F) y hojas de Annona muricata (A4L) en un modelo murino

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