Bitter orange ( Citrus aurantium L.) extract subchronic 90-day safety study in rats

Deshmukh, Narendra; Stohs, Sidney J.; Magar, C.C.; Kale, Anand S.; Sowmya, B.

doi:10.1016/j.toxrep.2017.11.002

Cited by 26 publications

(17 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanical pain sensation of mice tail was assessed by observation of tail clamp dislodgment attempts of mice as per Takagi et al method [44] with minor changes of Moon et al [45] and Deshmukh et al [46]. Clinically, it similar to mechanical compression type of pain sensation.…”

Section: Methodsmentioning

confidence: 99%

Ameliorative effect of gallic acid in paclitaxel-induced neuropathic pain in mice

Kaur¹,

Muthuraman

2019

Toxicology Reports

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

Ameliorative effect of gallic acid in paclitaxel-induced neuropathic pain in mice

Kaur¹,

Muthuraman

2019

Toxicology Reports

View full text Add to dashboard Cite

show abstract

“…For the sake of comparison, it should be noted that the oral LD50 of sodium chloride, common table salt, is about 3000 mg/kg. The oral administration of a 50% p ‐synephrine bitter orange extract at a dose of 2000 mg/kg to female rats for four consecutive days did not have any toxicological effects (Deshmukh et al ., ), while a dose of 1000 mg/kg for 90 days produced no deaths or serious adverse effects (Deshmukh et al ., ). The animals exhibited burrowing of the heads in the bedding material and piloerection, which disappeared by the end of the study.…”

Section: Animal Studiesmentioning

confidence: 97%

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

Stohs

2017

Phytotherapy Research

View full text Add to dashboard Cite

Citrus aurantium L. (bitter orange) extracts that contain p‐synephrine as the primary protoalkaloid are widely used for weight loss/weight management, sports performance, appetite control, energy, and mental focus and cognition. Questions have been raised about the safety of p‐synephrine because it has some structural similarity to ephedrine. This review focuses on current human, animal, in vitro, and mechanistic studies that address the safety, efficacy, and mechanisms of action of bitter orange extracts and p‐synephrine. Numerous studies have been conducted with respect to p‐synephrine and bitter orange extract because ephedra and ephedrine were banned from use in dietary supplements in 2004. Approximately 30 human studies indicate that p‐synephrine and bitter orange extracts do not result in cardiovascular effects and do not act as stimulants at commonly used doses. Mechanistic studies suggest that p‐synephrine exerts its effects through multiple actions, which are discussed. Because p‐synephrine exhibits greater adrenergic receptor binding in rodents than humans, data from animals cannot be directly extrapolated to humans. This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p‐synephrine are safe for use in dietary supplements and foods at the commonly used doses. Copyright © 2017 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.

show abstract

“…Our results on FCPE in this study were generally in line with the previous studies on other citrus species, but also there were different findings. Table 3 Absolute and relative organ weight of SD rats orally administered with fermented Citrus sunki peel extract for 90 days (Continued) Among a handful of citrus species whose toxicity has been preclinically evaluated, C. aurantium L. (bitter orange) extract has been most extensively studied [29]; > 5000 mg/kg for LD50 [30], 1000 mg/kg for NOAEL [31] and no developmental toxicity at 100 mg/kg [32]. A recent study on C. unshiu Marcow.…”

Section: Discussionmentioning

confidence: 99%

“…Among a handful of citrus species whose toxicity has been preclinically evaluated, C. aurantium L. (bitter orange) extract has been most extensively studied [ 29 ]; > 5000 mg/kg for LD50 [ 30 ], 1000 mg/kg for NOAEL [ 31 ] and no developmental toxicity at 100 mg/kg [ 32 ]. A recent study on C. unshiu Marcow.…”

Section: Discussionmentioning

confidence: 99%

In vivo and in vitro safety evaluation of fermented Citrus sunki peel extract: acute and 90-day repeated oral toxicity studies with genotoxicity assessment

Park

Cho

Kim

et al. 2020

BMC Complement Med Ther

View full text Add to dashboard Cite

Background Citrus sunki Hort. ex Tanaka peel has been traditionally used as an ingredient in folk medicine due to its therapeutic effects on promotion of splenic health and diuresis as well as relief of gastrointestinal symptoms. Although a growing interest in health-promoting natural products and the development of highly concentrated products have facilitated consumption of C. sunki peel, its safety assessment has not been explored, posing a potential health risk. In this study, we carried out a series of systemic and genetic toxicity tests on fermented C. sunki peel extract (FCPE) to provide the essential information required for safe use in human. Methods We conducted acute and 90-day repeated oral toxicity studies in Sprague-Dawley rats to evaluate systemic toxicity, and three genotoxicity assays to measure bacterial mutation reversion, cellular chromosome aberration and in vivo micronucleus formation. Results Single oral administration of FCPE did not cause any clinical signs and lethality in all animals, establishing LD50 to be over 2000 mg/kg BW. Repeated administration of up to 2000 mg/kg BW FCPE for 90 days revealed no test substance-related toxicity as demonstrated in analysis of body weight gain, food/water intake, blood, serum biochemistry, organ weight and histopathology, collectively determining that the no-observable-adverse-effect-level of FCPE is over 2000 mg/kg BW. In addition, we detected no mutagenicity and clastogenicity in FCPE at 5000 μg/plate for the in vitro assays and 2000 mg/kg BW for the in vivo micronucleus test. Conclusion FCPE did not cause systemic and genetic toxicity in our model systems at the tested dose levels. These results suggest a guideline for safe consumption of C. sunki peel in human.

show abstract

Bitter orange ( Citrus aurantium L.) extract subchronic 90-day safety study in rats

Abstract: Graphical abstract

Cited by 26 publications

References 25 publications

Ameliorative effect of gallic acid in paclitaxel-induced neuropathic pain in mice

Ameliorative effect of gallic acid in paclitaxel-induced neuropathic pain in mice

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

In vivo and in vitro safety evaluation of fermented Citrus sunki peel extract: acute and 90-day repeated oral toxicity studies with genotoxicity assessment

Contact Info

Product

Resources

About