Assessing the safety of an Ephedrae Herba aqueous extract in rats: A repeat dose toxicity study

Han, Hyoung-Yun; Huh, Jung-Im; Han, So-Ri; Kang, Myung-Gyun; Yoon, Seokjoo; Han, Ji-Seok; Lee, Byoung‐Seok; Kim, Jeong Ah; Min, Byung‐Sun

doi:10.1016/j.yrtph.2018.01.027

Cited by 18 publications

(13 citation statements)

References 12 publications

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“…EH, the dried aerial parts of E. sinica , has been widely used in Asian traditional medicine to treat bronchial asthma, cold, fever, headache, and cough (Han et al. 2018). Recently, and especially in the Republic of Korea, EH has been used in antiobesity prescriptions in traditional medicine clinics (Shin and Yoon 2012; Roh et al.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Ephedrae Herba methanol extract on high-fat diet-induced hyperlipidaemic mice

Lee

Lim

et al. 2019

Pharmaceutical Biology

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Context: Ephedrae Herba (EH), the dried stems and leaves of Ephedra sinica Stapf., E. intermedia Schrenk et C. A. Mey., or E. equisetina Bge. (Ephedraceae [Ephedra]) is used to treat respiratory diseases. Recently, especially in the Republic of Korea, EH has also been used for weight reduction. Objective: We evaluated the effects and molecular targets of methanol EH extract (EHM) on high-fat diet (HFD)-induced hyperlipidemic ICR mice. Materials and methods: EHM was orally administered (100 mg/kg body weight/day) for 3 weeks. We observed changes in body weight (BW), total cholesterol (TC), high-density lipoprotein-cholesterol, and triglycerides to evaluate the physiological changes induced by HFD or EHM administration. To evaluate lipid peroxidation and liver toxicity, malondialdehyde and blood alanine aminotransferase levels were measured. In addition to analyzing liver gene expression profiles, EHM target proteins were identified using a protein interaction database. Results: EHM administration for 3 weeks significantly (p < 0.05) decreased TC and triglyceride levels without altering BW in mice, and gene expression levels in the livers of EHM-treated mice were restored at 34.0% and 48.4% of those up-or down-regulated by hyperlipidaemia, respectively. Proteins related to DNA repair and energy metabolism were identified via protein interaction network analysis as molecular targets of EHM that play key roles in ameliorating hyperlipidaemia. Discussion and conclusions: EHM regulated hyperlipidaemia by decreasing total blood lipid and triglyceride levels in hyperlipidaemic mice. EHM showed preventive effects against hyperlipidaemia in mice, possibly via the regulation of DNA repair and the expression of energy metabolism-related genes and proteins.

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Section: Discussionmentioning

confidence: 99%

“…However, food supplements containing ephedrines also represent substantial health risks, and consequently, many countries have instituted bans of all over-the-counter drugs containing ephedrine (Han et al. 2018; Sellami et al. 2018).…”

Section: Introductionmentioning

confidence: 99%

Effect of Ephedrae Herba methanol extract on high-fat diet-induced hyperlipidaemic mice

Lee

Lim

et al. 2019

Pharmaceutical Biology

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“…These results suggest that Ephedra may contribute to increased blood pressure, causing kidney disorders. The NOAEL (No observed adverse effect level) was determined at 125 mg/kg/day dose [ 163 ]. Although the pathogenesis of the cardiac toxic effects of Ephedra species remains incomplete, the available evidence indicates that its use may be dangerous as it may be associated with some serious medical complications.…”

Section: Toxicitymentioning

confidence: 99%

A Review of the Ephedra genus: Distribution, Ecology, Ethnobotany, Phytochemistry and Pharmacological Properties

et al. 2020

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Ephedra is one of the largest genera of the Ephedraceae family, which is distributed in arid and semiarid regions of the world. In the traditional medicine from several countries some species from the genus are commonly used to treat asthma, cold, flu, chills, fever, headache, nasal congestion, and cough. The chemical constituents of Ephedra species have been of research interest for decades due to their contents of ephedrine-type alkaloids and its pharmacological properties. Other chemical constituents such as phenolic and amino acid derivatives also have resulted attractive and have provided evidence-based supporting of the ethnomedical uses of the Ephedra species. In recent years, research has been expanded to explore the endophytic fungal diversity associated to Ephedra species, as well as, the chemical constituents derived from these fungi and their pharmacological bioprospecting. Two additional aspects that illustrate the chemical diversity of Ephedra genus are the chemotaxonomy approaches and the use of ephedrine-type alkaloids as building blocks in organic synthesis. American Ephedra species, especially those that exist in Mexico, are considered to lack ephedrine type alkaloids. In this sense, the phytochemical study of Mexican Ephedra species is a promising area of research to corroborate their ephedrine-type alkaloids content and, in turn, discover new chemical compounds with potential biological activity. Therefore, the present review represents a key compilation of all the relevant information for the Ephedra genus, in particular the American species, the species distribution, their ecological interactions, its ethnobotany, its phytochemistry and their pharmacological activities and toxicities, in order to promote clear directions for future research.

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“…Furthermore, at least some cases presumed to be due to the herb consisted of multi-ingredient formulas where known hepatotoxic substances such as green tea extract and other potentially hepatotoxic herbs were also included [83,[101], [102], [103], [104]]. A recent study in F344 rats administered up to 1000 mg/kg of Ephedra extract containing ephedrine and pseudoephedrine failed to find adverse effects upon the liver [105], while Ephedra species demonstrated hepatoprotective effects in models of induced acute and chronic liver failure in mice with noted anti-inflammatory effects and inhibition of hepatocellular apoptosis [106,107]. Interestingly, an in vitro assay using human hepatoblastoma cells (HepG2) demonstrated that when Ephedra (ma-huang) extracts were normalized for their ephedrine content, they displayed greater cytotoxicity relative to ephedrine itself, indicating that there may be other constituents responsible for toxicity [108].…”

Section: Mechanism Of Amphetamine-induced Hepatotoxicitymentioning

confidence: 99%

Sympathomimetic amine compounds and hepatotoxicity: Not all are alike—Key distinctions noted in a short review

Willson¹

2019

Toxicology Reports

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Sympathomimetic amine compounds are often pooled together and incorrectly assumed to be interchangeable with respect to potential adverse effects. A brief and specific review of sympathomimetic compounds and one instance (i.e., hepatotoxicity) where these compounds have been improperly grouped together is covered. A review of the proposed mechanisms through which known hepatotoxic sympathomimetic agents (e.g., 3,4-methylenedioxymethamphetamine or MDMA, methamphetamine and amphetamine) cause liver injury, along with a corresponding review of in vitro data, interventional data, animal model studies and observational data allow for a comparison/contrast of different agents and reveals a lack of potential toxicity for some agents (e.g., pseudoephedrine, phenylephrine, ephedrine, 1,3-dimethylamylamine, phentermine) in this broad category. Data show that compounds within the broad group of sympathomimetics display divergent pharmacological and toxicological profiles and can be clearly distinguished with respect to liver injury. These data serve as a reminder to clinicians and others, that even small structural differences between molecules can lead to drastically different pharmacological/toxicological profiles and that one should not assume that all sympathomimetic agents are hepatotoxic. Such assumptions could lead to diagnostic errors and incorrect or insufficient treatment.

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Assessing the safety of an Ephedrae Herba aqueous extract in rats: A repeat dose toxicity study

Cited by 18 publications

References 12 publications

Effect of Ephedrae Herba methanol extract on high-fat diet-induced hyperlipidaemic mice

Effect of Ephedrae Herba methanol extract on high-fat diet-induced hyperlipidaemic mice

A Review of the Ephedra genus: Distribution, Ecology, Ethnobotany, Phytochemistry and Pharmacological Properties

Sympathomimetic amine compounds and hepatotoxicity: Not all are alike—Key distinctions noted in a short review

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