Pharmacokinetics and tissue distribution of Aegeline after oral administration in mice

Authors: MANDA, VAMSHI - University Of Mississippi; HARON, MONA - University Of Mississippi; MIR, TAHIR - University Of Mississippi; AVULA, BHARATHI - University Of Mississippi; ASHFAQ, MOHAMMAD - University Of Mississippi; HAIDER, SAQLAIN - University Of Mississippi; CHITTIBOYINA, AMAR - University Of Mississippi; KHAN, IKHLAS - University Of Mississippi; KHAN, SHABANA - University Of Mississippi

Submitted to: Planta Medica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/28/2019
Publication Date: 2/12/2019
Citation: Manda, V., Haron, M.H., Mir, T.M., Avula, B., Ashfaq, M.K., Haider, S., Chittiboyina, A.G., Khan, I.A., Khan, S.I. 2019. Pharmacokinetics and tissue distribution of Aegeline after oral administration in mice. Planta Medica. 85(06):491-495. https://doi.org/10.1055/a-0851-6879.
DOI: https://doi.org/10.1055/a-0851-6879

Interpretive Summary: Aegle marmelos (L.) Corrêa also known as “Bael” is a native to various parts of Asia. Different parts of this plant are used in traditional medicine of India and neighboring countries. Both aqueous and alcoholic extracts of A. marmelos leaves have been reported to exhibit some biological activities against diabetes and obesity. Aegeline is one of the alkaloids found in the leaves of A. marmelos and has been reported to be pharmacologically active. In recent years, clinical toxicity reports of acute and chronic liver injuries were attributed to aegeline-containing supplement, OxyElite Pro, which has been marketed for weight loss and exercise performance enhancement. Currently, there is no data describing the pharmacokinetics of this pharmacologically active phytochemical. Hence, this study was aimed at assessing the pharmacokinetics and tissue distribution of aegeline after oral administration of a human equivalent dose of 30 mg/kg (1X) and a 300 mg/kg (10X) dose in ND4 mice. Aegeline showed rapid distributed to liver, kidneys and brain with higher affinity for the liver. Unlike the brain and kidneys, especially at the higher dose, aegeline achieved higher concentrations in the liver and was eliminated more quickly, which indicates that the liver is the main organ of metabolism and clearance for aegeline. However, a single dose of aegeline by itself seems to be well tolerated in regard to metabolism and clearance, further studies are needed to assess possible adverse health effects that may result from the ingestion of aegeline and/or aegeline-containing products, if taken repetitively over short periods of time. Moreover, while individual compounds in a given herbal dietary supplement (HDS) may be nontoxic if taken alone, the combination of ingredients in any HDS when taken together could result in inducing adverse health effects. More studies are needed to evaluate the pharmacokinetics and pharmacodynamics of aegeline in humans if taken alone or in combination with other herbal/dietary supplement components and pharmaceutical drugs.

Technical Abstract: Aegeline is claimed to be a biologically active constituent of Aegle marmelos. Preclinical studies have reported possible therapeutic potential for aegeline against obesity and diabetes. In recent years, aegeline has been added to several weight loss products. However, the consumption of aegeline-containing supplements such as OxyELITE Pro and VERSA-1 has been linked to multiple cases of acute and chronic liver failure. This study was carried out to evaluate the pharmacokinetics and tissue distribution of aegeline in ND4 mice. Two doses of aegeline, a human equivalent dose (1×) 30mg/kg and a 10× dose (300mg/kg), were orally administered to the mice, and blood and tissue samples were collected over 8 h. The quantitative analysis of plasma and tissue homogenates (liver, kidney, and brain) was done by Ultra-High Performance Liquid Chromatography - Quadrupole Time Of Flight (UHPLC-QTOF) to determine aegeline concentrations. The peak plasma level of aegeline was achieved at a Tmax of 0.5 h, indicating its rapid absorption from the gastrointestinal tract. Aegeline was not detected in the plasma at 8 h after oral administration, with a half-life of 1.4 ± 0.01 and 1.3 ± 0.07 h for the 30 and 300mg/kg doses, respectively. The half-life of aegeline in the liver was 1.2 h and 1.7 h for 30 and 300mg/kg doses, respectively, with a Tmax of 1.9 h, which indicates relatively fast elimination of aegeline from the liver.