A Preliminary Pharmacokinetic Study of Betulin, the Main Pentacyclic Triterpene from Extract of Outer Bark of Birch (Betulae alba cortex)

Abstract

During the last two decades triterpenes have attracted attention because of their pharmacological potential. Triterpene extract (TE) from outer bark of birch consisting mainly of betulin is able to form an oleogel which was successfully tested in the treatment of actinic keratosis. Some aspects of TE in vitro pharmacology are already known. Now we show preliminary pharmacokinetics of betulin and results of a subchronic toxicity study of TE in rats and dogs. Because of poor aqueous solubility of the TE-triterpenes (< 0.1 µg/mL respectively), for pharmacokinetic studies it was suspended in sesame oil (rats, i.p.) and PEG 400 / 0.9 % NaCl (dogs, s.c.). I.p. administered, betulin, the main component of TE, shows time dependency over a period of 4 h and reaches a dose-independent serum level of 0.13 µg/mL. Dose dependency was observed with s.c. administration. At 300 mg/kg a maximum plasma concentration of 0.33 µg/mL betulin was detected after 28 daily applications. The subchronic toxicity study showed no toxicity of TE in rats (i.p.) and dogs (s.c.). In conclusion, triterpene extract from birch bark is safe, its betulin is bioavailable and in addition to published triterpene biological activities TE provides high potential for further pharmaceutical and pharmacological research.

Study of the betulin enriched birch bark extracts effects on human carcinoma cells and ear inflammation

“…A 34% content in betulin was reported by Jäger et al in 2008 [18]. However, few studies have been made on the specie, Betula pendula Roth, in terms of the content of betulin/betulinic acid in the outer bark.…”

Accelerated Reepithelialization by Triterpenes: Proof of Concept in the Healing of Surgical Skin Lesions

“…Under certain conditions, it is desirable to have longer application times for dressings since renewal may be associated with pain or with damage to the injured skin. Betulin, the main component of TE, appears not to be rapidly metabolized or excreted; after 4 weeks of daily subcutaneous application in dogs, a stable blood concentration was established which was only marginally influenced acutely by a further injection [26]. However, longer intervals should also be tested clinically.…”

Accelerating the aesthetic benefit of wound healing by triterpene

“…Triterpenes show the potential to enhance epidermal permeability barrier recovery (Lee et al, 2006) and to stimulate wound healing (Harish, 2008) via the induction of basal cell proliferation (Jäger et al, 2008). Woelfle et al (2010) have demonstrated the influence of highly purified triterpenes from birch cork to promote keratinocyte differentiation as the main process, including the terminal differentiation to corneocytes.…”