Rethinking the Cucurbitane-Type Triterpenoid Profile of Bitter Gourd ( L.): The Chemical Transformation of Momordicine I in Solution.

L., commonly known as bitter gourd, is a popular vegetable and medical herb in many countries. The most characteristic phytochemical profile of bitter gourd is its high content of cucurbitane-type triterpenoids, which are responsible for its bitter taste and therapeutic potential. More than 260 cucurbitane-type triterpenoids, including at least 11 5,19-hemiacetals, 40 5,19-methyl acetals, 46 methyl ethers, 6 5,19-ethyl acetals, and 7 ethyl ethers, have been identified from bitter gourd. In this work, by studying the chemical transformation of momordicine I, one of the most abundant cucurbitane-type triterpenoids in bitter gourd, we showed that under acidic conditions, 5,19-hemiacetals of cucurbitane-type triterpenoids could be formed from the intramolecular nucleophilic addition between the C-19 aldehyde and the C-7 hydroxyl group; furthermore, 5,19-acetals and methyl ethers could be generated if methanol was available. Using a UPLC-MS/MS quantification method, we showed that these momordicine I derivatives could not be detected from bitter gourd fruits when extracted with a nonmethanolic solution but could be detected when extracted with methanol after thermal treatment. Moreover, these momordicine I derivatives were detected in two of eight brands of bitter gourd dietary supplements. This might be concerning because these derivatives were not the natural components of bitter gourd, and their safety and efficacy profiles were unknown. Besides, the transformation reactions reported herein should apply widely to other cucurbitane-type triterpenoids as well. Therefore, we believe all 40 5,19-acetals, 46 methyl ethers, 6 5,19-ethyl acetals, and 7 ethyl ethers were the extraction and isolation artifacts and should not be regarded as the natural components of bitter gourd. This work will help to clarify the current misunderstanding of the real cucurbitane-type triterpenoid profile of bitter gourd.