Lemon Balm (Melissa officinalis) – Botany, Therapeutic Uses, Constituents, Pharmaco, Adverse Effects

When administered to rats orally, ursolic acid was rapidly absorbed and displayed a half-life in blood of between one and four hours. Widely distributed throughout the body, the highest concentrations of ursolic acid were found in the lung, spleen, and liver. A significant amount was also detected in rat brain, indicating this compound is capable of crossing the blood-brain barrier. While these data suggest that ursolic acid might affect brain function, its rapid elimination from the blood suggests that any pharmacological response would be brief.

Following oral administration of the plant extract, or its consumption as the purified compound, rosmarinic acid was found to be poorly absorbed and rapidly eliminated in rats. Data indicate that rosmarinic acid is metabolized by intestinal organisms so that only a small portion of an orally administered dose is available for passive diffusion into the systemic circulation. The metabolites formed in the intestines, which include meta-coumaric and hydroxylated phenylpropionic acids, are transferred to the blood by an active transport system. It is unclear whether these metabolites display any pharmacological activities on their own. In rats, the majority of the rosmarinic acid absorbed into the blood is extensively metabolized in the body and excreted in the urine. Taken together, these findings suggest that rosmarinic acid is an unlikely candidate as the constituent of lemon balm primarily responsible for any effects on the central nervous system.

The half-life of oleanolic acid following intravenous administration to various animal species is relatively short, ranging from 12 minutes in rats to 57 minutes in dogs. From these data it was predicted that the half-life in humans would be somewhere between 45 minutes and three hours. In a study involving 18 healthy volunteers, the measured half-life was up to eight hours following oral administration. However, this value was highly variable, with some subjects displaying much shorter half-lives. Nonetheless, these results indicate that oleanolic acid may remain in the body of some individuals for a sufficient time to induce a pharmacological effect. The wide variation in half-lives in humans suggests a behavioral response to oleanolic acid would be unpredictable.

In vivo and in vitro laboratory animal studies indicate that lemon balm constituents can affect the absorption, distribution, and metabolism of other chemical agents, such as prescription medications. Citronellal, for example, inhibits intestinal transporters responsible for the absorption of digoxin, a drug used to treat heart failure. Likewise, ursolic acid interacts with transporters involved in eliminating rosuvastatin, a cholesterol-lowering agent, from blood. Citral has been shown to be an inhibitor of a liver enzyme responsible for the metabolism of a variety of drugs. Lemon balm extract may also inhibit the absorption of thyroxine, a thyroid hormone. These data suggest that consumption of lemon balm can influence the responses to certain drugs, either prolonging or enhancing their actions, or reducing their effectiveness. However, given what is known about the pharmacokinetics of some of the major lemon balm constituents, it would probably be necessary to consume large quantities of the herb over a prolonged period of time to achieve the sustained blood levels needed to influence the response to conventional medications. The fact that there are few reports of adverse drug interactions associated with lemon balm consumption reinforces the conclusions drawn from pharmacokinetic studies. That is, the known constituents of this plant appear to be poorly absorbed, extensively metabolized, and rapidly cleared from the body, making them unlikely candidates as drugs or toxic agents.