Abstract

Rosmarinus officinalis L. (Rosemary) has been long claimed to have hypogylcemic-hypolipidemic dual effects in folkloric medicine. In an effort to explain rosemary's claimed benefits, numerous published studies have investigated an array of pharmacologic activities of the plant including anti-inflammatory, anticarcinogenic and metabolic effects. The question remained, however, as how rosemary would target both plasma lipids and glucose levels simultaneously. A newer mechanism has been suggested, in which targeting the hormone sensitive lipase (HSL) would be the common link between the two metabolic effects. In fact, HSL has been extensively studied for its effects on the metabolic switch between glucose and free fatty acids (FFAs) as an energy source. The current manuscript summarizes a significant amount of work that was undertaken to identify plant species native to Jordan with potential HSL and pancreatic lipase (PL) inhibitory activities. Our results demonstrated in vitroinhibitory effects of R. officnalis on both HSL and PL in a dose dependent manner. Interestingly, the rosemary extract had an IC₅₀ for PL that was several fold lower than the IC₅₀ for HSL, indicating a higher affinity to the former enzyme (13.8 and 95.2 μg/mL for PL and HSL, respectively). In addition, we have compared the inhibitory activities of purified constituents found in rosemary to the parent plant [rosmarinic acid (RA), chlorogenic acid (CA), caffeic acid (CaA) and gallic acid (GA)]. Our results showed that all the tested compounds (RA, CA, CaA, and GA) were able to inhibit the PL and HSL activities in a dose dependent manner, but with different potencies. PL and HSL IC₅₀ values were calculated for each compound and GA was found to be the most potent (IC₅₀ 10.1 and 14.5 for PL and HSL, respectively). Further work is necessary to determine whether our in vitro findings would correlate with the in vivo effects. Nonetheless, our results are a first step in fully understanding the long claimed hypoglycemic-hypolipidemic dual effects of rosemary. Simultaneous targeting of both HSL and PL is likely to open the door for a new era in our continuous battle against DM type 2 and its cardiovascular complications. Currently, we are working on identifying the most active constituents of the plant to evaluate a structure-activity relationship which would pave the road for future therapeutic use.

Key words: Rosmarinus officinalis, Rosemary, obesity, diabetes mellitus, pancreatic lipase, hormone sensitive lipase, phenolic compounds, rosmarinic acid.