ABSTRACT
The prevalence of metabolic disorders is rising worldwide. Botanicals, such as rosemary (Rosmarinus officinalis L.) and ash tree seeds (Fraxinus excelsior L.), may be an alternative to ameliorate these disorders. The objective of this doctoral thesis was to generate industrial extracts from the edible parts of these plants; identify their chief constituents by HPLC, HPLC-MS, and NMR; and determine their efficacy and safety. Three rosemary extracts were developed —standardized to 20% carnosic acid, 20% rosmarinic acid, and 40% ursolic acid. The ursolic acid-rich extract showed the lowest antioxidant capacity in ORAC and FRAP in vitro models, while the other two extracts had higher capacities. However, the carnosic acid-rich extract (RE) was better in inhibiting the oxidation of LDL ex vivo, and was the only one selected for further studies. An ash tree seed extract (FE) was developed according to its traditional use in Morocco, being identified salidroside and 9 secoiridoid glycosides, two of them were discovered for the first time: Excelside A and Excelside B. In in vitro studies, RE and FE activated nuclear receptors that regulate glucose and energy homeostasis, and acted on antiobesity and dyslipidemia mechanisms –RE activated PPAR? and inhibited pancreatic lipase, and FE stimulated PPARa and prevented preadipocyte differentiation. The capacities of both extracts to counteract metabolic disorders were confirmed in C57BL/6J mice administrated with low-fat diet; high-fat diet; or high-fat diet plus 0.5% RE (HFD.RE) or 0.5% FE (FED) during 16-weeks. HFD.RE limited the increase of body and epididymal fat weight by 69% (P<0.01) and 79% (P<0.001), respectively. HFD.RE also reduced fasting glycaemia (72%, P<0.01) and plasma cholesterol levels (68%, P<0.001). FED decreased blood glucose (76.52%, P<0.001), plasma insulin level (53.43%, P<0.05), and body weight gain (32.3%, P<0.05). Finally, a screening model against glucose (50g) was used to assess the effect of FE (1.0g) on plasma glucose and insulin levels in a RCT on 16 healthy volunteers. FE reduced the glycemic-AUC (P=0.02), but not the insulinemic-AUC. The two extracts were safe. Additional long-term interventions in humans are warranted.
Keywords: Antioxidant; glycaemia; body weight; FRAP; Fraxinus excelsior L.; insulin; ORAC; pancreatic lipase; polyphenols; PPAR; Rosmarinus officinalis L; secoiridoids.