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The marked hypotensitive effects of the methanolic extract evidenced in Lippia multiflora leaves prompted us to search for the active principle responsible for such an activity in anaesthetized rats. The methanolic extract was then fractionated according to a scheme of processes and by means of various solvents. Data obtained under the experimental conditions adopted, showed that the hypotensive principle of Lippia multiflora leaves are not flavonic: they are rather phenolic. From the phenolic fraction, two pure products were isolated: inactive verbascoside and Li 1, a cafeic acid ester, linked to 3,4-dihydroxyphenylethanol, the chemical structure of which has not been elucidated yet. Lii exhibited a marked and long-lasting hypotensive effect. The study of dose-response curves of the phenolic fraction and Li 1 showed that Li 1 could be one of the major -ifnot the only oneactive principles responsible for the hypotensive action of Lippia multi!bra leaves.

Plasma levels of glucose, insulin and glucagon were measured at various time intervals after pancreatic duct ligation (PDL) in rabbits. Two hyperglycemic periods were observed: one between 15–90 days (peak at 30 days of 15.1 ± 1.2mmol/l, p < 0.01), and the other at 450 days (11.2 ± 0.5 mmol/l, p < 0.02). The first hyperglycemic episode was significantly correlated with both hypoinsulinemia (41.8 ± 8pmol/l, r= –0.94, p < 0.01) and hyperglucagonemia (232 ± 21ng/l, r=0.95, p < 0.01). However, the late hyperglycemic phase (450 days), which was not accompanied by hypoinsulinemia, was observed after the hyperglucagonemia (390 days) produced by abundant immunostained A-cells giving rise to a 3-fold increase in pancreatic glucagon stores. The insulin and glucagon responses to glucose loading at 180, 270 and 450 days reflected the insensitivity of B- and A-cells to glucose. The PDL rabbit model with chronic and severe glycemic disorders due to the predominant role of glucagon mimicked key features of the NIDDM syndrome secondary to exocrine disease.

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