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Mode of Action

Mode of antihypertensive Action

Benolea® (EFLA®943) is an extract made from the leaves of olive tree. Since ancient times olive leaves have traditionally been used to support the cardiovascular system with a focus on reducing high blood pressure.

Benolea® combines at least two mechanisms decreasing blood pressure:

Angiotensin Converting Enzyme (ACE) inhibition Increased Nitric Oxide (NO) production

Angiotensin-converting enzyme (ACE) is an enzyme converting angiotensin I to angiotensin II.

ACE and the peptide hormones angiotensin I and angiotensin II are part of the renin-angiotensinsystem (RAS), which controls blood pressure by regulating the volume of fluids in humans.

Angiotensin II constricts blood vessels resulting in an increase in blood pressure.

ACE inhibitors, such as perindopril, captopril or Benolea®, bind to and inhibit ACE, resulting in the decreased formation of angiotensin II, leading to systematic dilation of the arteries and veins and a decrease in arterial blood pressure.

Secoiridiods (and their after intake hydrolyzed products) of Benolea® mediates ACE-inhibition.

Fig. 1: Renin-angiotensin-aldosterone system of Benolea®

AngiotensinogenDecrease in renal perfusion ( juxtaglo-merular apparatus)

Renin

Adrenal gland:cortex

Aldosteronesecretion

Arteriolar vasoconstriction. Increase in bloo pressure

Pituitary gland:posterior lobe

ADH secretion

Collecting duct:H

2O absorbtion

Arteriole

Tubular Na+ Cl- reabsorbtion and K+ excretion, H

2O

retention

Sympatheticactivity

Angiotensin I

Angiotensin II

Surface of pul-monary and renal endotheliumACE

Lungs

Kidney

Liver

Water and salt retention. Effective circulating volume increases. Perfusion of the juxtaglomerular apparatus increases.

Secret froman organism

Stimulatory signal

Inhibitory signal

Reaction

Active transport

Passive transport

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Fig. 2: Angiotensin Converting Enzyme (ACE) inhibition

Mode of cholesterol lowering ActionBeside the antihypertensive effect FRUTAROM could demonstrate significant reduction of blood lipids by Benolea®.Benolea® combines multiple components (Polyphenols like Oleuropein, several Secoiridiods, Hydroxytyrosol & others) and mechanisms to decrease blood lipids. Beside the mentioned mechanisms below probably are also further mechanisms involved in blood lipids lowering.

PPAR = Peroxisome proliferator-acticated receptor ACAT = Acyl-CoA: Cholesterol acyltransferase

Fig. 3: Benolea® as multicomponent system: Synergistc interplay of all components

Mode of antihypertensive Action