UPDATE ON THE CLINICAL PHARMACOLOGY OF PYCNOGENOL

Pycnogenol ® (PYC), obtained as a dry extract from the bark of the French maritime pine, has attracted the interest of researchers worldwide; more than 300 publications in Medline reflect this scientific interest. This review summarizes clinical studies published in scientific journals between 2010 and 2015. Knowledge of the metabolism of PYC was expanded during the last years. Its active metabolite M1, a valerolactone, is accumulated via active transport in blood cells and undergoes further intra-cellular metabolism. PYC exerts 4 basic functions: Inhibition of αglucosidase, stimulation of synthesis of hyaluronic acid and collagen, stimulation of nitric oxide production and inhibition of inflammatory mediators. The effects of PYC in inhibiting inflammatory processes and stimulating endothelial function have been corroborated by new clinical studies. Further insight into the effects of PYC in chronic venous insufficiency and hemorrhoids resulted from ex-vivo experiments and clinical studies. The improvement of local microcirculation terminated tinnitus and Meniere’s disease in 87% of the patients vs 35% in controls. Inhibition of aromatase and growth factors by PYC was correlated with substantial amelioration of endometriosis, 90% of patients became pain free. The spectrum of contributions of PYC to women’s health has been broadened by new positive effects on sexual function, evaluated by the Female Sexual Function Index. Erectile function of infertile men, evaluated by the Int. Index of Erectile Function was improved from moderate to normal values. Concentration of sperms increased by 79% to normal levels by administration of combinations of PYC with aminoacids and roburin. Furthermore, the administration of PYC exerted a significant positive influence on cognitive functions as memory, learning and daily capabilities. Hence the administration of PYC offers a multitude of health benefits. The improvements seen in vascular health need to be confirmed in further studies. New results regarding benefits in cognitive function may lead to new topics of research with PYC. Keywords—Pine bark extract, Pycnogenol, endothelium. Circulation. , antiinflammatory Medical Research Archives July 2015 Issue 3 Copyright © 2015, Knowledge Enterprises Incorporated. All rights reserved. 2 Introduction Pycnogenol ® (PYC), a proprietary extract of Horphag Research, produced from the bark of the French maritime pine (Pinus pinaster, subsp. atlantica) meets the requirements of the monograph: Maritime Pine Extract of the US Pharmacopoeia 37, Dietary Supplements. PYC is used worldwide as a dietary supplement, herbal drug, in cosmetics and for dental care. Since the first comprehensive review in 2002 [26] 9 reviews appeared covering publications about PYC until 2014. The present review refers to 33 clinical studies appearing between 2010 until 2015. 1. Source and composition The bark, the raw material for production of PYC, is tested according to the monograph Maritime Pine of the USP 37, Dietary Supplements. The bark contains predominantly procyanidins (Fig 1). The extract, as described in the USP 37, is standardized to contain not less than 75% procyanidins. The procyanidins are biopolymers, composed from catechin and epicatechin subunits. Phenolic acids, as ferulic acid, caffeic acid, protocatechuic acid (Fig. 2) and catechin and taxifolin (Fig. 3) are contained as glucosides as well as in free form as minor constituents. More details about the composition had been given in a previous review [26]. All components of PYC exert antioxidative and antiinflammatory properties and contribute to the manifold health benefits of the extract. Fig. 1 Example for a procyanidin molecule, procyanidin trimer