Protection from Inflammation, Immunosuppression and Carcinogenesis Induced by UV Radiation in Mice by Topical Pycnogenol®¶

Abstract

Pycnogenol is a standardized extract of the bark of the French maritime pine, Pinus pinaster Ait., that has multiple biological effects, including antioxidant, anti-inflammatory and anticarcinogenic properties. This study describes the effect of topical application of lotions containing Pycnogenol to Skh:hr hairless mice undergoing minimally inflammatory daily exposures to solar-simulated UV radiation (SSUV). We report that concentrations of Pycnogenol of 0.05-0.2% applied to the irradiated dorsal skin immediately after exposure resulted in dose-dependent reduction of the inflammatory sunburn reaction, measured as its edema component. When mice received three consecutive daily exposures of minimally edematous SSUV, their ability to raise a contact hypersensitivity (CHS) reaction was suppressed by 54%. Pycnogenol lotions applied postirradiation reduced this immunosuppression to 22% (0.05% Pycnogenol) and 13% (0.1% Pycnogenol). Furthermore, when CHS was suppressed by 71% with exogenous treatment with cis-urocanic acid, the putative epidermal mediator of photoimmunosuppression, 0.2% Pycnogenol lotion reduced the immunosuppression to 18%. Chronic exposure to SSUV on 5 days/week for 10 weeks induced skin tumors from 11 weeks in both control mice and in mice receiving daily applications of 0.05% Pycnogenol, but tumor appearance was significantly delayed until 20 weeks in mice receiving 0.2% Pycnogenol. Furthermore, whereas 100% of control mice had at least one tumor by 30 weeks, and mice treated with 0.05% Pycnogenol by 33 weeks, the maximum tumor prevalence in mice treated with 0.2% Pycnogenol was significantly reduced to 85%, with some mice remaining tumor free. Average tumor multiplicity was also significantly reduced by 0.2% Pycnogenol, from 5.2 in control mice to 3.5 at 35 weeks. Thus, topical Pycnogenol offered significant and dose-dependent protection from SSUV-induced acute inflammation, immunosuppression and carcinogenesis, when applied to the skin after daily irradiation. Pycnogenol, therefore, in addition to its recognized health benefits in other organs, appears to have potential in providing photoprotection for humans in a complementary role with sunscreens, having demonstrable activity when applied to the skin after, rather than before, UV exposure.

Flavonoids as Anti-Inflammatory and Analgesic Drugs: Mechanisms of Action and Perspectives in the Development of Pharmaceutical Forms

“…The postirradiation, topical application of lotions containing increasing levels of the plant extract, pycnogenol B, significantly inhibited the acute inflammation-edema response to solar-simulated UVR [190].…”

“…Studies that have focused on equol ([S]-4 0 ,7-dihydroxyisoflavane) because it was shown that its contribution to the protection against solar-simulated UVR-induced erythemal-associated edema and immunosuppression [190] showed a potential role in the prevention of human skin cancer [190] by acting as a sunscreen and, thus, inhibiting DNA photodamage [191] when topically applied as a lotion.…”

Photoaging: Mechanisms and repair

“…211 An antioxidant extract from pine trees was shown to protect mice from inflammation, immunosuppression, and carcinogenesis induced by UV light when applied immediately after UV exposure. 212 …”

Inhibitory effect of maritime pine bark extract (Pycnogenol®) on deterioration of bone structure in the distal femoral epiphysis of ovariectomized mice

“…Double-blind, placebo-controlled studies involving patients with asthma reported that patients receiving Pycogenol supplementation had reduced plasma and urine leukotriene concentrations as well as improved asthma symptom scores and pulmonary function [4,5]. Oral and topical application of Pycnogenol reduced inflammation and delayed skin-cancer formation following UV radiation in controlled experiments in mice [6]. Symptoms of osteoarthritis, such as pain and joint immobility, were decreased in a double-blind, placebo-controlled study [7].…”