Grape seed extract may help wound healing

COLUMBUS, Ohio ? Grape-seed extract may help skin wounds heal faster and with less scarring, a new study suggests.

The extract seemed to aid wound healing in two ways: It helped the body make more of a compound used to regenerate damaged blood vessels, and it also increased the amount of free radicals in the wound site. Free radicals help clear potentially pathogenic bacteria from a wound.

In two related experiments, the researchers tested the effects of grape-seed extract on mice and on human skin cells. It’s the first evidence suggesting that a natural extract could have such a profound effect on wound healing, said Chandan Sen, a study co-author and director the Laboratory of Molecular Medicine at Ohio State University’s Heart and Lung Research Institute.

“We saw the healing effects grape-seed extract had on wounds from day one,” said Sen, who is also an assistant professor of surgery at Ohio State. “It seemed to enhance the formation of epidermal tissue as well as the deposition of connective tissue.”

The researchers treated skin wounds on mice with a topical formulation of grape seed proanthocyanidin extract (GSPE). Proanthocyanidin, one of the main ingredients in grape-seed extract, is thought to be a potent antioxidant. But in a wound site, which is rich in free radicals, the extract assumes some pro-oxidant properties.

The study appears in a recent issue of the journal Free Radical Biology and Medicine.

Each of nine mice in the study was given two small puncture wounds on its back. The researchers applied GSPE to one of the wounds, and covered the other with saline solution as a control. Otherwise, the wounds were left to heal naturally.

The animals were euthanized five days after they were wounded. A small area of skin ? 1 to 1.5 millimeters ? was excised from the edges of the treated and untreated wounds. The researchers looked for signs of enhanced healing in the GSPE-treated samples, and compared these samples to the healing patterns of the saline-treated tissue.

“The skin treated with grape-seed extract was further along in the healing process compared to the saline-treated tissue,” Sen said. “The extract-treated skin showed signs of healing faster and the newly formed tissue was denser, meaning that its structure was stronger.”

The researchers saw increased levels of tenascin, a protein that helps build connective tissue, in the granulation tissue of the wounds treated with GSPE. Granulation tissue is the rough, pinkish tissue that normally forms as a wound heals. It contains new capillaries and connective tissue.

“Tenascin is a marker for skin wound healing,” Sen said. “There was much more tenascin present in the granulation tissue of the wounds treated with GSPE.”

The researchers also noted increased levels of VEGF, the compound that helps the body rebuild blood vessels. In previous research, Sen and his colleagues found that GSPE helped turn on the gene responsible for initiating the making of VEGF.

In a related experiment, the researchers also treated human skin cells with GSPE, finding that the extract helped the laboratory-grown cells produce more VEGF.

“More VEGF means blood vessels will form faster and that more nutrients will be carried by the blood to regenerate damaged tissue,” Sen said.

In addition to helping blood vessels regenerate, GSPE also seemed to increase free radical levels at the wound site. It may seem odd that an antioxidant could help oxidation ? the formation of free radicals ? flourish. But

“The extract assumed a mild pro-oxidant property while in an oxidant-rich environment,” Sen said. “Excessive amounts of free radicals are damaging. But every living cell makes free radicals. In controlled amounts, they help the body function.”

At low concentrations, free radicals can stimulate the proliferation of cells as well as the formation of connective tissue and new blood vessels, Sen said.

“Skin wounds are rich in free radicals,” he said. “There was a longer-lasting free radical effect in the wounds that had been treated with grape-seed extract. We think that’s partly why these wounds healed faster and better.”

While grape-seed extract is good news for wounded tissue, topical grape seed extract isn’t sold commercially. And consumers shouldn’t expect to get the same wound-healing benefits from taking grape-seed extract in vitamin form, Sen said.

“Taken orally, the extract functions like an antioxidant,” he said. “But in a wound, where free radicals are abundant, that proanthocyanidin assumes pro-oxidant behavior.”

A grant from the National Institutes of Health supported the work. InterHealth Nutraceuticals, Inc. supplied the grape-seed proanthocyanidin extract for this study.

Sen co-authored the study with Savita Khanna, Sashwati Roy, Nidhi Sharma and Prashant Trikha, all with Sen’s Laboratory of Molecular Medicine at Ohio State’s Heart and Lung Research Institute; Mika Venojarvi, who is also with Sen’s laboratory as well as the University of Kuopio, Finland; and Debasis Bagchi and Manashi Bagchi, who are both with Creighton University Medical Center in Omaha, Neb.