New Orleans, LA - Americans believe that “an apple a day keeps the doctor away.” In Japan, a similar saying holds true for the umeboshi, the Japanese plum. Recently, umeboshi plums started to become widely available in specialty stores throughout the United States. Could the Japanese plum replace the benefits of the all-American apple someday? Perhaps.

The pickled plum has been reported to aid the digestive system, increase saliva, and even act as a cure for a hangover. It is a fruit of legend, with one tale recounting that Samurai soldiers, dying of thirst, ate the fruit to excite their salivary glands, and therefore avoided death. Consumers today rub bainiku-ekisu to the cheek or forehead in the belief it cures their tooth- and headaches.

The flesh of the plum produces an abstract know as bainiku-ekisu. This by-product is the grated, condensed flesh (or “skin”) of the fruit. A recent study reported that a fruit juice concentrate of Asian plum improves human blood fluidity and identified a bioactive substance in it as Mumefral, which is produced during the plum processing.

Two physiologists from Vanderbilt University and a collaborator from Wakayama University (Japan) have focused on mechanisms of bainiku-ekisu to prevent various diseases. In addition to the effect of bainiku-ekisu on blood fluidity, it may have a direct effect on the vasculature, and thereby improve cardiovascular diseases such as hypertension and/or atherosclerosis. The scientific community has previously reported that the epidermal growth factor (EGF) receptor transactivation and subsequent extracellular signal-regulated kinase (ERK/MAP kinase) activation play central roles in signal transduction and gene expression of the AT₁ receptor that leads to abnormal growth of vascular smooth muscle cells (VSMCs).

A scientific hypothesis was recently developed asserting that bainiku-ekisu may prevent cardiovascular diseases by blocking the EGF receptor transactivation. This research investigated the effects of bainiku-ekisu on AngII-induced EGF receptor transactivation, ERK activation and protein synthesis in cultured aortic VSMCs in order to show the potential efficacy of bainiku-ekisu in reducing cardiovascular diseases.

The authors of a new study, “Fruit-juice concentrate of the Asian Plum Inhibits Growth Signals of Vascular Smooth Muscle Cells Induced by Angiotensin II (oriental plum),” are Satoru Eguchi, MD, PhD and Gerald Frank, PhD, both from the Dept. of Biochemistry, Vanderbilt University, Nashville, TN and Hirotoshi Utsunomiya, PhD, Wakayama Medical University (Japan). The researchers will present their findings in full during the American Physiological Society’s (APS) annual meeting, part of the "Experimental Biology 2002” conference. More than 12,000 attendees will attend the conference being held at the Ernest N. Morial Convention Center, New Orleans, LA from April 20-24, 2002.

The researchers employed the following methodology:

• Materials: Materials consisted of bainiku-ekisu, the fruit juice concentrate of Asian plum; AngII and H2O2; antibody for Tyr1068-phosphorylated EGF receptor; antibody for Tyr204-phosphorylated ERK 1/2, anti-ERK2 antibody and anti-EGF receptor antibody; and peroxidase linked secondary antibodies and ECL reagents.

• Cell Culture: The thoracic aorta from 12 week-old rats were used and cultured.

• Western Blotting: After VSMCs were stimulated with AngII, the cell lysates were subjected to gel electrophoresis and electrophoretically transferred to a nitrocellulose membrane. Phosphorylated proteins resulting from AngII-induced EGF receptor transactivation and ERK1/2 activation were detected using the phospho-specific antibodies.

Among the significant findings were the fact that:

• Bainiku-ekisu effectively inhibited AngII-induced EGF receptor transactivation and its downstream ERK activation, resulting in marked suppression of protein synthesis induced by AngII;

• Bainiku-ekisu had no noticeable non-specific effect on AngII-induced intracellular Ca²⁺ elevation or basal protein synthesis. These data support their hypothesis that bainiku-ekisu may be beneficial against hypertension and atherosclerosis by selectively inhibiting growth promoting signals of AngII in the vasculature;

The findings also confirmed that reactive oxygen species production and metalloprotease-dependent heparin-binding EGF-like growth factor production was indispensable in AngII-induced EGF receptor transactivation in VSMCs. Reactive oxygen species were also implicated in vascular remodeling induced by AngII. Here, the results showed that bainiku-ekisu inhibited H2O2-induced EGF receptor transactivation. Thus, bainiku-ekisu may act as an antioxidant in inhibiting the actions of AngII. In fact, the authors recently confirmed potent antioxidant activity of bainiku-ekisu.

This present study found that inhibition of EGF receptor transactivation by Bainiku-ekisu was almost complete, whereas the inhibition of ERK activation was partial. This is in agreement with their earlier observations that, although minor, an EGF receptor-independent pathway also contributes to AngII-induced ERK activation in VSMCs.

Bainiku-ekisu contains large amount of the known acids (citric acid, malic acid), as well as relatively small amounts of bioactive substances, such as Mumefural, produced in the manufacturing process. Given that a small amount of Mumefral has a strong potency to improve blood fluidity equal to a large amount of Bainiku-ekisu, the authors speculate that Mumefural may also inhibit EGF receptor transactivation.

Thus, these data suggests that Bainiku-ekisu could represent a potential new therapeutic agent for cardiovascular diseases such as hypertension and atherosclerosis.

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