Effects of Coffee Cherry, the Residue Left after Removal of the Beans from the Coffee Fruit, on Mammary Glands, Automatic Behavior and Related Parameters in Mice

American Journal of Chinese Medicine,  Wntr, 2001  by Hiroshi Nagasawa,  Erika Yada,  Yoko Udagawa,  Hideo Inatomi

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(Accepted for publication October 25, 2000)

Abstract: To clarify the mechanisms of the anti-mammary tumor activity of coffee cherry (CC), the residue left after the removal of beans from the fruit, the effects in SHN mice of CC on plasma and urine component levels, mammary gland growth, spontaneous motor activity and several related parameters were examined. Hot water extract of CC was given to 2-month-old mice in drinking water (0.5%) for 60 days. The treatment prevented the elevation of plasma and urine levels of alanin amino-transferase and asparate aminotransferase, indicating that CC can protect against metabolic abnormality, which is a cause of the high mammary tumor susceptibility of SHN mice. It also resulted in an inhibition of the formation of precancerous mammary hyperplastic alveolar nodules. Neither food and water intake nor spontaneous motor activity was affected by CC. The findings provide novel information on the mechanism of the protective effect of CC on mammary tumorigenesis and confirm the usefulness of CC as a safe chemopreventive agent of mammary and other types of tumors.

Coffee cherry (CC: the residue left after removal of beans from the coffee fruit) is mostly discarded: a small percentage is used locally as a health drink. We previously found that the hot water extract of CC markedly inhibited both the development (Nagasawa et al., 1995) and the growth (Nagasawa et al., 1996) of spontaneous mammary tumors in mice. It is well known that changes in the target tissue are important in the development of lesions and that emotional or mental state has some kind of effect on most diseases with long latent periods. In this respect, several natural products influence spontaneous motor activity, a reflection of the emotional or mental condition, relaxed or stressful (Nagasawa et al., unpublished). Furthermore, the general metabolic activity is considered to relate to mammary tumor potential in mice (Yasuda et al., 1996). Irradiation with far-infrared rays, which inhibited markedly the spontaneous mammary tumorigenesis of mice (Nagasawa et al., 1999b, 2000b; Udagawa et al., 1999) also suppressed the formation of precancerous hyperplastic aleveolar nodules in mammary tissue (Nagasawa et al., 2000b), stimulated spontaneous motor activity (Nagasawa et al., 2000b; Udagawa and Nagasawa, 2000a) and ameliorated the metabolism (Nagasawa et al., 2000c; Udagawa and Nagasawa, 2000a).

Thus, in this study, we examined the effects of CC on mammary glands, spontaneous behavior and plasma and urine component levels in young SHN mice given CC for limited periods as a step in clarifying the mechanisms of the protective role of CC in mammary tumorigenesis.

Materials and Methods

Coffee Cherry (CC)

Dry matter of CC (500 g) donated by Toarco JAYA (Jakarta, Indonesia) was soaked in distilled water (5 liter) and left at room temperature for 7 days with occasional shaking every day. This was repeated 5 times and the supernatants were pooled and dried in vacuo at 45 [degrees] C. The dried extract was diluted with tap water at the concentration of 0.5% (5 g/1 liter) and given as drinking water.

Animals and Treatments

A high mammary tumor strain of SHN/Mei virgin mice (Nagasawa et al., 1976; Staats, 1976) maintained by full-sib mating was used. At 2 months of age, the mice were divided into two groups, the control and the experimental groups, given tap water and CC solution, respectively. Throughout the experiments, mice were kept in plastic cages with wood shavings (16 x 28 x 13 cm), 4 each, maintained in a windowless animal room, which was air-conditioned (22 [+ or -] 0.5 [degrees] C and 60-70% relative humidity) and artificially illuminated (14 hr of light from 0500 hr to 1900 hr). The diet (Lab MR Breeder, Nihon Nosan Kogyo KK, Yokohama, Japan) and water were provided ad libitum.

The motor activity of each animal was measured after 30 days of treatments and shortly thereafter blood and urine were taken from each of these mice. This procedure was repeated for each of animals at 60 days and they were then sacrificed. All procedures were carried out according to the NIH Guide for the Care and Use of Laboratory Animals, USA (Natl. Res. Council, 1996).

Spontaneous Motor Activity

After 30 and 60 days of CC treatment (3 and 4 months of age), spontaneous motor activity was measured by Supermex (Muromachi Kikai, Tokyo, Japan) (Masuno et al., 1995), a sensor monitor which was mounted above the cage to detect changes in heat across multiple zones of the cage through an array of Freshnel lenses. The body heat radiated by an animal was detected with paired IR pyroelectric detectors on the sensor head of the monitor. In this way, the system could monitor and count all spontaneous movements, both vertical and horizontal, including locomotion, rearing, head-movement, etc. All counts were automatically totaled and recorded at an hourly interval.

Mice were individually placed in the measurement cages (15 x 28 x 11 cm) in the measurement room 24 hr before measurement so as to become accustomed to the conditions.