Biological & pharmaceutical bulletin
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We examined the inhibitory effect of two saponin preparations from Red ginseng, 20(R)- and 20(S)-ginsenoside-Rg3, in comparison with that of ginsenoside-Rb2, on lung metastasis produced by two highly metastatic tumor cells, B16-BL6 melanoma and colon 26-M3.1 carcinoma, in syngeneic mice. In an in vitro analysis, both saponin preparations showed a significant inhibition of adhesion to fibronectin (FN) and laminin (LM) by B16-BL6 melanoma. Similarly, they significantly inhibited the invasion of B16-BL6 cells into the reconstituted basement membrane (Matrigel)/FN in a dose-dependent manner. ⋯ When 20(R)- or 20(S)-ginsenoside-Rg3 was orally administered consecutively after tumor inoculation in a spontaneous metastasis model using B16-BL6 melanoma, both of them significantly inhibited lung metastasis. In the experiment involving neovasculization by tumor cells in vivo, both mice groups given each saponin preparation after tumor inoculation exhibited a significant decrease in the number of blood vessels oriented toward the tumor mass, with no repression of tumor size. These findings suggest that both ginseng saponins, 20(R)- and 20(S)-ginsenoside-Rg3, possess an ability to inhibit the lung metastasis of tumor cells, and the mechanism of their antimetastatic effect is related to inhibition of the adhesion and invasion of tumor cells, and also to anti-angiogenesis activity.
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Analgesic activities of Randia siamensis CRAIB (R. siamensis) extract and pseudoginsenoside-RP1, a constituent of the extract, were examined in the writhing test, hot plate test and Randall-Selitto test. Oral administration of R. siamensis extract dose-dependently decreased the number of writhings and stretchings induced by 0.6% acetic acid in the writhing test in mice. Moreover, in the Randall-Selitto test in rats, the extract raised the nociceptive threshold of the carrageenan-inflamed but not of non-inflamed paw. ⋯ The R. siamensis extract did not affect hexobarbital-induced sleep or spontaneous motor activity in mice, suggesting that it has no sedative effect. Pseudoginsenoside-RP1 produced similar effects to the R. siamensis extract, but its effective doses in the analgesic tests were lower than those with the extract. These results suggest that R. siamensis extract produces anti-nociceptive actions similar to those of a peripherally acting analgesic drug aspirin, and that pseudoginsenoside-RP1 may partly contribute, but is not the main contributor, to the antinociceptive action of the extract.
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Aloe-emodin-9-anthrone(AE-anthrone), produced from barbaloin in the rat large intestine, caused not only an increase in the intestinal water content but also stimulated mucus secretion. This might play an important role in the occurrence of diarrhea. ⋯ These results together with our previous data, which showed a relationship between increase in the intestinal water content and the stimulation of peristalsis, confirm that AE-anthrone is the principal agent responsible for the cathartic effect of barbaloin. We also propose that the increase in water content is a more important factor than stimulation of peristalsis in the induction of diarrhea by barbaloin.
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We studied the effect of ginsenoside-Rb2 extracted from Panax ginseng on angiogenesis and metastasis produced by B16-BL6 melanoma cells in syngeneic mice. Intravenous administration of ginsenoside-Rb2 on day 1, 3 or 7 after tumor inoculation achieved a remarkable reduction in the number of vessels oriented toward the tumor mass, but did not cause a significant inhibition of tumor growth. The anti-angiogenic effect was dose-dependent ranging from 10 to 500 micrograms/mouse. ⋯ The invasion of RLE cells into the reconstituted basement membrane (Matrigel), which is considered to be an essential event in tumor neovascularization, was inhibited by ginsenoside-Rb2 in a concentration-dependent fashion, while ginsenoside-Rb2 did not inhibit the haptotactic migration of endothelial cells to fibronectin-substrate. Multiple administrations of ginsenoside-Rb2 after the intravenous inoculation of B16-BL6 melanoma cells resulted in a significant inhibition of lung metastasis as compared with the untreated control. These results suggest that the inhibition of tumor-associated angiogenesis by ginsenoside-Rb2 may partly contribute to the inhibition of lung tumor metastasis.
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Charcoal transport, as an indicator of the degree of peristalsis, and water content in the large intestine after the intracaecal administration of barbaloin, were measured simultaneously in the same rat. Charcoal transport was significantly accelerated at both 3.5 and 6.5 h after the administration of barbaloin. ⋯ It appears that the increase in water content of the large intestine induced by barbaloin precedes the stimulation of peristalsis, attended by diarrhea. Therefore, it is suggested that the increase in water content is a more important factor than the stimulation of peristalsis in the diarrhea induced by barbaloin.