Chun-Ching Lin

Effects of oleanolic acid and ursolic acid on inhibiting tumor growth and enhancing the recovery of hematopoietic system postirradiation in mice

Two triterpene acids, oleanolic acid (OA) and ursolic acid (UA) were examined for their ability to inhibit the tumor growth and modify hematopoiesis after irradiation in three experimental systems: (a) in vivo anti-tumor activity of implanted tumor by ascitic cells was found to be augmented by addition of OA and UA at a high concentration and inhibited in a dose-dependent manner; (b) in the sublethal whole-body irradiated mice treated with the drugs in the 30 min preirradiation period, enhanced effects of OA and UA on peripheral leukocytes were observed by a different significance, and (c) when these chemicals were administered i.p. to mice 30 min before 4 Gy irradiation, both OA and UA enhanced the postirradiation responses of splenic blastogenesis by PHA. UA was a more potent tumorigenic inhibitor than OA. Combining with the gamma-irradiation, however, there was no significant synergetic effect on their anti-tumor activity. The beneficial effects of OA and UA on hematopoiesis and immunocompetence under this study, suggested they might partially play a role in anti-cancer and, furthermore, with the ability to decrease undesirable radiation damage to the hematopoietic tissue after radiotherapy.

Comparisons of geniposidic acid and geniposide on antitumor and radioprotection after sublethal irradiation

The antitumor effects of two iridoid compounds, geniposidic acid (GA) and geniposide (GP), were investigated in mice along with their possible effects on radioprotection after sublethal X-irradiation. Decreases in the growth of the implanted tumor by ascitic cells were a result of intraperitoneal administration of GA and GP at high concentrated levels. This result was achieved by exerting the levels of dosage in a dose-dependent manner. Except on the 12th day after treatment by the dosage of 500 mg/kg, reduced radiation effects of mice treated with the drugs in the 30 min preirradiated period by GA and GP on peripheral leukocytes were not observed significantly by the sublethal whole-body X-irradiation. And except on the 7th day after treatment, when these two compounds were administered i.p. to mice 30 min before 4 Gy irradiation, neither GA nor GP enhanced significantly the postirradiation responses of splenic blastogenesis by PHA. In addition, GA might be a more potent tumor growth inhibitor than GP when combined with the X-irradiation, though there was no significant synergetic effect on their combined antitumor activity. The preliminary results of GA and GP on hematological and blastogenic observations in this study suggested that they may very well, partially, play a role in an effective anticancer product with the ability to decrease undesirable radiation damage to the hematologic tissue after high dose irradiation.

Protection of mouse bone marrow by Si-Wu-Tang against whole body irradiation

The ability of Si-Wu-Tang to eliminate bone marrow damage after radiation was assessed using both a clonogenic assay (survival of colony forming units spleen--CFUs) of stem cell survival and a hematopoietic functional assay including the changes of hemograms and hematocrit. Cell survival curves and dose-response curves for radiation alone and Si-Wu-Tang administration with radiation were constructed over the dose range of 1 to 9 Gy. Si-Wu-Tang was given 7 days before irradiation at a consecutive fractionated dose of 20 mg/20 g body weight. The radioresistance of stem cells treated by Si-Wu-Tang was higher than that of those treated by irradiation alone. However, the anti-radiation effect of leukocytes was not as significant as that of erythrocytes, thrombocytes and hematocrit. These data suggest that the anti-radiation effect by Si-Wu-Tang is dependent on dose and will be less after 4 Gy irradiation. Hemograms with a short turnover period, such as leukocytes, may be less affected after Si-Wu-Tang administration.

Difference in the effects of radioprotection between aerial and root parts of Lycium chinense

Radiation protection from bone marrow death by consecutive injections of crude extracts from different parts of Lycium chinense (LC), root (LCR) and aerial part (LCA), before whole body X-irradiation was confirmed by tests with ICR strain mice. Both extracts were effective after intraperitoneal injection of a high dose, once a day, for seven consecutive days before irradiation. Based on the studies of endogenous hematopoietic spleen colony formation (CFUs), and the postirradiation behavior of hematograms and hematocrits, it was demonstrated that the LCR protects mice more effective when given in a dose of 500 mg/kg. Enhanced CFUs was found in the irradiation range of 4-8 Gy by various treatments. Recovery of leukocyte, erythrocyte and thrombocyte counts was significantly stimulated by the extract of LCR with 500 mg/kg administration. Stimulated recovery by the extract from the LCR was also observed in hematocrit. On the contrary, the extracts of both LCA and LCR did not markedly affect recovery of leukocyte, erythrocyte, thrombocyte counts and hematocrits by 250 mg/kg administration. It could be deduced that the uncertainly radioprotective action is induced by a possible process of enhanced regeneration of the hematopoietic stem cells due to either enhanced postirradiation repair or an increased proliferation of the hematopoietic stem cells under the suitable extract administration.

Radioprotective Effect of Ganoderma Lucidum (Leyss, ex. Fr.) Karst after X-ray Irradiation in Mice

Six to seven week old male mice of ICR strain were exposed to 500 or 650 cGy of X-ray during experiments to determine if Ganoderma lucidum could be a factor in modification of radiation damage. Continuous intraperitoneal injection of the extract from Ganoderma lucidum before or after irradiation of 500 and 650 cGy of X-ray was found to improve the 30-day survival fractions of ICR mice, but wasnt significant by statistical analysis. The administration also enhanced the recoveries of the body weights and increased the recovery of hemograms of irradiated mice from radiation damage by injecting before or after radiation exposure, especially for the treatment of 500 cGy irradiation. The 10-day CFUs was significantly higher for Ganoderma lucidum treated groups than for untreated groups. However, the differences of radioprotective effect between the X-ray irradiated groups with Ganoderma lucidum pretreated and post-treated were not significant (p greater than 0.05).

Toxic effects of Erycibe obtusifolia, a Chinese medicinal herb, in mice

Extract of stem of Erycibe obtusifolia (EO) at doses of 10, 20 and 30 mg/kg was experimentally tested through oral and intraperitoneal administration. Toxic effects of EO were assessed through functional changes of the liver and kidneys. Mice died immediately following the i.p. injection at the dose of 10 mg/kg. However, no death occurred after the oral administration at the dose of 10, 20 or 30 mg/kg under close observations for at least 2 weeks. Changes of several functional parameters in both the liver and kidney appeared simultaneously after the oral administration. Although the higher dose increased the levels of serum glutamate-oxalate-transaminase (sGOT), serum glutamate-pyruvate-transaminase (sGPT), and blood urea nitrogen (BUN), and decreased the levels of hematocrit at 6 h after the treatment, no distinct dose-dependent relationship existed between the administered doses and the changes in functional parameters observed.

Recovery of the hematopoietic system by Si-Jun-Zi-Tang in whole body irradiated mice

The herbal formulation Si-Jun-Zi-Tang reduced the decrease of leukocytes, erythrocytes, thrombocytes and hematocrit in irradiated mice. In general, its protection was more effective in leukocytes and thrombocytes than other hematocytes. Protection of bone marrow stem cells by Si-Jun-Zi-Tang was markedly enhanced by increased radiotolerance under the dose ranging from 0 to 5 Gy. This increased radiotolerance led to a prolonged shoulder in the survival curve but did not influence the D0 value. Si-Jun-Zi-Tang exerted a beneficial effect on clinical syndromes such as anemia. From the results in this study, we concluded preliminarily that the most effective concentration with least toxicity was about 20 mg/20 g body weight. At this dose, levels of leukocytes as well as thrombocytes were enhanced significantly after chi-irradiation. Elevation of erythrocytes and hematocrits could also be found but was not significant.

Comparative study on the immunocompetent activity of three different kinds of Peh-Hue-Juwa-Chi-Cao, Hedyotis diffusa, H. corymbosa and Mollugo pentaphylla after sublethal whole body x-irradiation

This brief communication describes the immunocompetent activity of the Chinese folk‐medicinal herbs, Hedyotis corymbosa, H. diffusa and Mollugo pentaphylla in mice after moderate whole body x‐irradiation. These antitumour drugs, given at doses of 500 and 1000u2009mg/kg/day for 7 consecutive days before x‐irradiation protected ICR strain mice from the sublethal effects of radiation at a dose of 4u2009Gy, especialy for the dose at 1000u2009mg/kg. Prior administration of H. corymbosa and H. diffusa ameliorated the leukopenia and splenic cellular decrease induced by sublethal irradiation, and slightly increased the immunocompetence of splenic cells after being stimulated by mitogens. However, administration of M. pentaphylla before x‐irradiation exerted a less protective effect on ameliorating leukopenia and on splenic cellular immunocompetence. These findings suggest that some types of Peh‐Hue‐Juwa‐Chi‐Caoi (PHJCC) may also be effective in the prevention of haematopoietic damage when used in combination with radiotherapy.

Preliminary study on antiradiation effect of kuei-pi-tang.

In order to evaluate the potential action of Kuei-Pi-Tang as an antiradiation agent, colony forming units of bone marrow cells in the spleen (CFUs) were used. Different sequences of X-ray irradiation with or without Kuei-Pi-Tang administration in the groups of ICR strain mice were intraperitoneally injected 10mg/20g or 20mg/20g, once a day, for consecutive seven days before or after 4Gy X-ray irradiation. After the different treatments, whole blood was collected from the tail endings to observe the fluctuation of leukocytes, erythrocytes and thrombocytes. The administration of 20mg/20g was more effective than that of 10mg/20g. Lower radiosensitivity was observed with the treatment of 20mg/20g of Kui-Pi-Tang than that of 10mg/20g. The injection of Kuei-Pi-Tang accelerated the recovery of blood cell counts of leukocytes, erythrocytes and thrombocytes in mice irradiated with 4Gy, especially for leukocytes under the treatments with 20mg/20g of Kuei-Pi-Tang administered after irradiation.

Preliminary study on the anti-radiation effect of Jen-Sheng-Yang-Yung-Tang

Six to seven week old male mice of ICR strain were exposed to different doses of x-rays to determine if jen-sheng-yang-yung-tang could be a modifier in the elimination of radiation damage. Colony forming units of bone marrow cells in the spleen (CFUs) were measured before and after x-ray irradiation with intraperitoneal injection of 10 mg/20 g or 20 mg/20 g body weight of jen-sheng-yang-yung-tang, once a day for seven consecutive days. The recovery of CFUs and hemocytes counts by 4 Gy irradiation with jen-sheng-yang-yung-tang administration was faster for a concentration of 20 mg/20 g than 10 mg/20 g. The measurement of 10-day CFUs showed an increase of radiotolerance in the treatment of 20 mg/20 g administration before x-ray irradiation. The injection of jen-sheng-yang-yung-tang accelerated the recovery of hemocyte counts in mice irradiated with 4 Gy x-ray; the effect was especially profound for leukocytes with 20 mg/20 g jen-sheng-yang-yung-tang administration after irradiation.