In vivo and in vitro antitumor effects of platycodin d, a saponin purified from platycodi radix on the h520 lung cancer cell.

Platycodin D is a major pharmacological constituent of Platycodi radix and has showed various pharmacological activities through oxidative stress defense mechanisms. Here, possible antitumor, anticachexia, and immunomodulatory activities of platycodin D were observed on the H520 tumor cell-bearing athymic nude mice after confirming the in vitro cytotoxicity. Platycodin D was orally administered at dose levels of 200, 100, and 50 mg/kg, once a day for 35 days from 15 days after implantation. The results were compared with gemcitabine 160 mg/kg intraperitoneally treated mice (7-day intervals). Platycodin D showed favorable cytotoxic effects on the H520 cells, and also dose-dependently decreased the tumor volumes and weights with increases of apoptotic cells (caspase-3 and PARP immunopositive cells), iNOS and TNF-α immunoreactivities, decreases of COX-2 immunoreactivities in tumor masses. Platycodin D also showed dose-dependent immunostimulatory and anticachexia effects. Gemcitabine showed favorable cytotoxity against H520 tumor cell and related in vivo antitumor effects but aggravated the cancer related cachexia and immunosuppress in H520 tumor cell-bearing athymic nude mice. Taken together, it is considered that oral treatment of platycodin D has potent antitumor activities on H520 cells through direct cytotoxic effects, increases of apoptosis in tumor cells, and immunostimulatory effects and can be control cancer related cachexia.

28 Days repeated oral dose toxicity test of aqueous extracts of mahwangyounpae-tang, a polyherbal formula.

Mahwangyounpae-tang (MT), consisting of 22 types of herbal extracts has been used for thousands of years in Korean traditional medicine for the oral treatment of respiratory diseases including asthma. As part of a safety evaluation of MT extract for use in asthma, the 28 day repeat oral dose toxicity of an aqueous MT extract was evaluated at 800, 400 and 200mg/kg per day dose levels. The results showed that no significant toxicological changes were observed when 200 and 400mg/kg per day of MT extract was administered to rats. But when the dose was increased to 800 mg/kg per day, increases of body weights, food consumptions, and heart and kidney weights were observed with hypertrophy of heart and tubular necrosis of kidney. Besides this, no other signs of toxicity were observed. Based on these results, it can be concluded that the no observed adverse effect level of MT extract is 400mg/kg per day. Therefore, the use of MT is expected to be safe because 30 mg/kg was shown to be pharmacologically effective in mice and the high dose heart and kidney findings are not considered to represent any safety concern for humans.

Genotoxicity testing of aqueous extracts of Mahwangyounpae-tang, a polyherbal formula.

Mahwangyounpae-tang (MT), consisting of 22 types of herbal extracts has been used for thousands of years in Korean traditional medicine for the oral treatment of respiratory diseases including asthma. As part of a safety evaluation of MT extracts for use in asthma, the potential genotoxicity of an aqueous MT extract was evaluated using the standard battery of tests (bacterial reverse mutation assay; chromosomal aberrations assay; mouse micronucleus assay) recommended by Korea Food and Drug Administration (KFDA). The MT extract was determined not to be genotoxic under the conditions of the reverse mutation assay, chromosomal aberrations assay and mouse micronucleus assay. Use of MT is presently expected to be safe, as anticipated intake is small compared to the doses administered in the genotoxicity assays and may, after further toxicity research, prove to be a useful anti-asthma agent.

Ameliorative anti-diabetic activity of dangnyosoko, a Chinese herbal medicine, in diabetic rats.

The preventive anti-diabetic effect of dangnyosoko (DNSK), a Chinese herbal medicine, was evaluated in STZ-induced diabetic rats. DNSK was orally administered once a day from 3 d after STZ-induction at 100, 200, and 500 mg/kg for 4 weeks, and the results were compared to those for glibenclamide. Dramatic decreases in body weight and plasma insulin levels and increases in blood and urine glucose levels were detected in STZ-induced diabetic animals with disruption and disappearance of pancreatic islets and increases in glucagon- and decreases in insulin-producing cells. However, these diabetic changes were significantly and dose-dependently inhibited by treatment with DNSK, and DNSK at 100 mg/kg showed more favorable effects than glibenclamide at 5 mg/kg. Based on these results, it is thought that DNSK has favorable effects in ameliorating changes in blood and urine glucose levels and body weight, and that histopathological changes in the pancreas in STZ induce diabetes.

Anti-diabetic activity of SMK001, a poly herbal formula in streptozotocin induced diabetic rats: therapeutic study.

The therapeutic anti-diabetic effect of SMK001, a poly herbal formula was evaluated in the streptozotocin (STZ; 60 mg/kg, single intraperitoneal injection) induced diabetic rats. For therapeutic study, test articles were orally dosed once a day from 21 d after STZ-dosing at 100, 200 and 500 mg/kg/5 ml dosage levels for 4 weeks. The body weight changes, blood and urine glucose level changes were monitored with changes on the pancreas weight, and after sacrifice, the histopathological changes of pancreas and the changes of insulin- and glucagon-producing cells were also observed by immunohistochemistry. The results were compared to that of glibenclamide 5 mg/kg-dosing group. Significantly (p<0.01 or p<0.05) decrease of body weight, blood and urine glucose levels were detected in STZ-induced diabetic animals with disruption and disappearance of pancreatic islets. In addition, significantly (p<0.01) increase of glucagon- and decrease of insulin-producing cells were detected in STZ induced diabetic rats. However, these diabetic changes were significantly (p<0.01 or p<0.05) and dose dependently decreased in SMK001-dosing groups, and SMK001 100 mg/kg showed more favorable effects compared to that of glibenclamide 5 mg/kg. Based on these results, it is considered that SMK001 has favorable effect to inhibit the changes on the blood and urine glucose levels, body weight and the histopathological changes of pancreas in STZ induce diabetes.

Changes of the intestinal endocrine cells in the C57BL/6 mouse after implantation of murine lung carcinoma (3LL): an immunohistochemical quantitative study.

AIM: To study the distributions and frequencies of intestinal endocrine cells in the C57BL/6 mouse with immunohistochemical method using seven types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, glucagons, gastrin, cholecystokinin (CCK)-8 and human pancreatic polypeptide (hPP) after abdominal subcutaneous implantation of murine lung carcinoma (3LL). METHODS: The experimental animals were divided into two groups, one is non-implanted Sham and the other is 3LL-implanted group. Samples were collected from six regions of intestinal tract at 28(th) d after implantation of 3LL cells (1X10(5) cell/mouse). RESULTS: In this study, five types of immunoreactive (IR) cells were identified except for gastrin and hPP. The regional distributions of the intestinal endocrine cells in the 3LL-implanted group were similar to those of the non-implanted Sham. However, significant decreases of IR cells were detected in 3LL-implanted group compared to those of non-implanted Sham. CGA- and serotonin-IR cells significantly decreased in 3LL-implanted groups compared to that of non-implanted Sham. Somatostatin-IR cells in the jejunum and ileum and CCK-8-IR cells in the jejunum of 3LL-implanted groups significantly decreased compared to that of non-implanted Sham. In addition, glucagon-IR cells were restricted to the ileum and colon of non-implanted Sham. CONCLUSION: Implantation of tumor cell mass (3LL) induced severe quantifiable changes of intestinal endocrine cell density and the abnormality in density of intestinal endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.

Effect of Mornidae Radix extracts on experimental osteoporosis in sciatic neurectomized mice.

The preventive and therapeutic effects of aqueous extracts of Mornidae Radix (MR) were observed in sciatic neurectomized mice, a disused osteoporotic model. The right hind limbs of 80 mice were neurectomized and 20 mice were sham-operated and served as a sham control. Then 50, 100 and 200 mg/kg of MR extracts were dosed 3 days after neurectomy for 6 weeks in the prevention study and were dosed 2 weeks after neurectomy for 12 weeks for the therapeutic study. After dosing with the MR extracts, the thickness of the hind limbs, tibia failure load, tibia bone mineral density (BMD), serum osteocalcin levels, tibia calcium (Ca) and phosphorus (P) contents were monitored with histomorphometrical changes of the tibia. In both the prevention and therapeutic studies, the MR extracts significantly and dose-dependently suppressed the decrease in hind limb thickness, tibia failure load, BMD, tibia Ca and P contents with an increase in serum osteoclacin levels. In addition, the MR extracts also significantly and dose-dependently suppressed the decrease in histomorphometrical parameters of the tibia such as volume, length and thickness of trabecular bone and thickness of cortical bone with an increase in osteoclast cells in both the prevention and therapeutic studies. Based on these results, the MR extracts may act as both a suppressor of bone resorption and an enhancer of bone formation in vivo and may have some favorable effects for preventing and treating the osteoporosis induced by sciatic neurectomy.

Wikyungtang inhibits proliferation of A549 human lung cancer cells via inducing apoptosis and suppressing cyclooxygenase-2 activity.

Wikyungtang, an oriental herbal formulation, has been known to exert anti-inflammatory and anti-tumoral activity. However, its molecular mechanism of action is not understood. The purpose of the present study was to examine the effect of the water extract of Wikyungtang (WKT) on the growth of A549 human lung cancer cells. Treatment with WKT resulted in a dose-dependent growth inhibition coupled with the characteristic morphological features of apoptosis. Apoptosis-inducing concentrations of WKT induced caspase-3 and caspase-9 activation accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase and phospholipase C-gamma1. In addition, WKT-induced apoptosis in A549 cells was associated with a decreased expression of the anti-apototic Bcl-XL expression. WKT treatment also inhibited the expression of cyclooxygenase (COX)-2 and the accumulation of prostaglandin E2 without significant changes in the levels of COX-1. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of WKT.