Hyuck Jai Choi

Anti-stress Effects of 20( S )-Protopanaxadiol and 20( S )-Protopanaxatriol in Immobilized Mice

Panax ginseng C.A. MEYER (Araliaceae), which contains ginsenosides as its main components, has been shown to have various biological effects, including anti-inflammatory, anxiolytic, anti-stress, and anti-tumor effects. Orally administered ginsenoside Rb1 and Re are metabolized to 20(S)-protopanaxadiol (PPD) and compound K via ginsenoside Rd and 20(S)-protopanaxatriol (PPT) and ginsenoside Rh1 via ginsenoside Rg1 by gut microbiota, respectively. Therefore, we investigated the anti-stress effects of these metabolites, PPD and PPT, by measuring their anxiolytic and anti-inflammatory effects in immobilized mice. Treatment with PPD and PPT prior to immobilization stress increased the time spent in open arms and open arm entries in the elevated plus-maze (EPM) test. The anxiolytic effects of PPD (10 mg/kg) and PPT (10 mg/kg) were comparable to that of buspirone (1 mg/kg). This observed anxiolytic effect of PPD was significantly blocked by flumazenil or bicuculline, and the effect of PPT was blocked by WAY-100635. Treatment with PPD also potently suppressed immobilization stress-induced serum levels of corticosterone and interleukin (IL)-6 by the enzyme-linked immunosorbent assay. However, PPT treatment did not suppress them. Based on these findings, PPD and PPT may exhibit the anxiolytic effect via γ-aminobutyrateA (GABAA) receptor(s) and serotonergic receptor(s), respectively, and PPD may have an anti-inflammatory effect that is more potent than that of PPT.

Heat-processed ginseng saponin ameliorates the adenine-induced renal failure in rats

To evaluate the effect of the saponin of heat-processed ginseng (Sun ginseng, SG), we investigated the protective effect of SG total saponin fraction against adenine-induced chronic renal failure in rats. SG saponin significantly decreased the levels of urea nitrogen and creatinine in the serum, but increased the urinary excretion of urea nitrogen and creatinine, indicating an improvement of renal function. SG saponin also inhibited adenine-induced kidney hypertrophy and edema. SG saponin reduced serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase activities increased by adenine. Based on these findings, the ameliorating effect of SG on chronic renal failure may result from its saponin.

The ethanolic extract of the Eclipta prostrata L. ameliorates the cognitive impairment in mice induced by scopolamine

ETHNOPHARMACOLOGICAL RELEVANCE Eclipta prostrata L. (Asteraceae) has been prescribed for whole body nourishment and nervine tonic in Asia. However, the effects of E. prostrata in learning and memory have not been fully explored. AIM OF THE STUDY To scientifically elucidate the effects of E. prostrata on cognitive functions, we examined whether E. prostrata could ameliorate a cholinergic blockade-induced memory impairment, and we also investigated the effects of E. prostrata on the synaptic plasticity in the hippocampus. MATERIALS AND METHODS Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist. The anti-amnesic effects of the ethanolic extract of Eclipta prostrata L. (EEEP) were measured in mice by the passive avoidance, Y-maze and Morris water maze tasks. To test the effects of EEEP on synaptic plasticity, we measured long-term potentiation (LTP) in the hippocampus. We also studied several signaling molecules related to learning and memory, such as phosphorylated protein kinase B (Akt) or phosphorylated glycogen synthase kinase-3β (GSK-3β). RESULTS In the passive avoidance task, EEEP (50 or 100mg/kg, p.o.) significantly ameliorated the shortened step-through latency induced by scopolamine. EEEP (100mg/kg, p.o.) also showed significant increase in alternation behavior during the Y-maze task. In the Morris water maze task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by EEEP (50 or 100mg/kg, p.o.). Moreover, EEEP (100μg/ml) significantly enhanced hippocampal LTP without affecting basal synaptic transmission. The administration of EEEP (100mg/kg) increased the phosphorylation levels of Akt and GSK-3β in the hippocampal region. CONCLUSION These results suggest that EEEP has memory-ameliorating activity against scopolamine-induced cognitive impairment and facilitates LTP in the hippocampus. This could be, at least in part, mediated by the activation of the Akt-GSK-3β signaling pathway.

Anti-fatigue Effects of 20( S )-Protopanaxadiol and 20( S )-Protopanaxatriol in Mice

Ginseng (Panax ginseng C.A. MEYER, Araliaceae), which contains protopanaxadiol-type and protopanaxatriol-type ginsenosides, has been used for inflammation, fatigue, stress, and tumor in Asian countries. Orally administered ginsenosides are metabolized to their aglycones 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT) by gut microbiota. However, their anti-fatigue effects have not been studied thoroughly. Therefore, we investigated the anti-fatigue activities of PPD and PPT in mice, using the weight-loaded swimming (WLS) and the rota-rod tests. Ginseng water extract (GW), ginseng saponin fraction (GWS) and ginseng polysaccharide fraction (GWP) at concentrations of 50 and 100 mg/kg and PPD and PPT at 5 and 10 mg/kg were orally administered to mice once daily for 5 d. GW, GWS, and PPT significantly increased the WLS time, however, GWP and PPD did not cause any significant change. PPT induced the most significant increase in WLS time. PPD (10 mg/kg) and PPT (5 and 10 mg/kg) inhibited the WLS-induced increase in corticosterone, lactate, lactate dehydrogenase (LDH), and creatinine levels as well as the reduction in glucose level. PPT increased the riding time in the rota-rod test, and also inhibited corticosterone, lactate, and creatinine levels. These findings suggest that the anti-fatigue effect of ginseng may be attributable to its saponins, particularly PPT, rather than to its polysaccharides.

Anti-stress effect of astragaloside IV in immobilized mice.

ETHNOPHARMACOLOGICAL RELEVANCE Astragaloside IV, a major component extracted from the roots of Astragalus membranaceus (AM), possesses anti-inflammatory, anti-oxidative, anti-fibrotic, anti-infarction and immunoregulatory effects. To clarify anti-stress effect of AM, anxiolytic and anti-inflammatory effects of 80% ethanol extract of AM and astragaloside IV were investigated in immobilization stress model. MATERIALS AND METHODS The mice were orally administered with AM (50, 200, and 500 mg/kg), astragaloside IV (5, 10, and 20 mg/kg) and buspirone, a positive drug, 1h before immobilization treated for 2h. For anxiolytic activity assay, EPM test was performed in mice. For anti-inflammatory activity assay, serum levels of corticosterone, IL-6 and TNF-α were measured using ELISA kits. RESULTS AM extract and astragaloside IV increased dose-dependently time spent on open arms and open arm entries in the EPM test. Anxiolytic effects of AM extract (500 mg/kg) and astragaloside IV (20 mg/kg) were comparable to those of buspirone (1 mg/kg). Their anxiolytic effects were blocked by WAY-100635 (0.5 mg/kg, i.p.), a 5-HT1A receptor antagonist (p<0.01), but not by flumazenil (3 mg/kg, i.p.) and bicuculline (0.5 mg/kg, i.p.), GABAA receptor antagonists. AM extract and astragaloside IV also reduced serum levels of corticosterone, IL-6 and TNF-α dose-dependently. CONCLUSIONS AM, particularly astragaloside IV, may ameliorate immobilized stress-induced anxiety and inflammation.

Anti-tumor Activities of Onbaekwon on Various Cancer Cells

Anti-tumor Activities of Onbaekwon on Various Cancer Cells Jee Young Lee, Hye Kyung Oh, Han Sung Ryu, Nam Jae Kim, Won-Yong Jung, Hyun-A Oh, Hyuck Jai Choi, Seong Woo Yoon, Bong-Ha Ryu 1 Department of Korean Internal Medicine, Kyung Hee University Hospital at Gangdong 2 East-West Medical Research Institute, Kyung Hee University Medical Center 3 Department of Korean Internal Medicine, Kyung Hee University Medical Center Received 15 November 2015, revised 19 December 2015, accepted 20 December 2015 Objective : The objective of this study was to investigate the experimental efficacy of anti-tumor activity of the complexed herbal formula, Onbaekwon (OBW), which was derived from the literature of Traditional Korean Medicine, Dongeuibogam. Methods : Nine Cancer cell lines, LoVo, MCF-7, HepG2, AGS, A549, NCI-H69, HL-60, Sarcoma 180, LL/2, were prepared and the cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-2,5-dephenyl tetrazolium bromide (MTT) assay. Four of them, NCI-H69, HL-60, Sarcoma 180, and LL/2, showed strong cytotoxic activities and they were additionally undergone flow cytometry to find out their effects on apoptosis. ICR male mice were implanted with Sarcoma 180 intraperitoneally and divided into 8 species for each group. Control group was treated with normal saline, positive control group was treated with cyclophosphamide 8mg/kg, and experimental group was treated with OBW 1 g/kg. Results : Among 9 cancer cell lines, NCI-H69, HL-60, Sarcoma 180, and LL/2, expressed less than 0.10 mg/ml of IC50 under 0.1~1mg/ml of OBW. NCI-H69, HL-60, Sarcoma 180, and LL/2, showed dose-dependent efficacy of apoptosis. When Sarcoma 180 cancer cell was implanted in ICR male mice and treated with the OBW, they prolonged the median overall survival for 0.8 days, from 17.5 to 18.3. 14 대한암한의학회지 2015;20(2):13-21 이지영.오혜경.류한성.김남재.정원용.오현아.최혁재.윤성우.류봉하 Conclusion : OBW showed strong cytotoxicity to some cancer cells, which are NCI-H69, HL-60, Sarcoma 180, and LL/2, and its apoptotic activity was dose-dependent. OBW prolonged the median survival of mice implanted with Sarcoma 180. Further researches would be expected to support the efficacy of OBW.

Effects of Osteo-F, a new herbal formula, on osteoporosis via up-regulation of Runx2 and Osterix

Osteoporosis is characterized by low bone mass and structural weakness, resulting in a high risk of fracture. The aim of this study is to investigate the ameliorative effects of a herbal formula, Osteo-F, containing Schizandra chinensis, Lycium chinensis and Eucommia ulmoides, on osteoporosis. Female ICR mice were randomly assigned to a sham-operated group (Sham) and five ovariectomized (OVX) groups: OVX with vehicle (OVX), OVX with calcium (Ca), and OVX with 1, 10 and 100 mg per kg per day Osteo-F (OF1, OF10 and OF100). Oral administration of Ca or Osteo-F started 7 weeks after OVX and lasted for 13 weeks. The femurs were collected to analyze the bone mineral content (BMC) and bone mineral density (BMD) and bone histology. Blood was collected to examine serum calcium concentration. In addition, the expressions of Runx2 and Osterix in SaOS-2 osteoblast cells were analyzed to confirm the mechanism on osteoblast differentiation. In the present study, Osteo-F treatment significantly restored the low BMC and BMD in the femur. As shown in histological analysis, hyperplasia of the growth plate in the epiphyseal plate was markedly recovered in Osteo-F-treated bone. In addition, serum calcium concentrations were increased with Osteo-F treatment. In the in vitro study, the expressions of Runx2 and Osterix were significantly increased in Osteo-F-treated SaOS-2 osteoblast cells. These results indicate that oral administration of Osteo-F, a newly developed formula, has ameliorative effects on osteoporosis by increasing osteoblast related markers, such as Runx2 and Osterix.