• The Korea Journal of Herbology
• /
• v.33 no.4
• /
• pp.1-7
• /
• 2018

Objectives : Diabetic nephropathy is one of the most significant chronic complications of diabetes. Advanced glycation end products (AGEs) have been implicated in the development of diabetic nephropathy. GS-E3D is an enzymatic modified red ginseng extract by pectin lyase and has an increased concentration of the ginsenoside Rd compared to an unmodified red ginseng extract. In this study, we evaluated the preventive effects of GS-E3D on renal dysfunction in the type 2 diabetic db/db mice. Methods : GS-E3D (100 or 250 mg/kg body weight per day) was given to db/db mice through oral gavage for 6 weeks. Body weight and blood glucose levels were examined. At the end of the experiment, albuminuria was measured. The renal tissues were collected for histological examination, and immunohistochemical staining was used to detect renal accumulation of AGEs and podocyte loss Results : In the db/db mice, severe hyperglycemia developed, and albuminuria was significantly increased. Diabetes induced markedly morphological alterations to the renal glomerular cells. AGE accumulations and podocyte loss were detected in renal glomeruli. No difference in blood glucose levels was noted between GS-E3D-treated and vehicletreated diabetic db/db mice. However, GS-E3D treatment significantly reduced albuminuria and AGE accumulations in diabetic mice. Moreover, the loss of podocytes was restored by GS-E3D treatment. Conclusions : GS-E3D might be beneficial for the treatment of diabetic nephropathy. The ability of GS-E3D on to attenuate albuminuria and podocyte dysfunction in the db/db mice may be mediated by the inhibition of AGE accumulation.

• Archives of Pharmacal Research
• /
• v.29 no.3
• /
• pp.256-264
• /
• 2006

Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of Salicornia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of met-formin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.

• Journal of Ginseng Research
• /
• v.37 no.1
• /
• pp.80-86
• /
• 2013

Korean red ginseng has been shown to possess a variety of biological activities. However, little is known about antiviral activity of ginsenosides of Korean red ginseng. Here, we investigated the protective effect by oral administration of various ginsenosides on the lethal infection of haemagglutinating virus of Japan (HVJ) in mice. In a lethal infection model in which almost all mice infected with HVJ died within 15 days, the mice were administered orally (per os) with 1 mg/mouse of dammarane-type (ginsenoside-Rb1, -Rb2, -Rd, -Re, and -Rg2) or oleanolic acid-type (ginsenoside-Ro) ginsenosides 3, 2, and 1 d before virus infection. Ginsenoside-Rb2 showed the highest protective activity, although other dammarane-type and oleanolic acid-type ginsenosides also induced a significant protection against HVJ. However, neither the consecutive administration with a lower dosage (300 ${\mu}g$/mouse) nor the single administration of ginsenoside-Rb2 (1 mg/mouse) was active. In comparison of the protective activity between ginsenoside-Rb2 and its two hydrolytic products [20(S)- and 20(R)-ginsenoside-Rg3], 20(S)-ginsenoside-Rg3, but not 20(R)-ginsenoside-Rg3, elicited a partial protection against HVJ. The protective effect of ginsenoside-Rb2 and 20(S)-ginsenoside-Rg3 on HVJ infection was confirmed by the reduction of virus titers in the lungs of HVJ-infected mice. These results suggest that ginsenoside-Rb2 is the most effective among ginsenosides from red ginseng to prevent the lethal infection of HVJ, so that this ginsenoside is a promising candidate as a mucosal immunoadjuvant to enhance antiviral activity.

• Journal of Ginseng Research
• /
• v.24 no.3
• /
• pp.143-147
• /
• 2000

In previous studies we have demonstrated that several individual ginsenosides such as Rc, Rd, Re and Ri relieves formalin-induced pain following systemic treatment. But it is unknown where these single ginsenosides induce antinociception. We investigated the antinoiceptive effect of four individual ginsenosides on formalin-induced pain after intrathecal (i.t.), intracereventricular (i.c.v.), or subcutaneous (s.c.) administration using mice. We found that ginsenoside Rc, Rd, and Re except Rf attenuated both acute and tonic phase of pain. Ginsenoside Rf attenuated only tonic phase of pain after i.t. administration. The ED$\_$50/ was 1.0 (0.55∼l.75 mg/kg) for Rc, 1.15 (0.6∼2.25 mg/kg) for Rd, and 8.9 (3.9∼20.5 mg/kg) for Re in acute phase of pain. The ED$\_$50/ was 0.3 (0.1∼0.85 mg/kg) for Rc, 0.6 (0.35∼l.1 mg/kg) for Rd, 2.45 (1.25∼4.65 mg/kg) for Re, and 1.9 (1.5∼4.25 mg/kg) for Rf in tonic phase of pain. We also found that ginsenoside Rc, Rd, Re, and Rf after i.c.v. administration attenuated both acute and tonic phase of pain. The ED5o for acute phase of pain was 0.9 (0.55∼l.4mg/kg) for Rc, 0.9 (0.45∼1.7 mg/kg) for Rd, 0.93 (0.5∼l .75 mg/kg) for Re, and 1.85 (0.95∼3.5 mg/kg) for Rf. The ED$\_$50/ for tonic phase of pain was 0.7 (0.45∼1.05 mg/kg) for Rc,1.25 (0.7∼2.2 mg/kg) for Rd, 0.85 (0.45∼1.6 mg/kg) for Re, and 0.8 (0.4∼1.45 mg/kg) for Rf. Thus, the order of the analgesic potency was Rc$\geq$Rd>Re>Rf in both i.t. and i.c.v. administration routes. However, s.c. pretreatment of four ginsenosides did not reduce formalin-induced pain. These results suggest that analgesic effect of ginsenosides is achieved through spinal or supraspinal site(s) in formalin test.

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.5
• /
• pp.345-352
• /
• 2010

The present study was undertaken to explore the potential of erythropoietin in memory deficits of mice. Memory impairment was produced by scopolamine (0.5 mg/kg, $i.p.$) and intracerebroventricular streptozotocin (i.c.v STZ, 3 mg/kg, $10{\mu}l$, $1^{st}$ and $3^{rd}$ day) in separate groups of animals. Morris water-maze test was employed to assess learning and memory. The levels of brain thio-barbituric acid reactive species (TBARS) and reduced glutathione (GSH) were estimated to assess degree of oxidative stress. Brain acetylcholinesterase enzyme (AChE) activity was also measured. Scopolamine/streptozotocin administration induced significant impairment of learning and memory in mice as indicated by marked decrease in Morris water-maze performance. Scopolamine/streptozotocin administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (an increase in TBARS and a decrease in GSH) levels. Treatment of erythropoietin (500 and 1,000 IU/Kg i.p.) significantly reversed scopolamine- as well as streptozotocin-induced learning and memory deficits along with attenuation of those-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that erythropoietin exerts a beneficial effect in memory deficits of mice possibly through its multiple actions including potential anti-oxidative effect.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.6
• /
• pp.443-448
• /
• 2009

For successful visual perception by visual prosthesis using electrical stimulation, it is essential to develop an effective stimulation strategy based on understanding of retinal ganglion cell (RGC) responses to electrical stimulation. We studied RGC responses to repetitive electrical stimulation pulses to develop a stimulation strategy using stimulation pulse frequency modulation. Retinal patches of photoreceptor-degenerated retinas from rd1 mice were attached to a planar multi-electrode array (MEA) and RGC spike trains responding to electrical stimulation pulse trains with various pulse frequencies were observed. RGC responses were strongly dependent on inter-pulse interval when it was varied from 500 to 10 ms. Although the evoked spikes were suppressed with increasing pulse rate, the number of evoked spikes were >60% of the maximal responses when the inter-pulse intervals exceeded 100 ms. Based on this, we investigated the modulation of evoked RGC firing rates while increasing the pulse frequency from 1 to 10 pulses per second (or Hz) to deduce the optimal pulse frequency range for modulation of RGC response strength. RGC response strength monotonically and linearly increased within the stimulation frequency of 1~9 Hz. The results suggest that the evoked neural activities of RGCs in degenerated retina can be reliably controlled by pulse frequency modulation, and may be used as a stimulation strategy for visual neural prosthesis.

• The Journal of Internal Korean Medicine
• /
• v.23 no.1
• /
• pp.123-131
• /
• 2002

Objective : It is well known that modern chemotherapy against cancer has side effects to a living body, especially hemopoietic and immunologial disfunctions. However, there are no effective ways to reduce them. Recently, traditional Korean herb medicine has been reported to have some biological modifying responses. Therefore, we hypothesized that additional application of herb medicine during chemotherapy is more effective to reduce its side effects. While we were studying the effects, we have observed the inhibitory effect of Soamgudamikgitang on formation of side effects derived from Cyclophosphamide, it has been used in clinical practice at Kyung Hee Medical Center. Methods : We injected 200mg/kg of Cyclophosphamide, one time, to an experimental group, consisting of ten mice. We divided them into eight groups: normal, CPX, SAKT 2mg, SAKT 10mg, SAKT 50mg, SAKT 2mg, CPX, SAKT 10mg+CPX, SAKT 50mg+CPX. We injected Soamgudamikgitang seven days, five days, three days, and one day before we injected CPX. One day, three days, and five days after CPX injection, we injected Soamgudamikgitang again and then killed all the mice. The parameters determined in this experiment were daily body weight liver and spleen weight, RBC, WBC, and platelet for hemopoietic dysfunction and AST, ALT for hepatotoxicity, BUN, creatine for renal toxcity, lymphocyte proliferation activity and lymphocyte subsets for immunological toxcity. Results : We have found that Soamgudamikgitang has inhibitory effects on the formation of Cyclophosphamide's side effects. Significant differences between the group, which contained Cyclophosphamide, and the other group, which contains Cyclophosphamide and 2, 10, 50mg of Soamgudamikgitang respectively were observed. Platelets(2mg of Soamgudamikgitang, p<0.05 ;10mg, p<0.01 ;50mg, p<0.001), liver weight(50mg, p<0.01), spleen weight(10mg, p<0.05), AST(all groups, p<0.01), ALT(2mg, p<0.01 ;10mg, p<0.05 ;50mg, p<0.01), BUN(2mg, p<0.01 ;50mg, p<0.05). Although immunological in both lymphocyte proliferation and its subsets were not observed, which shows that Soamgudamikgitang has a strong effect on T cell activities. Conclusions : From the above results, we can expect that the combined therapy of Soamgudamikgitang and Cyclophosphamide is more effective for treating cancer patients.

• The Journal of Internal Korean Medicine
• /
• v.34 no.2
• /
• pp.134-146
• /
• 2013

Objectives : Auklandia Lappa (ALE) is one of the herbs used frequently to treat abdominal pain and diarrhea and reported anti-inflammatory activity by suppressing proinflammatory cytokines. This study was designed to investigate whether ALE could show protective activities on experimental colitis induced by dextran sulfate sodium (DSS) models. Methods : Colitis was induced by DSS in Balb/c mice. ALE 10, 30, 100 and 300 mg/kg were orally administered twice a day for 7 days in DSS model. Mice weight was measured daily. Scoring of clinical findings was measured every other day. Colon length, edema, fecal blood and histological damages were assessed at day 7 in DSS model. In histological analysis, we checked cryptal glands, surface epithelium, submucosa, transmural, stroma and scored degree of inflammatory cell damage by modified histological scoring. We also calculated cytokines concentrations including IFN-${\gamma}$, TNF-${\alpha}$, IL-6, IL-$1{\beta}$, IL-17, IL-23, IL-10 and TGF-${\beta}1$ by Biometric Multiplex Cytokine Profiling method. Results : ALE showed the protective effects on DSS-induced experimental colitis. ALE inhibited shortening of colon length and histological damages of colon does-dependently, but it did not inhibit weight loss. ALE also inhibited IFN-${\gamma}$ and IL-6 expression, and upregulated cytokines (IL-10, TGF-${\beta}1$) related to regulatory T cell differentiation and proliferation. Conclusions : The current results demonstrate the clinical utility of ALE in traditional medicine and indicate the possibility of potent drug development of inflammatory bowel diseases from natural products. Further investigations for exact mechanisms will be needed.

• Journal of Acupuncture Research
• /
• v.18 no.1
• /
• pp.113-128
• /
• 2001

Objective : To investigate the effect of BUM aqua-acupuncture in treating the RA, the immunosis to logical analysis of LPS induced arthritis in mice to study this. For 14th day after the injection of LPS & BUM injection, the distribution of fibroblast, collagen, CD54(ICAM-1), CD106(VCAM-1), IL-$1{\beta}$, IL-2 receptor, CDl lb(macrophage) were examined on synovial capsule of mice knee joint. For 14th day after the injection of LPS & BUM injection, the distribucion of CD4(TH cell), CD8(TC cell), CD40(B cell) were examined on common iliac lymph node in mice. Methods : The experimental model of arthritis was induced by injection of 300${\mu}g$/kg LPS in BALB/c mice weighing 30g. The 100${\mu}l$ BUM aqua-acupuncture which compounded calculus bovis, fel ursi and moschus was injected into GB34 of mice every other day for 12 days. For 3rd, 7th, 14th day after the injection of LPS, the neutrophil, lymphocyte and monocytc counts in WBC were measured using hemacytometer. Results : The obstain results are summarized as follows ; 1. In sample group, the neutrophils counts were increased and the lympnocytes counts were decreased compared with control group. 2. The distribution of fibrosis & fibroblast on synovial membrane were decreased compared with control group. 3. The distribution of collagen fiber on synovial membrane were decreased compared' with control group. 4. The distribution of CD54(ICAM-1) & CD106(VCAM-1) on synovial membrane were decreased compared with control group. 5. The distribution of IL-$1{\beta}$ & IL-2 receptor on synovial membrane were decreased compared with control group. 6. The distribution of CDb(macrophage) on synovial membrane were decreased compared with control group. 7. The distribution of CD4(TH cell), CD8(TC cell) and CD40(B cell) in common iliac lymph nodes were decreased compared with control group. Conclusions : BUM aqua-acupuncture stimulation decreased inflammatory responses LPS induced arthritis in mice.

• Journal of Ginseng Research
• /
• v.40 no.2
• /
• pp.196-202
• /
• 2016

Background: Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits anti-inflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. Methods: To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10-100 mg/kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with $CD11b^+$, $iNOS^+$/interleukin-12/tumor necrosis factor-${\alpha}$ labeling. For the in vitro study, GSRd ($10-100{\mu}g/mL$) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. Results: In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylin-eosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-${\alpha}$. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. Conclusion: These findings demonstrate that GSRd possess a protective function against renal ischemia/reperfusion injury via downregulating M1 macrophage polarization.