Moonkyu Kang

The analgesic and anti-inflammatory effect of WIN-34B, a new herbal formula for osteoarthritis composed of Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE in vivo

ETHNOPHARMACOLOGICAL RELEVANCE Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE have been used for the treatment of a variety of inflammatory diseases, cold and infective diseases in many countries, including Korea and China. AIM OF THE STUDY This study aimed to assess the anti-nociceptive and anti-inflammatory activities of n-butanol fraction (WIN-34B) prepared from dried flowers of Lonicera japonica and dried roots of Anemarrhena asphodeloides as potential novel treatment of osteoarthritis. MATERIALS AND METHODS Anti-nociceptive activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were measured using acetic acid-induced writhing response, formalin-induced paw licking, hot plate, radiant heat tail-flick, carrageenan-induced paw pressure, and Hargreaves tests, respectively. Anti-inflammatory activities of WIN-34B (100, 200 and 400 mg/kg, p.o.) were assessed using acetic acid-induced vascular permeability, carrageenan-induced paw edema, and croton oil-induced ear edema. Anti-osteoarthritis effect of WIN-34B was analyzed using monosodium iodoacetate (MIA)-induced osteoarthritis animal model. RESULTS WIN-34B exhibited better anti-inflammatory activity than that of celecoxib in carrageenan at the dose of 200 mg/kg and croton oil-induced paw edema and ear edema at the doses of 200 and 400 mg/kg. WIN-34B exhibited significant anti-inflammatory effects on vascular permeability. WIN-34B also exhibited significant anti-nociceptive activities in the late phase of formalin-induced paw licking and writhing response model in mice. In radiant heat tail-flick and carrageenan-induced paw pressure tests, WIN-34B at the dose of 400 mg/kg and at the doses of 200 and 400 mg/kg presented similar activities to indomethacin and celecoxib. Compared to indomethacin WIN-34B at 400mg/kg showed similar or better anti-nociceptive activities after 1 and 2h of theraphy in the hot plate test and better anti-nociceptive activity than that of celecoxib in Hargreves test. In the MIA-induced osteoarthritis animal models, WIN-34B at 400 mg/kg exhibited similar or better anti-nociceptive property than that of celecoxib throughout the pain measurement periods. CONCLUSION When compared to celecoxib, WIN-34B exhibited similar or better anti-nociceptive and anti-inflammatory activities in osteoarthritic animal models, which may become a potential novel treatment for osteoarthritis.

The Anti-Depressant Effect of Nelumbinis Semen on Rats under Chronic Mild Stress Induced Depression-Like Symptoms

Nelumbinis Semen is a well-known traditional herbal medicine frequently used in treatment of depression in many Asian countries. In this study, its anti-depression effects in rats were investigated by comparing the test results of those treated with Nelumbinis Semen to those treated with other herbal anti-depressants, including Rehmanniae Radix Preparat, Corni Fructus, Lycii Fructus, Pinelliae Rhizoma and Hypericum Perforatum. In order to induce depression-like symptoms, the animals were placed under chronic mild stress in the form of overnight illumination for 2 consecutive days. They were treated with the respective herbal extract and forced swimming tests were conducted afterwards. The anti-depression effects of each extract were then evaluated based on a measured index, which consisted of struggling time, first latency and first rest duration. These test results show that Nelumbinis Semen provides greater anti-depression effects than the other herbal extracts. Specifically, only the rats treated with Nelumbinis Semen showed significant increases in struggling time (43.9%, p < 0.005, p = 0.0037) and in first latency time (90.2%, p < 0.05, p = 0.0116). However, the first rest duration for Nelumbinis Semen treated rats was not significantly different from the other rats. It appears that Nelumbinis Semen provides even greater anti-depression effects than Hypericum Perforatum (commonly referred to as St. Johns Wort, perhaps the most widely used natural antidepressant today). The anti-depression effects of Nelumbinis Semen might be due to the modulation of the amount of neurotransmitters involved in depression.

Yukmijihwang-Tang Derivatives Enhance Cognitive Processing in Normal Young Adults: A Double-Blinded, Placebo-Controlled Trial

Yukmijihwang-tang (YMJ), also known as Luweidihuang-tang in China, has been widely used as a general herbal tonic for hundreds of years in many Asian countries. This study examines whether YMJ derivatives (YMJd) enhance cognitive ability in normal human subjects and discusses its potential as treatment for dementia patients with deficient cognitive ability. Subjects were divided into two groups, the placebo-treated group (n = 15) and the YMJd-treated group (n = 20). K-WAIS tests, a Korean version of an individual intelligence quotient (IQ) test, and a P300 latency assessment of event-related potential (ERP) were conducted in order to measure changes in cognitive ability before and after 6 weeks of YMJd treatment. The K-WAIS mean scores of the group treated with YMJd were significantly higher than those of the placebo group (p < 0.05), and their mean P300 latency was substantially shorter (p < 0.005). These results suggest that YMJd treatment accelerates the speed of information processing and enhances cognitive ability. YMJd treatment may help dementia patients or the elderly recover from cognition deficiencies or degeneration in clinic.

Nelumbinis Semen reverses a decrease in hippocampal 5‐HT release induced by chronic mild stress in rats

Depression is associated with a dysfunctional serotonin system. Recently, several lines of evidence have suggested that a very important evoking factor in depression may be a serotonin deficit in the hippocampus. This study assessed the antidepression effects of Nelumbinis Semen (NS) through increasing serotonin concentrations under normal conditions and reversing a decrease in serotonin concentrations in rat hippocampus with depression‐like symptoms induced by chronic mild stress (CMS). Using an in‐vivo microdialysis technique, the serotonin‐enhancing effect of NS on rat hippocampus was investigated and its effects compared with those of two well‐known antidepressants, Hypericum perforatum (St Johns wort) and fluoxetine (Prozac). Rats were divided into five groups: saline‐treated normal, without CMS; saline‐treated stress control; NS‐, St Johns wort‐ and fluoxetine‐treated rats under CMS for 8 weeks or no stress treatment. NS and fluoxetine significantly increased serotonin in normal conditions and reversed a CMS‐induced decrease in serotonin release in the hippocampus (P< 0.05 compared with normal group or control group under CMS). These results suggest that NS increases the serotonin levels normally decreased in depression, resulting in an enhancement of central serotonergic transmission and possible therapeutic action in depression. It is suggested that NS may present an antidepressant effect through enhancement of serotonin.

Nelumbinis Semen reverses a decrease in 5-HT1A receptor binding induced by chronic mild stress, a depression-like symptom.

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of 5-HT1A receptors. The present study assessed ifNelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in 5-HT1A receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a 5-HT1A receptor binding assay, with a specific 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect ofN. s. on rats was investigated, and the effects compared with two well-known anti-depressants,Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, theNelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, theHyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect ofN. s. TheN. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, bothN. s. andH. p. reversed the CMS-induced decrease in 5-HT1A receptor binding. In the I to II regions of the frontal cortex,N. s. andH. p. also reversed the CMS-induced decrease in 5-HT1A receptor binding, and even showed a significant increase in 5-HT1A receptor binding compared to the F treatment group (N. s. vs. P, p<0.05,H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMS-induced decrease in 5-HT1A receptor binding. This reversal effect ofN. s. on the decrease in 5-HT1A receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that ofH. p, but different from that of F. It is concluded thatN. s. presents an anti-depression effect through enhancing 5-HT1A receptor binding.Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of 5-HT1A receptors. The present study assessed if Nelumbinis Semen (N.s.) had an anti-depression effect through reversing a decrease in 5-HT1A receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a 5-HT1A receptor binding assay, with a specific 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N.s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N.s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H.p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N.s. The N.s. treatment significantly reversed the decreased sucrose intake under CMS (P < 0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N.s. and H.p. reversed the CMS-induced decrease in 5-HT1A receptor binding. In the I to II regions of the frontal cortex, N.s. and H.p. also reversed the CMS-induced decrease in 5-HT1A receptor binding, and even showed a significant increase in 5-HT1A receptor binding compared to the F treatment group (N.s. vs. P, p < 0.05, H.p. vs. P, p < 0.05). However, in the hypothalamus, all treatments reversed the CMS-induced decrease in 5-HT1A receptor binding. This reversal effect of N.s. on the decrease in 5-HT1A receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H.p, but different from that of F. It is concluded that N.s. presents an anti-depression effect through enhancing 5-HT1A receptor binding.

Anti-diabetic effect of standardized herbal formula PM021 consisting of Mori Folium and Aurantii Fructus on type II diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

PM021, which consists of two herbal components, Mori Folium and Aurantii Fructus, is routinely used to treat diabetes in Korea. In this study, the anti-diabetic effect of PM021 on an animal model of developing type 2 diabetes of Otsuka Long-Evans Tokushima Fatty (OLETF) rats was investigated. Eight weeks of age male OLETF rats were treated daily with PM021 or vehicle for five months. Specifically, changes in body weight, blood glucose, urine volume, food intake and oral glucose tolerance were measured in rats for five months. The rats in this study were divided into four groups: a Long-Evans Tokushima Otsuka (LETO) rat group, which is a genetic control group for OLETF, that received no treatment; a PM021 treatment group of LETO rats; OLETF rats that received no treatment; and OLETF rats that received PM021 treatment. The results showed that PM021 significantly prevented increases in body weight, blood glucose, and urine and food intake that resulted from the induction of obesity and diabetes. PM021 also improved glucose tolerance in OLETO rats. However, PM021 had no effect on LETO rats, a control group of OLETF rats. Taken together, these findings indicate that PM021 has distinct anti-diabetic effects without any adverse effects or toxicities.

Effects ofNelumbinis semen on contractile dysfunction in ischemic and reperfused rat heart

Nelumbinis Semen (NS), or lotus seed, is one of the most well-known traditional herbal medicines and is frequently used to treat cardiovascular symptoms in Korea. The anti-ischemic effects of NS on ischemia-induced isolated rat heart were investigated through analyses of changes in blood pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into two groups: a control, untreated ischemia-induced group, and an ischemia-induced group treated with NS. There were no significant differences in perfusion pressure, aortic flow, coronary flow and cardiac output between the groups before ischemia was induced. The supply of oxygen and buffer was stopped for ten minutes to induce ischemia in isolated rat hearts, and NS was administered during ischemia induction. NS treatment significantly prevented decreases in perfusion pressure aortic flow, coronary flow and cardiac output under ischemic conditions (p<0.01). In addition, the mechanism of the anti-ischemic effects of NS was also examined through quantitation of intracellular calcium content in rat neonatal cardiomyocytes. NS significantly prevented intracellular calcium increases induced by isoproterenol (p<0.01). These results suggest that NS has distinct anti-ischemic effects through calcium antagonism.