The American Journal of Chinese Medicine

We examined the levels of vitreous chemokines and Sho (Zheng in Chinese) of Chinese-Korean-Japanese medicine in diabetic patients. Patients undergoing vitrectomy were classified into Group 1 (no diabetic retinopathy), Group 2 (diabetic retinopathy with no or a few new vessels), and Group 3 (diabetic retinopathy with many new vessels). The levels of IL-8, MCP-1, MIP-1α, MIP-1β, and RANTES in the vitreous fluid were measured using cytometric bead array method. Sho was determined by the standard diagnostic method of Chinese-Korean-Japanese medicine. Vitreous levels of IL-8 and MCP-1 in Groups 2 and 3 were higher than those in Group 1. MIP-1α, MIP-1β, and RANTES levels in Groups 2 and 3 were almost the same as those in Group 1. The percentage of patients with Keishibukuryo-gan (Guizhifuling-wan in Chinese) sho in Group 3 was higher than that in Group 1. In conclusion, vitreous levels of IL-8 and MCP-1 were high in patients with diabetic vitreoretinopathy. Keishibukuryo-gan sho may be associated with diabetic vitreoretinopathy.

In this study, we evaluated the synergistic effect of ginger and nifedipine on anti-platelet aggregation in normal human volunteers and hypertensive patients. The results showed that the percentage of platelet aggregation induced by collagen, ADP and epinephrine in hypertensive patients was larger than that in normal volunteers. Either aspirin or ginger could potentiate the anti-platelet aggregation effect of nifedipine in normal volunteer and hypertensive patients. These results suggested that ginger and nifedipine possessed synergistic effect on anti-platelet aggregation. A combination of 1 g ginger with 10 mg nifedipine per day could be valuable for cardiovascular and cerebrovascular complication due to platelet aggregation.

Arterial stiffness is an important, independent determinant of cardiovascular risk. Pulse wave velocity (PWV) has been used as a valuable index of arterial stiffness and as a surrogate marker for atherosclerosis. Chunghyul-dan (CHD) has anti-hyperlipidemic activity, anti-inflammatory activity and anti-atherogenic effects. To determine its clinical effect on increased arterial stiffness, we examined whether CHD improves arterial stiffness in patients with increased brachial-ankle PWV (baPWV). Thirty-five subjects with increased baPWV (> 1400 cm/sec) were recruited and randomized to a treatment group (20 subjects) or a control group (15 subjects). The treatment group was administered CHD at a dose of 600 mg three times a day for 8 weeks, and the control group received no medication (observation only). baPWV was assessed using a pulse pressure analyzer at baseline and after 8 weeks. Blood pressure and serum lipid profile were monitored in the treatment group. Our results indicate that baPWV was lowered significantly in the treatment group after 8 weeks of medication (p < 0.05), but not in the control group. Moreover, there were no significant changes in blood pressure and serum lipids profile except triglyceride level suggesting that the effect is largely independent of CHD's lipid-lowering effect or a blood pressure change. In conclusion, CHD appears to improve arterial stiffness in patients with increased PWV.

This study examined the antinociceptive effect of electroacupuncture (EA) to heterotopic acupoints on formalin-induced pain in rats. EA (2 ms, 10 Hz, and 3 mA) was delivered to heterotopic acupoints HE₇ and PE₇, or non-acupoints at the right fore limb, for 30 min and was immediately followed by subcutaneous formalin injection into the left hind paw, respectively. The quantified pain score, electromyogram (EMG) response of the C-fiber reflex, and cFos immunoreactivity were assessed, respectively. EA to heterotopic acupoints significantly reduced both early- and late-phase pain-like behaviors and significantly decreased the EMG responses of the C-fiber reflex after formalin injection. By contrast, EA to non-acupoints had no significant effects on pain-like behavior or the EMG response. In addition, EA to heterotopic acupoints decreased cFos immunoreactivity in the lumbar spinal dorsal horn. Therefore, EA induced pre-emptive antinociception via the extra-segmental inhibition of the formalin-induced pain, suggesting that EA to heterotopic acupoints is a useful treatment for inflammatory pain.

Previous work from our laboratory has demonstrated that the percentage differences of 2nd (C2) and 3rd (C3) pulse harmonics related to Kidney and Spleen were both increased toward another steady state in rats after acute hemorrhage. Therefore, it is suggested that changes in pulse spectra might represent the ability of animals to survive a model of progressive hemorrhage. In this study, the difference of the pulse spectra patterns between survivors and non-survivors after progressive hemorrhage (by loss of 5%, 10% or 20% of the estimated blood volume) in anesthetized rats is determined. Seven rats, dead within 2 hours after a loss of 20% of the estimated blood volume hemorrhage, were defined as 'non-survivors'. The other eleven rats, more than 2 hours after hemorrhage, were defined as 'survivors'. Pulse waves of arterial blood pressure before and after the hemorrhage were measured in parallel to the pulse spectrum analysis. Data among different phases were analyzed using one-way analysis of variance (ANOVA) with Duncan's test for pairwise comparisons. Differences between survivor and non-survivor groups at each phase were analyzed using Student's t-test. A mixed-effects linear regression model was applied to evaluate the relationship in harmonics, which significantly differed between the two groups. The study results showed that in rats, during progressive hemorrhage, the percentage differences of 2nd harmonic proportion increased significantly; however, the result failed to show any significant difference between survivors and non-survivors. After the third blood withdrawal process, the percentage differences of 3rd harmonic proportion increased more significantly in the survivors. In addition, the percentage differences of 1st harmonic proportion related to the Liver for the survivor group was significantly lower than that of the non-survivors. After analysis with the mixed linear regression model, C3 and C1 demonstrated a linear regression relationship, and there existed significant differences between survivors and non-survivors. These results suggest that C3 might play an important role in physiology regarding surviving capability after progressive hemorrhage.

Shengmai San (SMS) is a traditional Chinese medicine (TCM) comprising three different herbal components, Panax ginseng, Ohiopogon japonicus and Fructus schisandrae and has been used for treating coronary heart diseases (Bensky and Barolet, 1990). It was shown that SMS effectively prevented cerebral oxidative injury in rats when it administered into the duodenum before cerebral ischemia-reperfusion.

In the present study, we examined whether post-ischemic administration of SMS can ameliorate cerebral ischemia-reperfusion injury in rats as well. Results showed that SMS injected immediately after ischemia also prevented the ischemia-reperfusion injury, when the effect was evaluated by the formation of protein carbonyl and thiobarbituric acid reactive substance (TBARS), and the loss of glutathione peroxidase (GPX). The preventative potential of SMS was decreased rapidly dependent on the time lag until SMS was injected after ischemia. However, it was noted that intravenously administered SMS protected the oxidative injury approximately 30% even after 60 min of reperfusion in terms of protein carbonyl formation. It is thus suggested that SMS injection might be useful for preventing the progression of injury in cerebral infarction after stroke.

The effects of Korean Safflower (Carthamus tinctorius L) seed oil (SSO) on osteoporosis induced-ovariectomized rats were investigated. A total of 90 female Sprague-Dawley rats, 4-month-old, weighing 200–230 g were randomly assigned into 3 groups (30 animals/group). The animals in group I were sham operated and those of group II and III were ovariectomized (Ovx). After eight weeks, the animals of group I and II received solvent vehicle daily, whereas those of group III were administered SSO orally (1 ml/kg) daily for 30 days. The changes in the serum levels of insulin-like growth factor-I (IGF-I), IGF-II, insulin-like growth factor binding protein-3 (IGBP-3), estrogen, total alkaline phosphatase (TALP), bone-specific alkaline phosphatase (BALP), calcium and phosphorous in serum, and also the histomorphology of the proximal tibia metaphysis and femur/body weight (F/B) ratio were examined in all the groups at every 10 days interval. Thirty days later, IGF-I, IGF-II, IGBP-3 and BALP levels were significantly increased (p < 0.05) in group III as compared to groups I and II. There were no significant differences in serum levels of estrogen, TALP and F/B ratio between groups II and III, but estrogen levels were higher in group I. These results suggest that the safflower seeds have possible roles in the improvement of osteoporosis induced-ovariectomized rats.

Sepsis is associated with the highest risk of progression to acute lung injury or acute respiratory distress syndrome. Shen-Fu has been advocated to treat many severely ill patients. Our study was designed to investigate the effect of Shen-Fu on endotoxin-induced acute lung injury in vivo. Adult male Wistar rats were randomly divided into 6 groups: controls; those challenged with endotoxin (5 mg/kg) and treated with saline; those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (1 mg/kg); those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (10 mg/kg); increase challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (100 mg/kg); saline injected and treated with Shen-Fu (100 mg/kg). TNF-α, IL-6, and NF-kappa B were investigated in the lung two hours later. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated six hours later. Intravenous administration of endotoxin provoked significant lung injury, which was characterized by increment increase of MPO activity and wet/dry lung weight ratio, and TNF-α and IL-6 expression and NF-kappa B activation. Shen-Fu (10,100 mg/kg) decreased MPO activity and wet/dry weight ratio and inhibited TNF-α and IL-6 production, endotoxin-induced NF-kappa B activation. Our results indicated that Shen-Fu at a dose of higher than 10 mg/kg inhibited endotoxin-induced pulmonary inflammation in vivo.

This study was to investigate the inhibitive effect of resveratrol (RESV) on nuclear factor kappa B (NF-κB) expression and activity induced by lipopolysaccharide (LPS) in rat peritoneal macrophages (PMA). Male Sprague-Dawley (SD) rats were randomly divided into 7 groups, including control group, LPS group and RESV I-V group. In the LPS group, PMA were incubated in DMEM containing LPS (10 μg/ml), whereas in control group, PMA were incubated in DMEM only. In the RESV I-V groups, PMA were incubated in DMEM containing LPS (10 μg/ml) and different concentrations of RESV. After 24 hours of incubation, NF-κB activity in PMA, and the levels of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1) and nitric oxide (NO) in the culture medium were measured. In the concentrations of 1.25-5 μg/ml, RESV had a dose- dependent inhibitive effect on NF-κB activity in PMA as well as the expressions of TNF-α, IL-1 and NO in the culture medium contrasted with the LPS group. There was no significant difference in the levels of these pro-inflammatory factors between the groups of 5 μg/ml and 10 μg/ml RESV. In conclusion, RESV has the potential for the future application of preventing inflammatory diseases involving PMA.

Yu-Ping-Feng-Powder (YP), a traditional Chinese medicine prescription, is widely applied in China for the cure and prevention of diseases related to immunodeficiency. To test whether the fractioned polysaccharides (YPF-P) isolated from YP have immunomodulating activities, the effects of YPF-P on cyclophosphamide (Cy)-treated mice were studied in relation to phagocytosis of macrophage, splenocyte proliferation, and humoral, and cellular immunity parameters. It was found that YPF-P enhances phagocytic activity, augments ConA- or LPS-stimulated T cell proliferation, increases the quantitative haemolysis of SRBC (QHS) and delayed-type hypersensitivity reaction (DTH) to dinitrofluorobenzene. Hence, YPF-P restored the immuno-competence suppressed by Cy. YPF-P also augmented IL-2 and IFN-γ production, but failed to increase IL-4 production, which indicates that there is high probability that it enhance Th1 function. These results suggested that YPF-P has immunomodulating effects and that the polysaccharides constitute one of the active components of YP.

To prevent bone loss that occurs with increasing age, certain nutritional and pharmacological factors are needed. In the present study, the ethanol extract from the fruit of Rubus coreanus Miq. (RCE) was investigated for its effect on the function of osteoblastic MC3T3-E1 cells. RCE (10~50 μg/ml) caused a significant elevation in cell viability, alkaline phosphatase (ALP) activity, collagen content, and osteocalcin secretion in the cells. The effect of RCE (50 μg/ml) in increasing cell viability, ALP activity, and collagen content was prevented by the presence of 10^-6 M cycloheximide and 10^-6 M tamoxifen, suggesting that RCE's effect results from a newly synthesized protein component and might be partly involved in estrogen action. We then examined the effect of RCE on the H₂O₂-induced apoptosis and production of local factors in osteoblasts. Treatment with RCE (10~50 μg/ml) decreased the 0.2 mM H₂O₂-induced apoptosis and production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide (NO) in osteoblasts. Our data indicate that the enhancement of osteoblast function by Rubus coreanus Miq. may result in the prevention of osteoporosis and inflammatory bone diseases.

The butanol extract of Phellinus igniarius (BPI) induced relaxation of the phenylephrin e-precontracted rat aorta in a dose-dependent manner, and its effect was abolished by the removal of functional endothelium. Pretreatment of the aortic tissues with N^G-nitro-L-arginine methyl ester (L-NAME), methylene blue, or 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin1-one (ODQ) inhibited the vascular relaxation induced by BPI. BPI-induced vascular relaxations were also markedly attenuated by the addition of verapamil or diltiazem, while the relaxant effect of BPI was not blocked by pretreatment with indomethacine, glibenclamide, tetraethylammonium (TEA), atropine, or propranolol. Incubation of endothelium-intact rat aorta with BPI increased the production of cGMP in a dose-dependent manner. These results suggest that BPI dilates vascular smooth muscle via endothelium-dependent nitric oxide-cGMP signaling pathway, with the possible involvement of L-type Ca²⁺ channels.

Our previous studies had reported that morin decreased the interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-α) production in lipopolysaccharide (LPS)-activated macrophages, suggesting that morin may promote helper T type 2 (Th2) response in vivo. Dendritic cells (DCs) are the most potent antigen presenting cells and known to play a major role in the differentiation of helper T type 1 (Th1) and Th2 responses. This study aimed to reveal whether morin is able to control the Th differentiation through modulating the maturation and functions of DCs. Bone marrow-derived dendritic cells (BM-DCs) were incubated with various concentrations of morin and their characteristics were studied. The results indicated that morin significantly affects the phenotype and cytokine expression of BM-DCs. Morin reduced the production of IL-12 and TNF-α in BM-DCs, in response to LPS stimulation. In addition, the proliferative response of stimulated alloreactive T cells was significantly decreased by morin in BM-DCs. Furthermore, allogeneic T cells secreted higher IL-4 and lower IFN-γ in response to morin in BM-DCs. In conclusion, these results suggested that morin favors Th2 cell differentiation through modulating the maturation and function of BM-DCs.

Fever, an elevation in body temperature, is thought to be terminally mediated by prostaglandin E₂ (PGE₂). Both Guizhi Tang (GZT) and its active fraction A (Fr.A) showed an antipyretic effect in rats. 3-Phenyl-2-propene-1-ol was one of the active compounds isolated from Fr.A. In the present study, we examined the influence of interleukin-1β (IL-1β) on prostaglandin E₂ (PGE₂) release, and the effect of 3-phenyl-2-propene-1-ol on IL-1β-induced PGE₂ release from rat cerebral endothelial cells (rCMEC). Cultured rCMEC were used in the study. In vitro, cells express typical phenotypic markers of brain endothelium. Using a monoclonal antibody against von Willebrand factor, immunocytochemical analysis revealed positive immunoreactivity in the cytoplasm of cultured cells. rCMEC were incubated in M199 medium containing IL-1β in the presence or absence of 3-phenyl-2-propene-1-ol. After incubation, the conditioned media were collected and the amount of PGE₂ was measured by enzyme-linked immunosorbent assay (ELISA). IL-1β increased the production of PGE₂ in a dose- and time-dependent manner. 3-Phenyl-2-propene-1-ol significantly decreased IL-1β-induced PGE₂ release in a dose-dependent manner. Our results indicate that 3-phenyl-2-propene-1-ol inhibits the PGE₂ release from rCMEC stimulated by IL-1β, and may have an antipyretic effect.

Samul extract, containing Radix Rehmanniae, Radix Angelicae Gigantis, Radix Paeoniae, and Rhizoma Cnidii, has been traditionally used for treatment of ischemic heart and brain damages in Oriental medicine. However, little is known about the mechanism by which Samul rescues cells from cytotoxic damage. This study was designed to investigate the protective mechanisms of Samul on H₂O₂-induced death of H9c2 cells. Treatment with H₂O₂ markedly decreased the viability of H9c2 cells in a dose- and time-dependent manner, which was significantly prevented by pre-treatment with Samul. The nature of death of H9c2 cells by H₂O₂ was demonstrated by apoptotic features, including ladder-pattern fragmentation of genomic DNA and chromatin condensation, which were markedly abolished by pretreatment of Samul in H₂O₂-treated cells. We further demonstrated that MEK inhibitor, PD98059, dose-dependently attenuated the protective effects of Samul against H₂O₂, whereas inhibitors of Jnk and p38 did not. Consistently, Samul induced the early phosphorylation of Erk, p44, in H₂O₂-treated cells. In addition, treatment with Samul also resulted in an increase of expression of anti-apotogenic Bcl2 protein, which was decreased by H₂O₂. However, it inhibited the expression of apotogenic Bax protein in H₂O₂-treated cells. Taken together, these results suggest that the protective effects of Samul against oxidative damage may be achieved via activation of MAP kinase, Erk as well as Bcl2 family proteins.

Glossogyne tenuifolia (Labill) Cass. (Compositae) is a special medicinal plant in the Pescadores Islands. Ethanolic, cold and hot water extracts were prepared from the dried herb and their antioxidant properties and components were studied. Ascorbic acid, α-tocopherol, butylated hydroxyanisole, citric and ethylenediaminetetraacetic acids were used in assays for comparison. With regard to EC₅₀ values in antioxidant activity, ethanolic and hot water extracts (0.08 and 0.09 mg/ml) were much more effective than the cold water extract (0.76 mg/ml). At 1.0 mg/ml, reducing capacities were 1.57, 0.31 and 1.04 for ethanolic, cold water and hot water extracts, respectively. Scavenging abilities on 1,1-diphenyl-2-picrylhydrazyl radicals were in descending order: ethanolic > cold water > hot water extracts. At 20 mg/ml, the hot water extract chelated all hydroxyl ions (100%) whereas the scavenging ability of the cold water extract was 68.86%. Chelating abilities on ferrous ions were in descending order: cold water > hot water > ethanolic extracts. Phenols were found to be the major antioxidant components. All EC₅₀ values were below 20 mg/ml, and some even below 0.1 mg/ml, indicating that all three extracts from G. tenuifolia were rich in antioxidant properties.