The American Journal of Chinese Medicine

The mechanism of acupuncture analgesia (AA) has been widely explored since the 1970s. Early studies investigated the relationship between acupuncture and endogenous opiates (β-endorphin, enkephalin, endomorphin and dynorphin). Before the 1990s, most experts agreed on the concept that in normal animal models, lower frequency electroacupuncture (EA) stimulates the release of β-endorphin, enkephalin and endomorphin, which in turn activates the μ- and δ-opioid receptors, and that higher frequency EA stimulates dynorphin which activates the κ-opioid receptor. Besides endogenous opiates, our studies have focused on serotonin. The serotoninergic descending inhibitory pathway is suggested to be an important mechanism of acupuncture analgesic, collaborating with endogenous opiates. Many efforts have been made to clarify these mechanisms, but to date no satisfactory consensus has been reached. In the late 1990s, researchers began to focus on the different analgesic effects of EA between normal and hyperalgesic animal models. Published data from these studies imply that normal and hyperalgesic animals respond differently to EA. Results from experiments on the anti-hyperalgesia effect of EA have raised a new issue about the influences of EA on receptors to excitatory amino acid in the spinal cord level. Results from various studies have shown that these receptors play a role in the mechanism of AA. Recently, research on the autonomic nervous system (ANS) seem to indicate its connection with acupuncture. The inflammatory reflex (via the ANS) might be a crucial part of anti-hyperalgesia elicited by acupuncture, and this reflex, which regulates the immune system in the organism, can elucidate not only the mechanism of AA but also the mechanism of acupuncture applied to other inflammatory conditions. Innovation of functional image study enables us to analyze the responses of cortex on living human body to acupuncture. However, results of these experiments are still controversial. After 30 years of acupuncture research, there are still many puzzles left to be solved regarding the mechanism of AA.

The present study investigated the effects of 14 weeks of practicing Tai Ji Quan (TJQ) on metabolic control and lipid metabolism in women with type 2 diabetes. Twenty Beijing female residents (57.4 ± 6.2 years) were recruited and were randomly assigned to either the TJQ training or the control group. In the TJQ group, the exercise duration was 1 hour per day and 5 days a week for 14 weeks. FPG, GSP, FPI, TC, HDL-C, LDL-C, TG, resting blood pressures and heart rate were measured before and after the 14 weeks in the 2 groups. It was found that after 14 weeks, the TJQ group had significantly lower FPG, GSP, TG and higher FPI concentration, whereas there were no significant differences in TC, HDL-C and LDL-C. It was concluded that TJQ exercise could be used as an intervention tool to improve glycaemic control and serum TG level in the elderly people. Future research with TJQ of different styles and exercise of different intensities were recommended.

Yin-Deficiency (YD), representing a status of the human body under lack of nutrition and fluid in traditional Chinese medicine, is commonly seen in late stage of cancer patients. It is not known whether the severity of YD related symptoms/signs can predict the survival rate of cancer patients. This study evaluated the distribution of Yin-deficiency symptoms/signs (YDS) in cancer patients with YD, and investigated whether the severity of YDS can predict the survival rate of cancer patients with YD. From 5 January 2007 to 5 May 2007, we selected 43 cancer patients with diagnosis of YD from hospitalized patients and outpatients. The severity of YD was evaluated by a questionnaire. We further estimated the cumulative probabilities of the survival rates over 4 months since the start of study by the Kaplan-Meier product-limit method, and compared the differences among groups with various severities in each symptom/sign with the use of the log-rank test. The results revealed that, the 3 most common YDS were sleeplessness with annoyance, less or non-coated tongue with or without redness and dry mouth. In the survival rate analysis, only 2 parameters, rapidly small pulse (p = 0.002) and less-or non-coated tongue with paleness (p = 0.017), were found to be related to the decrease of cancer patients with YD. This suggests that, both rapidly small pulse and less-or non-coated tongue without redness may be used as predictors for the estimation of survival rate in cancer patients with YD.

A randomized phase II study using mitomycin (MMC)/cisplatin (DDP) regimen with or without Kanglaite (KLT, a traditional Chinese medicine) as salvage treatment was conducted to exploit KLT's potential effects on patients with advanced breast cancer (ABC). Triweekly regimen consisted of mitomycin (8 mg/m²) administered intravenously on day 1, and cisplatin (25 mg/m²) intravenously on days 1 to 3. KLT (100 ml) was given intravenously per day on days 1 to 14 every 3 weeks. Between April 2006 and July 2007, 60 patients with a median age of 48 years were randomized into MMC/DDP with or without KLT treatment. In all, the objective response rate (ORR) was 17.5%. There were no significant differences between experimental and control treatments in terms of ORR (14.3% vs. 20.7%, p = 0.730), clinical benefit rates (24.1% vs. 28.6%, p = 0.468), median time to progression (TTP; 3.63 vs. 4.0, p = 0.872), and overall survival (OS; 7.17 vs. not reached, p = 0.120). The median TTP for patients with complete or partial responses was 6.0 months, but only 2.1 months for patients with stable or progressive disease (SD or PD; p = 0.028). While the median OS for patients who obtained clinical benefit from chemotherapy was not reached, that of patients with SD of no more than 6 months or PD was only 7.17 months (p = 0.004). There is no additional benefit when KLT is added to the MMC/DDP doublet in the management of ABC. Patients who obtained clinical benefit from chemotherapy had a longer TTP and OS.

The predictive roles of symptom combination traditionally evaluated in traditional Chinese medicine (TCM) in the treatment of rheumatoid arthritis (RA) were explored. Three hundred and ninety six patients were randomly divided into 197 subjects receiving Western medicine therapy (WM) and 199 subjects receiving TCM therapy (TCM). A complete physical examination and 18 clinical manifestations typically assessed in TCM were recorded before the randomization. The ACR responses were used for efficacy evaluation. ACR20 and 50 responses with WM treatment were higher than in the TCM group. The 18 symptoms in RA could be clustered into 4 symptom combinations with factor analysis, which represent joint symptoms, cold pattern, deficiency pattern and hot pattern in TCM respectively. TCM would be more effective in patients with weak-symptom combination 3 (deficiency pattern in TCM), and WM would be more effective in patients with symptom combination 2 (cold pattern in TCM). Symptom combinations judged with TCM may have influence on the efficacy of therapy in the treatment of RA.

Panax Notoginseng Burk (PN) has been reported to improve blood circulation, as well as learning and memory functions. The purpose of the present study was to investigate the effect of PN on learning and memory functions in chronic cerebral infarct rats. A cerebral infarct animal model was established by blocking the blood flow of both common carotid arteries and right middle cerebral artery for 90 min followed by reperfusion for 4 weeks. PN (0.5 g/kg) was administered orally 3 days per week for 4 weeks, whereas the control group provided bait and water only. The learning and memory functions were estimated by measuring how successful rats were able to negotiate an 8-arm radial maze test; the test was performed after operation once a week for 4 weeks. Finally, the rats were sacrificed and their brains were removed. The brains were sectioned and analyzed for ED1, glial fibrillary acid protein (GFAP), nuclear factor-κB, and brain derivative neurotrophin factor (BDNF) and β-secretase by immunostaining. Cerebral infarct rats given PN were able to successfully navigate the 8-arm radial maze test four weeks after cerebral infarction. PN also increased ED1, BDNF and β-secretase immunoreactive cells, but did not increase GFAP and NF-κB immunoreactive cells. PN attenuated the reduction in learning and memory functions induced by cerebral infarction in cerebral ischemia-reperfusion injured rats; it also increased the amount of activated microglia and BDNF. These data suggest that the effect of PN, at least in part, is closely related to the increase in BDNF that was generated by activated microglia. The effect that PN has on astrocytes, NF-κB and β-secreatase immunoreactive cells requires further study.

Chrysanthemum is a traditional Chinese medicine used in China to treat inflammatory diseases. The total flavonoids Chrysanthemum indicum (TFC) were extracted from the dried bud of Chrysanthemum indicum. Our previous study had demonstrated that TFC was a new class of effective anti-inflammation, analgesia and immunoloregulation agents. In this study, we established an adjuvant arthritis (AA) model by injection of Freund's Complete Adjuvant (FCA) to investigate the effect of TFC on the apoptosis of synoviocytes in AA Rats. Synoviocytes isolated from knee joint of rats were treated with different doses of TFC in vitro. Synoviocytes proliferation was measured by MTT assay, and DNA fragmentations were evaluated on agarose gel electrophoresis. The levels of caspase-3 cleaved fragments were analyzed by Western blot. The annexin V stain assay was used to explore the inhibition of caspase-3 on the amelioration of synoviocytes apoptosis. The results showed that TFC inhibited the proliferation of synoviocytes. Electrophoresis showed higher ladders of DNA bands in the TFC group. Cleaved fragments of caspase-3 were increased significantly. Furthermore, the apoptotic synoviocytes were markedly decreased by the caspase-3 specific inhibitor. These results suggest that TFC could induce synoviocytes apoptosis and suppress proliferation of synoviocytes in adjuvant-induced arthritis rats.

The present study was undertaken to determine the effect of Yi-Qi-Yang-Yin-Ye (Y-Q-Y-Y-Y), a compound of Traditional Chinese Herbal Medicine, on insulin resistance (IR) in the diet-induced obese rat model induced by intravenous injection with a low dose of streptozotocin and fed a high fat and high caloric diet. Y-Q-Y-Y-Y (2, 4, 8 g/kg) was administered via gavage daily for 4 weeks. The results showed that Y-Q-Y-Y-Y treatment decreased the levels of body weight, total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), free fatty acid (FFA), insulin (INS) and fast blood glucose (FBG) and increased the level of high density lipoprotein-cholesterol (HDL-C) in the diet-induced obese rats. Glucose tolerance was improved in the diet-induced obese rats treated with Y-Q-Y-Y-Y as well as GIR (glucose infusion rate) in the hyperinsulinemic euglycemic clamp experiment compared to the model control rats (p < 0.01). Moreover, treatment with Y-Q-Y-Y-Y up-regulated glycogen contents in both liver and skeletal muscle and increased insulin receptor amounts on the erythrocytes surface as assessed by using ¹²⁵I-labeled auto-antibodies against insulin receptors. Taken together, our data suggested that Yi-Qi-Yang-Yin-Ye ameliorates insulin resistance in the diet-induced obese rats.

Borneol is consumed excessively in China and Southeast Asian countries particularly in combined formula for preventing cardiovascular disease, but few studies were conducted on its effects on thrombosis. In this study, the antithrombotic and antiplatelet activities of borneol were investigated on thrombosis in vivo and on platelet aggregation ex-vivo. In addition, the coagulation parameters and influence on fibrinolytic activity were also assessed. The results showed that borneol had concentration dependent inhibitory effects on arterio-venous shunt and venous thrombosis but no effect on ADP and AA-induced platelet aggregation. Meanwhile, borneol prolonged the coagulation parameters for prothrombin time (PT) and thrombin time (TT), but did not show any fibrinolytic activity. It suggested that the antithrombotic activity of borneol and its action in combined formula for preventing cardiovascular diseases might be due to anticoagulant activity rather than antiplatelet activity.

Anticarcinogenic effects attributed to phytochemicals may be based on synergistic, additive, or antagonistic interactions of many compounds. In our previous study, we demonstrated that the chloroform fraction (CHCl₃-F) from Z. jujuba has anticancer activity in HepG2 cells. In China, many people drink jujuba tea and believe in the synergic effects of jujuba and tea for better health. We therefore investigated the effects of CHCl₃-F and green tea extract (GTE), and their underlying mechanisms of action in HepG2 cells. Our results showed that GTE enhanced the effect of CHCl₃-F on cell viability in HepG2 cells, without cytotoxicity in rat hepatocytes, which was used as a normal cell model. Furthermore, combination of CHCl₃-F and GTE caused an effect on G1 phase arrest but not on apoptosis. Interestingly, the mechanism of the G1 arrest was associated, not with an increase in p27^Kip1 levels and the hypohosphorylation of Rb, which are pathways used by CHCl³-F on G1 arrest in HepG2 cells, but with increases in p53 and p21^Waf1/Cip1 levels, and a decrease in cyclin E levels. Collectively, our findings suggest that combination of CHCl₃-F and GTE produces an enhanced cell growth inhibition effect, and that the resultant G1 arrest was caused via a different mechanism as that of CHCl₃-F treatment alone.

Baicalin, one kind of Chinese herbal medicine with anti-inflammatory and anti-oxidant property, has been commonly used as a clinical medicine. However, little has been known about the effects of Baicalin on ultraviolet (UV) induced photo-aging and photo-carcinogenesis. The photoproduct is critical to the initial event of UV-induced photo-carcinogenesis. The purpose of the present study was to investigate whether Baicalin, in immortalized human keratinocyte HaCaT cells, could inhibit ultraviolet-B (UVB) induced skin damage and its possible underlying mechanisms, such as inhibiting UVB-induced cytotoxicity and apoptosis, cyclobutane pyrimidine dimers (CPDs), down-regulating the expression of regulatory proteins which are related to cell apoptosis and DNA damage/repair. Our study revealed that Baicalin treatment could inhibit the UVB-induced cytotoxicity, apoptosis and CPD level. It also decreased the mRNA expression of apoptosis-regulatory genes (p53-p21 and c-fos), the protein levels of p53, proliferating cell nuclear antigen (PCNA) and repair protein A (RPA), and the secretion of cytokines [interleukin(IL)-6 and tumor necrosis factor (TNF-α)]. These results suggested that Baicalin may have an inhibitory effect on the UVB-induced photo-damage by blocking the relevant cytokine secretion and expression of p53-p21, c-fos, PCNA and RPA genes.

Wen-Pi-Tang, a traditional Chinese prescription, has been widely used for the treatment of patients with moderate chronic renal failure in China. Although the protective effect of Wen-Pi-Tang on peroxynitrite (ONOO^-)-induced renal tubular epithelial LLC-PK₁ cell damage was elucidated in our previous research, the active components of Wen-Pi-Tang have not yet been fully clarified. Therefore in the present study, we investigated the active components by using a cellular ONOO^-generation system. As a result, p-coumaric acid, 4-(4'-hydroxylphenyl)-2-butanone 4'-O-glucopyranoside, gallic acid 3-O-(6'-O-galloyl)-β-d-glucopyranoside, procyanidin B-1, procyanidin B-3, and (+)-catechin were isolated as active compounds inhibiting cellular ONOO^- formation and cytotoxicity. In particular, the content of (+)-catechin was significantly higher than those of the other compounds, and the (+)-catechin structure was located in procyanidins B-1 and B-3. Therefore, the major bioactivity of Wen-Pi-Tang against ONOO^--induced cytotoxicity in LLC-PK₁ cells was thought to be mediated by (+)-catechin. Although we cannot disregard the synergetic effect of various components in Wen-Pi-Tang, (+)-catechin is a major active compound protecting against ONOO^--induced LLC-PK₁ cell damage and may be used as an index to qualify the ONOO^--inhibitory activity of Wen-Pi-Tang extract.

Recently, modern scientific research has been required to understand pharmacological basis of traditional Chinese medicine (TCM) theory based on the ancient clinical experience, and to investigate the molecular mechanisms of action of Chinese herbs. Here, 20 Chinese herbs, classified into 4 properties (hot, warm, cold and cool) of TCM, were analyzed for their ability to exhibit antioxidant action, to enhance glucose uptake by murine microglia N9 cells, and to influence neurotransmitter norepinephrine (NE) release from rat pheochromocytoma PC12 cells. We found a generally protective effect of both hot/warm-natured and cold/cool-natured herbs against H₂O₂-induced N9 cell death, partially by elevating superoxide dismutase (SOD) activity. Glucose uptake was elevated after treatment with some hot/warm-natured herbs. In addition, most herbs with hot/warm nature tended to stimulate NE release, while such stimulatory effect was not observed in the herbs with cold/cool nature. Two cold/cool-natured herbs, Rhizoma coptidis and Radix scutellariae, even significantly suppressed the release. These results suggest that the distinct abilities of Chinese herbs to regulate neural cell functions appear to be correlated with their natures identified in traditional TCM theory, and may be a useful guide for their utility in neural degenerative diseases.

Traditional Chinese medicine (TCM) has been used for thousands of years. Most Chinese herbal formulae consist of several herbal components and have been used to treat various diseases. However, the mechanisms of most formulae and the relationship between formulae and their components remain to be elucidated. Here we analyzed the putative mechanism of San-Huang-Xie-Xin-Tang (SHXXT) and defined the relationship between SHXXT and its herbal components by microarray technique. HepG2 cells were treated with SHXXT or its components and the gene expression profiles were analyzed by DNA microarray. Gene set enrichment analysis indicated that SHXXT and its components displayed a unique anti-proliferation pattern via p53 signaling, p53 activated, and DNA damage signaling pathways in HepG2 cells. Network analysis showed that most genes were regulated by one molecule, p53. In addition, hierarchical clustering analysis showed that Rhizoma Coptis shared a similar gene expression profile with SHXXT. These findings may explain why Rhizoma Coptis is the principle herb that exerts the major effect in the herbal formula, SHXXT. Moreover, this is the first report to reveal the relationship between formulae and their herbal components in TCM by microarray and bioinformatics tools.

The isolation and characterization of rat lens aldose reductase inhibitors from the Viola hondoensis W. Becker et H Boss were conducted. The extracts and organic fractions from V. hondoensis were tested. The MeOH extract and EtOAc fraction were found to exhibit potent rat lens aldose reductase inhibition in vitro, their IC₅₀ being 1.2 and 0.6 μg/ml, respectively. One major isoflavonoid glycoside was isolated from the ethyl acetate soluble fraction of V. hondoensis. Kakkalide was found to be the potential rat lens aldose reductase inhibitor (IC₅₀ = 0.34 μg/ml), and may be useful for the prevention and/or treatment of diabetic complications.

Rhein, an anthraquinone derivative of rhubarb, inhibits the proliferation of various human cancer cells. In this paper, we focused on studying the effects of rhein on human hepatocelluar carcinoma BEL-7402 cells and further understanding the underlying molecular mechanism in an effort to make the potential development of rhein in the treatment of cancers. Using MTT assay and flow cytometry, we demonstrate a critical role of rhein in the suppression of BEL-7402 cell proliferation in a concentration- and time-dependent manner. The increase of apoptosis rate was observed after incubation of BEL-7402 cells with rhein at 50–200 μM for 48 hours, and the cells exhibit typical apoptotic features including cellular morphological change and chromatin condensation. Moreover, rhein-induced cell cycle S-phase arrest. Additionally, after rhein treatment, expression levels of c-Myc gene were decreased, while those of caspase-3 gene were increased in a dose-dependent manner by using real-time PCR assay. The results demonstrate for the first time that cell cycle S-phase arrest is one of the mechanisms of rhein in inhibition of BEL-7402 cells. Rhein plays its role by inducing cell cycle arrest via downregulation of oncogene c-Myc and apoptosis through the caspase-dependent pathway. It is expected that rhein will be effective and useful as a new agent in hepatocelluar carcinoma treatment in the future.