The American Journal of Chinese Medicine

Proteomics technologies can be applied to simultaneously study the function, organization, diversity, and dynamic variety of a cell or a whole tissue. The integrative approach of proteomics is in line with the holistic concept and practices of traditional Chinese medicine (TCM). In this review, the technologies of proteomics, their adoption leverages the depth and breadth of TCM research are introduced. This article presents some examples to illustrate the use of proteomics technologies in the study of pharmacological effects and their action mechanisms relevant to TCM. Proteomics technologies could be used to screen the target molecules of the TCM actions, identify new bioactive components, and elucidate the underlying mechanisms of their effects. With proteomics approaches, it was found that the Siwu decoction could regulate the protein expression of the bone marrow of blood (Xue) deficient mice, including some proteins and enzymes involved in the hemopoiesis system. Ganoderma lucidum spores might promote the survival and axon regeneration of injured spinal motor neurons in rats by regulating the expression levels of proteins involved in the energy and tissue regeneration system. Polygonatum zanlanscianense Pamp exhibited cytotoxicity towards human myeloblast leukemia HL-60 cells through multiple apoptosis-including pathways. Panax ginseng might be beneficial to patients suffering from diabetes mellitus and its complications by alleviating inflammation. Taken together with a discussion on the challenges and perspectives, this paper provides an overview of the recent developments of proteomics technologies in TCM research, and contends that proteomics will play an important role in the modernization and internationalization of TCM.

Proteomics technology is based on the vast analytical power for protein/peptide identification and quantification offered by modern mass spectrometry coupled with hyphenated separation techniques such as two-dimensional gel electrophoresis (2DE) and micro- or nano-scale multidimensional liquid chromatography. The rapid growth of proteomics field provides an array of new tools for the integration of traditional Chinese medicine (TCM) with modern technology and systems biology, and is potentially advancing the progress of modernization and internationalization of TCM. Cho, in this issue of the American Journal of Chinese Medicine, highlights the recent application of 2DE-based and bottom-up proteomics in Chinese medicine research, including the exploration of pharmacological mechanisms of the actions of TCM, the facilitation of herb authentication and identification, and the profiling of protein expression following acupuncture treatment in animal models. Recent development in proteomics has provided further refinement on the analysis of proteins posttranslational modifications as well as quantitative comparison of different proteomes, and enabled the study of proteomes of specific diseases or biological processes under clinically relevant conditions. It is conceivable that the application of technologies developed in proteomics, genomics and metabonomics in the clinical practice and basic research of Chinese medicine will eventually lead to the reconciliation and integration of TCM and contemporary medicine. Chinese medicine is fundamentally a highly personalized medicine; perhaps it is time to embrace the arrival of TCM OMICS era in Chinese medicine research.

The therapeutic effect of crude rhubarb on intestinal permeability was investigated in septic patients. Forty septic patients were enrolled in this study and randomly divided into two groups: the crude rhubarb treatment group (n = 18) and the control group (n = 22). The same treatments were given to both groups except that the crude rhubarb treatment group was administrated with crude rhubarb powders (3 g, tid, p.o). The levels of procalcitonin, D-lactate in plasma and lactulose/mannitol (L/M) ratio in the urine were determined on the first day and the sixth day after treatment with or without crude rhubarb. There were no significant differences in procalcitonin, L/M ratio and D-lactate on the first day between the crude rhubarb treatment group and the control group (p > 0.05). However, the ratio of L/M on the sixth day for the control group was 0.167 ± 0.036, while that of the crude rhubarb treatment group was 0.062 ± 0.013 (p < 0.05). Moreover, the levels of procalcitonin and D-lactate in the crude rhubarb treatment group were obviously lower than those in the control group on the sixth day (procalcitonin: 4.11 ± 1.40 μg/L vs. 2.21 ± 0.61 μg/L; D-lactate: 0.24 ± 0.06 ng/L vs. 0.09 ± 0.03 ng/L, p < 0.05, both). These data confirmed that crude rhubarb's effects on septic patients of ameliorating intestinal permeability.

In this study, 4 male Qigong masters (aged 60 ± 12) who had Qigong practicing experience for more than 30 years were tested. By using the technique of fMRI, the change of brain function under the state of Qigong was observed through the peripheral pain stimulation generated by potassium penetrating method. The fMRI examination was running on a GE signa VH/3.0 T MRI machine and block design was used. The test was repeated several times, which was carried out before and 15 min after Qigong practicing. The heart and respiration rate of these 4 Qigong masters were monitored during the whole test. SPM2 was used for the data analysis, and the result showed that before Qigong practicing, besides SI and SII-insula regions, many other Brodmann areas, the cigulate cortex, the thalamus, and the cerebellum were all activated, while 15 min after that, the activated areas were decreased obviously, which were mainly at the SII-insula region and some other Brodmann areas. Since the SII-insula region was activated in both of these two states, further analysis of the response curve was focused on it. Its response amplitude under the state of Qigong (3.5%) was greater than that before Qigong (1.2%). Our result indicated that the main manifestation of brain functional change under Qigong was functional suppressing, but in some particular regions such as SII-insula region in our study, the response amplitude was increased. Further study of the exact physiological mechanism of Qigong is needed.

This study was conducted to test the effectiveness of moxibustion therapy for patients with post-stroke urinary symptoms using International Prostate Symptom Score (IPSS). Stroke patients with urinary symptoms were enrolled and assigned into the moxibustion group (MO group) and the control group by stratified randomization. The MO group received moxibustion treatment on Zhong-Ji (CV-3), Guan-Yuan (CV-4) and Qi-Hai (CV-6) for 10 days, and the control group did not receive it. The effectiveness of urinary symptoms and activities of daily living were measured by IPSS and Barthel Index (BI), respectively. These scales were examined by an independent blinded neurologist before treatment, and 10 days after therapy. Thirty nine subjects (20 in the MO group and 19 in the control group) were included in the final analysis. The MO group showed more improvement on urinary symptoms than the control group. In conclusion, we suggest that moxibustion on Zhong-Ji (CV-3), Guan-Yuan (CV-4) and Qi-Hai (CV-6) is effective to post-stroke urinary symptoms.

We investigated the effect of acupuncture therapy on obese women's body weight and peripheral blood levels of serum immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin E (IgE). Sixty-three healthy women were assigned into 3 groups: placebo electroacupuncture (n = 13; mean age, 40.5 ± 4.2 years; body mass index [BMI], 33.5 ± 4.2), diet restriction (n = 23; mean age, 42.9 ± 4.0 years; BMI, 34.6 ± 2.9), and electroacupuncture (n = 24; mean age, 40.1 ± 5.9 years; BMI, 33.9 ± 2.7). Electroacupuncture was applied to the Hunger and Shen Men ear points and to the LI 4, LI 11, St 36, St 44, and Ren 6 body points for 30 min once daily for 20 days. A restricted diet of 1400 kilocalories was given to participants in all 3 groups for 20 days. Weight was lost significantly in subjects in the electroacupuncture group compared to those in the diet restriction and placebo electroacupuncture groups (p < 0.000, Tukey test). Modulations in serum IgG (p < 0.001) were apparent in women treated with electroacupuncture compared with women treated with placebo electroacupuncture and restricted diet only. No significant changes were seen in serum IgA, IgM, and IgE levels among the 3 groups. Our results suggest that electroacupuncture can be effectively used to treat obesity. We also observed a modulating effect of serum IgG, which is associated with weight loss, in patients in the electroacupuncture group.

The purpose of this study is to select acupoints for acupuncture treatment of peripheral facial paralysis according to the temperature on the face of the patient detected by thermogram, to determine an objective acupoint selection method for acupuncture treatment. In the test group of 60 cases of facial paralysis, the infrared thermogram on the face was detected at the first visit, and then acupuncture was given at the acupoints on the affected side with a temperature difference of over 0.5°C from the healthy side for one therapeutic course, and in each successive course the acupoints were re-determined according to the results of thermogram examination and were administrated till the end of the total therapeutic course, and 120 cases of the control group were treated with acupuncture at conventionally selected acupoints. The results showed that the cured and basically cured rate was 90.0% (54 cases) in the test group and 77.5% (93 cases) in the control group with a significant difference between the two groups (p < 0.05); and the total sessions of acupuncture were less and the course of treatment was shorter in the test group than those in the control group (both p < 0.001). The utilization rate of the acupoints selected by facial thermogram in the test group was in order of Dicang (ST 4, 92.3%), Yingxiang (LI 20, 90.6%), Taiyang (EX-HN 5, 85.5%), Yangbai (GB 14, 76.6%), Quanliao (SI 18, 72.3%), and so on. In conclusion, acupuncture at the acupoints selected by thermogram for treatment of facial paralysis in the cured rate, the therapeutic course and sessions of acupuncture is significantly superior to acupuncture at the conventionally selected acupoints, and the thermogram-aided acupoint selection method is beneficial to objectivity and modernization of acupoint selection for acupuncture and moxibustion treatments.

In clinical acupuncture, when acupuncture points are stimulated, several types of reflex responses can be evoked. Consequently, different categories of physiological responses are induced, which include changes in the activities of internal organs and tissues. The acupuncture point Sanyinjiao (SP6) has been used successfully to treat different human gastrointestinal conditions. The aim of this work was to investigate the effects of end-organ response induced by acupuncture point SP6 on the bioavailability of the radiopharmaceutical sodium pertechnetate (Na^99mTcO₄) in Wistar rats. Healthy rats were allocated into 2 groups, control-CG and treated-TG. TG was bilaterally stimulated at acupuncture point SP6 with stainless steel needles. Ocular plexus administration of Na^99mTcO₄ (3.7MBq) was carried out 10 min after every needle insertion in all animals. Ten minutes later, the animals were killed, the organs were isolated, the radioactivity was determined in a well gamma counter, and the percentage of injected dose per gram of tissue (%ID/g) was determined for each organ. The %ID/g was significantly altered (p < 0.05) in the small intestine of TG (0.56 ± 0.09) when compared to CG (0.82 ± 0.18). These results may suggest that this stimulation might induce physiological responses capable of altering the bioavailability of the radiopharmaceutical sodium pertechnetate. These findings aid in providing a better understanding of acupuncture and its effects on various organs and tissues.

We investigated whether the 2 Hz electroacupuncture (EA) analgesia is associated with phosphorylation of N-methyl-D-aspartate receptor (NMDAR) NR-1 subunits and NMDAR antagonism in the lumbar spinal cord of rats. EA stimulation produced an increase of serine phosphorylation of NMDAR NR-1 subunits in the spinal cord as compared with normal conditions. However, the intrathecal injection of NMDAR antagonist D-2-amino-5-phosphonopentanoic acid significantly prevented serine phosphorylation of NMDAR NR-1 subunits induced by EA stimulation in the dorsal horn of spinal cord. These results indicate that EA analgesia by stimulation of peripheral nerves may be involved in an increase of NR-1 serine phosphorylation in the dorsal horn of the spinal cord.

This study investigated the effects of the combined extracts of Ginkgo biloba, Panax ginseng, and Schizandra chinensis at different doses on hepatic antioxidant status and fibrosis in rats with carbon tetrachloride (CCl₄)-induced liver injury. Male Sprague-Dawley rats (n = 8–12 per group) were divided into the control, CCl₄, CCl₄ + silymarin (0.35%), CCl₄ + low-dose herbal extract (0.24% of Ginkgo biloba, Panax ginseng, and Schizandra chinensis extract at 1:1:1; LE), and CCl₄ + high-dose herbal extract (1.20% of the same herbal extract; HE) groups. Silymarin or herbal extract was orally given to rats a week before chronic intraperitoneal injection with CCl₄ for 6 weeks. The pathological results showed that herbal extract suppressed hepatic bile duct proliferation, and low-dose herbal extract inhibited liver fibrosis. Hepatic superoxide dismutase (SOD) activity was lower in the CCl₄ group, but there was no difference in the silymarin or herbal extract treated groups compared to the control group. Hepatic catalase activity and the ratio of reduced to oxidized glutathione were significantly higher (p < 0.05) in the HE group than those in the CCl₄ group. Silymarin and herbal extract reversed the impaired hepatic total antioxidant status (p < 0.05). Herbal extract partially reduced the elevated hepatic lipid peroxides. Hepatic transforming growth factor-β1 (TGF-β1) level decreased significantly (p < 0.05) in the LE group. Therefore, high-dose herbal extract improved hepatic antioxidant capacity through enhancing catalase activity and glutathione redox status, whereas low-dose herbal extract inhibited liver fibrosis through decreasing hepatic TGF-β1 level in rats with CCl₄-induced liver injury.

Ligustrazine is an alkaloid isolated from the rhizome of Chuanxiong (Ligusticum chuanxiong Hort), which is known to possess antioxidant, anti-inflammatory, anti-fibrosis and immunomodulative effects. It is used clinically to treat asthma as an assistant therapy of glucocorticoid. The purpose of this study was to explore the effects of intraperitoneal ligustrazine on Th1/Th2 cytokines in a rat asthma model and the underlying mechanism. SD rats were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. Within 24 hours after the last ovalbumin challenge, changes in airway histology were observed. The concentrations of IL-4 and IFN-γ in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). The protein expressions of GATA-3 and T-bet in lung were measured by Western blot. The results showed that an increase of Th2 cytokine and an inhibition of Th1 cytokine were accompanied by an increased expression of GATA-3 protein and a decreased expression of T-bet protein in rat asthmatic airways compared to those in normal control group. Intraperitoneal ligustrazine administration could significantly lower the level of IL-4 in BALF and the expression of GATA-3 protein in lung and also increase the level of IFN-γ and T-bet in asthmatic rats, resulting in a decreased percentage of eosinophils (EOS) in BALF and ameliorated airway inflammatory cell infiltration. In conclusion, ligustrazine inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in reversing the Th2 cytokine patterns in asthma.

Tetramethylpyrazine (TMP) is the major component extracted from the Chinese herb, Chuanxiong, which is widely used in China for the treatment of cardiovascular problems. The aims of this study were to examine whether TMP may alter angiotenisn II (Ang II)-induced proliferation and to identify the putative underlying signaling pathways in rat aortic smooth muscle cells. Cultured rat aortic smooth muscle cells were preincubated with TMP and then stimulated with Ang II, [³H]-thymidine incorporation and the ET-1 expression was examined. Ang II increased DNA synthesis which was inhibited by TMP (1-100 μM). TMP inhibited the Ang II-induced ET-1 mRNA levels and ET-1 secretion. TMP also inhibited Ang II-increased NAD(P)H oxidase activity, intracellular reactive oxygen species (ROS) levels, and the ERK phosphorylation. Furthermore, TMP and antioxidants such as Trolox and diphenylene iodonium decreased Ang II-induced ERK phosphorylation, and activator protein-1 reporter activity. In summary, we demonstrate for the first time that TMP inhibits Ang II-induced proliferation and ET-1, partially by interfering with the ERK pathway via attenuation of Ang II-increased NAD(P)H oxidase and ROS generation. Thus, this study delivers important new insight in the molecular pathways that may contribute to the proposed beneficial effects of TMP in cardiovascular disease.

Insulin resistance, which precedes type 2 diabetes mellitus (T2DM), is a widespread pathology associated with the metabolic syndrome, myocardial ischemia, and hypertension. Finding an adequate treatment for this pathology is an important goal in medicine. The purpose of the present research was to investigate the effect of an extract from Aloe vera gel containing a high concentration of polyphenols on experimentally induced insulin resistance in mice. A polyphenol-rich Aloe vera extract (350 mg/kg) with known concentrations of aloin (181.7 mg/g) and aloe-emodin (3.6 mg/g) was administered orally for a period of 4 weeks to insulin resistant ICR mice. Pioglitazone (50 mg/kg) and bi-distilled water were used as positive and negative controls respectively. Body weight, food intake, and plasma concentrations of insulin and glucose were measured and insulin tolerance tests were performed. The insulin resistance value was calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula. Results showed that the polyphenol-rich extract from Aloe vera was able to decrease significantly both body weight (p < 0.008) and blood glucose levels (p < 0.005) and to protect animals against unfavorable results on HOMA-IR, which was observed in the negative control group. The highest glucose levels during the insulin tolerance curve test were in the negative control group when compared to the Aloe vera extract and pioglitazone treated mice (p < 0.05). In conclusion, Aloe vera gel could be effective for the control of insulin resistance.

Pseudomonas aeruginosa is well-recognized as a nosocomial pathogen, which exhibits inherent drug resistance. In this study, the antibacterial activity of ethanol extracts of 58 Chinese herbal medicines used in Taiwan were tested against 89 nosocomial antibiotic resistant strains of Pseudomonas aeruginosa. The results gathered by the disc diffusion method showed that 26 out of the 58 herbal extracts exhibited antibacterial activity. Among the 26 herbal extracts, 10 extracts showed broad-spectrum antibacterial activities and were selected for further antibacterial property assay. The minimum inhibitory concentrations (MIC) of the active partition fractions ranged from 0.25 to 11.0 mg/L. The presence of flavonoid compounds in the active fractions of test herbal extracts was observed by the TLC-bioautography. The results from the time-kill assay revealed that most of the herbal extracts completely killed the test organisms within 4 hours. Exposure of the test strains to a sub-MIC level of the herbal extracts for 10 consecutive subcultures did not induce resistance to the active components. A combination of the active herbal fractions with antibiotics showed that one of the herbal medicines, the hexane fraction of Ramulus Cinnamomi, possessed a synergistic effect with tetracycline, gentamycin, and streptomycin. In conclusion, the tested Chinese medical herbs have the potential to be developed into natural antibiotics. This is the first evaluation for screening large amounts of medical plants against nosocomial antibiotic resistant bacteria in Taiwan.

Twelve species of Huperziaceae have been identified for resolving the resource depletion of Huperziaceae plants. The chloroplast genes rbcL, rpL16, and psbA-trnH intergenic spacers were used in this study. Identification of different species of Huperziaceae is possible by analyzing the information obtained from rbcL, rpL16, and psbA-trnH intergenic spacer sequences. The result also can provide information with regard to the use of plant tissue culture and cuttage propagation to solve the problem of the resource depletion of these plants.