Screening Study on the Anti-Angiogenic Effects of Traditional Chinese Medicine - Part II: Wild Chrysanthemum.

Background and Aims: Part 2 of our ongoing research with anti-angiogenic effects focuses on Wild chrysanthemum; a heat-clearing and detoxicating Traditional Chinese Medicine (TCM). We screened six heat-clearing and detoxicating TCM and noticed that wild chrysanthemum has a potent anti-angiogenic effect in zebrafish. This study aims to determine the genetic mechanisms underlying the anti-angiogenic effects of wild chrysanthemum. Methods: Wild chrysanthemum was decocted, concentrated, sieved and desiccated to attain the water extract. 200µg/mL wild chrysanthemum water extract (WCWE) was diluted in 0.1% dimethyl sulfoxide (DMSO) and given to zebrafish via fish water. 48h post-fertilization (hpf) fli1a-EGFP transgenic zebrafish were used to assay angiogenesis. mRNA-seq, qRT-PCR assay and a parallel reaction monitor (PRM) were carried out to reveal the underlying mechanisms. Results: WCWE showed a significant anti-angiogenic effect in zebrafish. The results of mRNA-seq showed that there were 1119 genes up-regulated and 1332 genes down-regulated by WCWE. The bioinformatic analysis based on mRNA-seq demonstrated that the proteasome signaling pathway was significantly down-regulated. The results of the qRT-PCR assay were consistent with those of the mRNA-seq assay. The results of the PRM assay showed that nine proteins involved in proteasome signaling and the protein expression level of ctnnb2 were significantly down-regulated. The results of the KEGG pathway analysis based on PRM assay demonstrated that WCWE may have an inhibitory action on the regulatory particle of the proteasome. Conclusion: Wild chrysanthemum has a significant anti-angiogenic effect in zebrafish and it may have an inhibitory action on the regulatory particle of the proteasome. The mechanisms underlying the anti-angiogenic effects of wild chrysanthemum may be related to the down-regulation of proteasome/ß-catenin signaling in zebrafish.

"Yellow-dragon Wonderful-seed Formula" for hyperuricemia in gout patients with dampness-heat pouring downward pattern: a pilot randomized controlled trial.

BACKGROUND: In Traditional Chinese Medicine (TCM) theories, the typical clinical manifestations of gout are attributed to the "dampness-heat pouring downward." Therefore, TCM practitioners always consider prescribing the formulae which are believed to clear heat and drain dampness for the management of gout. This clinical trial aims: (1) to determine the hypouricemic effect of "Yellow-dragon Wonderful-seed Formula" (YWF) decoction in gout patients with dampness-heat pouring downward pattern and (2) to determine if gypsum could provide additional significant benefits to YWF. METHODS: A total of 72 hyperuricemic individuals with gout and dampness-heat pouring downward pattern were included with 62 of them completing the trial. Participants were randomly assigned to the YWF group, the YWF + gypsum group, or the allopurinol group. YWF and YWF + gypsum decoctions were orally administered for four weeks. Allopurinol was also orally administered for four weeks as the active control. Serum uric acid (sUA) level was the primary outcome measure. Urine urate level, scores on the SF-36 scale, erythrocyte sedimentation rate (ESR), X ray film, and C reactive protein (CRP) level were the secondary outcome measures. RESULTS: Compared with the values at week 0, YWF and YWF + gypsum did not significantly decrease the sUA level at each weekend reading. YWF, YWF + gypsum, and allopurinol decreased the urine urate levels and there were significant differences between the YWF group and the YWF + gypsum group. All the changes in the eight structures of SF-36 during the intervention period were not significantly different among the three groups and there was no significant difference in the CRP level among the three groups at each weekend reading. CONCLUSIONS: YWM, which modified on the basis of Two Wonderful Herbs Powder (2WHP), does not show significant hypouricemic effect. There is a possibility that Gypsum Fibrosum may provide additional effects to YWF in decreasing the urine urate levels but cannot add benefits to YWF in other outcome measures. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-TRC-12001933 . Registered on 10 February 2012.

Screening study on the anti-angiogenic effects of Traditional Chinese Medicine - Part I: Heat-clearing and detoxicating TCM.

ETHNOPHARMACOLOGICAL RELEVANCE: Few studies have explored the anti-angiogenic effects of TCM - even more so, as it applies to cancer treatment research. Heat-clearing and detoxicating TCM is the most frequently used category in the treatment of cancerous tumors, but lacks sufficient validation studies. AIM OF THE STUDY: The present research (in our series of studies) aims to explore the anti-angiogenic effects of TCM; so we begin with heat-clearing and detoxicating TCM. MATERIALS AND METHODS: Six typical heat-clearing and detoxicating TCM (Philippine Violet Herb, Wild Chrysanthemum, Heartleaf Houttuynia Herb, Chinese Lobelia Herb, Spreading Hedyotis Herb and Uniflower Swisscentaury Root) were decocted, concentrated, sieved and desiccated to attain the water extract. This study utilized the vascular organism research model for Fli1a-EGFP zebrafish, which were raised and maintained under standard conditions. 22h post-fertilization (hpf) embryos were distributed into 12-well plates for a treatment period of 26h. The TCM water extracts which were diluted in 0.1% dimethyl sulfoxide (DMSO), were added to each well at a concentration of 200µg/ml. The positive control was 5µg/ml PTK787 (vatalanib) and the vehicle control was 0.1% DMSO. At 48hpf larvae were tricaine anesthetized and imaged. To demonstrate if TCM shows angiogenesis defects, ten larvae were randomly chosen to conduct a quantitative assay. Quantitative real-time PCR was conducted to dissect the mechanisms involved by analyzing the contributions of signaling pathways and molecules concerning angiogenesis, with a total of ten genes examined. RESULTS: All 30 larvae treated with Wild Chrysanthemum, Uniflower Swisscentaury Root and PTK787 showed angiogenesis defects. Embryos treated with Wild Chrysanthemum and Uniflower Swisscentaury Root showed a lower number of complete intersegmental vessels (ISVs) and there was statistically significant differences between TCM and the vehicle control. Wild Chrysanthemum and Uniflower Swisscentaury Root have a higher inhibition rate and the statistical difference between TCM and the vehicle control was significant. Compared with vehicle controls, Wild Chrysanthemum could significantly modulate the relative mRNA expression of all ten genes. Whereas, Uniflower Swisscentaury Root could significantly regulate the relative mRNA expression of seven genes, it did not show a significant impact on the remaining three genes. CONCLUSIONS: The present research demonstrates that Wild Chrysanthemum and Uniflower Swisscentaury Root have anti-angiogenic effects in zebrafish and that they could regulate both proangiogenic mechanisms and negative angiogenesis regulators. Their anti-angiogenic effects result from effects on negative regulators overriding their effects on proangiogenic mechanisms. The results provide new insights into their clinical application and therapeutic potential for the management of angiogenesis-dependent diseases such as cancer.

'Huang Qi Elixir' for proteinuria in patients with diabetic nephropathy: a study protocol for a randomized controlled pilot trial.

BACKGROUND: Diabetic nephropathy (DN) is the major complication of diabetes; proteinuria is the hall mark of DN. Currently, the treatment for proteinuria is mainly limited to angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). According to Traditional Chinese Medicine (TCM) theory, Chinese medicinals 'securing essence and tonifying the kidney' may be appropriate for proteinuria. The most promising Chinese medicinals and formulae are introduced in the present study to form a potent formula for DN proteinuria. To make oral administration convenient, the formula will be processed in the form of granules. METHODS/DESIGN: A randomized, multi-center pilot trial will be conducted. Forty eight participants with DN will be randomly assigned to one of four treatment groups: 1. A granule group, at 10 grams, three times daily (G10 group, n = 12); 2. A granule group, at 20 grams, three times daily (G20 group, n = 12); 3. A decoction group (D group, n = 12); and 4. An irbesartan group (Aprovel group, n = 12).The following outcome measures will be used: the percentage change of the albumin-to-creatinine ratio; and the changes in serum creatinine, glomerular filtration rate, fasting plasma glucose and hemoglobulin from baseline to the end of the trial. DISCUSSION: It is notable that most published clinical trials which assessed the efficacy of TCM on DN were of poor methodology and, therefore, their results have been invalidated. It is necessary to carry out well-designed clinical trials to provide sound evidence. The present trial is a study with potentially great value, for it will provide the parameters for future randomized, placebo-controlled, clinical trials with large sample sizes. TRIAL REGISTRATION: The trial is registered on the Chinese Clinical Trial Registry: ChiCTR-TRC-12002718 (http://www.chictr.org/cn/proj/show.aspx?proj=3820).

Fructus mume formula in the treatment of type 2 diabetes mellitus: a randomized controlled pilot trial.

Background. "Fructus Mume or Dark Plum" (pilule form) has been used for many years in Traditional Chinese Medicine (TCM) and may be a valid treatment for type 2 diabetes mellitus (T2DM). Aim. One aspect toward efficacy validation is the evaluation of the blood glucose-lowering effect of Fructus Mume (FM) with T2DM patients in a randomized controlled trial (RCT). Methods. This pilot study uses a RCT procedure to assess efficacy of FM and Metformin. The trial was for 12 weeks, with 80 T2DM subjects. Both groups were standardized in their diet and exercise routine. Comparisons of several variables were analyzed. Results. No significant differences were found between groups in the fasting and postprandial glucose levels although both had significant decreases. The values of glycosylated hemoglobin were significantly reduced in both groups. For patients whose body mass index (BMI) was <23, neither FM nor Metformin had an effect on BMI; for those with a BMI between 23 and 25 or the BMI was >25, both FM and Metformin significantly reduce the BMI. Conclusions. In this pilot study, it was demonstrated that Fructus Mume formula may reduce the levels of blood glucose in patients with type 2 diabetes.

Advances in heroin addiction treatment with traditional Chinese medicine: a systematic review of recent Chinese language journals.

The aim of this review is to critically examine the clinical trial research on Traditional Chinese Medicine (TCM) as an intervention in treating heroin addiction in People's Republic of China. This review examines Chinese-language-only publications for the patent medicines: Shenfu Tuodu, Fukang Pian, and Shifu Sheng. Other compound medicines will be reviewed in future publications. A systematic review of the literature was conducted in Western and Chinese databases. Most trials were excluded because they did not declare randomization and had poor methodology or reporting. The majority of clinical evidence in the random controlled trials demonstrates good evidence for TCM patent medicines in heroin addiction treatment. When compared to typical Western medications, TCMs demonstrate fewer side-effects, in addition to equal measures of treatment efficacy and safety.

Acupuncture treatment for opiate addiction: a systematic review.

A review of the efficacy of acupuncture as treatment for opiate addiction, covering 33 years of reported literature in western scientific journals, was systematically undertaken. Some abstracts from Chinese language journals were also briefly reviewed. Supportive evidence often came from non-controlled nonblinded methodologies. When well-designed clinical trials (randomized, controlled, single-blind methodologies) were used, there was no significant evidence for acupuncture being a more effective treatment than controls. Some of the current supportive evidence for efficacy came from Chinese journals that have not been translated into English yet.