Enhanced efficacy with reduced toxicity of chemotherapy drug 5-fluorouracil by synergistic treatment with Abnormal Savda Munziq from Uyghur medicine.

BACKGROUND: Abnormal Savda Munziq (ASMq) is a traditional prescription in Uyghur Medicine, and its treatment of complex diseases such as tumors and asthma has been proven to be effective in Uyghur medical clinical practice. The efficacy-enhancing and toxicity-reducing properties of ASMq were studied on mice with transplanted cervical cancer (U27) tumors, which were treated with 5-fluorouracil (5-FU) in this work. METHODS: To investigate the synergistic effect of ASMq and 5-FU on U27 cells, inhibitory effects on cell proliferation were determined through a MTT assay. 48 Kunming mice which were randomly divided in to 6 groups: control group, model group, 5-FU group, 5-FU combine with ASMq low-dose group, 5-FU combine with ASMq medium-dose group, and 5-FU combine with ASMq high- dose group, the inhibition rate of the tumor, the viscera indexes, and the content of serum tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. The expression levels of transforming growth factor-ß1 (TGF-ß1) and human papillomavirus type 16 E2 (HPV16 E2) protein were assessed by Western blot. Pathological changes in the liver were observed. RESULT: The inhibition rates of tumors, the 5-FU + ASMq.H group(80.64%), 5-FU + ASMq.M group (90.67%), 5-FU + ASMq.L group (72.03%) and 5-FU group (66.89%), clearly indicated that the effects of tumor inhibition. The thymus index and spleen index were increased, and the serum concentration of TNF-α increased while ALT and AST concentrations were decreased, and TNF-α protein expression were increased while TGF-ß1 and HPV16 E2 were decreased. ASMq might can improve livers central vein hyperemia and interstitial edema, and preserve the radial structure of the hepatic cords. CONCLUSIONS: The results suggested that ASMq might reduce toxicity and enhance the efficacy of the chemotherapeutic drug 5-fluorouracil in the treatment of cervical carcinoma.

Association study of gene polymorphisms and depression with abnormal humor in traditional Uighur medicine.

BACKGROUND: According to the humor theory of Traditional Uighur Medicine (TUM), a same disease is classified into different abnormal humor types and corresponding methods are applied to treat the diseases according to the type of abnormal humor characteristics. To date the biological foundation of classification of diseases by humor theory has been little studied and the mechanism of action is still unclear. In the present study, we aimed to investigate the association between some related gene polymorphisms and depression with abnormal humor in TUM. METHODS: 201 cases of depression patients in a Uighur population were divided into two groups as: 107 cases of depression patients with abnormal black bile (ABB), 94 cases of depression patients with none abnormal black bile (nABB), and 50 healthy people were served as control group. Venous blood was used to isolate DNA samples, and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for genotyping of single nucleotide polymorphisms (SNPs). Polymorphisms in the serotonin 2A (5-HT2A) receptor gene, brain derived neurotrophic factor (BDNF), serotonin 1A (5-HT1A) receptor gene were investigated in each groups, respectively. RESULTS: The 5-HT2A A-1438G, 5-HT2A T102C, BDNF Val66Met, and 5-HT1A C-1019G gene polymorphisms showed significant association with ABB. However, no difference between nABB and controls was found for those genotype distribution and allele frequency. Moreover, the T102C and A1438G SNPs in the 5-HT2A receptor gene polymorphisms were in linkage disequilibrium. In addition, the OR associated with the combination of Val66Met-Val/Val genotype plus the presence of -1019C allele was 8.393 for ABB compared with controls (OR 8.393; 95% CI 1.807 ~ 38.991; P = 0.003). Moreover, the OR associated with the presence of -Met plus -1019C alleles was 12.194 for ABB compared with controls (OR 12.194; 95% CI 1.433 ~ 103.776; P = 0.005). The OR associated with the presence of -1438C/C plus Val/Val genotypes was 7.738 for ABB compared with controls (OR 7.738; 95% CI 1.566 ~ 38.241; P = 0.005). CONCLUSION: It was concluded that there were significant relationship between the gene polymorphisms and classification of depression with abnormal humor in TUM. The 5-HT2A A-1438G, 5-HT2A T102C, BDNF Val66Met, and 5-HT1A C-1019G gene polymorphisms might predict the incidence of depression with ABB.

Ethanol Extract of Abnormal Savda Munziq, a Herbal Preparation of Traditional Uighur Medicine, Inhibits Caco-2 Cells Proliferation via Cell Cycle Arrest and Apoptosis.

Aims. Study the effect of Abnormal Savda Munziq (ASMq) ethanol extract on the proliferation, apoptosis, and correlative gene, expression in colon cancer cells (Caco-2) to elucidate the molecular mechanisms responsible for the anticancer property of Abnormal Savda Munziq. Materials and Methods. ASMq ethanol extract was prepared by a professional pharmacist. Caco-2 cells were treated with different concentration of ASMq ethanol extract (0.5-7.5 mg/mL) for different time intervals (48 and 72 h). Antiproliferative effect of ASMq ethanol extract was determined by MTT assay; DNA fragmentation was determined by gel electrophoresis assay; cell cycle analysis was detected by flow cytometer; apoptosis-related gene expression was detected by RT-PCR assay. Results. ASMq ethanol extract possesses an inhibition effect on Caco-2 cells proliferation, induction of cell apoptosis, cell cycle arrest in sub-G1 phase, and downregulation of bcl-2 and upregulation of Bax gene expression. Conclusion. The anticancer mechanism of ASMq ethanol extract may be involved in antiproliferation, induction of apoptosis, cell cycle arrest, and regulation of apoptosis-related gene expression such as bcl-2 and Bax activity pathway.

Immunomodulatory and antitumour effects of abnormal Savda Munziq on S180 tumour-bearing mice.

BACKGROUND: Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. This study attempts to confirm these effects in vivo and measure effects on the immune system. METHODS: Kunming mice transplanted with Sarcoma 180 cells were treated with ASMq (2-8 g/kg/day) by intra-gastric administration compared to model and cyclophosphamide (20 mg/kg/day). After the 14th day post tumour implant, thymus, liver, spleen and tumours were removed, weighed, and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses including TNF-α , IL-1 ß and IL-2. Splenic lymphocyte function was measured with MTT; lymphocyte subpopulations were measured by flow cytometry. RESULTS: ASMq treated animals had reduced tumour volume compared to model and increased concentrations of TNF-α, IL-1ß and IL-2 compared to untreated and to cyclophosphamide-treated animals. No histopathological alterations were observed. The absence of viable S180 cells and the presence of necrotic cells and granulation tissue were observed in tumour tissue of treated animals. The effect on T lymphocytes was unclear. CONCLUSIONS: ASMq confirmed in vivo anti-tumour effects observed in vitro, which may be at least in part mediated by increased immune activity.

Abnormal Savda Munziq, an Herbal Preparation of Traditional Uighur Medicine, May Prevent 1,2-dimethylhydrazine-Induced Rat Colon Carcinogenesis.

The study tried to assess the chemoprotective effect of abnormal Savda Munziq (ASMq) on 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Male F344 rats were randomized into eight groups: Group 1 was served as control, no DMH injection was given and treated daily with normal saline. Rats in Groups 2-8 were given a single intraperitoneal injection of DMH (20 mg/kg body weight) at the beginning of the study. Group 2 was served as negative control, administered with normal saline until the end of the experiment after the single DMH injection. Groups 3-5 were served as pretreatment group, administered with ASMq ethanol extract at 400, 800 and 1600 mg/kg body weight, respectively, until the 45th day, continued by normal saline administration for another 45 days. Groups 6-8 were served as the treatment group, administered with normal saline for the first 45 days from the day of DMH injection, ASMq ethanol extract at three different doses to be administered until the end of the second 45th day. All rats were sacrificed at 91st day and the colons were analyzed for aberrant crypt foci (ACF) formation and crypt multiplicity. Results showed that ASMq ethanol extract reduced the number of ACF, AC and crypt multiplicity significantly (P < .05). It suggested that ASMq ethanol extract had chemoprotective effects on DMH-induced colon carcinogenesis, by suppressing the development of preneoplastic lesions, and probably exerted protection against the initiation and promotion steps of colon carcinogenesis.

Inhibition of Cell Growth and Cellular Protein, DNA and RNA Synthesis in Human Hepatoma (HepG2) Cells by Ethanol Extract of Abnormal Savda Munziq of Traditional Uighur Medicine.

Abnormal Savda Munziq (ASMq) is a traditional Uighur medicinal herbal preparation, commonly used for the treatment and prevention of cancer. We tested the effects of ethanol extract of ASMq on cultured human hepatoma cells (HepG2) to explore the mechanism of its putative anticancer properties, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide, neutral red and lactate dehydrogenase (LDH) leakage assays, testing the incorporation of (3)[H]-leucine and (3)[H]-nucleosides into protein, DNA and RNA, and quantifying the formation of malondialdehyde-thiobarbituric acid (MDA) adducts. ASMq ethanol extract significantly inhibited the growth of HepG2 and cell viability, increased the leakage of LDH after 48 hours or 72 hours treatment, in a concentration- and time-dependent manner (P < .05). Cellular protein, DNA and RNA synthesis were inhibited in a concentration- and time-dependent manner (P < .05). No significant MDA release in culture medium and no lipid peroxidation in cells were observed. The results suggest that the cytotoxic effects of ASMq ethanol extract might be related to inhibition of cancer cell growth, alteration of cell membrane integrity and inhibition of cellular protein, DNA and RNA synthesis.

[Study on mechanism of abnormal savda munziq flavonoids in induction of apoptosis of Hep2 cells].

OBJECTIVE: To investigate the effect of Abnormal Savda Munziq (ASMq) flavonoids on proliferation, apoptosis and apoptosis-related gene expression in human hepatoma (HepG2) cells in vitro and to probe the mechanism. METHOD: The effects of ASMq flavonoids on proliferation, apoptosis and apoptosis-related gene expression of HepG2 cells were investigated respectively by MTT assay, gel electrophoresis, flow cytometry and RT-PCR. RESULT: ASMq flavonoids significantly inhibited growth of HepG2 cells in vitro, arrested HepG2 in the sub-G, phase, induced cell apoptosis and significantly down-regulated expression level of Bcl-2 mRNA, and up-regulated expression of p53, p21, Bax gene mRNA expressions. CONCLUSION: ASMq flavonoids has significantly regulative action on growth, apoptosis and apoptosis-related gene expression of cancer cells in vitro, which possibly are the important way to excert anticancer effect, and flavonoids are possibly a main active component of ASMq for exerting the anticancer effect.

Attenuation effect of Abnormal Savda Munziq on liver and heart toxicity caused by chemotherapy in mice.

Abnormal Savda Munziq (ASMq), an Uighur medicine formula commonly used in the treatment of cancer, has been speculated to possess antioxidative and antiproliferative effects, and to regulate immune activity. The present study was designed to systematically elucidate the toxicity-reducing activity of ASMq in mice undergoing combination chemotherapy with doxorubicin and 5-fluorouracil (5-FU). The mice were divided into normal (saline, 10 ml/kg) and doxorubicin + 5-FU groups (doxorubicin, 2.5 mg/kg; 5-FU, 10 mg/kg on alternate days). In addition, three groups received different doses of ASMq (2, 4 and 8 g/kg), in addition to doxorubicin (2.5 mg/kg) and 5-FU (10 mg/kg) treatment on alternate days. The histology of the heart and liver, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, malondialdehyde (MDA) concentrations in heart homogenate, and various biochemical parameters of the liver were evaluated. Compared with the normal control group, ASMq dose-dependently improved a number of variables, including body weight, liver index, transaminase and total protein, and partially normalized liver and cardiac pathology. ASMq restored activities of defense antioxidant enzymes SOD and GSH-Px towards normal levels, and decreased MDA concentration in dose-dependent manner. These results demonstrated that ASMq provides significant protection against doxorubicin + 5-FU combination induced hepatotoxicity and cardiotoxicity. Further studies are required to determine the effects of ASMq against doxorubicin + 5-FU-induced toxicity during chemotherapy in vivo.

Cytotoxicity of abnormal Savda Munziq aqueous extract in human hepatoma (HepG2) cells.

Abnormal Savda Munziq (ASMq) is a traditional Uighur medicinal herbal preparation commonly used to treat diseases such as diabetes, cardiovascular diseases, chronic asthma and especially digestive cancer. Earlier studies have shown that ASMq is a free radical scavenger and could prevent mitochondrial and DNA oxidative damage. In this study, we tested the effects of aqueous extract of ASMq on human hepatoma cells (HepG2) to explore the possible mechanism of its putative anticancer properties. Aqueous extract of ASMq was tested on HepG2 proliferation (MTT assay) at 72 h, cell viability at 48 h (neutral red assay), lactate dehydrogenase release over 48 or 72 h as a measure of cytoplasmic leakage, lipid peroxidation (malondialdehyde-thiobarbituric acid adducts) at 48 h, and incorporation of [3H]-leucine, [3H]-thymidine and [3H]-uridine into cellular protein, DNA and RNA, respectively, at 24 or 48 h to assess the inhibition effects to cellular macromolecule synthesis. Our results showed a significant (P < 0.05) time- and concentration-dependent inhibition of HepG2 proliferation and viability, with increased cytoplasmic leakage, and time- and concentration-dependent inhibition of protein, DNA and RNA synthesis. No lipid peroxidation was found at these concentrations. The results of the present study suggest that the putative anticancer mechanisms of ASMq may at least involve cytotoxicity.

Protective effects of Munziq and Mushil of abnormal Savda to mitochondrial oxidative damage.

Munziq and Mushil of Abnormal Savda are traditional Uighur herbal medicinal products, which could have antioxidant properties protecting mitochondria against oxidative damage. Mitochondria were isolated from rat livers. A FeSO4/VitC hydroxyl radical-generating system was used to induce mitochondrial oxidative damage. Alterations in mitochondrial membrane structure were observed by electron microscopy, and mitochondrial superoxide dismutase (SOD) activity, malondialdehyde (MDA) level and Ca2+-Mg2+-ATPase activity were measured. Muziq or Mushil were added, at concentrations ranging from 10(-5) to 10(-1) g/mL. Mitochondrial membrane structure was damaged after exposure to hydroxyl radical; mitochondrial SOD and Ca2+-Mg2+-ATPase activities decreased (by 80 and 55%, respectively, both P < 0.01), and MDA level increased 4.6-fold (P < 0.01). Munziq and Mushil protected mitochondrial membranes from structural damage. They inhibited the changes in mitochondrial functions in a dose-dependent manner. At the highest concentrations, values were equal to initial normal values. Munziq and Mushil of Abnormal Savda can reduce the oxidative damage induced by hydroxyl radical and protect the mitochondrial membrane structure and its functions.

Interactions between aspirin and COX-2 inhibitors or NSAIDs in a rat thrombosis model.

Recent in vitro studies, clinical trials and epidemiological studies have suggested possible interactions between aspirin and other cyclo-oxygenase (COX) inhibitors, such as ibuprofen of the COX-2 inhibitors celecoxib and rofecoxib. The objective of this study was to test the effects of aspirin (1, 2.5 and 5 mg/kg), and ibuprofen (4 and 15 mg/kg), diclofenac (2.5 mg/kg), flurbiprofen (2 mg/kg), celecoxib (7.5 mg/kg), and rofecoxib (1 mg/kg), alone or combined on a rat model of arterial thrombosis. Drugs were given orally daily for 7 days, before insertion of an arterio-venous shunt thrombosis system, left in place for 15 min. Main parameter was thrombus weight. Five to 12 rats were used per experiment, and 35 controls overall. Aspirin inhibited thrombus formation in a dose-dependent manner. All NSAIDS given alone also inhibited thrombus formation to approximately the same level as aspirin 1 mg/kg/day. Ibuprofen, celecoxib and rofecoxib inhibited the effects of aspirin, but not diclofenac or flurbiprofen. The interactions with aspirin do not seem to affect all NSAIDs to equal levels. The clinical impact of this needs to be confirmed in adequately powered clinical trials or pharmaco-epidemiological studies.

The impact of the Uighur medicine abnormal savda munziq on antitumor and antioxidant activity in a S180 and Ehrlich ascites carcinoma mouse tumor model.

AIM: This study was designed to study the antitumor and antioxidant activity of Uighur medicine abnormal savda munziq (ASMq) in the S180 and Ehrlich ascites carcinoma mice tumor model. MATERIALS AND METHODS: The serum levels of superoxide dismutase (SOD), malonaldehyde (MDA), and glutathione-catalase (GSH-PX) were analyzed, and the mice were also subjected to a hypoxia tolerance test. Their climbing ability was also analyzed. RESULTS: The findings of the study revealed that ASMq-treatment leads to an increase in blood serum SOD and GSH-PX levels but a decrease in blood serum MDA levels. Moreover, ASMq-treatment enhanced the survival time of mice maintained under hypoxic conditions and improved their mice climbing ability. CONCLUSIONS: The results of this study indicate that ASMq has obvious antitumor and antioxidative effects.

Aspects of sino-Japan complementary and alternative medicine and development on the traditional uighur medicine.

Two consecutive conferences on 'Sino-Japan Complementary and Alternative Medicine and Development on the Traditional Uighur Medicine' were held in Xinjiang Medical University on July 3 and Kanazawa Medical University on October 6, 2007. The Vice president Halmurat Upur presided over the meeting and gave congratulatory address on holding of the conference. In order to understand mutually and discuss the possibility of the Uighur Medicine as CAM and the situation of medicine in the global sense, specialist scholars of Traditional Uighur Medicine and postgraduates attended this conference. In the meeting of the CAM, the achievements on the research of Traditional Uighur Medicine were exchanged and warmly discussed. Presentations were made in the consecutive conference.