[Mechanism and research progress of classical prescriptions and non-classical prescriptions in prevention and treatment of side effects of radiotherapy and chemotherapy].

Although targeted therapy and immunotherapy will become the trend of systematic therapy for tumor in the future, radiotherapy and chemotherapy are still regarded as one of the main means to treat cancer due to their low price and wide application. The toxic and side effects of radiotherapy and chemotherapy can limit the therapeutic effect and affect the body immunity, which is very difficult to deal with by modern medical means, and in this process, patients are prone to develop resistance to the application of radiotherapy and chemotherapy, which makes it difficult to implement follow-up treatment, leading to disease progression and ultimately affecting the prognosis of patients. In recent years, a large number of traditional Chinese medicine(TCM)-related clinical studies have found that classical prescriptions and non-classical prescriptions can markedly alleviate the toxic and side effects caused by radiotherapy and chemotherapy, with clear and significant efficacy, and to some extent, they can improve the quality of life and prolong the survival period of patients. Therefore, TCM decoction may provide new opportunities for intervening in the refractory and high-incidence toxic and side effects. To further explore the application of classical prescriptions and non-classical prescriptions in tumor, this study reviewed the mechanism of toxic and side effects caused by radiotherapy and chemotherapy, the mechanism of classical prescriptions and non-classical prescriptions in the treatment of toxic and side effects, and the classical prescriptions and non-classical prescriptions used for treating common toxic and side effects in recent five years. This study was expected to promote the application and development of classical prescriptions and non-classical prescriptions in the field of cancer treatment by systematically summarizing their research progress in the prevention and treatment of toxic and side effects caused by radiotherapy and chemotherapy.

Microwave coagulation/ablation in combination with sorafenib suppresses the overgrowth of residual tumor in VX2 liver tumor model.

OBJECTIVES: Our study is to evaluate the effect of thermal ablation on residual VX2 tumor tissue and the efficiency of sorafenib as an adjuvant therapy after insufficient microwave coagulation (MWC) on a rabbit VX2 liver tumor model. METHODS: Thirty-seven rabbits with orthotic VX2 liver tumors were randomly divided into MWC group (n=11), combination treatment group (n=14), and control group (n=12). The therapeutic efficacy was evaluated by contrast enhanced ultrasound (CEUS), magnetic resonance imaging (MRI), pathological and immunohistochemical examinations. Analysis of enhancement characteristics included enhancement level, pattern, and location. The necrotic degree of tumor was analyzed by semi-quantitative classification. The apparent diffusion coefficiency (ADC) was calculated using diffused weighted image (DWI). RESULTS: The tumor growth was accelerated in MWC group compared with control group and combination treatment group. A low metastasis rate was shown in combination treatment group compared with other two groups. The degree of necrosis in combination treatment group was greater than that in MWC group. The ADC value on DWI was higher compared with that of the control and MWC group, with statistical significance (P<0.05). With adjuvant therapy of sorafenib after insufficient ablation, the microvessel density (MVD) was lower than that of control group, whereas in MWC group the MVD was higher than that of control group, with statistical significance (P<0.05). CONCLUSION: Insufficient thermal ablation promotes residual tumor progression. While the adjuvant therapy of sorafenib serves as an effective way to suppress the overgrowth and neovascularization of residual tumor after insufficient thermal ablation.

[Analysis on traditional Chinese medicine prescriptions treating cancer based on traditional Chinese medicine inheritance assistance system and discovery of new prescriptions].

Malignant tumor is one of the main causes for death in the world at present as well as a major disease seriously harming human health and life and restricting the social and economic development. There are many kinds of reports about traditional Chinese medicine patent prescriptions, empirical prescriptions and self-made prescriptions treating cancer, and prescription rules were often analyzed based on medication frequency. Such methods were applicable for discovering dominant experience but hard to have an innovative discovery and knowledge. In this paper, based on the traditional Chinese medicine inheritance assistance system, the software integration of mutual information improvement method, complex system entropy clustering and unsupervised entropy-level clustering data mining methods was adopted to analyze the rules of traditional Chinese medicine prescriptions for cancer. Totally 114 prescriptions were selected, the frequency of herbs in prescription was determined, and 85 core combinations and 13 new prescriptions were indentified. The traditional Chinese medicine inheritance assistance system, as a valuable traditional Chinese medicine research-supporting tool, can be used to record, manage, inquire and analyze prescription data.

[Academic discussion of adverse reaction of clinical trials of new traditional Chinese medicines and relevant influencing factors].

Data of clinical trial projects involved by clinical trial institutions certified by the State Food and Drug Administration from 2002 to November 2012 were collected to summarize adverse reactions in project summary/statistical reports, analyze the rate of adverse reactions of clinical trials of new traditional Chinese medicines and relevant influencing factors, and increase the awareness of the safety of new traditional Chinese medicines. A total of 73 050 cases in 209 projects of 14 specialties were collected, including 49 689 cases in the new traditional Chinese medicine group and 271 adverse reaction cases, with an incidence rate of adverse reactions at 0.55%. The adverse reaction rate in 3 months < middle long course ≤ 6 months was the highest (1.04%), whereas that in short course ≤ half a month was the lowest (0.48%). The adverse reaction was closely related with the route of administration, 1.28% for topical > 0.63% for injection > 0.50% for oral. In the administration of only the test drug, the adverse reaction rate of patches was the highest (2.68%), whereas that of aerosols and suppositories was lowest (0). In the combined administration of the test drug and the simulation agent, the adverse reaction rate of external test patch + capsule was the highest (3.38%), whereas that of capsule + oral liquid, pills + granules, tablets + oral liquid, tablets + pills, tablet + capsule was the lowest (0). In the administration of only the test drug, the adverse reaction rate was 0.47%; In the combined administration with simulation agent (drug volume increase), the adverse reaction rate was 0.74%. Different doses caused adverse reaction different rates; The adverse reaction rate of drugs with whole-course dose between 1 100-1 200 g was the highest (3.36%), that for whole-course doses of 500-600, 900-1 000, 1 400-1 500, 1 600-1 700, 1 800-1 900 g was the lowest (0). In conclusion, the adverse reaction rate of new traditional Chinese medicines was still up to 0.55%, with the adverse reaction rate between 0.47% and 0.72% over the 11 years, without significant difference in each year. The adverse reaction rate was closely related to course of treatment, approach of administration, dosage form and medication dosage, with no significant correlation with medication dosage during the course of treatment. The adverse reaction rate increased with the rise in trial duration and drug volume. In the administration of only the test drug, the adverse reaction rates of external formulations and injections were higher than that of oral dosage forms. It is suggested to give more attention to the adverse reactions of drugs with long course of treatment and large volumes, injections and external patches in clinical trials of new traditional Chinese medicines.

Early treatment response to sorafenib for rabbit VX2 orthotic liver tumors: evaluation by quantitative contrast-enhanced ultrasound.

The aim of our study was to investigate the application of contrast-enhanced ultrasound (CEUS) and its quantification analysis for the prediction of early treatment response of sorafenib on rabbit VX2 liver tumor model. Rabbits were implanted VX2 tumor mass to establish a liver tumor model. Fourteen days after tumor implantation, rabbits presented with single liver tumor were randomly divided into two groups. Rabbits in treatment group were given by gavage once a day for 14 days with sorafenib suspension at a dose of 30 mg/kg, whereas rabbits in control group were given saline by gavage of the same volume. CEUS was performed before treatment and 3, 7, 14 days after treatment for the analysis of tumor size, enhancement pattern, and necrosis range. The time intensity curve (TIC) was used to obtain quantitative parameters of enhancement patterns. Before sorafenib administration, tumor volumes ranged from 0.24 to 0.75 cm(3) (mean 0.49 ± 0.18 cm(3)) in treatment group and 0.24 to 0.44 cm(3) (mean 0.30 ± 0.12 cm(3)) in control group. The dynamic enhancement patterns of tumors were homogeneous hyper-enhancement (n = 8), heterogeneous hyper-enhancement (n = 4), and peripheral rim-like enhancement (n = 2). All tumors of the treatment group presented with peripheral rim-like enhancement with large necrotic area after sorafenib administration, whereas tumors of the control group showed heterogeneous hyper-enhancement (n = 5) and peripheral rim-like enhancement (n = 2). There was a significant difference in area under the curve (AUC) before and after sorafenib treatment (P = 0.045). CEUS may be of value in the evaluation of early therapeutic response after sorafenib administration.

Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets: application to a pharmacokinetic study.

A rapid, reliable, and sensitive method was developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionization (ESI) source for determination of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets (GBTs). The method simultaneously detects bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF), and isorhamnetin (ISR) for pharmacokinetic study. The analytes and internal standard (IS) were extracted from rat plasma by acetidin. An MS/MS detection was conducted using multiple reaction monitoring (MRM) and operating in the negative ionization mode. The calibration curve ranges were 5-500, 5-500, 2.5-250, 1-100, 1-100, 1-100, and 1-100 ng/ml for BB, GA, GB, GC, QCT, KMF, and ISR, respectively. The mean recovery of the analytes ranged from 68.11% to 84.42%. The intra- and inter-day precisions were in the range of 2.33%-9.86% and the accuracies were between 87.67% and 108.37%. The method was used successfully in a pharmacokinetic study of GBTs. The pharmacokinetic parameters of seven compounds were analyzed using a non-compartment model. Plasma concentrations of the seven compounds were determined up to 48 h after administration, and their pharmacokinetic parameters were in agreement with previous studies.

[Preparation and optimization of zhitong micro-emulsion formula].

To prepare Zhitong micro-emulsion in this study, with the empirical formula of Zhitong preparation as the model medicine, the essential oil in the formula as the oil phase, and the water decoction as the water phase. The types of surfactant and co-surfactant were investigated. The changes in micro-emulsion conductivity and construction, the water percentage in the micro-emulsion system, the changing curve of conductivity and the fine pseudo-ternary phase diagram of micro-emulsion were drawn to determine the surfactant-co-surfactant mass ratio (K(m)). Subsequently, the D-mixture design was used to optimize Zhitong Micro-emulsion formula, with particle size and surface tension of micro-emulsion as the indexes. Finally, efforts were made to determine part of physical parameters of Zhitong micro-emulsion and preliminarily detect its stability. The results showed that the micro-emulsion was optimal with the EL-35-tween 20 ratio of 4:1 in surfactant, whereas the absolute ethyl alcohol was recommended as the co-surfactant. The ratio between surfactant and co-surfactant (K(m)) was 1.5. The finalized micro-emulsion formula contains 12% surfactant, 8% co-surfactant, 70% 1 g x mL(-1) water decoction and 8% oil. The results of the preliminary stability experiment showed a better stability of Zhitong micro-emulsion.

Cytotoxicity and enhancement activity of essential oil from Zanthoxylum bungeanum Maxim. as a natural transdermal penetration enhancer.

The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil (essential oil from Z. bungeanum Maxim.) on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cytotoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum corneum (SC) were determined using attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to understand its related mechanisms of action. It was found that the half maximal inhibitory concentration (IC50) values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation enhancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.

[Effect of microemulsion technology on release of compounds in Zhitong cataplasm and content variation].

To study the varieties of adhesives in gels on the basis of previous studies, dosage of adhesives required for forming of gels by using the single factor design, as well as the drug loading capacity of gels with the adhesiveness and stickiness as the scoring indicators, in order to determine the forming method of analgesic micro-emulsion gel. Subsequently, the improved Franz diffusing cell method was adopted to study the release of water-soluble components and liposoluble components in analgesic gels, with imperatorin and ferulic acid as index components. The results showed that analgesic micro-emulsion gel could promote the release of imperatorin and ferulic acid. Finally, HPLC was used to detect that the loss amount of volatile components in analgesic micro-emulsion gel was 23.13% lower than that in the original analgesic gel. In the experiment, we finally prepared finished products of micro-emulsion gel, discovered that the micro-emulsion technology is helpful to improve the synchronous release of water-soluble components and liposoluble components in prescriptions and can reduce the loss of volatile components.

[Studies on evaluation of sustained release tablets of extracts of Ginkgo biloba releasing rate in vitro by pharmacological indicatrix].

Using sustained release tablets of Ginkgo bibolia extract as model drug,discuss technical feasibility of using biotic index to evaluate sustained release tablets. Chosing two pharmacological indicatrix: antioxidant ability and inhibition of platelet aggregation, to investigate the influence factors on experimental result, optimize the method and experiment condition, and set up pharmacological indicatrix evaluation method. Using those methods to determinate biological effects of dissolved liquid. Drawing release curves and biological effects curves, discussing their correlation. A good correlation was observed, illustrating that pharmacological indicatrix could evaluate sustained release tablets.

[Study on in vitro release and percutaneous absorption for Zhitong cataplasm].

To evaluate in vitro release and transdermal behaviors of Zhitong cataplasm, modified Franz diffusion cell method was applied to investigate in vitro transdermal absorption of Zhitong cataplasm and the content of tetrahydropalmatine was determined by HPLC. In 24 hours, accumulative release rate of tetrahydropalmatine was 81. 9%, transmission rate was 2.26 microg x cm(-2) x h(-1). In 48 hours, accumulative transdermal rate and transmission rate of tetrahydropalmatine were 20.31%, 0.22 pg x cm(-2) x h(-1). So Zhitong cataplasm had a good release and transdermal properties and transdermal actions were consistent with zero-order kinetics process.

Xiaopiyishen Herbal Extract Granule Improves the Quality of Life among People with Fatigue-Predominant Subhealth and Liver-Qi Stagnation and Spleen-Qi Deficiency Syndrome.

To observe the effects of Xiaopiyishen Herbal Extract Granule (XPYS-HEG) on the quality of life in people with fatigue-predominant subhealth (FPSH) and liver-qi stagnation and spleen-qi deficiency syndrome, the participants were allocated randomly to the treatment group (XPYS, n = 100) and the control group (placebo, n = 100) in this study. The study period was 18 weeks (6 weeks for the intervention and 12 weeks for followup). The results show that there were no differences between the two groups for the scores of eight factors on the SF-36 (Chinese version of the SF-36 universal quality-of-life scale) at baseline. Compared with the baseline score, intervention with XPYS-HEG led to a significant increase in scores for the factor of bodily pain at the end of the 6th week. Compared with the score at the end of the 6th week, the score for the factor of mental health in the XPYS group significantly increased at the end of the 18th week. Therefore, XPYS-HEG could partially improve the quality of life for people with FPSH and liver-qi stagnation and spleen-qi deficiency syndrome, which can ease bodily pain, stimulate a positive mood, and ease a negative mood.

In vitro and in vivo inhibitory effect of the combination of Wenxia Changfu formula [see text] with cisplatin in non-small cell lung cancer.

OBJECTIVE: To observe the effect of the combination of Wenxia Changfu Formula ([see text], WCF) with cisplatin (CDDP) on inhibiting non-small cell lung cancer (NSCLC) in vitro and In Vivo and explore its mechanism from its effect on cell cycle. METHODS: In vitro, WCF-containing serum was prepared and the rhubarb b1, emodin, and aconitine were detected qualitatively by high-performance liquid chromatogram (HPLC). A549 cell lines were treated with blank control (dimethyl sulfoxide), normal serum, normal serum with CDDP (1.25, 2.5, and 5.0 µg/mL, respectively), WCF-containing serum plus different doses of CDDP (1.25, 2.5, and 5.0 µg/mL, respectively). The inhibitory effect was detected by 3-(4,5)-dimethylthiazo(-zy1)-3,5-diphenylterazolium bromide (MTT). The cell cycle was detected by flow cytometry. The protein and mRNA expressions of cyclin D1, proliferating cell nuclear antigen (PCNA), retinoblastoma (Rb), and p16 were observed with immunofluorescence and RT-PCR, respectively. In Vivo, nude mice xenograft model was established and grouped into the control, CDDP, WCF, and combination groups. The combination's inhibition of tumor growth and influence on the weight, spleen, and thymus gland were observed. RESULTS: The inhibitory rate of the combination against A549 cell lines excelled the CDDP alone significantly (P <0.05); the combination showed a synergism inhibitory effect (Q=1.19). Compared with the monotherapy, the combination increased the cell percentage in G(0)/G(1) phase and decreased the cell percentage in S phase significantly (P <0.05); the protein and mRNA expressions of cyclin D1, PCNA, and Rb were significantly reduced; the protein and mRNA expressions of p16 were significantly enhanced. Compared with the monotherapy, the combination inhibited the tumor growth significantly In Vivo and reduced the weight of tumor (P <0.05); compared with the CDDP group, the spleen and thymus gland index of the combination group were enhanced significantly (P <0.05). CONCLUSIONS: The combination of WCF with CDDP significantly inhibited the A549 cell lines proliferation in vitro and the growth of the tumor In Vivo; it inhibited effectively the atrophy of the immune organ caused by chemotherapy. The combination inhibited overproliferation of A549 cell lines by arresting the G(0) /G(1) phase of cell cycle and affecting the protein and mRNA expressions of cell cycle-related proteins, cyclin D1, etc.

[Effects of Xiaopi Yishen herbal extract granules in treatment of fatigue-predominant subhealth due to liver-qi stagnation and spleen-qi deficiency: a prospective, randomized, placebo-controlled and double-blind clinical trial].

BACKGROUND: The demand for effective intervention for subhealth conditions is growing with increasing numbers of people being in a state of subhealth with a poor quality of life. Future research and evaluation of the treatment methods for subhealth conditions from the perspective of traditional Chinese medicine (TCM) may provide an important direction for developing effective management of these conditions. OBJECTIVE: To evaluate the efficacy and safety of Xiaopi Yishen herbal extract granules (XPYS-HEG), a compound traditional Chinese herbal medicine for relieving fatigue and promoting a cheerful spirit for the treatment of people with fatigue-predominant subhealth due to liver-qi stagnation and spleen-qi deficiency. DESIGN, SETTING PARTICIPANTS AND INTERVENTIONS: A multi-center, randomized, double-blinded, placebo-controlled clinical study was undertaken. The study period was 18 weeks, including 6 weeks for intervention and 12 weeks for follow-up. Participants were recruited from medical center and outpatient clinics of three hospitals in China, i.e. Xiaotangshan Hospital of Beijing, the First Affiliated Hospital of Henan University of TCM and the Affiliated Hospital of Liaoning University of TCM. Two hundred participants who met the criteria of fatigue-predominant subhealth and liver-qi stagnation and spleen-qi deficiency in TCM were allocated randomly to the treatment group (XPYS, n=100) and control group (placebo, n=100). MAIN OUTCOME MEASURES: The total score of Fatigue Scale-14 (FS-14) was used to evaluate the fatigue status of subjects and the extent of liver-qi stagnation and spleen-qi deficiency syndrome was also recorded. RESULTS: Three cases in the XPYS group withdrew from the trial. There were 200 subjects who entered to full analysis set (FAS) analysis and 197 subjects fitted in the per-protocol set (PPS) analysis. (1) According to the score changes of FS-14, the effectiveness rates in the XPYS and placebo group were as follows: 14.0% vs 9.0% (FAS) and 14.4% vs 9.0% (PPS) for complete remission, 19.0% vs 15.0% (FAS) and 19.6% vs 15.0% (PPS) for obvious effects, 39.0% vs 26.0% (FAS) and 39.2% vs 26.0% (PPS) for effective, and 72.0% vs 50.0% (FAS) and 73.2% vs 50.0% (PPS) for complete efficacy. The efficacy of XPYS-HEG was superior to the placebo statistically (P<0.05). (2) According to the score changes of TCM syndrome, the effectiveness rates in the XPYS group and placebo group were as follows: 1.0% vs 0.0% (FAS) and 1.0% vs 0.0% (PPS) for complete remission, 20.0% vs 7.0% (FAS) and 19.6% vs 7.0% (PPS) for obvious effects, 29.0% vs 24.0% (FAS) and 29.9% vs 24.0% (PPS) for effective, and 50.0% vs 31.0% (FAS) and 50.5% vs 31.0% (PPS) for complete efficacy. The efficacy of XPYS-HEG was superior to that of placebo statistically (P<0.05). (3) The follow-up results at 12 weeks and 18 weeks showed that the efficacy of XPYS-HEG was superior to that of placebo statistically (P<0.05). (4) No adverse effects were found in the XPYS group. CONCLUSION: It can be concluded that XPYS-HEG is effective and safe for the treatment of people with fatigue-predominant subhealth due to liver-qi stagnation and spleen-qi deficiency.

[Osmotically controlled oral drug delivery systems: an update review].

Osmotically controlled oral drug delivery systems (OCODDSs) utilize osmotic pressure for controlled delivery of active agents. The release of drugs from osmotic systems is governed by various formulations and processing factors such as solubility and pressure of the core components, properties of the semi-permeable membrane. In the present review, the references on OCODDSs have systematically been summarized in the following aspects: prescription design, industrial processing and equipments, methods for quality evaluation, and general situation of application. Prospect of applying the osmotic-pump technology into Chinese patent drugs is also discussed.

[Formulation optimization of controlled porosity osmotic-pump tablets of total paeony glycosides].

OBJECTIVE: To prepare controlled porosity osmotic-pump tablets of total paeony glycosides (TPG) and establish the relationship between formulation factors of membrane and drug release rate. METHOD: Uniform design was used to achieve the quantitative relationship between the release rate and formulation factors of membrane. Optimized prescription was calculated from the regression equation. RESULT: A significant correlation and a fine precision of the regession equation were obtained. Controlled porosity osmotic-pump tablets of TPG were prepared based on the calculations, and the drug release profile was in accord with zero-order kinetics (r = 0.9902). CONCLUSION: Uniform design is a convenient and efficient approach for formulation optimization of controlled porosity osmotic-pump tablets.

[Biological effects of toosendanin, an active ingredient of herbal vermifuge in Chinese traditional medicine].

The fact that the fruit and bark of plant belonging to family Melia could be used as digestive tract-parasiticide and agricultural insecticide was recorded about two thousand years ago in ancient China. Toosendanin (TSN, C30H38O11, FW=574), a triterpenoid derivative, was extracted from the bark of Melia toosendan Sieb. et Zucc. by Chinese scientists in 1950os and used as an ascarifuge in China instead of imported sendanin. Studies have demonstrated that TSN possesses special biological actions as well as considerable various values in scientific research, clinic medicine and agriculture. The first is that by interfering with neurotransmitter release by causing an initial facilitation, TSN eventually blocks synaptic transmission at both the neuromuscular junction and central synapses. The action might result from TSN-induced Ca(2+)-sensitivity change and final elimination of transmitter release machinery. The second is that despite sharing many similar actions with botulinum neurotoxin (BoNT) on blocking neuromuscular transmission, TSN has a markedly antibotulismic action in vivo and in vitro: TSN-treatment saves the botulism mice or monkeys from death; TSN-incubation in vitro or TSN-injection in vivo endows neuromuscular junction with a high tolerance to BoNT. Studies suggest that the antibotulismic action is achieved by preventing BoNT from approaching its enzymatic substrate, SNARE protein. The third, in recent years, it is also observed that TSN can induce differentiation and apoptosis in several cell lines, and suppress proliferation of various human cancer cells. The TSN-induced differentiation is Ca(2+)-dependent and the mitochondria-dependent apoptosis pathway is involved in the TSN-induced apoptosis. The fourth is that TSN inhibits various K(+) channels and selectively facilitates Ca(2+) current through L-type Ca(2+) channels and hence elevates [Ca(2+)](i). The TSN-induced [Ca(2+)](i) increase and overload could be responsible for the TSN-induced biphasic effect on neurotransmitter release, cell differentiation, apoptosis as well as the cytotoxicity of TSN.

Ion-channels in human sperm membrane and contraceptive mechanisms of male antifertility compounds derived from Chinese traditional medicine.

Ion channel plays a key role in maturation, capacitation and acrosome reaction of sperm. However, as it is difficult to record channel currents from a mature mammal sperm directly by patch-clamp technique, there were no basic data on the types and properties of the channels in human sperm until the method reconstituting the channels into bilayer was used. By reconstituting the channel proteins isolated from sperm membrane into phospholipid-forming bilayer, we have characterized several kinds of Ca2+-, Na+-, K+-, and Cl--permeable channels with different conductance and properties in human sperm membrane. To study the channels in spermatogenic cells is another approach to understand the ion-channels in mature sperm. The cell is used as a model to analyze the effects of male antifertility agents on Ca2+-channel. To date, several male contraceptives derived from Chinese traditional medicine have been attached worldwide interest, a lot of compounds have been purified from them, and the antifertility effects of some compounds were demonstrated. We studied the effects of gossypol and several compounds isolated from Tripterygium wilffordii on Ca2+ channel in mouse spermatogenic cells and found that each of them inhibited the channel and sperm acrosome reaction at a proximate concentration, suggesting that the inhibition of Ca2+ channels may be one mechanism of the antifertility effects of these contraceptives.