Stephaniae Tetrandrae Research Articles

The Extracts of Evodiae Fructus and Stephaniae Tetrandrae Radix Show Synergy in Blocking the Entry of SARS-CoV-2

Given the fact that herbal extracts have been effectively used in clinical applications and have well-established safety records, our current findings suggest that these drug combinations might be considered as potential anti-COVID-19 treatments.

Dissection of the antitumor mechanism of tetrandrine based on metabolite profiling and network pharmacology

RationaleTetrandrine, the Q‐marker in Stephaniae Tetrandrae Radix, was proven to present an obvious antitumor effect. Until now, the metabolism and antitumor mechanism of tetrandrine have not been fully elucidated.MethodsThe metabolites of tetrandrine in rats were profiled using ultra‐high‐performance liquid chromatography coupled with time‐of‐flight mass spectrometry. The potential antitumor mechanism of tetrandrine in vivo was predicted using network pharmacology.ResultsA total of 30 metabolites were characterized in rats after ingestion of tetrandrine (10 mg/kg), including 0 in plasma, 7 in urine, 11 in feces, 9 in liver, 8 in spleen, 4 in lung, 5 in kidney, 5 in heart, and 4 in brain. This study was the first to show the metabolic processes demethylation, hydroxylation, and carbonylation in tetrandrine. The pharmacology network results showed that tetrandrine and its metabolites could regulate AKT1, TNF, MMP9, MMP2, PAK1, and so on by involving in proteoglycan tumor pathway, PI3K‐Akt signaling pathway, tumor pathway, MAPK signaling pathway, and Rap1 signaling pathway.ConclusionsThe metabolism features of tetrandrine and its potential antitumor mechanism were summarized, providing data for further pharmacological validation.

An innovative extraction strategy for herbal medicine by adopting p-sulphonatocalix[6]/[8]arenes.

Alkaloids exist in various herbal medicine widely and exhibit diverse biological and pharmacological activities. p-Sulphonatocalix[6]arenes (SC6A) and p-sulphonatocalix[8]arenes (SC8A) are water-soluble supramolecular macrocycles and are applied to the extraction of alkaloids from herbal products. In this study, an innovative method of SC6A/SC8A assisted extraction of the alkaloids from herbs was established. SC6A and SC8A were designed to extract 27 alkaloids from seven herbal medicines. Based on the significant solubilisation and extraction effect, Stephaniae Tetrandrae Radix (Fangji, FJ) was selected to obtain the optimal extraction process by adopting single factor test and orthogonal experiment. Then, the alkaloids and SC6A/SC8A were separated by one-step alkalisation and SCnA were reused. The host-guest complexes between alkaloids and SCnA were determined by competitive fluorescence titration, differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) and proton nuclear magnetic resonance (1 H-NMR) analysis. The optimum condition for SC6A assisted extraction was 5:1:80 (g/g/mL) for herbs/SC6A/solution ratio, 355-250 μm particle size and ultrasonicate 0.5 h, whilst 10:1:40 (g/g/mL) for herbs/SC8A/solution ratio, 355-250 μm particle size and ultrasonicate 0.5 h for SC8A assisted extraction. The total yield of alkaloids (fangchinoline and tetrandrine) from FJ was increased by 4.87 times and 5.97 times with SC6A and SC8A. Moreover, a good reusability of SC6A/SC8A was achieved by alkalisation dissociation. Host-guest complexes were determined by competitive fluorescence titration at a molar ratio of 1:1 between most alkaloids (25/27, except evodiamine and rutaecarpine) and SC6A/SC8A. The complex structure was proved by DSC, FTIR and 1 H-NMR analysis. The study provided an effective eco-friendly and energy-saving extraction method of alkaloids from herbal medicine.

UHPLC-MS/MS Method for Quantifying Fangchinoline, Tetrandrine and Calycosin-7-O-β-D-Glucoside of Fangji Huangqi Decoction in Rat Plasma and Its Application to a Pharmacokinetic Study.

Fangji Huangqi Decoction is composed of Stephaniae Tetrandrae Radix, Astragli Radix, Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix Et Rhizoma. It is a classic traditional Chinese medicine formula for the treatment of chronic glomerulonephritis in China. However, its pharmacokinetic characteristics in vivo are still unclear. In this study, a method for quantifying fangchinoline, tetrandrine and calycosin-7-O-β-D-glucoside, the main active constituents of Fangji Huangqi Decoction, in rat plasma by using ultrahigh-performance liquid chromatography-tandem mass spectrometry technique was developed. Plasma samples were processed with a deproteinization procedure using acetonitrile, followed by chromatographic separation on a Shim-pack XR-ODS C18 column using gradient elution of 0.1% aqueous formic acid and acetonitrile at 0.4mL/min. The analytes and internal standard, diphenhydramine hydrochloride, were detected using positive electrospray ionization in multiple reactions monitoring mode. The optimized mass transition ion-pairs (m/z) were 609.3/367.3 for fangchinoline, 623.3/174.3 for tetrandrine, 447.2/285.1 for calycosin-7-O-β-D-glucoside and 256.2/167.1 for diphenhydramine hydrochloride, respectively. The developed method was validated for intraday and interday precision and accuracy whose values fell in the acceptable limits. Recovery efficiency of all the analytes was found to be >90.5%. Matrix effect was found to be negligible. Stability results showed that the analytes were stable under all conditions. The validated method was successfully used for studying the pharmacokinetics of the three compounds in rat plasma after oral administration of Fangji Huangqi Decoction.

Ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry and database-driven automatic peak annotation for the rapid profiling and characterization of the multicomponents from stephaniae tetrandrae radix (Fang-Ji)

Objective: Quality control of traditional Chinese medicine (TCM) begins with the chemical basis elucidation. The root of Stephania tetrandra has long been utilized as an antirheumatic, analgesic, and diuretic TCM, Stephaniae Tetrandrae Radix (STR; Fang-Ji). Powerful analytical strategies enabling its multicomponent characterization is still rare. Methods: A rapid, reliable, and enhanced profiling approach, by ultra-high performance liquid chromatography coupled with ion mobility/quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) and automatic peak annotation facilitated by computational matching of in-house library, was established and utilized to characterize the multicomponents from STR. A knockout strategy was utilized by automated valve switching to overcome the interference of predominant peaks. Results: Good chromatographic separation was achieved within 17 min on a reversed-phase BEH C18 column eluted with acetonitrile/0.1% ammonium hydroxide in water, while data-independent high-definition MSE (HDMSE) in positive mode was applied to acquire the MS2 data by using a VionTM IM-QTOF instrument, which in theory, could cover all the profiled precursor ions. An in-house library of 163 compounds was established and incorporated into the UNIFITM platform. By feat of these efforts, we were able to identify or tentatively characterize 76 alkaloids from the methanolic extract of STR, including 14 aporphine-type, four morphine-type, 48 bisbenzylisoquinoline-type, seven tetrahydroprotoberberine-type, one protopine-type, one benzylisoquinoline-type, and one other. Four-dimensional information, such as the retention time, collision cross section (CCS), high-accuracy MS1 and MS2 data, for each component was provided. Conclusions: The systematic multicomponent characterization of STR was accomplished with high coverage, high degree of automation, and high reliability.

Synergistic Inhibition of Acetylcholinesterase by Alkaloids Derived from Stephaniae Tetrandrae Radix, Coptidis Rhizoma and Phellodendri Chinensis Cortex.

Alkaloids having acetylcholinesterase (AChE) inhibitory activity are commonly found in traditional Chinese medicine (TCM); for example, berberine from Coptis chinensis, galantamine from Lycoris radiata, and huperzine A from Huperzia serrata. In practice of TCM, Stephaniae Tetrandrae Radix (STR) is often combined with Coptidis Rhizoma (CR) or Phellodendri Chinensis Cortex (PCC) as paired herbs during clinical application. Fangchinoline from STR and coptisine and/or berberine from CR and/or PCC are active alkaloids in inhibiting AChE. The traditional usage of paired herbs suggests the synergistic effect of fangchinoline–coptisine or fangchinoline–berberine pairing in AChE inhibition. HPLC was applied to identify the main components in herbal extracts of STR, CR, and PCC, and the AChE inhibition of their main components was determined by Ellman assay. The synergism of herb combination and active component combination was calculated by median-effect principle. Molecular docking was applied to investigate the underlying binding mechanisms of the active components with the AChE protein. It was found that fangchinoline showed AChE inhibitory potency; furthermore, fangchinoline–coptisine/berberine pairs (at ratios of 1:5, 1:2, 1:1, and 2:1) synergistically inhibited AChE; the combination index (CI) at different ratios was less than one when Fa = 0.5, suggesting synergistic inhibition of AChE. Furthermore, the molecular docking simulation supported this enzymatic inhibition. Therefore, fangchinoline–coptisine/berberine pairs, or their parental herbal mixtures, may potentially be developed as a possible therapeutic strategy for Alzheimer’s patients.

Chemical components and pharmacological action of Aconiti Radix

Aconiti Radix is a commonly used traditional Chinese medicine( TCM) herb in clinic,with the effects in expelling wind and removing damness,warming menstruation and relieving pain. With a long medicinal history and high medicinal value,it was used for anemofrigid-damp arthralgia,arthralgia,cold hernia and anesthesia analgesia. Modern pharmacological studies have shown that Aconiti Radix has a good therapeutic effect on rheumatoid arthritis,neuropathic pain and hypertension. As a well-known toxic TCM herb,its main pharmacodynamic and toxic components are alkaloids,which can lead to neurotoxicity and cardiotoxicity while exerting anti-inflammatory,analgesic,anti-tumor and other pharmacodynamic effects. Therefore,it is often processed to reduce its toxicity or combined with Paeoniae Radix Alba and Stephaniae Tetrandrae Radix to achieve the purpose of reducing toxicity and increasing efficacy in clinic.In recent years,with the deepening of the study on the incompatibility of TCM represented by " eighteen incompatible herbs",there have been new findings about TCM incompatibility. It has been found complementary effect,rather than no obvious toxic and side effects after the combination with incompatible herbs of Aconiti Radix. To provide the basis for further study and clinical application of Aconiti Radix,this paper reviewed chemical components,pharmacological action,toxicity and compatibility of Aconiti Radix by consulting relevant literatures published in recent years at home and abroad. Meanwhile,this paper also described the relationship between chemical constituents,as well as anti-inflammatory,analgesic,anti-tumor and other pharmacological effects and toxicity.

Tetrandrine, an Activator of Autophagy, Induces Autophagic Cell Death via PKC-α Inhibition and mTOR-Dependent Mechanisms.

Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes. In addition, tetrandrine induces cell death in a panel of apoptosis-resistant cell lines that are deficient for caspase 3, caspase 7, caspase 3 and 7, or Bax-Bak respectively. We also showed that tetrandrine-induced cell death is independent of necrotic cell death. Mechanistically, tetrandrine induces autophagy that depends on mTOR inactivation. Furthermore, tetrandrine induces autophagy in a calcium/calmodulin-dependent protein kinase kinase-β (CaMKK-β), 5′ AMP-activated protein kinase (AMPK) independent manner. Finally, by kinase profiling against 300 WT kinases and computational molecular docking analysis, we showed that tetrandrine is a novel PKC-α inhibitor, which lead to autophagic induction through PKC-α inactivation. This study provides detailed insights into the novel cytotoxic mechanism of an anti-tumor compound originated from the herbal plant, which may be useful in promoting autophagy mediated- cell death in cancer cell that is resistant to apoptosis.

Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells.

Fangchinoline is a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae S. Moore. Fangchinoline and its structure analogue, tetrandrine, exhibited direct binding affinity with recombinant human proteasome β1 subunit and also inhibited its activity in vitro. In cultured prostate PC-3 cells and LnCap cells, fangchinoline could dose-dependently inhibit cell proliferation and caspase-like activity of cellular proteasome which was mediated by proteasome β1 subunit. The inhibitive effect of fangchinoline on caspase-like activity of proteasome was also observed in purified human erythrocyte 20S proteasome. In PC-3 cells, fangchinoline induced cell cycle arrest at G0/G1 phase and apoptosis. Treatment of PC-3 tumor-bearing nude mice with fangchinoline inhibited tumor growth, induced apoptosis and also caused decrease in proteasome activities in tumor xenografts. Dose-dependent and time-dependent accumulation of ubiquitinated proteins and important proteasome substrates such as p27, Bax and IκB-α were observed in fangchinoline-treated cells. Over-expression of proteasome β1 subunit by plasmid transfection increased sensitivity of cells to the cytotoxicity of fangchinoline while knockdown of proteasome β1 subunit ameliorated cytotoxicity of fangchinoline in PC-3 cells. Results of the present study suggested that proteasome inhibition was involved in the anti-cancer effects of fangchinoline. Fangchinoline and its structure analogues might be new natural proteasome inhibitors targeting β1 subunit.

Salvianolic acid A, a novel matrix metalloproteinase-9 inhibitor, reduces microvascular damage induced by hypertension

Salvianolic acid A, a novel matrix metalloproteinase-9 inhibitor, reduces microvascular damage induced by hypertension

Molecular identification and cytotoxicity study of herbal medicinal materials that are confused by Aristolochia herbs

Herbal materials derived from Aristolochia species contain carcinogenic aristolochic acids (AAs) and have been used as traditional Chinese medicines (TCMs) or adulterants of other TCMs. The purpose of this study is to identify the TCMs Stephaniae Tetrandrae Radix, Akebiae Caulis, Aucklandia Radix and Aristolochiae Fructus by sequencing the matK, rbcL, trnH-psbA and trnL-trnF DNA regions. The cytotoxicities of AAs and these TCMs were also studied in COS-7 and HEK-293 cells. Diagnostic polymorphic sites were identified in all the four DNA loci for the differentiation of genuine herbs from their adulterants/substitute. The 48h IC50 of AAI were 78μM (COS-7) and 70μM (HEK-293) while the IC50 of AAII were higher than 100μM in both cell lines. Except Aucklandia Radix, cytotoxicity study also showed that AA-containing herbs were more toxic than their corresponding genuine herbs and substitute.

Effects of Qishe Pill, a compound traditional Chinese herbal medicine, on cervical radiculopathy: study protocol for a randomized controlled trial

BackgroundNeck pain is a common symptom in most patients suffering from cervical radiculopathy. However, some conservative treatments are limited by their modest effectiveness. On the other hand, surgical intervention for cervical disc disorders is indicated when symptoms are refractory to conservative treatments and neurological symptoms are progressive. Many patients use complementary and alternative medicine, including traditional Chinese medicine, to address their symptoms. The purpose of the present study is to examine the efficacy and safety of Qishe Pill, a compound traditional Chinese herbal medicine, for neck pain in patients with cervical radiculopathy.Methods/designA multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of the Qishe Pill is proposed. The study will include 240 patients from five sites across China and diagnosed with cervical radiculopathy, according to the following inclusion criteria: age 18 to 65 with pain or stiffness in the neck for at least 2 weeks (neck disability index score 25 or more) and accompanying arm pain that radiates distally from the elbow. Qualified participants will be randomly allocated into two groups: Qishe Pill group and placebo group. The prescription of the trial medications (Qishe Pill/placebo) are 3.75 g each twice a day for 28 consecutive days. The primary outcome is pain severity. Secondary outcomes are functional status, patient satisfaction, and adverse events as reported in the trial.DiscussionQishe Pill is composed of processed Radix Astragali, Muscone, Szechuan Lovage Rhizome, Radix Stephaniae Tetrandrae, Ovientvine, and Calculus Bovis Artifactus. According to modern research and preparation standards, Qishe Pill is developed to improve on the various symptoms of cervical radiculopathy, especially for neck pain. As it has a potential benefit in treating patients with neck pain, we designed a double-blind, prospective, randomized-controlled trial and would like to publish the results and conclusions later. If Qishe Pill can alleviate neck pain without adverse effects, it may be a unique strategy for the treatment of cervical radiculopathy.Trial registrationThis study is registered at ClinicalTrials.gov, NCT01274936

Fangchinoline Inhibits Human Immunodeficiency Virus Type 1 Replication by Interfering with gp160 Proteolytic Processing

The introduction of highly active antiretroviral therapy has led to a significant reduction in the morbidity and mortality of acquired immunodeficiency syndrome patients. However, the emergence of drug resistance has resulted in the failure of treatments in large numbers of patients and thus necessitates the development of new classes of anti-HIV drugs. In this study, more than 200 plant-derived small-molecule compounds were evaluated in a cell-based HIV-1 antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (fangchinoline). Fangchinoline, a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae, exhibited antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 µM. Mechanism-of-action studies showed that fangchinoline did not exhibit measurable antiviral activity in TZM-b1 cells but did inhibit the production of infectious virions in HIV-1 cDNA transfected 293T cells, which suggests that the compound targets a late event in infection cycle. Furthermore, the antiviral effect of fangchinoline seems to be HIV-1 enve1ope-dependent, as the production of infectious HIV-1 particles packaged with a heterologous envelope, the vesicular stomatitis virus G glycoprotein, was unaffected by fangchinoline. Western blot analysis of HIV envelope proteins expressed in transfected 293T cells and in isolated virions showed that fangchinoline inhibited HIV-1 gp160 processing, resulting in reduced envelope glycoprotein incorporation into nascent virions. Collectively, our results demonstrate that fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing. Fangchinoline may serve as a starting point for developing a new HIV-1 therapeutic approach.

Prescription profile of potentially aristolochic acid containing Chinese herbal products: an analysis of National Health Insurance data in Taiwan between 1997 and 2003

BackgroundSome Chinese herbal products (CHPs) may contain aristolochic acid (AA) or may be adulterated by the herbs suspected of containing AA which is nephrotoxic and carcinogenic. This study aims to identify the risk and the prescription profile of AA-containing CHPs (AA-CHPs) in Taiwan.MethodsA longitudinal analysis was conducted on a randomly sampled cohort of 200,000 patients using the data from the National Health Insurance (NHI) in Taiwan between 1997 and 2003.ResultsDuring the 7-year study period, 78,644 patients were prescribed with AA-CHPs; most patients were females, or middle-aged, or both. A total of 526,867 prescriptions were made to use 1,218 licensed AA-CHPs. Over 85% of the AA-exposed patients took less than 60 g of AA-herbs; however, about 7% were exposed to a cumulated dose of over 100 g of Radix et Rhizoma Asari (Xixin), Caulis Akebiae (Mutong) or Fructus Aristolochiae (Madouling). Patients of respiratory and musculoskeletal diseases received most of the AA-CHP prescriptions. The most frequently prescribed AA-CHPs Shujing Huoxie Tang, Chuanqiong Chadiao San and Longdan Xiegan Tang, containing Radix Stephaniae Tetrandrae, Radix et Rhizoma Asari and Caulis Akebiae, respectively.ConclusionAbout one-third of people in Taiwan have been prescribed with AA-CHPs between 1997 and 2003. Although the cumulated doses were not large, further actions should be carried out to ensure the safe use of AA-CHPs.

Microcalorimetric study on the bacteriostatic activity of isoquinoline alkaloids

The isoquinoline alkaloids were isolated from traditional Chinese drugs of Phellodendri Cortex, Radix Stephaniae Tetrandrae, Corydalis Yanhusuo and Corydalis Bungeana. The power-time curves of growth of E. coli at different concentrations of isoquinoline alkaloid at 37°C were determined by a 2277 Thermal Activity Monitor. The rate constant of bacteriostastic activity was calculated. The relationship between growth rate constant and concentration was established. The optimum bacteriostastic concentration was determined. Experimental results have indicated that all the isoquinoline alkaloids isolated from the four kinds of traditional Chinese drugs have bacteriostastic activity and the order is Phellodendri Cortex>Radix Stephaniae Tetrandrae>Corydalis Yanhusuo>Corydalis Bungeana.

Nonaqueous capillary electrophoresis for rapid and sensitive determination of fangchinoline and tetrandrine in Radix Stephaniae tetrandrae and its medicinal preparations

A simple, rapid, and sensitive non-aqueous capillary electrophoresis procedure with head-column field-amplified sample stacking concentration for the analysis of fangchinoline and tetrandrine is established. Optimum separation and stacking conditions were obtained when the sample was injected at 8 kV for 50 s after preliminary pressure injection of ethanol (16.9 kPa) for 0.6 s and separated with the buffer containing 50 mM ammonium acetate, 0.5% (v/v) acetic acid, and 50% (v/v) acetonitrile in methanol medium at 24 kV applied voltage. The analytes were detected by UV at 214 nm. The two bisbenzylisoquinoline alkaloids can be separated within 6 min and quantified with high sensitivity. The detection limits were 0.30 ng mL(-1) for fangchinoline and 0.34 ng mL(-1) for tetrandrine, which indicated that the sensitivities were at least 1000-fold enhanced over those reported in the literature as obtained by UV detection. The method was applied to the analysis of fangchinoline and tetrandrine in Radix Stephaniae tetrandrae and its medicinal preparations with good results.

An easy and rapid method to determine aristolochic acids I and II with high sensitivity

Aristolochic acid (AA), a natural component in some Chinese medicinal plants, is nephrotoxic and carcinogenic, and is involved in a specific type of renal fibrosis, called Chinese herbs nephropathy (CHN). In this paper, we report the electrochemistry of AA and a novel method to detect the species based on the electrochemical studies. The detection limit is estimated to be 1.0x10(-8) M with a linear range from 5.0x10(-8) M to 1.3x10(-6) M. Meanwhile, this method is applicable in detection in real samples, such as Caulis Aristolochiae Manshuriensis (CAM), Radix Aristolochiae (RA), Fructus Aristolochiae (FA) and Radix Stephaniae Tetrandrae (RST). The concentration of AA in the CAM sample was 3.50 +/- 0.12x10(-4) M. Consistent results have been obtained from both the electrochemical approach described here and the previously reported HPLC method.

Cardiac effects of the extract and active components of radix stephaniae tetrandrae: II. Myocardial infarct, arrhythmias, coronary arterial flow and heart rate in the isolated perfused rat heart

The primary purpose of the present study was to compare the cardioprotective effects of the extract from radix stephaniae tetrandrae (RST) and its individual compounds, tetrandrine (Tet) and fanchinoline (Fan). Secondly, we also compared the cardiac effects of the individual compounds and the RST extract with those of verapamil, a classical Ca 2+ channel blocker. The Langendorff isolated perfused rat heart preparation was used. Regional ischaemia and reperfusion was employed to induce myocardial infarct and arrhythmia. Infarct, arrhythmia, heart rate and coronary artery flow were determined in hearts treated with vehicle, RST extract, Tet, Fan, or verapamil. It was found that RST extract, of which only 9% was Tet, and Tet alone produced equally potent ameliorating effects on arrhythmia and infarct induced by ischaemia and reperfusion without further inhibiting ischaemia-reduced heart rate and coronary artery flow. Fan had no effects on arrhythmia and infarct induced by ischaemia and reperfusion; but it induced S-T segment elevation and further reduced heart rate and coronary artery flow during ischaemia. Verapamil also ameliorated the effects of ischaemia and reperfusion on arrhythmia and infarct. It should be noted that 1 μM verapamil, that produced comparable effects on infarct and arrhythmia to the RST extract and Tet, further inhibited heart rate during ischaemia. The results indicate that the RST extract produces equally potent cardioprotective and anti-arrhythmic effects as Tet alone. Both RST extract and Tet may be better choices for the treatment of arrhythmia and infarct induced by myocardial ischaemia and reperfusion than the classical Ca 2+ channel blocker, verapamil as they do not further reduce heart rate during ischaemia.

Cardiac effects of the extract and active components of radix stephaniae tetrandrae: I. Electrically-induced intracellular calcium transient and protein release during the calcium paradox

The present study was designed to compare the cardiac actions of the extract and individual components, tetrandrine (Tet) and fangchinoline (Fan), of Radix stephaniae tetrandrae (RST). We measured the electrically induced [Ca 2+] i transient in single rat ventricular myocytes and protein release following perfusion with a Ca 2+ free solution (the Ca 2+ paradox) from the isolated perfused rat heart, both of which are known to relate to Ca 2+ influx. We found that Tet inhibited both electrically induced [Ca 2+] i transient and protein release during the Ca 2+ paradox, while Fan had no significant effects. The RST extract containing 9% Tet and 6% Fan by weight also affected the [Ca 2+] i transient, and was only slightly, though significantly, less effective/potent than Tet alone. On the other hand, RST extract had a significantly greater inhibitory effect on protein release during the Ca 2+ paradox than Tet alone. The observations suggest that the RST extract, which contains a mixture of components, may have more potent effects in the heart than its main active component.

Experimental study of analgesic effect of combined aconitum and Stephania tetrandra

To explore the changes of analgesic effect of combined Radix Aconiti (Ac) and Radix Stephaniae Tetrandrae (ST). Methods: Rabbits and mice were divided randomly into following groups: the blank control group, the positive control group, the Ac group, the ST group, the combined Ac:ST(1:1) group and the combined Ac:ST (1:2) group. Using chemical, heat and electrical stimuli, four kinds of pain models were established to observe the changes of pain threshold of mice before and after using combined Ac and ST therapy. Results: Remarkable analgesic effect was obtained in the positive control group and all the groups treated with Ac and ST within 3 hours ( P 0.01), and the effect was more obvious in the combined Ac ST groups and the Ac group. The analgesic effect of the positive control group, the ST and the Ac group weakened gradually 3 hours later, and disappeared after 24 hrs in the positive control group and the ST group, but it is still remarkable in the combined Ac ST group, which showed a significant difference from that in the positive control group or in the groups treated with one single herb (As or ST). Conclusion:The analgesic effect of the combined Ac ST is superior to the AC and the ST used alone.