Tetrandrine (TET) and fangchinoline (FAN) are dominant bisbenzylisoquinoline (BBIQ) alkaloids from the roots of Stephania tetrandra of the family Menispermaceae. BBIQ alkaloids comprise two benzylisoquinoline units linked by oxygen bridges. The molecular structures of TET and FAN are exactly the same, except that TET has a methoxy (-OCH
Alkaloids/pharmacology* ; Benzylisoquinolines/pharmacology* ; Stephania tetrandra

Han stephania, also known as Stephania tetrandra, expelling wind, relieve pain and inducing diuresis for removing edema, is a traditional Chinese medicine for treating rheumatic arthralgia. Alkaloids have an important pharmacodynamic basis in S. tetrandra, and tetrandrine is one kind content of bisbenzylisoquinoline alkaloids, which has many biological activities. These activities include anti-tumor in many ways, clinically inhibiting multiple inflammatory factors, preventing and treating liver fibrosis and renal fibrosis and many other kinds of fibrotic diseases, and in addition, tetrandrine could work synergistically with other drugs. In recent years, through in-depth research by scholars at home and abroad, it has been found that tetrandrine has a protective effect on the nervous system and ischemia-reperfusion injury. At the same time, as a calcium ion antagonist, tetrandrine could effectively block the deposition of calcium ions inside and outside the cell. In summary, the application prospect of tetrandrine in clinical practice is very extensive. In this paper, the pharmacological effects of tetrandrine and the possible mechanisms for these effects are summarized, and review its current research progress. It is hoped that the possible application direction of tetrandrine can be revealed more comprehensively, and provide better enlightenment and ideas for clinical application.
Benzylisoquinolines/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Stephania tetrandra/chemistry*

Tetrandrine (Tet), the main active constituent of Stephania tetrandra root, has been demonstrated to alleviate adjuvant-induced arthritis in rats. The present study was designed to investigate the effects of Tet on the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and explore the underlying mechanisms. By using cultures of primary FLS isolated from synoviums of RA patients and cell line MH7A, Tet (0.3, 1 μmol·L(-1)) was proven to significantly impede migration and invasion of RA-FLS, but not cell proliferation. Tet also greatly reduced the activation and expressions of matrix degrading enzymes MMP-2/9, the expression of F-actin and the activation of FAK, which controlled the morphologic changes in migration process of FLS. To identify the key signaling pathways by which Tet exerts anti-migration effect, the specific inhibitors of multiple signaling pathways LY294002, Triciribine, SP600125, U0126, SB203580, and PDTC (against PI3K, Akt, JNK, ERK, p38 MAPK and NF-κB-p65, respectively) were used. Among them, LY294002, Triciribine, and SP600125 were shown to obviously inhibit the migration of MH7A cells. Consistently, Tet was able to down-regulate the activation of Akt and JNK as demonstrated by Western blotting assay. Moreover, Tet could reduce the expressions of migration-related proteins Rho GTPases Rac1, Cdc42, and RhoA in MH7A cells. In conclusion, Tet can impede the migration and invasion of RA-FLS, which provides a plausible explanation for its protective effect on RA. The underlying mechanisms involve the reduction of the expressions of Rac1, Cdc42, and RhoA, inhibition of the activation of Akt and JNK, and subsequent down-regulation of activation and/or expressions of MMP-2/9, F-actin, and FAK.
Animals ; Arthritis ; Arthritis, Rheumatoid ; metabolism ; prevention & control ; Benzylisoquinolines ; pharmacology ; therapeutic use ; Cell Movement ; drug effects ; Cell Proliferation ; Cells, Cultured ; Disease Models, Animal ; Down-Regulation ; Fibroblasts ; drug effects ; metabolism ; Humans ; MAP Kinase Signaling System ; Phosphatidylinositol 3-Kinases ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Roots ; Protein-Serine-Threonine Kinases ; metabolism ; Signal Transduction ; Stephania ; chemistry ; Synovial Membrane ; cytology ; drug effects ; metabolism ; rac1 GTP-Binding Protein ; metabolism ; rhoA GTP-Binding Protein ; metabolism

A new hasubanan alkaloid, hernsubanine E (1), as well as two known compounds p-hydroxybenzaldehyde (2) and (-)-syringaresinol (3) have been isolated from the whole plants of Stephania hernandifolia by various column chromatographic methods. Their structures were identified by physicochemical properties and spectral analyses. Compounds 2 and 3 were isolated from the genus of Stephania for the first time.
Alkaloids ; chemistry ; Heterocyclic Compounds, 4 or More Rings ; chemistry ; isolation & purification ; Stephania ; chemistry

AIM: To study the effects of crebanine on voltage-gated Na(+) channels in cardiac tissues. METHODS: Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltage-dependent Na(+) current was recorded using the whole cell voltage-clamp technique. RESULTS: Crebanine reversibly inhibited Na(+) current with an IC50 value of 0.283 mmol·L(-1) (95% confidence range: 0.248-0.318 mmol·L(-1)). Crebanine at 0.262 mmol·L(-1) caused a negative shift (about 12 mV) in the voltage-dependence of steady-state inactivation of Na(+) current, and retarded its recovery from inactivation, but did not affect its activation curve. CONCLUSION In addition to blocking other voltage-gated ion channels, crebanine blocked Na(+) channels in guinea-pig ventricular myocytes. Crebanine acted as an inactivation stabilizer of Na(+) channels in cardiac tissues.
Animals ; Aporphines ; pharmacology ; Cells, Cultured ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; drug effects ; metabolism ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; Stephania ; chemistry ; Voltage-Gated Sodium Channel Blockers ; pharmacology ; Voltage-Gated Sodium Channels ; metabolism

Eight alkaloids were isolated from the thin sulfuric acid extracts of the fresh roots of Stephania dentifolia by aluminum oxide, silica and Sephadex LH-20 column chromatography methods. Based on the spectroscopic analysis and chemical evidence, the structures of these alkaloids were identified as sinoacutine (1), sinomenine (2), cephamonine (3), tetrahydropalmatine (4), capaurine (5), stepharanine (6), (+)-stepharine (7) and palmatine (8). All compounds were obtained from this plant for the first time.
Alkaloids ; chemistry ; isolation & purification ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Plant Roots ; chemistry ; Stephania ; chemistry

OBJECTIVETo study the alkaloids in the stems and leaves of Stephania cepharantha.

METHODThe dried stems and leaves of S. cepharantha were percolated with 95% ethanol and the solvent was removed by rotary evaporation to give a concentrate, and the concentrate was extracted by petroleum ether and chloroform. Column chromatograghy on MCI CHP 20P, silica gel, Rp-18, Sephadex LH-20 and polyamide were applied for the isolation and purification of the chloroform fraction. The structures were elucidated by their physicochemical properties and spectral data.

RESULTEleven alkaloids were obtained and identified as lysicamine (1), tetrahadropalmatine (2), palmatine (3), isocorydione (4), corydalmine (5), corypalmine (6), sinoracutine (7), sinoacutine (8), cepharamine (9), isocorydine (10) and corydine (11).

CONCLUSIONCompounds 2-7 were isolated from S. cepharantha for the first time, and compound 7 was isolated from the genus Stephania for the first time, compound 4 was isolated from the Menispermaceae family for the first time.

Alkaloids ; analysis ; isolation & purification ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Stephania ; chemistry

OBJECTIVECombined the blood biochemical markers, the renal histopathological changes and the metabonomics profile were investigated to study the toxicity differences between Aristolochia fangchi and Stephania tetrandra.

METHODTen rats were randomly selected from 70 male Wistar rats as blank control group. The remaining 60 rats were divided into three groups. The two treated groups were orally administrated by 8.1 g x kg(-1) of A. fangchi and S. tetrandra respectively and the control group by equal volume of distilled water for 4weeks. Before the administrated and every 2 weeks, urine and plasma were collected and their 1H-NMR spectra were acquired, and then subjected to data process and PCA. Blood biochemical analysis and histopathological examination were carried out.

RESULTOn the 2nd weekend, the BUN of the two treated groups, the AST of A. fangchi group were all markedly higher than that of the control group (P < 0.05). Compared with the A. fangchi group, the SCr higher in the S. tetrandra group (P < 0.05). The kidney pathological changes were apparently in the two treated groups and the pathological changes in the liver apparently in the S. tetrandra group. Along with the lasting of administration to the 4th week, the BUN, ALT and AST of the two treated groups, the SCr of A. fangchi group were all significantly higher than that of the control group (P < 0.01). The renal and liver injuries in the two treated groups were all become more seriously. Comparing the A. fangchi group, the BUN, SCr and AST were all higher in the S. tetrandra group (P < 0.05). Compared with control group, the urinary concentrations of citrate, 2-oxo-glutarate, taurine, hippurate, TMAO, creatine and the plasma concentrations of 3-D-hydroxybutyrate, acetone, NAC, OAC, creatinine were all changed.

CONCLUSIONThe A. fangchi and S. tetrandra all can induce the renal and liver lesion and its seriousness is correspondent to the lasting of administration. The liver and kidney toxicity of S. tetrandra are all more serious than the A. fangchi.

Animals ; Aristolochia ; chemistry ; Blood Chemical Analysis ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; metabolism ; Kidney ; chemistry ; drug effects ; metabolism ; pathology ; Liver ; chemistry ; drug effects ; metabolism ; pathology ; Male ; Metabolomics ; Random Allocation ; Rats ; Rats, Wistar ; Stephania tetrandra ; chemistry ; Urine ; chemistry

OBJECTIVETo study the hasubanan type alkaloids in Stephania hernandifolia.

METHODThe dried herbs of S. hernandifolia. were extracted with 95% ethanol. After removal of the solvent, the residue was first partitioned between acid water and petroleum ether, then the aqueous layer was basified and extracted with chloroform to obtain crude alkaloids. Column chromatograghic methods with on silica gel, Rp-18, MCI CHP 20P, Sephadex LH-20 were applied for the isolation and purification of the crude alkaloid fraction. The structures were elucidated by their physicochemical properties and spectral data.

RESULTNine hasubanan type alkaloids were obtained and identified as aknadinine(1), longanone(2), stephasunoline (3), N-methylstephuline(4), epistephamiersine(5), prostephabyssine(6), aknadilactam(7), dihydroepistephamiersine(8), hasubanonine(9).

CONCLUSIONCompounds 2-8 were isolated from this plant for the first time.

Alkaloids ; chemistry ; isolation & purification ; Chemical Phenomena ; Molecular Structure ; Plant Extracts ; chemistry ; isolation & purification ; Stephania ; chemistry

OBJECTIVETo develop the system for the exclusive control substance of plant drug (CSPD) in traditional Chinese herbal medicines (TCHM), this paper investigated the (CSPD) of Radix Stephaniae Tetrandrae as well as its proton nuclear magnetic resonance (1H-NMR) and high performance liquid chromatography (HPLC) analytical methods for the purpose of original identification and quality control of the crude drug.

METHODThe CSPDs and their 1H-NMR and HPLC profiles of Radix Stephaniae Tetrandrae were obtained by standardized procedure. Chemical components were isolated from the CSPD by silica gel column chromatography. The assignments of the characteristic signals in 1H-NMR and HPLC profiles were achieved on the basis of elucidation of the isolates structures.

RESULTFor nine samples from the different sources in this paper, the 1H-NMR and HPLC profiles from eight sources had wonderful reproducibility and characteristics, and the other gave differences compared with the eight samples in the signal strength of the main components. Furthermore, seven compounds were isolated from CSPD and their chemical structures were authenticated by spectral analysis as tetrandrine, fangchinoline, tetrandrine-2'-N-beta-oxide, tetrandrine-2'-N-alpha-oxide, dicentrine, dicentrinone, and adenine, respectively. The 1H-NMR and HPLC profiles of the CSPD of Radix Stephaniae Tetrandrae showed mainly the characteristic signals of the bisbenzylisoquinoline alkaloids isolated in this work.

CONCLUSIONThe 1H-NMR and HPLC profiles of the CSPD of Radix Stephaniae Tetrandrae exhibit the structures and total composition of the main active constituents in it, and can be used for its original identification and quality evaluation.

Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; Magnetic Resonance Spectroscopy ; methods ; Quality Control ; Stephania tetrandra ; chemistry