Quick Navigation

Stephania tetrandra

Stephania tetrandra (Fang Ji) is a medicinal herb from Traditional Chinese Medicine that is sometimes used alongside Astragalus membranaceus for kidney protection and diabetes prevention; it is moderately antiinflammatory.

Our evidence-based analysis on stephania tetrandra features 75 unique references to scientific papers.


Things To Know & Note

Is a Form Of

Primary Function:

Also Known As

hangfangji, Fangchi, Hang Fang Chi

Do Not Confuse With

Sinomenium acutum, Cocculus trilobus, and Aristolochia fangchi (also referred to as Fangchi)

Goes Well With

Caution Notice

Examine.com Medical Disclaimer

  • Tetrandrine (a main bioactive) can inhibit CYP3A4 with moderate potency

  • Tetrandrine is able to inhibit P-glycoprotein, which underlies its synergism with berberine but may cause undesirable increases in some pharmaceuticals

  • The herb Aristolochia fangchi is also known as Fang Chi, but is a kidney toxin; if buying stephania ternatea it should be ensured that the former plant is not in the supplement by mistake

Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects stephania tetrandra has on your body, and how strong these effects are.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-d Lipid Peroxidation Minor - See study
A minor decrease in levels of lipid peroxidation in serum were noted, to the tune of 17%.
grade-d Serum Elastase Minor - See study
A decrease in serum neutrophil elastase has been noted, and this is thought to be related to symptoms of rheumatoid arthritis
grade-d Lymphocyte Count - - See study
Lymphocytes (both B and T cells) are unchanged in their overall quantity with 12 weeks of supplementation.
grade-d White Blood Cell Count - - See study
No significant alterations in white blood cell count are noted with oral supplementation of this plant.

Scientific Research on Stephania tetrandra

Click on any below to expand the corresponding section. Click on to collapse it.

Click here to fully expand all sections or here to fully collapse them.

1Sources and Composition

1.1Sources

Stephania tetrandra (of the family Menispermaceae) is a traditional chinese medicine that is also used in Japanese traditional medicine (Kampo), bearing the name hangfangji in Chinese medicine.[1] It is traditionally used against autoimmune diseases and rheumatism,[2] as well as antipyretic, diuretic, antiphlogistic, anti-diabetic as well as therapy for hepatic fibrosis.[3]

For medicinal usage, stephania tetrandra is sometimes referred to as 'Fangchi' or 'Fangji'; a term that also applies to the plants Sinomenium acutum, Cocculus trilobus, and Aristolochia fangchi[4][5] although cocculus trilobus and aristolochia fanchi are further classified as "Mu Fangchi" and "Guang Fangchi".[4]

1.2Composition

  • The bis-benzylisoquinoline alkaloid Fangchinoline at 43.50+/-0.024mg/g in the root[6] although lower concentrations of 3.14-8.08mg/g,[4] 0.40%,[7] or 0.97-2.37%[8] have been reported

  • Tetrandrine (another bis-benzylisoquinoline alkaloid[9]) at 82.31+/-0.003mg/g of the root[6] although lower concentrations of 2.80-10.31mg/g,[4] 0.78%,[7] or 1.28-2.84%[8] have been reported. Other similar structures include 2-N-methyltetrandrine and (+)-2-N-merhylfangchinoline[10]

  • Cassameridine and cassythicine[3]

  • Corydione[3]

  • Nantenine and Oxonantenine[3]

  • Aristolochic acid I and II (potential contaminants from Aristolochia fangchi)[11]

  • Oblongine (2.90+/-0.024mg/g of the root)[6]

  • Cyclanoline (59.09+/-0.009mg/g of the root)[6]

  • Magnoflorine (140-580µg/g[4])

  • A 4,5-Dioxoaporphine alkaloid (aerial parts)[12]

  • The biflavones Stephaflavone A-B (aerial parts)[13]

  • β-sitosterol (aerial parts)[13]

Although it is subject to variance, some reports suggest that the total alkaloid content of the dry root of stephania tetrandra is approximately 2.3% of which tetrandrine and fangchinoline constitute 1% and 0.5% (total weight), respectively.[9][14]

The main bioactives appears to be the two bis-benzylisoquinoline alkaloids, fangchinoline and tetrandrine

1.3Formulations

The formulation known as Boi-ogi-to (Fang-ji-huang-qi-tang) is a Kampo medicine containing this herb alongside astragalus membranaceus, the rhizome of Atractylodes Lancea, licorice, ginger, and ziziphus jujuba.[15] This formulation appears to be recommended for the treatment of arthritis and edema, and may have indirect effects on glucose and lipid metabolism associated with obesity.[15]

2Pharmacology

2.1Enzymatic Interactions

Tetrandrine appears to inhibit the P-glycoprotein efflux transporter,[16] with inhibition detectable at 1-2µM in vitro and an oral intake of 10-20mg/kg tetrandrine being able to increase the bioavailability of berberine (normally effluxed by P-glycoprotein);[17] this inhibition of P-glycoprotein also underlies some potential chemotherapeutic roles of tetandrine by overcoming drug resistance.[18][19]

Appears to be a relatively potent and biologically relevant P-glycoprotein inhibitor

Moderate inhibitory potential on CYP3A4 activity with tetrandrine with an IC50 of 3.9µM in vitro.[17]

Tetrandrine has been noted to have no significant inhibitory activity on CYP1A2 (IC50 is somewhere above 100µM) nor CYP2D6 (IC50 is 58.3µM).[17]

The inhibition of CYP3A4 has not been confirmed in vivo, but it seems potent enough to be of concern

3Molecular Targets

3.1Ion Channels

Tetrandrine appears to be a nonselective calcium channel blocker which influences L-type, N-type, and T-type channels; similar in structure and effects as other calcium channel blockers like berbamine (Bereris soulieana) and hernandezine (Thalictrum glandulosissimum).[20][21] It binds to the benzothiazepine/diltiazem recognition site.[22][23][24]

Some sources have also suggested that tetrandrine can inhibit calcium efflux from intracellular stores (calcium channel antagonists tend to inhibit efflux from extracellular compartments to intracellular).[21][25]

3.2Adrenergic Receptors

Tetrandrine appears to directly interact with α1-adrenergic receptors via competing with prazosin and phenylephrine binding[20] with a Ki value of 690+/-120nM yet IC50 values of 252.8µM (in inhibiting adrenaline induced calcium influx), 11.6µM (inhibiting spontaous basal contractions), and 7.4µM (refilling of calcium stores sensitive to noradrenaline).[26]

Tetrandrine appears to be able to displace ligands of the α1-adrenergic receptors at the prazosin binding site, and moderately to weakly inhibits calcium influx via this receptor

4Neurology

4.1Glutaminergic Neurotransmission

A water extract of stephania tetrandra was able to inhibit NMDA induced currents by 38.65+/-7.50%, which was less effective than both scutellaria baicalensis (83.45+/-4.34%) and salvia miltiorrhiza (52.97+/-1.78%); as these plants had a magnesium content and the study was conducted in vitro, this may not apply to oral ingestion of this herb.[27]

Requires more research to confirm if there are any actual interactions with glutaminergic neurotransmission

4.2Neuroinflammation

25-50µM tetrandrine appears to attenute LPS-induced microglial activation, reaching around 35% inhibition at 50µM (assessed by superoxide and nitric oxide formation) and appeared to be traced back to NF-kB inhibition.[28]

4.3Neurprotection

In response to strokes, cells around the infarct area tend to undergo endoplasmic reticulum stress resulting in their apoptosis (cell death).[29][30]

An infusion of 30mg/kg tetrandrine (immediately and 2 hours after ischemia) appears to slightly attenuate cognitive impairment from stroke alongside reducing infarct size and brain edema.[1] While the mechanism was not ascertained, it appeared that the ischemia-induced changes of three proteins (GRP78, DJ-1 and HYOU1) was significantly attenuated, which the authors thought reflected less endoplasmic reticulum stress.[1]

5Cardiovascular Health

5.1Cardiac Tissue

Tetrandrine's main mechanism of action, blocking calcium channels nonspecifically, appears to extend to cardiac tissue where it exerts antiarrythmic effects[14] and has shown anti-arrythmic effects in response to cesium in rabbits[31] as well as ischemia/reperfusion.[32][33]

Tetrandrine appears to reversibly block sodium (Na+) channels in the myocardium in the 60-120μM range by 28.1-87.5% and an IC50 of 74.4-76.9μM.[34]

May possess anti-arrythmic properties on heart tissue via inhibiting ion channels

6Interactions with Glucose Metabolism

6.1Mechanisms

When incubated with HepG2 cells, tetrandrine fails to increase glucose consumption in vitro and failed to interact with both the insulin receptor (expression) and AMPK.[17]

6.2Blood Glucose

In Streptozotocin induced diabetic mice, the water extract of stephania tetrandra appears to reduce blood glucose in a dose-dependent manner in the range of 0.48—16mg/kg, which is due to fangchinoline as tetrandrine was ineffective.[15] The reduction in blood glucose reached 52.7+/-6.7% with 3mg/kg fangchinoline and was attributed to increased insulin release[15] and this increase in insulin secretion is augmented with calycosin and formononectin form astragalus membranaceus (wherein the combination of 300µg/kg fangchinoline, normally too low a dose, paired with either 30-100µg/kg calycosin or formononectin becomes effective despite the latter two flavonoids not being effective on their own).[35]

Fangchinoline appears to be an effective insulin secretagogue (causes insulin release) in diabetic rats at very low oral doses, and this is synergistic with flavonoids from astragalus membranaceus (a traditional pairing for glucose control)

6.3Diabetes

Tetrandrine at an oral dose of 20mg/kg daily in rats who normally spontaneously develop diabetes (BB rats) was able to reduce the cumulative occurrence from 75.5 to 10.9% associated with less pancreatic inflammation[36] and FK506 (an immunosuppressive agent that also appears to reduce spontaneous diabetes risk in this same rat model[37]) given for five days alongside tetrandrine appears to be synergistic as delayed administration of tetrandrine reduced diabetes occurrence from 73.1 to 41.7%, whereas the combination with FK506 reduced it to 3.6%.[38]

7Skeleton and Bone Metabolism

7.1Osteoclasts

In osteoclasts, a signalling molecule produced by osteoblasts called 'receptor activator of NF-kB ligand' (RANKL) binds to its receptor (RANK) which then mediates proliferation of osteoclasts[39] via downstream proteins such as MAPKs (ERK and JNK),[40] AP-1,[41] as well as NF-kB itself.[42] An important mediator may be nuclear factor of activated T cells c1 (NFATc1), which can induce the effects associated with RANKL independent of RANKL itself[43] (suggesting that RANKL works via NFATc1).

Tetrandrine at 300-1,000nM is able to inhibit the RANKL-induced activation of NFATc1; specifically, while there was minimal suppressive effect initially the autoamplification of NFATc1 was halved.[44]

Although the exact mechanisms are not known, tetrandrine appears to dysregulate the ability of NFATc1 to autoamplify, which ultimately causes less osteoclastogenesis over the long run

In sciatic-neurectomized mice, injections of 600-2,000µg/kg tetrandrine every other day for four weeks prevented the losses in bone mineral density and trabecular volume, insofar that trabecular bone density in the 600µg/kg group (despite neurectomy) was increased relative to non-neurectomized control.[44]

Injections of very low dose tetrandrine appear to be highly protective of bone mass, insofar to abolish losses in mice subject to neurectomy

8Inflammation and Immunology

8.1Macrophages

Tetrandrine appears to cause macrophage toxicity in vitro (J774 macrophages) with an IC50 value of 50µM, somewhat higher than other mechanisms.[45]

8.2Neutrophils

Tetrandrine is able to inhibit Mac-1 upregulation at a concentration of 0.1–10μM,[46] Mac-1 which promotes neutrophil adhesion[47] and itself is stimulated by oxidation[48] and calcium ions;[49] tetrandrine suppreses Mac-1 activation secondary to reducing calcium influx[46] although its known antioxidant property[50] also seems to contribute somewhat. The overall anti-adhesive effect is concentration dependent, and can reduce fMLP and PMA induced adhesion to around 60% of baseline at 10µM.[46]

At quite low concentrations, tetrandrine is able to prevent neutrophil adhesion via suppressing both calcium influx and oxidation products within neutrophils

8.3T Cells

Tetrandrine appears to downregulate PKC dependent signalling in T lymphocytes, and shows suppressive effects on both acute phase T cell activation (calcium influx and IL-2 secretion) at 2-5µM as well as late phase stimulation (CD71 antigen production).[2] This was thought to be independent of calcium signalling since CD40 was unaffected (and CD40 interacts with calcium but not PKC).[2]

8.4Rheumatism

Traditionally, stephania tetrandra appears to be used against autoimmune diseases such as rheumatism and lupus.[3]

12 weeks supplementation of a water extract of stephania ternatea thrice daily (10g total daily) to persons with diagnosed rheumatoid arthritis was able to reduce human granulocyte elastase (pathogenic factor in some autoimmune diseases[51]) in serum by 56%;[52] actual symptoms of rheumatism were not measured.

8.5Virology

Fangchinoline appears to inhibit HIV1 replication against multiple strains (NL4-3, LAI, BaL, PM1; inactive in TZM-b1) with an IC50 in the range of 0.8-1.7µM.[53] It appears to target late stages of the infection cycle, and appears to interfere with gp160 proteolytic processing,[53] gp160 being the inactive polypeptide precursor for the envelope proteins that allow HIV replication.[54][55]

At least in vitro, fangchinoline appears to be relatively potent in suppressing HIV1 replication

8.6Bacteria

Tetrandrine appears to have antibacterial properties against Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 250μg/mL, with an MIC of 125μg/mL against the strains 3102 and 3091 specifically[56] and a similar potency against methicillin resistant strains of Staphylococcus aureus (MRSA).[57]

It appears that tetrandrine can bind directly to peptidoglycan[56] and MRSA tetrandrine appears to be synergistically anti-bacterial with ethidium bromide, reducing the 125-250μg/mL MIC to 31.2-125μg/mL (2 to 4-fold reduction).[57] Elsewhere against strains of candida albicans, tetrandrine appears to be synergistically anti-bacterial when used alongside ketoconazole.[58]

Appears to have some anti-bacterial properties itself (although not overly potent), yet is somewhat synergistic with other pharmacological anti-bacterial agents

9Interactions with Oxidation

9.1In vitro

Tetrandrine appears to be capable of scavenging superoxide radicals in vitro in a concentration dependent manner up to 30µM.[50]

10Interactions with Organs

10.1Kidneys

In isolated rat primary mesangial cells (kidney cells) stimulated with IL-1β (to induce glomerulonephritis in vitro[59]) isolated tetrandrine was able to inhibit the activation of ERK/NF-kB as well as subsequent secretion of MMP9,[60] which are known to correlate with and encourage renal pathology.[61] Tetrandrine was active in the concentration range of 2-10μg/mL, and was more effective (near complete suppression) in regards to iNOS, ERK, and IKK activity but less potent in suppressing IkBα.[60]

Appears to reduce the effects of inflammation upon isolated kidney cells, which appears to occur at a low enough concentration that it may apply to oral supplementation of this herb

10.2Liver

In rats subject to bile duct ligation, tetrandrine (1-5mg/kg) appears to show anti-fibrotic effects associated with less gene expression (TGF-β, α-SMA, collagen 1α2 and angiogenesis gene products) which was attributed to its NF-kB inhibition.[62] Stephania tetradra (200mg/kg water extract) itself has shown anti-fibrotic potential as assessed by histology (fibrotic area) and stellate cell activation, again attributed to NF-kB inhibition.[63]

When compared to other agents, 5mg/kg tetrandrine is equally effective at reducing collagen accumulation as 50mg/kg silymarins (from milk thistle)[62] and 200mg/kg of the water extract of stephania tetrandra five times weekly for five weeks was as effective as 300mg/kg Salvia miltiorrhiza (water extract) in reducing liver enzymes but more effective in reducing fibrosis from CCl4;[63] pairing stephania tetrandra and salvia miltiorrhiza was not additive in efficacy.[63]

Stephania tetrandra appears to have anti-fibrotic potential that has a comparable or greater potency than other anti-fibrotic supplements

10.3Penis

In the isolated rabbit corpus cavernosum, tetrandine appears to concentration-dependently (between 100nM and 100µM) increase cAMP concentrations and was able to augment PGE1-induced cAMP accumulation.[64] The authors thought this may reflect PDE enzyme inhibition, but this was not confirmed.[64] Previously, tetrandrine has been noted to inhibit calcium influx into penile tissue[65] and this is known to occur with increases in cAMP concentrations.[66]

Tetrandrine failed to have any influence on cGMP concentrations in the rabbit corpus cavernosum inherently and failed to augment SNP-induced increases in cGMP.[64]

Possibly related to the aforementioned increase in cAMP, tetrandine is known to cause relaxation in precontracted corpus cavernosum penile tissue.[67][68]

May have pro-erectile properties associated with increasing cAMP concentrations, and while the concentration that maximal effects occur is likely too high there may be some benefits (since the lowest active concentration is feasible); no studies using oral ingestion currently exist

11Nutrient-Nutrient Interactions

11.1Astragalus Membranaceus

Astragalus membranaceus appears to be synergistic with stephania tetrandra in reducing blood glucose, as inactive levels of astagalus (3-100mg/kg) and isolated fangchinoline (0.3mg/kg) appear to be active when ingested together in diabetic mice, insofar that 0.3mg/kg fangchinoline in the presence of 30mg/kg astragalus was as effective as 1mg/kg fangchinoline.[15] This appears to be due to the flavonoids known as formononetin and calycosin from astragalus, as these isolated flavonoids at 0.03-0.1mg/kg oral ingestion potentiated 0.3mg/kg fangchinoline.[35]

Astragalus may be synergistic with stephania tetrandra in regards to reducing blood glucose, thought to be secondary to promoting insulin secretion from the pancreas. The oral doses the isolated bioactives are effective is remarkably low, showing a good deal of promise

11.2Berberine

Berberine is an anti-diabetic alkaloid that works via activating the protein known as AMPK.[69] It is effluxed from the body into the intestines via P-glycoprotein transporters (reducing bioavailability), and the inhibition of P-glycoprotein by tetrandrine increases berberine bioavailability both in vitro[70] and in vivo.[17] Berberine appears to have intestinal efflux (Caco-2) pretty much abolished in vitro with 1µM tetrandrine whereas it was only slightly hindered in liver (HL-7702) cells and not influence in muscle (C2C12) cells which do not express P-glycoprotein.[70]

Furthermore, it appears that the upregulation of P-glycoprotein that berberine exhibits[71][72] is effectively overcome with tetrandrine.[17][70]

Tetrandrine inhibits the transporter that effluxes berberine into the intestines, and by inhibiting this transporter it increases berberine absorption. Tetrandrine may also prevent berberine from upregulating (creatine more) of these transporters

When looking at pharmacokinetic data, 10-20mg/kg tetrandrine alongside 100mg/kg berberine in rats was able to increase the Cmax of berberine in plasma in a dose-dependent manner by 36-62% (reaching 15.4ng/mL and 18.3ng/mL, from 11.3ng/mL in control) and the overall AUC increased to a similar 33-61%.[17] Three weeks of treatment noted that the decreases of blood glucose seen in diabetic rats with 100mg/kg berberine (20.6%) was significantly increased with coingestion of 10mg/kg tetrandrine (55.2%) which even exceeded a double dose of berberine at 200mg/kg (39.5%).[17]

Tetrandrine is able to increase the glucose lowering and anti-diabetic properties of berberine, insofar that adding 1/10th the dose of tetrandrine to berberine is more effective than doubling the berberine dose

12Safety and Toxicology

12.1Case Studies

There are a series of case studies (end stage renal disease) of which causation was placed upon a weight loss supplement said to include stephania tetrandra which was instead cut with another plant bearing the name of Fang Chi, Aristolochia fangchi (or Birthwort);[73] this latter plant contains high levels of the nephrotoxin aristolochic acid.[74][75]

The plant Aristolochia fangchi is one of the four plants, alongside Stephania tetrandra, that is referred to as 'Fang Chi'. It also appears to have a relatively potent kidney toxin in it, and thus supplements that contain aristolochia fangchi rather than stephania tetrandra may cause significant kidney damage

References

  1. ^ a b c Ruan L, et al. Tetrandrine Attenuated Cerebral Ischemia/Reperfusion Injury and Induced Differential Proteomic Changes in a MCAO Mice Model Using 2-D DIGE. Neurochem Res. (2013)
  2. ^ a b c Ho LJ, et al. Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells. Eur J Pharmacol. (1999)
  3. ^ a b c d e The genus Stephania (Menispermaceae): Chemical and pharmacological perspectives.
  4. ^ a b c d e Sim HJ, et al. Simultaneous determination of structurally diverse compounds in different Fangchi species by UHPLC-DAD and UHPLC-ESI-MS/MS. Molecules. (2013)
  5. ^ Joshi VC, Avula B, Khan IA. Authentication of Stephania tetrandra S. Moore (Fang Ji) and differentiation of its common adulterants using microscopy and HPLC analysis. J Nat Med. (2008)
  6. ^ a b c d DETERMINATION OF TETRANDRINE, FANGCHINOLINE, CYCLANOLINE AND OBLONGINE IN RADIX STEPHANIAE TETRANDRAE BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY.
  7. ^ a b Liu L, Li S, Chen Z. Simultaneous determination of tetrandrine and fangchinoline in herbal medicine Stephania tetrandra S. Moore by liquid chromatography with electrochemical detection. J Pharm Biomed Anal. (2012)
  8. ^ a b Tang Y, et al. Simultaneous determination of fangchinoline and tetrandrine in Stephania tetrandra S. Moore by using 1-alkyl-3-methylimidazolium-based ionic liquids as the RP-HPLC mobile phase additives. Anal Chim Acta. (2013)
  9. ^ a b THE ALKALOIDS OF HAN-FANG-CHI.
  10. ^ A New Monoquaternqry Bisbenzylisoquinoline Alkakoid from Stephania testrandra.
  11. ^ Hong Kong samples of the traditional Chinese medicine “Fang Ji” contain aristolochic acid toxins.
  12. ^ A 4,5-Dioxoaporphine from the Aerial Parts of Stephania tetrandra.
  13. ^ a b Si D, et al. Biflavonoids from the aerial part of Stephania tetrandra. Phytochemistry. (2001)
  14. ^ a b Wong TM, et al. Cardiovascular actions of Radix Stephaniae Tetrandrae: a comparison with its main component, tetrandrine. Acta Pharmacol Sin. (2000)
  15. ^ a b c d e Tsutsumi T, et al. Anti-hyperglycemic effect of fangchinoline isolated from Stephania tetrandra Radix in streptozotocin-diabetic mice. Biol Pharm Bull. (2003)
  16. ^ Fu L, et al. Characterization of tetrandrine, a potent inhibitor of P-glycoprotein-mediated multidrug resistance. Cancer Chemother Pharmacol. (2004)
  17. ^ a b c d e f g h Shan YQ, et al. Tetrandrine potentiates the hypoglycemic efficacy of berberine by inhibiting P-glycoprotein function. Biol Pharm Bull. (2013)
  18. ^ Fu LW, et al. The multidrug resistance of tumour cells was reversed by tetrandrine in vitro and in xenografts derived from human breast adenocarcinoma MCF-7/adr cells. Eur J Cancer. (2002)
  19. ^ Liu ZL, et al. Persistent reversal of P-glycoprotein-mediated daunorubicin resistance by tetrandrine in multidrug-resistant human T lymphoblastoid leukemia MOLT-4 cells. J Pharm Pharmacol. (2003)
  20. ^ a b Kwan CY, et al. Tetrandrine, a calcium antagonist of Chinese herbal origin, interacts with vascular muscle alpha 1-adrenoceptor. Life Sci. (1996)
  21. ^ a b Leung YM, et al. Effects of tetrandrine and closely related bis-benzylisoquinoline derivatives on cytosolic Ca2+ in human leukaemic HL-60 cells: a structure-activity relationship study. Clin Exp Pharmacol Physiol. (1996)
  22. ^ Wang G, Lemos JR. Tetrandrine: a new ligand to block voltage-dependent Ca2+ and Ca(+)-activated K+ channels. Life Sci. (1995)
  23. ^ Takemura H, et al. Tetrandrine as a calcium antagonist. Clin Exp Pharmacol Physiol. (1996)
  24. ^ Felix JP, et al. Bis(benzylisoquinoline) analogs of tetrandrine block L-type calcium channels: evidence for interaction at the diltiazem-binding site. Biochemistry. (1992)
  25. ^ Leung YM, Kwan CY, Loh TT. Dual effects of tetrandrine on cytosolic calcium in human leukaemic HL-60 cells: intracellular calcium release and calcium entry blockade. Br J Pharmacol. (1994)
  26. ^ Catret M, et al. Alpha-adrenoceptor interaction of tetrandrine and isotetrandrine in the rat: functional and binding assays. J Pharm Pharmacol. (1998)
  27. ^ Sun X, et al. N-methyl-D-aspartate receptor antagonist activity in traditional Chinese stroke medicines. Neurosignals. (2003)
  28. ^ Xue Y, et al. Tetrandrine suppresses lipopolysaccharide-induced microglial activation by inhibiting NF-kappaB pathway. Acta Pharmacol Sin. (2008)
  29. ^ Duan SR, et al. Ischemia induces endoplasmic reticulum stress and cell apoptosis in human brain. Neurosci Lett. (2010)
  30. ^ Paschen W. Endoplasmic reticulum dysfunction in brain pathology: critical role of protein synthesis. Curr Neurovasc Res. (2004)
  31. ^ Effects of Tetrandrine on early after depolarizations and arrhythmias induced by Cesium Chloride in rabbits.
  32. ^ Yu XC, et al. Antihypertensive and anti-arrhythmic effects of an extract of Radix Stephaniae Tetrandrae in the rat. J Pharm Pharmacol. (2004)
  33. ^ Yu XC, et al. 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. Life Sci. (2001)
  34. ^ Chen L, et al. Inhibitory effects of tetrandrine on the Na(+) channel of human atrial fibrillation myocardium. Acta Pharmacol Sin. (2009)
  35. ^ a b Ma W, et al. Combined effects of fangchinoline from Stephania tetrandra Radix and formononetin and calycosin from Astragalus membranaceus Radix on hyperglycemia and hypoinsulinemia in streptozotocin-diabetic mice. Biol Pharm Bull. (2007)
  36. ^ Lieberman I, et al. Prevention by tetrandrine of spontaneous development of diabetes mellitus in BB rats. Diabetes. (1992)
  37. ^ Wakugami T, et al. Effect of FK506 on the development of diabetes in BB rats in comparison with that of cyclosporin. Tohoku J Exp Med. (1993)
  38. ^ Lieberman I, et al. Synergy between tetrandrine and FK506 in prevention of diabetes in BB rats. Life Sci. (1993)
  39. ^ Induction and Activation of the Transcription Factor NFATc1 (NFAT2) Integrate RANKL Signaling in Terminal Differentiation of Osteoclasts.
  40. ^ Lee SE, et al. The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation. Bone. (2002)
  41. ^ Grigoriadis AE, et al. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science. (1994)
  42. ^ Darnay BG, et al. Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif. J Biol Chem. (1999)
  43. ^ Matsuo K, et al. Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos. J Biol Chem. (2004)
  44. ^ a b Takahashi T, et al. Tetrandrine prevents bone loss in sciatic-neurectomized mice and inhibits receptor activator of nuclear factor κB ligand-induced osteoclast differentiation. Biol Pharm Bull. (2012)
  45. ^ Pang L, Hoult JR. Cytotoxicity to macrophages of tetrandrine, an antisilicosis alkaloid, accompanied by an overproduction of prostaglandins. Biochem Pharmacol. (1997)
  46. ^ a b c Shen YC, et al. Impediment to calcium influx and reactive oxygen production accounts for the inhibition of neutrophil Mac-1 Up-regulation and adhesion by tetrandrine. Mol Pharmacol. (1999)
  47. ^ Lefer AM, Lefer DJ. The role of nitric oxide and cell adhesion molecules on the microcirculation in ischaemia-reperfusion. Cardiovasc Res. (1996)
  48. ^ Simms HH, D'Amico R. Subcellular location of neutrophil opsonic receptors is altered by exogenous reactive oxygen species. Cell Immunol. (1995)
  49. ^ Lawson MA, Maxfield FR. Ca(2+)- and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils. Nature. (1995)
  50. ^ a b Cao ZF. Scavenging effect of tetrandrine of active oxygen radicals. Planta Med. (1996)
  51. ^ Siedle B, et al. Sesquiterpene lactones as inhibitors of human neutrophil elastase. Bioorg Med Chem. (2002)
  52. ^ Sekiya N, et al. Suppressive effects of Stephania tetrandra on the neutrophil function in patients with rheumatoid arthritis. Phytother Res. (2004)
  53. ^ a b Wan Z, et al. Fangchinoline inhibits human immunodeficiency virus type 1 replication by interfering with gp160 proteolytic processing. PLoS One. (2012)
  54. ^ Checkley MA, Luttge BG, Freed EO. HIV-1 envelope glycoprotein biosynthesis, trafficking, and incorporation. J Mol Biol. (2011)
  55. ^ Moulard M, Decroly E. Maturation of HIV envelope glycoprotein precursors by cellular endoproteases. Biochim Biophys Acta. (2000)
  56. ^ a b Lee YS, et al. The mechanism of antibacterial activity of tetrandrine against Staphylococcus aureus. Foodborne Pathog Dis. (2012)
  57. ^ a b Lee YS, et al. Synergistic effect of tetrandrine and ethidium bromide against methicillin-resistant Staphylococcus aureus (MRSA). J Toxicol Sci. (2011)
  58. ^ Zhang H, et al. Synergistic anti-candidal activity of tetrandrine on ketoconazole: an experimental study. Planta Med. (2010)
  59. ^ Timoshanko JR, et al. Leukocyte-derived interleukin-1beta interacts with renal interleukin-1 receptor I to promote renal tumor necrosis factor and glomerular injury in murine crescentic glomerulonephritis. Am J Pathol. (2004)
  60. ^ a b Wu CJ, et al. Tetrandrine down-regulates ERK/NF-κB signaling and inhibits activation of mesangial cells. Toxicol In Vitro. (2011)
  61. ^ Masaki T, et al. Activation of the extracellular-signal regulated protein kinase pathway in human glomerulopathies. J Am Soc Nephrol. (2004)
  62. ^ a b Hsu YC, et al. Anti-fibrotic effects of tetrandrine on bile-duct ligated rats. Can J Physiol Pharmacol. (2006)
  63. ^ a b c Chor JS, et al. Stephania tetrandra prevents and regresses liver fibrosis induced by carbon tetrachloride in rats. J Gastroenterol Hepatol. (2009)
  64. ^ a b c Chen J, et al. Effects of tetrandrine on cAMP and cGMP levels in rabbit corpus cavernosum in vitro. Nat Prod Res. (2010)
  65. ^ Liu JH, et al. Effects of tetrandrine on cytosolic free calcium concentration in corpus cavernosum smooth muscle cells of rabbits. Asian J Androl. (2006)
  66. ^ Liu J, Chen J. Ion channels and penile erection. Zhonghua Nan Ke Xue. (2004)
  67. ^ Chen J, et al. The relaxation effects of six extracts from Chinese herbs on the corpus cavernosum tissue of rabbit in vitro. Zhonghua Nan Ke Xue. (2005)
  68. ^ Chen J, et al. The relaxation effects of tetrandrine on the corpus cavernosum tissue of rabbit in vitro. Zhonghua Nan Ke Xue. (2003)
  69. ^ Lee YS, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. (2006)
  70. ^ a b c Shan YQ, et al. Berberine analogue IMB-Y53 improves glucose-lowering efficacy by averting cellular efflux especially P-glycoprotein efflux. Metabolism. (2013)
  71. ^ Maeng HJ, et al. P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers. J Pharm Sci. (2002)
  72. ^ Lin HL, et al. Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel. Br J Cancer. (1999)
  73. ^ Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs.
  74. ^ Aristolochic acid and the etiology of endemic (Balkan) nephropathy.
  75. ^ Cosyns JP. Aristolochic acid and 'Chinese herbs nephropathy': a review of the evidence to date. Drug Saf. (2003)

This page is regularly updated, to include the most recently available clinical trial evidence.

Each member of our research team is required to have no conflicts of interest, including with supplement manufacturers, food companies, and industry funders. The team includes nutrition researchers, registered dietitians, physicians, and pharmacists. We have a strict editorial process.

This page features 75 references. All factual claims are followed by specifically-applicable references. Click here to see the full set of references for this page.

Examine.com is intended to be used for educational and information purposes only. Examine.com and its Editors do not advocate nutritional supplementation over proper medical advice or treatment and this sentiment will never be expressed through pages hosted under Examine.com. If using any pharmaceuticals or drugs given to you by a doctor or received with a prescription, you must consult with the doctor in question or an equally qualified Health Care Professional prior to using any nutritional supplementation. If undergoing medical therapies, then consult with your respective Therapist or Health Care Professional about possible interactions between your Treatment, any Pharmaceuticals or Drugs being given, and possible nutritional supplements or practices hosted on Examine.com.

Examine.com does not assume liability for any actions undertaken after visiting these pages, and does not assume liability if one misuses supplements. Examine.com and its Editors do not ensure that unforeseen side effects will not occur even at the proper dosages, and thereby does not assume liability for any side effects from supplements or practices hosted under the domain of Examine.com.

Popular Supplements

TOP NUTRITION ARTICLES

Never miss an update!

Your e-mail is safe with us. We don’t share personal data.
Tweet