Tetrandrine and related bis-benzylisoquinoline alkaloids from medicinal herbs: cardiovascular effects and mechanisms of action.
Abstract
Tetrandrine (TET), a bis-benzylisoquinoline alkaloid purified and identified an
active ingredient in a Chinese medicinal herb, radix stephanae tetrandrae, has
been used traditionally for the treatment of congestive circulatory disorder and
inflammatory diseases. TET, together with a few of its structural analogues, has
long been demonstrated to have antihypertensive action in clinical as well as
animal studies. Presumably, the primary anti-hypertensive action of TET is due to
its vasodilatory properties. TET prevents or inhibits vascular contraction
induced by membrane depolarization with KCl or alpha-adrenoceptor activation with
phenylephrine (PE). TET (30 micromol/L) also inhibits the release of
endothelium-derived nitric oxide (NO) as well as NO production by inducible NO
synthase. TET apparently inhibits multiple Ca2+ entry pathways as demonstrated in
cell types lacking the L-type Ca2+ channels. In cardiac muscle cells, TET
inhibits both L- and T-type Ca2+ channels. In addition to its actions on
cardiovascular tissues, TET may also exert its anti-hypertensive action via a
Ca2+-dependent manner on other tissues intimately involved in the modulation of
blood pressure control, such as adrenal glands. In adrenal glomerulosa cells,
KCl- or angiotensin II-induced aldosterone synthesis is highly dependent on
extracellular Ca2+. Steroidogenesis and Ca2+-influx in bovine adrenal glomerulosa
cells have been shown to be potently inhibited by TET. In bovine adrenal
chromaffin cells, TET inhibits Ca2+ currents via L- and N-type channels as well
as other unidentified channels with IC50 of 10 micromol/L. Other than the Ca2+
antagonistic effects, TET also interacts with the alpha-adrenergic receptors and
muscarinic receptors based on functional as well as radioligand binding studies.
Apart from its functional effects, TET and related compounds also exert effects
on tissue structures, such as remodelling of hypertrophied heart and inhibition
of angiogenesis, probably by causing apoptotic responses. TET is also known for
its anti-inflammatory and anti-fibrogenic actions, which make TET and related
compound potentially useful in the treatment of lung silicosis, liver cirrhosis,
and rheumatoid arthritis.
Keywords:
active ingredient in a Chinese medicinal herb, radix stephanae tetrandrae, has
been used traditionally for the treatment of congestive circulatory disorder and
inflammatory diseases. TET, together with a few of its structural analogues, has
long been demonstrated to have antihypertensive action in clinical as well as
animal studies. Presumably, the primary anti-hypertensive action of TET is due to
its vasodilatory properties. TET prevents or inhibits vascular contraction
induced by membrane depolarization with KCl or alpha-adrenoceptor activation with
phenylephrine (PE). TET (30 micromol/L) also inhibits the release of
endothelium-derived nitric oxide (NO) as well as NO production by inducible NO
synthase. TET apparently inhibits multiple Ca2+ entry pathways as demonstrated in
cell types lacking the L-type Ca2+ channels. In cardiac muscle cells, TET
inhibits both L- and T-type Ca2+ channels. In addition to its actions on
cardiovascular tissues, TET may also exert its anti-hypertensive action via a
Ca2+-dependent manner on other tissues intimately involved in the modulation of
blood pressure control, such as adrenal glands. In adrenal glomerulosa cells,
KCl- or angiotensin II-induced aldosterone synthesis is highly dependent on
extracellular Ca2+. Steroidogenesis and Ca2+-influx in bovine adrenal glomerulosa
cells have been shown to be potently inhibited by TET. In bovine adrenal
chromaffin cells, TET inhibits Ca2+ currents via L- and N-type channels as well
as other unidentified channels with IC50 of 10 micromol/L. Other than the Ca2+
antagonistic effects, TET also interacts with the alpha-adrenergic receptors and
muscarinic receptors based on functional as well as radioligand binding studies.
Apart from its functional effects, TET and related compounds also exert effects
on tissue structures, such as remodelling of hypertrophied heart and inhibition
of angiogenesis, probably by causing apoptotic responses. TET is also known for
its anti-inflammatory and anti-fibrogenic actions, which make TET and related
compound potentially useful in the treatment of lung silicosis, liver cirrhosis,
and rheumatoid arthritis.