Drug info - Salvia Miltiorrhiza

Discussion in 'Ethnobotanicals' started by QGdoxl, Dec 13, 2006.

  1. QGdoxl

    QGdoxl Gold Member

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    Has anyone heard of this herb? Suposedly it is a cousin of the salvia divnorum, but effects are much different. The Salvia Miltiorrhiza is asid to have very strong sedative properties. As someone with some occasional extended sleeping problems I was interested in checking this stuff out. Anyone ever heard of it before?
     
  2. Bajeda

    Bajeda Super Moderator Platinum Member & Advisor

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    Abstract

    Salvia miltiorrhiza (Labiatae, Laminaceae), danshen, is an annual sage mainly found in China and neighboring countries. The crude drug (dried root) and its preparations are currently used in China to treat patients suffering from heart attack, angina pectoris, stroke and some other conditions. The use of S. miltiorrhiza has been increasing in the management of stroke. Pharmacological examinations showed that the plant and its active ingredients, tanshinones and salvianolic acids, have anticoagulant, vasodilatory, increased blood flow, anti-inflammatory, free radical scavenging, mitochondrial protective and other activities. This review discusses the pharmacology, medicinal chemistry and clinical studies published, especially in China, for danshen and tanshinone preparations. Clinical examinations are evaluated in terms of S. miltiorrhiza preparation, dose, double blinding, control, clinical assessments of outcomes and other parameters. Meta-analyses of S. miltiorrhiza are also discussed.


    Background


    Danshen is an annual sage plant, Salvia miltiorrhiza (Labiatae, Laminaceae) which grows in China, Mongolia, Korea and Japan. In China, it is found in hilly areas of the west, southwest and southeast. S. miltiorrhiza is among the most popular medicinal herbs used in China. It has been used in the treatment of stroke since 1970, angina and heart attack, as an antihypertensive and a sedative. S. miltiorrhiza contains several compounds that are pharmacologically active, especially the diterpenoids known as tanshinones. A related plant, Salvia columbariae, from California, USA also contains tanshinones, especially cryptotanshinone. This plant has been used by Californian Indians to treat people suffering from strokes.
    S. miltiorrhiza is often used in fufang with other herbs in Chinese herbal medicine. Fufang in Chinese herbal medicine means a formula comprising multiple herbs. One of the widely prescribed Chinese fufang for stroke patients is 30 g of the roots of Astragalus membranaceus and Hedysarum coronarium, 10 g of cinnamon twig (Cinnamomum verum), 10 g of peach kernel (Prunus persica), 10 g of safflower (Carthamus tinctorius), 12 g of Angelica sinensis root, 12 g of the rhizome of Ligustica chuanxiong, 12 g of the root of Paeonia rubra, 12 g of earthworm (Lumbricus), 30 g of the root of S. miltiorrhiza and 15 g of the root of Achyranthis bidentata. The ingredients are added to water and boiled for an hour or two until the required volume is attained. The preparation is orally administered to the patient. Other plants can be added to this as needed by the patient for severe blood stasis, deficiency of qi and some other conditions. Qi is the life force that comes from air, food and the genetic background. The therapeutic principle of the treatment is to supplement qi, nourish the blood and promote blood circulation in order to remove obstructions of the channels, which are the acupuncture channels, not blood vessels.





    Pharmacology

    Danshen


    S. miltiorrhiza has been shown to inhibit angiotensin converting enzyme (ACE), to lower blood pressure, dilate arteries, and to decrease blood clotting. Inhibition of ACE may be involved in the ability of S. miltiorrhiza to alter angiotensin II levels, and indirectly, the levels of atrial natriuretic peptide. ACE inhibitors have been extensively studied in cardiovascular disease and have been shown in several clinical trials to decrease the risk of suffering a primary or secondary stroke. ACE inhibitors are known to decrease the risk of having a stroke. Unfortunately, Western ACE inhibitor drugs have not been tested as treatments for stroke after its occurrence. The primary mechanism of this protection appears to be in lowering blood pressure. However, other mechanisms are also probably involved including decreasing clot formation by decreasing cardiac fibrillation, and decreasing the levels of angiotensin. Angiotensin has several potentially dangerous effects in regard to stroke, including hypertension, increasing noradrenergic nerve activity and blocking norepinephrine reuptake in the brain. Brain ischemia and reperfusion, during stroke, cause the release of many neurotransmitters including norepinephrine, in part due to ATP depletion. These neurotransmitters may be damaging to the brain by inducing excitotoxicity, by oxidizing to produce oxygen radicals or other mechanisms. The effects of angiotensin on extracellular neurotransmitter levels during ischemia and reperfusion in the brain could be devastating. S. miltiorrhiza has been shown to decrease the release of norepinephrine, dopamine and serotonin during brain ischemia.
    Thrombosis secondary to atherosclerosis is a major cause of stroke. Small thrombi lodge in small arteries of the brain, especially the middle cerebral artery, and cause ischemia. Fibrinolytic enzymes normally found in the blood such as plasmin, break down clots within a few hours and allow reperfusion. Clot dissolution with tissue plasminogen activator is known to be beneficial in some stroke patients, provided that it is used within 3 hours of stroke. Inhibition of clot formation and potential clot dissolution has been demonstrated in many clinical trials of S. miltiorrhiza as discussed below. S. miltiorrhiza has been found to increase the proteolysis of fibrinogen to fibrinogen degradation products. This is a unique mechanism of anticoagulation in comparison to other anticoagulant drugs that tend to prevent clot formation by interfering with platelet function or interfering with the action of thrombin or vitamin K. S. miltiorrhiza induced arterial dilation in the brain could help reperfuse the brain better allowing a faster recovery. Ischemia causes ATP and NAD levels to decrease in the brain. Reperfusion allows oxygen to reflow into the brain and form reactive oxygen radicals, especially when mitochondrial and cellular enzymes are not functioning efficiently due to low oxygen tensions. These oxygen radicals can damage cellular macromolecules, including DNA, and induce apoptosis and necrosis.
    S. miltiorrhiza has other effects on stroke including anti-inflammation, free radical scavenging, antioxidant and mitochondrial protection effects. Tanshinone I from S. miltiorrhiza inhibits arachidonic acid metabolism, interleukin-12 production and has anti-inflammatory effects. Neutrophil activation is inhibited by an unspecified tanshinone which is an anti-inflammatory agent. S. miltiorrhiza antioxidant activity is also expressed as increases in superoxide dismutase, catalase, glutathione peroxidase and glutathione transferase activities . Free radical scavenging and mitochondrial protective activities of S. miltiorrhiza have been found.




    Fufang danshen

    Clinical trials demonstrated that fufang danshen enhanced stroke survival and recovery in comparison to S. miltiorrhiza alone as discussed below. The idea is that additional herbs will synergize the desirable effects or decrease the side effects of S. miltiorrhiza. Commercially available fufang danshen can be in two forms, one containing S. miltiorrhiza and jiangxiang (Dalbergia odorifera), the other containing S. miltiorrhiza, Panax notoginseng and Ligusticum wallichii. Most published clinical trials used the Dalbergia odorifera form of fufang danshen.
    Dalbergia odorifera contains medicarpin and 6-hydroxy-2-(2-hydroxy-4-methoxyphenyl) benzofuran(IV) that inhibit leukotriene synthesis. Dalbergia odorifera also contains anti-inflammatory flavonoids such as (S)-4-methoxydalbergione, cearoin, butein, koparin, bowdichione, 3'-O-methylviolanone and xenognosin B. Platelet aggregation and prostaglandin synthesis are inhibited by cinnamylphenols, isoflavans, isoflavene and a benzoic acid derivative from Dalbergia odorifera. Vasorelaxant compounds are found in Dalbergia odorifera such as butein and isoliquiritigenin Panax notoginseng, which contains several ginsenosides and has anti-platelet activity, has been found to improve survival in patients of cerebral trauma and cerebral ischemia reperfusion. Ligusticum wallichii contains tetramethylpyrazine that is protective in ischemia reperfusion injury of the brain, has anti-platelet activity and is hypotensive perhaps due to calcium antagonism. Ligusticum wallichii also contains ferulinolol that is a β1 blocker and a partial β2 agonist.






    Medicinal Chemistry



    As S. miltiorrhiza, especially fufang danshen, have many pharmacologically active compounds in the preparation, one would ask which compound is the active one for stroke and ischemic diseases. The answer is that many active compounds in the preparations are beneficial in stroke and ischemic diseases. Among all active compounds, diterpenoids and salvianolic acid derivatives are most studied.
    The diterpenoids of S. miltiorrhiza are characterized by tanshinones (Figure 1) and isotanshinones (Figure 2). Miltirone, salviol (Figure 3) and other diterpenoids are also present. Miltirone has sedative activity and is a benzodiazepine receptor agonist. Purified tanshinone IIA and IIB are neuroprotective in cerebral ischemia and reperfusion. Tanshinone I, cryptotanshinone and tanshinone V are protective against myocardial ischemia and reperfusion. Tanshinones are also anti-inflammatory agents. Tanshinone I, dihydrotanshinone and cryptotanshinone inhibit interleukin-12 and interferon-γ production. Tanshinone I inhibits arachidonic acid metabolism by phospholipase A2.
    Salvianolic acids in S. miltiorrhiza appear to be synthesized from monoterpenoids such as danshensu (Figure 4). Acetylsalvianolic acid A, a semi-synthetic derivative of salvianolic acid from S. miltiorrhiza is neuroprotective in middle cerebral artery thrombosis and inhibits platelet aggregation. Salvianolic acids (Figure 5) from S. miltiorrhiza increase cerebral blood flow after ischemia. Salvianolic acid A is protective against cerebral and myocardial ischemia and reperfusion. Lithospermic acid B (Figure 6), also called tanshinoate B or salvianolic acid B, increases NO production by endothelial cells and inhibits ACE . NO is a vasorelaxant that should bring down local blood pressure. Lithospermic acid B is antihypertensive and is protective against cerebral and myocardial ischemia and reperfusion. Rosmarinic acid and salvianolic acids in S. miltiorrhiza inhibit thrombosis, thromboxane B2 formation and platelet aggregation.
    Danshensu literally means the active ingredient in S. miltiorrhiza and has been used to refer to different active compounds. Early investigators identified 2-hydroxy-4-catecholbutyric acid (Figure 4) in S. miltiorrhiza, assumed it was the active ingredient in S. miltiorrhiza, and named it danshensu. Later work identified tanshinone IIA as the primary active ingredient in the treatment of ischemic diseases. Most Chinese publications in the last 20 years refer to tanshinone IIA as danshensu. As the salvianolic acids in S. miltiorrhiza are also responsible for the effects of S. miltiorrhiza in ischemic disorders, salvianolic acid B has recently been referred to as danshensu as well by some Chinese manufacturers.





    Adams, J. D., Wang, R., Yang, Jun. Preclinical and clinical examinations of Salvia miltiorrhiza and its tanshinones in ischemic conditions. Chinese Medicine 2006, 1:3
     
  3. bob_arctor

    bob_arctor Titanium Member

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    It would be really interesting to see some more references and discussion of the supposed action on benzodiazepine receptors. Bioassays?
     
  4. bob_arctor

    bob_arctor Titanium Member

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    Returning to this thread - has anyI had experience with the 40% tanshinones bulk extract which seems to be available? I couldn't find a specification for the amounts of different tanshinones, and assumes this is a "balanced" extract.
     
  5. snapper

    snapper Gold Member

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    I have tried a few different dan shen extracts as well as the whole herb. Benzo-like effects are modest at best. Combines well with corydalis for sleep, but kava is much more effective.
     
  6. bob_arctor

    bob_arctor Titanium Member

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    A 10x extract has been ordered, will report back after bioassay!
     
  7. Handle

    Handle Titanium Member

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    Hmm, I was thinking that miltiorrhiza could be combined with chamomile, because they keep suspecting chamomile has benzo type effects, but they've never been able to pin down the "ligand" that could be doing it.
    I'm trying to find corydalis here in Aus, it don't seem to be illegal. I would much rather find a shop front rather than order online.
     
  8. Br00klynB0y87

    Br00klynB0y87 Titanium Member

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    As snapper stated, s. milt will combine nicely with corydalis as they seem to compliment each other. -Btw, that mixture is commonly referred to as 'golden bells' I believe, and is a commonly prepared admixture in Chinese medicine. -Just thought I'd throw that out there for those who may have not known. :vibes:

    My buddy Freddy has noticed s. milt to actually be quite potent, and when he first prepared it experienced a severe hangover the next morning due to his lack of knowledge on dosing and what not.

    Anyhow my buddy has come to conclude s. milt which contains miltirone to be quite effective as a sleep aid and combines synergetically with other substances that bind/act on benzo receptors, caution should indeed be taken as it should with any substance going into ones body.

    Lastly I think it might of significance to state my buddy's preparation method in which he received such substantial results:

    He let his desired s. milt dosage (which was about 2.5gm) (shredded bark in which he pre-powder) sit in about a cap full of 40% alcohol / diluted water for an hour. After which he strained and threw the bark material into about a cup of simmering hot water for about ten minutes, strained and discarded the bark, and lastly combined both liquids, added a little honey and then - ;)

    .peace.
     
    Last edited: Jul 1, 2008