What is danshen?What is Tanshinone IIA?Application and function of Tanshinone IIA.Modern Developments and application research of Radix Salvia miltiorrhiza.

  seminal trace...Dan-shen Extract,Tanshinones,CAS.RN.NO:568-73-0;54693-68-4,Tanshinone IIA.20%40%95%CAS.NO:568-72-9,M.F.:C19-H18-O3.Radix Salvia miltiorrhiza; Salvia miltiorrhiza B.Salvia miltiorrhiza BUNGE.Red-Rooted Salvia,Dan Shen,Red Sage...

   Basic Botanical Data of Radix Salvia miltiorrhiza

 Chemical Name: Tanshinones,Tanshinone IIA,etc.
 Botanical Source:Radix Salvia miltiorrhiza; Salvia miltiorrhiza B. (Salvia miltiorrhiza BUNGE,Labiatae,Tanshen)
 Botanical Synoms:Red-Rooted Salvia,Dan Shen,chinese danshen,Red Sage,red sage root,Red-rooted Sage,Chinese sage,Red Ginseng,Tan-Shen,Tzu Tan-Ken(roots of purple sage),Hung Ken(red roots),Shu-Wei Ts'ao(rat-tail grass),Ch'ih Shen(scarlet sage),Pin-Ma Ts'ao(horse-racing grass).,if still not clear, please read:
 Differentiation from transliteration:the Wade-Giles transliteration of danshen is tan-shen,hence the quinones from Radix Salvia miltiorrhiza(danshen) were called tanshinones,others such as tanshinone IIA,etc.
 Plant Part Used:Root.
 
 Botanical Scientific Name:Salvia miltiorrhiza; Salvia miltiorrhiza B.

 Salvia(chinese danshen)here refers to the root of Salvia miltiorrhiza (Figure as following:Salvia Root,Radix Salvia miltiorrhiza), sometimes described as Chinese sage or red sage root. Any herb of the Salvia genus may be called sage, but most people are familiar with the common garden plant-and the common Western kitchen herb-obtained from Salvia officinalis. There are significant differences in medicinal components of the tops and roots of the Salvia plants that influence their uses. The Western sage leaves are used medicinally to treat dyspepsia and excessive perspiration. The tops of Salvia plebia (lichicao) and the whole plant of Salvia chinensis (shijianchuan) are used medicinally by the Chinese, but infrequently; the former is said to treat bleeding and turbid urine, the latter treats swellings and infections. Salvia root (danshen), as employed in Chinese medicine and the subject of the rest of this article, is different in nature from the other sage herbs, despite the botanical relationship.

  

 Narrative and differentiation& Name Identification of Sage Spectrum Family:

 Family:Labiatae
 Branches:
 1.Salvia officinalis(Common names:Sage, Garden Sage, Salvia, Meadow Sage; Spanish: Salvia, Alhucerna de la Costa, T?de Mar, Yerba de Santa Maria, Chia, Mejorana, Mirto, Salvia Real, Salvia Virgen; Nahuatl: Chianzotzolli)
 2.Salvia miltiorrhiza(Common names:Red-Rooted Salvia,Dan Shen,chinese danshen,Red Sage,red sage root,Red-rooted Sage,Chinese sage,Red Ginseng,Salvia miltiorrhiza BUNGE,Salvia miltiorrhiza B.etc.)
 3.Salvia microphylla(Red Texas Sage,Mirto,Salvia,Chia,T de Monte)
 4.Salvia sclarea(Clary Sage,Clear Eye)
 5.Salvia triloba(Greek Sage,Three-Lobed Sage,Turkish Sage)
 


 Basic Botanical Data of Radix Salvia miltiorrhiza.
 Salvia and the History of Microcirculation Research in China.
 Status of Salvia In Ancient Chinese Medicine---danshen(Radix Salvia miltiorrhiza) as the heart (mind) stimulator.
 Active Constituents and phytochemicals of Radix Salvia miltiorrhiza(Danshen).
 What is Tanshinone IIA? Application and function of Tanshinone IIA.
 Modern Developments and application research of Radix Salvia miltiorrhiza(Danshen).
 More About Sage Family.:History,Key Actions,Key Components,Medicinal Parts,Remedies,Traditional Uses of Sage Family world wide.
 Dosage, Toxicity,And Adverse Effects of Danshen.


   Salvia and the History of Microcirculation Research in China:

 Danshen(Radix Salvia miltiorrhiza) was used infrequently in ancient Chinese medicine, yet it has become an important herb in modern Chinese clinical practice. The transformation of salvia from a rarely used and minor component of formulas to a key herb is a story that sheds light on the evolution of the Chinese medical tradition.
 A review of herb formula guides shows that salvia appears in very few traditional formulas that are studied by modern practitioners. The only frequently mentioned traditional formula that includes this herb is Tianwang Buxin Dan (the Heavenly Emperor's Heart Nourishing Pill; Ginseng and Zizyphus Formula). The prescription has been made into a popular patent remedy, mainly used for insomnia, poor memory, and mental agitation (see: Tianwang Buxin Dan). The formula has 16 ingredients, with only a small amount of salvia, which has been included for its heart nourishing and spirit pacifying actions.
 In modern Chinese clinical practice, salvia is one of the most commonly used Chinese herbs: it appears in numerous formulations, sometimes as the key ingredient. In addition, salvia is sometimes given as a single herb remedy, and is even prepared in injection form for IV administration. The elevation of salvia to a key herb took place in two steps: recognition of salvia as a valuable blood-vitalizing agent leading to incorporation of the herb in modern formulas for angina pectoris; and then, investigations of its effectiveness in treating microcirculation disorders, leading to its use in treating liver fibrosis and cirrhosis.
    


   Status of Salvia In Ancient Chinese Medicine---danshen(Radix Salvia miltiorrhiza) as the heart (mind) stimulator.:

 The Chinese name for salvia, danshen, carries much meaning. Here, dan is the term used to describe cinnabar (dansha; sha = sand, depicting the small crystals of the mineral); in this context dan refers, in part, to the deep red color of salvia roots, which are likened to the color of cinnabar. Beyond the color, however, using this name for salvia may have been intended to convey the high value of the herb, since cinnabar has long been regarded as the premier substance of Chinese medicine. Red colors in Chinese herbs are usually described by the term hong (as in honghua: carthamus), or by chi (as in chishao: red peony); purple might also apply (zi; salvia is sometimes called zidanshen); so using dan is a rather unique designation. Shen refers to ginseng (renshen; ren = man, alluding to the man-shaped roots), long regarded as the most highly respected herb in China (see: The meaning of shen in renshen). Only about a dozen herbs, most of them deemed suitable as substitutes for ginseng, have been given the name hen.
 Salvia first appeared in the Shennong Bencao Jing (ca. 100 A.D.); in that text, the highest position for all medicinal materials was held by cinnabar and the highest position for all herbs was ginseng (and the mushroom ganoderma). Here are the descriptions of properties of cinnabar, ginseng, and salvia:
 Salvia is bitter and slightly cold. It is nontoxic, treating mainly evil qi in the heart and abdomen, continual gurgling of the intestines like water running, cold and heat, and gatherings and accumulations. It breaks concretions and eliminates conglomerations, relieves vexatious fullness, and boosts the qi.
 It is evident that salvia does not have the same level of desirable properties nor broad uses as do cinnabar and ginseng. Like ginseng, it is said to treat evil qi, and like cinnabar, it boosts the normal qi (an effect noted for ginseng in all later texts). The original Tianwang Buxin Dan formulation includes all three: ginseng, cinnabar, and salvia; the "dan" in the formula name refers to pills containing cinnabar (modern versions of the formula often delete cinnabar because of concerns about mercury, its main active component). Each of these three herbs were traditionally considered important for treating disorders of the heart, as applies to mental functions, and for treating hot swellings (all have a slightly cold nature). Thus, salvia was described in the Rihuazi Bencao (713 A.D.) this way: "Salvia nourishes the heart (mind), reinforces the will power, unblocks the guan pulse, and cures goiter and pyrogenic infections [fire toxins]."


   Active Constituents and phytochemicals of Radix Salvia miltiorrhiza(Danshen):

 The main active constituents of salvia are diterpene quinones, known as tanshinones (the Wade-Giles transliteration of danshen is tan-shen, hence the quinones were called tanshinones). Most of these compounds are colored, providing the reddish appearance of the roots. The group of components, labeled tanshinone I, tanshinone II, cryptotanshinone, etc. (see Figure 3), were first described by researchers in 1968, though investigations had been underway since the pigments were isolated from salvia in 1934. More recently, nearly 40 variants of the basic tanshinone structures have been found in the roots. The tanshinones are unique chemical constituents, and similar compounds are not found in other Chinese herbs. The total tanshinone content of the roots is about 1%, with tanshinone I and II and cryptotanshinone being present in the largest amount. In one recent study, the concentration of Radix Salvia miltiorrhiza yielded tanshinone II 0.29%; cryptotanshinone 0.23%; tanshinone I: 0.11%.

 Figure 3: The primary active constituents of Radix Salvia miltiorrhiza(Danshen):

 :(A) (B):
 :(C) (D): 

   (A):Cryptotanshinone    (B):Tanshinone I   (C):Tanshinone II   (D):Tanshinone VI
 The isolated tanshinones have been shown to inhibit bacteria, reduce fever and inflammation, inhibit platelet aggregation, dilate the blood vessels, and aid urinary excretion of toxins,also many other good benefits.


   What is Tanshinone IIA? Application and function of Tanshinone IIA.:

 Tanshnone IIA is a diterpenoid naphthoquinone extracted and isolated from Radix Salvia miltiorrhiza(Danshen).
 

 Figure: Molecular Structure of Tanshinoneiia
 Physical Appearance:Orange Solid (m.p. 205-207 deg C)
 Molecular Formula: C19H18O3      M.W.:294.3
 Purity: 98%(TLC:30% Ethyl Acetate/Petroleum ether; Rf=0.47)
 Solubility: Soluble in DMSO (25mg/ml) and ethanol (5mg/ml)
 Tanshinone IIA show good function and inhibits AP-1 activity by suppressing junfos-DNA complex formation(IC50=0.22¦Ìm),and displays anti-inflammatory activity and induces apoptosis in a variety of cell lines.

 Tanshinone IIA isolated from Salvia miltiorrhiza BUNGE induced apoptosis in HL60 human premyelocytic leukemia cell line.

 1. Abstract
 Apoptosis is a new therapeutic target of cancer research. Tanshinone IIA isolated from Salvia miltiorrhiza BUNGE, a traditional oriental medical herb, was observed to induce apoptosis in HL60 human premyelocytic leukemia cell line. Tanshinone IIA induced DNA fragmentation into the multiples of 180 bp and increased the percentage of hypodiploid cells in flow cytometry after propidium iodide (PI) staining. Tanshinone IIA-induced apoptosis is accompanied by the specific proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) and the activation of caspase-3, a major component in apoptotic cell death mechanism.

 2. Introduction
 Apoptosis is cellular suicide or programmed cell death which is mediated by the activation of an evolutionary conserved intracellular pathway. Recently the relation of apoptosis and cancer has been emphasized and increasing evidence suggests that the processes of neoplastic transformation, progression and metastasis involve alteration of normal apoptotic pathways. Apoptosis also gives some clues about effective anticancer therapy, and many chemotherapeutic agents were reported to exert their anti-tumor effects by inducing apoptosis of cancer cells.
 Salvia miltiorrhiza BUNGE is a traditional oriental medical herb which belongs to the family of Labiatae, and has been used for treatment of coronary heart disease, particularly angina pectoris and myocardial infarction. According to several phytochemical reports, major constituents of the root of Salvia miltiorrhiza BUNGE are composed of phenolics such as lithospermate B and diterpene quinone pigments such as tanshinones. Medical researchers have studied on the effect of magnesium lithospermate B on renal failure, and diterpene quinones have been reported for anti-platelet aggregation effect. Recently, it was found the growth inhibitory effects of various tanshinones on five tumor cell lines, and it was shown that HCTIS/CL02, a multidrug-resistant tumor cell line, did not exhibit resistance to tanshinones even though it has resistance to doxorubicin.
 In this study, apoptosis-inducing effect of tanshinone IIA which is most abundant and structurally representative among the tanshinones of Salvia miltiorrhiza BUNGE was investigated in HL60 human premyelocytic leukemia cell line.

 3. Results and Discusssion
 Recently, the anti-tumour effect of tanshinones isolated from Salvia miltiorrhiza BUNGE was elucidated using human tumour cell lines. Since many anticancer drugs induce apoptosis of tumour cells, the apoptosis-inducing activity of the crude extract of Salvia miltiorrhiza BUNGE was investigated. Human premyelocytic leukemia cell line, HL60, was treated with various concentrations of the ether extract of Salvia miltiorrhiza BUNGE for 4 h, and it was found that it induced internucleosomal DNA fragmentation, one of the biochemical hall mark of apoptosis, at the concentration above 10 ¦Ìg/ml. UV radiation was used as a positive control for the induction of apoptosis. Among the constituents of Salvia miltiorrhiza BUNGE, tanshinone IIA was focused on, because it is most abundant and structurally representative having a basic tanshinone skeleton. Using a similar phytochemical procedure with the previous report, tanshinone IIA was successfully purified and the structure of it was clearly identified compared with the previous report. When HL60 cells were treated with various concentrations of tanshinone IIA, internucleosomal DNA fragmentation was induced by the concentrations as low as 1 ¦Ìg/ml. In time course experiment in which 3 ¦Ìg/ml of tanshinone IIA was treated, 180 bp ladder was generated at 2 or 3 hours after the treatment. Microscopic observation showed that the crude ether extract of Salvia miltiorrhiza BUNGE and purified tanshinone IIA both induced cellular morphological changes characteristic of apoptosis including membrane blebbing and apoptotic body formation. Flow cytometry analysis of tanshinone IIA-treated HL60 cells showed the increase of hypodiploid apoptotic cells and the decrease of the cells at G1 phase of cell cycle, suggesting a possibility that tanshinone IIA induced apoptosis occurs at G1 phase of cell cycle. PARP is a nuclear enzyme which is involved in DNA repair process, and recently, it was found that 113 kDa PARP protein is cleaved into 89 and 24 kDa fragments by the action of CPP32, a protease recently named as caspase-3.
 Since the specific proteolytic cleavage of PARP is considered to be a biochemical characteristic of apoptosis, the Western blotting experiment was carried out using the antibody against PARP. The results demonstarted that PARP is cleaved into 89 kDa fragment 4 hours after the addition of tanshinone IIA suggesting that caspase-3 was activated. To measure the caspase-3 activity directly and quantitatively, Ac-DEVD-pNA was used, a specific colorimetric substrate of caspase-3. The results demonstrated that caspase-3 is activated during tanshinone IIA-induced apoptotic process. Recently, many papers reported that internucleosomal DNA fragmentation is not essential in apoptotic cell death, and some necrotic cell death is accompanied by internucleosomal DNA fragmentation, suggesting the possibility that internucleosomal DNA fragmentation may be not enough as an indicator of apoptotic cell death. It is, however, clear that the central mechanism of apoptosis is evolutionary conserved and caspase activation is an essential step in this complex apoptotic pathways. The results of the study, therefore, give more important evidences that tanshinone IIA-induced cell death is apoptosis.

 :A B: 

 Note:Normal and Adoptotic Morphology of HL-60 Cells.:
 A:Control HL-60 cells are majority premylocytes which usually appear in ovoid shape with large nucleus(arrow).H&E stain,at x 1000.
 B:After incubation at 0.1mg of Danshen for 48hrs,HL-60 cells exhibit characteristic apoptotic features with condensed chromatin along the margin of the nucleus(arrow).H&E stain,at x 1000.

 In this study the apoptosis inducing activity of tanshinone IIA, a main ingredient of Salvia miltiorrhiza BUNGE, was examined. Other tanshinone components structurally related to tanshinone IIA such as cryptotanshinone and tanshinone I also exist in the root of Salvia miltiorrhiza BUNGE, and the apoptosis-inducing activity of other tanshinones will be examined later especially focusing on caspase activity which is central component of apoptotic pathway.


   Modern Developments and application research of Radix Salvia miltiorrhiza(Danshen).:

 Mechanism of Action Category:Mast cell degranulation Inhibitor:

  1.Blood-vitalizing properties of Radix Salvia miltiorrhiza(Danshen).
  2.Blood circulation vitalizing function of Radix Salvia miltiorrhiza(Danshen).
  3.Radix Salvia miltiorrhiza(Danshen) as general anti-aging tonic.
  4.Inhibition of mast cell degranulation by tanshinones from the roots of Salvia miltiorrhiza,Radix Salvia miltiorrhiza(Danshen).
  5. Anti-Hypertensive Effect of Water Extract of Danshen on Renovascular Hypertension Through Inhibition of the Renin Angiotensin System.
  6.Cardiovascular disease, angina, high cholesterol control of Radix Salvia miltiorrhiza(Danshen).
  7.Liver cirrhosis, hepatitis B of Radix Salvia miltiorrhiza(Danshen).
  8. Asthmatic bronchitis of Radix Salvia miltiorrhiza(Danshen).
  9.Glaucoma therapy of Radix Salvia miltiorrhiza(Danshen) and extracts.
  10.Burn healing--danshen speed healing of burns and wounds.
  11.Danshen Increased rate of peritoneal dialysis.
  12.Unproven Uses of Radix Salvia miltiorrhiza(Danshen).
  13.More application and function in brief of Radix Salvia miltiorrhiza(Danshen).
  14.Anti-myocardial ischemia:  15.Protecting the lung:  16.Effects on the liver:
  17.Anti-neoplastic effects:  18.Anti-free radicals:  19.Promoting healing of wounds:
  20.Effects on vascular smooth cell migration:  21.Effects on the production of osteoclasts:  22.Anti-cell injury:
  23.Promoting cognitive function:  24.Effects on the phenotype of fibroblasts:  25.Effects on pancreatitis:
  26.Effects on stellate cells' proliferation and apoptosis:  27.Protecting human osteoblasts from ischemia-reperfusion injuries:

  1.Blood-vitalizing properties of Radix Salvia miltiorrhiza(Danshen):
 It was only during the 20th Century that salvia became known for its blood-vitalizing properties; until then, salvia was more commonly reputed to treat bleeding disorders (e.g., menstrual bleeding) than blood stasis (4).

  2.Blood circulation vitalizing function of Radix Salvia miltiorrhiza(Danshen):
 Formal acknowledgement of the value of salvia for vitalizing blood circulation finally appeared in the 1930s.
 Qin Bowei, a famous physician born at the turn of the 20th Century who was instrumental in the spread of TCM in modern China (after the revolution in 1949), included salvia in some of the formulas he used. He described the herb this way (5):
 Salvia is bitter and slightly cold and enters the channels of the heart and liver. It quickens the blood, moves the blood, and regulates transportation of blood fluid. The Da Ming[Mingyi Bielu ca. 500 A.D.] and Ri Hua[Rihuazi Bencao, 713 A.D., mentioned above] refer to this as "eliminating stasis and engendering the new," with the implication of freeing and supplementing. Salvia is most often used in the treatment of longstanding costal pain and hard obstruction in the early stage.


  3.Radix Salvia miltiorrhiza(Danshen) as general anti-aging tonic:
 A relatively new area of concern for blood stasis is in relation to aging. In the theoretical framework of ancient Chinese medicine, aging was understood to be related to a degradation of the essence (jing) that is stored in the kidney and which helps nourish the liver yin and blood and also helps stimulate the nutritive functions associated with the spleen. Decline in essence results in drying of the blood, contraction of the ligaments, withering of the flesh, and overall reduction in vitality, mental function, and health. During the 20th Century, possibly due to changes in the environment, diet, and lifestyle (as well as progress in medical research into aging), it was generally agreed that disorders associated with aging additionally involve blood stasis.
 The same basic observation technique was applied to examination of capillaries in the finger nail beds (see Figure 2). The nail bed is easy to view and is richly endowed with capillaries very close to the skin surface beneath the nail. It was theorized that the condition of the capillaries at this site would reflect the condition of the capillaries elsewhere in the body. One of the first applications of the nail bed measurements was reported at the Hong Kong conference (14). A group of researchers at the Huashan Hospital of the Shanghai First Medical College reported that nail bed circulation in patients with chronic viral hepatitis was abnormal, and that as treatment of hepatitis with Chinese herbs progressed, with reduction of symptoms and liver inflammation, the nail bed circulation improved. Salvia was a featured herb in the treatment for hepatitis in these studies. The authors concluded their presentation thus:
 
 Figure 2: Images of nail bed capillaries before and after treatment with salvia.


  4.Inhibition of mast cell degranulation by tanshinones from the roots of Salvia miltiorrhiza,Radix Salvia miltiorrhiza(Danshen):
 research show: the activity-guided fractionation of the extract of the root of Salvia miltiorrhiza B. (Labiatae, Tanshen), led to the isolation of four active components responsible for the anti-allergic activity in vitro.
 Among them, 15,16-dihydrotanshinone-1 and cryptotanshinone demonstrated significant inhibition of the release of beta-hexosaminidase from cultured RBL-2H3 cells in a dose-dependent manner; the ICS, values were calculated as 16 and 36 mu M, respectively.

  5. Anti-Hypertensive Effect of Water Extract of Danshen on Renovascular Hypertension Through Inhibition of the Renin Angiotensin System :
 A study was designed to elucidate the mechanism of anti-hypertensive effects of Danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive model, which is the renin-angiotensin system (RAS)-dependent hypertensive model. We investigated the effects of water extracts of Danshen on the angiotensin converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of Danshen extract in a dose-dependent manner. SBP was decreased significantly after administration of Danshen extract in 2K1C, whereas plasma renin activity (PRA) was not changed.
 The plasma concentration of aldosterone (PAC) was decreased significantly in 2K1C group administered with Danshen extract, whereas the plasma concentration of ANP was increased by administration of Danshen extract for three weeks. These results suggest that Danshen has an anti-hypertensive effect through the inhibition of ACE, an essential regulatory enzyme of RAS.

  6.Cardiovascular disease, angina, high cholesterol control of Radix Salvia miltiorrhiza(Danshen):
 A small number of studies suggest that danshen may provide benefits for treating disorders of the heart and blood vessels, including chest pain, heart attacks, ischemic stroke, myocarditis and high cholesterol. Danshen is frequently used for these problems in combination with other herbs. There is only limited research in humans specifically evaluating danshen in the treatment of these diseases. In addition, these studies have been small, with flaws in their designs. The results of different studies have disagreed with each other. Therefore, it is unclear whether there is any benefit from danshen for these conditions.
 


  7.Liver cirrhosis, hepatitis B of Radix Salvia miltiorrhiza(Danshen):
 Some studies suggest that danshen may provide benefits for treating liver diseases such as cirrhosis and chronic hepatitis B. Danshen is frequently used for these problems in combination with other herbs. Although early research in humans suggests a possible reduction in liver fibrosis in people with cirrhosis and some benefits in chronic hepatitis, these studies have been small, with flaws in their designs. Therefore, it is unclear whether there is any benefit from danshen for these conditions.

  8. Asthmatic bronchitis of Radix Salvia miltiorrhiza(Danshen):
 A small amount of research in humans suggests that danshen may improve breathing and lessen cough and wheeze in patients with chronic asthmatic bronchitis.Further studies are needed to compare danshen with other common treatments for this condition.

  9.Glaucoma therapy of Radix Salvia miltiorrhiza(Danshen) and extracts:
 Clinical studies proved that Danshen has been proposed as possible glaucoma therapy.

  10.Burn healing--danshen speed healing of burns and wounds:
 Although animal studies suggest that danshen may speed healing of burns and wounds,there are no studies in humans evaluating this claim.

  11.Danshen Increased rate of peritoneal dialysis:
 One study suggests that danshen may speed peritoneal dialysis and ultrafiltration rates when added to dialysate solution. Although danshen appears to be effective for this use, it is not known whether it is safe.

  12.Unproven Uses of Radix Salvia miltiorrhiza(Danshen).:
 Danshen has been suggested for many other uses, based on tradition or on scientific theories. However, these uses have not been thoroughly studied in humans, and there is limited scientific evidence about safety or effectiveness. Some of these suggested uses are for conditions that are potentially very serious and even life-threatening. You should consult a health care provider before taking danshen for any unproven use.


  13.More application and function in brief of Radix Salvia miltiorrhiza(Danshen):

 *Acne:Intrauterine growth retardation
 *Anoxic brain injury:Liver cancer
 *Anxiety:Lung fibrosis
 *Blood clotting disorders:Menstrual problems
 *Bruising:Preeclampsia
 *Cancer:Psoriasis
 *Circulation:Radiation-induced lung damage
 *Clogged arteries:Restlessness
 *Diabetic nerve pain:Sleep difficulties
 *Eczema:Stimulation of GABA (gamma-aminobutyric acid) release
 *Gentamicin toxicity:Stomach ulcers
 *Heart palpitations :Wound healing
 Summary:Although Radix Salvia miltiorrhiza(Danshen) has been suggested as a treatment for many illnesses, there is not enough scientific evidence to support the use of danshen for any medical condition. Danshen is frequently used in combination with other herbs.
 Radix Salvia miltiorrhiza(Danshen) may increase the risk of bleeding and should be used cautiously with anticoagulants (blood thinners) and some anti-inflammatory drugs. It should be avoided in pregnant or breast-feeding women and in children. Consult your health care provider immediately if you have any side effects.
 The information in this monograph was prepared by the professional staff at Natural Standard, based on thorough systematic review of scientific evidence. The material was reviewed by the Faculty of the Harvard Medical School with final editing approved by Natural Standard.


  14.Anti-myocardial ischemia:
 Dan Shen can decrease the magnitude of abnormal ST changes in the electrocardiogram of myocardial infarction in rabbits, reduce the occurrence of pathological Q waves, inhibit the formation of lipoperoxides, and decrease the severity of myocardial necrosis.

  15.Protecting the lung:
 Dan Shen has protective and therapeutic effects on rats with acute respiratory distress syndrome (ARDS). In rats with ARDS, Dan Shen inhibits hyperactivity of alveolar macrophage, decreasing the secretion of tumor necrosis factor Alfa and interleukin-1.

  16.Effects on the liver:
 Dan Shen extract can improve liver tissue injuries and reduce the magnitude of fibrosis in rats with CCl4 and DMN (dimethylnitrosamine)-induced hepatic fibrosis. Dan Shen can also decrease the hypoxanthine and MDA (malondialdehyde) levels in the liver tissue.Administered at 3ml, Dan Shen injections can effectively protect rats from passive smoking-induced liver function changes. It is speculated that this effect of Dan Shen may have been achieved by its potential anti-oxygen free radical properties.

  17.Anti-neoplastic effects:
 In vitro experiments show that at 10 ml/ml, Dan Shen can inhibit K562 and BCaP-37 tumor cells with an inhibition rate of 70 to 80%; for K562 cells, Dan Shen's IC50 is 7.5 ml/ml, and for BCaP-37 cells, its IC50 is 6.96ml/ml.

  18.Anti-free radicals:
 Experiments show that Dan Shen injections can decrease the MDA levels and increase the SOD levels in the blood and spinal tissues of rabbits with spinal injuries.

  19.Promoting healing of wounds:
 By optimizing the ratio of NO and ET, Dan Shen can decrease the synthesis of ET and NO, increase surface tissue activity in rats with second degree scalding injuries, and lessen early-stage injury progression, thus promoting injury recovery.

  20.Effects on vascular smooth cell migration:
 Experiments show that in rats whose proliferation of vascular smooth cells has been inhibited by hydroxycarbamide, Dan Shen can inhibit vascular smooth cell migration induced by bovine serum of newborn calves. Dan Shen can also inhibit cell migration-related bone protein gene expression, and decrease the activity of creatine kinase.

  21.Effects on the production of osteoclasts:
 At 1.0g/L, Dan Shen can inhibit the production of osteoclasts in in-vitro bone marrow cell cultures. It mainly inhibits the transformation of osteoclast metrocytes into mature osteoclasts.

  22.Anti-cell injury:
 Dan Shen extract can delay the lowering of survival rate of gastric mucosa chief cells, increase lactic dehydrogenase transudation, and raise the level of free calcium in cells.

  23.Promoting cognitive function:
 Administered to rats, with a single temporal line ischemic injury, by an intraperitoneal injection at 10g/kg, Dan Shen can shorten the time it takes the subjects to react and find a solution in Morris labyrinth. Dan Shen also notably reduces the volume of temporal line infarct and the expression of HSP32.

  24.Effects on the phenotype of fibroblasts:
 A 0.2% Dan Shen solution can promote the fusiform to squamous transformation of fibroblasts and increase the number of fibroblasts and collagen synthesis.

  25.Effects on pancreatitis:
 Administered to rats with biliary pancratitis at 5g/kg, Dan Shen injections can reduce Ca2+ concentrations in pancreatic acinar cells and lessen the extent of pancreatic injury.

  26.Effects on stellate cells' proliferation and apoptosis:
 In-vitro experiments show that Dan Shen can inhibit the proliferation of stellate cells and promote apoptosis of in vitro-cultivated stellate cells.

  27.Protecting human osteoblasts from ischemia-reperfusion injuries:
 Experiments show that pre-treatment with Dan Shen can increase the survival rate of human osteoblasts in ischemia-reperfusion.

   More About Sage Family:

 More info about Sage Spectrum and Identification:
 Family:Labiatae ;Branches:
 1.Salvia officinalis(Common names:Sage, Garden Sage, Salvia, Meadow Sage; Spanish: Salvia, Alhucerna de la Costa, T?de Mar, Yerba de Santa Maria, Chia, Mejorana, Mirto, Salvia Real, Salvia Virgen; Nahuatl: Chianzotzolli)
 2.Salvia miltiorrhiza(Common names:Red-Rooted Salvia,Dan Shen,chinese danshen,Red Sage,red sage root,Red-rooted Sage,Chinese sage,Red Ginseng,Salvia miltiorrhiza BUNGE,Salvia miltiorrhiza B.etc.)
 3.Salvia microphylla(Red Texas Sage,Mirto,Salvia,Chia,T de Monte)
 4.Salvia sclarea(Clary Sage,Clear Eye)
 5.Salvia triloba(Greek Sage,Three-Lobed Sage,Turkish Sage)

 Native to the Mediterranean, sage is cultivated all over the world. There are an estimated 500 species of Salvia, with at least 280 found in Mexico alone. They can be found in all shapes and sizes and of varying medicinal values. Spanish sage (S. lavandulifolia) is the most familiar culinary variety, and does not contain thujone, which is strongly antiseptic and carminative; and that is the reason that it is rarely used medicinally. Sage is not related to Big Sagebrush (Artemisia tridentata).
 The Red Texas Sage is an ornamental plant native to Mexico, producing attractive, tubular, red flowers. It is an evergreen plant, growing to about thirty-two inches in height producing square stems and hairy gray-green or purple leaves. The leaves are harvested during the summer, and the whole plant is replaced after three or four years.
 Dan Shen is native to China and cultivated in northeastern China and Inner Mongolia. It is a hardy perennial, growing to about thirty-two inches in height producing toothed, oval leaves and clusters of purple flowers. The roots are harvested from late autumn through to early spring.
 Greek Sage is indigenous to Greece, the Commonwealth of Independent States, Albania, Turkey, and Cyprus. Various species are prevalent throughout the Mediterranean region. It is a semi-shrub that grows to over forty inches in height, producing squarish green leaves that are grayish-white underneath. The flowers are long and often purplish-lilac or pink, but occasionally white.
 Clary Sage is native to southern Europe and the Middle East, and is now cultivated in France and Russia for its essential oil. It is a square-stemmed biennial, growing to about three feet in height, producing hairy wrinkled leaves and whorls of pale blue flowers. It is gathered in summer during its second year.
 The desert that stretches for hundreds of miles along the US-Mexico border is covered with all sorts of plants with the name of "sage". Some are related to the true sage (members of the Salvia genus), but many are not even distantly related. One such is the genus Leucophyllum, known as purple sage and native to the long, dry corridor shared by the US and Mexico. It is completely unrelated to Salvia officinalis. The plant that is called "sagebrush" in English and "chamiso" in Spanish is from yet another family, Compositae. True sage (Salvia spp) is often confused with native Mexican plants of the genus Buddleia and commonly called "royal sage" or salvia real. The two plants are used interchangeably for many of the same remedies, however. Adding to the confusion, true sage has many other names in the lexicon of Mexican herbal remedies, including alhucerna de la costa (lavender of the coast), t?de mar (tea of the sea), and yerba de Santa Maria, a name that is shared with many other plants.
 Therefore, asking a Latin American botanica owner what is in the packets labeled "cenizo", the answer will simply be "sage". Cenizo is the word for any gray-leafed sage-like plant and often refers to some species of Leucophyllum, but not necessarily. Look for small egg-shaped gray-green leaves and perhaps a few tiny pale purple flowers.


  1.History of Sage Family.
  2.Key Actions of Sage Family.
  3.Key Components from Sage Family.
  4.Medicinal Parts of Sage Family.
  5.Remedies of Sage Family.
  6.Traditional Uses of Sage Family world wide.

  1.History of Sage Family:

 Its botanical name is a clue to its medicinal importance. Salvia comes from salvare which, in Latin, means "to cure."
   
 The earliest of all the Chinese herbal texts, The Divine Husbandman's Classic (Shen nong Bencaojing) listed Dan Shen as an herb that invigorates the blood. It is still used as a circulatory remedy.
 Clary sage has long been perceived as a weaker version of true sage, but it is still significant and was once commonly used to treat eye problems. In 1652, Culpeper recommended a decoction of the seeds to draw out splinters and thorns.
 Sage has long had the reputation for restoring failing memory in the elderly; and, like other memory-enhancing herbs, for some unknown reason, it was planted on graves.
 It is said that when the British started importing tea from China, the Chinese so valued sage that they would trade two cases of tea for one of dried English sage. However, it is noted that in the 17th century, Dutch merchants were trading three chests of China tea for one of sage leaves.
 The Romans considered it a sacred herb and would gather it with ceremony. The appointed person would make sacrifices of bread and wine, wear a white tunic, and approach with bare feet and, of course, be well washed. Roman instructions also advised against using iron tools. This is sensible being that iron salts are incompatible with the herb.
 The Aztecs used seeds from the Salvia species as a food. They were toasted, ground into a flour, and added to cornmeal to make a thick drink called "chianzotzolatol?. "Chia" seeds are still used today to prepare cold beverages with lemon and sugar -- as well as being a popular fast-growing plant sold on ceramic animals.
 Native American healers mixed sage with bear grease and applied it as a salve to heal skin sores and wounds. They also used the woody stems as a toothbrush. The Cherokee used sage to relieve asthma, coughs, and colds. They also used a leaf infusion to treat diarrhea. The Mohegans used it to treat intestinal worms.
 Thujone is the notorious ingredient in absinthe, which is said to have been the cause of Vincent Van Gogh's insanity.


  2.Key Actions of Sage Family:

  (a)Sage:antispasmodic,astringent,antiseptic,antibacterial,antibiotic,aromatic,carminative,estrogenic,expectorant,promotes bile flow relaxes peripheral blood vessels, reduces blood sugar levels,reduces perspiration,salivation and lactation tonic,uterine stimulant
  (b) Dan Shen:antibacterial,circulatory stimulant,clears heat (fevers),dilates blood vessels
  (c) Greek Sage:antimicrobial,antiseptic,anti-inflammatory,lowers blood pressure and blood sugar levels
  (d) Clary Sage:antispasmodic,digestive aid,estrogenic,sedative,tonic


  3.Key Components from Sage Family:

  (a) Sage:volatile oil(cimene,cineole,limonene,terpinene,camphor,and thujone),diterpene bitters,tannins,triterpenoids,resin,flavonoids,estrogenic substances,saponins
  (b) Dan Shen:vitamin E,tanshinones,salviol,volatile oil.
  (c) Greek Sage:volatile oil,flavonoids,caffeic acid derivatives(rosmarinic acid),diterpenes,triterpenes
  (d) Clary Sage:volatile oil(linalyl acetate,linalool),diterpenes,tannins


  4.Medicinal Parts of Sage Family:

 Leaves (sage), root (Dan Shen), leaves (Greek sage), aerial parts/seeds/essential oil (Clary sage)
 Sage is active against: Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Klebsiella pneumoniae, Salmonella spp.
 The essential oil is a broad-spectrum antibiotic.


  5.Remedies of Sage Family:

  (a) Sage:
 Fresh or dried leaves are used, but fresh leaves are a useful first aid remedy to be placed on insect stings and bites.
 Tincture is a digestive tonic and a menopausal remedy. It is also prescribed to reduce salivation in Parkinson's disease.
 Infusions can be used as a gargle for sore throats or used as a tonic and liver stimulant, as well as improving digestive function and circulation. It can also reduce lactation during weaning and relieve night sweats during menopause.
 Compresses are soaked in infusions and applied to slow healing wounds.
 Gargle or mouthwash from weak infusions are used for sore throats, tonsillitis, mouth ulcers, or gum disease. It can also be used in toothpowders.
 Hair rinses from infusions are used for dandruff control or to restore colour to graying hair.
  (b) Dan Shen:
 Tincture of the roots is used to treat angina and other circulatory problems.
 Decoctions of the root are taken for painful menstration, angina and coronary heart disease.
  (c) Greek Sage:
 Decoctions and infusions of the leaves are used to lower blood pressure and blood sugar levels. Because of its antiseptic and anti-inflammatory action, it is often used for sore throats and mouth ulcers.
  (d) Clary Sage:
 Decoctions of the seeds have long been used to draw out splinters and thorns.
 Infusions are used to treat digestive problems and as a calming tonic to relieve menstrual pain.


  6.Traditional Uses of Sage Family world wide:

 A strong tea is an effective wash for infected and inflamed cuts. Sage is especially helpful for women. Taken internally and used as a compress, it soothes painful, lumpy breasts. It also helps to regulate periods or bring on delayed periods, and dries up breast milk. In addition, it is used to diminish hot flashes and lift depression in menopause.
 Clary sage is especially valuable for menopausal complaints, including hot flashes and, because of its estrogen-stimulating action, clary sage is most effective when this hormone is low. Sage tea also stop night sweats of those suffering from TB (tuberculosis). Some reports indicate that sweat reduction can be as much as 50%.
 Purple varieties are more often used in medicine as they are generally more effective than the common green plant. The leaves have a special affinity for the mouth and throat, making it ideal to be used in gargles or mouthwashes. Purple sage is used mainly for colds, fever, and colic as it has a sedating qualtiy while inducing perspiration to break a fever. Medicinally, the leaf, stems, and flowers are used for such things as diaper rash.
 In Israel and Cyprus, and elsewhere, Greek sage is used for cardiac symptoms, lung complaints, colds, coughs, nervousness, and digestive problems. Externally, it is used to treat skin problems.
 In Costa Rica, sage is used for wounds, arthritis, asthma, and problems with the prostate gland.
 In Europe, sage is used to lower blood sugar in diabetics.
 Germany markets a natural antiperspirant containing sage.
 Cautions of Sage Family:
 All varieties of sage contain thujone, except for the common culinary variety (S. Lavandulifolia).
 Thujone is toxic in excess amounts. It can cause convulsions and reduce breast-milk production.
 Thujone can also trigger epileptic seizures.
 Do not take essential oil during pregnancy.
 Pure sage oil should not be ingested or applied full strength to the skin.
 The herb can interact with anticonvulsants, disulfiram, insulin, and other diabetic therapies.


   Dosage, Toxicity,And Adverse Effects of Danshen:

 Acute Toxicity:LD50 (mice/intraperitoneal injection):[ 32.9g/kg~40.5g/kg.]

 At the higher dosage levels, salvia may on rare occasions cause dry mouth, dizziness, lassitude, numbness, shortness of breath, and other symptoms that will usually disappear spontaneously without interrupting the treatment. Rare Chinese Materia Medica notes that salvia is not suitable for patients who have deficiency but not stasis, or deficiency accompanied by cold, or with tendency to bleed. However, most materia medica guides do not present these cautions. Salvia has very low acute toxicity, with an LD50 by injection of 40-80 g/kg.

 The Pharmacopoeia of the People's Republic of China indicates a recommended dosage of 9-15 grams per daily dose in decoction form. In a few instances, higher doses are administered, up to 20 grams per day, in the treatment of inflammatory diseases, including viral hepatitis. According to English-Chinese Rare Chinese Materia Medica, up to 30-60 grams can be used in cases of angina and heat-type arthritis. The relatively high dosage of salvia, compared to most other Chinese herbs (typical dosage recommendations are 3-9 grams for many herbs) may be attributed to the relatively low level of active constituents and their poor solubility in water.

 It is recommended that salvia, or its preparations used for treatment of poor blood circulation, not be combined with coumadin (Warfarin), as there is a possibility of increasing the anticoagulant effects (see: The interactions of herbs and drugs). In a literature survey conducted through October 2000, three cases of increased anticoagulant activity were reported in the literature in persons taking salvia along with Warfarin. Such effects may be rare and are likely to be dose dependent, as the mechanism appears to be a simple additive effect of anticoagulant activity of salvia along with that produced by Warfarin. Therefore, persons using coumadin should either avoid using salvia, or use it in relatively low dosage (not more than the equivalent of 6-9 grams per day in decoction) while paying attention to blood coagulation tests that are routinely performed for persons taking the drug.
 Dosing:The doses listed below are based on scientific research, publications or traditional use. Because most herbs and supplements have not been thoroughly studied or monitored, safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients even within the same brand. Combination products often contain small amounts of each ingredient and may not be effective. Appropriate dosing should be discussed with a health care provider before starting therapy; always read the recommendations on a product?s label. The dosing for unproven uses should be approached cautiously, because scientific information is limited in these areas.
 There are no standard or well-studied doses of danshen, and many different doses are used traditionally. Danshen is frequently used in combination with other herbs.
 Adults (Aged 18 Or Older):
 Internal administration: decoction of 5 to 15g, large dosages can reach up to 30g. 5:1 concentrated extract: 1 to 3 grams/day; (6 grams/day in large-dose use).
 By mouth: Oral dosing has not been studied in well-conducted trials in humans, and therefore no specific dose can be recommended.
 By injection: Danshen injections have been used for the treatment of ischemic stroke, but safety and effectiveness have not been established.
 Children (Younger Than 18):There are not enough scientific data to recommend danshen for use in children, and danshen is not recommended because of potential side effects.


  Scientific References:

  1.What is danshen?What is Tanshinone IIA?Application and function of Tanshinone IIA.Modern Developments and application research of Radix Salvia miltiorrhiza.