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International Journal of Pharmacognosy & Chinese Medicine Research Article 20 min read

Astragalus Membranaceus and Salvia Miltiorrhizae: An Overview of Ethnopharmacology and Phytochemistry

Alex Boye
ISSN: 2576-4772  10.23880/ipcm-16000252  Received: July 31, 2023  Published: November 08, 2023
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Keywords
Astragalus Membranaceus Bioactivity Chinese Herbal Medicine Danshen Huan Qi Salvia Miltiorrhiza
Abstract

Mostly a common argument is made against use of plant - based alternative and complementary medicine such as Traditional Chinese Medicine (TCM) that their use is based on empiricism, which is considered by adherents of conventional medicine to be unscientific and anti intellectual. It is in this light that the onus now is on natural product scientists to prove the superiority of plant-based medicines as epitomized by TCM through expanding knowledge on the superiority of medicinal plants as the mainstay of human pharmacopoeia. Major scientific databases including but not limited to Scopus, PubMed, PubMed Central, Web of Science, Web of Science Core Collections, Google Scholar, Science Direct etc were critically searched by using a combination of terms. Precisely, Salvia miltiorrhiza and Astragalus membranaceus were searched from the various databases in combination with chemical composition, isolated compounds, medicinal uses, bioactivity, ethnopharmacology, chemical elucidation using the Boolean operators. It was observed that the two medicinal plants are phytochemically rich with diverse phytocompounds. Most of the phytocompounds isolated from the two medicinal plants were structurally elucidated together with their key biological properties. Most of the compounds from the two medicinal had their anti-cancer properties demonstrated in vitro and in vivo. Herewith, this review highlighted the centrality of Astragalus membranaceus and Salvia miltiorrhizha as key sources of bioactive compounds with demonstrable anti-cancer and anti-inflammatory properties.

Introduction

The ethnobotanical heritage of Asia, specifically China from antiquity has been incorporated into important traditional healing systems such as Traditional Chinese Medicine (TCM). Chinese herbal medicine (CHM) has been practiced more than two millennia with a lot of success in terms of efficacy for many clinical disease conditions. Currently, it is one of the most popular complementary medicines in the world. Traditional Chinese herbal medicine use and practice embodies accumulation of empirical evidence, theoretical assumptions, and philosophical thoughts in relation to man, disease, and herbs. Importantly, the choice and selection of herbs for the treatment of any particular disease is guided by a system of herbology. Mostly, the main herb for the treatment of the disease, which is figuratively referred to as the ‘emperor herb’ or ‘king herb’ is first chosen followed by other herbs, which play various auxiliary functions such as enhancing target site recognition, aiding absorption, reducing toxicity, potentiating the effect of the ‘king herb’ etc.

Indeed, use of herbs as food and medicine is well entrenched in China. Currently, many studies are not only validating the ethnobotanical claims of Chinese herbs but also exploring the pharmacology, safety, efficacy, and molecular mechanisms of action of some of these herbs. This new trend is welcoming, especially at a time when international demand for Chinese herbal products is soaring. Two of the Chinese herbs, which have enjoyed long uneventful use in traditional Chinese herbal medicine for the treatment of various diseases including cancer, are Astragalus membranaceus and Salvia miltiorrhiza. This review highlights the biological properties, phytochemical profile and drug discovery prospects of Astragalus membranaceus and Salvia miltiorrhiza.

Astragalus Membranaceus

Astragalus membranaceus (Bunge) is an age old medicinal herb with immense ethnobotanical usage in China and other Asian countries. In view of its usefulness as a medicinal herb, it has many common names in different Asian countries [1]. For example, ‘huang qi’ (Chinese), ‘hwangqi’ (Korea) and commonly referred to as membranous milk-vetch root in English. A. membranaceus is referred to as Radix Astragali in most Chinese literatures including the pharmacopoeia of the People’s Republic of China, 2005.

Traditional Uses of Astragalus membranaceus

The traditional medicinal uses of A. membranaceus are well documented in TCM application. For instance, it has been prescribed over thousands of years for general weakness, chronic illness and also to improve general vitality. Also, ancient Chinese writings have recorded the use of Astragalus as having a tonic effect on the spleen, blood and ‘qi’. It tonifies the qi of the spleen [2], improves the ‘yang qi’ of the spleen and stomach, tonifies lung ‘qi’, cold, sweating, and shortness of breath. Also, it treats night sweat, chronic ulcerations and sores, numbness, limb paralysis and edema [2, 3].

The genus Astragalus comprises over 2,000 species distributed worldwide [3]. Most studies on A. membranaceus have concentrated on its immuno - modulatory polysaccharides. Also, other studies have demonstrated effects of non-polysaccharide phyto-components on immune deficiency disorders. It is therefore not surprising that various formulations of A. membranaceus are currently being used in China and other countries as adjunctive therapy in the management of cancers. Also, it is used to improve functional capacity of many organs such as the heart, liver and kidneys in view of its adaptogenic properties [4].

Parts of a Membranaceus Used in TCM

Dry roots, powdered or in decoction is used for most of its traditional medicinal applications. It is also used in combination with other Chinese medicinal herbs in various combinations to achieve a specific therapeutic objectives [4].

Phytochemical Composition of a Membranaceus

The major phytocompounds well characterized in A. membranaceus include, polysaccharides, saponins, flavonoids, amino acids and some trace elements [5]. The polysaccharides of A. membranaceus that have received much investigative attention includes polysaccharide fraction F3, polysaccharides A, B and C (Identified as glucans), and polysaccharides D (A heteropolysaccharides) [5]. Also, the roots of A. membranaceus were shown to contain a series of cycloartene triterpene glycosides, also identified as astragalosides I – VII (Saponins). Their structures are based on the aglycone cycloastragenol and were shown to contain 1-3 sugars located on 3-, 6-, and 25- positions [6].

Additionally, several other saponins have been reported with their structures based on the oleanene skeleton [6]. The flavonoids identified in the roots of A. membranaceus by using high performance liquid chromatography - electrospray ionization mass spectrometry include calycosin-7-0-beta-D-glucoside, calycosin-7-0-beta-D- glucoside-6’-0-malonate (2), ononin, (6aR, 11a R)-3- hydroxy-9, 10-dimethoxypterocarpan-3-0-beta-D-glucoside, Calycosin, (3R)-7, 2’-dihydroxy-3’, 4’-dimethoxy-isoglyvan- 7-0-beta-D-glucoside, formononetin-7-O-beta-D-glucoside- 6’-O-malonate, and formononetin [7]. Other phytochemicals identified in A. membranaceus are phytosterols (A volatile oil), amino acids (e.g. Gamma amino butyric acid (GABA)), L-canavanine, zinc, iron, copper, magnesium, manganese, calcium, potassium, sodium, colbalt, rubidium, molybdenum, chromium, vanadium, tin, silver, tantalum, hafnium, europium, thorium [7]. Organic compounds from the roots of A. membranaceus include choline, betaine, gluconic acid, β - sitosterols, aromatic compounds (Essential oil linoleic acid, bitter compounds, and asparagine).

Biological Activities of a Membranaceus

Due to the usefulness of A. membranaceus, a number of studies have investigated its biological and pharmacological properties in a view to explain some of its ethno-medicinal claims and uses as elaborated (Table 1).

Name of Isolated
Compound		IUPAC Name of Isolated
Compound		Chemical
Formula
of Isolated
Compound		Chemical Structure of Isolated
Compound		Bioactivity of Isolated
Compound		Refer
ence
Astragaloside I(2R,3R,4S,5S,6R)-2-[[(1S,3R
,6S,8R,9S,11S,12S,14S,15R,1
6R)-14-hydroxy-15-[(2R,5S)-
5-(2-hydroxypropan-2-yl)-2-
methyloxolan-2-yl]-7,7,12,16-
tetramethyl-6-[(2S,3R,4S,5R)-
3,4,5-trihydroxyoxan-
2-yl]oxy-9-pentacyc
lo[9.7.0.01,3.03,8.012,16]octadecanyl]
oxy]-6-(hydroxymethyl)oxane-
3,4,5-triol		C41 H68
014		Immuno
modulation
Increase proliferation and
antibody production from T-
and B-lymphocytes		[8]
Isoliquiritigenin(E)-1-(2,4-dihydroxyphenyl)-3-(4-
hydroxyphenyl)prop-2-en-1-one		C15 H12
O4		Anti-inflammatory
Inhibits IL-6, IL-12 p40, and
TNF-a		[9]
Liquiritigenin(E)-1-(2,4-dihydroxyphenyl)-3-(4-
hydroxyphenyl)prop-2-en-1-one		C15 H12
O4		Anti-inflammatory
Inhibits IL-6, IL-12 p40, and
TNF-a		[9]
Formononetin7-hydroxy-3-(4-methoxyphenyl)
chromen-4-one		C16 H12
O4		Anti-cancer
initiates growth-inhibitory
and pro-apoptotic activities
in human colon cancer cells
Anti-angiogenic property
downregulated the
expression of the key pro-
angiogenic factors, including
vascular endothelial growth
factor (VEGF) and matrix
metalloproteinases		[10]
Astragalus
Polysaccharide
(APS)		2-(chloromethyl)-4-(4-
nitrophenyl)-1,3-thiazole		C10 H7
CIN2 O2 S		Macrophage activation
stimulates macrophages
to express iNOS (inducible
NO synthase) gene through
the activation of NF-κB/Rel
(nuclear factor-κB/Rel).		[11]
Astragaloside V(2S,3R,4S,5S,6R)-2-[(2S,3R,4S,5R)-
2-[[(1S,3R,6S,8R,9S,11S,12S,1
4S,15R,16R)-9,14-dihydroxy-
7,7,12,16-tetramethyl-15-
[(2R,5S)-2-methyl-5-[2-
[(2S,3R,4S,5S,6R)-3,4,5-
trihydroxy-6-(hydroxymethyl)
oxan-2-yl]oxypropan-2-yl]
oxolan-2-yl]-6-pentacyc
lo[9.7.0.01,3.03,8.012,16]octadecanyl]
oxy]-4,5-dihydroxyoxan-3-yl]
oxy-6-(hydroxymethyl)oxane-
3,4,5-triol		C47 H78
O19		Inhibition of advanced
glycation end product
(AGE)
inhibits the formation of
NE - (carboxymethyl) lysine
(CML) and pentosidine		[12]
Astragalus
Polysaccharide
(APS)		2-(chloromethyl)-4-(4-
nitrophenyl)-1,3-thiazole		C10 H7
CIN2 O2 S		Renal protective effect
(glomerulonephritis
therapeutic potential)
significantly decreased
the proteinuria and
morphological changes on
glomerulonephritis rats		[13]
Astragalus
Saponin I		(2R,4S,5R,10S,13R,14R,18S,20R)-
10-[(2S,3R,4S,5S)-3-
[(2S,3R,4S,5S,6R)-4,5-
dihydroxy-6-(hydroxymethyl)-
3-[(2R,3R,4S,5S,6R)-3,4,5-
trihydroxy-6-(hydroxymethyl)
oxan-2-yl]oxyoxan-2-yl]
oxy-4-[(2R,3R,4S,5S,6R)-3,4,5-
trihydroxy-6-(hydroxymethyl)
oxan-2-yl]oxy-5-[(2S,3R,4S,5R)-
3,4,5-trihydroxyoxan-2-yl]
oxyoxan-2-yl]oxy-2-hydroxy-
4,5,9,9,13,20-hexamethyl-24-oxah
exacyclo[15.5.2.01,18.04,17.05,14.08,13]
tetracosane-20-carbaldehyde		C58 H94
O24		Anti-Diabetic Nephropathy
reduced oxidative stress
intensity, and the blood
glucose level of Diabetic
Nephropathy rats.
Reduced microalbuminuria
level, advanced glycated
end-products either in serum
or in kidney cortex, and the
aldose reductase activity.
The expression of
transforming growth factor
Beta-1 mRNA in kidney
cortex by RT-PCR analysis
was markedly declined.
Both the relative grade of
mesangium hyperplasia by
microscopical observation
and the thickness of
glomerular base membrane
by electron microscope
measurement were
decreased significantly		[14]

Table 1: Isolated Compounds from _Astragalus membranaceus._

Water-soluble polysaccharide (RAP)

2-(chloromethyl)-4-(4- nitrophenyl)-1,3-thiazole C10 H7 CIN2 O2 S

Astragalus polysaccharide (APS)

2-(chloromethyl)-4-(4- nitrophenyl)-1,3-thiazole C10 H7 CIN2 O2 S

2-(chloromethyl)-4-(4- nitrophenyl)-1,3-thiazole C10 H7 CIN2 O2 S

Astragalus polysaccharide (APS)

2-(chloromethyl)-4-(4- nitrophenyl)-1,3-thiazole C10 H7 CIN2 O2 S

(Acidic Polysaccharide (AMon-S))

Figure 1
Click to enlarge
Figure 1

immunomodulating effects stimulates the proliferation of human peripheral blood mononuclear cells and enhances its interleukin production.

[15]

Growth-promoting effect. enhances ileal digestabilities and serum concentrations of amino acids in early weaned piglets regulates amino acid metabolism to beneficially increase the entry of dietary amino acid into the systemic circulation [16]

Activates Mouse B cells and macrophages

[17]

significant reticuloendothelial system- potentiating activity [18]

Astragaloside VII(2R,3S,4S,5R,6R)-2-
(hydroxymethyl)-6-[[(1S,3R,6S,
8R,9S,11S,12S,14S,15R,16R)-14-
hydroxy-7,7,12,16-tetramethyl-
15-[(2R,5S)-2-methyl-5-
[2-[(2S,3R,4S,5S,6R)-3,4,5-
trihydroxy-6-(hydroxymethyl)
oxan-2-yl]oxypropan-2-yl]
oxolan-2-yl]-6-[(2S,3R,4S,5R)-
3,4,5-trihydroxyoxan-2-yl]oxy-
9-pentacyclo[9.7.0.01,3.03,8.012,16]
octadecanyl]oxy]oxane-3,4,5-triol		C47 H78
O19		Immunomodulatory and
anticancer effects.
prominent IL-2 inducing
activity;
IL-2 has shown powerful
immuno stimulatory
and antineoplastic properties		[19]
Afrormosin7-hydroxy-6-methoxy-3-(4-
methoxyphenyl) chromen-4-one		C17 H14
O5		Anti-oxidant[20]
Calycosin7-hydroxy-3-(3-hydroxy-4-
methoxyphenyl) chromen-4-one		C16 H12
O5		Anti-oxidant[20]
Odoratin7-hydroxy-3-(3-hydroxy-
4-methoxyphenyl)-6-
methoxychromen-4-one		C17 H14
O6		Anti-oxidant[20]
Isoflavones5,7-dihydroxy-3-(4-
hydroxyphenyl)chromen-4-one;7-
hydroxy-3-(4-hydroxyphenyl)
chromen-4-one;7-hydroxy-3-(4-
hydroxyphenyl)-6-
methoxychromen-4-one		C17 H14
O6		Anti-oxidant[20]
Astragaloside IV(2R,3R,4S,5S,6R)-2-[[(1S,3R
,6S,8R,9S,11S,12S,14S,15R,1
6R)-14-hydroxy-15-[(2R,5S)-
5-(2-hydroxypropan-2-yl)-2-
methyloxolan-2-yl]-7,7,12,16-
tetramethyl-6-[(2S,3R,4S,5R)-
3,4,5-trihydroxyoxan-
2-yl]oxy-9-pentacyc
lo[9.7.0.01,3.03,8.012,16]octadecanyl]
oxy]-6-(hydroxymethyl)oxane-
3,4,5-triol		C41 H68
014		Anti-inflammatory action
Inhibit NF-κB and expression
of adhesion molecules in LPS-
stimulated endothelial cells.		[21]
Astragaloside IV(2R,3R,4S,5S,6R)-2-[[(1S,3R
,6S,8R,9S,11S,12S,14S,15R,1
6R)-14-hydroxy-15-[(2R,5S)-
5-(2-hydroxypropan-2-yl)-2-
methyloxolan-2-yl]-7,7,12,16-
tetramethyl-6-[(2S,3R,4S,5R)-
3,4,5-trihydroxyoxan-
2-yl]oxy-9-pentacyc
lo[9.7.0.01,3.03,8.012,16]octadecanyl]
oxy]-6-(hydroxymethyl)oxane-
3,4,5-triol		C41 H68
014		Anti-inflammation action
Suppress airway
inflammation and hyper-
responsiveness in chronic
asthma animal model		[22]

Table 2: Isolated Compounds from _Astragalus membranaceus._

Herb Drug Interactions Involving a Membranaceus

Not much scientific reports are currently available regarding herb-drug interactions involving A. membranaceus. However, there are some few reports that seem to indicate possible herb-drug interactions involving A. membranaceus. For example, it was demonstrated that effect of recombinant IL - 2 was potentiated 10 fold by Astragalus extracts [23]. Similarly, the effect of recombinant IL - 1 was shown to be improved by Astragalus extracts in chronic viral cervicitis [24]. Speculatively, Astragalus extracts were said to have the potential to reduce immunosuppressive effects of corticosteroids and cyclosporine and this view was based on the T cell stimulatory effect of Astragalus extracts.

Toxicity related effects of A. membranaceus So far, there has not been any toxicity reports associated with the use of Astragalus membranaceus preparations in both pre - clinical and clinical studies, largely confirming its long uneventful ethnobotanical usage. Indeed, Astragalus is safe, in view of the fact that doses as high as 100 mg/kg administered to rats produced no observable adverse effects. In a study involving use of mice, the LD50 for Astragalus was determined to be almost 40 g/kg when administered through the intra peritoneal route yet presented no observable adverse effects or organ related toxicities.

Salvia Miltiorrhiza

S. miltiorrhiza is an important Asian medicinal herb, common in China. In China, S. miltiorrhiza is integral in traditional Chinese herbal medicine. It is perhaps for this reason that it is prominently captured in the Chinese herbal pharmacopoeia as ‘Danshen’. Indeed, S. miltiorrhiza has many folk uses as well as demonstrated therapeutic application in China and other countries.

Traditional Uses of S. Miltiorrhiza

Locally, in China various formulations of S. miltiorrhiza have been used primarily to treat coronary heart diseases, myocardial infarction, and hypertension [25, 26, 27]. ‘Huoxue Huayu’ (TCM - promote blood circulation and removes blood stasis), used over 1000 years [28].

Ecological Distribution of S. Miltiorrhiza

S. miltiorrhiza is widely distributed in Asia, particularly in China.

Parts of S Miltiorrhiza Used in TCM

In most historical documentations on the medicinal uses of S. miltiorrhiza as well as pre -clinical and clinical studies, the dry roots are normally used [29, 30].

Phytochemical Composition of S. Miltiorrhiza

Well over 80 different phyto-compounds are reportedly identified from S. miltiorrhiza [30]. Of these 80 phytochemicals 50 were identified as water soluble while the remaining were said to be fat – soluble [31]. The water - soluble compounds comprises mainly polyphenolic acids, of which the main ones are salvianolic acids, protocatechuic aldehyde, salvianolic acid A and B [31]. On the other hand, the fat - soluble phytochemicals are mainly diterpenes of the tanshinone subclass, which includes tanshinone IIA and cryptotanshinone. Other phytochemicals of S. miltiorrhiza includes beta - sitosterol, ursolic baicalin, tannins and vitamin E [28].

Biological and Pharmacological Properties of S. Miltiorrhiza

Various preparations of S. miltiorrhiza have been reported in cell, animal as well as clinical studies. Importantly, the various biological activities of S. miltiorrhiza have been attributed to its phyto-constituents Table 2.

Name of Isolated
Compound		IUPAC Name of Isolated
Compound		Chemical
Formula
of Isolated
Compound		Chemical Structure of
Isolated Compound		Bioactivity of Isolated
Compound		Refer
ences
Tanshinone I1,6-dimethylnaphtho[1,2-g][1]
benzofuran-10,11-dione		C18 H12 03Anti-cancer
Induce apoptosis in colon
cancer cells		[32]
Tanshinone IIA1,6,6-trimethyl-8,9-dihydro-
7H-naphtho[1,2-g][1]
benzofuran-10,11-dione		C19 H18 O3Anti-cancer
cytotoxic compounds in human
leukemia cells		[33]
Neo-tanshinlactone6,14-dimethyl-
12,17-dioxatetracyc
lo[8.7.0.02,7.011,15]heptadeca-
1(10),2,4,6,8,11(15),13-
heptaen-16-one		C17 H12 O3Anti-breast cancer
Inhibits estrogen receptor
over-expressing breast cancer
cell		[34]
Tanshinone I1,6-dimethylnaphtho[1,2-g][1]
benzofuran-10,11-dione		C18 H12 03Anti-cancer
Inhibits the migration and
invasion of human lung
adenocarcinoma cell line,
CL1-5		[35]
Cryptotanshinone(1R)-1,6,6-trimethyl-2,7,8,9-
tetrahydro-1H-naphtho[1,2-g]
[1]benzofuran-10,11-dione		C19 H20 O3Anti-bacterial activity[36]
Dihydrotanshinone I(1R)-1,6-dimethyl-1,2-
dihydronaphtho[1,2-g][1]
benzofuran-10,11-dione		C18 H14 O3Anti-bacterial activity[36]
Lithospermic acid4-[3-[1-carboxy-2-
(3,4-dihydroxyphenyl)
ethoxy]-3-oxoprop-1-enyl]-
2-(3,4-dihydroxyphenyl)-
7-hydroxy-2,3-dihydro-1-
benzofuran-3-carboxylic acid		C27 H22 O12Anti-viral activity
exhibited potent effect against
HIV-1 integrase activity in vitro
and viral replication in vivo		[37]
Lithospermic acid B(2R)-2-[(E)-3-[(2S,3S)-
3-[(1R)-1-carboxy-2-
(3,4-dihydroxyphenyl)
ethoxy]carbonyl-2-(3,4-
dihydroxyphenyl)-7-
hydroxy-2,3-dihydro-1-
benzofuran-4-yl]prop-2-enoyl]
oxy-3-(3,4-dihydroxyphenyl)
propanoic acid		C36 H30 016Anti-viral activity
exhibited potent effect against
HIV-1 integrase activity in vitro
and viral replication in vivo		[37]
Tanshinone I1,6-dimethylnaphtho[1,2-g][1]
benzofuran-10,11-dione		C18 H12 03Anti-inflammatory
Inhibits IL-12 production in
mouse macrophages and on
IFN-γ production		[38]
Dihydrotanshinone1,6-dimethyl-1,2-
dihydronaphtho[1,2-g][1]
benzofuran-10,11-dione		C18 H14 O3Anti-inflammatory
Inhibits IL-12 production in
mouse macrophages and on
IFN-γ production		[38]
Cryptotanshinone(1R)-1,6,6-trimethyl-2,7,8,9-
tetrahydro-1H-naphtho[1,2-g]
[1]benzofuran-10,11-dione		C19 H20 O3Anti-inflammatory
Inhibits IL-12 production in
mouse macrophages and on
IFN-γ production		[38]
Tanshinone VIRetrieved from Chemspider.
com
1-Hydroxy-2-(1-hydroxy-
2-propanyl)-8-methyl-3,4-
phenanthrenedione		C18 H16 O14Anti-inflammatory.
protects the myocardium
against hypoxia/reoxygenation
injury and attenuates
progression of in vitro
myocardial remodeling (heart
disease).		[39]
Salvianolic acid B
(Sal-B)		(2R)-2-[(E)-3-[(2R,3R)-
3-[(1R)-1-carboxy-2-
(3,4-dihydroxyphenyl)
ethoxy]carbonyl-2-(3,4-
dihydroxyphenyl)-7-
hydroxy-2,3-dihydro-1-
benzofuran-4-yl]prop-2-enoyl]
oxy-3-(3,4-dihydroxyphenyl)
propanoic acid		C36 H30 O16Anti-Cancer activity
Inhibits head and neck
squamous cell carcinoma
(HNSCC).
Effectively suppress COX-
2 expression and induce
apoptosis in a variety of cancer
cell lines		[40]
Rosmarinic acid(2R)-3-(3,4-dihydroxyphenyl)-
2-[(E)-3-(3,4-
dihydroxyphenyl)prop-2-
enoyl]oxypropanoic acid		C18 H16 O8Anti-oxidant activity
Potential natural phenolic
antioxidants for food,
pharmaceutical, cosmetics or
nutraceutical industries		[41]
Salvianolic acid B(2R)-2-[(E)-3-[(2R,3R)-
3-[(1R)-1-carboxy-2-
(3,4-dihydroxyphenyl)
ethoxy]carbonyl-2-(3,4-
dihydroxyphenyl)-7-
hydroxy-2,3-dihydro-1-
benzofuran-4-yl]prop-2-enoyl]
oxy-3-(3,4-dihydroxyphenyl)
propanoic acid		C36 H30 O16Anti-oxidant activity
Potential natural phenolic
antioxidants for food,
pharmaceutical, cosmetics or
nutraceutical industries		[41]
Magnesium
lithospermate B
(MLB)		Magnesium;(2R)-2-
[(E)-3-[(2S,3S)-3-
[(1R)-1-carboxylato-2-
(3,4-dihydroxyphenyl)
ethoxy]carbonyl-2-(3,4-
dihydroxyphenyl)-7-
hydroxy-2,3-dihydro-1-
benzofuran-4-yl]prop-2-enoyl]
oxy-3-(3,4-dihydroxyphenyl)
propanoate		C36 H28Mg
O16		Vasodilation.
regulate Ca2+ homeostasis in
cultured rat thoracic aorta
vascular smooth muscle
cells (VSMCs)		[42]
Sodium rosmarinate
(SR)		(2S)-3-(3,4-dihydroxyphenyl)-
2-[(E)-3-(3,4-
dihydroxyphenyl)prop-2-
enoyl]oxypropanoic acid		C18 H16 O8Vasodilation.
regulate Ca2+ homeostasis in
cultured rat thoracic aorta
vascular smooth muscle cells
(VSMCs)		[42]
Magnesium
lithospermate (ML)		Magnesium;(2R)-2-
[(E)-3-[(2S,3S)-3-
[(1R)-1-carboxylato-2-
(3,4-dihydroxyphenyl)
ethoxy]carbonyl-2-(3,4-
dihydroxyphenyl)-7-
hydroxy-2,3-dihydro-1-
benzofuran-4-yl]prop-2-enoyl]
oxy-3-(3,4-dihydroxyphenyl)
propanoate		C36 H28
MgO16		Vasodilation.
regulate Ca2+ homeostasis in
cultured rat thoracic aorta
vascular smooth muscle cells
(VSMCs)		[42]
Tanshinone II-A1,6,6-trimethyl-8,9-dihydro-
7H-naphtho[1,2-g][1]
benzofuran-10,11-dione		C19 H18 O3Modulates collagen
metabolism
prevented cardiac fibrosis and
improved cardiac function		[43]
Magnesium
tanshinoate B (MTB)		Magnesium;(2R)-2-
[(E)-3-[(2S,3S)-3-
[(1R)-1-carboxylato-2-
(3,4-dihydroxyphenyl)
ethoxy]carbonyl-2-(3,4-
dihydroxyphenyl)-7-
hydroxy-2,3-dihydro-1-
benzofuran-4-yl]prop-2-enoyl]
oxy-3-(3,4-dihydroxyphenyl)
propanoate		C36 H28
MgO16		Anti-hypertensive[44]
Tanshinone IIA1,6,6-trimethyl-8,9-dihydro-
7H-naphtho[1,2-g][1]
benzofuran-10,11-dione		C19 H18 O3Anti-oxidant activity
inhibits NADPH oxidase		[45]
Cryptotanshinone(1R)-1,6,6-trimethyl-2,7,8,9-
tetrahydro-1H-naphtho[1,2-g]
[1]benzofuran-10,11-dione		C19 H20 O3Anti-Cancer
suppress prostate cancer
growth and androgen
signaling.		[46]
Tanshinone IIA1,6,6-trimethyl-8,9-dihydro-
7H-naphtho[1,2-g][1]
benzofuran-10,11-dione		C19 H18 O3Anti-Cancer
suppress prostate cancer
growth and androgen
signaling.		[46]
Tanshinone I1,6-dimethylnaphtho[1,2-g][1]
benzofuran-10,11-dione		C18 H12 03Anti-Cancer
suppress prostate cancer
growth and androgen
signaling.		[46]
Tanshinone IIA1,6,6-trimethyl-8,9-dihydro-
7H-naphtho[1,2-g][1]
benzofuran-10,11-dione		C19 H18 O3Anti-Cancer
Inhibits Osteosarcoma
by inducing
cell apoptosis and inhibiting
proliferation, migration,
and invasion in vitro		[46]
Dihydrotanshinone
I (DI)		(1R)-1,6-dimethyl-1,2-
dihydronaphtho[1,2-g][1]
benzofuran-10,11-dione		C18 H14 O3Anti-Cancer
inhibits the growth of human
cervical cancer cells		[47]
Cryptotanshinone
(CT)		(1R)-1,6,6-trimethyl-2,7,8,9-
tetrahydro-1H-naphtho[1,2-g]
[1]benzofuran-10,11-dione		C19 H20 O3Inhibitor of both human
acetylcholinesterase (AChE)
and butyrylcholinesterase
(BuChE)
Potential drug for treatment of
Alzheimer’s disease		[48]
15, 16-Dihydrotan
shinone I (DHTS)		(1R)-1,6-dimethyl-1,2-
dihydronaphtho[1,2-g][1]
benzofuran-10,11-dione		C18 H14 O3Anti- Cancer
Induces apoptosis in human
colorectal cancer cells		[49]
Tanshinone II-A1,6,6-trimethyl-8,9-dihydro-
7H-naphtho[1,2-g][1]
benzofuran-10,11-dione		C19 H18 O3Anti- Cancer
inhibited migration and
invasion of human colon
carcinoma (CRC) cells		[50]
Retrieved from
Chemspider.com
Tanshinone VI		1-Hydroxy-2-(1-hydroxy-
2-propanyl)-8-methyl-3,4-
phenanthrenedione		C18 H16 O14Anti-Cancer
inhibits the expression
of intercellular adhesion
molecule-l and vascular cell
adhesion molecule-l		[51]
lithospermic acid in
Salvianolate		(2S,3S)-4-[(E)-3-
[(1R)-1-carboxy-2-
(3,4-dihydroxyphenyl)
ethoxy]-3-oxoprop-1-enyl]-
2-(3,4-dihydroxyphenyl)-
7-hydroxy-2,3-dihydro-1-
benzofuran-3-carboxylic acid		C27 H22 O12Anti-Oxidant Activity
inhibits Reactive Oxygen
Species (ROS) and iNOS
production and increases total
antioxidant capacity (TAOC)
and NO levels in H O -treated
2 2
cardiomyocytes in vitro via
downregulation of Smad2/3
and TGFβ1 expression.		[52]
Cryptotanshinone(1R)-1,6,6-trimethyl-2,7,8,9-
tetrahydro-1H-naphtho[1,2-g]
[1]benzofuran-10,11-dione		C19 H20 O3Antibacterial activity
Inhibits clinic isolated
methicillin and vancomycin-
resistant Staphylococcus
aureus (MRSA and VRSA)		[53]
Sodium tanshinone
IIA sulfonate (STS)		sodium;1,6,6-trimethyl-
10,11-dioxo-8,9-dihydro-7H-
naphtho[1,2-g][1]benzofuran-
2-sulfonate		C19 H17
NaO6 S		Cardioprotective activity.
reduce myocardial infarct size		[54]

Table 3: Isolated Compounds from _Salvia miltiorrhiza._ Herb-Drug Interactions Involving S. Miltiorrhiza Concomitant use of ‘Dans

Table 2: Isolated Compounds from Salvia miltiorrhiza. Herb-Drug Interactions Involving S. Miltiorrhiza Concomitant use of ‘Danshen’ and warfarin (An anti - coagulant / anti - thrombotic drug) has been linked to bleeding and prolonged prothrombin time [55]. Warfarin prevents atrial fibrillation, valvular heart disorders, deep vein thrombosis [55]. Similarly, ‘Danshen’ inhibits platelet adhesion and aggregation to suppress the formation of thromboxane A2 [55]. As a result, co - administration of ‘Danshen’ and warfarin at enhances anti- coagulation and possible bleeding. Indeed, the herb - drug interaction between ‘Danshen’ and warfarin was linked to active components of ‘Danshen’. For example, tanshinones inhibit CYP1A1, CYP2C6 and CYP2C11 - dependent hepatic metabolism of warfarin, leading to increased plasma concentration of warfarin [56]. Again, interaction between ‘Danshen’ and aspirin has been reported [57, 58].

Similarly, ‘Danshen’ was shown to augment the effects of aspirin, through reduction of aspirin protein binding, which leads to increased plasma concentration of aspirin and its effects thereof. Also, ‘Danshen’ has been reported to exert digoxin - like immune reactivity, and this observation was reported to have led to a false interference of digoxin plasma concentration [57]. ‘Danshen’ has been shown to alter the pharmacokinetic profile of theophylline, a drug mostly metabolized by CYP1A2 and CYP2E1 [59, 60]. Similarly, ‘Danshen’ was shown to have influenced the metabolism and excretion of losartan and EXP3174 in vivo [61].

Adverse Effects of S. Miltiorrhiza

Reported adverse effects of S. miltiorrhiza include thirst, and gastrointestinal discomfort, especially when one uses the dripping pill formulation.

Toxicity of S. Miltiorrhiza

In a study using mice, the LD50 for ‘Danshen’ was reported to be 25.807 g/kg which is many folds higher than the therapeutic dose (6.56 mg/kg body weight), indicating that ‘Danshen’ is safe at least in mice [31].

Studies on Combined Effects of a Membranaceus and S. Miltiorrhiza

Undoubtedly, the ethno-botanical use of both A. membranaceus and S. miltiorrhiza in China coupled with their recent therapeutic application in China has stimulated vigorous scientific investigations on these two herbs. In most studies either the extracts of the two herbs or their phyto-compounds are combined in various combinations not only to reflect their ethno- botanical uses but also to achieve specific therapeutic objective. From Table 3, some of the studies that investigated combined effects of phytocomponents A. membranaceus and S. miltiorrhiza are exemplified.

Herbal Components / ExtractsInvestigated Disease
Condition		Putative Mechanism of ActionReferences
A. membranaceus and S.
miltiorrhiza extracts		Liver fibrosis indicesLowered serum fibrosis indices including HA, LN,
IV-C, PCIII in fibrotic patients		[62,63]
Astragalus, Astragalus
polysaccharide and Salvianolic
acid		Liver fibrosis in an CCl -
4
induced rat model		CASE inhibited Smad2 C/L phosphorylation
and also reduced the expression of α-SMA in
myofibroblast		[64]
CASECancer cell proliferation
and invasion		CASE ameliorated HepG2 cell proliferation and
invasion by modulating TGF-β/Smad pathway		[65]
CASEKeloid fibroblast cell
proliferation and invasion		CASE inhibited Keloid cell proliferation and invasion
via modulation of TGF-β/Smad and MAPK pathway		[66]
CASEHCC in ratsCASE ameliorates DEN-induced HCC in rats by
modulating TGF-β/Smad signaling to decrease PAI-I
mRNA transcripts		[67]
CASEHCC in rats and HepG2 cellsCASE inhibited HepG2 cell proliferation and
invasion by modulating Smad3L phosphorylation		[68]
CASEKeloid fibroblast cells in
rabbits		CASE reduced keloid formation by modulating the
TGF-β/Smad signaling pathway		[69]
CASEHSCs, HepG2 cellsModulation of MAPK - regulated TGF-β/Smad
signaling		[68]

Table 4: Studies on combined extracts of Astragalus membranaceus and Salvia miltiorrhiza.

Compound astragalus and Salvia miltiorrhiza extract (CASE), mitogen activated protein kinase (MAPK), hepatic stellate cells (HSCs), plasminogen activator inhibitor protein 1 (PAI-1), transforming growth factor beta (TGF-β), diethylnitrosamine (DEN), hepatocellular carcinoma (HCC), hyaluronic acid (HA)

Conclusion

On the basis of these impressive highlights on Astragalus membranaceus and Salvia miltiorrhiza with regards to their potential as sources of small molecules for pharmacotherapy and also as natural templates for pharmaceutical semi- synthesis of analog drugs, their bio-sustainability should engage the attention of natural product scientists. Further, research efforts should focus on translational studies particularly on some of the promising small molecule compounds isolated from Astragalus membranaceus and Salvia miltiorrhiza for clinical trials.

Funding

Authors received no financial support for the research, authorship, and/or publication of this article.

Acknowledgement

My appreciation goes to Prof. S. Tayman (Department of Chemistry, University of Cape Coast, Cape Coast, Ghana) for inspiration. Institutional Review Board Statement Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interests

The author (s) declares no potential conflicts of interest with regards to the research, authorship, and/or publication of this article.

Sample Availability

Not applicable.

References

  1. Che CT, Wang ZJ, Chow MSS, Lam CWK (2013) Herb herb combination for therapeutic enhancement and advancement theory practice and future perspectives. Molecules 18(5): 5125-5141.
  2. Liu J, Yang H, Zhu X, Zhao Z, Chen H (2011) Comparative study of wild and cultivated Astragali radix in Daqingshan district in Wuchuan of Neimenggu. Zhongguo Zhong yao za zhi 36(12): 1577-1581.
  3. Shi LP, Ou QM, Cui WJ, Chen YL (2014) Study on method and its optimization of improving seed germination of Astragalus membranaceus as gansu traditional medicinal herb. Zhong yao cai 37(4): 548-552.
  4. Fu J, Wang Z, Huang L, Zheng S, Wang D, et al. (2014) Review of the botanical characteristics phytochemistry and pharmacology of Astragalus membranaceus Huangqi. Phytheraphy Research 28(9): 1275-1283.
  5. Ma XQ, Shi Q, Duan JA, Dong TXX, Tsim KWK (2002) Chemical analysis of Radix Astragali Huangqi in China a comparison with its adulterants and seasonal variations. Journal of Agriculture Food Chemistry 50(17): 4861- 4866.
  6. Kitagawa I, Yoshikawa M, Yoshihara M, Hayashi T, Taniyama T (1983) Chemical studies of crude drugs 1 Constituents of Ginseng radix rubra. Yakugaku Zasshi 103(6): 612-622.
  7. Lin LZ, He XG, Lindenmaier M, Nolan G, Yang J, et al. (2000) Liquid chromatography electrospray ionization mass spectrometry study of the flavonoids of the roots of Astragalus mongholicus and A membranaceus. Journal of Chromatography A 876(1-2): 87-95.
  8. Wang YP, Li XY, Song CQ, Hu ZB (2002) Effect of astragaloside IV on TB lymphocyte proliferation and peritoneal macrophage function in mice. Acta Pharmacologica Sinica 23(3): 263-266.
  9. Li W, Sun YN, Yan XT, Yang SY, Kim S, et al. (2014) Flavonoids from Astragalus membranaceus and their inhibitory effects on LPS stimulated pro inflammatory cytokine production in bone marrow derived dendritic cells. Archieve Pharmacal Research 37(2): 186-192.
  10. Auyeung KKW, Law PC, Ko JKS (2012) Novel anti angiogenic effects of formononetin in human colon cancer cells and tumor xenograft. Oncology Reports 28(6): 2188-2194.
  11. Kun YL, Young JJ (2006) Macrophage activation by polysaccharide isolated from Astragalus membranaceus. International Immunopharmacology 5(7-8): 1225-1233.
  12. Motomura K, Fujiwara Y, Kiyota N, Tsurushima K, Takeya M, et al. (2009) Astragalosides isolated from the root of astragalus radix inhibit the formation of advanced glycation end products. Journal of Agricultural Food Chemistry 57(17): 7666-7672.
  13. Li S, Zhang Y (2009) Characterization and renal protective effect of a polysaccharide from Astragalus membranaceus. Carbohydrates Polymers 78(2): 343- 348.
  14. Yin X, Zhang Y, Wu H, Zhu X, Zheng X, et al. (2004) Protective Effects of Astragalus Saponin I on Early Stage of Diabetic Nephropathy in Rats. Journal Pharmacology Science 95: 256-266.
  15. Yin JY, Chan BCL, Yu H, Lau IYK, Han XQ, et al. (2012) Separation structure characterization, conformation and immunomodulating effect of a hyperbranched heteroglycan from Radix Astragali. Carbohydrates Polymers 87(1): 667-675.
  16. Yin FG, Liu YL, Kong XF, Huang RL, Li TJ, et al. (2009) Dietary supplementation with Astragalus polysaccharide enhances ileal digestibilities and serum concentrations of amino acids in early weaned piglets. Amino Acids 37: 263-270.
  17. Shao BM, Xu W, Dai H, Tu P, Li Z, et al. (2004) A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus a Chinese medicinal herb. Biochemical and Biophysical Research Communication 320(4): 1103-1111.
  18. Shimizu N, Tomoda M, Kanari M, Gonda R (1991) An acidic polysaccharide having activity on the reticuloendothelial system from the root of Astragalus mongholicus. Chemical and Pharmaceutical Bulletin 39(11): 2969-2972.
  19. Yesilada E, Bedir E, Çalış I, Takaishi Y, Ohmoto Y (2005) Effects of triterpene saponins from Astragalus species on in vitro cytokine release. Journal of Ethnopharmacology 96(1-2): 71-77.
  20. Shirataki Y, Takao M, Yoshida S, Toda S (1997) Antioxidative components isolated from the roots of Astragalus membranaceus Bunge Astragali Radix. Phytotheraphy Research 11(8): 603-605.
  21. Zhang WJ, Hufnagl P, Binder BR, Wojta J (2003) Anti inflammatory activity of astragaloside IV is mediated by inhibition of NF-κB activation and adhesion molecule expression. Thrombosis Haemostasis 90(5): 904-914.
  22. Du Q, Chen Z, Zhou L, Zhang Q, Huang M, et al. (2008) Inhibitory effects of astragaloside IV on ovalbumin- induced chronic experimental asthma. Canadian Journal of Physiology Pharmacology 86(7): 449-457.
  23. Yoshida Y, Wang MQ, Liu JN, Shan BE, Yamashita U (1997) Immunomodulating activity of Chinese medicinal herbs and Oldenlandia diffusa in particular. International Journal of Immunopharmacology 19(7): 359-370.
  24. Qian ZW, Mao SJ, Cai XC, Zhang XL, Gao FX, et al. (1990) Viral etiology of chronic cervicitis and its therapeutic response to a recombinant interferon. Chinese Medical Journal (Engl) 103(8): 647-651.
  25. Ng CF, Koon CM, Cheung DWS, Lam MY, Leung PC, et al. (2011) The anti-hypertensive effect of Danshen Salvia miltiorrhiza and Gegen Pueraria lobata formula in rats and its underlying mechanisms of vasorelaxation. Journal of Ethnopharmacology 137(3): 1366-1372.
  26. Wang Y, Cao SH, Cui YJ, Kong LK, Tian H, et al. (2015) Salvia miltiorrhiza Bge f alba ameliorates the progression of monocrotaline induced pulmonary hypertension by protecting endothelial injury in rats. Tohoku Journal of Experimental Medicine 236(2): 155-162.
  27. Woo KS, Yip TWC, Chook P, Kwong SK, Szeto CC, et al. (2013) Cardiovascular protective effects of adjunctive alternative medicine Salvia miltiorrhiza and Pueraria lobata in high risk hypertension. Evidence based Complement Alternative Medicine 2013: 132912.
  28. Chen X, Li W, Xia W, Luo H, Liu X (1997) A comparative study on the chemical components of Salvia miltiorrhiza Bge. collected from Zhongjiang of Sichuan and from other habitats. Zhongguo Zhong yao za zhi 22(9): 522- 524.
  29. Park EJ, Zhao YJ, Kim YC, Sohn DH (2007) PF2401 SF standardized fraction of Salvia miltiorrhiza and its constituents tanshinone I tanshinone IIA and cryptotanshinone protect primary cultured rat hepatocytes from bile acid induced apoptosis by inhibiting JNK phosphorylation. Food and Chemical Toxicology 45(10): 1891-1898.
  30. Yin HQ, Choi YJ, Kim YC, Sohn DH, Ryu SY, et al. (2009) Salvia miltiorrhiza Bunge and its active component cryptotanshinone protects primary cultured rat hepatocytes from acute ethanol induced cytotoxicity and fatty infiltration. Food Chemical Toxicology 47(1): 98- 103.
  31. Zhou L, Zuo Z, Chow MSS (2005) Danshen an overview of its chemistry pharmacology pharmacokinetics and clinical use. Journal of Clinical Pharmacology 45(1): 1345-1359.
  32. Su CC, Chen GW, Lin JG (2008) Growth inhibition and apoptosis induction by tanshinone I in human colon cancer Colo 205 cells. International Journal of Molecular Medicine 22(5): 613-618.
  33. Efferth T, Kahl S, Paulus K, Adams M, Rauh R, et al. (2008) Phytochemistry and pharmacogenomics of natural products derived from traditional Chinese medicine and Chinese materia medica with activity against tumor cells. Molecular Cancer Theraphy 7(1): 152-161.
  34. Wang X, Bastow KF, Sun CM, Lin YL, Yu HJ, et al. (2004) Antitumor Agents 239 Isolation Structure Elucidation Total Synthesis and Anti Breast Cancer Activity of Neo tanshinlactone from Salvia miltiorrhiza. Journal of Medicinal Chemistry 47(23): 5816-5819.
  35. Lee CY, Sher HF, Chen HW, Liu CC, Chen CH, et al. (2008) Anticancer effects of tanshinone I in human non-small cell lung cancer. Molecular Cancer Therapeutics 7(11): 3527-3538.
  36. Lee DS, Lee SH, Noh JG, Hong SD (1999) Antibacterial activities of cryptotanshinone and dihydrotanshinone I from a medicinal herb Salvia miltiorrhiza Bunge. Bioscience Biotechnology and Biochemistry 63(12): 2236-2239.
  37. Elazem ISA, Chen HS, Bates RB, Huang RCC (2002) Isolation of two highly potent and non-toxic inhibitors of human immunodeficiency virus type 1 HIV-1 integrase from Salvia miltiorrhiza. Antiviral Res 55(1): 91-106.
  38. Kang BY, Chung SW, Kim SH, Ryu SY, Kim TS (2000) Inhibition of interleukin 12 and interferon γ production in immune cells by tanshinones from Salvia miltiorrhiza. Immunopharmacology 49(3): 355-361.
  39. Yagi A, Takeo S (2003) Anti inflammatory constituents aloesin and aloemannan in Aloe species and effects of tanshinon VI in Salvia miltiorrhiza on heart. Yakugaku Zasshi Japanase for Pharmaceutical Science 123(7): 517-532.
  40. Zhao Y, Hao Y, Ji H, Fang Y, Guo Y, et al. (2010) Combination Effects of Salvianolic Acid B with Low-Dose Celecoxib on Inhibition of Head and Neck Squamous Cell Carcinoma Growth In vitro and In vivo. Cancer Prevention Research 3(6): 787-796.
  41. Zhang Y, Li X, Wang Z (2010) Antioxidant activities of leaf extract of Salvia miltiorrhiza Bunge and related phenolic constituents. Food and Chemical Toxicology 48(10): 2656-2662.
  42. Chen LI, Xuan LJ, Wang YP (2009) Effects of magnesium lithospermate B and its analogues on Ca2+ homeostasis in cultured rat thoracic aorta vascular smooth muscle cells. Planta Medica 75(15): 1573-1579.
  43. Fang J, Xu SW, Wamg P, Tang FT, Zhou SG, et al. (2010) Tanshinone II-A attenuates cardiac fibrosis and modulates collagen metabolism in rats with renovascular hypertension. Phytomedicine 18(1): 58-64.
  44. Leung SWS, Zhu D, Man RYK (2010) Effects of the aqueous extract of Salvia Miltiorrhiza danshen and its magnesium tanshinoate B‐enriched form on blood pressure. Phytheraphy Research 24(5): 769-774.
  45. Wang P, Wu X, Bao Y, Fang J, Zhou S, et al. (2011) Tanshinone IIA prevents cardiac remodeling through attenuating NAD P H oxidase derived reactive oxygen species production in hypertensive rats. Die Pharmazie 66(7): 517-524.
  46. Zhang Y, Won SH, Jiang C, Lee HJ, Jeong SJ, et al. (2012) Tanshinones from Chinese medicinal herb Danshen Salvia miltiorrhiza Bunge suppress prostate cancer growth and androgen receptor signaling. Pharmaceutical Research 29: 1595-1608.
  47. Ye Y, Xu W, Zhong W, Li Y, Wang C (2012) Combination treatment with dihydrotanshinone I and irradiation enhances apoptotic effects in human cervical cancer by HPV E6 down regulation and caspases activation. Molecular and Cellular Biochemistry 363: 191-202.
  48. Wong KKK, Ho MTW, Lin HQ, Lau KF, Rudd JA, et al. (2010) Cryptotanshinone an acetylcholinesterase inhibitor from Salvia miltiorrhiza ameliorates scopolamine induced amnesia in Morris water maze task. Planta Medica 76(3): 228-234.
  49. Suk FM, Jou WJ, Lin RJ, Lin SY, Tzeng FY, et al. (2013) 15,16 Dihydrotanshinone I-induced apoptosis in human colorectal cancer cells Involvement of ATF3. Anticancer Research 33(8): 3225-3231.
  50. Shan YF, Shen X, Xie KY, Chen JC, Shi HQ, et al. (2009) Inhibitory effects of tanshinone II A on invasion and metastasis of human colon carcinoma cells. Acta Pharmacologica Sinica 30(11): 1537-1542.
  51. Nicolin V, Bossi F, Viggiano A, Valentini R, Nori SL (2013) Tanshinone VI inhibits the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule 1. International Journal Immunopathology and Pharmacology 26(4): 977-982.
  52. Fei AH, Cao Q, Chen SY, Wang HR, Wang FL, et al. (2013) Salvianolate inhibits reactive oxygen species production in H2O2 treated mouse cardiomyocytes in vitro via the TGFβ pathway. Acta Pharmacologica Sinica 34(4): 496-
  53. Cha JD, Lee JH, Choi KM, Choi SM, Park JH (2014) Synergistic effect between cryptotanshinone and antibiotics against clinic methicillin and vancomycin resistant Staphylococcus aureus. Evidence Based Complement. Alternative Medicine 2014: 450572.
  54. Wu TW, Zheng LH, Fung KP, Wu J, Pang H, et al. (1993) Effect of sodium tanshinone IIA sulfonate in the rabbit myocardium and on human cardiomyocytes and vascular endothelial cells. Biochemical Pharmacology 46(12): 2327-2332.
  55. Cheng TO (2006) Danshen a popular Chinese cardiac herbal drug. Journal of the American College of Cardiology 47(7): 1498.
  56. Wu WWP, Yeung JHK (2010) Inhibition of warfarin hydroxylation by major tanshinones of Danshen Salvia miltiorrhiza in the rat in vitro and in vivo. Phytomedicine 17(3-4): 219-226.
  57. Cheng TO (2007) Warfarin interaction with herbal drugs and food. International Journal of Cardiology 119(1): 107-108.
  58. Gupta D, Jalali M, Wells A, Dasgupta A (2002) Drug herb interactions unexpected suppression of free Danshen concentrations by salicylate. Journal of Clinical Laboratory Analysis 16(6): 290-294.
  59. Qiu F, Zhang R, Sun J, Jiye A, Hao H, et al. (2008) Inhibitory effects of seven components of danshen extract on catalytic activity of cytochrome P450 enzyme in human liver microsomes. Drug Metabolism Disposition 36(7): 1308-1314.
  60. Sarkar MA, Hunt C, Guzelian PS, Karnes HT (1992) Characterization of human liver cytochromes P-450 involved in theophylline metabolism. Drug Metabolism Disposition 20(1): 31-37.
  61. Yuan Y, Zhang H, Ma W, Sun S, Wang B, et al. (2013) Influence of compound danshen tablet on the pharmacokinetics of losartan and its metabolite EXP3174 by liquid chromatography coupled with mass spectrometry. Biomedical Chromatography 27(9): 1219- 1224.
  62. Yang Y, Yang S, Chen M, Zhang X, Zou Y (2008) Compound Astragalus and Salvia miltiorrhiza extract exerts anti-fibrosis by mediating TGF-β/Smad signaling in myofibroblasts. Journal of Ethnopharmacology 118(2): 264-270.
  63. Wang L, Chi YF, Yuan ZT, Zhou WC, Yin PH, et al. (2014) Astragaloside IV inhibits renal tubulointerstitial fibrosis by blocking TGF β/Smad signaling pathway in vivo and in vitro. Experimental Biology and Medicine 239(10): 1310-1324.
  64. Wang XP, Wang S, Wang Y, Xu DS, Feng Y (2010) Effect of Astragalus membranaceus polysaccharide on the expression of inflammation cytokines in THP-1 cells. Chinese Journal of Applied Physiology 26(4): 410-411.
  65. Liu X, Yang Y, Zhang X, Xu S, He S, et al. (2010) Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor‐β/ Smad in HepG2 cell. Journal of Gastroenterology Hepatology 25(2): 420-426.
  66. He S, Yang Y, Liu X, Huang W, Zhang X, et al. (2012) Compound Astragalus and Salvia miltiorrhiza extract inhibits cell proliferation invasion and collagen synthesis in keloid fibroblasts by mediating transforming growth factor‐β/Smad pathway. British Journal of Dermatology 166(3): 564-574.
  67. Rui W, Xie L, Liu X, He S, Chao W, et al. (2014) Compound Astragalus and Salvia miltiorrhiza extract suppresses hepatocellular carcinoma progression by inhibiting fibrosis and PAI-1 mRNA transcription. Journal of Ethnopharmacology 151(1): 198-209.
  68. Boye A, Wu C, Jiang Y, Wang J, Wu J, et al. (2015) Compound Astragalus and Salvia miltiorrhiza extracts modulate MAPK regulated TGF-β/Smad signaling in hepatocellular carcinoma by multi target mechanism. Journal of Ethnopharmacology 169: 219-228.
  69. Wu C, Jiang J, Boye A, Jiang Y, Yang Y, et al. (2014) Compound Astragalus and Salvia miltiorrhiza extract suppresses rabbits hypertrophic scar by modulating the TGF-β/Smad signal. Dermatology 229(4): 363-368.
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@article{alex2023,
  title   = {Astragalus Membranaceus and Salvia Miltiorrhizae: An Overview
of Ethnopharmacology and Phytochemistry},
  author  = {Alex Boye},
  journal = {International Journal of Pharmacognosy & Chinese Medicine},
  year    = {2023},
  volume  = {7},
  number  = {2},
  doi     = {10.23880/ipcm-16000252}
}
Alex Boye (2023). Astragalus Membranaceus and Salvia Miltiorrhizae: An Overview
of Ethnopharmacology and Phytochemistry. International Journal of Pharmacognosy & Chinese Medicine, 7(2). https://doi.org/10.23880/ipcm-16000252
TY  - JOUR
TI  - Astragalus Membranaceus and Salvia Miltiorrhizae: An Overview
of Ethnopharmacology and Phytochemistry
AU  - Alex Boye
JO  - International Journal of Pharmacognosy & Chinese Medicine
PY  - 2023
VL  - 7
IS  - 2
DO  - 10.23880/ipcm-16000252
ER  -