Volume 155, Issue 3, 29 September 2014, Pages 1401–1416
Review
Salvia miltiorrhiza: An ancient Chinese herbal medicine as a source for anti-osteoporotic drugs
Abstract
Ethnopharmacological relevance
Red sage (Salvia miltiorrhiza
Bunge), also known as Danshen in Chinese, has been used historically
and is currently exploited in combination with other herbs to treat
skeletal diseases in traditional Chinese medicine (TCM). With the
advance of modern analytical technology, a multitude of bone-targeting,
pharmaceutically active, compounds has been isolated and characterized
from various sources of TCM including those produced in Salvia miltiorrhiza root. The aim of the review is to provide a comprehensive overview about the historical TCM interpretation of the action of Salvia miltiorrhiza
in osteoporosis, its use clinical trials, its main phytochemical
constituents, and its action on bone-resorptive and bone
formation-stimulating mechanisms in in vitro and in vivo studies.
Materials and methods
Literature
sources used were Pubmed, CNKI.net, Cqvip.com, PubChem, and the Web of
Science. For the inquiry, keywords such as Salvia, danshen,
osteoporosis, bone, osteoclast and osteoblast were used in various
combinations. About 130 research papers and reviews were consulted.
Results
In TCM, the anti-osteopororotic effect of Salvia miltiorrhiza
is ascribed to its action on liver and blood stasis as main therapeutic
targets defining osteoporosis. 36 clinical trials were identified which
used Salvia miltiorrhiza in combination with other herbs and
components to treat post-menopausal, senile, and secondary osteoporosis.
On average the trials were characterized by high efficacy (>80%) and
low toxicity problems. However, various limitations such as small
patient samples, short treatment duration, frequent lack of detailed
numerical data, and no clear endpoints must be taken into consideration.
To date, more than 100 individual compounds have been isolated from
this plant and tested in various animal models and biochemical assays.
Compounds display anti-resorptive and bone formation-stimulating
features targeting different pathways in the bone remodeling cycle.
Pathways affected include the activation of osteoblasts, the modulation
of osteoclastogenesis, and the inhibition of collagen degradation by
cathepsin K.
Conclusions
The inclusion of Salvia miltiorrhiza
in more than 30% of all herbal clinical trials successfully targeting
osteoporosis has stimulated significant interest in the identification
and characterization of individual constituents of this herb. The review
highlights the anti-osteoporotic potential of Salvia miltiorrhiza
in clinical applications and the potential of the herb to provide
potent compounds targeting specific pathways in bone resorption and bone
formation.
Graphical abstract
Abbreviations
- ALP, alkaline phosphatase;
- AKT, also known as protein kinase B;
- BGP, bone-Gla protein;
- BMC, bone mineral content;
- BMD, bone mineral density;
- c-Fos, cellular proto-oncogene;
- COX-2/PGE2, cyclooxygenase-2/prostaglandin E2;
- DEXA, dual-energy x-ray absorptiometry, ERK, extracellular-signal regulated kinase;
- Il-6, interleukin-6;
- MAP kinases, mitogen-activated protein kinases;
- NFATc1, nuclear factor of activated T-cells 1;
- µCT, micro computed tomography, NFκB, nucleic factor kappa-B;
- ovx, ovariectomized;
- RANKL, receptor activator of nuclear factor kappa-B ligand;
- Sal A, salvianolic acid A;
- Sal B, salvianolic acid B;
- TCM, traditional Chinese medicine;
- TNF-α, tissue necrosis factor-alpha;
- TRAP-5b, tartrate resistant alkaline phosphatase 5b
Chemical compounds studied in this article
- Salvianolic acid A, CID 5281793;
- salvianolic acid B (Synonym: Salvianic acid B), CID 11629084;
- tanshinone I, CID 114917;
- tanshinone IIA, CID 164676;
- cryptotanshinone, CID 160254;
- caffeic acid, CID 689043;
- p-coumaric acid, CID 637542;
- ursolic acid, CID 64945;
- oleanolic acid, CID 10494;
- raloxifene, CID 5035
Keywords
- Salvia miltiorrhiza;
- Danshen;
- Osteoporosis;
- Anti-resorptive activity;
- Pro-anabolic activity
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