Study ids alternative to HRT in 800-yr-old decoction
CM NEWS – It’s well known that menopausal women using estrogen replacement therapy are exposed to an increased risk of developing breast cancer. A group of scientists have found hope in an 800-year-old Chinese herbal decoction which has been used in age-related illness of women. The science behind the decoction and the optimal proportion of each herb have been uncovered. Scientists are hopeful the formula might offer alternative to HRT for menopausal women.
The study was a joint project by scientists of the Hong Kong University of Science and Technology, Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine and Beijing Friendship Hospital.
The researchers note that estrogen deficiency is the major cause in developing post-menopausal osteoporosis. Estrogen acts on both osteoblast and osteoclast to inhibit bone breakdown at all stages of life. After menopause, estrogen replacement therapy is an effective treatment for osteoporosis as well as to allay other menopausal symptoms. However, estrogen therapy recently became a subject of debate because clinical studies revealed an increased risk of breast cancer and coronary artery disease in women who take estrogen.
Amongst thousands of herbal formulae from traditional Chinese medicine, Danggui Buxue Tang (????? DBT; a herbal decoction) is a simple combination of two herbs. DBT was first described in Neiwaishang Bianhuo Lun (??????) by Li Dongyuan (???) in China in AD 1247. In other words, DBT is a 800-year-old decoction formula.
Li described the DBT formula should include:
- Radix Astragali (huangqi ??) 30g
- Radix Angelicae Sinensis (danggui ??) 6g
In preparing DBT, the mixed herbs were recommended to boil in two bowls of water over a moderate heat until the final volume was reduced by half. Traditionally, DBT has been prescribed to women in China as a remedy for menopausal symptoms. According to Chinese medicinal theory, the daily intake of DBT could raise the ‘Qi’ and nourish the ‘Blood’ of menopausal women.
What is the use of DBT? Pharmacological results indicated that DBT has the abilities to promote hematopoietic functions:
- to stimulate cardiovascular circulation;
- to prevent osteoporosis;
- to increase anti-oxidation activity,
- to stimulate immune response and to mimic estrogen effects in the receptor phosphorylation.
In traditional Chinese medicine, huangqi and danggui are commonly used in treating age-related diseases, which have been demonstrated in stimulating bone cell proliferation, increasing bone formation and reducing bone re-sorption in patients. By determining the chemical and biological properties of DBT, the optimized conditions of extraction have been established, which, interestingly, are in accordance with the weight ratio of 5:1 for huangqi to danggui in the ancient preparation.
In the present study, cultured csteosarcoma cells were used to determine the effectiveness of DBT. Primary cultures of rat osteoblasts were treated with 1 mg ml–1 DBT, huangqi or danggui extract for 12 hours.
To further support the beneficial roles of DBT on bone development, the primary culture of rat osteoblasts was employed as another study model. The osteoblastic cultures were treated with different extracts for 96 hours and collected to perform cell proliferation and alkaline phosphatase assays. As expected, DBT increased the cell proliferation and alkaline phosphatase activity by approx. 20%.
The researchers were also able to confirm scientifically the optimal proportion of the two herbs used in DBT. By discovering the amounts of two chemical markers in huangqi (calycosin and formononetin) and two others in danggui (ferulic acid and ligustilide), the researchers were able to standardize the optimal DBT. They found that the standardized DBT should contain (per 1 g dried weight of DBT):
- 0.186 mg calycosin
- 0.155 mg formononetin
- 0.351 mg ferulic acid
- 0.204 mg ligustilide
In addition, a standardized extract of huangqi in 1 g should contain 0.088 mg calycosin and 0.142 mg formononetin, while the extract of danggui in 1 g should have 0.293 mg ferulic acid and 0.316 mg ligustilide.
Application of DBT onto osteoblastic cells triggered the downstream signaling cascades including the Erk-dependent and ER (estrogen receptor)-dependent pathways. These actions would trigger cell death, or apoptosis.
What are Erk-dependent pathways? The ErK pathway is a signal transduction pathway that couples intracellular responses to the binding of growth factors to cell surface receptors. This pathway is very complex and includes many protein components. In many cell types, activation of this pathway promotes cell division.
Such signaling activations finally resulted in stimulating cell proliferation, osteogenic differentiation and a set of DBT-regulated gene transcription. DBT possesses a better effect in stimulating cell proliferation and differentiation in cultured osteosarcoma cells and primary osteoblasts, as compared to that of the extracts derived from huangqi or danggui or huangqi + danggui (boiled separately and then mixed together in 5:1 ratio).
Genomic analysis revealed a specific set of genes being regulated by DBT, but not by huangqi or danggui alone. These results therefore provide evidence of the uniqueness of specific combination of huangqi and danggui in creating the formulation of DBT.
In addition, the insufficient stimulating effect of huangqi + danggui in cultured osteosarcoma cells suggests tat boiling of the two herbs together is essential; this method of DBT preparation, indeed, has long been recommended by Chinese medicinal practitioners.
The scientists suggest that DBT could be developed as alternative medicines for the patients, because:
- DBT has been used over 800 years in China, which has been proven to be safe for human;
- DBT does not alter the proliferation of the breast cancer cells, even at higher concentration;
- DBT improves biochemical and physiological responses, both in vitro and in vivo that are related to menopausal women.