Xinxiang Wang

Puerariae radix prevents bone loss in ovariectomized mice

Puerariae radix (PR), the root of Pueraria labata (Willd.) Ohwi, a wild creeper leguminous plant, is one of the earliest and most important crude herbs used in Chinese medicine for various medicinal purposes. PR contains a high amount of isoflavonoids such as daidzein and genistein, which are known to prevent bone loss induced by estrogen deficiency. We have demonstrated that soybean isoflavones prevent bone loss in an osteoporotic animal model. To examine the possible role of PR in bone metabolism, female mice were ovariectomized (OVX), and some OVX mice were fed a diet containing low, middle, and high doses (5%, 10%, and 20% of diet, respectively) of PR for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight. The total femoral bone mineral density (BMD) was significantly reduced by OVX, and the decrease in BMD caused by OVX was significantly inhibited by intake of the diet with the low dose of PR and completely prevented by the middle dose of PR. Histological analysis of the femoral metaphysis showed that intake of the diet with the middle dose of PR completely prevented decrease in trabecular bone volume (BV/TV) and trabecular thickness (Tb.Th) and restored the increase in trabecular separation (Tb.Sp) in OVX mice. In contrast, intake of the diet with the high dose of PR further increased BV/TV and Tb.Th and decreased Tb.Sp in OVX mice compared with that in the sham-operated mice. These results suggest that PR may represent a potential alternative medicine for hormone replacement therapy (HRT) in the prevention of osteoporosis in postmenopausal women.

Effects of Geranylgeranoic Acid in Bone: Induction of Osteoblast Differentiation and Inhibition of Osteoclast Formation

Retinoids are known to be of special importance for normal bone growth and development. Recently, we reported that retinoids not only induced osteoblast differentiation, but also inhibited osteoclast formation in vitro. In this study, we examined the osteogenic effects of geranylgeranoic acid (GGA), a chemically synthesized acyclic retinoid, in bone in vitro and in vivo. GGA not only suppressed proliferation of osteoblastic MC3T3‐E1 cells, but also up‐regulated differentiation markers of osteoblasts such as alkaline phosphatase (ALP) activity and expression of osteopontin (OP) messenger RNA (mRNA). In contrast, GGA inhibited osteoclast formation induced by 1α,25‐dihydroxyvitamin D3 [1α,25(OH)2D3] in cocultures of mouse bone marrow cells and primary osteoblasts. Treatment of stromal ST2 cells with GGA restored the 1α,25(OH)2D3‐ or prostaglandin E2 (PGE2)‐induced suppression of osteoprotegerin (OPG) mRNA expression. GGA inhibited osteoclast formation induced by macrophage colony‐stimulating factor (M‐CSF) and soluble receptor activator of nuclear factor κB ligand (sRANKL) in the culture of bone marrow macrophages. Thus, it is likely that GGA inhibits osteoclast formation by affecting both osteoblasts and osteoclast progenitors in the coculture system. Furthermore, in vivo, GGA increased bone mineral density (BMD) of total as well as distal femur in a P6 strain of senescence‐accelerated mice (SAMP6). These results indicate that GGA increases bone mass by maintaining a positive balance of bone turnover by inducing osteoblast differentiation and suppressing osteoclast formation.

Puerarin prevents bone loss in ovariectomized mice and inhibits osteoclast formation in vitro

The present study aimed at investigating the effects of Puerarin (PR), a major isoflavonoid isolated from the Chinese medicinal herb Puerariae radix, on bone metabolism and the underlying mechanism of action. The in vivo assay, female mice were ovariectomized (OVX), and the OVX mice were fed with a diet containing low, middle, and high doses of PR (2, 4, and 8 mg·d(-1), respectively) or 17β-estradiol (E2, 0.03 μg·d(-1)) for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight, compared with the control. The total femoral bone mineral density (BMD) was significantly reduced by OVX, which was reversed by intake of the diet with PR at any dose, especially at the low dose. In the in vitro assay, RAW264.7 cells were used for studying the direct effect of PR on the formation of osteoclasts. PR reduced the formation of tartrate resistant acid phosphatase (TRAP)-positive multi-nucleated cells in the RAW 264.7 cells induced by receptor activator for nuclear factor-κB Ligand (RANKL). MC3T3-E1 cells were used for studying the effects of PR on the expression of osteoprotegerin (OPG) and RANKL mRNA expression in osteoblasts. The expression of OPG mRNA and RANKL mRNA was detected by RT-PCR on Days of 5, 7, 10, and 12 after PR exposure. PR time-dependently enhanced the expression of OPG mRNA and reduced the expression of RANKL mRNA in MC3T3-E1 cells. In conclusion, our results suggest that PR can effectively prevent bone loss in OVX mice without any hyperplastic effect on the uterus, and the antiosteoporosis activity of PR may be related to its effects on the formation of osteoclasts and the expression of RANKL OPG in osteoblasts.

The Influence of BuqiHuoxueTongluo Formula on Histopathology and Pulmonary Function Test in Bleomycin-Induced Idiopathic Pulmonary Fibrosis in Rats

BuqiHuoxueTongluo Formula (BHTF) is an effective herbal prescription based on traditional Chinese medicine for idiopathic pulmonary fibrosis (IPF). The aim of this study was to elucidate the influence of BHTF on induced IPF model through the aspect of histopathology and pulmonary function test. Wistar rats with bleomycin-induced IPF were given BHTF via intragastric gavage. After 14 days and 28 days of treatment, respectively, on these two time points, we first performed pulmonary function test, performed ventilation measure, and traced the Pressure-Volume Loop under anesthesia. Then, rats were sacrificed for hematoxylin-eosin and Massons trichrome staining, immunohistochemistry staining of TGF-β1 and α-SMA, and observation through transmission electron microscope. BHTF reduced infiltration of inflammation cells, collagen deposition, and fibrosis proliferation in pulmonary mesenchyme, inhibited the expression of TGF-β1 and α-SMA, and avoided the abnormality of ultrastructure and quantities of lamellar bodies. It also ameliorated the parameters of FVC, MVV, PEF, FEF25, and Cdyn, maintained the shape of the Pressure-Volume Loop, and improved hysteresis. BHFT relieved the histopathologic changes, improved ventilation function, compliance, and work of breathing, meliorated the capacity and elasticity of the lungs, and stabilized the alveolar surface tension. Further speaking, it had a potential impact on the secretion of pulmonary surfactant.