Puerarin Exerted Anti-Osteoporotic Action Independent of Estrogen Receptor-Mediated Pathway

Michihara, Seiwa; Tanaka, Teruyoshi; Uzawa, Yuki; Moriyama, Tatsuya; Kawamura, Yukio

doi:10.3177/jnsv.58.202

Cited by 46 publications

(30 citation statements)

References 21 publications

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“…Some preclinical in vivo and in vitro studies reported that puerarin was able to enhance new bone formation, [22][23][24] and prevent bone loss through an estrogen-like effect. 10,25,26) Consistent with their results, puerarin inhibited LPS-induced TRAP(+) MNCs formation in a dosedependent manner (Fig. 2), and the maximal concentration for inhibiting osteoclast formation at 50 µmol/L was higher than that of genistein (0.01-1 µmol/L) or daidzein (0.1-10 µmol/L) on osteoclastogenesis induced by TNF-α or RANKL in the same cells, respectively.…”

Section: Discussionsupporting

confidence: 74%

Puerarin Prevents LPS-Induced Osteoclast Formation and Bone Loss via Inhibition of Akt Activation

Zhang

Yan

et al. 2016

Biological & Pharmaceutical Bulletin

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Osteolysis induced by chronic Gram-negative bacterial infection underlies many bone diseases such as osteomyelitis, septic arthritis, and periodontitis. Drugs that inhibit lipopolysaccharide (LPS)-induced osteolysis are critically needed for the prevention of bone destruction in infective bone diseases. In this study, we assessed the effect of puerarin, a natural isoflavone isolated from Pueraria lobata OHWI root, on LPS-induced osteoclastogenesis and bone loss. Our in vitro study showed that puerarin significantly inhibited LPS-induced osteoclast differentiation from osteoclast precursor RAW264.7 cells. The inhibition occurred through suppressing the production of osteoclast activating factor tumor necrosis factor (TNF)-α, interleukin (IL)-1β and prostaglandin E 2 (PGE 2 ), which led to down-regulating mRNA expression of osteoclastogenic genes including tartrate-resistant acid phosphatase (TRAP), cathepsin K and matrix metalloprotein 9 (MMP-9). Furthermore, LPS triggered activation of Akt in osteoclast precursor RAW264.7 cells, which was inhibited by puerarin treatment. In vivo, puerarin attenuated LPS-induced bone loss in a murine calvarial osteolysis model. Collectively, puerarin prevents LPS-induced osteoclast formation, function and bone loss, where the inhibition of Akt activation plays an important role. These findings provide evidences that puerarin might be beneficial as a promising candidate drug for the prevention and treatment of bacteria-induced bone destruction disease, and give new insights for understanding its possible mechanism.

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Section: Discussionsupporting

confidence: 74%

Puerarin Prevents LPS-Induced Osteoclast Formation and Bone Loss via Inhibition of Akt Activation

Zhang

Yan

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Thus, PVEE and puerarin appeared to behave in a different manner to E2. We previously reported that puerarin did not bind to estrogen receptor a or b, while daidzein can bind to estrogen receptors (26). Therefore, the mechanism by which puerarin improved glucose metabolism probably does not involve estrogen-like activity.…”

Section: Discussionmentioning

confidence: 99%

Anti-Hyperglycemic Effect of a Kudzu (Pueraria lobata) Vine Extract in Ovariectomized Mice

Tanaka

Yukihiro

Tang

et al. 2016

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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Summary Postmenopausal diabetes is exacerbated by estrogen deficiency. Ovariectomized (OVX) animal models can be used to develop strategies for preventing or treating postmenopausal symptoms. We previously found that a diet containing kudzu (Pueraria lobata) vine ethanol extract (PVEE) suppressed weight gain in OVX mice. Therefore, this study further elucidated how PVEE affected OVX mice. Ten-week-old OVX or sham-operated mice were fed diets containing either no PVEE (control) ·d 21 puerarin (daidzein-8-C-glucoside), a major isoflavone present in PVEE, for 10 wk. The effects of puerarin on glucose tolerance were also tested in OVX mice. The experimental diets were not associated with any abnormalities in any mice tested in the present study. Weight gain and serum glucose levels were increased in OVX mice and these effects were significantly attenuated in OVX mice that consumed PVEE (5 or 20 mg·kg 21 ·d 21 ) or puerarin. Puerarin-treated OVX mice also showed reduced serum glucose levels following administration of 1,000 mg·kg 21 glucose. These results suggested that puerarin contributed to PVEE-mediated improvements in glucose metabolism in OVX mice. Although further studies are needed to clarify the molecular mechanism underlying these observations, PVEE and puerarin could provide effective approaches to the amelioration of postmenopausal diabetes. Key Words Kudzu, Pueraria lobata, postmenopausal diabetes, puerarin, glucose metabolism Postmenopausal women have an increased risk for metabolic diseases such as obesity and diabetes (1, 2), which increase their risk of developing other serious conditions including cancers, neurological disorders, hypertension, and other kinds of cardiovascular disease (3). Postmenopausal diabetes is induced by estrogen deficiency, which exacerbates insulin resistance (4, 5). The number of postmenopausal patients with diabetes has recently increased, due to the increasing age of the population. Therefore, dietary strategies to reduce the risk for diabetes are expected to be necessary in order to improve postmenopausal health.Kudzu (Pueraria lobata) is a creeping vine of the Leguminosae family. The plant has spread worldwide and is predominantly found in temperate climates. Dried kudzu roots (Puerariae radix) are traditionally used in Asian countries, including Japan, as an herbal medicine to treat the common cold, headaches, diarrhea, and hypertension. Prasain et al. demonstrated that kudzu root extract ameliorated impaired glucose and lipid metabolism in obese male mice (6). They also reported that in addition to lowering arterial blood pressure, a kudzu root extract diet significantly reduced blood cholesterol, glucose, and insulin levels in stroke-prone spontaneously hypertensive rats (7).Pharmaceutical legislation in Japan classifies the kudzu root as a medicinal resource, rather than a food, and we therefore investigated whether dietary consumption of other parts of the plant had beneficial effects on postmenopausal diabetes. Our previous study of a kudzu vine ethanol extract ...

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“…However, our previous experiments showed that uterine atrophy due to estrogen deficiency was unaltered by a puerarin-rich diet in OVX mice (7,40). Moreover, although the puerarin aglycone daidzein bound to estrogen receptors, puerarin did not bind estrogen receptors ␣ or ␤ (40).…”

Section: Discussionmentioning

confidence: 99%

Puerarin Suppresses Macrophage Activation via Antioxidant Mechanisms in a CaPO4-Induced Mouse Model of Aneurysm

Tanaka

Moriyama

Kawamura

et al. 2016

J Nutr Sci Vitaminol

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SummaryAneurysm is characterized by balloon-like expansion of the arterial wall and eventual rupture of the aorta. The pathogenesis of aneurysm is associated with the degradation of matrix proteins by matrix metalloproteinases (MMPs) produced by activated macrophages. Although aneurysm is associated with significant mortality and morbidity, surgical intervention is the only proven treatment strategy. Therefore, development of therapeutic agents for aneurysm is greatly anticipated. Here, we demonstrated the protective effects of the major isoflavone puerarin, which is found in kudzu roots and vines. Aneurysms were surgically induced in ten-wk-old male mice using CaPO4. Subsequently, animals were intraperitoneally injected daily with puerarin at 2.5 mg/kg body weight or with vehicle alone for 2 wk. CaPO4-induced aneurysm was significantly suppressed by puerarin administration. In subsequent macrophage activation assays using Tumor necrosis factor (TNF␣) and CaPO4 crystals in vitro, puerarin decreased Mmp9 mRNA expression and secreted protein levels. Moreover, induction of IB, ERK, and p38 phosphorylation by TNF␣ and CaPO4 in macrophages was suppressed by puerarin treatments. Finally, puerarin attenuated reactive oxygen species production, following induction by TNF␣ and CaPO4. Taken together, the present data demonstrate that puerarin suppresses macrophage activation by inhibiting IB, ERK, and p38 activity and reactive oxygen species production in a CaPO4-induced mouse model of aneurysm.

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Puerarin Exerted Anti-Osteoporotic Action Independent of Estrogen Receptor-Mediated Pathway

Cited by 46 publications

References 21 publications

Puerarin Prevents LPS-Induced Osteoclast Formation and Bone Loss <i>via</i> Inhibition of Akt Activation

Puerarin Prevents LPS-Induced Osteoclast Formation and Bone Loss <i>via</i> Inhibition of Akt Activation

Anti-Hyperglycemic Effect of a Kudzu (<i>Pueraria lobata</i>) Vine Extract in Ovariectomized Mice

Puerarin Suppresses Macrophage Activation via Antioxidant Mechanisms in a CaPO<sub>4</sub>-Induced Mouse Model of Aneurysm

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