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Effects of Dihydrophaseic Acid 3'-O-?-d-Glucopyranoside Isolated from Lycii radicis Cortex on Osteoblast Differentiation.

ABSTRACT: Our previous study showed that ethanol extract of Lyciiradicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the bone formation-enhancing effect of LRC extract. A known sesquiterpene glucoside, (1'R,3'S,5'R,8'S,2Z,4E)-dihydrophaseic acid 3'-O-?-d-glucopyranoside (abbreviated as DPA3G), was isolated from LRC extract and identified as a candidate constituent. We investigated the effects of DPA3G on osteoblast and osteoclast differentiation, which play fundamental roles in bone formation and bone resorption, respectively, during bone remodeling. The DPA3G fraction treatment in mesenchymal stem cell line C3H10T1/2 and preosteoblast cell line MC3T3-E1 significantly enhanced cell proliferation and alkaline phosphatase activity in both cell lines compared to the untreated control cells. Furthermore, DPA3G significantly increased mineralized nodule formation and the mRNA expression of osteoblastogenesis markers, Alpl, Runx2, and Bglap, in MC3T3-E1 cells. The DPA3G treatment, however, did not influence osteoclast differentiation in primary-cultured monocytes of mouse bone marrow. Because osteoblastic and osteoclastic precursor cells coexist in vivo, we tested the DPA3G effects under the co-culture condition of MC3T3-E1 cells and monocytes. Remarkably, DPA3G enhanced not only osteoblast differentiation of MC3T3-El cells but also osteoclast differentiation of monocytes, indicating that DPA3G plays a role in the maintenance of the normal bone remodeling balance. Our results suggest that DPA3G may be a good candidate for the treatment of osteoporosis.

SUBMITTER: Park E

PROVIDER: S-EPMC6274582 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Effects of Dihydrophaseic Acid 3'-O-β-d-Glucopyranoside Isolated from Lycii radicis Cortex on Osteoblast Differentiation.

Park Eunkuk E Kim Mun-Chang MC Choi Chun Whan CW Kim Jeonghyun J Jin Hyun-Seok HS Lee Ryunjin R Lee Ji-Won JW Park Jin-Hyok JH Huh Dam D Jeong Seon-Yong SY

Molecules (Basel, Switzerland) 20160921 9

Our previous study showed that ethanol extract of Lyciiradicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the bone formation-enhancing effect of LRC extract. A known sesquiterpene glucoside, (1'R,3'S,5'R,8'S,2Z,4E)-dihydrophaseic acid 3'-O-β-d-gluc ...[more]

PMID: 27657033

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Project description:Lycii radicis cortex (LRC) has been used to regulate high blood pressure, body temperature, pain and bone disorders in East Asia. Glucocorticoids (GCs), also known as steroids, are potent immunity regulators widely used in the treatment of inflammatory diseases. However, despite their effectiveness, GC usage is strictly controlled due to severe side‑effects, such as osteoporosis. However, further research is required as to date, at least to the best of our knowledge, there is no appropriate model to overcome secondary osteoporosis as a side‑effect of GC use. Thus, the aim of the present study was to establish an experimental model of osteoporosis induced by GC. Furthermore, the present study aimed to establish the research methodology for medical evaluations of the effectiveness and side‑effects of GCs. A secondary osteoporosis animal model was established, and the animals were divided into two groups as follows: The allergic contact dermatitis (ACD)‑induced group and the non‑ACD‑induced group. In the ACD‑induced group, a GC topical application group was compared with a GC subcutaneous injection group. The results revealed that the presence of ACD affected the induction of GC‑mediated osteoporosis. Therefore, the group exhibiting induced ACD that was treated with a topical application of GC was selected for examining the side‑effects of GCs. The effects of LRC on secondary osteoporosis were confirmed in vivo and in vitro. The results indicated that LRC regulated dexamethasone‑induced osteoblast apoptotic markers, including caspase‑6, caspase‑9, X‑linked inhibitor of apoptosis, apoptosis inhibitor 1 and apoptosis inhibitor 2, and increased the expression of osteoblast differentiation‑related genes, such as Runt‑related transcription factor 2 and bone morphogenetic protein 2 in the MC3T3E‑1 cell line. LRC also significantly reduced GC‑induced osteoporosis and exerted anti‑inflammatory effects in vivo. In addition, LRC inhibited the reduction of calbindin‑D28k in the kidney. Overall, the results of the present study suggest that the use of LRC alleviates GC‑induced secondary osteoporosis.

Dataset Information

Effects of Dihydrophaseic Acid 3'-O-?-d-Glucopyranoside Isolated from Lycii radicis Cortex on Osteoblast Differentiation.

Publications

Effects of Dihydrophaseic Acid 3'-O-β-d-Glucopyranoside Isolated from Lycii radicis Cortex on Osteoblast Differentiation.

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