Quercetin prevents bone loss in hindlimb suspension mice via stanniocalcin 1-mediated inhibition of osteoclastogenesis.

Recent studies demonstrate that diet quercetin (Quer) has obvious bone protective effects on ovariectomized rodents but thus far there is no direct evidence to support the inhibitory effect of Quer on bone loss caused by long-term unloading. In the present study, we investigated whether Quer could prevent bone loss induced by unloading in mice. Mice were subjected to hindlimb suspension (HLS) and received Quer (25, 50, 100 mg· kg-1 ·day-1, ig) for 4 weeks. Before euthanasia blood sample was collected; the femurs were harvested and subjected to MicroCT analysis. We showed that Quer administration markedly improved bone microstructure evidenced by dose-dependently reversing the reduction in bone volume per tissue volume, trabecular number, and bone mineral density, and the increase of trabecular spacing in mice with HLS. Analysis of serum markers and bone histometric parameters confirmed that Quer at both middle and high doses significantly decreased bone resorption-related markers collagen type I and tartrate-resistant acid phosphatase 5b, and increased bone formation-related marker procollagen 1 N-terminal propeptide as compared with HLS group. Treatment with Quer (1, 2, 5 µM) dose-dependently inhibited RANKL-induced osteoclastogenesis through promoting the expression of antioxidant hormone stanniocalcin 1 (STC1) and decreasing ROS generation; knockdown of STC1 blocked the inhibitory effect of Quer on ROS generation. Knockdown of STC1 also significantly promoted osteoclastogenesis in primary osteoclasts. In conclusion, Quer protects bones and prevents unloading-caused bone loss in mice through STC1-mediated inhibition of osteoclastogenesis. The findings suggest that Quer has the potential to prevent and treat off-load bone loss as an alternative supplement.

Antiosteoporosis effect of radix scutellariae extract on density and microstructure of long bones in tail-suspended sprague-dawley rats.

Radix Scutellariae (RS), a medicinal herb, is extensively employed in traditional Chinese medicines and modern herbal prescriptions. Two major flavonoids in RS were known to induce osteoblastic differentiation and inhibit osteoclast differentiation, respectively. This study aimed to investigate the effect of Radix Scutellariae extract (RSE) against bone loss induced by mechanical inactivity or weightlessness. A hindlimb unloading tail-suspended rat model (TS) was established to determine the effect of RSE on bone mineral density and bone microarchitecture. Treatment of RSE at 50 mg/kg/day and alendronate (ALE) at 2 mg/kg/day as positive control for 42 days significantly increased the bone mineral density and mechanical strength compared with TS group. Enhanced bone turnover markers by TS treatment were attenuated by RSE and ALE administration. Deterioration of bone trabecula induced by TS was prevented. Moreover, both treatments counteracted the reduction of bone volume fraction, trabecular thickness and number, and connectivity density. In conclusion, RSE was demonstrated for the first time to prevent osteoporosis induced by TS treatment, which suggests the potential application of RSE in the treatment of disuse-induced osteoporosis.

A systematic review of the efficacy and pharmacological profile of Herba Epimedii in osteoporosis therapy.

The purpose of this systematic review is to assess the efficacy and pharmacological profiles of Herba Epimedii in osteoporosis therapy. Four databases were extensively retrieved that include two Chinese electronic databases (VIP Information and CNKI) and two English electronic databases (CA and MEDLINE). Herba Epimedii has been an important traditional herbal medicine for centuries in China and other Asian countries. Recently, quite a few pharmacological effects of Herba Epimedii, its extracts and active components have been identified that include improving bone health and cardiovascular function, regulating hormone level, modulating immunological function, and inhibiting tumor growth. The anti-osteoporosis activity of Herba Epimedii and its extracts have attracted world-wide attention. The literature search has revealed that a lot of studies have recently been carried out related to the bone-strengthening activity of Herba Epimedii and some of its active compounds, such as total flavonoids and icariin. Pharmacokinetic and toxicity studies have confirmed the efficacy and safety of Herba Epimedii and its most abundant active component icariin, while only a few authors have reviewed the anti-osteoporosis properties of the plants. So we summarize the work of various investigators on the effects of Herba Epimedii, its extracts and active components against osteoporosis. The underlying mechanism of osteoprotective action, derivatives of icariin, animal models and cell lines used in the research were also reviewed in this paper.

[Effects of naringin on proliferation, differentiation and maturation of rat calvarial osteoblasts in vitro].

OBJECTIVE: To investigate the effects of naringin on the proliferation, differention and maturaion of rat calvarial osteoblasts (ROB). METHOD: Segregated neonatal SD rat skull, enzyme digestion to obtain ROB. The culture medium was replaced every three days. Serial subcultivation proceeded when cells covered with 80% culture dish. Naringin supplemented into the culture at 1 x 10(-4), 1 x 10(-5), 1 x 10(-6), 1 x 10(-7) mol x L(-1) respectively. MTT method was adopted in proliferation analysis and the activity of ALP was examined after induced 9 days. Search the best concentration and supplemented into the medium, then the osteogenic differentiation markers including the secretion amount of osteocalcin, osteopontin and bone morphogenetic protein-2 were compared between the naringin-supplemented group and the control. Total RNA was isolated and the mRNA level of bFGF, IGF-1, Runx-2, Osterix, ERa and ERbeta was investigated by Real time RT-PCR. Total protein also was isolated and the expression ERa, ERbeta and collagen I was examined by Western blot. After the addition of ICI 182.780, an inhibitor of the estrogen signal pathway, these index also was examined and the changes were compared. RESULT: The ROB proliferation was motivated by naringin dose-dependently. And it evidently leads to osteogenic process and maturation. 1 x 10(-5) mol x L(-1) is the best concentration. Naringin improved the secretion of osteocalcin, osteopontin, bone morphogenetic protein-2 and collagen I significantly. Besides, it can also enhanced the mRNA level of bFGF, IGF-1, Runx-2, Osterix, ERalpha and ERbeta. While all these effects can be restrained by ICI 182.780. CONCLUSION: The naringin with final concentration of 1 x 10(-5) mol x L(-1) enhances the osteogenic differentiation and maturation of ROB significantly, while the promoting effects vanished after the addition of ICI 182.780. These results suggesting that naringin is one of the phytoestrogens and have the activity of bone formation may via estrogen signal pathway, it can be developed into a new drug for osteoporosis therapy.

In vitro and in situ evaluation of herb-drug interactions during intestinal metabolism and absorption of baicalein.

ETHNOPHARMACOLOGICAL RELEVANCE: Baicalein (B), a bioactive flavone isolated from the root of a traditional Chinese medicinal herb Scutellaria baicalensis Georgi, was found to undergo extensive intestinal Phase II metabolism during its absorption process. Compounds sharing the same metabolic pathways with B or being inhibitors of enzymes UGT and SULT are expected to interfere with the metabolism of B leading to alteration of the absorption of B. The present study aims to identify potential intestinal absorption and metabolism interactions between B and four selected compounds, namely acetaminophen (APAP), (-)-epicatechin (EC), piperine (PIP) and curcumin (CUR) using in vitro and in situ models. MATERIALS AND METHODS: Three in vitro and one in situ methods were employed to investigate the effect of selected compounds on the metabolism and absorption on B. Incubation studies using rat intestinal s9 and Caco-2 cell lysate were used to study the effect of selected compounds on glucuronidation and sulfation of B. Sigmoidal dose-response curves were plotted and IC(50) values were estimated. Apical to basolateral absorption study using Caco-2 cell monolayer model was also employed to study the effect of selected compounds on absorption of B. The most potent inhibitor identified was selected to further investigate its potential herb-drug interaction with B using in situ rat intestinal perfusion model. LC/MS/MS was used for the analysis of B and its metabolites in collected samples. RESULTS: It was found that all the four selected compounds could produce a dose-dependent inhibition on the glucuronidation and sulfation of B. Moreover, the presence of CUR and high-dose EC demonstrated a subsequent increase in the absorption of B. In general, the order of potency on glucuronidation inhibition is: CUR>PIP>EC>APAP; while the potency order on sulfation inhibition is: CUR>EC>PIP>APAP. CUR was selected to further study its in vivo effect on B using in situ rat intestinal perfusion model. It was found that CUR could significantly increase the absorption of B via the inhibition on formation of its metabolites. CONCLUSIONS: Our findings indicated that the intestinal metabolism of B could be inhibited by all the selected compounds with CUR being the most potent inhibitor, which could result in subsequent increase of absorption of B. The current study had significant implications for further investigation on the in vivo evaluations of the herb-drug and herb-herb interactions between B and selected compounds, especially CUR.

Simultaneous determination of vitexin-4''-O-glucoside and vitexin-2''-O-rhamnoside from Hawthorn leaves flavonoids in rat plasma by HPLC method and its application to pharmacokinetic studies.

The present study was to investigate the pharmacokinetics of the two similar flavonoid glycosides, vitexin-4''-O-glucoside (VGL) and vitexin-2''-O-rhamnoside (VRH) in rats after intravenous administration of hawthorn leaves flavonoids (HLF). Blood samples were collected via tail vein at time intervals after drug administration and the plasma concentrations of the studied ingredients were analyzed by HPLC after the plasma protein was precipitated directly with methanol. VGL and VRH were successfully separated using a C(18) column with a UV detection at 330 nm and a mobile phase of methanol-acetonitrile-tetrahydrofuran-0.5% acetic acid (1:1:19.4:78.6, v/v/v/v). The assay linearities of VGL and VRH were confirmed over the range 0.23-138.42 and 0.36-218.49 microg/ml, respectively. The accuracy and precision of the two analytes at high, medium and low concentration were within the range of -3.13% to 3.51% and below 4%, the mean assay recoveries of them (n=5) ranged from 96.87% to 101.75% and 96.88% to 103.51% for intra- and inter-day assays and the mean extraction recoveries of them (n=5) varied from 92.68% to 95.74% for VGL and 93.45% to 99.26% for VRH, respectively. After intravenous administration of HLF to rats over the doses range of 10-40 mg/kg, the plasma concentration--time curves of VGL and VRH were both conformed to the three-compartment open pharmacokinetic model and linear pharmacokinetic characteristics.

[Value of mixed embolus transarterial chemoembolization in the treatment of hepatocellular carcinoma].

OBJECTIVE: To investigate the value of transarterial chemoembolization (TACE) using mixed emboli for hepatocellular carcinoma (HCC). METHODS: 188 patients with HCC were divided into two groups according to the treatment modality: 103 patients in group A treated by routine iodine embolus agent; 85 patients in group B by mixed iodine embolus agent (ultra-liquified iodinized oil + gelatin sponge + chemotherapeutic agents). The pattern of the arrested iodine deposition in the tumor, response, resectability during follow-up, pathological changes, survival and complications in the two groups were analyzed and compared. RESULTS: The pattern of full-and-dense iodine deposition in the tumor and the response rate (CR + PR) were 59.2% and 32.0% in group A, 89.4% and 56.5% in group B. Surgical resection after TACE was possible in 5.8% (6/103) of group A versus 15.3% (13/85) of group B. Complete tumor necrosis was observed in 1.0% and 4.7% in groups A and B, respectively. 1-, 2- and 3-year actual survival rates were 57.7%, 42.8% and 8.4% in group A, and 79.8%, 55.3%, 38.5% in group B. The difference in results between the two groups was statistically significant, however, the incidence of complication in the two groups was similar. CONCLUSION: Transarterial chemoembolization with mixed iodine emboli is more effective than with the routine iodine emboli in the treatment of bulky or nodular hepatocellular carcinoma rich in blood supply. Mixed iodine emboli is tolerable without increase in severe complications.