Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study.

UNLABELLED: In this study, we found out a previously undefined function of icariin which restored the dynamic balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in patients with osteonecrosis of femoral head (ONFH) via ABCB1-promoter demethylation. These findings provided important information regarding potential implication of icariin targeting epigenetic changes for the treatment of steroid -associated ONFH. INTRODUCTION: Here, we investigated whether icariin can also exert a beneficial role in the reactivation of MSCs in the patients with steroid-associated ONFH via ABCB1-promoter demethylation. METHODS: Bone marrow was collected from the proximal femur in patients with steroid-associated ONFH (n = 20) and patients with new femoral neck fractures (n = 22), and then MSCs were isolated. We investigated cell viability, intracellular reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), P-glycoprotein (P-gp) activity, the transcript levels of ABCB1 and oxidative stress-related genes, methylation extent at CpG islands of ABCB1 promoter, and osteogenic and adipogenic differentiation ability of MSCs from the femoral neck fractures group and from the steroid-associated ONFH group treated with or without icariin. RESULTS: We observed that MSCs from the steroid-associated ONFH group showed reduced proliferation ability, elevated ROS level, depressed MMP, weakened osteogenesis, and enhanced adipogenesis while low P-gp activity, transcription level of ABCB1, and oxidative stress-related genes as well as aberrant CpG islands hypermethylation of ABCB1 were also noted in steroid-associated ONFH group. Treatment with icariin obviously induced de novo P-gp expression, decreased oxidative stress, and promoted osteogenesis. CONCLUSION: Icariin may be a potential drug targeting epigenetic changes for the treatment of steroid-associated ONFH.

Meta-analysis of association between IL-6 -634C/G polymorphism and osteoporosis.

Osteoporosis is a common disease in the aging population and studies have shown that interleukin-6 (IL-6) is potentially implicated in its pathogenesis. This study was designed to assess the association between the IL-6 gene -634C/G polymorphism and osteoporosis. PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched for eligible studies published up to and including December 2014 in English or Chinese. Meta-analysis was conducted by the RevMan5.2 software. Weighted mean difference and 95% confidence interval (95%CI) were calculated by a fixed-effect or random-effect model. Bone mineral density (BMD) was regarded as the assessment index. As a result, a total of four articles with 3068 subjects were included. Differences in BMD between the CC and GG genotypes were 0.03 g/cm(2) (95%CI = 0.01 to 0.05) at total body, 0.01 g/cm(2) (95%CI = 0.00 to 0.03) at femoral neck, and 0.03 g/cm(2) (95%CI = 0.00 to 0.06) at the lumbar spine (P < 0.05). For the CG versus GG genotypes, the differences in BMD were 0.03 g/cm(2) (95%CI = 0.02 to 0.05) at total body and 0.02 g/cm(2) (95%CI = 0.00 to 0.03 at the femoral neck (P < 0.05). For the CC versus CG genotypes, the differences in BMD were not significant (P > 0.05). In conclusion, the GG genotype of the -634C/G polymorphism in IL-6 appears to play a role in reducing BMD, which affects normal bone metabolism and leads to osteoporosis.

Antitumor agent, physalin F from Physalis angulata L.

Physalin F and physalin D were isolated and characterized from the ethanolic extract of the whole plant of Physalis angulata L. (Solanaceae). Systematic fractionation of the ethanolic extract of the plant led to characterization of physalin F from the fraction PAIV-2 as an active ingredient which showed cytotoxicity in vitro by DEA and MTT assays on 8 cancer cell lines, five human cancer cell lines: HA22T(hepatoma), HeLa(cervix uteri), KB(nasopharynx), Colo-205(colon) and Calu-1(lung); and three animal cancer cell lines: H1477(melanoma), Hep-2(laryngeal) and 8401(glioma). It was found that the anti-hepatoma action is the strongest, and the anti-HeLa is the next. Physalin F also had an antitumor effect in vivo against P388 lymphocytic leukemia in mice whereas physalin D was inactive both in vitro and in vivo.

Immunomodulatory activity of various fractions derived from Physalis angulata L extract.

The immunomodulatory effects of Physalis angulata L. extract fraction VII (PA-VII), PA-VII-A, PA-VII-B and PA-VII-C were investigated in this study. The results showed that PA-VII and PA-VII-C strongly enhanced blastogenesis response, PA-VII-B had moderate activity, and PA-VII-A exerted only slight effect on cell proliferation. A synergistic effect was observed when the suboptimal dosage of phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was added to the culture. Furthermore, PA-VII and PA-VII-C possessed stimulatory activity on B cells and less effect on T cells. The antibody responses were also augmented by PA-VII, PA-VII-B and PA-VII-C, but not by PA-VII-A. The enhancement of antibody response could be observed both in BALB/c and C3H/HeJ mice.

Experimental antitumor agents from Solanum indicum L.

beta-Sitosterol (SI-0), beta-sitosterol glucoside (SI-1), dioscin (SI-2), methyl protoprosapogenin A of dioscin (SI-3), methyl protodioscin (SI-4) and protodioscin (SI-5) were isolated and characterized from the whole plant of Solanum indicum L. (Solanaceae). Except for beta-sitosterol, these compounds have not been previously isolated from Solanum indicum L. Both CHCl3 soluble (SI-IV) and insoluble (SI-V) fractions of the ethanolic extract (SI-I) showed cytotoxicity on seven cancer cell lines: Colo-205 (colon), KB (nasopharynx), HeLa (uterine cervix), HA22T (hepatoma), Hep-2 (laryngeal epidermoid), GBM8401/TSGH (glioma) and H1477 (melanoma). The purified constituents, SI-2 and SI-4 showed more potent effects by DEA and MTT assay. SI-2,3,4 and 5 also demonstrated cytotoxicity on cultured C6 glioma cells by PRE assay, ans SI-3,4 and 5 showed a tumor inhibitory effect in vivo in C6 glioma cells. In addition, SI-2 had an inhibitory effect on the DNA synthesis of C6 glioma cells at 10 micrograms/ml.

Medicinal plants used for the treatment of hepatitis in Taiwan.

In an extensive ethnobotanical survey of the folk medicines of Taiwan, 69 kinds of crude drugs and 107 species of medicinal plants were found to be used for hepatitis treatments. The present paper is to update a list of medicinal plants used in the treatment of hepatitis and evaluate their liver protection by ethnopharmacological and pathological studies. Results show that some of these drugs have prominent therapeutic effects. Further investigation regarding the anti-hepatotoxic principles will be made.

Sources of the anti-implantation alkaloid yuehchukene in the genus Murraya.

The genus Murraya has been widely used in traditional medicine in east Asia. In view of the recent isolation of the anti-implantation alkaloid yuehchukene from M. paniculata a search has now been made for other natural sources of this alkaloid within the genus. In this paper we report findings for nine taxa of Murraya.