Anti-osteoporosis Activity Research Articles

An O-acetyl-glucomannan from the rhizomes of Curculigo orchioides: Structural characterization and anti-osteoporosis activity in vitro

Osteoporosis is characterized by a reduction in bone mass and bone mineral density, which weakens the bone. Due to the side effects associated with drugs that are currently used to treat this disease, an increasing number of studies have focused on the research of effective ingredients derived from natural products. In particular, polysaccharides extracted from Chinese herbal medicines have received increasing attention. In this study, we isolated a homogeneous polysaccharide (COP90-1) from the dried rhizomes of Curculigo orchioides, a famous traditional Chinese medicine that is widely used in China, and determined its structure using the combined methods of chemical and spectral analyses. In addition, its effects on the proliferation and differentiation of primary mouse osteoblasts were assessed. The results showed that COP90-1 can effectively promote the proliferation and differentiation of primary osteoblasts in vitro. Additional studies are warranted to study the effects of this compound in vivo.

Morphological studies and meiotic chromosome analysis of Epimedium elatum (Morr & Decne) - Rare endemic medicinal plant of Northwestern Himalayas in India.

<p><em>Epimedium elatum</em> (Berberidaceace) is a rare endemic medicinal herb of Northwestern Himalayas in India. Recent ethnopharmacological reports have demonstrated its traditional medicinal use against various bone related diseases in the Kashmir Himalayas. It owes its pharmaceutical importance due to high concentration of flavonoid glycosides like Epimedin A, B, C and Icariin which are known mainly for aphrodisiac, antiosteoporosis, anticancer, antioxidant, antiaging, antifatigue and antiviral activities. It is a neglected medicinal plant in Northwestern Himalayan region and may fall in the list of endangered species due to continuous anthropogenic pressures in its native habitats. In this study, we investigated distributional and altitudinal range of this prized species from twenty diverse eco-geographical zones of Kashmir Himalayas for the first time. We also report here its diversity in morphological attributes both in wild and captive cultivation. The species has a very small population size in most of the surveyed habitats with no natural protection. Under cultivation it showed increased plant height (63.09±4.9cm), more number of leaves (95.53±11cm) and flowers (160.76±20cm), indicating importance of high altitude medicinal garden for its immediate <em>ex situ</em> conservation. Further, the acetocarmine staining and squashing of young anthers confirmed it as a diploid species (2n=12) like other <em>Epimedium</em> species. Chromosome number and meiotic abnormalities are also reported for the first time in the species. Finally, constant anthropogenic pressures in Northwestern Himalayas demand immediate <em>in situ</em> and <em>ex situ</em> conservation programmes for <em>E.elatum</em>.<strong></strong></p>

Simultaneous Quantification of Multiple Representative Components in the Xian-Ling-Gu-Bao Capsule by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry.

Xian-Ling-Gu-Bao capsule (XLGB), a famous traditional Chinese medicine prescription, is extensively used for the treatment of osteoporosis in China. However, few studies on the holistic quality control of XLGB have been reported. In this study, a reliable method using 18 representative components in XLGB was successfully established and applied to evaluate 34 batches of XLGB samples by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). The choice of quantitative markers mostly followed four principles, i.e., absorbed components in plasma, bioactive compounds with in vitro anti-osteoporosis activity, those derived from multiple individual medicinal herbs in XLGB with multiple representative structure types, and quantitative chemical markers in the Chinese Pharmacopoeia. The results showed chemical consistency was good except for individual batches. Multivariate statistical analysis indicated that asperosaponin VI from Radix Dipsaci, epimedin C, magnoflorine, and icariin from Herba Epimedii as well as timosaponin BII from Rhizoma Anemarrhenae varied significantly in multiple samples, which hinted an assay for these four components should be completed during all of the manufacturing processes. Taken together, this study provided a feasible method for holistic quality control of XLGB by multiple chemical markers, which could play a vital role in guaranteeing the safety, effectiveness, and controllability of administering the capsules as a medication in clinics.

Glucuronidation of icaritin by human liver microsomes, human intestine microsomes and expressed UDP-glucuronosyltransferase enzymes: identification of UGT1A3, 1A9 and 2B7 as the main contributing enzymes

1. Icaritin is a natural flavonoid with anti-osteoporosis activity. This study aimed to characterize icaritin glucuronidation by pooled human liver microsomes (HLM) and pooled human intestine microsomes (HIM), and to determine the contribution of individual UDP-glucuronosyltrans-ferase (UGT) enzyme to icaritin glucuronidation.2. Glucuronidation rates were determined by incubating icaritin with uridine diphosphate glucuronic acid (UDPGA)-supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. Relative activity factors and activity correlation analysis were performed to identify main UGT isoforms.3. UGT1A3, 1A7, 1A8, 1A9 and 2B7 were mainly responsible for catalyzing the formation of two glucuronides (G1 and G2). Icaritin 3-O-glucuronidation (G1) was significantly correlated with Chenodeoxycholic acid (CDCA) glucuronidation (r = 0.787, p = 0.002), propofol glucuronidation (r = 0.661, p = 0.019) and Zidovudine (AZT) glucuronidation (r = 0.805, p = 0.002). Similarly, icaritin 7-O-glucuronidation (G2) was also correlated with CDCA glucuronidation (r = 0.640, p = 0.025), propofol glucuronidation (r = 0.592, p = 0.043) and AZT glucuronidation (r = 0.661, p = 0.019). In addition, UGT1A3, 1A9 and 2B7 contributed 37.5, 33.8 and 21.3% for G1 in pooled HLM, respectively. Also, UGT1A3, 1A9 and 2B7 contributed 34.3, 20.0 and 8.6% for G2 in pooled HLM, respectively.4. Icaritin was subjected to significant glucuronidation, wherein UGT1A3, 1A7, 1A8, 1A9 and 2B7 were main contributing enzymes.

Rapid, microwave-accelerated synthesis and anti-osteoporosis activities evaluation of Morusin scaffolds and Morusignin L scaffolds

Described herein is a facile and efficient methodology toward the synthesis of Morusin scaffolds and Morusignin L scaffolds 4–9 and 12via a novel three-step approach (Michael addition or prenylation, cyclization and cyclization) and use a rapid, microwave-accelerated cyclization as the key step. Furthermore, their biological activities have been preliminarily demonstrated by in vitro evaluation for anti-osteoporosis activity. These Morusin, Morusignin L and newly synthesized compounds 5b, 6a, 8e, 8f greatly exhibited the highest potency, especially at the 10−5mol/L (P<0.01), and had good in vitro anti-osteoporosis activities using the commercially available standard drug Ipriflavone as a positive control. The mechanisms associated with anti-osteoporosis effects of these compounds may be through the inhibition of TRAP enzyme activity and bone resorption in osteoclasts, and promotion effect of osteoblast proliferation in vitro. The results indicated that Morusin scaffolds and Morusignin L scaffolds may be useful leads for further anti-osteoporosis activity screenings.

Ulam Herbs of &lt;I&gt;Oenanthe javanica&lt;/I&gt; and &lt;I&gt;Cosmos caudatus&lt;/I&gt;: an overview on their Medicinal Properties

In Southeast Asia, ulam herbs are consumed raw as a condiment. It is believed that these herbs have medicinal benefits and their regular intake can prevent degenerative diseases, delay aging and improve overall health. In this review, the current knowledge on the phytochemistry and pharmacology of &lt;em&gt;Oenanthe javanica&lt;/em&gt; (water dropwort) and &lt;em&gt;Cosmos caudatus&lt;/em&gt; (wild cosmos) is updated with some descriptions of their botany and uses. Water dropwort has constituents of phenylpropanoids, flavonoids and phenolic acids, notably, persicarin and isorhamnetin. Antioxidant, anti-quorum sensing, melanogenic, anti-diabetic, anti-arrhythmic, anti-inflammatory, neuroprotective, neurogenesis, alcohol detoxification, antitoxic, anti-coagulant, hepatoprotective, anti-hepatitis B virus and memory improvement are pharmacological properties of water dropwort. Wild cosmos, with flavonoids, phenolic acids and diterpenoids as major metabolites, possesses antioxidant, antibacterial, anti-quorum sensing, antifungal, anti-inflammatory, anti-diabetic, anti-hypertensive, hepatoprotective, detoxification, anti-osteoporosis and anti-hyperlipidemic activities. There are several patents on some of the pharmacological properties of water dropwort while a clinical trial has been conducted on the anti-diabetic effects of wild cosmos. Both these ulam herbs possess a wide array of pharmacological properties, which confer their traditional uses as food and medicine.

Biotransformation of furanocoumarins by fungi: preparation of imperation analogs

Imperation analogs have the furanocoumarin skeleton, with the isopentenyl group, which displayed significant bioactivities. The biotransformation of furanocoumarins imperation, isoimperation and phellopterin (1–3) by fungi has been proved to be an efficient method for the structural modification. Ten transformed furanocoumarin analogs were obtained by fungal biotransformation, including one new highly oxygenated furanocoumarin (4c). Aspergillus niger AS 3.739 displayed selectively transformed capability toward furanocouamrins (1–3) with one or two major products. So, seven hydroxylation and hydrolysis derivatives have been prepared efficiently. Additionally, the biotransformation of phellopterin gave multiple products (4a, 4b, 4c) by Cunninghamella blakesleana AS 3.970. The biotransformation time-courses of furanocoumarins have been established, which suggested the preferred incubation time. The bioactivities of furanocoumarin analogs have been investigated in an in vitro bioassay. And, furanocoumarins 1–3, 2a, and 2c displayed moderate anti-osteoporosis activities using MCET3-E1 cell line at the concentrations of 1, 10, and 100 μM.

A Review on the Medicinal Plant Dalbergia odorifera Species: Phytochemistry and Biological Activity.

The crucial medicinal plant Dalbergia odorifera T. Chen species belongs to genus Dalbergia, with interesting secondary metabolites, consisting of main classes of flavonoid, phenol, and sesquiterpene derivatives, as well as several arylbenzofurans, quinones, and fatty acids. Biological studies were carried out on extracts, fractions, and compounds from this species involved in cytotoxic assays; antibacterial, antioxidative, anti-inflammatory, antithrombotic, antiplatelet, antiosteosarcoma, antiosteoporosis, antiangiogenesis, and prostaglandin biosynthetic enzyme inhibition activities; vasorelaxant activities; alpha-glucosidase inhibitory activities; and many other effects. In terms of the valuable resources for natural new drugs development, D. odorifera species are widely used as medicinal drugs in many countries for treatment of cardiovascular diseases, cancer, diabetes, blood disorders, ischemia, swelling, necrosis, or rheumatic pain. Although natural products from this plant have been increasingly playing an important role in drug discovery programs, there is no supportive evidence to provide a general insight into phytochemical studies on D. odorifera species and biological activities of extracts, fractions, and isolated compounds. To a certain extent, this review deals with an overview of almost naturally occurring compounds from this species, along with extensive coverage of their biological evaluations.

Chlorogenic Acid Prevents Osteoporosis by Shp2/PI3K/Akt Pathway in Ovariectomized Rats.

Cortex Eucommiae is used worldwide in traditional medicine, various constituents of Cortex Eucommiae, such as chlorogenic acid (CGA), has been reported to exert anti-osteoporosis activity in China, but the mechanism about their contribution to the overall activity is limited. The aims of this study were to determine whether chlorogenic acid can prevent estrogen deficiency-induced osteoporosis and to analyze the mechanism of CGA bioactivity. The effect of CGA on estrogen deficiency-induced osteoporosis was performed in vivo. Sixty female Sprague-Dawley rats were divided randomly among a sham-operated group and five ovariectomy (OVX) plus treatment subgroups: saline vehicle, 17α-ethinylestradiol (E2), or CGA at 9, 27, or 45 mg/kg/d. The rats’ femoral metaphyses were evaluated by micro-computed tomography (μCT). The mechanism of CGA bioactivity was investigated in vitro. Bone mesenchymal stem cells (BMSCs) were treated with CGA, with or without phosphoinositide 3-kinase (PI3K) inhibitor LY294002. BMSCs proliferation and osteoblast differentiation were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and alkaline phosphatase, with or without Shp2 interfering RNA (RNAi). The results display that CGA at 27 and 45 mg/kg/day inhibited the decrease of bone mineral density (BMD) that induced by OVX in femur (p< 0.01), significantly promoted the levels of bone turnover markers, and prevented bone volume fraction (BV/TV), connectivity density (CoonD), trabecular number (Tb.N), trabecular thickness (Tb.Th) (all p< 0.01) to decrease and prevented the trabecular separation (Tb.Sp), structure model index (SMI)(both p< 0.01) to increase. CGA at 1 or 10 μM enhanced BMSC proliferation in a dose-dependent manner. CGA at 0.1 to 10 μM increased phosphorylated Akt (p-Akt) and cyclin D1. These effects were reversed by LY294002. CGA at 1 or 10 μM increased BMSC differentiation to osteoblasts (p< 0.01), Shp2 RNAi suppressed CGA-induced osteoblast differentiation by decreasing Shp2, p-Akt, and cyclin D1. This study found that CGA improved the BMD and trabecular micro-architecture for the OVX-induced osteoporosis. Therefore, CGA might be an effective alternative treatment for postmenopausal osteoporosis. CGA promoted proliferation of osteoblast precursors and osteoblastic differentiation of BMSCs via the Shp2/PI3K/Akt/cyclin D1 pathway.

Genetic diversity, LCMS based chemical fingerprinting and antioxidant activity of Epimedium elatum Morr & Decne

Epimedium elatum Morr & Decne is a perennial herb, endemic to shady coniferous forests of north-western Himalayas, India. It owes its pharmaceutical importance to high concentration of flavonoid glycosides particularly epimedins and Icariin. A lot of medicinal properties are attributed to them like aphrodisiac (PDE-5 inhibition), anti-osteoporosis, anticancer, antioxidant, anti-fatigue and antiviral activities. In the present study, twenty accessions of E. elatum were investigated for their genetic diversity and chemo-profiling through molecular markers and fingerprinting, respectively. Further, their phyto-chemical variation and related antioxidant activities are also being reported. Molecular fingerprinting resulted in 277 total loci, out of which 254 were polymorphic, displaying an overall polymorphism of 91.1%. Moreover, fourteen unique bands were amplified, maximum (6) were amplified in GL accession from 3 primers (UBC900, UBC834 & UBC823). The dendrogram topology indicated moderate to high genetic diversity corroborating with diversity index (0.36). Chemo-profiling revealed epimedin B and epimedin C as the major prenylated flavonoids in leaves, while Icariin was found highest in underground parts. However, no correlation could be deduced between molecular and prenylated flavonoid profiling in the present study. Furthermore, ethanolic extracts of rhizomes exhibited stronger antioxidant ability. The study has great implications as the wild resource conservation, germplasm assessment, quality resource explorations have become critical for the sustainability of the species. Efforts are thus needed to conserve the elite accessions of E. elatum.

Icariin Metabolism by Human Intestinal Microflora.

Icariin is a major bioactive compound of Epimedii Herba, a traditional oriental medicine exhibiting anti-cancer, anti-inflammatory and anti-osteoporosis activities. Recently, the estrogenic activities of icariin drew significant attention, but the published scientific data seemed not to be so consistent. To provide fundamental information for the study of the icaritin metabolism, the biotransformation of icariin by the human intestinal bacteria is reported for the first time. Together with human intestinal microflora, the three bacteria Streptococcus sp. MRG-ICA-B, Enterococcus sp. MRG-ICA-E, and Blautia sp. MRG-PMF-1 isolated from human intestine were reacted with icariin under anaerobic conditions. The metabolites including icariside II, icaritin, and desmethylicaritin, but not icariside I, were produced. The MRG-ICA-B and E strains hydrolyzed only the glucose moiety of icariin, and icariside II was the only metabolite. However, the MRG-PMF-1 strain metabolized icariin further to desmethylicaritin via icariside II and icaritin. From the results, along with the icariin metabolism by human microflora, it was evident that most icariin is quickly transformed to icariside II before absorption in the human intestine. We propose the pharmacokinetics of icariin should focus on metabolites such as icariside II, icaritin and desmethylicaritin to explain the discrepancy between the in vitro bioassay and pharmacological effects.

The effect of atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (HMG-CoA), on the prevention of osteoporosis in ovariectomized rabbits.

Osteoporosis is a most frequent systemic skeletal disease characterized as low bone mineral density and microarchitectural deterioration of bone tissue, resulting in increased bone fragility and fracture risk. Although several drugs such as bisphosphonates, estrogen replacement treatment, and selective estrogen receptor modulators have been used to treat osteoporosis, all these are not the ideal drugs because of insufficient curative ability and adverse side effects. Recently, atorvastatin has ordinarily been prescribed as an anti-hyperlipidemia drug, not as an anti-osteoporosis drug. However, its clinical outcome and potential treatment mechanism are still unclear. In this study, the bilateral ovariectomy of rabbits was duplicated to develop osteoporosis animal model. The effect of atorvastatin on in vivo was determined, and the functional mechanism was studied in vitro after the curative effect was explored. Atorvastatin was observed to significantly increase the mechanical parameters such as maximum load, stiffness, and energy-absorbing capacity, and it improved the microarchitecture. The anti-osteoporosis activity of atorvastatin may be the result of the promotion of differentiation of osteoblasts by inducing synthesis of vascular endothelial growth factor, bone morphogenetic protein 2 (BMP2), core-binding factor alpha 1 (CBFα1), and inhibition of osteoclast formation through the osteoprotegerin (OPG)-receptor activator for the nuclear factor κB ligand (RANKL) system. Our study observations give reliable experimental evidence for clinical application of atorvastatin to treat the disorder of osteoporosis.

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.

Limonin enhances osteoblastogenesis and prevents ovariectomy-induced bone loss

Limonin, the most prevalent limonoid in citrus fruits, is widely used as a dietary supplement because of its biological activities. Although studies have shown that limonin inhibits bone resorption in osteoclasts and improves bone quality in orchidectomised rats, the anti-osteoporosis activity of limonin in ovariectomised (OVX) animal models is still unknown, and its exact molecular mechanisms remain undefined. Therefore, the effect of limonin on osteoblastogenesis in MC3T3-E1 cells and an OVX-induced osteoporosis rat model was investigated. Limonin stimulated alkaline phosphatase (ALP) activity, mineralisation, and increased osteoblast differentiation gene marker expression via extracellular signal-regulated kinase (ERK) and p38 signalling in osteoblastic MC3T3-E1 cells. In animals, limonin decreased OVX-induced body weight increase, affected the trabecular bone structure and biochemical properties, and facilitated bone mineral density and content regulation. These findings demonstrated that limonin has beneficial bone metabolism effects based on bone formation and might have potential as a functional food ingredients and a dietary supplement for osteoporosis.

Altitudinal variation in pharmacologically active compounds of wild and cultivated populations of Epimedium elatum

Epimedium is a well known genus of Chinese pharmacopoeia, possessing various medicinal properties such as aphrodisiac, antioxidant, immunomodulatory, vasodilatory, hepatoprotective, cardioprotective, antidepressant, anticancerous and antiosteoporosis activities. The active principle has been found to be its flavonoid glycosides, especially Icariin and Icariside-II. In the present study, Epimedium elatum, the only species of this genus growing in Indian subcontinent and endemic to Kashmir Himalayas, has been studied for its active principle content at different habitats. The plants were collected from wild populations (W-I W-II &W-III) growing at three different sites of different altitudes and cultivated at low altitudes of Central Kashmir. After two years, the plants from wild populations as well as cultivated populations were collected, shade dried, grinded and prepared for HPLC analysis. The results showed that the content of active principles in leaves vary significantly between plants growing at different habitats. The Icariin and Icariside-II yield (per plant) of wild populations significantly increased with a decrease in altitude of habitat. Cultivated population growing at higher altitude had significantly more yield than all other populations, except the W-III. The content of active principles as a percentage of leaf dry mass increased with increase in altitude. However, the harvest index of wild populations showed a decreasing trend with increasing altitude. The content of active principles as a percentage of dry mass of whole plant was comparable in all the habitats, including the cultivated populations. The present study suggests that Epimedium plants cultivated at lower altitudes are equally or more productive in terms of Icariin and Icariside-II content than that of wild plants growing at higher altitudes.

Genus Tinospora: Ethnopharmacology, Phytochemistry, and Pharmacology

The genus Tinospora includes 34 species, in which several herbs were used as traditional medicines by indigenous groups throughout the tropical and subtropical parts of Asia, Africa, and Australia. The extensive literature survey revealed Tinospora species to be a group of important medicinal plants used for the ethnomedical treatment of colds, headaches, pharyngitis, fever, diarrhea, oral ulcer, diabetes, digestive disorder, and rheumatoid arthritis. Indian ethnopharmacological data points to the therapeutic potential of the T. cordifolia for the treatment of diabetic conditions. While Tinospora species are confusing in individual ingredients and their mechanisms of action, the ethnopharmacological history of those plants indicated that they exhibit antidiabetic, antioxidation, antitumor, anti-inflammation, antimicrobial, antiosteoporosis, and immunostimulation activities. While the clinical applications in modern medicine are lacking convincing evidence and support, this review is aimed at summarizing the current knowledge of the traditional uses, phytochemistry, biological activities, and toxicities of the genus Tinospora to reveal its therapeutic potentials and gaps, offering opportunities for future researches.

Preparative Purification of Bioactive Compounds from Flos Chrysanthemi Indici and Evaluation of Its Antiosteoporosis Effect.

To understand the material basis and underlying molecular machinery of antiosteoporosis activity of the Flos Chrysanthemi Indici (FCI), the consequences of ethanol extract on the bone loss in mice induced due to ovariectomy (OVX) was evaluated. Also, the antiosteoporosis fraction obtained from the FCI ethanol extract was isolated and purified using a preparative high-speed countercurrent chromatography (HSCCC). The in vitro impact of the compounds was investigated on osteoblast proliferation and differentiation. The results revealed that ethyl acetate fraction with robust in vivo antiosteoporosis activity was obtained. The important compounds purified by HSCCC using gradient elution system included acacetin, apigenin, luteolin, and linarin. The four compounds enhanced the differentiation and proliferation of osteoblasts in MC3T3-E1 cells. They also augmented the mRNA levels of runt-related transcription factor 2 (Runx2), osteocalcin (OCN), osteopontin (OPN), and type I collagen (COL I). The AKT signaling pathway was also activated in MC3T3-E1 cells by the four compounds. The present study demonstrated that the antiosteoporosis effects of FCI did not depend on a single component, and HSCCC efficiently isolated and purified the antiosteoporosis bioactive compounds from FCI.

Research achievements on biological activities of calycosin

Calycosin, which is a kind of typical phytoestrogen, can bind with estrogen receptor and produce estrogen-like effects. Calycosin were reported to have antioxidant, anti-osteoporosis, anti-tumor and immunomodulating activities. This review covers biological activities and its mechanism of calycosin. It will provide a useful reference for clinical research and rational utilization of monomericompound.

Synthesis, estrogenic activity, and anti-osteoporosis effects in ovariectomized rats of resveratrol oligomer derivatives

Three series of resveratrol oligomer derivatives were synthesized, including the indenone-type, indene-type and octahydropentalene-type derivatives, among which ten derivatives were novel compounds. Compounds 2, 14f, and 4d were confirmed as ERβ agonists by yeast two-hybrid assay, and compound 2 (isopaucifloral F) was further chosen to evaluate its anti-osteoporosis activity in vivo. Compared with the sham-operated and the positive control groups, isopaucifloral F (10 μg/kg) showed a notable anti-osteoporosis effect in the ovariectomized (OVX) female rats based on a micro-CT analysis and the following measurements: bone mineral density, bone volume/tissue volume, trabecular thickness, trabecular separation/spacing, and the serum biochemical parameters. LD50 of isopaucifloral F was found to be greater than 5 mg/kg and its effective dose (ED) was found to be about 10 μg/kg. Therefore, isopaucifloral F may be a promising lead compound for the treatment of postmenopausal osteoporosis.

Biotransformation of major flavonoid glycosides in herb epimedii by the fungus Cunninghamella blakesleana

Biotransformation of icariin (1), epimedin C (2), epimedoside A (3), epimedin A (4) and epimidin B (5), five major components of E. koreanum, were performed by using Cunninghamella blakesleana. And they could be metabolized efficiently to icariside II (1a), 2″-O-rhamnosylikarisoside II (2a), epimedoside b (3a), baohuoside VII (4a) and sagittatoside B (5a) with high yields of 95.1%, 97.7%, 93.7%, 95.8% and 96.4%, respectively. And these transformed products as major forms of herb epimedii in vivo exhibited the more significant anti-osteoporosis activities. Our method could be applied for enriching these rare flavonoids in herb epimedii, for further development of anti-osteoporosis medicines or functional foods.