Disease relevance of Osthole

• The secretion of hepatitis B surface antigen (HBsAg) in culture medium of MS-G2 and HuH-7 cells transfected with HBV DNA decreased by 60% to 70% after osthole treatment, without any detectable cytotoxic effects [1].
• The effects of osthole, a coumarin isolated from Cnidium monnieri (L.) Cusson, on ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105-18, were investigated with the aid of the whole-cell voltage-clamp technique [2].
• AIM: To evaluate the effects of osthole on fatty liver, and investigate the possible mechanism [3].
• Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals [3].
• The purpose of this study was to examine effects of osthole on postmenopausal osteoporosis using ovariectomized (OVX) rats [4].

High impact information on Osthole

• Osthole increases glycosylation of hepatitis B surface antigen and suppresses the secretion of hepatitis B virus in vitro [1].
• During screening of Chinese herbal medicines for the activities against hepatitis B virus (HBV), a known pure compound, osthole, was found to inhibit the secretion of HBV surface antigens in vitro [1].
• These data indicate that the inhibitory effect of osthole on platelet aggregation and release reaction was due to the inhibition of thromboxane formation and phosphoinositides breakdown [5].
• Osthole-mediated cell differentiation through bone morphogenetic protein-2/p38 and extracellular signal-regulated kinase 1/2 pathway in human osteoblast cells [6].
• Cotreatment of p38 inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole] or p38 small interfering RNA (siRNA) expression inhibited osthole-mediated activation of ALP but only slightly affected osteocalcin production [6].

Chemical compound and disease context of Osthole

• Effects of osthole on postmenopausal osteoporosis using ovariectomized rats; comparison to the effects of estradiol [4].

Biological context of Osthole

• Kinetic studies revealed that osthole increased the glycosylation rate of HBsAg, thus altering the ratio of glycosylated to unglycosylated HBsAg [1].
• The livers of mice treated with anti-Fas antibody contained apoptotic and dead cells; osthole attenuated the development of this apoptosis and cell death [7].
• Under a current-clamp mode, osthole could decrease the firing frequency of action potentials [2].
• The cell cycle progression block was gradually lost as the delay from serum to osthole application was increased from 6 to 18 h [8].
• Vasorelaxation of rat thoracic aorta caused by osthole isolated from Angelica pubescens [9].

Anatomical context of Osthole

• By means of alkaline phosphatase (ALP) activity, osteocalcin, osteopontin, and type I collagen, enzyme-linked immunosorbent assay, we have shown that osthole exhibits a significant induction of differentiation in two human osteoblast-like cell lines, MG-63 and hFOB [6].
• CONCLUSION: The data suggested that osthole possesses a relaxant effect on rabbit corpus cavernosal tissues which is attributable to the release of NO from sinusoidal endothelium and to the potentiation of the cGMP and/or cAMP signal mediating relaxation of cavernosal smooth muscle by inhibiting phosphodiesterase [10].
• These data suggest that BMP-2/p38 pathway links to the early phase, whereas ERK1/2 pathway is associated with the later phase in osthole-mediated differentiation of osteoblast cells [6].
• However, the addition of osthole (up to 10(-4)M) to a liver cytosol fraction isolated from mice treated with anti-Fas antibody did not inhibit caspase-3 activity in vitro [7].
• The antiproliferative effect of osthole on rat vascular smooth muscle cells was examined in this study [8].

Associations of Osthole with other chemical compounds

• The coumarin osthol attenuates the binding of thyrotropin-releasing hormone in rat pituitary GH4C1 cells [11].
• Bioassay-directed fractionation led to the identification of four known coumarins, osthole (1), imperatorin (2), xanthotoxin (3), and isopimpinellin (4), from the ethanolic extract of the fruit of Cnidium monnieri (L.) Cusson [12].
• RESULTS: After treatment with osthole the levels of serum total cholesterol (TC), triglyceride (TG), lower density lipoprotein-cholesterol (LDL-C), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased [3].
• From the leaves of Phellolophium madagascariense Baker (Apiaceae), an endemic herb to Madagascar, three known coumarins (osthol, murraol and meranzin hydrate) have been isolated and identified [13].
• Single administration of osthol did not inhibit SP-induced scratching, and imperatorin very weakly subsided scratching [14].

Gene context of Osthole

• Thus, treatment of mice with osthole inhibited caspase-3 activity by an effect upstream of caspase-3 activation [7].
• In contrast, the production of osteocalcin induced by osthole was inhibited by the mitogen-activated protein kinase kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) or by expression of an ERK2 siRNA [6].
• The present results show that osthole prevented anti-Fas antibody-induced hepatitis by inhibiting the Fas-mediated apoptotic pathway [7].
• Pretreatment of mice with osthole (10, 50, and 100 mg/kg, i.p.) prevented the elevation of plasma alanine aminotransferase (ALT) caused by anti-Fas antibody (175 microg/kg, i.v.). Administration of osthole to mice even at a dose of 10 mg/kg significantly inhibited of anti-Fas antibody-induced elevation of plasma ALT [7].
• The results show that osthol modulates TRH-evoked responses by interacting with the TRH receptor [11].

Analytical, diagnostic and therapeutic context of Osthole

• We conclude that osthole suppresses the secretion of HBV in cell culture probably because of its novel function in increasing the glycosylation of HBsAg [1].
• The steady-state level of HBV-specific messenger RNA (mRNA) was not altered by osthole treatment, as revealed by Northern blot analysis, Immunoprecipitation of culture medium showed that the ratio of glycosylated versus nonglycosylated HBsAg increased after osthole treatment [1].
• After 48 h deprivation of serum, cells were re-stimulated with serum and the cell cycle was observed by flow cytometry; treatment of cells with osthole (100 microM) caused a block of serum-inducible cell cycle progression at a point before the G1-S boundary [8].
• Pharmacokinetics of osthole in rat plasma using high-performance liquid chromatography [15].
• We conclude that osthole will become a leading chemical for synthesizing a compound which prevents HCC on oral administration [16].

References