This paper reviews the latest understanding of biological and pharmacological properties of osthole (7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one), a natural product found in several medicinal plants such as Cnidium monnieri and Angelica pubescens. In vitro and in vivo experimental results have revealed that osthole demonstrates multiple pharmacological actions including neuroprotective, osteogenic, immunomodulatory, anticancer, hepatoprotective, cardiovascular protective, and antimicrobial activities. In addition, pharmacokinetic studies showed osthole uptake and utilization are fast and efficient in body. Moreover, the mechanisms of multiple pharmacological activities of osthole are very likely related to the modulatory effect on cyclic adenosine monophosphate (cAMP) and cyclic adenosine monophosphate (cGMP) level, though some mechanisms remain unclear. This review aims to summarize the pharmacological properties of osthole and give an overview of the underlying mechanisms, which showcase its potential as a multitarget alternative medicine.

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Osthole: A Review on Its Bioactivities, Pharmacological Properties, and Potential as Alternative Medicine.

To explore the effects of Osthole on the proliferation, cell cycle and apoptosis of human lung cancer A549 cells. Human lung cancer A549 cells were treated with Osthole at different concentrations. Cell proliferation was measured using the MTT assay. Cell cycle was evaluated using DNA flow cytometry analysis. Induction of apoptosis was determined by flow cytometry and fluorescent microscopy. The expressions of Cyclin B1, p-Cdc2, Bcl-2, Bax, t-Akt and p-Akt were evaluated by Western blotting. Osthole inhibited the growth of human lung cancer A549 cells by inducing G2/M arrest and apoptosis. Western blotting demonstrated that Osthole down-regulated the expressions of Cyclin B1, p-Cdc2 and Bcl-2 and up-regulated the expressions of Bax in A549 cells. Inhibition of PI3K/Akt signaling pathway was also observed after treating A549 cells with Osthole. Our findings suggest that Osthole may have a therapeutic application in the treatment of human lung cancer.

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Osthole induces G2/M arrest and apoptosis in lung cancer A549 cells by modulating PI3K/Akt pathway.

Background
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed tumors worldwide and is known to be resistant to conventional chemotherapy New therapeutic strategies are urgently needed for treating HCC Osthole, a natural coumarin derivative, has been shown to have anti-tumor activity However, the effects of osthole on HCC have not yet been reported

Growth Inhibition and Apoptosis Induced by Osthole, A Natural Coumarin, in Hepatocellular Carcinoma

Coumarins are fused benzene and pyrone ring systems with a wide spectrum of bioactivities, including antitumor, anti-inflammation, antiviral, and antibacterial effects. In this paper, the current development of coumarin-based drugs is introduced, and their structure-activity relationship is discussed by reviewing the relevant literature published in the past 20 years. Coumarin molecules can be customized by the target site to prevent systemic side effects by virtue of structural modification. The ortho-phenolic hydroxyl on the benzene ring has remarkable antioxidant and antitumor activities. Coumarins with aryl groups at the C-4 position have good activities in anti-HIV, antitumor, anti-inflammation, and analgesia. C-3 phenylcoumarins have strong anti-HIV and antioxidant effects. Tetracycline pyranocoumarins can significantly inhibit HIV; osthol structural analogues have antimicrobial activity. Praeruptorin C and its derivatives play an important role in lowering blood pressure and dilating coronary arteries, and khellactone derivatives have significant inhibitory effects on AIDS, cancer, and cardiovascular diseases. It is concluded that the specific site on the core structure of coumarin exhibits one or more activities due to the electronic or steric effects of the substituents. This review is intended to be conducive to rational design and development of more active and less toxic agents with a coumarin scaffold.

Pharmacological and Nutritional Effects of Natural Coumarins and Their Structure-Activity Relationships

Osthole, a natural coumarin derivative, is extracted from the fruit of Cnidium monnieri Cusson. Breast cancer is one of the most commonly diagnosed cancers and the leading cause of death in women. Recent studies have shown that Osthole has anti-tumor activity. However, the effects of Osthole on the migration and invasion of cancer cells have not yet been reported. Here, we found that Osthole is effective in inhibiting the migration and invasion of breast cancer cells by wound healing and transwell assays. Luciferase and zymography assays revealed that Osthole effectively inhibits matrix metalloproteinase-2 promoter and enzyme activity, which might be one of the causes that lead to the inhibition of migration and invasion by Osthole. This is the first report on the inhibitory function of Osthole in migration and invasion in breast cancer cells. Our findings indicate a need for further evaluation of Osthole in breast cancer chemotherapy and chemoprevention.

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C Fourneau

Papers

Antiproliferative effects of isopentenylated coumarins isolated from Phellolophium madagascariense Baker.