Cancer is caused by uncontrolled cell proliferation which has the potential to occur in different tissues and spread into surrounding and distant tissues. Despite the current advances in the field of anticancer agents, rapidly developing resistance against different chemotherapeutic drugs and significantly higher off-target effects cause millions of deaths every year. Osthol is a natural coumarin isolated from Apiaceaous plants which has demonstrated several pharmacological effects, such as antineoplastic, anti-inflammatory and antioxidant properties. We have attempted to summarize up-to-date information related to pharmacological effects and molecular mechanisms of osthol as a lead compound in managing malignancies. Electronic databases, including PubMed, Cochrane library, ScienceDirect and Scopus were searched for in vitro, in vivo and clinical studies on anticancer effects of osthol. Osthol exerts remarkable anticancer properties by suppressing cancer cell growth and induction of apoptosis. Osthol’s protective and therapeutic effects have been observed in different cancers, including ovarian, cervical, colon and prostate cancers as well as chronic myeloid leukemia, lung adenocarcinoma, glioma, hepatocellular, glioblastoma, renal and invasive mammary carcinoma. A large body of evidence demonstrates that osthol regulates apoptosis, proliferation and invasion in different types of malignant cells which are mediated by multiple signal transduction cascades. In this review, we set spotlights on various pathways which are targeted by osthol in different cancers to inhibit cancer development and progression.

Doxorubicin (DOX) is a potent, broad-spectrum chemotherapeutic drug used for treatment of several types of cancers. Despite its effectiveness, it has a wide range of toxic side effects, many of which most likely result from its inherent prooxidant activity. It has been reported that DOX has toxic effects on normal tissues, including brain tissue. In the current study, we investigated the protective effect of osthole isolated fromPrangos ferulacea(L.) Lindl. on oxidative stress and apoptosis induced by DOX in PC12 as a neuronal model cell line. PC12 cells were pretreated with osthole 2 h after treatment with different concentrations of DOX. 24 h later, the cell viability, mitochondrial membrane potential (MMP), the activity of caspase-3, the expression ratio of Bax/Bcl-2, and the generation of intracellular ROS were detected. We found that pretreatment with osthole on PC12 cells significantly reduced the loss of cell viability, the activity of caspase-3, the increase in Bax/Bcl-2 ratio, and the generation of intracellular ROS induced by DOX. Moreover, pretreatment with osthole led to an increase in MMP in PC12 cells. In conclusion, our results indicated that pretreatment with nontoxic concentrations of osthole protected PC12 cells from DOX-mediated apoptosis by inhibition of ROS production.

Isofraxidin (7-hydroxy-6, 8-dimethoxy coumarin) (IF) is a hydroxy coumarin with several biological and pharmacological activities. The plant kingdom is of the most prominent sources of IF, which, among them, Eleutherococcus and Fraxinus are the well-known genera in which IF could be isolated/extracted from their species. Considering the complex pathophysiological mechanisms behind some diseases (e.g., cancer, neurodegenerative diseases, and heart diseases), introducing IF as a potent multi-target agent, which possesses several herbal sources and the multiple methods for isolation/purification/synthesis, along with the unique pharmacokinetic profile and low levels of side effects, could be of great importance. Accordingly, a comprehensive review was done without time limitations until February 2020. IF extraction methods include microwave, mechanochemical, and ultrasound, along with other conventional methods in the presence of semi-polar solvents such as ethyl acetate (EtOAc). In addition to the isolation methods, related synthesis protocols of IF is also of great importance. From the synthesis point of view, benzaldehyde derivatives are widely used as precursors for IF synthesis. Along with the methods of isolation and biosynthesis, IF pharmacokinetic studies showed hopeful in vivo results of its rapid absorption after oral uses, leading to different pharmacological effects. In this regard, IF targets varieties of inflammatory mediators including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), and matrix metalloproteinases (MMPs). thereby indicating anticancer, cardioprotective, and neuroprotective effects. This is the first review on the synthesis, biosynthesis, isolation, and pharmacokinetic and pharmacological properties of IF in combating different diseases.