Xanthotoxin (8‐methoxypsoralen): A review of its chemistry, pharmacology, pharmacokinetics, and toxicity

Abstract

Xanthotoxin (XAT) is a natural furanocoumarins, a bioactive psoralen isolated from the fruit of the Rutaceae plant Pepper, which has received increasing attention in recent years due to its wide source and low cost. By collecting and compiling literature on XAT, the results show that XAT exhibits significant activity in the treatment of various diseases, including neuroprotection, skin repair, osteoprotection, organ protection, anticancer, antiinflammatory, antioxidative stress and antibacterial. In this paper, we review the pharmacological activity and potential molecular mechanisms of XAT for the treatment of related diseases. The data suggest that XAT can mechanistically induce ROS production and promote apoptosis through mitochondrial or endoplasmic reticulum pathways, regulate NF‐κB, MAPK, JAK/STAT, Nrf2/HO‐1, MAPK, AKT/mTOR, and ERK1/2 signaling pathways to exert pharmacological effects. In addition, the pharmacokinetics properties and toxicity of XAT are discussed in this paper, further elucidating the relationship between structure and efficacy. It is worth noting that data from clinical studies of XAT are still scarce, limiting the use of XAT in the clinic, and in the future, more in‐depth studies are needed to determine the clinical efficacy of XAT.

Coumarins of Lovage Roots (Levisticum officinale W.D.J.Koch): LC-MS Profile, Quantification, and Stability during Postharvest Storage

“…Regarding the bioactive properties of lovage coumarins, apterin has been previously determined to be a common apiaceous coumarin [ 65 ] and showed antioxidant [ 66 ], anti-tumor [ 67 ], anticholinesterase [ 68 ], antidiabetic [ 69 , 70 ], and anti-inflammatory activities [ 71 ]. Xanthotoxin has demonstrated various bioactivities, such as anticancer, anti-inflammatory, antioxidative stress and antibacterial activities [ 72 ], while pimpinellin was determined to be an effective preventer of platelet-related thromboembolic diseases (such as atherosclerosis [ 73 ]), and isopimpinellin is antibacterial agent against methicillin-resistant Staphylococcus aureus [ 74 ]. Thus, lovage roots are a valuable source of bioactive coumarins.…”

Zanthoxylum bungeanum Maxim: A Review of Its Phytochemistry, Pharmacology, and Pharmacokinetics

“…They measured the concentration of XAT ( 190 ) in plasma by UPLC-MS and found that XAT( 190 ) was rapidly absorbed after oral administration of XAT ( 190) , with T max of about 55 min and T 1/2 of about 90 min. 88…”

“…rate ofXAT (190) is very low, and the absolute bioavailability of XAT (190) in rat plasma after oral administration is less than 1%. They measured the concentration of XAT (190) in plasma by UPLC-MS and found that XAT(190) was rapidly absorbed after oral administration of XAT (190), with T max of about 55 min and T 1/2 of about 90 min 88. …”

Furanocoumarins as Enhancers of Antitumor Potential of Sorafenib and LY294002 toward Human Glioma Cells In Vitro

“…It has also been shown that the pro-apoptotic activity of the compound is related to its ability to inhibit PI3K kinase activity in MCF-7 and ZR-75 breast cancer cells [10][11][12]. In the case of the bergapten isomer-xanthotoxin-the induction of apoptosis in HepG2 cells is associated with the inhibition of survival signals through the intracellular RAS-RAF-MEK-ERK pathway [13,14]. Another furanocoumarin with defined biological activity is imperatorin.…”