Introduction Quassinoids are natural products formed through
Quassinoids are natural products formed through the oxidative degradation of triterpene derivatives with anti-inflammatory, antimicrobial, antineoplastic, and antiplasmodial effects (Chakraborty and Pal, 2013; Houël et al., 2013). They are characteristic ingredients of the family Simaroubaceae, which includes the Ailanthus, Brucea, and Picrasma genera.
Simaroubaceae family includes 16 genera that are widely distributed in tropical, subtropical, and temperate areas. Picrasma quassioides belongs to Simaroubaceae family (Zhao et al., 2012) and are used as an essential Chinese traditional folklore medicine. Although the branches and nearly of P. quassioides are generally used for medicinal parts in Chinese Pharmacopoeia, their chemical constituents and bioactivities are rarely reported. To further clarify the chemical constituents and identify bioactive metabolites from this folk medicine, we conducted a systematic phytochemical study on the leaves of P. quassioides.
Cytochrome P450 family (CYP450) belongs to hemoprotein superfamily that oxidizes endogenous compounds and xenobiotics. CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4 represent greater than 90% of the total human hepatic CYPs and metabolizes nearly 80% of therapeutic drugs (Zhao et al., 2011). For example, CYP2C19 is a variously expressed enzyme accountable to the metabolism of several clinical drugs, including cyclophosphamide, etoposide, vincristine, diazepam, proguanil, clopidogrel, midazolam, and omeprazole (Hirota et al., 2013; Li, et al., 2002; Shirasaka et al., 2013; Tangamornsuksan et al., 2017). The inhibitors of CYP3A4 also have various chemical structures and are present in many drugs, including ritonavir, clarithromycin, chloramphenicol, ketoconazole, and rifampicin (Das et al., 2009; Park et al., 2003); therefore, these drugs are used carefully or prohibited to be used together.
Quassin and neoquassin from P. excelsa potently inhibit the activity of CYP1A1 (Shields et al., 2009). In light of the widespread use of P. quassioides and incomplete knowledge regarding the effects of multiple components on CYP450 enzymes, isolating the components in the leaves of P. quassioides and analyzing their inhibitory effect to CYP450 enzymes are needed.
Hence, isolation and structure elucidation of three new nigakilactone derivatives 1–3, together with 13 known ones from the leaves of P. quassioides were conducted. The inhibitory effect of these compounds was tested torward six major CYP enzymes including CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4.
Acknowledgement This work was financially supported by the Shanghai Science and Technology Development Foundation (17XD1403500).
Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-pyretic, analgesic and anti-inflammatory . They are widely used in different pathological cases, such as rheumatoid arthritis, fever, back pain and headache . The mechanism of NSAID action is the inhibition of cyclo-oxygenase (cox) enzymes and the decreased metabolism of arachidonic acid (ARA) to inflammatory and pain sensitizing prostaglandin (pg) mediators . Examples of commonly used clinical NSAIDs in different countries are diclofenac, ibuprofen and meloxicam . Mefenamic acid is still used in some cases, such as dysmenorrhea . The cardiotoxicity of NSAIDs, except for aspirin, are well reported in many studies, and the food and drug administration (FDA) of the USA warned about the cardiovascular toxicities of NSAIDs . NSAID treatment is associated with elevated blood pressure, stroke, and myocardial infarction [6,7]. Although cardiotoxicity was reported more among COX2 selective NSAIDs, it was shown that even nonselective NSAIDs increase the risk of developing cardiovascular events . However, the exact mechanism by which NSAIDs exhibit cardiovascular events is not fully understood. It is suggested that NSAIDs decrease aldosterone excretion through inhibition of aldosterone glucuronidation and hence may increase the anti-diuretic effect of aldosterone and lead to elevated blood pressure . In addition, inhibition of COX2 might disturb the cardioprotective pgs, such as pgI2 and H2 .