Cytotoxic and Antileishmanial Components from the Bark Extract of Ruyschia phylladenia from Monteverde, Costa Rica

Abstract

The bark of Ruyschia phylladenia was collected from Monteverde, Costa Rica, and extracted with acetone. Bioactivity-directed chromatographic separation of the crude acetone bark extract of R. phylladenia led to isolation and identification of lupeol, betulinic acid, and isofraxidin. Lupeol and betulinic acid showed in-vitro cytotoxic activity to MCF-7, MDA-MB-231, and 5637 human tumor cell lines. Isofraxidin was not cytotoxic, but did show antileishmanial activity to Leishmania amazonensis promastigotes.

Isofraxidin: Synthesis, Biosynthesis, Isolation, Pharmacokinetic and Pharmacological Properties

“…Artemisia incisa Asteraceae aerial parts [56] Artemisia abrotanum Asteraceae aerial parts [57] Artemisia keiskeana Asteraceae whole plant [58] Artemisia scoparia Asteraceae aerial parts [59] Artemisia selengensis Asteraceae aerial parts [60] Impatiens balsamina Balsaminaceae root [61] Chimonanthus salicifolius Calycanthaceae aerial parts [62] Chloranthus anhuiensis Chlorantaceae whole plant [63] Chloranthus japonicus Chlorantaceae root [39] Daboecia cantabrica Ericaceae flower [21] Erica spp Ericaceae flower [21] Euphorbia lagascae Euphorbiaceae seed [64] Fraxinus exelsior Oleaceae bark [65] Fraxinus japonicus Oleaceae bark [66] Fraxinus ornus Oleaceae bark, flowers, leaves [67] Greenea corymbose Rubiaceae stem bark, leaves [43] Greenea montana Rubiaceae stem bark, root bark, leaves [43] Ixora cibdela Rubiaceae stem bark, root bark [68] Ixora javanica Rubiaceae stem bark, root bark [43] Morus alba Moraceae leaves [69] Micrandra elata Euphorbiaceae twig [70] Pelargonium reniforme Geraniaceae root [71] Peucedanum praeruptorum Apiaceae root [72] Rhododendron rubiginosum Ericaceae leaves [73] Ruyschia phylladenia Marcgraviaceae bark [29] Saposhnikovia divaricata Apiaceae root [74] Sarcandra glabra Chloranthaceae whole plant [75] Sapium discolor Euphorbiaceae stem, leaves [76] Solanum indicum Solanaceae seed [77] 2.…”

“…The pure IF, isolated from Micrandera elata, also showed cytotoxic activities against murine leukemia (P388, ED50 = 1.7 µg/mL), with no effects on human mouth epidermal carcinoma (KB, ED50 > 100 µg/mL) [70]. Also, Steinberg and co-workers reported that IF, isolated from Ruyschia phylladenia, had no cytotoxicity on cancer cell lines including two lines of human breast adenocarcinoma (MCF-7, MDA-MB-231) and human bladder carcinoma cells with low activity (IC50 = 51.9 µg/mL) on BALB/c mouse macrophages [29].…”

“…The pure IF (0.3 mg/mL and 0.22 mg/mL) reduced the arachidonic acid and collagen activity at 100% and 54%, respectively and the EtOAc fraction (10 µg/mL) showed these inhibitory effects at 81% and 70%, respectively [55]. Purified IF from Artemisia abrotanum also showed an antimalarial effect against Plasmodiurn falciparum (IC50 = 7.95 µg/mL) [57], and antileishmanial activity against promastigotes of Leishmania amazonensis with IC50 of 11.1 µg/mL [29]. Although IF isolated from sarcandra glabra had no effects on Staphylococcus aureus [141], hopeful analgesic effects were reported for IF, isolated from Saposhnikovia divaricata Root, by Okuyama and co-workers.…”

“…Several strategies are used toward the isolation and purification of coumarin compounds. Maceration, reflux, ultrasonic-assisted, and microwave extraction are current methods for the preparation of the crude extract containing IF [ 29 , 78 , 79 , 80 ]. These methods of extractions were conducted in the presence of various solvents including medium polar or non-polar solvents such as ethyl acetate (EtOAc) [ 69 ], diethyl ether [ 44 ], and hot polar ones such as hot ethanol (EtOH) [ 81 ], hot methanol (MeOH) [ 39 ], and hot deionized water (W) [ 82 ].…”

“…IF and related compounds attenuate multiple destructive signaling mediators and therapeutic targets in some diseases [ 19 , 20 , 21 , 22 , 23 , 24 ]. In this regard, IF has shown several biological and pharmacological activities including antioxidant [ 25 ], cardioprotective [ 26 ], weight loss [ 27 ], anti-osteoarthritis [ 28 ], antimalarial [ 29 ], and neuroprotective [ 30 ] effects, with promising anticancer and anti-inflammatory effects. Accordingly, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), toll-like receptors (TLRs), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), inhibitory kappa B (IκBα), mitogen-activated protein kinases (MAPKs), and c-Jun N -terminal kinase (c-JNK) are the most targeted pathway for anticancer and anti-inflammatory effects of IF [ 27 , 31 , 32 , 33 , 34 ].…”