A geranylated chalcone with antiplatelet activity from the leaves of breadfruit (Artocarpus altilis)

Abstract

Platelet plays a crucial role in cardiovascular diseases (CVDs) development. Abnormalities in platelet aggregation provokes thromboembolism, eventually leading to death. In Indonesia, breadfruit (Artocarpus altilis) leaf is traditionally used to treat CVDs. This study aimed to evaluate the antiplatelet activity of A. altilis leaf extract (AAE) and to identify its active compound. A. altilis leaves were extracted with ethanol, and the antiplatelet activity was assessed using ADP-induced platelet aggregation. The major compound was isolated with column chromatography followed by preparative TLC, and the structure was determined on the basis of UV, MS, IR, and NMR spectra. The binding mode of the active compound to platelet receptors was characterized in in silico study. AAE exhibited an antiplatelet activity (IC50 of 252.23 µg/mL). A geranylated chalcone, 2-geranyl-2ʹ,3,3,4ʹ-tetrahydroxydihydrochalcone (GTDC) was identified as the antiplatelet compound (IC50 of 9.09 µM). GTDC actions with P2Y12 platelet receptor involving three amino acid residues.

Profil Fitokimia dan Aktivitas Antioksidan Beberapa Tumbuhan Genus Artocarpus di Indonesia

“…Daun sukun yang diekstraksi dengan metanol dan dipartisi dengan kloroform dapat ditemukan adanya senyawa auron H, auron I dan auron J serta 2 senyawa flavonoid yaitu 8-geranil-4',5,7trihidroksiflavon dan sikloaltilisin 7 [25]. Fraksi etil asetat mengandung senyawa geranil dihidrokalkon yang dilaporkan merupakan senyawa utama dalam daun sukun [26]. Senyawa lain yang berhasil diisolasi dari buah dan kulit pohon sukun adalah senyawa golongan terpenoid dengan kerangka sikloartan yaitu sikloartenol [21], sikloeukalenol, 2,4-metilensikloartenon, dan sikloartenon [27].…”

In vivo Anti-Inflammatory Activity of Coleus atropurpureus Leaves Extract and Fractions

“…10 Another study showed the oedema reduction in rat paw oedema experimental model treated with 140 mg/kg BW of C. atropurpureus water extract. 12 In addition, a combination of the water extract of C. atropurpureus leaf with other herbal medicine, Clitoria ternatea flower at the dose of 328 mg/kg BW was able to reduce paw oedema with 9.1 mg/kg BW of Potassium diclofenac in mice. 11 In this study, the investigation of the anti-inflammatory activity of C. atropurpureus leaf was done by testing the ethanol extract (EE), nhexane fraction (HF), and ethanol-water fraction (EWF) in carrageenan-induced paw oedema in rat.…”

“…Previous study reported that C. atropurpureus contained flavonoid, saponin, polyphenol, and terpenoid in the leaves of C. atropurpureus. 11,12 The water extract of C. atropurpureus (at the doses of 100; 200; dan 400 mg/kg BW) demonstrated anti-inflammatory effect. 10 Another study showed the oedema reduction in rat paw oedema experimental model treated with 140 mg/kg BW of C. atropurpureus water extract.…”

Synthesis of Chalcones Derivatives and Their Biological Activities: A Review

“…Chalcones are used in several biosynthetic pathways as initial intermediate structures in the production of flavonoids, isoflavonoids, and aurones . A significant part of medicinal chemistry research in the 21st century has been focused on both natural and synthetic chalcones because of their various pharmacological potential including activities and characteristics such as antibacterial, − anti-inflammatory, − analgesic, , anticholinergic, antiplatelet, antiulcer, antioxidant, , antimalarial, anticancer, , antiviral, − antileishmanial, antidiabetic, , immunomodulatory, , aldose reductase inhibition, estrogenic, acetylcholinesterase inhibition, and as non-purine xanthine oxidase inhibitors . Chalcones are highly attractive molecules because of their simple structure, ease of construction, and promising biological applications.…”