Cytotoxic and Anti-inflammatory Terpenoids from the Whole Plant of Vaccinium emarginatum

Abstract

<jats:title>Abstract</jats:title><jats:p>Two new Δ12 ursene-type triterpenoid coumaroyl esters (1 and 2), one new Δ7,15 isopimarane-type diterpenoid glycoside (20), and two new irido-δ-lactone-type iridoids (21 and 22), together with 17 known pentacyclic triterpenoids (3 – 19), were isolated during the phytochemical investigation of a methanol extract of the whole plant of Vaccinium emarginatum. Their structures were determined by detailed analysis of standard spectroscopic data (MS, IR, 1D, and 2D NMR) and comparison with data of known analogs. The isolates were evaluated for their cytotoxicity against the PC-3 and Du145 prostate cancer cell lines (as assessed by an MTT cell proliferation assay), as well as for their anti-inflammatory activity via the inhibition of nitric oxide production in lipopolysaccharide-induced murine macrophage RAW 264.7 cells. Among the isolates, the triterpenoid coumaroyl and feruloyl esters (1, 3, and 4) exhibited strong cytotoxicity against PC-3 prostate cancer cells, with 85.6 – 90.2% inhibition at 10.0 µg/mL. The pomolic acid coumaroyl and feruloyl esters (1 and 3) also showed moderate anti-inflammatory activity against nitric oxide production in lipopolysaccharide-induced RAW 264.7 cells, with 59.2 (± 1.0) and 47.1% (± 0.2) inhibition at 12.5 µg/mL, respectively.</jats:p>

HPLC/ESI-MS and NMR Analysis of Chemical Constitutes in Bioactive Extract from the Root Nodule of Vaccinium emarginatum

“…Previously, the new flavonoid emarginin C, which was isolated from the whole plants of V. emarginatum, exhibited anti-inflammatory activity with an IC 50 value of 27.99 µM [5]. In addition, the triterpenoid coumaroyl and feruloyl esters exhibited strong cytotoxicity against PC-3 prostate cancer cells, with 85.6-90.2% inhibition at 10.0 µg/mL [9]. In this study, the anti-proliferative activities of isolated compounds were determined by measuring the IC 50 of hepatocellular carcinoma (HepG2), lung carcinoma (A549) and gastric adenocarcinoma (AGS).…”

“…It has been reported as one of the rich sources of naturally occurring bioactive phytochemicals, including phenolic acids, flavonoids, anthocyanins, proanthocyanidins and tannins [2][3][4][5]. Vaccinium berries are well-known for their high antioxidant metabolite contents, which have high potential in anti-oxidant [6,7], anti-bacterial [7], antiinflammatory [8,9], anti-diabetic [10,11], and anti-proliferative activities [12,13]. According to their broad-spectrum activities, various Vaccinium leaf and berry extracts have been developed as commercial products for dietary supplements [14,15].…”

“…In Taiwan, the root nodules are used in traditional medicine, which is supposed to be as effective as Lu Rong (the developing antlers of deer; velvet antler). Its leaves are used to treat urinary tract infections and rheumatic pain, while the fruits are used to treat dysentery and enteritis, respectively [9]. To date, few phytochemical studies were reported for V. emarginatum [5,9].…”

“…Its leaves are used to treat urinary tract infections and rheumatic pain, while the fruits are used to treat dysentery and enteritis, respectively [9]. To date, few phytochemical studies were reported for V. emarginatum [5,9]. Previously, one epicatechin derivative and three new flavonoids, emarginin A, B, and C, were isolated from the methanolic extract of the whole plants of V. emarginatum.…”

“…Emarginin C exhibited moderate anti-inflammatory activity [5]. Recently, the cytotoxic and antiinflammatory activity of terpenoids from the whole plant of V. emarginatum was also investigated [9]. Although those studies indicated the high potential of V. emarginatum in anti-inflammatory and cytotoxicity against prostate cancer cells, the anti-infective activity on human pathogens and anti-proliferative effect on tumor cells are still unknown.…”