In vivoAnti-Cancer Activity of KoreanAngelica Gigasand its Major Pyranocoumarin Decursin

Abstract

We have reported that a 10-herbal traditional formula containing Korean Angelica gigas Nakai (AGN) exerts potent anti-cancer efficacy and identified decursin and decursinol angelate (DA) from AGN as novel anti-androgens. Here, we determined whether AGN would exert in vivo anti-cancer activity and whether decursin or DA could account for its efficacy. The AGN ethanol extract was tested against the growth of mouse Lewis lung cancer (LLC) allograft in syngenic mice or human PC-3 and DU145 prostate cancer xenograft in immunodeficient mice. The pharmacokinetics of decursin and DA were determined. The AGN extract significantly inhibited LLC allograft growth (30 mg/kg) and PC-3 and DU145 xenograft growth (100 mg/kg) without affecting the body weight of the host mice. Biomarker analyses revealed decreased cell proliferation (Ki67, PCNA), decreased angiogenesis (VEGF, microvessel density) and increased apoptosis (TUNEL, cPARP) in treated tumors. Decursin and DA injected intraperitoneally were rapidly hydrolyzed to decursinol. Decursinol and decursin at 50 mg/kg inhibited LLC allograft growth to the same extent, comparable to 30 mg AGN/kg. Therefore the AGN extract possessed significant in vivo anti-cancer activity, but decursin and DA only contributed moderately to that activity, most likely through decursinol.

Restoration of Spermatogenesis Using a New Combined Herbal Formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an Luteinizing Hormone-Releasing Hormone Agonist-Induced Rat Model of Male Infertility

“…It is likely that the therapeutic effects of KH-465 are at least in part attributable to suppression of ROS production or free radical scavenging activities, with eventual beneficial effects on sperm function and spermatogenesis. Basic and clinical research has been carried out over the last few decades to explore the effectiveness of herbal medicine in treating male infertility via the improvement of sperm production, sperm quality, and libido, and reductions in oxidative stress [9]. Ginseng expected to be effective in treating male infertility by improving sperm count or motility, and by promoting DNA synthesis or protein metabolism in spermatogenic cells or Sertoli cells of the testes [18].…”

“…Angelica gigas Nakai is known to exert anticancer and neuroprotective effects through apoptosis, but has also been reported to inhibit fat accumulation and to reduce adipocytokine secretion [89]. In addition, decursin, a major active component of Angelica gigas Nakai, has demonstrated a cellular antioxidant defense capacity through free radical scavenging activity in cryptorchidism-induced male infertility [1011].…”

Are there new therapeutic options for treating lung cancer based on herbal medicines and their metabolites?

“…Grape seed proanthocyanidins (GSPs) from Quercus petraea (Fagaceae) inhibited the growth of A549 and H1299 in mice by targeting insulin-like growth factor binding protein 3, tumor cell proliferation, and angiogenic factors (Akhtar et al, 2009). Decursin from Korean Angelica gigas (Apiaceae) (Lee et al, 2009) and 4-hydroxyderricin from Angelica keiskei roots (Kimura et al, 2004) at 50 mg/kg exerted anti-tumorigenic activity in LLCbearing mice. Similarly, two active substances, cassigarol A (Kimura et al, 2000a) and piceatannol (Kimura et al, 2000b) from Cassia garrettiana (Lauraceae) heartwood, at 50 or 100 mg/kg revealed inhibitory effects on tumor growth and lung metastasis in LLCbearing mice.…”

Antiangiogenic phytochemicals and medicinal herbs

“…aromaticum or Lobelia chinensis inhibited VEGF and angiogenesis through suppression of HIF-1α expression and Akt activation in human lung cancer cells, suggesting a possible mechanism to prevent lung cancer (Liu et al, 2005). Furthermore, a variety of natural compounds have been reported to inhibit angiogenesis via down-regulation of the MAPK signaling pathway: morellofl avone (Pang et al, 2009), thymoquinone (Yi et al, 2008a), sulforaphane (Yao et al, 2008), epoxyquinol B (Kamiyama et al, 2008), delphinidin (Lamy et al, 2008), decursin (Jung et al, 2009;Lee et al, 2009a) and 11,11′-dideoxyverticillin (Chen et al, 2005) in cancer. Our group reported that PGG diminished ERK 1/2 and JNK phosphorylation and increased phospho-p38 MAPK in a dose-dependent manner in bFGFtreated HUVECs (Huh et al, 2005).…”