Octyl ester of ginsenoside compound K as novel anti‐hepatoma compound: Synthesis and evaluation on murine H22 cells in vitro and in vivo

Abstract

Ginsenoside compound K (M1) is the active form of major ginsenosides deglycosylated by intestinal bacteria after oral administration. However, M1 was reported to selectively accumulate in liver and transform to fatty acid esters. Ester of M1 was not excreted by bile as M1 was, which means it was accumulated in the liver longer than M1. This study reported a synthetic method of M1-O, a mono-octyl ester of M1, and evaluated the anticancer property against murine H22 cell both in vitro and in vivo. As a result, both M1 and M1-O showed a dose-dependent manner in cytotoxicity assay in vitro. At lower dose of 12.5 μm, M1-O showed moderate detoxification. Instead, M1-O exhibited significantly higher inhibition in H22-bearing mice than M1. M1-O induced murine H22 tumor cellular apoptosis in caspase-dependent pathway given that pan-caspase inhibitor, Z-VAD-FMK, could reverse the cytotoxicity induced by M1-O. Additionally, pro- and anti-apoptosis proteins, Bcl-2 and Bax, altered and consequently induced increased expression of cleaved caspase-3. Interestingly, cyclophosphamide regimen significantly induced atrophy of spleen and thymus, main immune organs, while M1-O treatment greatly alleviated this atrophy. Collectively, we propose M1-O as a candidate for live cancer treatment.

Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing

“…Wound healing is a highly complex process, with many critical factors influencing normal wound recovery and impaired wound healing caused severe consequences, even death 24 . With the increase in chronic wounds due to accidents, aging populations, and incidences of diseases such as diabetes, wound healing continues to be a considerable challenge in clinical treatment 14 . Although several drugs reportedly promote wound healing, including vascular endothelial growth factor (VEGF) and erythropoietin (EPO), they have yet not to achieve ideal effects 25 .…”

“…Thus, identifying novel molecules for the treatment of wounds is still of great necessity. Compared with traditional drugs, peptides exhibit many advantages such as high activity, specificity, and stability, and have thus provoked considerable scientific attention worldwide 14 .…”

“…Odorrana andersonii lives in relatively harsh environments, which can increase the incidence of skin damage 14 . Thus, given the high UV-irradiative plateau habitats of O. andersonii , cathelicidin-OA1 may facilitate frog survival in severe environments.…”

“…Compared with such drugs, bioactive peptides, which are distinguished from proteins and contain approximately 50 or fewer amino acids, exhibit high activity, specificity, and stability. These advantages have aroused considerable global interest in their identification, including antimicrobial peptides (AMPs), analgesic peptides, and antineoplastic polypeptides 14 . However, peptides exhibiting potent wound-healing promoting potency have been reported rarely 15 .…”

Immunomodulatory Effects of (24R)-Pseudo-Ginsenoside HQ and (24S)-Pseudo-Ginsenoside HQ on Cyclophosphamide-Induced Immunosuppression and Their Anti-Tumor Effects Study

“…In addition, ginsenoside compound K, the active form of major ginsenosides deglycosylated by intestinal bacteria after oral administration, was found to selectively accumulate in the liver and transform to mono-octyl ester derivatives. Study on its potential metabolite (m1- O ) showed that m1- O could induce apoptosis of H22 tumor cells and alleviate the atrophy of immune organs compared with the chemotherapy drug, cyclophosphamide [19].…”