Lucidenic acid B

Ganoderma lucidum is known as a medicinal mushroom used in traditional Chinese medicine. In the present study, the effect of lucidenic acids (A, B, C, and N) isolated from a new G. lucidum (YK-02) on induction of cell apoptosis and the apoptotic pathway in HL-60 cells were investigated. The results demonstrated that lucidenic acids decreased cell population growth of HL-60 cells, assessed with the MTT assay. The cell cycle assay indicated that treatment of HL-60 cells with lucidenic acid A, C, and N caused cell cycle arrest in the G 1 phase. Lucidenic acid B (LAB) did not affect the cell cycle profile; however, it increased the number of early and late apoptotic cells but not necrotic cells. Treatment of HL-60 cells with LAB caused loss of mitochondria membrane potential. Moreover, the ratio of expression levels of pro- and antiapoptotic Bcl-2 family members was changed by LAB treatment. LAB-induced apoptosis involved release of mitochondria cytochrome c and subsequently induced the activation of caspase-9 and caspase-3, which were followed by cleavage of poly(ADP-ribose) polymerase (PARP). Pretreatment with a general caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) prevented LAB from inhibiting cell viability in HL-60 cells.

A new triterpenoid and 18 analogues were isolated from the water extract of Ganoderma lucidum by column chromatographic techniques, including silica gel, ODS, Sephadex LH-20, and HPLC. The new compound was elucidated as 2β-acetoxy-3β,25-dihydroxy-7,11,15-trioxo-lanost-8-en-26-oic acid on the basis of analyses of extensive spectroscopic data and its physicochemical properties. Comparison of NMR data with those reported in literature, the known analogues were determined as ganoderic acid H (2), 12β-acetoxy-3β,7β-dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid (3), ganoderenic acid D (4),ganoderic acid C1 (5),ganoderic acid G (6),3β,7β-dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid (7),ganoderic acid B (8),ganoderic acid C6 (9),3β,15α-dihydroxy-7,11,23-trioxo-lanost-8,16-dien-26-oic acid (10),ganoderic acid A (11),ganolucidic acid A (12),lucidenic acid E2 (13),lucidenic acid N (14),lucidenic acid P (15), lucidenic acid B (16),lucidenic acid A (17),lucidenic acid C (18),and lucidenic acid L (19), respectively. Compound 1 is new compound and compounds 2-19 have been reported from G. lucidum. The present study enriches the knowledge of the chemical constituent of G. lucidum and completes chemical investigation of water decoction that is traditional use of G.

Ganoderma lucidum has been reported to be associated with suppressed motility, invasion and metastasis of several types of cancers, but its mechanism of action remains unclear. In our previous study, lucidenic acids A, B, C and N were isolated from a new strain of G.lucidum and all of them were found to have potential anti-invasive activity on phorbol-12-myristate-13-acetate (PMA)-induced HepG(2) cells by suppressing the matrix metalloproteinase (MMP)-9 activity. Here, the lucidenic acid B (LAB) was used to explore its mechanisms underlying MMP-9 expression of HepG(2) cells. The results showed that the LAB suppressed PMA-induced MMP-9 activity in a dose-dependent transcriptional level. The suppression of PMA-induced MMP-9 expression of HepG(2) cells by LAB was through inactivating phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. The treatment of mitogen-activated protein kinase kinase (MEK) inhibitors (PD98059 and U0126) and LAB to HepG(2) cells could result in a synergistic reduction on the MMP-9 expression along with an inhibition on cell invasion. Moreover, LAB also strongly inhibited PMA-stimulated nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) DNA-binding activities of HepG(2) cells in dose-dependent manners.