Ionone Derivatives from the Mycelium of Phellinus linteus and the Inhibitory Effect on Activated Rat Hepatic Stellate Cells

Abstract

Three new γ-ionylideneacetic acid derivatives, phellinulins A–C (1–3), were characterized from the mycelium extract of Phellinus linteus. The chemical structures were established based on the spectroscopic analysis. In addition, phellinulin A (1) was subjected to the examination of effects on activated rat hepatic stellate cells and exhibited significant inhibition of hepatic fibrosis.

Hepatoprotective Principles and Other Chemical Constituents from the Mycelium of Phellinus linteus

“…Successively, the powder of dried P. linteus mycelium was refluxed with ethanol and the afforded syrup was extracted with chloroform to yield CHCl 3 and H 2 O fractions. The chloroform fraction was further isolated by a series of column (CC) and thin layer (TLC) chromatography to result in three derivatives of γ-ionylideneacetic acid, phellinulins A–C ( 1 – 3 ) [ 19 ] and eleven new ionone derivatives ( 4 – 14 ) ( Figure 2 ) along with other chemical constituents. The chemical structures of ionone derivatives 4 – 14 were elucidated as shown below according to their spectroscopic and spectrometric analytical data.…”

“…The stereochemical configurations of C-1, C-6, C-7 and C-8 were established as shown according to the nuclear Overhauser effect spectroscopy (NOESY) analysis ( Figure 3 ). Conclusively, the chemical structure of 4 was established as shown in Figure 2 and the trivial name phellinulin D was given according to the previous convention [ 19 ].…”

“…Activated HSCs could mediate the release of pro-inflammatory cytokines and tissue inhibitor of metallo-proteinases (TIMP), which would cause the deposition of collagen and further fibrosis [ 12 ]. Due to these reasons, to induce the apoptosis of activated HSCs has been claimed to be a potential method of anti-fibrosis [ 19 , 49 ]. More and more scientific reports have evidenced the efficacy of traditional Chinese herbs for treating chronic liver diseases since these herbs usually displayed multi-ingredients, multi-mechanism and low adverse effects [ 19 , 49 , 50 ].…”

“…Due to these reasons, to induce the apoptosis of activated HSCs has been claimed to be a potential method of anti-fibrosis [ 19 , 49 ]. More and more scientific reports have evidenced the efficacy of traditional Chinese herbs for treating chronic liver diseases since these herbs usually displayed multi-ingredients, multi-mechanism and low adverse effects [ 19 , 49 , 50 ]. Various experimental data demonstrated that dimethylnitrosamine (DMN) and transforming growth factor-1 (TGF-1) can induce activated quiescent hepatic stellate cells into proliferating myofibroblast-like cells resulting in hepatic accumulation of extracellular matrix and liver fibrosis [ 51 , 52 ].…”

“…In the previous reports, P. linteus exhibited wide spectrum of bioactivities, such as anti-platelet aggregation, anti-diabetic, anti-dementia, antioxidant, anti-inflammatory, cytotoxic and anti-viral effects [ 13 , 14 , 15 , 16 , 17 , 18 ]. In our previous paper, the mycelium ethanol extract of P. linteus and purified compound phellinulin A ( 1 ) displayed significant protection against hepatic fibrosis [ 19 ]. Although various compounds had been identified from the cultured mycelium of P. linteus and reported significant antioxidant and anti-inflammatory activities [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ], there were no comprehensive investigations regarding the bioactive compounds to inhibit hepatic fibrosis.…”