Anti-tumour Effect and Pharmacokinetics of an Active Ingredient Isolated from <i>Inonotus hispidus</i>

Abstract

Inonotus hispidus is an anti-tumour drug used in folk medicine. (4S,5S)-4-Hydroxy-3,5-dimethoxycyclohex-2-enone (HDE) is a compound isolated from Inonotus hispidus for the first time. However, the mechanisms underlying its therapeutic effects have not been elucidated. In this study, the in vitro screening, in vivo anti-tumour effects, mechanism of action, pharmacokinetics, and tissue distribution of HDE were investigated. HDE could inhibit the proliferation of HepG2 cells. Additionally, its half-maximal inhibitory concentration was 7.9 µg/mL. Increasing HDE concentrations significantly increased apoptosis rate in a dose-dependent manner. Furthermore, HDE was rapidly absorbed into mouse plasma, reaching a maximum concentration at 30 min. The area under the plasma HDE concentration-time curves for the studied organs were as follows: spleen > liver > lung > kidney > muscle > thymus > heart > brain. HDE also inhibited tumour growth up to 69%. The weights of organs harvested from HDE-treated mice were not significantly different from those harvested from control mice. Furthermore, HDE upregulated Fas expression and downregulated FasL expression in HepG2 cells. HDE significantly increased caspase-3 and caspase-8 activity. The antitumour effect of HDE might be realized by activating the Fas-mediated apoptotic pathway. We also found that HDE undergoes enterohepatic circulation or is quickly absorbed by the body, and the drug is released back into systemic circulation. In conclusion, HDE significantly inhibited H22 hepatocarcinoma cells (H22) tumour growth in mice without damaging organs; therefore, it may be suitable for treating liver cancer.

Diverse Metabolites and Pharmacological Effects from the Basidiomycetes Inonotus hispidus

“…In their experiments to examine the fatty acid composition of fruiting bodies, Zan et al discovered two hydrocarbons, squalene ( 56 ) and docosane ( 57 ), and one phthalate, 1,2-benzenedicarboxylic acid mono(2-ethylhexyl) ester ( 58 ) [ 15 ]. In the separation of anticancer active components, Yang et al isolated a new compound from the methanol extract of fruiting bodies in 2019 and confirmed its structure as (4S,5S)-4-Hydroxy-3,5-dimethoxycyclohex-2-enone (HDE, 59 ) by LC-MS and NMR [ 27 ]. When analyzing the methanol extract composition of I. hispidus fruiting bodies, Yang et al identified a nucleoside compound, inosine ( 60 ), based on a comparison of UV absorption characteristics and retention time with a standard [ 20 ].…”

Comparative Analysis of Metabolic Compositions and Trace Elements of Inonotus hispidus Mushroom Grown on Five Different Tree Species

“… 2 Previous chemical studies showed that it produced a series of active compounds such as polysaccharides, polyphenols, triterpenes, sterols, and melanin. 1 , 3 , 4 Recent investigations have revealed that fruiting body extracts of I. hispidus have antitumor, 5 , 6 antiviral, 7 immunomodulatory, 8 antioxidant, 9 and hypolipidemic activities. 10 The I. hispidus mushroom has great application value and development potential in the field of functional food and medicine in the future.…”

Influence of selenium on the mycelia of the shaggy bracket fungus, Inonotus hispidus

“…34,35 Extracts of I. hispidus have been reported to possess a wide range of beneficial properties including antiviral activity, antioxidant activity, antitumor, immunomodulation activities and hypolipidemic activity. [36][37][38][39][40][41][42] Inonotus hispidus extracts have also been shown to provide a protective effect for acute alcoholic liver injury. 43 A number of studies have sought to identify bioactive ingredients such as polysaccharides, triterpenoids and phenolic compounds.…”

“…Extracts of I . hispidus have been reported to possess a wide range of beneficial properties including antiviral activity, antioxidant activity, antitumor, immunomodulation activities and hypolipidemic activity 36‐42 . Inonotus hispidus extracts have also been shown to provide a protective effect for acute alcoholic liver injury 43 .…”