A network pharmacology-based strategy to explore the pharmacological mechanisms of Antrodia camphorata and antcin K for treating type II diabetes mellitus.

BACKGROUND: Diabetes mellitus is a chronic carbohydrate metabolism disorder, which could develop a series of complications and thus lead to poor quality of life or even mortality. Antrodia camphorata is a rare parasitic fungus and has been proven to be effective for treating type II diabetes. PURPOSE: This study aims to evaluate the anti-diabetic activities of A. camphorata and its main compound antcin K, as well as to demonstrate the mechanisms. STUDY DESIGN AND METHODS: Network pharmacology was used to explore the potential targets of 12 major compounds of A. camphorata on diabetes. The core targets were analyzed by protein-protein interactions and the key pathways were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG). The anti-diabetic effects of A. camphorata and antcin K were evaluated using a high-fat diet (HFD)-induced diabetic mice model and oral glucose tolerance test (OGTT). The mRNA expressions were assessed using qPCR. RESULTS: Network pharmacology revealed 17 core targets between the 12 compounds and diabetes. The insulin resistance and NF-κB signaling pathways were enriched using KEGG. Five insulin resistance-related targets were focused on and antcin K (1/2) was discovered in the compound-target-pathway network. In vivo studies exhibited that A. camphorata and antcin K could dose-dependently reduce blood levels of glucose and lipids, decrease serum levels of insulin and leptin, and increase serum levels of adiponectin in HFD mice (p < 0.05). The mechanism could be through modulating the expressions of Tnfα, Il6, and Pparγ. The OGTT test also showed the down-regulatory effects of A. camphorata and antcin K on blood glucose. CONCLUSION: This study demonstrates that A. camphorata and its major compound antcin K possess potent anti-diabetic effects. The mechanism may be through the insulin resistance pathway.

Chemical constituents from the dish-cultured Antrodia camphorata and their cytotoxic activities.

One new meroterpenoid, antroquinonol Y (1), a new ergostane-type sterol, antcamphin Y (2), and a new ergostane-type triterpenoid, antcamphin Z (3), together with 10 known ones (4-13), were isolated from the dish-cultured fungus Antrodia camphorata. Their structures were characterized by extensive NMR and HRESIMS data analyses. The absolute configurations were elucidated by experimental and calculated electronic circular dichroism (ECD) spectral analyses and chemical semi-synthesis. Compounds 1, 3, and 5 exhibited potent inhibitory activities against four human cancer cell lines (U251, HL60, SW480, and A549 cells) with IC50 values of 4.6 to 11.7 µM.

Hepatoprotective activities of Antrodia camphorata and its triterpenoid compounds against CCl4-induced liver injury in mice.

ETHNOPHARMACOLOGY RELEVANCE: Antrodia camphorata (AC) is a rare and precious fungus indigenous to Taiwan used as a traditional medicine for the treatment of liver injury. Triterpenoids are the major bioactive constituents of A. camphorata and have been reported to possess hepatoprotective activities. To meet the increasing demand, artificial cultivation techniques have been developed. AIM OF THE STUDY: This study aims to evaluate the hepatoprotective activities of AC samples derived from different cultivation techniques and to dissect the main active triterpenoid compounds. MATERIALS AND METHODS: The ethanol extracts of five batches of AC samples, including wild growing fruiting bodies, cutting wood culture fruiting bodies, dish cultures, cutting wood culture mycelia, and submerged fermentation mycelia were orally administered (50mg/kg or 200mg/kg) to ICR mice for 7 days. On the last day, CCl4 (0.2%, 7mL/kg, i.p.) was used to induce liver injury, and the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined 24h after the injection. Moreover, a HepG2 cell model treated with CCl4 (0.35%) was used to screen the protective activities of 29 AC triterpenoids. After incubation for 6h, viabilities of the cells were tested using MTS assay. The in vivo hepatoprotective activities of antcin B and antcin K were further studied on the mice model by ALT and AST tests and histopathologic examinations. To elucidate the mechanisms, the mRNA levels of iNOS, COX2, TNF-α and IL-1ß, and the protein levels of NF-κB (p65/p-p65), iNOS and COX2 in liver tissues were determined. RESULTS: The wild growing or cutting wood culture fruiting bodies, and the dish cultures of AC showed more potent activities than the mycelia (P<0.001). At 20µM, 16 of 29 triterpenoids showed significant protective activities, increasing HepG2 cell viability from 46% of the CCl4 group to >90%. Antcin B and antcin K could dose-dependently (10 or 50mg/kg, 7 days, i.g.) decrease the serum levels of ALT and AST, and decrease the incidence of liver necrosis. The effects of 50mg/kg of antcin K or antcin B were almost identical to those of 100mg/kg silymarin. Furthermore, qRT-PCR and Western blotting analyses revealed they could down-regulate IL-1ß, TNF-α, iNOS, COX-2 and NF-κB in liver tissues at both transcriptional and translational levels. CONCLUSION: The results indicate that cultivation techniques remarkably affect the hepatoprotective activities of AC. Antcin K and antcin B are the major hepatoprotective compounds of A. camphorata, and the mechanism is related with anti-inflammation. Given its high natural abundance and good oral absorption, antcin K could be a promising drug candidate for liver injury.