Abstract
Triterpene acids (TAs) are the major bioactive constituents in the medicinal fungus Ganoderma lingzhi. However, fermentative production of TAs has not been optimized for commercial use, and whether the TAs isolated from G. lingzhi submerged culture mycelia possess antitumor activity needs to be further proven. In this study, enhanced TA yield and productivity were attained with G. lingzhi using response surface methodology. The interactions of three variables were studied using a Box-Benhnken design, namely initial pH, dissolved oxygen (DO) and fermentation temperature. The optimum conditions were an initial pH of 5.9, 20.0% DO and 28.6 °C. These conditions resulted in a TA yield of 308.1 mg/L in a 5-L stirred bioreactor. Furthermore, the optimized conditions were then successfully scaled up to a production scale of 200 L, and maximum TA production and productivity of 295.3 mg/L and 49.2 mg/L/day were achieved, which represented 80.9% and 111.5% increases, respectively, compared with the non-optimized conditions. Additionally, the triterpene acid extract (TAE) from G. lingzhi mycelia was found to be cytotoxic to the SMMC-7721 and SW620 cell lines in vitro, and the TAE exhibited dose-dependent antitumor activity against the solid tumor sarcoma 180 in vivo. Chemical analysis revealed that the key active triterpene compounds, ganoderic acid T and ganoderic acid Me, predominated in the extract.
Highlights
Ganoderma (Ganodermaceae) is a genus of edible and medicinal mushroom that is known as “reishi” in Japanese and “lingzhi” in Chinese [1]
Previous studies have demonstrated that ganoderic acids A, T, Me, DM and lucidenic acid F isolated from the fruiting bodies or spores of G. lucidum exhibit antitumor activities [5,27,28,29,33,34], and ganoderic acid B exhibits inhibitory activity against HIV-1
Exhibited the same inhibitory effects against the two cell lines in the first 8 h (p > 0.05) and induced greater mortality against the SW620 cells than the SMMC-7721 cells when the treatment time reached 12 h or longer (p < 0.05). These results indicate that the crude triterpene acid extract (TAE) was cytotoxic to human hepatoma SMMC-7721 and human colon carcinoma SW620 cells, and the SW620 cells were more sensitive to the Triterpene acids (TAs) from submerged culture G. lingzhi mycelium
Summary
Ganoderma (Ganodermaceae) is a genus of edible and medicinal mushroom that is known as “reishi” in Japanese and “lingzhi” in Chinese [1]. The medicinal values of this mushroom were documented thousands of years ago [1]. Among the species of the genus, G. lucidum Karst was originally described as coming from Europe and is known in East Asia, Europe and North America. A new species G. lingzhi Sheng H. Cao & Y.C. Dai, which is distributed in East Asia, was proposed. The most striking characteristics that differentiate G. lingzhi
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