Translesion DNA synthesis (TLS) can bypass DNA lesions caused by chemotherapeutic drugs, which usually result in drug resistance. Given its key role in mutagenesis and cell survival after DNA damage, inhibition of the TLS pathway has emerged as a potential target for improving the efficacy of DNA-damaging agents such as cisplatin (CDDP), a widely used anticancer agent. Unfortunately, few suitable natural TLS inhibitors have been reported. Here, we found that a triterpenoid compound Ganoboninketal C (26-3) from Ganoderma boninense, a traditional Chinese medicine, can impair CDDP-induced TLS polymerase eta (Polη) focus formation, PCNA monoubiquitination as well as mutagenesis. Moreover, 26-3 can significantly sensitize tumor cells to CDDP killing and reduce the proportion of cancer stem cells in AGS and promote apoptosis after CDDP exposure. Interestingly, 26-3 can also sensitize tumor cells to Gefitinib therapy. Mechanistically, through RNA-seq analysis, we found that 26-3 could abrogate the CDDP-induced upregulation of Polη and PIDD (p53-induced protein with a death domain), two known factors promoting TLS pathway. Furthermore, we found that activating transcription factor 3 is a potential novel TLS modulator. Taken together, we have identified a natural TLS inhibitor 26-3, which can be potentially used as an adjuvant to improve clinical efficacy. 

Sugarcane leaves-derived polyphenols (SLP) have been demonstrated to have diverse health-promoting benefits, but the mechanism of action has not been fully elucidated. This study aimed to investigate the anti-metabolic disease effects of SLP and the underlying mechanisms in mice. In the current study, we prepared the SLP mainly consisting of three flavonoid glycosides, three phenol derivatives, and two lignans including one new compound, and further demonstrated that SLP reduced body weight gain and fat accumulation, improved glucose and lipid metabolism disorders, ameliorated hepatic steatosis, and regulated short-chain fatty acids (SCFAs) production and secondary bile acids metabolism in ob/ob mice. Notably, SLP largely altered the gut microbiota composition, especially enriching the commensal bacteria Akkermansia muciniphila and Bacteroides acidifaciens. Oral gavage with the above two strains ameliorated metabolic syndrome (MetS), regulated secondary bile acid metabolism, and increased the production of SCFAs in high-fat diet (HFD)-induced obese mice. These results demonstrated that SLP could be used as a prebiotic to attenuate MetS via regulating gut microbiota composition and further activating the secondary bile acids-mediated gut-adipose axis.

During a field survey of cultivated Morchella mushroom diseases, Diploöspora longispora and Paecilomyces penicillatus, causal agents of pileus rot or white mould disease were detected, which resulted in up to 80% of yield losses. Multi-locus phylogenic analysis revealed that the fungi were affiliated in a distinct clade in Hypocreales. We further constructed a phylogenetic tree with broader sampling in Hypocreales and estimated the divergence times. The D. longispora and P. penicillatus clades were estimated to have diverged from Hypocreaceae around 129 MYA and Pseudodiploösporeaceae fam. nov is herein proposed to accommodate species in this clade. Two new genera, i.e. Pseudodiploöspora and Zelopaecilomyceswere, were introduced based on morphological characteristics and phylogenic relationships of Diploöspora longispora and Paecilomyces penicillatus, respectively. Five new combinations – Pseudodiploöspora cubensis, P. longispora, P. fungicola, P. zinniae, and Zelopaecilomyces penicillatus – were proposed.

Ophiocordyceps sinensis is a well-known entomogenous fungus with its fruiting bodies or cultural mycelium as food and herbal medicines in Asia. While metabolites which could responsible for its potent pharmaceutical effects has long remained to be elucidated. In this work, chemical investigation on the solid culture of O. sinensis strain LY34 led to the discovery of six digalactosyldiacylglycerols (DGDGS, 1–6) including one new. The structure of compound 1 was determined based on the comprehensive spectra analysis, including NMR, MSⁿ, IR, and chemical derivatisation. Bioactivity studies showed a weak cytotoxicity of compounds 1–6 against 293 T cell and medium anti-inflammatory activity of compounds 1 and 2 on Raw 264.7 cell. The discovery of DGDGs in O. sinensis provides new insight into the pharmacologically active substances.

Previous study demonstrated that Ganoderma meroterpene derivative (GMD) increased the abundance of butyrate-producing bacteria in gut and subsequently delivered anti-metabolic disorder effect of host. To specify the key commensal bacteria associating with the beneficial effects, we tried to isolate and compare the microbiota from the cecal samples of GMD- and vehicle-treated ob/ob mice, and further identified butyrate-producing bacterial strains. It was found that Faeciroseburia intestinalis was enriched and 11 strains affiliated to F. intestinalis were cultivated from the gut of GMD-treated mice. In vitro assay attested butyrate production by representative strain of F. intestinalis. Oral administration with F. intestinalis further demonstrated its benefits on regulating hyperglycemia and hyperlipidemia, on decreasing plasma lipopolysaccharide (LPS) and inflammation, and on improving hepatic injuries. Treatment with F. intestinalis effectively enhanced the level of gut butyrate, which subsequently ameliorated the intestinal barrier function and activated epithelial PPAR-γ signaling pathway to regulate microbiome homeostasis in gut. Our study demonstrated that the causal relationship between the butyrate-producing bacteria and the GMD's therapeutic effects and confirmed the important function of the butyrate-producing F. intestinalis in maintaining host metabolism homeostasis.

A polyphenolic alkaloid-enriched extract (PAE) was prepared from the fruiting bodies of a wild edible mushroom Sarcodon leucopus. Oral administration of PAE reduced hyperglycemia, hyperlipidemia, hepatic steatosis, and LPS-related inflammation in high fat diet-induced obese (DIO) mice. Furthermore, we show that PAE produces taxonomic and predicted functional changes in the gut microbiome of DIO mice. A significant decrease in the family of Ruminococcaceae, especially the secondary bile acid-producing bacteria of Intestinimonas and Anaerotruncus, is detected in the gut microbiome of PAE-treate mice. Accordingly, reductions of deoxycholic acid and lithocholic acid are found in the feces of PAE-treated DIO mice, which benefits for the intestinal integrity and the reduction of inflammation. A gut microbiota related mechanism for the anti-metabolic syndrome effects of the PAE is proposed. We suppose the polyphenolic alkaloid extract from S. leucopus be a new and beneficial prebiotic regulating glucose and lipid metabolisms.

Medicinal mushroom Ganoderma sp. is considered to be a key source for the production of therapeutic agents. Our current review indicates that a limited number (<19%; 79 out of >430) of isolated compounds have been tested and known to be active against several microorganisms and parasites. In this review, we aim to summarise all the antimicrobial and anti-parasitic works on Ganoderma sp. displayed on web of science, google scholar and endnote X7 from 1932 to August 2016. We further present and discuss the structure of active compounds against microorganisms and parasites. In addition, we also discuss the possible further research to identify lead compounds from Ganoderma sp. as a novel strategy to combat the potential global emergence of bad bugs and parasites.

The present research was the first to compare nutritive and bioactive components of Pleurotus eryngii-fermented rice with untreated rice. After fermentation, the total content of crude protein, crude fat, polysaccharides, reducing sugar, and polyphenols was significantly increased in fermented rice. The total content of amino acid in fermented rice was enhanced to 557.71 mg/g in comparison with 258.83 mg/g in non-fermented rice. The content of essential amino acid increased from 79.32 mg/g to 140.36 mg/g. The content of adenosine in fermented rice (175.64 μg/g) is much higher than that of non-fermented rice (14.38 μg/g). In antioxidant assay, the ethanol extract of the P. eryngii-fermented rice showed a strong reducing ability with EC₅₀ value less than 0.25 mg/ml. These results indicated that rice fermented by P. eryngii could be useful as a new functional food.