The complete mitochondrial genome of medicinal fungus Taiwanofungus camphoratus reveals gene rearrangements and intron dynamics of Polyporales

Taiwanofungus camphoratus is a highly valued medicinal mushroom that is endemic to Taiwan, China. In the present study, the mitogenome of T. camphoratus was assembled and compared with other published Polyporales mitogenomes. The T. camphoratus mitogenome was composed of circular DNA molecules, with a total size of 114,922 bp. Genome collinearity analysis revealed large-scale gene rearrangements between the mitogenomes of Polyporales, and T. camphoratus contained a unique gene order. The number and classes of introns were highly variable in 12 Polyporales species we examined, which proved that numerous intron loss or gain events occurred in the evolution of Polyporales. The Ka/Ks values for most core protein coding genes in Polyporales species were less than 1, indicating that these genes were subject to purifying selection. However, the rps3 gene was found under positive or relaxed selection between some Polyporales species. Phylogenetic analysis based on the combined mitochondrial gene set obtained a well-supported topology, and T. camphoratus was identified as a sister species to Laetiporus sulphureus. This study served as the first report on the mitogenome in the Taiwanofungus genus, which will provide a basis for understanding the phylogeny and evolution of this important fungus.

The Regulatory Effects of a Formulation of Cinnamomum osmophloeum Kaneh and Taiwanofungus camphoratus on Metabolic Syndrome and the Gut Microbiome

The number of people with metabolic syndrome (MetS) is increasing year by year, and MetS is associated with gut microbiota dysbiosis. The demand for health supplements to treat or prevent MetS is also growing. Cinnamomum osmophloeum Kaneh (CO) and Taiwanofungus camphoratus (TC) are endemic to Taiwan. Both have been shown to improve the symptoms of MetS, such as dyslipidemia and hyperglycemia. Herein, we investigated the effect of CO, TC and their formulations on diet-induced obese mice. Male C57BL/6J mice were fed with a high-fat diet (HFD) for 10 weeks to induce MetS. After that, the mice were fed with HFD supplemented with CO, TC, and various CO/TC formulations, respectively, for 14 weeks. The changes in physiological parameters and the composition of the gut microbiome were investigated. The results indicated that CO, TC, and their formulations effectively reduced hyperglycemia, and tended to alleviate MetS in obese mice. Moreover, we also observed that CO, TC, and their formulations improved gut microbiota dysbiosis by decreasing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of Akkermansia spp. Our results revealed that CO and TC might have potential for use as a prebiotic dietary supplement to ameliorate obesity-related metabolic disorders and gut dysbiosis.

Zhankuic Acids A, B and C from Taiwanofungus camphoratus Act as Cytotoxicity Enhancers by Regulating P-Glycoprotein in Multi-Drug Resistant Cancer Cells

Since P-glycoprotein (P-gp)-related multidrug resistance (MDR) remains the most important unsolved problem in cancer treatment, scientists are attempting to find potential structures from natural resources. The aim of the present study was to elucidate whether the triterpenoids from Taiwanofungus camphoratus could reverse cancer MDR by influencing P-gp efflux pump. Substrates efflux assay and P-gp ATPase activity assay were conducted to reveal the molecular mechanisms of P-gp inhibition, while SRB assay, cell cycle analyses and apoptosis analyses were performed to confirm the cancer MDR modulating effects. The results indicated that Zhankuic acids A, B and C (ZA-A, ZA-B and ZA-C) impacted P-gp efflux function in competitive, noncompetitive and competitive manners, respectively. Furthermore, these triterpenoids all demonstrated inhibitory patterns on both basal P-gp ATPase activity and verapamil-stimulated ATPase activity. In terms of MDR reversal effects, ZA-A sensitized the P-gp over-expressing cell line (ABCB1/Flp-InTM-293) and MDR cancer cell line (KB/VIN) toward clinically used chemotherapeutic drugs, including doxorubicin, paclitaxel and vincristine, exhibiting the best cytotoxicity enhancing ability among investigated triterpenoids. The present study demonstrated that ZA-A, ZA-B and ZA-C, popular triterpenoids from T. camphoratus, effectively modulated the drug efflux transporter P-gp and reversed the cancer MDR issue.

Constituents and Anti-Multidrug Resistance Activity of Taiwanofungus camphoratus on Human Cervical Cancer Cells

Resistance to anti-cancer drugs is one of the main factors of treatment failure resulting in high morbidity. Among the reasons of resistance, overexpression of efflux pumps leading to multidrug resistance is an important issue that needs to be solved. Taiwanofungus camphoratus has been used as a nutritional supplement to treat various cancers. However, its effects on the resistance to chemotherapeutic agents are still unknown. In this study, we report four new chemical constituents of T. camphoratus isolated from an ether extract: camphoratins K (1) and N (2) and benzocamphorins G (3) and I (4). Furthermore, we evaluated zhankuic acids A–C for their P-glycoprotein (P-gp) inhibitory effects. The results showed that zhankuic acid A was the most potent P-gp inhibitor compound and (at 20 μM) could reverse drug resistance in human cancer cells, restoring an IC50 of 78.5 nM for doxorubicin, of 48.5 nM for paclitaxel, and of 321.5 nM for vincristine, indicating a reversal fold of 48, 38, and 45 times, respectively. This study provides support for the use of T. camphoratus in the further development of cancer therapy.

Immunomodulatory Effects of Fruiting Body Extract and Solid-State-Cultivated Mycelia of Taiwanofungus camphoratus

Taiwanofungus camphoratus is a rare and valuable medicinal mushroom indigenous to Taiwan. It has traditionally been used to promote good health. This study aimed to explore the immunomodulatory effects of “Leader Deluxe Taiwanofungus camphoratus capsule” (LDAC). LDAC is a healthy food product composed of fruiting body extract and solid-state-cultivated mycelia of T. camphoratus. Two complementary studies were performed. In the first, LDAC was orally administered to BABL/c female mice for 6 weeks as part of a non-specific immune study. In the second, mice were treated with LDAC for 8 weeks and immunized with ovalbumin (OVA) in a specific immune study. LDAC increased the growth of splenic immune cells and enhanced the activity of macrophages and natural killer cells. It increased the levels of interleukin (IL)-2, interferon (IFN)-γ, serum immunoglobulin (Ig)G, and OVA-IgG, and decreased the levels of IL-4, IL-5, tumor necrosis factor (TNF)-α, serum IgE, and OVA-IgE. Thus, the findings of this study strongly supported the idea that LDAC possesses immunomodulatory activity.

Medicinal Mushroom Taiwanofungus camphoratus: A potential cure for cancer

Background: Based on traditional and folk medicine, mushrooms have been developed into anti-cancer therapeutics. In this article, a brief overview is given of the most important medical mushroom species and their specific anti-cancer functions and mechanisms. Taiwanofungus camphoratus (Antrodia cinnamomea), is a medical fungus chosen to examine the process from ethnomedicine to developing new products for the market based on scientific, analytic, and experimental evidence. The bioactive compounds have indirect effects in cancer treatment by benefiting the immune system as well as having direct cytotoxic effects on cancer cells.Taiwanofungus camphoratus is a fungus endemic to Taiwan and one of the most popular known alternative remedies for liver cancer in Taiwan. To date, more than 150 liver cancer patients have survived using T. camphoratus. The treatment has caused tumor shrinking, as well as the disappearance of a tumor altogether in some cases. The ratio between male and female patients has been nearly equal, with ages ranging between 20-79 years. The most effective candidates are those between the ages of 40-60 years.The complex mixture of bioactive compounds in natural fruit bodies is a challenge for artificial production in vitro. Particular problems in developing T. camphoratus into therapeutics for the global market are its rarity in nature and its close dependence on an endemic tree in Taiwan. These challenges can help promote new solutions which could be utilized in the future with other medical fungiKeywords: Medicinal mushrooms, anti-cancer therapeutics, Taiwanofungus camphoratus, liver cancer.