Camphoratins A−J, Potent Cytotoxic and Anti-inflammatory Triterpenoids from the Fruiting Body of Taiwanofungus camphoratus

Abstract

Ten new triterpenoids, camphoratins A-J (1-10), along with 12 known compounds were isolated from the fruiting body of Taiwanofungus camphoratus. Their structures were established by spectroscopic analysis and chemical methods. Compound 10 is the first example of a naturally occurring ergosteroid with an unusual cis-C/D ring junction. Compounds 2-6 and 11 showed moderate to potent cytotoxicity with EC 50 values ranging from 0.3 to 3 μM against KB and KB-VIN human cancer cell lines. Compounds 6, 10, 11, 14-16, 18, and 21 exhibited antiinflammatory NO-production inhibition activity with IC 50 values of less than 5 μM, which was more potent than the nonspecific NOS inhibitor N ω -nitro-L-arginine methyl ester (L-NAME).Taiwanofungus camphoratus (synonym: Ganoderma camphoratum; Antrodia cinnamomea; Antrodia camphorata) (Polyporaceae, Aphyllophorales), is a rare and precious medical fungus in Taiwan and is called a "national treasure of Taiwan".1 Its Chinese name is ZhanKu or Niu-Chang-Chih. The microorganism is parasitic to the inner heart-wood wall of old hollow trunks of Cinnamomum kanehirai Hay. (Lauraceae). The growth rate of natural T. camphoratus in the wild is very slow, and it is difficult to cultivate in a greenhouse, making fruiting bodies expensive to obtain. In traditional Taiwanese folk medicine T. camphoratus has been used as an important health food for treating food, alcohol, and drug intoxication, -methylergost-8,24(28)-diene-3,11-dion-26-oate (21),10 and ergosterol peroxide (22).11 Cytotoxic activity, inhibition of nitric oxide (NO) or reactive oxygen species (ROS) production, and free radical-scavenging activity of the isolates were evaluated in our study. NIH Public Access Results and DiscussionCamphoratin A (1) was obtained as a colorless powder. , suggested a 4-methylergost-8-en-11-one skeleton similar to that of antcin C (16).5 The 3α-OH functionality was deduced by the correlations from H-3 (δ 3.89, 1H, d, J = 1.6 Hz, β-orientation) to C-4 and C-1 and from H 3 -29 to C-3, C-4, and C-5 in the HMBC spectrum of 1. The hydroxy groups attached at C-7 and C-12 were further designated by the correlations from H-7 (δ 4.52, 1H, t, J = 8.4 Hz) to C-6 and C-8 and from H-12 (4.44, 1H, s) to C-13, C-14, and C-17, respectively. The C-25 carboxylic functionality was assigned due to the presence of an HMBC correlation from H-25 (δ 3.45, 1H, q, J = 6.8 Hz) to the carbon resonance at δ 176.9. A comparison of the NMR spectroscopic data of 1 with those of 165 confirmed the above elucidation and unambiguously established the structure of 1. The relative configuration of 1 was determined by the NOE correlations observed in a NOESY experiment. In the NOESY spectrum of 1, H-7 showed NOE enhancements with both H-5 and H-14, suggesting that these protons had α-orientations. Furthermore, NOE correlations between H-3 and H-4 as well as between H-12 and H 3 -18 disclosed that these protons are β-oriented.Camphoratin B (2) was obtained as a colorless syrup. The HRESIMS of 2 gave an [M + Na] + peak at m/z 495.3089 ...

Zhankuic Acid A Isolated from Taiwanofungus camphoratus Is a Novel Selective TLR4/MD-2 Antagonist with Anti-Inflammatory Properties

“…ZAA was isolated from T. camphoratus as previously described (10,15). The compound was dissolved at a concentration of 2 mg/ml in 40% cyclodextrin (Sigma-Aldrich, St. Louis, MO) for use as stock solutions, stored at 220˚C, and diluted with cell culture medium prior to each experiment.…”

“…Zhankuic acid A (ZAA), the predominant pharmacologically active compound in the fruiting body of T. camphoratus, has been shown to prevent inflammatory responses by human neutrophils, without exerting significant cytotoxicity (9). Moreover, ZAA also displays potent anti-inflammatory activity by inhibiting LPS-induced NO production (10). However, the mechanisms of regulations and ameliorations of inflammation by ZAA have not been well elucidated.…”

Zhankuic acid A as a novel JAK2 inhibitor for the treatment of concanavalin A-induced hepatitis

“…ZAA was isolated from T. camphoratus as previously described [15,16]. The compound was dissolved in 40% cyclodextrin (SigmaAldrich, St. Louis, MO) at a concentration of 2 mg/mL for use as stock solution, stored at À20 8C, and diluted with cell culture medium prior to each experiment.…”

Drimane-type Sesquiterpenes with a Dioxabicyclooctane Skeleton from the Fruiting Bodies ofNigrofomes melanoporusand Their Cytotoxicity

“…The constituents of the fruiting bodies of these fungi have been evidenced to be rich sources of biological properties, such as anti-inflammatory [1,2], antihypertensive [3,4], antitumor [5][6][7][8][9], and immunomodulatory and adjuvant activities [10]. We had previously reported the cytotoxicity of benzenoids and triterpenoids from Taiwanofungus camphorates [11,12], triterpenoids from Ganoderma lucidum [13], and the chemical constituents from Cordyceps sinensis [14]. In our continuing program aimed to search for potential antitumor agents from natural sources, the fruiting bodies of Nigrofomes melanoporus (Mont.)…”