Keywords

1 Introduction

Edible and medicinal fungi have been widely consumed as food ingredients for centuries, not only for their good flavor and texture but also for their substantial nutritional value and potential medicinal value (Zjawiony 2004). It is commonly accepted that there are about 10,000 fungi species and 473 medicinal fungi species in China (Dai and Yang 2008). The fruiting bodies of these mushrooms were used in Chinese traditional medicine to treat various diseases, such as the fruiting bodies of Hericium erinaceus was used to treat gastricism and hyperglycemia (Mizuno 1999); Antrodia camphorata for treating liver diseases, food and drug intoxication, diarrhea, abdominal pain, hypertension, allergies, skin itching, and tumorigenic diseases (Ao et al. 2009); Ganoderma lucidum and Ganoderma sinense for the treatment of neurasthenia, insomnia, anorexia, dizziness, chronic hepatitis, hypercholesterolemia, coronary heart disease, hypertension, and carcinomas (China Pharmacopoeia Committee 2010); and so on. Recently, edible and medicinal fungi were recognized as a prolific source of natural products with diverse structures and distinct pharmacological potential, such as davallialactone from Inonotus xaranticus improving the aging process (Yang et al. 2013a); thelephantin O from Thelephora aurantiotincta inhibiting the proliferation of cancer cells (Norikura et al. 2013); 4,7-dimethoxy-5-methyl-1,3-benzodioxole (DMB) from A. camphorata exhibiting antiproliferative, antitumor, and anti-inflammatory effects (Chen et al. 2007; Tu et al. 2012); erinacines A-K from H. erinaceus possessing stimulatory activity for the biosynthesis of nerve growth factor (Kawagishi et al. 1994, 1996a, b, 2006; Lee et al. 2000); and so on. Herein, we review the studies on isolation, structural elucidation, and biological activities of the bioactive compounds derived from edible and medicinal fungi conducted by Chinese scientists after 2007. The names, fungi sources, and bioactivities, along with the references of these bioactive compounds, have been listed in Table 9.1.

Table 9.1 Bioactive compounds isolated from edible and medical fungi in China
Full size table

2 Terpenoids

Terpenoids are the most abundant and structurally diverse higher fungi natural products. Sesquiterpenoids gained attention because of their roles for finding new lead structures for medicinal chemistry. More than 30 skeletons of sesquiterpenoids have been reported in edible and medicinal fungi, including humulane, illudane, tremulane, lactarane, marasmane, and drimane. Diterpenoids have fewer structures than sesquiterpenoids. In this review, we mainly concentrate on cyathane. As for triterpenoids, lanostane is the most classic type.

2.1 Monoterpenoids

Five monoterpenoids (1–5) were obtained from the solid culture of Pleurotus cornucopiae. Compounds 1–5 showed moderate inhibition against nitric oxide production in lipopolysaccharide-activated macrophages, with an IC50 value of 81.8, 88.8, 80.4, 65.6, and 72.8 μM, respectively (Wang et al. 2013a). A monoterpenoid, 5-(hydroxymethyl)-2-(prop-1-en-2-yl) cyclohexanol (6), was isolated from the fruiting body of Flammulina velutipes (Cai et al. 2013).

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2.2 Sesquiterpenoids

2.2.1 Flammulina velutipes

F. velutipes is a rich source of sesquiterpenoids with the various skeleton and interesting medicinal properties. More than 40 sesquiterpenoids have been obtained in recent years. Twelve new cuparene-type sesquiterpenes, flamvelutpenoids A–F (7–12) and enokipodins E–J (13–18), and three known sesquiterpenoids, 2,5-cuparadiene-1,4-dione (19) and enokipodins B (20) and D (21), were isolated from the solid culture of F. velutipes (Wang et al. 2012a, b; Tao et al. 2016a). Flamvelutpenoids A–D (7–10) showed weak antibacterial activity against Escherichia coli, Bacillus subtilis, and methicillin-resistant Staphylococcus aureus with MIC values larger than 100 μM (Wang et al. 2012a). Enokipodins F–G (14–15) and enokipodin I (17) showed weak antifungal activity against Aspergillus fumigatus; compounds 18–21 showed both moderate cytotoxicity against the human tumor cell lines (HepG2, MCF-7, SGC7901, and A549) and antioxidant activity in DPPH scavenging assay (Wang et al. 2012b). Flammufuranones A (22) and B (23) are two seco-cuparane sesquiterpenoids which may share a common precursor with cuparene-type sesquiterpene and biosynthesized from 1,6-cyclization (Tao et al. 2016a). Sterpurols A (24) and B (25), two new sterpurane sesquiterpenes, and sterpuric acid (26), a known sterpurane sesquiterpene, were isolated from the solid culture of F. velutipes (Wang et al. 2012b). Eight sesquiterpenoids including flammulinol A (27) with a new carbon skeleton and flammulinolides A–G (28–34), seven isolactarane-related norsesquiterpenes, were obtained from F. velutipes cultivated on cooked rice (Wang et al. 2012c). Flammulinolides A–B (28–29) and F (33) showed strong cytotoxicity against KB cell line with the IC50 of 3.9, 3.6, and 4.7 μM, respectively. Flammulinolide C (30) showed strong cytotoxicity against HeLa cell line with the IC50 of 3.0 μM. Ten new sesquiterpenes with nor-eudesmane skeletons, flammuspirones A–J (35–44), as well as two new cadinene sesquiterpenes, 7,13,14-trihydroxy-4-cadinen-15-oic acid methyl ester (45) and 1,2,6,10-tetrahydroxy-3,9-epoxy-14-nor-5(15)-eudesmane (46), were obtained from the ethyl acetate extract of the solid culture of F. velutipes which is a wild strain collected in Yunnan province of China (Tao et al. 2016a). Among these compounds, compounds 35, 37, and 45–46 were found to inhibit the HMG-CoA reductase (HMGR) with IC50 of 114.7, 77.6, 55.5, and 87.1 μM, respectively. Compounds 37–39, 42, 44 and 46 showed DPP-4 inhibitory activity with IC50 of 75.9, 83.7, 70.9, 79.7, 80.5, and 74.8 μM, respectively. Identification of more than 40 sesquiterpenes with diverse skeletons and bioactivity provided evidence for the future application of F. velutipes as a functional food.

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2.2.2 Pleurotus cystidiosus

Pleurotons A–B (47–48), two bisabolane-type sesquiterpenoids, and clitocybulols D–F (49–51), three clitocybulol derivatives, were isolated from the ethyl acetate extract of the solid culture of P. cystidiosus (Zheng et al. 2015). Compounds 47–51 showed significant cytotoxicity against two human prostate cancer DU-145 and C42B cells. The IC50 of compounds 47–51 was 174, 28, 233, 162, and 179 nM, respectively, against the DU-145 cell and was 104, 52, 163, 120, and 119 nM, respectively, against the C42B cell. A further chemistry investigation of the solid culture of the P. cystidiosus led to the identification of clitocybulols G–O (52–60) (Tao et al. 2016b). Clitocybulols G (52) and L (57) exhibited moderate inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 36.0, 49.5, and 38.1 μM, respectively. All compounds had no significant inhibition against α-glucosidase, sucrose, and maltase.

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2.2.3 Pleurotus cornucopiae

Pleurospiroketals A–E (61–65), five new sesquiterpenes, as well as three related sesquiterpenes (66–68) were obtained from the solid culture of P. cornucopiae (Wang et al. 2013b). Compound pleurospiroketals A–C (61–63) showed inhibitory activity against nitric oxide production in lipopolysaccharide-activated macrophages with IC50 values of 6.8, 12.6, and 20.8 μM, respectively. Compounds 66 and 68 exhibited slight growth inhibition against HeLa cells (IC50 values of 36.0 and 70.6 μM) and HepG2 (IC50 values of 68.6 and 76.8 μM).

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2.2.4 Pleurotus citrinopileatus

Seven new sesquiterpenes, pleurospiroketal F (69) and pleurotins A–F (70–75), as well as a known sesquiterpene pleuroton B (48), were obtained from the solid culture of P. citrinopileatus (Tao et al. 2016c). Pleurotins A (70) and E (74) exhibited inhibitory activity on PTP1B with IC50 of 32.1 μM and 30.5 μM, respectively.

2.2.5 Laetiporus sulphureus

Seven new drimane-type sesquiterpenoids, sulphureuines B–H (76–82), were isolated from cultures of mushroom Laetiporus sulphureus (He et al. 2015a). Sulphureuine B (76) induces apoptosis in glioma cells through endoplasmic reticulum stress, mitochondrial, and death receptor signaling pathways. Two illudin-type sesquiterpenoids, phellinuin J (83) and sulphureuine A (84), were obtained from the fermentation extract of L. sulphureus (He et al. 2015b). The two compounds were purposely evaluated for their cytotoxicity against HL-60, SMMC-7721, A549, MCF-7, and SW480 cell lines. Unfortunately, no significant inhibitory activity was found.

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2.2.6 Xylaria nigripes

Xylaria nigripes has long been used as a traditional Chinese medicine (TCM) for enhancing memory, immunity, and hematopoiesis, treating insomnia and trauma, and as a diuretic, nerve tonic, and antidepressant (Liang et al. 2011; Ko et al. 2011; Zhao et al. 2014). Six new eremophilane-type sesquiterpenes, nigriterpenes A–F (85–90), were isolated from the ethyl acetate extracts of the fermented broths of termite nest-derived X. nigripes (Chang et al. 2017). These compounds were evaluated against lipopolysaccharide-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) expression, and NO production in murine brain microglial BV-2 cells. Nigriterpene C (87) exerted significant inhibitory effects on two induced enzymes and NO production without any significant cellular toxicity. Nigriterpene C (87) exhibited concentration-dependent inhibition on NO production and iNOS and COX-2 expression with IC50 values of 21.7 ± 4.9, 8.1 ± 2.3, and 16.6 ± 5.5 μM, respectively. The results indicated that the potential anti-inflammatory effects of nigriterpene C (87) on murine brain microglial BV-2 cells might provide a rationale for the traditional medical uses of X. nigripes for treating insomnia and depression.

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2.2.7 Boletus edulis

Three non-isoprenoid botryane sesquiterpenoids, named boledulins A–C (91–93), were isolated from the cultures of basidiomycete B. edulis (Feng et al. 2011). Boledulin A (91) exhibited moderate inhibitory effects on HL-60, SMMC-7721, A-549, MCF-7, and SW480 with IC50 values of 2.6, 8.4, 8.3, 3.4, and 3.5 μM, respectively.

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2.2.8 Inonotus vaninii

I. vaninii has been used in Chinese folk medicine as “sang huang” for the treatment of cancer, diabetes, liver, and heart diseases and stomach ailments in Northeastern China (Dai et al. 2010). A novel sesquiterpene, inonolane A (94), was isolated from the EtOAc extract of the medicinal fungus I. vaninii (Yang et al. 2013b). Inonolane A (94) represents the first bisabolane-type sesquiterpene from the genus Inonotus.

2.2.9 Ganoderma sinense

Ganosinensine (95), a new sesquiterpene, was isolated from the fruiting bodies of the fungus G. sinense (Liu et al. 2012).

2.2.10 Dictyophora indusiata

A sesquiterpene antibiotic, albaflavenone (96), was isolated from the dried fruiting body of D. indusiata by solvent extraction and column chromatography (Huang et al. 2011). The content of albaflavenone (96) in the dried fruiting body of D. indusiata was quantified by GC through an external standard method to be about 0.0063%. Albaflavenone (96) has a camphor-like odor.

2.3 Diterpenoids

2.3.1 Cyathus spp.

The species belonging to the genus Cyathus (Nidulariaceae family) are recognized as prolific producers of bioactive cyathane diterpenoids with a unique [5-6-7] tricyclic ring skeleton. Cyathane diterpenoids represent a group of natural products with great diversity in both structure and bioactivity (Shen et al. 2009). Five novel cyathane diterpenes, cyathins D–H (97–101), as well as three known diterpenes, neosarcodonin O (102), cyathatriol (103), and 11-O-acetylcyathatriol (104), were isolated from the solid culture of Cyathus africanus (Han et al. 2013). Compounds 99, 101, 102, and 104 showed potent inhibition of nitric oxide production in lipopolysaccharide-activated macrophages with an IC50 value of 2.57, 1.45, 12.0, and 10.73 μM, respectively. Neosarcodonin O (102) and 11-O-acetylcyathatriol (104) showed strong cytotoxicity against HeLa and K562 cell lines with the IC50 value less than 10 μM. Cyathin R (105), a new cyathane diterpenoid, was isolated from the solid culture of C. africanus (Huang et al. 2015). A further chemistry investigation of the solid culture of the C. africanus led to the identification of three new cyathane diterpenoids, cyathin T (106), cyathin V (107), and cyathin W (108) (Han et al. 2015). Cyathins T (106) and W (108) showed moderate inhibition against nitric oxide production in lipopolysaccharide-activated macrophages with an IC50 value of 88.87 and 80.07 μM, respectively. In cytotoxicity assay, cyathin W (108) showed weak cytotoxicity against K562 cell line with the IC50 value of 12.1 μM. Cyathin Q (109), a new cyathane-type diterpene, was obtained from the culture of the fungus C. africanus by bioactivity-guided separation (He et al. 2016). The bioactivity evaluation shows that cyathin Q (109) exhibited anticancer activity via induction of mitochondria- and autophagy-dependent apoptosis in HCT116 cells. Cyathin I (110), a new cyathane diterpene, and two related diterpenes, (12R)-11a,14a-epoxy-13a,14b,15-trihydroxycyath-3-ene (111) and erinacine I (112), were obtained from the fermentation broth of Cyathus hookeri (Xu et al. 2013). Compounds 110–112 showed inhibition against nitric oxide production in macrophages with an IC50 value of 15.5, 52.3, and 16.8 μM, respectively. Seven new cyathane-type diterpenes, cyathins J–P (113–119), and two known diterpenes (120–121) were isolated from the solid culture of Cyathus gansuensis (Wang et al. 2014a). Bioactivity screening indicated that cyathins J–K (113–114), M (116), and compound 120 showed moderate inhibitory activity against NO production in lipopolysaccharide-activated macrophages with an IC50 value of 42, 78, 80, and 16 μM, respectively. A chemical investigation of the solid culture of Cyathus striatus led to the identification of six new cyathane xylosides, striatoids A–F (122–127) (Bai et al. 2015). The bioactivity evaluation shows that striatoids A–F (122–127) dose-dependently enhanced nerve growth factor (NGF)-mediated neurite outgrowth.

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2.3.2 Hericium erinaceus

The fruiting bodies of this mushroom were used in Chinese folk medicine to treat the tumors of the digestive systems, such as esophageal, stomach, and duodenum cancers and hyperglycemia. The chemical constituents of H. erinaceum were widely investigated. Aromatic compounds and diterpenoids with various bioactivities have been isolated from H. erinaceus. A new diterpene (128) was isolated from the fungal mycelia of H. erinaceus by the tracking method of antibacterial activity (Zhang et al. 2015a). Compound 128 showed good cytotoxicity against tumor cell lines (K562 and HEP2) with IC50 < 200 μM.

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2.3.3 Pleurotus eryngii

Eryngiolide A (129), a new diterpenoid with unprecedented skeleton, was obtained from the mycelia of edible mushroom P. eryngii fermented on rice (Wang et al. 2012d). This compound was tested for their cytotoxic effects against two human cancer cell lines, HeLa and HepG2, using the MTT method. Eryngiolide A (129) showed moderate toxicities against two cell lines with IC50 values of 20.6 and 28.6 μM, respectively. This macrocyclic diterpene can be formed by a [6 + 6] cycloaddition from two molecules of geranyl pyrophosphate (GPP).

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2.4 Triterpenoids

2.4.1 Ganoderma boninense

In a searching for new bioactive agents from medicinal mushrooms, the fruiting bodies of G. boninense collected from the Hainan province of China (Quinlan Nature Reserve) were chemically investigated. As a result, ganoboninketals A–C (130–132), three new nortriterpenes, were obtained from the fruiting bodies of G. boninense (Ma et al. 2014). Ganoboninketals A–C (130–132) exhibited significant antiplasmodial activity against Plasmodium falciparum with IC50 values of 4.0, 7.9, and 1.7 μM, respectively. Ganoboninones A–F (133–138), six new nortriterpenes, were also isolated from the fruiting bodies of the medicinal mushroom G. boninense (Ma et al. 2015). Ganoboninones A–B (133–134) and F (138) showed antimalarial effects with IC50 values of 27.36, 15.68, and 2.03 μM, respectively. In a transactivation assay, ganoboninketals A–C (130–132) and ganoboninone E (137) showed agonistic activity to LXRβ with an EC50 value of 8.32, 257.00, 86.70, and 203.00 nM, respectively.

2.4.2 Ganoderma leucocontextum

G. leucocontextum, also called “White Lingzhi” due to its white fleshy fruiting bodies, enjoys a strong reputation for being one of the top high-quality Lingzhi in China for its health function from folk usage. Chemical investigation of cultivated and wild G. leucocontextum led to the discovery of more than 50 triterpenoids with diverse bioactivity. Ganoleucoins A–P (139–154), 16 new lanostane triterpenes, were obtained from the cultivated fruiting bodies of G. leucocontextum (Wang et al. 2015a). Compounds 139, 141, 144, and 148–152 exhibited strong inhibitory activity against HMG-CoA reductase. Compounds 139–140, 144–145, 148, 150, and 154 showed cytotoxicity against K562 cells with IC50 values in the range 10–20 μM.

A chemical research on the fruiting bodies of wild G. leucocontextum led to the identification of 18 new triterpenoids, leucocontextins A–R (155–172), (Zhao et al. 2016a). Leucocontextin R (172) presented weak cytotoxicity against K562 and MCF-7 cell lines with the IC50 of 20.35 and 28.66 μM, respectively. Leucocontextins S–X (173–178), six new triterpenoids, were obtained from the fruiting bodies of wild G. leucocontextum (Zhao et al. 2016b). The inhibitory activities against K562, SMMC-7721, and MCF-7 cell lines for leucocontextins S–X (173–178) were evaluated. Unfortunately, none of them showed significant activity.

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2.4.3 Ganoderma lucidum

G. lucidum, a TCM called Lingzhi, is one of the most highly ranked herbal medicines by Asian people, whose fruiting body, mycelia, and spores were traditionally used as a folk medicine for treatment of debility and weakness, insomnia, hepatitis, cardiovascular diseases, cancer, etc. (Lin 2001; Gao and Zhou 2004; Lin and Zhang 2004). Modern research revealed the bioactivity components of G. lucidum to be triterpenes and polysaccharides, which were reported to possess antivirus (Li and Wang 2006), anti-inflammation (Akihisa et al. 2007), antitumor (Nonaka et al. 2006), immunity-promoting (Zhu et al. 2007), and antidiabetic effects (He et al. 2006). In the latest 10 years, chemical investigation of the metabolites in G. lucidum led to identification of 11 new triterpenes, ganoderitriol M (179), ethyl lucidenate A (180), ethyl 7β-hydroxy-4,4,14α-trimethyl-3,11,15-trioxo-5α-chol-8-en-24-oate (181), 23S-hydroxy-3,7,11,15-tetraoxo-lanost-8,24E-diene-26-oic acid (182), 12β-acetoxy-3β-hydroxy-7,11,15,23-tetraoxo-lanost-8,20E-diene-26-oic acid (183), and compounds 184–189 (Chen et al. 2009; Li et al. 2013a; Zhang et al. 2011; Guan et al. 2008; Cheng et al. 2010). Ethyl lucidenate A (180) exhibited cytotoxicity against HL-60 and CA46 cell with IC50 values of 25.98 and 20.42 μgmL−1, respectively (Li et al. 2013a). Compound 181 had NGF-like neuronal survival-promoting activities (Zhang et al. 2011). Compounds 182–183 exhibited cytotoxicity against four human tumor cell lines, p388, HeLa, BEL-7402, and SGC-7901, with the IC50 values in the range of 8–25 μM (Guan et al. 2008).

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2.4.4 Ganoderma sinense

G. sinense, a well-known species of Ganoderma, is widely distributed in Yunnan province, in the southwest of China. Compared with G. lucidum, chemical studies on G. sinense have rarely been reported. Ganolactone B (190) and ganoderiol A triacetate (191), two novel lanostane-type triterpenes, were isolated from the fruiting bodies of G. sinense (Qiao et al. 2007). To further discover structurally diverse and biologically significant compounds from the G. sinense, three new triterpenoids, methyl ganosinensate A (192), ganosinensic acid A (193), and ganosinensic acid B (194), with an unusual four-membered ring produced by linkage of C-1 with C-11 were isolated from the fruiting body of G. sinense (Wang et al. 2010). In 2011, nine new triterpenoids ganosineniol A (195), ganosinoside A (196), ganoderic acid Jc (197), ganoderic acid Jd (198), ganodermatetraol (199), ganolucidic acid γa (200), ganolucidate F (201), ganoderiol J (202), and methyl lucidenate Ha (203) were isolated from the fruiting bodies of the fungus G. sinense (Liu et al. 2012). Among these compounds, ganoderic acid Jc (197) displayed selective inhibitory activity against HL-60 cells (IC50 = 8.30 μM). Ganodermatetraol (199) and ganolucidate F (201) showed induction ability of hPXR-mediated CYP3A4 expression.

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2.4.5 Ganoderma cochlear

G. cochlear has the same morphological characteristics as G. sinense, but the fungus stipe of G. cochlear lies in the back of the pileus. Initial phytochemical investigation on G. cochlear resulted in the identification of two new 3,4-secotrinorlanostane triterpenoids, fornicatin G (204) and H (205) (Peng et al. 2012). To discover additional biologically functional triterpenoids from G. cochlear, the chemical constitutes of G. cochlear were studied. As a result, cochlates A (206) and B (207), two novel trinorlanostanes with a 3,4-seco-9,10-seco-9,19-cyclo skeleton, as well as six new triterpenoids, fornicatins D–F (208–210) and ganodercochlearins A–C (211–213), were obtained from the fruiting bodies of G. cochlear (Peng et al. 2014a). Fornicatins D (208) and F (210) lowered the ALT and AST levels in HepG2 cells treated with H2O2, suggesting that both compounds could display in vivo hepatoprotective activities. In 2015, a rearranged hexanorlanostane triterpenoid featuring with a γ-lactone ring and a five-membered carbon ring, ganocochlearic acid A (214), and 11 new lanostane triterpenoids cochlate C (215), cochlearic acid A (216), ganodecochlearin D (217), ganodercochlearin E (218), cochlearic acid B (219), and ganodercochlearins F–K (220–225) were isolated from the fruiting bodies of G. cochlear (Peng et al. 2015a). Ganodercochlearins F–H (220–222) and J–K (224–225) showed moderate cytotoxic activities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) with IC50 values ranging from 8 to 30 μM. Ganodecochlearin D (217) exhibited relatively potent cytotoxic activity against MCF-7 cells (IC50: 9.15 μM), compared to the positive control (cisplatin, IC50: 12.7 μM).

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2.4.6 Laetiporus sulphureus

Two 3,4-seco-lanostane-type triterpenes, 15α-hydroxy-3,4-secolanosta-4(28),8,24-triene-3,21-dioic acid (226) and 5α-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid 3-methyl ester (227), and one lanostane triterpene 15α-acetoxylhydroxytrametenolic acid (228) together with versisponic acid D (229) were isolated from the fruiting bodies of L. sulphureus (Yin et al. 2015). Compounds 226–229 were evaluated by MTT method for their cytotoxicities against five human cancer cell lines, breast cancer MCF-7, hepatocellular carcinoma SMMC-7721, human myeloid leukemia HL-60, colon cancer SW480, and lung cancer A-549. However, none exhibited inhibitory effects. From the EtOAc extracts of the same fungal culture broth, compounds 230 and 231 were obtained (He et al. 2015a). Compound 230 showed moderate activities against four cells HL-60, SMMC-721, A-549, and SW-480, with IC50 values of 37.5, 14.8, 15.6, and 36.1 μM, respectively. Eburicoic acid (232) is the main bioactive component in the L. sulphureus (Wang et al. 2015b). Eburicoic acid (232) protected the gastric mucosa from gastric lesions morphologically and especially attenuated H+/K+-ATPase activity.

2.4.7 Pleurotus eryngii

2,3,6,23-Tetrahydroxy-urs-12-en-28-oic acid (233), 2,3,23-trihydroxyurs-12-en-28-oic acid (234), and lupeol (235) were identified from the EtOAc-soluble portion of P. eryngii extract (Xue et al. 2015). The three isolated compounds were evaluated for the proliferation inhibition activity against the human breast cancer cell line MCF-7 using the MTT assay. All of the compounds significantly inhibited MCF-7 cell proliferation. The IC50 values were 15.71, 48.00, and 66.89 μM, respectively. Compound 233 showed greater antitumor activity than compound 234, indicating that the presence of an additional hydroxyl group at C-6 enhances the cytotoxic effect. Compounds 233–234, with the carboxylic acid at C-28, showed slightly more potent inhibitory activities in MCF-7 cells than 235, which lacks a carboxy group at C-28. These results suggest that a free carboxylic group at C-28 may be important to exert antiproliferative activity.

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3 Meroterpenoids

Meroterpenoids are hybrid natural products of both terpenoid and nonterpenoid origin. They have attracted much attention due to their unusual structure features, wide range of bioactivities and interesting biosynthetic mechanisms (Geris and Simpson 2009). Based on the biosynthetic origins, meroterpenoids can be classified into two groups: polyketide-terpenoids and shikimate-terpenoids.

3.1 Shikimate-Terpenoids

3.1.1 Ganoderma lucidum

(+)-Lingzhiol (236) and (−)-lingzhiol (237), a pair of rotary door-shaped meroterpenoidal enantiomers, were isolated from G. lucidum (Yan et al. 2013). Lingzhiols (236–237) bears an unusual 5/5/6/6 ring system characteristic of sharing a C-3-C-7 axis. The biological evaluation showed that (+)-lingzhiol (236) or (−)-lingzhiol (237) could selectively inhibit the phosphorylation of Smad3 in TGF-β1-induced rat renal proximal tubular cells and activate Nrf2/Keap1 in mesangial cells under diabetic conditions. Further chemistry investigation on the fruiting body of G. lucidum led to the isolation of six new meroterpenoids, chizhines A–F (238–243) (Luo et al. 2015a). Chizhines A–F (238–243) are isolated as racemic mixtures. Chiral HPLC was utilized to obtain the individual (+)- and (−)-antipodes of these substances. The renoprotective effects of chizhines A–F (238–243) were evaluated by using the ELISA technique and high glucose-induced rat mesangial cells. The results show that the individual enantiomers of these substances significantly inhibit monocyte chemotactic protein 1 (MCP-1) and fibronectin production in a dose-dependent manner. Lingzhifuran A (244) and lingzhilactones D–F (245–247), four new phenolic meroterpenoids, were isolated from the fruiting bodies of G. lucidum (Ding et al. 2016). Lingzhifuran A (244) and lingzhilactone D (245) could selectively inhibit TGF-β1-induced Smad3 phosphorylation in rat renal tubular epithelial cells, representing novel scaffolds of selective Smad3 activation inhibitors.

3.1.2 Ganoderma lingzhi

G. lingzhi is a valuable, edible, and medicinal fungus that has been widely used for the prevention and treatment of a broad range of diseases. Spirolingzhines A–D (248–251), four new meroterpenoids with aspiro[benzofuran-2,10-cyclopentane] motif, and lingzhines A–F (252–257), six new meroterpenoids with diverse ring systems, were isolated from the fruiting bodies of G. lingzhi (Yan et al. 2015a). (−)-Spirolingzhine A (248) was shown to affect NSC cell cycle progression using the 5-bromo-2-deoxyuridine (BrdU) incorporation assay. Three new lingzhilactones A–C (258–260) containing a fused lactone moiety were isolated from G. lingzhi (Yan et al. 2015b). Lingzhilactone B (259) could inhibit ROS generation in a dose-dependent manner; inhibit mRNA expression of collagen IV, fibronectin, and IL-6; and increase expression of Nrf2 in rat tubular epithelial cells. Furthermore, we found that compound 259 could reduce urinary albumin levels, abrogate myofibroblastic activation, and inhibit the phosphorylation of Smad3 in Adriamycin-induced mice.

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3.1.3 Ganoderma sinensis

(−)-Sinensilactam A (261) and (+)-sinensilactam A (262), novel hybrid metabolites possessing a unique 2Hpyrrolo[2,1-b] [1,3]oxazin-6(7H)-one ring system, were isolated from the fruit bodies of G. sinensis (Luo et al. 2015b). (−)-Sinensilactam A (261) was found to be a Smad3 phosphorylation inhibitor in TGF-β1-induced human renal proximal tubular cells. Zizhines A–F (263–268), six new meroterpenoid, were also isolated from the fruiting bodies of G. sinensis (Cao et al. 2016).

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3.1.4 Ganoderma cochlear

Four pairs of new polycyclic-meroterpenoid enantiomers, ganocins A–C (269–271) possessing a spiro[4,5]decane ring system, along with ganocin D (272) with an eight-membered ring, were isolated from the fruiting bodies of G. cochlear (Peng et al. 2014b). Ganocin D (272) had weak anti-AChE activity with an inhibition of 32% (50 μM). (+)- and (−)-Cochlearols A (273) and B (274), two meroterpenoids with novel polycyclic skeletons, were isolated from the fruiting bodies of the fungus G. cochlear (Dou et al. 2014). Biological studies showed that (−)-cochlearol B (274) is a strong inhibitor of p-Smads, exhibiting renoprotective activities in TGF-β1-induced rat renal proximal tubular cells. Cochlearoids A–E (275–279) and cochlearines A (280) and B (281) were obtained from G. cochlear (Zhou et al. 2015). Compounds (+)-275, (−)-278, and (±)-280 exhibited significantly inhibited Cav3.1 TTCC and showed noticeable selectivity against Cav1.2, Cav2.1, Cav2.2, and Kv11.1 (hERG) channels. Five novel meroterpenoids, ganoderin A (282) and ganocochlearins A–D (283–286), with the polycyclic skeleton and two new prenylated phenols, fornicin D (287) and ganomycin C (288) with a carbon chain, were isolated from the fruiting bodies of G. cochlear (Peng et al. 2015b). All compounds showed an antioxidant effect in radical scavenging assays. Six novel meroterpenoids cochlearoids F–K (289–294) were isolated by utilizing phytochemical approaches (Wang et al. 2016a). The biological evaluation shows that compounds 289–292 and 294 exhibit potent inhibitory activity on fibronectin overproduction in TGF-β1-induced HKC-8 cells.

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3.1.5 Ganoderma applanatum

Applanatumin A (295), a novel meroterpenoid dimer, was isolated from the fungus G. applanatum (Luo et al. 2015c). Applanatumin A exhibits potent antifibrotic activity in TGF-β1-induced human renal proximal tubular cells. Applanatumols A (296) and B [(±)-297], two unique meroterpenoids, respectively, with a novel spiro[benzofuran-2,2′-bicyclo[3.2.2] nonane] ring system and a naturally unusual dioxacyclopenta[cd]inden motif, were isolated from G. applanatum (Luo et al. 2016a). The biological evaluation shows that 296 and (+)-297 are potent ECM inhibitors in TGF-β1-induced rat proximal tubular epithelial cells, suggesting that these metabolites could be used as novel structure templates for synthesizing more potent agents which are beneficial for CKD. (±)-Ganoapplanin (298), a pair of novel meroterpenoid enantiomers featuring an unprecedented dioxaspirocyclic skeleton constructed from a 6/6/6/6 tetracyclic system and an unusual tricyclo-[4.3.3.03′,7′]dodecane motif, were isolated from G. applanatum (Li et al. 2016a). Spiroapplanatumines A–Q (299–315), 17 new spiro meroterpenoids, respectively, bearing a 6/5/7 or 6/5/5 ring system, were isolated from the fruiting bodies of the fungus G. applanatum (Luo et al. 2017). Biological evaluation of spiroapplanatumines A–Q disclosed that spiroapplanatumines G–H (305–306) inhibited JAK3 kinase with IC50 values of 7.0 ± 3.2 and 34.8 ± 21.1 μM, respectively. Twenty-six new meroterpenoids, applanatumols C–Z (316–339), Z1 (340), and Z2 (341), were isolated from the fruiting bodies of G. applanatum (Luo et al. 2016b). Applanatumols C (316) was found to have COX-2 inhibitory effect with an IC50 value of 25.5 μM.

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3.1.6 Ganoderma leucocontextum

Three new meroterpenoids, ganoleucins A–C (342–344), were isolated from the fruiting bodies of G. leucocontextum (Wang et al. 2016b). Ganoleucins A (342) and C (344) showed noncompetitive inhibitory activity against α-glucosidase. (+)- and (–)-Ganodilactone (345), a pair of novel meroterpenoid dimers possessing a unique 5′H-spiro[chroman-4,2′-furan]-2,5′-dione ring system, were discovered from the fruiting bodies of G. leucocontextum (Chen et al. 2016). (±)-, (+)-, and (–)-Ganodilactone (345) showed pancreatic lipase inhibitory activities and exhibited the IC50 values as 27.3, 4.0, and 2.5 μM, respectively.

3.1.7 Ganoderma capense

Two new macrocyclic meroterpenoids, ganocapensins A–B (346–347), together with three new aromatic meroterpenoids, ganomycins E–F (348–349) and fornicin E (350), were isolated from the fruiting bodies of G. capense (Peng et al. 2016). Compounds 346–350 exhibited antioxidant effects with IC50 values ranging from 6.00 ± 0.11 to 8.20 ± 0.30 μg/ml in the DPPH radical scavenging assay.

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3.2 Polyketide-Terpenoids

3.2.1 Hericium erinaceus

H. erinaceus is an important edible and medicinal mushroom. The fruiting bodies and mycelia of this mushroom have been used as an herbal medicine for the treatment of gastricism and hyperglycemia in China. The chemical constituents of H. erinaceum were widely investigated. Aromatic compounds and diterpenoids with various bioactivities have been isolated from H. erinaceus. Fourteen new meroterpenoids, erinacerins C–L (351–360) and erinacerins Q–T (361–364), were obtained from the mycelia of H. erinaceus fermented on rice (Wang et al. 2015c, d). Compounds 352–364 exhibited inhibitory activity against α-glucosidase with IC50 values ranging from 5.3 to 145.1 μM. Erinacerins Q–T (361–364) showed inhibitory activities against PTP1B. Erinaceolactams A–E (365–369), five new isoindolinones, were isolated from 70% ethanol extract of the fruiting bodies of H. erinaceus (Wang et al. 2016c). Five new meroterpenoid, erinaceolactones D–F (370–372), hericenone K (373), and hericenone L (374), were isolated from the fruiting bodies of H. erinaceus (Wang et al. 2016d; Zhang et al. 2015b; Ma et al. 2012). Hericenone L (374) exhibited cytotoxic activity against EC109 cell line with an IC50 of 46 μg·L−1. Hericenone K (373) exhibited weak neurite outgrowth-promoting activity in NGF-induced PC12 cells.

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3.2.2 Antrodia camphorata

Four ubiquinone derivatives, antrocamol LT1 (375), antrocamol LT2 (376), antrocamol LT3 (377), and antroquinonol (378), were isolated from A. camphorata mycelium (Yen et al. 2015). Compounds 375–378 showed cytotoxicities against CT26, A549, HepG2, PC3, and DU-145 cell lines with IC50 values ranging from 0.01 to 1.79 μΜ. Antroquinonol B (379) and 4-acetyl-antroquinonol B (380) were obtained from the mycelium of A. camphorata (Yang et al. 2009). The two compounds were evaluated for their effects on the inhibition of NO production in LPS-activated murine macrophages. The bioassay displayed that compounds 379 and 380 possessed effects on NO inhibition, with IC50 values of 16.2 ± 0.8 and 14.7 ± 2.8 μg/mL, respectively. Moreover, antroquinonol D (381), a ubiquinone derivative, was isolated from the solid-state fermented mycelium of A. camphorata (Wang et al. 2014b). Some research illuminated that antroquinonol D induces DNA demethylation and the recovery of multiple tumor suppressor genes while inhibiting breast cancer growth and migration potential.

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3.2.3 Armillaria mellea

A. mellea is an important TCM used in dispelling the wind and removing an obstruction in the meridians and strengthening tendons and bones. Two new protoilludane sesquiterpene aryl esters, 5′-methoxy-armillasin (382) and 5-hydroxyl-armillarivin (383), as well as eight known protoilludane sesquiterpene aryl esters, armillaridin (384), armillartin (385), armillarin (386), melleolide B (387), armillarilin (388), armillasin (389), armillarigin (390), and melleolide (391), were isolated from the mycelium of A. mellea (Li et al. 2016b). Compounds 383–385 and 388–391 exhibited highly cytotoxic activity against HepG2 cells (4.95–37.65 μg/mL). Among all the ten compounds, melleolide (391) showed the best cytotoxic activity for HepG2 cells (4.95 μg/mL) and lower activity for L02 cells (16.05 μg/mL).

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4 Polyketide

4.1 Neolentinus lepideus

N. lepideus is a basidiomycete mushroom of the genus Neolentinus, previously well known as Lentinus lepideus. It is one of the popular edible mushrooms in China, Japan, and Korea. Three new polyketides, 5-methoxyisobenzofuran-4,7(1H,3H)-dioneone (392), 1,3-dihydroisobenzofuran-4,6-diol (393), and benzoquinone derivative (394), were obtained from the solid culture of N. lepideus fermented on cooked rice (Li et al. 2013b). In the DPPH scavenging assay, compound 393 displayed antioxidant activity with IC50 of 68.6 μM. Compounds 392–394 showed potent inhibition of nitric oxide production in macrophages with an IC50 value of 6.2, 88.8, and 100 μM, respectively.

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4.2 Pleurotus spp.

6-Dimethoxyisobenzofuran-1(3H)-one (395), a known polyketide, was isolated from the culture broth of the fungus P. eryngii (Liu et al. 2013). Three polyketides, 5, 7-dimethoxyisobenzofuran-1(3H)-one (396), 3, 5-dihydroxybenzyl acetate (397), and 2,4-dihydroxy-6-(hydroxymethyl) benzaldehyde (398), were isolated from the solid culture of P. citrinopileatus (Li et al. 2013c). Compounds 396–398 showed moderate chelating capacity with percent chelating value of 28.77%, 29.72%, and 39.47% at a concentration of 200 μmol/L, respectively. Compound 396 showed weak reducing ability with percent reducing the value of (22.22 ± 5.44) % at the concentration of 200 μmol/L.

5 Alkaloids and Other Nitrogen-Containing Compounds

5.1 Hericium erinaceus

Four new alkaloids, erinacerins M–P (399–402), were obtained from the mycelia of H. erinaceus fermented on rice (Wang et al. 2015d). Erinacerins M–P (399–402) showed moderate cytotoxicity against K562 cells with IC50 values of 16.3, 18.2, 15.9, and 11.4 μM, respectively, and also weak cytotoxicity against doxorubicin-resistant K562 cells.

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5.2 Lepista sordida

L. sordida, a basidiomycetous fungus of the family Tricholomataceae, is an edible agaric species. Three new 3,6-dioxygenated diketopiperazines, lepistamides A–C (403–405), along with a known compound, diatretol (406), were isolated from the mycelial solid cultures of the L. sordida (Chen et al. 2011). Compounds 403–406 were all found to be inactive (IC50 > 100 μg/ml) in the evaluation of the cytotoxic activity against Astc-a-1 (lung cancer), Bel-7402 (liver cancer), and HeLa (cervical carcinoma) cell lines by means of the MTT assay method.

5.3 Ganoderma spp.

Five new alkaloids, sinensines A–E (407–411), were isolated from the fruiting bodies of G. sinense (Liu et al. 2010, 2011). Sinensine A (407) exhibited activity in protecting the injury induced by hydrogen peroxide oxidation on human umbilical cord endothelial cells (HUVEC), with EC50 value of 6.2 mmol/L. Four new polycyclic alkaloids, lucidimines A–D (412–415), were isolated from the fruiting bodies of G. lucidum (Zhao et al. 2015).

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6 Conclusion

In the past 10 years, substantial progress has been made by Chinese scientists in the field of bioactive metabolites from edible and medicinal fungi. Chemical investigations of the fruiting bodies and culture broth of the edible and medicinal fungi collected in China have resulted in 415 compounds including 90 sesquiterpenoids and 115 meroterpenoids belonging to shikimate-terpenoids. These compounds exhibit various bioactivities including antibacterial, antioxidant, anticancer, antiplasmodial, antiproliferative, antifibrotic, and neurite outgrowth-promoting activities. Edible and medicinal fungi produce enormously diverse metabolites, but only a small number has been explored. It is promising to search for leads of new drugs by continuing the further chemical investigations of edible and medicinal fungi.