Co-reporter:Weifa Zheng;Meimei Zhang;Yanxia Zhao;Kangjie Miao;Shenyuan Pan;Feng Cao;Yucheng Dai
Phytochemical Analysis 2011 Volume 22( Issue 2) pp:95-102
Publication Date(Web):
DOI:10.1002/pca.1225
Abstract
Introduction – The sclerotia of Inonotus obliquus (Chaga) are effective therapeutic agents to treat several human malignant tumours and other diseases without unacceptable toxic side-effects.
Objective – To investigate solvent effects on metabolic profiles and antioxidant activities of extracts of Chaga.
Methodology – Chaga was extracted by petroleum ether, chloroform, ethyl acetate, acetone, ethanol and water. Solvent effects on metabolites in the extracts were assayed by NMR-based metabolomic analysis. Antioxidant activities were indicated as capacities for scavenging superoxide anion, DPPH and hydroxyl radicals.
Results – Petroleum ether and chloroform extracts contained primarily lanostane-type triterpenoids (LT), whereas the extracts of ethyl acetate, acetone and ethanol were characterised by the predominant presence of hispidin analogues and LT, and water extracts by polysaccharides and phenolic compounds. The ethyl acetate, acetone, ethanol and water extracts revealed remarkable potential for scavenging the tested radicals, while those of petroleum ether and chloroform did not. Polyphenols are the major contributors for quenching the tested free radicals, while in LT only compounds 16, 17 and 22 participated in scavenging hydroxyl radicals.
Conclusion – Polyphenols in Chaga are the principles for quenching free radicals while polysaccharides and a few LT compounds contribute partially in scavenging DPPH and hydroxyl radicals, respectively. NMR-based metabolomic analysis is a useful method by which to correlate 1H-NMR spectra of Chaga extracts with their antioxidant activities, and this allows the prediction of potentials for scavenging free radicals by 1H-NMR spectroscopy. Copyright © 2011 John Wiley & Sons, Ltd.
Co-reporter:Weifa Zheng;Yanxia Zhao;Xin Zheng;Yubing Liu
Applied Microbiology and Biotechnology 2011 Volume 89( Issue 1) pp:157-167
Publication Date(Web):2011 January
DOI:10.1007/s00253-010-2846-2
While Inonotus obliquus produces a diverse range of bioactive metabolites in its natural habitats, it accumulates less in its submerged cultures. We show here that coculture of I. obliquus with Phellinus punctatus resulted in less production of mycelial biomass but an increased accumulation of phenolic compounds, melanins, and lanostane-type triterpenoids. Metabolites increased in production by coculture include phelligridin C, phelligridin H, methyl inoscavin A, inoscavin C, inoscavin B, davallialactone, methyl davallialactone, foscoparianol D, 21,24-cyclopentalanosta-3β,21,25-triol-8-en, lanosta-7,9(11),23-triene-3β,22,25-triol, and inotodisaccharide and melanins. Metabolites from coculture also showed an increased potential for scavenging free radicals and inhibiting the proliferation of HeLa 229 cells. Davallialactone, methyl davallialactone, and minor phenolic components are the major contributors for scavenging DPPH and hydroxyl radical in monoculture, and phelligridin C, phelligridin H, methyl inoscavin A, inoscavin C, methyl davallialactone, foscoparianol D, and inotodisaccharide are those for scavenging the tested radicals in coculture. Lanostane-type triterpenoids indicated limited roles in scavenging free radicals. Nearly all the detected metabolites correlate positively with inhibiting proliferation of HeLa 229 cells. Thus, coculture of I. obliquus with other fungi seems to be a cost-effective strategy for upregulating biosynthesis of bioactive metabolites.
Co-reporter:Weifa Zheng;Yubing Liu;Shenyuan Pan
Applied Microbiology and Biotechnology 2011 Volume 90( Issue 5) pp:
Publication Date(Web):2011 June
DOI:10.1007/s00253-011-3241-3
Nitric oxide (NO) has been evidenced to mediate biosynthesis of polyphenols in Inonotus obliquus. However, it remains unknown how NO regulates their biosynthesis. Here we show that higher cellular NO levels coincided with higher accumulation of S-nitrosothiols (SNO; the products of NO combined with a specific residue in glutathione or proteins) and polyphenols, and higher activity of denitrosylated S-nitrosoglutathione reductase (GSNOR) and thioredoxin reductase (TrxR). This homeostasis was breached by GSNOR or TrxR inhibitors. Inhibiting GSNOR boosted TrxR activity, but reduced SNO formation, coinciding with an enhanced production of polyphenols. Likewise, inhibiting TrxR increased GSNOR activity and SNO production, but downregulated accumulation of polyphenols. Inhibiting GSNOR or TrxR also modified the polyphenolic profiles of I. obliquus. Suppressing GSNOR-enhanced biosynthesis of phelligridins C and H, inoscavin C and methyl inoscavin B, but reduced that of phelligridin D, methyl inoscavin A, davallialactone and methyl davallialactone, the typical polyphenols in I. obliquus. Similarly, downregulating TrxR increased production of phelligridin D, methyl inoscavin A, davallialactone, and methyl davallialactone, but shrinking that of phelligridins C and H, methyl inoscavin B and inoscavin C. Thus, in I. obliquus, the state of S-nitrosylation and denitrosylation affects not only the accumulation of polyphenols, but also their metabolic profiles.
Co-reporter:Weifa Zheng;Kangjie Miao;Yubing Liu
Applied Microbiology and Biotechnology 2010 Volume 87( Issue 4) pp:1237-1254
Publication Date(Web):2010 July
DOI:10.1007/s00253-010-2682-4
Inonotus obliquus (Fr.) Pilat is a white rot fungus belonging to the family Hymenochaetaceae in the Basidiomycota. In nature, this fungus rarely forms a fruiting body but usually an irregular shape of sclerotial conk called ‘Chaga’. Characteristically, I. obliquus produces massive melanins released to the surface of Chaga. As early as in the sixteenth century, Chaga was used as an effective folk medicine in Russia and Northern Europe to treat several human malicious tumors and other diseases in the absence of any unacceptable toxic side effects. Chemical investigations show that I. obliquus produces a diverse range of secondary metabolites including phenolic compounds, melanins, and lanostane-type triterpenoids. Among these are the active components for antioxidant, antitumoral, and antiviral activities and for improving human immunity against infection of pathogenic microbes. Geographically, however, this fungus is restricted to very cold habitats and grows very slowly, suggesting that Chaga is not a reliable source of these bioactive compounds. Attempts for culturing this fungus axenically all resulted in a reduced production of bioactive metabolites. This review examines the current progress in the discovery of chemical diversity of Chaga and their biological activities and the strategies to modulate the expression of desired pathways to diversify and up-regulate the production of bioactive metabolites by the fungus grown in submerged cultures for possible drug discovery.
Co-reporter:Feng Shi, Chunmei Li, Ming Xia, Kangjie Miao, Yanxia Zhao, Shujiang Tu, Weifa Zheng, Ge Zhang, Ning Ma
Bioorganic & Medicinal Chemistry Letters 2009 Volume 19(Issue 19) pp:5565-5568
Publication Date(Web):1 October 2009
DOI:10.1016/j.bmcl.2009.08.046
The green chemoselective synthesis of thiazolo[3,2-a]pyridine derivatives was achieved in water via microwave-assisted three-component reactions of malononitrile, aromatic aldehydes and 2-mercaptoacetic acid with molar ratios of 2:1:1.5 and 2:2.2:1, respectively. These compounds were subject to the experiments of antioxidant activity and cytotoxicity to carcinoma HCT-116 cells and mice lymphocytes. Nearly all of the tested compounds possessed potent capacities for scavenging free radicals. In addition, most of these compounds showed cytotoxicity to HCT-116 cells and mice lymphocytes with no selectivity. Of these, only thiazolo[3,2-a]pyridine derivative 5d suggested selective cytotoxicity to tumor cell line HCT-116 cells.The green chemoselective synthesis of thiazolo[3,2-a]pyridines was achieved in water via microwave-assisted three-component reactions with different molar ratios of the reactants. Their antioxidant activity and cytotoxicity to carcinoma HCT-116 cells and mice lymphocytes were bioassayed. Compound 5d suggested selective cytotoxicity to tumor cell line HCT-116 cells.
