Nyasol

Appl Microbiol Biotechnol. 2017 Jun;101(11):4521-4532.

General assay for enzymes in the heptose biosynthesis pathways using electrospray ionization mass spectrometry.[Pubmed: 28280867 ]

The ADP-L-glycero-β-D-manno-heptose and the GDP-6-deoxy-α-D-manno-heptose biosynthesis pathways play important roles in constructing lipopolysaccharide of Gram-negative bacteria. Blocking the pathways is lethal or increases antibiotic susceptibility to pathogens. Therefore, the enzymes involved in the pathways are novel antibiotic drug targets.
METHODS AND RESULTS:
Here, we designed an efficient method to assay the whole enzymes in the pathways using mass spectrometry and screened 148 compounds. One promising lead is (-)-Nyasol targeting D-glycero-α-D-manno-heptose-1-phosphate guanylyltransferase (HddC) included in the GDP-6-deoxy-α-D-manno-heptose biosynthesis pathway from Burkholderia pseudomallei.
CONCLUSIONS:
The inhibitory activity of the lead compound against HddC has been confirmed by blocking the system transferring the guanosine monophosphate (GMP) moiety to α-D-glucose-1-phosphate. (-)-Nyasol exhibits the half maximal inhibitory concentration (IC50) value of 17.6 μM. A further study is going on using (-)-Nyasol derivatives to find better leads with high affinity.
CONCLUSIONS:
The inhibitory activity of the lead compound against HddC has been confirmed by blocking the system transferring the guanosine monophosphate (GMP) moiety to α-D-glucose-1-phosphate. (-)-Nyasol exhibits the half maximal inhibitory concentration (IC50) value of 17.6 μM. A further study is going on using (-)-Nyasol derivatives to find better leads with high affinity.

Phytochemistry. 2003 Nov;64(5):997-1001.

Isolation and anti-oomycete activity of nyasol from Anemarrhena asphodeloides rhizomes.[Pubmed: 14561517]

METHODS AND RESULTS:
The methanol extract of Anemarrhena asphodeloides rhizomes exhibited strong antifungal activity against the plant pathogenic fungi Magnaphothe grisea, Rhizoctonia solani, and the plant pathogenic oomycete Phytophthora capsici. The antifungal substance isolated from the rhizomes of A. asphodeloides was identified to be Nyasol, (Z)-1,3-bis(4-hydroxyphenyl)-1,4-pentadiene by NMR and mass spectral analysis. Nyasol effectively inhibited the mycelial growth of Colletotrichum orbiculare, P. capsici, Pythium ultimum, R. solani, and Cladosporium cucumerinum in a range of 1-50 mug/ml, but did not affect the growth of bacteria and yeast.
CONCLUSIONS:
In a greenhouse test, treatment with the antifungal compound Nyasol was significantly effective in suppressing the Phytophthora blight on pepper plants.

J Nat Prod. 1997 Oct;60(10):1017-22.

Antiprotozoal compounds from Asparagus africanus.[Pubmed: 9358645 ]

METHODS AND RESULTS:
Two antiprotozoal compounds have been isolated from the roots of Asparagus africanus Lam. (Liliaceae), a new sapogenin, 2 beta, 12 alpha-dihydroxy-(25R)-spirosta-4,7-dien-3-one (1), which was named muzanzagenin, and the lignan (+)-Nyasol (2), (Z)-(+)-4,4'-(3-ethenyl-1-propene-1,3-diyl)-bisphenol. The structure of the sapogenin was elucidated by MS and by 1D and 2D NMR methods and established by a single crystal X-ray analysis.
CONCLUSIONS:
(+)-Nyasol potently inhibits the growth of Leishmania major promastigotes, the IC50 being 12 microM, and moderately inhibits Plasmodium falciparum schizonts with the IC50 49 microM. These concentrations only moderately affect the proliferation of human lymphocytes. Muzanzagenin showed a moderate in vitro activity in all three tests, the IC50 against leishmania promastigotes was 70 microM, and against four different malaria schizont strains the IC50 values were 16, 163, 23, and 16 microM, respectively.

Chem Biodivers. 2014 May;11(5):749-59.

Suppression of inducible nitric oxide synthase expression by nyasol and broussonin A, two phenolic compounds from Anemarrhena asphodeloides, through NF-κB transcriptional regulation in vitro and in vivo.[Pubmed: 24827684 ]

Anemarrhena asphodeloides is widely used in traditional Chinese medicine, and is known to possess antidiabetic and anti-inflammatory properties.
METHODS AND RESULTS:
Because inducible nitric oxide synthase (iNOS) plays an important role in inflammation, we investigated the inhibitory effects of two known phenolic compounds, Nyasol (1) and broussonin A (2), from A. asphodeloides, on iNOS and its plausible mechanism of action. Compounds 1 and 2 exhibited inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Compounds 1 and 2 also suppressed the expressions of iNOS protein and mRNA. Moreover, compounds 1 and 2 suppressed the expression of inflammatory cytokines such as interleukin-1β (IL-1β) and interferon-β (IFN-β). They also inhibited the transcriptional activity of NF-κB and degradation of IκB-α, as well as the activation of Akt and ERK in LPS-stimulated RAW 264.7 cells. In in vivo animal model, compounds 1 and 2 significantly inhibited TPA-induced mouse ear edema. These results suggest that 1 and 2 suppress LPS-stimulated iNOS expression at the transcriptional level through modulating NF-κB and down-regulation of the Akt and ERK signaling pathways.
CONCLUSIONS:
Taken together, these findings indicate that the suppressive effects of 1 and 2 on iNOS expression might provide one possible mechanism for their anti-inflammatory activities.

Biomed Pharmacother. 2016 Dec;84:1061-1066.

Inhibitory effects of norlignans isolated from Anemarrhena asphodeloides on degranulation of rat basophilic leukemia- 2H3Cells.[Pubmed: 27780134 ]

Anemarrhena asphodeloides is known to suppress inflammation and lower various fevers.
METHODS AND RESULTS:
To determine the active component of A. asphodeloides, ethanol (EtOH) extract of A. asphodeloides rhizomes was fractionized. The compounds isolated from the dichloromethane (CH2Cl2) soluble fraction were identified as 4'-O-methylNyasol (1), Nyasol (2), 3″-methoxyNyasol (3), 3″-hydroxy-4″-methoxy-4″-dehydroxyNyasol (4), 4-hydroxybenzaldehyde (5), and 4-hydroxyacetophenone (6). The four norlignans (1-4) potently inhibited the release of β-hexosaminidase from immunoglobulin E (IgE)/dinitrophenol-conjugated bovine serum albumin (DNP-BSA)-treated rat basophilic leukemia (RBL)-2H3 and A23187 plus phorbol 12-myristate 13-acetate co-treated isolated rat primary mast cells, as markers of degranulation and histamine release. The intraperitoneal treatment with the EtOH extract significantly suppressed the fetal reaction, and serum histamine release induced by compound 48/80 in mice.
CONCLUSIONS:
These results suggest that the four active norlignan compounds and the EtOH extract of A. asphodeloides may have potential to be developed as medicines for the treatment of allergies by inhibiting the activation of mast cells.