Yong-Xian Cheng

Antioxidant, Anti-Inflammatory and Anti-Influenza Properties of Components from Chaenomeles speciosa

The fruit of Chaenomeles speciosa is a traditional Chinese medicine used for the treatment of dyspepsia and various inflammatory diseases. In the present study, we evaluated the potential radical scavenging capacity, and activity against nitrous oxide, inflammatory cytokines production and neuramindase (NA) of its isolates. The results showed that 3,4-dihydroxybenzoic acid (1) displayed higher inhibitory activities on DPPH and NA with IC50 values of 1.02 μg/mL and 1.27 μg/mL respectively, and quercetin (2) also showed significant inhibitory action on DPPH and NA, with IC50 values of 3.82 μg/mL and 1.90 μg/mL. Compounds 1, 2 and methyl 3-hydroxybutanedioic ester (3) could inhibit the production of TNF-α by 22.73%, 33.14% and 37.19% at 5 μg/mL (P < 0.05) compared with the control. In addition, compound 2 was found to be active on the release of IL-6 in RAW264.7 macrophage cells, with an inhibitory rate of 39.79% (P < 0.05). The anti-inflammatory effect of compound 3 is disclosed for the first time in this study. Avian influenza is usually accompanied by virus invasion followed by the occurrence of oxidative stress and serious inflammation, so the multiple effects of the isolates may play a cocktail-like role in the treatment of avian influenza, and C. speciosa components, especially quercetin, might be a potent source for anti-viral and anti-inflammatory agents.

Antioxidant Lignans from the Fruits of Broussonetia papyrifera.

Nine new lignans, chushizisins A-I (1-9), and three known lignans, threo-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol (10), erythro-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol (11), and 3-[2-(4- hydroxyphenyl)-3-hydroxymethyl-2,3-dihydro-1-benzofuran-5-yl]propan-1-ol (12), were isolated from the fruits of Broussonetia papyrifera. Their structures were elucidated using spectroscopic methods. Compounds 1, 5, 6, 8, 9, and 11 exhibited antioxidant activities against H(2)O(2)-induced impairment in PC12 cells, while compounds 1, 2, 4, 7, and 11 showed DPPH radical-scavenging activities with IC(50) values of 236.8, 156.3, 273.9, 281.1, and 60.9 microM, respectively.

(±)-Sinensilactam A, a Pair of Rare Hybrid Metabolites with Smad3 Phosphorylation Inhibition from Ganoderma sinensis

(+)- and (-)-Sinensilactam A (1), novel hybrid metabolites possessing a unique 2H-pyrrolo[2,1-b][1,3]oxazin-6(7H)-one ring system, were isolated from the fruit bodies of Ganoderma sinensis. The structures of these substances and absolute configurations at their stereocenters were assigned using spectroscopic and computational methods along with X-ray crystallographic analysis. A plausible pathway for the biosynthesis of 1 is proposed. (-)-1 was found to be a Smad3 phosphorylation inhibitor in TGF-β1 induced human renal proximal tubular cells.

Compounds from Acorus tatarinowii: Determination of Absolute Configuration by Quantum Computations and cAMP Regulation Activity

A new cadinane-type sesquiterpenoid, tatarinowin A (1), two phenylpropanoids, tatarinoids A (2) and B (3), and a trinorlignan, tatarinoid C (4), along with 15 known compounds including two pairs of mixtures were isolated from the rhizome of Acorus tatarinowii. The absolute configurations of 1-4 were established by computation of specific rotation values. The isolated compounds were evaluated for their cAMP regulatory activity by the AlphaScreen assay.

Antibacterial Thymol Derivatives Isolated from Centipeda minima

Two new monoterpenoids, 8,10-dihydroxy-9(2)-methylbutyryloxythymol (1) and 10-hydroxy-8,9-dioxyisopropylidene-thymol (2), together with five known thymol derivatives: 8,9,10-trihydroxythymol (3), thymol-beta-glucopyranoside (4), 9-hydroxythymol (5), 8,10-dihydroxy-9-isobutyryloxythymol (6), and 8-hydroxy-9,10-diisobutyryloxythymol (7), were isolated from Centipeda minima. Their structures were identified by means of spectroscopic analyses. Interestingly, compound 2 is not an extraction artifact according to a close HPLC examination of material after extraction by analytical MeOH at ambient temperature. The antibacterial activities of compounds 1-7 were evaluated against eight microbial strains by the agar dilution method.

Two New Classes of T-Type Calcium Channel Inhibitors with New Chemical Scaffolds from Ganoderma cochlear.

T-type calcium channel (TTCC) inhibitors hold great potential for the treatment of a variety of neurological disorders. Cochlearoids A-E (1-5), five pairs of dimeric meroterpenoid enantiomers, and cochlearines A (6) and B (7), two pairs of enantiomeric hybrid metabolites, were isolated and characterized from Ganoderma cochlear. Biological evaluation found that compounds (+)-1, (-)-3, and (±)-6 significantly inhibited Cav3.1 TTCC and showed noticeable selectivity against Cav1.2, Cav2.1, Cav2.2, and Kv11.1 (hERG) channels.

GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-β–Induced Smad3 Phosphorylation

TGF-β1, via Smad-dependent or Smad-independent signaling, has a central role in the pathogenesis of renal fibrosis. This pathway has been recognized as a potential target for antifibrotic therapy. Here, we identified GQ5, a small molecular phenolic compound isolated from the dried resin of Toxicodendron vernicifluum, as a potent and selective inhibitor of TGF-β1-induced Smad3 phosphorylation. In TGF-β1-stimulated renal tubular epithelial cells and interstitial fibroblast cells, GQ5 inhibited the interaction of Smad3 with TGF-β type I receptor (TβRI) by blocking binding of Smad3 to SARA, suppressed subsequent phosphorylation of Smad3, reduced nuclear translocation of Smad2, Smad3, and Smad4, and downregulated the transcription of major fibrotic genes such as α-smooth muscle actin (α-SMA), collagen I, and fibronectin. Notably, intraperitoneal administration of GQ5 in rats immediately after unilateral ureteral obstruction (UUO) selectively inhibited Smad3 phosphorylation in UUO kidneys, suppressed renal expression of α-SMA, collagen I, and fibronectin, and resulted in impressive renal protection after obstructive injury. Late administration of GQ5 also effectively attenuated fibrotic lesions in obstructive nephropathy. In conclusion, our results suggest that GQ5 hinders renal fibrosis in rats by selective inhibition of TGF-β1-induced Smad3 phosphorylation.

Small Compound 6-O-Angeloylplenolin Induces Mitotic Arrest and Exhibits Therapeutic Potentials in Multiple Myeloma

Background Multiple myeloma (MM) is a disease of cell cycle dysregulation while cell cycle modulation can be a target for MM therapy. In this study we investigated the effects and mechanisms of action of a sesquiterpene lactone 6-O-angeloylplenolin (6-OAP) on MM cells. Methodology/Principal Findings MM cells were exposed to 6-OAP and cell cycle distribution were analyzed. The role for cyclin B1 to play in 6-OAP-caused mitotic arrest was tested by specific siRNA analyses in U266 cells. MM.1S cells co-incubated with interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or bone marrow stromal cells (BMSCs) were treated with 6-OAP. The effects of 6-OAP plus other drugs on MM.1S cells were evaluated. The in vivo therapeutic efficacy and pharmacokinetic features of 6-OAP were tested in nude mice bearing U266 cells and Sprague-Dawley rats, respectively. We found that 6-OAP suppressed the proliferation of dexamethasone-sensitive and dexamethasone-resistant cell lines and primary CD138+ MM cells. 6-OAP caused mitotic arrest, accompanied by activation of spindle assembly checkpoint and blockage of ubiquitiniation and subsequent proteasomal degradation of cyclin B1. Combined use of 6-OAP and bortezomib induced potentiated cytotoxicity with inactivation of ERK1/2 and activation of JNK1/2 and Casp-8/-3. 6-OAP overcame the protective effects of IL-6 and IGF-I on MM cells through inhibition of Jak2/Stat3 and Akt, respectively. 6-OAP inhibited BMSCs-facilitated MM cell expansion and TNF-α-induced NF-κB signal. Moreover, 6-OAP exhibited potent anti-MM activity in nude mice and favorable pharmacokinetics in rats. Conclusions/Significance These results indicate that 6-OAP is a new cell cycle inhibitor which shows therapeutic potentials for MM.

Two dimeric lignans with an unusual α,β-unsaturated ketone motif from Zanthoxylum podocarpum and their inhibitory effects on nitric oxide production

Two new dimeric lignans, zanthpodocarpins A (1) and B (2), and five known lignans, eudesmin (3), (1R,2R,5R,6S)-2-(3,4-dimethoxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (4), dimethoxysamin (5), rel-(1R,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-3,7-dioxabicyclo[3.3.0]octan-2-one (6), and magnone A (7), were isolated from the barks of Zanthoxylum podocarpum. Their structures were identified by using spectroscopic methods. Compounds 1 and 2 are rare dilignans bearing an unusual α,β-unsaturated ketone group from a natural source. Bioassay showed that compounds 1 and 2 could inhibit nitric oxide (NO) production in LPS stimulated RAW 264.7 cells with IC(50) values of 5.31 μM and 12.15 μM, respectively.

Identification of blapsins A and B as potent small-molecule 14-3-3 inhibitors from the insect Blaps japanensis.

In this study, we report three novel naturally occurring compounds, blapsins A (1) and B (2), and blapsamide (3) from the ethanol extract of the stink beetle, Blaps japanensis. The structures of these compounds were determined using spectroscopic methods. Compound 3 is a phenolic compound bearing a formamido group in the structure. Functional studies revealed that compounds 1 and 2 potently inhibited 14-3-3 protein-protein interactions (PPIs) with IC(50) values of 9.2 and 10.0 μM as determined by an ELISA assay, and 2.0 and 2.5 μM in an FP assay, respectively. These compounds represent the first example of natural small-molecule 14-3-3 inhibitors.