Shengqian Yang

Diarylheptanoids from Alpinia officinarum

A new diarylheptanoid, along with five known diarylheptanoids, was isolated from the rhizomes of Alpinia officinarum (Zingiberaceae). The structure of the new compound was determined to be trans,trans-1(3′-methoxy-4′-hydroxyphenyl)-7-phenyl-5-ol-4,6-dien-3-heptanone on the basis of spectral and chemical evidence.

Therapeutic effect of methyl salicylate 2-O-β-d-lactoside on LPS-induced acute lung injury by inhibiting TAK1/NF-kappaB phosphorylation and NLRP3 expression

Acute lung injury (ALI), characterized by pulmonary edema and inflammatory cell infiltration, is a common syndrome of acute hypoxemic respiratory failure. Methyl salicylate 2-O-β-d-lactoside (MSL), a natural derivative of salicylate extracted from Gaultheria yunnanensis (Franch.) Rehder, was reported to have potent anti-inflammatory effects on the progression of collagen or adjuvant-induced arthritis in vivo and in vitro. The aim of this study is to investigate the therapeutic effect of MSL on lipopolysaccharide (LPS)-induced acute lung injury and reveal underlying molecular mechanisms. Our results showed that MSL significantly ameliorated pulmonary edema and histological severities, and inhibited IL-6 and IL-1β production in LPS-induced ALI mice. MSL also reduced MPO activity in lung tissues and the number of inflammatory cells in BALF. Moreover, we found that MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation, as well as the expression of NLRP3 protein in lung tissues. Furthermore, MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation in Raw264.7 cells. In addition, MSL significantly inhibited nuclear translocation of NF-κB p65 in cells treated with LPS in vitro. Taken together, our results suggested that MSL exhibited a therapeutic effect on LPS-induced ALI by inhibiting TAK1/NF-κB phosphorylation and NLRP3 expression.

Xanthones from the roots of Cudrania fruticosa Wight.

Chemical investigation on the roots of Cudrania fruticosa resulted in the isolation of two new xanthones, 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone (1) and 3,6,7-trihydroxy-1-methoxyxanthone (2), together with three known ones, 1,3,5-trihydroxy-4-(3-hydroxy-3-methylbutyl)xanthone (3), 1,3-dihydroxy-6,7-dimethoxyxanthone (4) and 3,5,6-trihydroxy-1-methoxyxanthone (5), respectively. Their structures were elucidated on the basis of spectral and chemical techniques.

Two new cardenolides from the roots of Streptocaulon griffithii

Two new cardenolides, 3β,5β,14β-trihydroxyl-card-16,20(22)-dienolide (1) and 3-O-β-d-glucopyranosyl-5β,14β-dihydroxyl-card-16,20(22)-dienolide (2), together with seven known compounds identified as digitogenin (3), 16-O-acetylgitoxigenin (4), periplogenin (5), 16-O-acetylperiplogenin (6), periplogenin digitoxoside (7), periplogenin-3-O-β-d-glucopyranoside (8) and periplogenin-3-O-β-d-glucopyranosyl-(1 → 4)-O-β-d-digitoxopyranoside (9) were isolated from the roots of Streptocaulon griffithii. Their structures were elucidated on the basis of spectroscopic data.

Prevention of vascular smooth muscle cell proliferation and injury-induced neointimal hyperplasia by CREB-mediated p21 induction: An insight from a plant polyphenol.

Cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element (CRE)-binding protein (CREB) signaling cascade negatively regulates platelet-derived growth factor BB (PDGF-BB)-induced smooth muscle cell (SMC) proliferation, which is a critical event in the initiation and development of restenosis and atherosclerotic lesions. Salvianolic acid A (SAA) is one of the most abundant polyphenols extracted from salvia. The aim of this study is to investigate whether SAA exerts an action on PDGF-BB-induced proliferation via cAMP/PKA/CREB mechanism. SAA blunts PDGF-BB-induced human umbilical artery smooth muscle cell (hUASMC) proliferation via p21 induction, as evidenced by its increased mRNA and protein expression levels. The SAA-induced upregulation of p21 involves the cAMP/PKA signaling pathway; a cAMP analog mimicked the effects of SAA and a specific cAMP/PKA inhibitor opposed these effects. SAA also activated CREB, including phosphorylation at Ser133, and induced its nuclear translocation. Deletion and mutational analysis of p21 promoters, co-immunoprecipitation, and western blot analysis showed that CRE is essential for SAA-induced p21 protein expression. Transfection of dominant-negative CREB (mutated Ser133) plasmids into hUASMCs attenuated SAA-stimulated p21 expression. SAA upregulated p21 expression and activated CREB in the neointima of balloon-injured arteries in vivo. Our results indicate that SAA promotes p21 expression in SMCs through the cAMP/PKA/CREB signaling cascade in vitro and prevents injury-induced neointimal hyperplasia.

The natural product bergenin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting NF-kappaB activition

ETHNOPHARMACOLOGICAL RELEVANCE Bergenin, an active constituent of the plants of the genus Bergenia, was reported to have anti-inflammatory effects in the treatment of chronic bronchitis and chronic gastritis clinically. However, its therapeutic effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its potential mechanisms of actions were still unknown. AIM OF THIS STUDY To evaluate the effect of bergenin on murine model of acute lung injury induced by LPS and also to explore its potential mechanisms. MATERIALS AND METHODS Half an hour and 12h after an intranasal inhalation of LPS, male BALB/c mice were treated with bergenin (50,100 and 200mg/kg) or dexamethasone (DEX, 5mg/kg) by gavage. Twenty-four hours after LPS exposure, the lung wet/dry ratio, histological changes, myeloperoxidase (MPO) in lung tissues, inflammatory cells (in BALF) and cytokines (in BALF and serum) were detected. Meanwhile, the protein expression of MyD88 and the phosphorylation of NF-κB p65 in lung tissue were analyzed using immunoblot analysis. Moreover, the nuclear translocation and the phosphorylation of NF-κB p65 in Raw264.7 cells were also analyzed. The viability of Raw264.7 cells was determined by MTT assay. RESULTS Results showed that bergenin significantly decreased pulmonary edema, improved histological changes and reduced MPO activity in lung tissues. Moreover, bergenin obviously decreased inflammatory cells, IL-1β and IL-6 production in BALF, as well as IL-1β, TNF-α and IL-6 production in serum of LPS-induced ALI mice. Furthermore, bergenin markedly inhibited LPS-induced NF-κB p65 phosphorylation, as well as the expression of MyD88 but not the expression of NF-κB p65 in lung tissues. Additionally, bergenin also significantly inhibited the nuclear translocation and the phosphorylation of NF-κB p65 stimulated by LPS in Raw264.7 cells. CONCLUSIONS These findings suggested that bergenin had a therapeutic effect on LPS-induced ALI by inhibiting NF-κB activition.

A new cerebroside from Uvaria tonkinensis var. subglabra

A new cerebroside, subglain A (1), together with five known compounds (2–6) have been isolated from the stems of Uvaria tonkinensis var. subglabra. The structure of 1 has been determined to be 1-O-β-D-glucopyranosyl-(2S,3S,4R,8Z,2′R)-2-[N-(2′-hydroxytetracosanyl)-N-(1″,2″-dihydroxyethyl)-amide]-8-tetradecene-1,3,4-triol by spectroscopic evidence. The known compounds were identified as schisandriside (2), erythritol (3), β-D-glucopyranose (4), kaempferol-3,7-O-α-L-dirhamnoside (5), and (+)-lyoniresinol (6).

Two new triterpene saponins from Lysimachia capillipes.

Two new saponins, capilliposide G (1) and capilliposide H (2), were isolated from the whole plants of Lysimachia capillipes. Their structures were determined by 1D and 2D NMR, MS technique and chemical methods.

Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice

A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase (XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7th day to induce hyperuricemia. Meanwhile, J99745 (3, 10, and 30 mg/kg), allopurinol (20 mg/kg) or benzbromarone (20 mg/kg) were orally administered to mice for 7 days. On the 7th day, uric acid and creatinine in serum and urine, blood urea nitrogen (BUN), malondialdehyde (MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin (H&E) staining. Hepatic XOD, renal urate transporter 1 (URAT1), glucose transporter type 9 (GLUT9), organic anion transporter 1 (OAT1) and ATP-binding cassette transporter G2 (ABCG2) were detected by Western blot and real time polymerase chain reaction (PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid (FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our results suggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.

Actinomycin D synergistically enhances the cytotoxicity of CDDP on KB cells by activating P53 via decreasing P53–MDM2 complex

Abstract The aim of this study is to investigate the synergism of low dose of actinomycin D (LDActD) to the cytotoxicity of cisplatin (CDDP) on KB cells. The role of P53 reactivation by LDActD in the synergism and its mechanism were further studied. Cell viability was determined by MTT assay. Apoptosis was determined by AnnexinV-FITC/PI staining. Mitochondrial membrane potential (MMP) was detected by JC-1 staining. Expression of proteins was detected by Western blotting (WB) and/or immunofluorescence (IF). Molecular docking of actinomycin D (ACTD) to Mouse double minute 2 homolog (MDM2) and Mouse double minute 2 homolog X (MDMX). MDMX was analyzed by Discovery Studio. The content of P53–MDM2 complex was detected by ELISA assay. The cytotoxicity of CDDP was increased by the combination of LDActD in kinds of cancer cells. Molecular docking showed strong interaction between ACTD and MDM2/MDMX. Meanwhile, LDActD significantly decreased P53–MDM2 complex. Significant increase of the apoptotic activity by the combination therapy in KB cells is P53 upregulated modulator of apoptosis (PUMA) dependent. In addition to the decrease in MMP, LDActD increased P53 regulated protein and decreased BCL-XL in KB cells. LDActD efficiently enhanced the cytotoxicity of CDDP in cancer cells and induced P53-PUMA-dependent and mitochondria-mediated apoptosis in KB cells. The reactivation of P53 was probably achieved by disturbing the interaction of P53 and MDM2/MDMX.