Guoyong Xie

Four new eudesmane-type sesquiterpenes from the basal leaves of Salvia plebeia R. Br.

Four new eudesmane-type sesquiterpenes, named plebeiolide A-C (1-3) and plebeiafuran (4), together with a known eudesmanolide (5), were isolated from the basal leaves of Salvia plebeia R. Br. Their structures were elucidated by extensive spectroscopic analysis including 1D and 2D NMR, HR-ESI-MS spectra. The absolute configuration of compound 1 was confirmed by single-crystal X-ray analysis and CD spectra. The inhibitory activity of isolated compounds toward NO production in lipopolysaccharide-induced RAW264.7 cells was evaluated and compounds 3 and 4 showed moderate inhibitory activity. In addition, the sesquiterpene lactones in Lamiaceae plants may possess some chemosystematic implications at intergeneric and intrageneric levels.

Tectorigenin Attenuates Palmitate-Induced Endothelial Insulin Resistance via Targeting ROS-Associated Inflammation and IRS-1 Pathway

Tectorigenin is a plant isoflavonoid originally isolated from the dried flower of Pueraria thomsonii Benth. Although its anti-inflammatory and anti-hyperglycosemia effects have been well documented, the effect of tectorigenin on endothelial dysfunction insulin resistance involved has not yet been reported. Herein, this study aims to investigate the action of tectorigenin on amelioration of insulin resistance in the endothelium. Palmitic acid (PA) was chosen as a stimulant to induce ROS production in endothelial cells and successfully established insulin resistance evidenced by the specific impairment of insulin PI3K signaling. Tectorigenin effectively inhibited the ability of PA to induce the production of reactive oxygen species and collapse of mitochondrial membrane potential. Moreover, tectorigenin presented strong inhibition effect on ROS-associated inflammation, as TNF-α and IL-6 production in endothelial cells was greatly reduced with suppression of IKKβ/NF-κB phosphorylation and JNK activation. Tectorigenin also can inhibit inflammation-stimulated IRS-1 serine phosphorylation and restore the impaired insulin PI3K signaling, leading to a decreased NO production. These results demonstrated its positive regulation of insulin action in the endothelium. Meanwhile, tectorigenin down-regulated endothelin-1 and vascular cell adhesion molecule-1 overexpression, and restored the loss of insulin-mediated vasodilation in rat aorta. These findings suggested that tectorigenin could inhibit ROS-associated inflammation and ameliorated endothelial dysfunction implicated in insulin resistance through regulating IRS-1 function. Tectorigenin might have potential to be applied for the management of cardiovascular diseases involved in diabetes and insulin resistance.

New isoflavones with cytotoxic activity from the rhizomes of Iris germanica L.

Two new compounds, 5-methoxy-3′,4′-dihydroxy-6,7-methylenedioxy-4H-1-benzo-pyran-4-one(iriskashmirianin A) (1) and 5,3′-dihydroxy-3-(4′-β-d-glucopyranosyl)-6,7-methylenedioxy-4H-1-benzo-pyran-4-one (germanaism H) (2), along with eight known compounds (3–10), were isolated from the rhizomes of Iris germanica L. The cytotoxicities of these compounds were tested using Ehrlichs ascites carcinoma (EAC) cancer cell line by 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazoli-umbromide (MTT) and ATP assays. The results showed that these compounds possessed antiproliferative effects on EAC cell line. Among them, compound 1 possessed the best cytotoxic activity with IC50 ± SD of 20.9 ± 2.7 and 4.3 ± 0.9 μM for MTT and ATP assay methods, respectively.

New flavonoids with cytotoxicity from the roots of Flemingia latifolia.

Flemingia latifolia is a folk medicine in China, which is used for treating rheumatism, arthropathy, chronic nephritis and menopausal syndrome. The phytochemicals of the plant have seldom been studied so far. In present study, three new compounds, a flavanone quinone (flemingiquinone A) (1), a prenylated dihydroflavonoid (khonklonginol I) (2) and an isoflavonoid (flemilatifolin B) (3) were isolated from the roots of F. latifolia. Their structures were established by (1)H and (13)C NMR spectra and 2D NMR experiments, including COSY, HMQC, HMBC and ROESY. Meanwhile, the compounds were evaluated for cytotoxicity against two human cancer cell lines, SMMC-7721 and A-549. The results showed that compounds 1 and 2 possessed moderate antiproliferative effects on SMMC-7721 and A-549 cell lines.

Baicalin regulates SirT1/STAT3 pathway and restrains excessive hepatic glucose production

HIGHLIGHTSSirT1 induction and STAT3 inactivation promote hepatic glucose production.Deacetylation of STAT3 by SirT1 is required for PGC‐1&agr; activity on hepatic gluconeogenesis.Baicalin suppresses hepatic SirT1 induction by downregulating the levels of NAD+ in the fasting state.Preserving STAT3 acetylation and activation by baicalin contributes to restrain excessive hepatic glucose production. ABSTRACT Sirtuin 1 (SirT1) and signal transducer and activator of transcription 3 (STAT3) oppositely regulate hepatic gluconeogenic genes and the association remains to be elucidated. Baicalin is a natural flavonoid with beneficial effects on glucose and lipid metabolism. This study aims to investigate the effect of baicalin on hepatic gluconeogenesis with focus on the regulation of fatty acid mobilization and SirT1/STAT3 pathway. In HFD feeding or fasting state, hepatic gluconeogenesis and fatty acid oxidation induced SirT1 expression due to the increased nicotinamide adenine dinucleotide+ (NAD+) contents. Baicalin reduces endogenous glucose production via suppression of hepatic gluconeogenesis and decreased SirT1 induction via reducing NAD+ accumulation in an energy‐sensing way. Fasting increased SirT1 protein in STAT3 immunoprecipitation products and less in the liver of baicalin‐treated mice, indicating that baicalin blocked the binding of SirT1 to STAT3 and thus preserved STAT3 acetylation. SirT1 knockdown enhanced the protective effect of baicalin on pyruvate‐induced STAT3 phosphorylation and acetylation, these results further indicated that the regulation of STAT3 activity by baicalin was dependent on SirT1. Moreover, HFD feeding increased gene expression for PGC‐1&agr; in the liver, but the transcriptional regulation was inhibited by baicalin treatment. SirT1 overexpression and STAT3 inhibition enhanced pyruvate‐mediated PGC‐1&agr; gene expression, suggesting that deacetylation of STAT3 by SirT1 is required for PGC‐1&agr; activity on hepatic gluconeogenesis. Taken together, these results showed that baicalin restrained HGP via inhibiting SirT1 activity coupled with STAT3 acetylation and subsequent PGC‐1&agr; suppression, suggesting that hepatic SirT1 and STAT3 pathway may provide therapeutic advantages for the control of hyperglycemia.

Chemical profiles and quality evaluation of Buddleja officinalis flowers by HPLC-DAD and HPLC-Q-TOF-MS/MS

Graphical abstract The total of 54 compounds were identified or tentatively identified in the extracts of B. offinalis flowers by HPLC‐Q‐TOF‐MS/MS. Meanwhile, HPLC fingerprints have been developed, together with the simultaneous quantification of 11 constituents for the quality evaluation of B. officinalis. In addition, the antioxidant capacities of the extracts of B. offinalis flowers from 12 habitats were reported. Figure. No Caption available. Highlights54 compounds were detected from B. officinalis flowers by HPLC‐Q‐TOF‐ MS/MS method.Seven alkaloids were found from B. officinalis for the first time.HPLC fingerprint of B. officinalis flower were established.Eleven principal components were quantified for B. officinalis.The extracts of B. officinalis flowers show strong antioxidant capacities. Abstract The dried flowers and inflorescences of Buddleja officinalis Maxim are used as traditional medicines in China, and aqueous extracts of the flowers have also been used since ancient times as a yellow rice colorant at local festivals. In this study, HPLC‐Q‐TOF‐MS/MS was used to determine the overall chemical composition of this medicine‐food plant. A total of 54 compounds, including 23 flavonoids, 19 phenylethanoid glycosides, 7 alkaloids and 5 other compounds, were detected in the methanol extracts of the herb using this method. Among them, 35 compounds were found firstly in this herb. HPLC fingerprints were also developed, together with a method for the simultaneous quantification of 11 constituents that could be used for quality evaluation of B. officinalis. Fingerprint analysis, using 28 characteristic fingerprint peaks, was used to assess the similarities among 12 samples collected from different geographic areas and showed that the similarity was >0.900. Simultaneous quantification of 11 markers in B. officinalis was then performed to determine consistency of quality. Additionally, the total phenolic content and antioxidant capacity of extracts of the 12 samples of B. officinalis flowers were measured using spectroscopic methods. B. officinalis was found to have good antioxidant capacity and to be a potential natural antioxidant. The highest antioxidant capacity was found in the samples from Guizhou, Sichuan and Guangxi Province. Our results provide valuable information for further understanding and exploiting the herb.

Alkaloids from the Rhizomes of Iris germanica

The genus Iris (Iridaceae) comprises over 300 species, which is distributed mainly in the northern hemisphere. Iris germanica L., a perennial herb, is cultivated as an ornamental and aromatic plant in many areas of the world. The rhizomes of I. germanica are traditionally used in Pakistan for dropsy and gall bladder diseases, and as a diuretic, antispasmodic, stimulant, and aperient [1]. Previous phytochemical investigations of the Iris plants have revealed a variety of compounds, including flavones, isoflavones and their glycosides, benzoquinones, triterpenoids, and stilbene glycosides [2–6]. In this study, nine alkaloid compounds were reported from the plant. The rhizomes of Iris germanica L. were purchased from Qianxiang Town, Dongyang City, Zhejiang Province of China, in August 2010. The plant was identied by Prof. Minjian Qin, and a voucher specimen (No. Xie 2010001) was deposited in the Herbarium of Medicinal Plants of China Pharmaceutical University. Air-dried rhizomes of I. germanica (5 kg) were extracted with 95% ethanol by heat reflux extraction. The extract was filtered, combined, and concentrated in vacuum to obtain a residue (ca. 300 g), which was isolated by silica gel column chromatography with a gradient elution system of CHCl3–MeOH (100:0–0:100) to obtain 18 fractions (F1–F18). Fraction F14 (CHCl3–MeOH, 9:1, 4:1) was separated on a silica gel column with a gradient of CHCl3–MeOH (50:1–1:1) and Sephadex LH-20 (CHCl3–MeOH, 1:1) to give four compounds: 5 (9 mg), 7 (11 mg), 8 (8 mg), and 9 (12 mg). Fraction F18 (CHCl3–MeOH, 1:1) was separated by column chromatography over RP-18 with a gradient of MeOH–H2O (4:6, 5:5, 7:3, 8:2) and Sephadex LH-20 (CHCl3–MeOH, 1:1) to yield five compounds: 1 (20 mg), 2 (10 mg), 3 (9 mg), 4 (9 mg), and 6 (16 mg). All compounds were isolated for the first time from the family of Iridaceae. By a comparison of their NMR and MS data with those reported in the literatures, the structures were identified as: 1,2,3,4-tetrahydro-carboline-3-carboxylic acid (1) [7], S-(–)-methyl-1,2,3,4-tetrahydro-9H-pyrido [3,4-b]indole-3-carboxylate (2) [8], (1S,3R)-methyl 1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate (3) [9], (1R,3R)-methyl 1-methyl2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate (4) [10], 4-(9H-carbolin-1-yl)-4-oxobut-2-enoic acid methyl ester (5) [11], 2-(furan-2-yl)-5-(2,3,4-trihydroxybutyl)-1,4-diazine (6) [12], 3-D-ribofuranosyluracil (7) [13], 6-hydroxymethyl3-pyridinol (8) [14], and 2-amino-1H-imidazo-[4,5-b]pyrazine (9) [15]. 1,2,3,4-Tetrahydro-carboline-3-carboxylic Acid (1). C12H12N2O2. White powder. 1H NMR (500 MHz, DMSO-d6, , ppm, J/Hz): 7.44 (1H, d, J = 7.8, H-5), 7.32 (1H, d, J = 8.1, H-8), 7.07 (1H, t, J = 7.4, 7.2, H-7), 6.98 (1H, t, J = 7.4, 7.3, H-6), 4.20 (1H, d, J = 15.3, H-1a), 4.15 (1H, d, J = 15.4, H-1b), 3.59 (1H, dd, J = 5.1, 10.1, H-3), 3.10 (1H, dd, J = 4.6, 16.0, H-4a), 2.81 (1H, dd, J = 5.1, 16.0, H-4b). 13C NMR (125 MHz, CD3OD, , ppm): 169.3 (C=O), 136.2 (C-8a), 127.9 (C-9a), 126.2 (C-4b), 121.2 (C-7), 118.7 (C-6), 117.7 (C-5), 111.1(C-8), 106.6 (C-4a), 79.1 (C-3), 56.6 (C-1), 22.9 (C-4). ESI-MS m/z 217 [M + H]+. S-(–)-Methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate (2). C13H14N2O2. White powder. 1H NMR (500 MHz, CD3OD, , ppm, J/Hz): 7.39 (1H, d, J = 7.7, H-5), 7.26 (1H, d, J = 7.9, H-8), 7.04 (1H, t, J = 7.6, 7.2, H-7), 6.97 (1H, t, J = 7.7, 7.1, H-6), 4.12 (1H, d, J = 15.8, H-1a), 4.03 (1H, d, J = 15.3, H-1b), 3.81 (1H, dd, J = 9.3, 4.7, H-3), 3.78 (3H, s, OCH3), 3.10 (1H, dd, J = 14.6, 4.7, H-4a), 2.88 (1H, dd, J = 9.2, 15.9, H-4b). 13C NMR (125 MHz, CD3OD, , ppm): 174.9 (C=O), 138.0 (C-8a), 132.9 (C-9a), 128.4 (C-4b), 122.1 (C-7), 119.8 (C-6), 118.3 (C-5), 111.9 (C-8), 107.1 (C-4a), 56.6 (OCH3), 54.5 (C-3), 42.6 (C-1), 25.9 (C-4). ESI-MS m/z 231 [M + H] +.