Deqiang Dou

Lipoprotein lipase activation by red Ginseng saponins in hyperlipidemia model animals

The effect of ginseng saponins isolated from red ginseng (a steamed and dried root of Panax ginseng) has been studied in a cyclophosphamide (CPM)-induced hyperlipidemia model in fasted rabbits. In this model, chylomicrons and very low density lipoprotein (VLDL) accumulation was known to occur as a result of reduction in lipoprotein lipase (LPL) activity in the heart and heparin-releasable heart LPL. Oral administration of ginseng saponins at a dose of 0.01 g/kg for 4 weeks was found to reverse the increase in serum triglycerides (TG) and concomitant increase in cholesterol produced by CPM treatment, especially in chylomicrons and VLDL. In addition, ginseng saponins treatment led to a recovery in postheparin plasma LPL activity and heparin-releasable heart LPL activity, which were markedly reduced by CPM treatment. In rats given 15% glycerol/15% fructose solution, postheparin plasma LPL activity declined to two third of normal rats, whereas ginseng saponins reversed it to normal levels. In the present study we first demonstrated that ginseng saponins sustained LPL activity at a normal level or protected LPL activity from being decreased by several factors, resulting in the decrease of serum TG and cholesterol.

Dammarane-type saponins from Panax quinquefolium and their inhibition activity on human breast cancer MCF-7 cells

A new compound, named quinquefoloside-L(c) (1), together with nine known compounds, was isolated from leaves of Panax quinquefolium, and its structure was elucidated as 3beta,12beta, 20S-trihydroxy-25-methoxydammar-23-ene 3-O-beta-D-glucopyranosyl (1-->2)beta-D-glucopyranosyl-20-O-beta-D-xylopyanosyl (1-->6) beta-D-glucopyranoside (1), on the basis of MS, 1D-and 2D-NMR experiments as well as by chemical degradation. The cytotoxicity of these compounds against human breast cancer MCF-7 cell line was also tested by MTT method.

Studies on the chemical constituents from the roots of Platycodon grandiflorum

Three known monodesmosidic saponins: 3-O-β-d-glucopyranosyl-2β,3β,16α,23,24-pentahydroxyolean-12-ene-28-oic acid, 3-O-β-d-glucopyranosyl polygalacic acid, and 3-O-β-d-glucopyranosyl-(1→3)-β-d-glucopyranosyl polygalacic acid; and two known nonsaponin compounds: a mixed compound of n-tetracosanoic acid (lignoceric acid), n-hexacosanoic acid (cerotic acid), and n-octacosanoic acid, and α-monopalmitin; were isolated for the first time from the root of Platycodon grandiflorum A. DC. together with another seven known compounds: platycoside G1 (3-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-2β,3β,16α,23,24-pentahydroxyolean-12-ene-28-oic acid 28-O-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside), deapio-platycodin D, Polygalacin D, deapio-platycodin D3, platycoside A, α-spinasterol, and α-spinasteryl-3-O-β-d-glucopyranoside. Alkaline hydrolysis of platycoside G1 afforded a new monodesmosidic prosaponin: 3-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-2β,3β,16α,23,24-pentahydroxyolean-12-ene-28-oic acid. Their chemical structures were elucidated on the basis of their spectral data and chemical evidence.

Studies on the anti-psoriasis constituents of Oplopanax elatus Nakai.

Seven compounds were isolated from roots and stems of Oplopanax elatus, of which compounds 3, 4, 5 and 6 were isolated for the first time from the title plant; compounds 1 and 2 are new compounds and characterised to be 3,3′-dimethoxy-4,9,9′-trihydroxy-4′,7-epoxy-5′8-lignan-4,9-bis-O-β-D-glucopyranoside and 5-methoxylariciresinol-4-O-β-D-glucopyranoside on the basis of NMR spectra and CD spectrum.

Integrative analysis of proteomics and metabolomics of anaphylactoid reaction induced by Xuesaitong injection.

Injection with natural compounds is an important method in the application of natural medicine, but its adverse drug reactions (ADRs) occur frequently, particularly the anaphylactoid reaction, which accounts for more than 77% of all reactions and has become a serious threat to public health. Here, the Xuesaitong injection (XSTI) was employed as an example to elucidate its anaphylactoid mechanism and look for potential biomarkers to assay the anaphylactoid reaction of herbal medicine injection by proteomics and metabolomics. These results disclosed that 13 differential proteins and 28 metabolites, which were further approved using the ELISA method and reference standards, respectively, were suggested as potential biomarkers to examine the anaphylactoid mechanism. The up-regulated expression of Gpx1, Sc5b9, C4d and down-regulated expression of F12, Kng1, C2 and C6 revealed that the XSTI-induced anaphylactoid reaction occurs via direct stimulation, complement and the kallikrein-kinin pathway. In addition, substances that induce an anaphylactoid effect include histamine, LTB4, uric acid and other drugs, which have been confirmed to be involved in arginine and proline metabolism, histidine metabolism, arachidonic acid metabolism purine metabolism and the TCA cycle. Furthermore, separation experiments have indicated that 10-kDa molecules of XSTI are the main allergenic factor inducing an anaphylactoid reaction.

The anaphylactoid constituents in Xue-Sai-Tong injection.

Xue-Sai-Tong injection, a traditional Chinese medicine with total saponins of Sanqi ginseng as active ingredients, has been used for more than 500 years to treat coronary artery disease in China. Anaphylactoid reaction induced by Xue-Sai-Tong injection was one of the main adverse drug reactions which has occurred frequently in recent years. It is of importance to elucidate its anaphylactoid constituents. The in vivo anaphyalctoid tests indicated that the anaphylactoid mediators could be used as indexes to evaluate the anaphylactoid action. Further, the in vitro model based on determining the mediators release from the degranulation of mast cells and RBL-2H3 cells stimulated by Xue-Sai-Tong injection was explored. Mediators released from mast cells and RBL-2H3 cells caused by Xue-Sai-Tong injection were determined by comparison of the methods of fluorospectrophotometry, ELISA, and spectrophotometry, respectively, revealing that the histamine release induced by the Xue-Sai-Tong injection could not be assayed accurately by the method of fluorospectrophotometry because of the interference of saponins and unknown components in the injection. The rat peritoneal mast cell was also not an optimal cell model for determining histamine and β-hexosaminidase release due to the higher spontaneous release ratio during the cell collection. Thus, ELISA determination of the histamine release from RBL-2H3 cells is a suitable in vitro model to assay the anaphylactoid reaction of Xue-Sai-Tong injection. Previously, abnormal hemolysis in some batches of Xue-Sai-Tong injection was observed in the course of their HD₅₀ (half hemolytic dosage) determination. This study further found that injections which exhibited an abnormal hemolysis phenomenon also caused a higher release of the anaphylactoid mediators from RBL-2H3 cells, indicating the HD₅₀ could be an auxiliary index to evaluate anaphylactoid action of the herbal injection indirectly. Research for anaphylactoid components in Xue-Sai-Tong injection indicated that proteins with over 10 KDa of molecular weight, but not ginsenosides, could be the main constituents inducing the release of anaphylactoid mediators from RBL-2H3 cells. An HPLC method for protein determination in the Xue-Sai-Tong injection was established subsequently, and the content of proteins with molecular weights of over 10 KDa in the injections showed an obviously positive correlation with the histamine release induced by the injections. In addition, taking ginsenoside-Rd coupled with BSA as an example, the hapten property of ginsenosides was studied and the ratio of ginsenoside-Rd to BSA was determined to be 8:1 by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the ginsenoside-BSA conjugate showed a stronger action to stimulate histamine release from the RBL-2H3 cells.

A new angeloylated triterpenoid saponin from the husks of Xanthoceras sorbifolia Bunge

A new angeloylated oleanane-type triterpenoid saponin, sorbifoliaside (1), and a known saponin, xanifolia O54, were isolated from the husks of Xanthoceras sorbifolia Bunge. Their chemical structures were elucidated on the basis of various spectroscopic analyses coupled with chemical degradation. To our knowledge, compound 1 is the first example of a naturally occurring triterpenoid saponin with an angeloyl group at C-2 of the sugar moiety.

Protective effect of arctigenin against MPP+ and MPTP-induced neurotoxicity.

The potential protective effects of arctigenin on 1-methyl-4-phenylpyridinium ion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride-induced neurotoxicity were examined, and the results indicated that arctigenin could improve the movement behaviors and upregulate dopamine and γ-aminobutyric acid levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride-induced neurotoxicity mouse model. A further in vitro experiment showed that the pretreatment with arctigenin on cultured human neuroblastoma SH-SY5Y cells could obviously attenuate the decrease of cell survival rates caused by treatment with 1-methyl-4-phenylpyridinium ion by way of acting against cell apoptosis through the decrease of Bax/Bcl-2 and caspase-3, and by antioxidative action through reduction of the surplus reactive oxygen species production and downregulation of mitochondrial membrane potential. It is for the first time that a neuroprotective activity of arctigenin in both in vitro and in vivo experiments was reported, enlightening that arctigenin could be useful as a potential therapeutic agent for Parkinsons disease.

Pharmacokinetic study of arctigenin in rat plasma and organ tissue by RP-HPLC method

A high-performance liquid chromatography (HPLC) technique was developed for the determination of arctigenin in plasma and various organs of rats after the oral administration of 30, 50 and 70 mgkg−1 of arctigenin to the Sprague–Dawley rats. Results showed that the validated HPLC method was simple, fast, reproducible and suitable to the determination of arctigenin in rat plasma and organ tissue and one-compartmental model with zero-order absorption process can well describe the changes of arctigenin concentration in the plasma. The concentration of compound was highest in the spleen, less in the liver and the least in the lung.

Studies on chemical constituents of the leaves of Smallantus sonchifolius (yacon): Structures of two new diterpenes

The extract from the leaves of Smallantus sonchifolius (yacon) was found to show potent anti-diabetic activity. Two new diterpenes, named ent-kaurane-3β,16β,17, 19-tetrol (1) and ent-kaurane-16β,17,18,19-tetrol (2), were isolated from the extract, together with six known compounds. The structures of the new compounds were determined on the basis of chemical and physicochemical evidence.