Leucine-derived cyanoglucosides from the aerial parts of Sorbaria sorbifolia (L.) A. Braun.

Six new cyanoglucosides, 2S-cardiospermin-5-benzoate (1), 2R-cardiospermin-5-p-hydroxybenzoate (2), 2S-cardiospermin-5-cis-p-coumarate (3), isocardiospermin-5-p-hydroxybenzoate (4), sutherlandin-5-p-hydroxybenzoate (5), and sutherlandin-5-cis-p-coumarate (6), together with 17 known compounds were isolated from Sorbaria sorbifolia. The structures of the new compounds were elucidated by extensive spectroscopic methods, including 1D and 2D NMR, HR-ESI-MS and ECD experiments. The biosynthetic relationship of 1-9 was also discussed. The cyanoglucosides (1-9) and 15 exhibited moderate inhibitory effect on nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide (LPS).

New abietane norditerpenoid from Salvia miltiorrhiza with cytotoxic activities.

One new abietane-type norditerpenoid, named militibetin A (1), was isolated from the dry roots of Salvia miltiorrhiza, along with two known diterpenoids, yunnannin A (2) and ferruginol (3). Their structures were established by means of extensive spectroscopic analyses. In vitro, compounds 1-3 were found to show cytotoxicities against selected cancer cells, including P-388, HONE-1, and HT-29, and gave ED(50) values in the range of 2.9-5.4 µg ml(- 1).

Two new C13-norisoprenoids from Solanum lyratum.

Two new C(13)-norisoprenoids, named lyratols E and F (1-2), were isolated from the whole plant of Solanum lyratum Thunb, and their structures were elucidated by extensive spectroscopic analyses. In vitro, two new compounds were found to show significant cytotoxicity against selected cancer cells including P-388 and HT-29.

Two new cytotoxic ent-clerodane diterpenoids from Scutellaria barbata.

Two new ent-clerodane diterpenoids have been isolated from Scutellaria barbata, and their structures were established by detailed spectroscopic analyses as (13R)-6α,7ß-dihydroxy-8ß,13-epoxy-11ß-nicotinyloxy-ent-clerodan-3-en-15,16-olide (scutelinquanine D, 1) and (11E)-6α-acetoxy-7ß,8ß-dihydroxy-ent-clerodan-3,11,13-trien-15,16-olide (6-acetoxybarbatin C, 2). In vitro, the isolated two new compounds showed significant cytotoxic activities against three human cancer cell lines (HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells), and gave IC(50) values in the range of 2.5-6.6 µM.

New neo-clerodane diterpenoids from Scutellaria barbata with cytotoxic activities.

Two new neo-clerodane diterpenoids have been isolated from the whole plant of Scutellaria barbata D. Don, and their structures were established by detailed spectral analyses as scutehenanine H (1) and 6-(2,3-epoxy-2-isopropyl-n-propoxyl)barbatin C (2). In vitro, the isolated two new compounds showed significant cytotoxic activities against three human cancer lines, and gave IC(50) values in the range OF 2.0-4.2 µΜ.

In vitro and in vivo antifibrotic effects of rosmarinic acid on experimental liver fibrosis.

This study was carried out to investigate whether rosmarinic acid (RA) has antifibrotic effect on experimental liver fibrosis in vitro and in vivo and its possible mechanism. Culture of hepatic stellate cells (HSCs) determine proliferation and expression of transforming growth factor-beta1 (TGF-beta1), connective transforming growth factor (CTGF) and alpha-smooth muscle actin (alpha-SMA). In carbon tetrachloride (CCL(4))-induced rat liver fibrosis model, determined biochemical indicator, liver fibrosis grade and histopathological changes, immunohistochemical detected liver TGF-beta1 and CTGF expression. The results indicated that RA could inhibit HSCs proliferation, inhibit TGF-beta1, CTGF and alpha-SMA expression in cultured HSCs. It has marked evident in reducing fibrosis grade, ameliorating biochemical indicator and histopathological morphology, reducing liver TGF-beta1 and CTGF expression in CCL(4)-induced liver fibrosis. These findings suggest that RA has potentially conferring antifibrogenic effects.

Effect of astilbin on experimental diabetic nephropathy in vivo and in vitro.

Astilbin, a flavonoid compound, was isolated from the rhizome of Smilax glabra Roxb. This study was conducted to investigate the efficacy of astilbin on experimental diabetic nephropathy (DN) in vivo and in vitro and its possible mechanisms. Astilbin was added in high glucose stimulated HK-2 cells, streptozotocin-induced experimental DN, randomized to receive intragastric ( I. G.) astilbin to observe its anti-renal lesion effect. Results showed that astilbin inhibited high glucose stimulated HK-2 cell production of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) in vitro, especially CTGF; analogic results was also found in vivo. I. G. of astilbin 2.5 mg/kg or 5 mg/kg significantly ameliorated renal function, reduced kidney index, while it increased body weight and survival time in animals. In addition there was no significant difference in blood glucose level between the STZ-treated group and the astilbin groups. Furthermore, astilbin ameliorated the pathological progress of renal morphology. Astilbin can exert an early renal protective role to DN, inhibit production of TGF-beta1 and especially of CTGF. We suggest that astilbin inhibition of CTGF may be a potential target in DN therapy. This work provides the first evidence for astilbin as a new candidate of DN therapeutic medicine.

Rosmarinic acid protects against experimental sepsis by inhibiting proinflammatory factor release and ameliorating hemodynamics.

The present study was to investigate the effects of rosmarinic acid (RA) in cultured RAW264.7 cells and experimental model of sepsis induced by cecal ligation and puncture in rats and the potential mechanism. Results showed that RA concentration dependently down-regulated the levels of TNF-alpha, IL-6, and high-mobility group box 1 protein in LPS-induced RAW264.7 cells, inhibited the IkappaB kinase pathway, and modulated nuclear factor-kappaB. Intravenous injection of RA alone or in combination with imipenem reduced cecal ligation and puncture-induced lethality in rats. In addition, serum levels of TNF-alpha, IL-6, high-mobility group box 1 protein, triggering receptor expressed on myeloid cells, and endotoxin were down-regulated; in contrast, serum level of IL-10 was up-regulated. Amelioration of hemodynamics and decrease in serum enzyme activities and myeloperoxidase in lung, liver, and small intestine were also observed after RA injection. These data indicate that the antisepsis effect of RA was mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. This article provides the first evidence that RA has the capacity to inactivate inflammatory response in sepsis. The anti-inflammatory mechanism of RA may inhibit activation of the nuclear factor- kappaB pathway by inhibiting IkappaB kinase activity.