Su Zeng

Cytotoxic, cytoprotective and antioxidant effects of isolated phenolic compounds from fresh ginger.

Twenty-nine phenolic compounds were isolated from the root bark of fresh (Yunnan) ginger and their structures fully characterized. Selected compounds were divided into structural categories and twelve compounds subjected to in-vitro assays including DPPH radical scavenging, xanthine-oxidase inhibition, monoamine oxidase inhibition, rat-brain homogenate lipid peroxidation, and rat pheochromocytoma PC12 cell and primary liver cell viability to determine their antioxidant and cytoprotective properties. Isolated compounds were also tested against nine human tumor cell lines to characterize anticancer potency. Several diarylheptanoids and epoxidic diarylheptanoids were effective DPPH radical scavengers and moderately effective at inhibiting xanthine oxidase. An enone-dione analog of 6-shogaol (compound 2) was isolated and identified to be most effective at protecting PC12 cells from H₂O₂-induced damage. Almost all tested compounds inhibited lipid peroxidation. Three compounds, 6-shogaol, 10-gingerol and an enone-diarylheptanoid analog of curcumin (compound 6) were identified to be cytotoxic in cell lines tested, with KB and HL60 cells most susceptible to 6-shogaol and the curcumin analog with IC₅₀<10 μM. QSAR analysis revealed cytotoxicity was related to compound lipophilicity and chemical reactivity. In conclusion, we observed distinct compounds in fresh ginger to have biological activities relevant in diseases associated with reactive oxygen species.

Diarylheptanoids and a monoterpenoid from the rhizomes of Zingiber officinale: antioxidant and cytoprotective properties

Three new diarylheptanoids and one new monoterpenoid were isolated from the rhizomes of Zingiber officinale together with four known diarylheptanoids, 5-8. Their structures were elucidated mainly by spectroscopic methods, and they were deduced as 5-[4-hydroxy-6-(4-hydroxyphenethyl)tetrahydro-2 H-pyran-2-yl]-3-methoxybenzene-1,2-diol (1), sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3 S-sulfonate (2), sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3 R-sulfonate (3), and hydroxycineole-10-O-beta-D-glucopyranoside (4), respectively. Among the isolated compounds, compounds 1, 5, and 8 exhibited strong superoxide anion radical scavenging activities in a phenazine methosulfate-NADH system. In a more biological system, these compounds were demonstrated to exhibit potent protection against lipid peroxidation in mouse liver microsomes exposed to oxidative conditions. These compounds were subsequently tested on primary cultures of rat hepatocytes exposed to oxidative damage, and definitive cytoprotective actions were found.

Design, Synthesis, and Examination of Neuron Protective Properties of Alkenylated and Amidated Dehydro-Silybin Derivatives†

A series of C7-O- and C20-O-amidated 2,3-dehydrosilybin (DHS) derivatives ((+/-)-1a-f and (+/-)-2), as well as a set of alkenylated DHS analogues ((+/-)-4a-f), were designed and de novo synthesized. A diesteric derivative of DHS ((+/-)-3) and two C23 esterified DHS analogues ((+/-)-5a and (+/-)-5b) were also prepared for comparison. The cell viability of PC12 cells, Fe(2+) chelation, lipid peroxidation (LPO), free radical scavenging, and xanthine oxidase inhibition models were utilized to evaluate their antioxidative and neuron protective properties. The study revealed that the diether at C7-OH and C20-OH as well as the monoether at C7-OH, which possess aliphatic substituted acetamides, demonstrated more potent LPO inhibition and Fe(2+) chelation compared to DHS and quercetin. Conversely, the diallyl ether at C7-OH and C20-OH was more potent in protection of PC12 cells against H(2)O(2)-induced injury than DHS and quercetin. Overall, the more lipophilic alkenylated DHS analogues were better performing neuroprotective agents than the acetamidated derivatives. The results in this study would be beneficial for optimizing the therapeutic potential of lignoflavonoids, especially in neurodegenerative disorders such as Alzheimers and Parkinsons disease.

Preparation of two sets of 5,6,7-trioxygenated dihydroflavonol derivatives as free radical scavengers and neuronal cell protectors to oxidative damage

An unusual class of 5,6,7-trioxygenated dihydroflavonols (3a-e and 4a-j) were designed and prepared. Their antioxidative properties were assessed by examining their capacities in several in vitro models, including superoxide anion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, rat liver homogenate lipid peroxidation inhibition, PC12 cells protection from oxidative damage, and xanthine oxidase inhibition. These dihydroflavonols displayed positive quenching abilities towards O(2)(-) and DPPH free radicals, in which the majority exhibited superior antioxidant properties to Vitamin C. cis-Configurated compound (+/-)-3e demonstrated remarkable inhibition to LPO with an IC(50) value of 1.9+/-0.3 microM, which was apparently stronger than that of quercetin (IC(50)=6.0+/-0.4 microM). trans-Configurated dihydroflavonol (+/-)-4h exhibited significant protective effect on PC12 cells against oxidative damage with an EC(50) value of 41.5+/-5.3 microM, more effective compared to that of quercetin (EC(50)=81.8+/-8.7 microM). The 6-OH-5,7-dimethoxy analogue (+/-)-3d showed significant inhibition of xanthine oxidase with an IC(50) value of 16.0+/-0.8 microM, which is superior to that of allopurinol (IC(50)=23.5+/-2.0 microM). In addition to the hypothesized action mechanism of the bio-active compounds, 3D modeling was used to analyze the relationship between the minimized-energy structures and antioxidant activities.

Preparation of C-23 esterified silybin derivatives and evaluation of their lipid peroxidation inhibitory and DNA protective properties

A diverse series of C-23 esterified silybin derivatives (1a-n) were designed and synthesized. The antioxidative properties of these compounds were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radical scavenging, ferrous ion chelation, and inhibition of rat liver homogenate lipid peroxidation. Their protective effects on the prevention of hydrogen peroxide induced DNA damage were also investigated. Most of the synthesized compounds exhibited more effective antioxidant activities than silybin. The esterified silybin analogues displayed satisfactory performance especially on iron chelation and antiperoxidative activity. Compound 1n in particular exhibited remarkable antiperoxidative effect with an IC(50) value of 0.2+/-0.1 microM, which was stronger than that of quercetin (IC(50)=1.8+/-0.6 microM). Compounds 1c, 1e, 1g, 1h and 1k displayed potent, dose-dependent protective properties against DNA cleavage. The results of the bioassays support the antioxidative and DNA protective effects of these synthesized silybin derivatives.

Chemotherapeutic Effects of Bioassay-Guided Extracts of the American Cockroach, Periplaneta americana

The organic extract of Periplaneta americana L. (Dictyoptera; Blattidae) has been traditionally used in southwestern China as an alternative medicine against disorders such as hepatitis, trauma, gastric ulcers, burns, and heart disease. The present study describes bioassay-guided purification and chemotherapeutic evaluation of the 60% ethanolic fraction of P americana organic extracts (PAE60). The most effective cytotoxic fraction was determined by way of repeated in vitro screenings against 12 distinct cultured human carcinoma cell lines: Eca 109, BGC823, HO8910, LS174T, CNE, HeLa, K562, PC-3, A549, BEL 7404, HL-60, and KB, followed by in vivo antitumor assays of the lead fraction (PAE60). The complexity of enriched active fraction was qualitatively evaluated using thin layer chromatography. Reconstituted PAE60 was effective at inhibiting HL-60, KB, CNE, and BGC823 cell growth with IC50 values <20 µg mL−1. PAE60 reduced tumor growth in S180-bearing immunocompetent mice by 72.62% after 10 days following oral doses of 500 mg kg d−1 compared with 78.75% inhibition following 40 mg kg d−1 of cyclophosphamide (CTX). Thymus and spleen indices of S180-bearing mice treated with PAE60 were significantly greater (P < .05) than CTX treatment groups, suggesting potential immunomodulation of antitumor host defenses by PAE60. Antiviral activity was also investigated and PAE60 inhibited herpes simplex type-2 replication (IC50 = 4.11 ± 0.64 µg mL−1) with a selectivity index (CC50 to IC50 ratio) of 64.84 in Vero cells but was less effective on type-1 virus (IC50 of 25.6 ± 3.16 µg mL−1). These results support future clinical trials on P. americana as an alternative or complementary medicinal agent.