Gunther Burkhardt

Reduction of cisplatin toxicity in cultured renal tubular cells by the bioflavonoid quercetin.

Abstract Quercetin (QC), a polyphenolic compound widely distributed in fruits and vegetables has recently gained interest due to its cisplatin (CP) sensitizing properties in cancer cells. It is currently unknown, whether quercetin also increases the susceptibility of the kidneys to cisplatin toxicity. We studied the effects of various bioflavonoids on CP toxicity in an in vitro model of cultured tubular epithelial cells (LLC-PK1). Viability of LLC-PK1 cells, as assessed by lactate dehydrogenase (LDH) release and MTT-test, was affected by CP (100–400 μM) in a time and dose dependent fashion. Pretreatment of cells with QC for 3 h significantly reduced the extent of cell damage. The protective activity of QC was concentration dependent, starting at 10–25 μM and reaching a plateau between 50 and 100 μM. Other bioflavonoids (catechin, silibinin, rutin) did not diminish cellular injury, even at higher concentrations (100–500 μM). Quercetin itself showed some intrinsic cytotoxicity at concentrations exceeding 75 μM. Our data indicate that quercetin reduces cisplatin toxicity in cultured tubular epithelial cells. The exact mechanism of protection is unclear, though scavenging of free oxygen radicals may play an important role.

Improved cold preservation of kidney tubular cells by means of adding bioflavonoids to organ preservation solutions

Background. Cold ischemia and reperfusion during renal transplantation result in release of reactive oxygen species. The aim of this study is to examine whether cold storage induced cell injury can be ameliorated by adding flavonoids directly to preservation solutions. Methods. Cultured renal tubular epithelial cells (LLC-PK1) were stored in University of Wisconsin (UW) or Euro-Collins (EC) solution at 4°C for 20 hours. Preservation solutions were supplemented with various flavonoids. After rewarming, structural and metabolic cell integrity was measured by lactate dehydrogenase (LDH) release and MTT-test, and lipid peroxidation was assessed from generation of thiobarbituric acid-reactive substances (TBARS). Results. Twenty hours of cold storage resulted in a substantial loss of cell viability in both preservation solutions (in EC: LDH release 92.4±2.7%; MTT-test 0.5±0.7%). Addition of luteolin, quercetin, kempferol, fisetin, myricetin, morin, catechin, and silibinin significantly reduced cell injury (for luteolin in EC: LDH release 2.4±1.6%; MTT-test 110.3±10.4%, P<0.01; TBARS-production (related to cold stored control cells) 8.9±2.6%). No cytoprotection was found for apigenin, naringenin, and rutin. Protective potency of flavonoids depends on number of hydroxyl-substituents and lipophilicity of the diphenylpyran compounds. Conclusion. Cold storage induced injury of renal tubular cells was substantially ameliorated by adding selected flavonoids directly to preservation solutions.

Riccionidins a and b, anthocyanidins from the cell walls of the liverwort Ricciocarpos natans☆

Abstract A new anthocyanidin (riccionidin A) and a dimer (riccionidin B) were isolated from cell walls of the liverwort Ricciocarpos natans . The structure of riccionidin A was established; riccionidin B was characterized by 13 C 1 H correlation NMR spectroscopy and high resolution FAB mass spectroscopy. Both pigments were also detected in the liverworts Marchantia polymorpha , Riccia duplex and Scapania undulata .

Sphenolobane and fusicoccane diterpenoids from the liverwort Anastrophyllum auritum

Abstract An ether extract of the liverwort Anastrophyllum auritum yielded seven new sphenolobane-type diterpenoids, 3α,4α-epoxy-5α,18-dihydroxysphenoloba-13Z(15),16E-diene, 3α,4α-epoxy-18-hydroxysphenoloba-13E(15),16E-diene, 3α,4α-epoxy-18-hydroxysphenoloba-13Z(15),16E-diene, 3α,4α-epoxy-5α-hydroxysphenoloba-13E(15),16E,18-triene, 3α,4α-epoxysphenoloba-13E(15),16E,18-triene, 3α,4α-epoxy-5α-hydroxysphenoloba-13,15E,17-triene, 3α,4α-epoxysphenoloba-13E(15),17-diene and a new fusicoccane-type diterpenoid, named fusicoauritone, together with the previously known 3α4α-epoxy-5α,18-dihydroxysphenoloba-13E(15),16E-diene, fusicogigantone A and fusicogigantone B. In addition some known sesqui- and diterpenoids were detected, among which (−)-ar-curcumene was isolated from a liverwort for the first time.

Biphenyls and xanthones from the podostemaceae

Abstract Investigation of the fruiting parts of Mourera fluviatilis afforded 6-desoxyjacareubin, trapezifoliaxanthone and a series of eight new biphenyl derivatives; 3,5-dimethoxybiphenyl; 2,2-dimethyl-5-methoxy-7-phenylchromene; 2,2-dimethyl-7-methoxy-5-phenylchromene; 2-(3,3-dimethylallyl)-3-hydroxy-5-methoxybiphenyl; 2,3-dihydro-6-methoxy-4-phenyl-2,3,3-trimethylcoumarone; [(2,3-dihydro-3,3-dimethyl-6-methoxy-4-phenyl)-2-coumaronyl]methanol; 2,3-dihydro-3,3-dimethyl-6-methoxy-2-oxo-4-phenylcoumarone; and a dimeric biphenyl.

Epi-neoverrucosane- and epi-homoverrucosane-type diterpenoids from Fossombronia alaskana

Fossombronia alaskana, a rare arctic liverwort, was axenically cultured. Phytochemical investigation of the gametophytes afforded five new epi-neoverrucosane-type diterpenoids (5-oxo-epi-neoverrucosane, 13-hydroxy-5-oxo-epi-neoverrucosane, 8α-acetoxy-13-hydroxy-5-oxo-epi-neoverrucosane, 8α,16-diacetoxy-13-hydroxy-5-oxo-epi-neoverrucosane and 8α,13-dihydroxy-5-oxo-epi-neoverrucosane) together with the previously known 5β-hydroxy-epi-neoverrucosane. The overall number of natural products with the epi-neoverrucosane skeleton is now seven. In addition, the new homoverrucosane-type diterpene 5,18-dihydroxy-epi-homoverrucosane was isolated. The structures were elucidated by X-ray crystallography (5-oxo-epi-neoverrucosane), two-dimensional NMR spectroscopy and chemical degradation, resulting in some unsaturated epi-neoverrucosane structures.

Triterpenes from Fossombronia liverworts

In vitro cultured gametophytes of Fossombronia alaskana and F. pusilla were investigated for their terpene contents. Three new triterpenes, 22-hydroxy-29-methylhopanoatet 20-hydroxy-22(29)-hopen and 22(30)-hopen-29-oic acid were isolated together with adianton, diplopterol, tetrahymanol, caryophyllene-6,7-epoxide and α-tocopherol.

Hypnogenols and other dihydroflavonols from the moss Hypnum cupressiforme

Abstract Six new aromadendrin-derived flavanoids have been isolated from Hypnum cupressiforme; hypnogenol A; hypnogenol B; 3,5,7,4′,3″,5″,7″,3″′4″−nonahydroxy-3′-6″-biflavanone, 3,5,7,4′,3″,5″,7″-heptahydroxy-3′-O-4″ -biflavanone; 1″′,2″′,3″′,4″′-tetrahydro-3,3″,5,5″,7,7″-hexahydroxy-4″′-keto-3′-1″′,4′-O-2″′-biflavanone and 3,5,7, 4′-tetrahydroxy-3′-(3″-formyl-6″-hydroxyphenyl)-flavanone.

Bioactive chromenes fromRhyncholacis penicillata

Investigation of the aerial parts of Rhyncholacis penicillata afforded the new chromenes, 7-hydroxy-6-(3-methylbutyryl)-5-oxymethyl-chromene (rhynchonin A) and 7-hydroxy-6-(2-methylbutyryl)-6-oxymethylchromene (rhynchonin B). Structures were elucidated by spectroscopic methods and independent synthesis. Rhynchonin A showed broad insecticidal, acaricidal and nematicidal potency including strong biological activity against Heliothis zea.

Effect of quercetin on hypoxic injury in freshly isolated rat proximal tubules

The bioflavonoid quercetin, which has antioxidant properties, protects renal tubular epithelial cells from oxidant-induced injury by inhibiting lipid peroxidation. We examined the effect of quercetin on hypoxia-induced injury in freshly isolated rat renal proximal tubules. Hypoxia induced rapid loss of cellular ATP, followed by functional and structural alterations measured as a decrease in tubular potassium content and sequentially by an increase in lactate dehydrogenase release. Furthermore, hypoxia increased lipid peroxidation, measured as thiobarbituric acid-reactive substances. Quercetin significantly inhibited hypoxia-induced functional and structural tubular injury in addition to lipid peroxidation but did not alter hypoxia-induced ATP depletion. These results demonstrate the potency of the bioflavonoid quercetin in protecting proximal tubules from hypoxic injury, which is independent of tubular energy metabolism and may be related to the inhibition of lipid peroxidation.