A. Nahrstedt

Cinchonain Ib isolated from Eriobotrya japonica induces insulin secretion in vitro and in vivo.

AIMS OF THE STUDYnEriobotrya japonica leaves had been used traditionally for the treatment of diabetes mellitus by immersing the dried leaves in a hot water drink. Few studies have shown the hypoglycemic effect of Eriobotrya japonica using crude alcoholic extract and isolated methanolic compounds. These studies proposed that the mechanism of action could be by stimulating the beta-islets of Langerhans to secrete insulin, however with no scientific evidence.nnnMETHODSnEriobotrya japonica water extract (EJWE) and the compounds derived from it: cinchonain Ib, procyanidin B-2, chlorogenic acid and epicatechin, were tested for their effects on insulin secretion from INS-1 cells and following oral administration in rats.nnnRESULTSnThe present study showed that EJWE increased significantly (p<0.05) insulin secretion from INS-1 cells in dose-dependent manner. Oral administration of EJWE at 230 mg/kg to rats, however, decreased plasma insulin level for as long as 240 min post-administration and caused a transient drop of blood glucose at 15 and 30 min post-administration. On the other hand, cinchonain Ib enhanced significantly (p<0.05) insulin secretion from INS-1 cells, whereas epicatechin inhibited significantly (p<0.05) insulin secretion from INS-1 cells. In addition, cinchonain Ib enhanced significantly (150%: p<0.05) plasma insulin level in rats for as long as 240 min after 108 mg/kg oral administration but did not induce any change in blood glucose level.nnnCONCLUSIONnThese data indicate that cinchonain Ib has an insulinotropic effect and suggest the possible use of cinchonain Ib for managing type 2 diabetes.

Willow bark extract: The contribution of polyphenols to the overall effect

ZusammenfassungDie Wirksamkeit von Weidenrindenextrakten in der Behandlung schmerzhafter Erkrankungen des Bewegungsapparates, wie Rückenschmerzen und Arthritis, wurde dem Gehalt an Salicinderivaten als Prodrugs für Salicylate zugeschrieben. Aus der Erfahrung klinischer Studien und pharmakologischer Testmodelle heraus kann jedoch die Gesamtsalicinfraktion nicht als zufriedenstellende Erklärung für die Wirksamkeit der Weidenrinde herangezogen werden. Darüber hinaus fehlt den Salicinen und ihren Metaboliten das Acetylierungspotenzial der ASS, so dass hier ein anderer Wirkmechanismus vorliegen muss. Ein detailliertes pharmakologisches Screening des wässrigen Weidenrindenextraktes STW 33-I zielte auf die Frage nach der Identifizierung von Fraktionen mit einem Anteil am Gesamteffekt ab. Alle angewandten in vitro- und in vivo-Modelle ließen auf einen relevanten Beitrag der Fraktion der Polyphenole und Flavonoide schließen. Die Aufklärung der für diesen Effekt verantwortlichen Einzelsubstanzen bzw. ihrer Kombinationen wird Thema zukünftiger Untersuchungen sein.SummaryThe efficacy of willow bark extract in the treatment of painful mobility disorders, such as back pain and arthritis, has been attributed to the content of salicin and its derivatives as pro-drugs of salicylates. However, based on clinical experience and the evidence of experimental pharmacological studies, the fraction of total salicin cannot satisfactorily explain the clinical efficacy of willow bark. In addition, salicins and their metabolites lack the acetylating potential of ASA and must therefore possess a different mechanism of action. A detailed pharmacological screening of the aqueous willow bark extract STW 33-I addressed the question of the identification of fractions contributing to the overall effect. All in vivo and in vitro models studied pointed to relevant contributions of the fraction of polyphenols and flavonoids. The single compounds or their combinations responsible for the effect remain to be elucidated.

Polyphenols from Ginkgo biloba

By Sephadex LH-20 gel chromatography of an extract from Gingko biloba leaves, polymeric proanthocyanidins were eluted after the fractions of flavonol glycosides and biflavone glycosides. A purified proanthocyanidin polymer accounted for 86.6% of the total proanthocyanidins, and for 37.7% of the total antioxidant activity of this leaf extract. For structure elucidation, the polymer was submitted to acidic depolymerization in the presence of phloroglucinol. The structures of the resulting flavan-3-ols and phloroglucinol adducts were determined on the basis of 1D-and reverse 2D-NMR (HSQC, HMBC) spectra of their peracetylated derivatives, MALDI-TOF-MS and CD-spectroscopy. The observations resulting from the degradation with phloroglucinol were confirmed by 13C-NMR spectroscopy of the polymer. The mean molecular weight of the polymeric fraction was estimated to be 9–10 flavan-3-ol-units.

Proanthocyanidins from Ginkgo biloba leaf extract and their radical scavenging activity

Context: Ginkgo biloba L (Ginkgoaceae) is a traditional herbal medicinal plant for the treatment of mild to moderate cognitive disorders, tinnitus, and dementia. These uses may be correlated with the presence of radical scavenging compounds. Objective: The chemical composition and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of the flavan-3-ols and proanthocyanidins from G. biloba were studied. Material and methods: The compounds have been isolated using column chromatography on Sephadex LH-20 and MCI gel and the structures were determined on the basis of 1D- and 2D-NMR (HSQC, HMBC) experiments of their peracetylated derivatives, MALDI-TOF-MS and by acid-catalyzed degradation with phloroglucinol. The DPPH radical scavenging activities of the compounds were investigated. Results: The new trimeric prodelphinidin, epigallocatechin-(4β→8)-epigallocatechin-(4β→8)-catechin (compound 7), has been isolated from the air-dried leaves of the title plant, in addition to catechin, epigallocatechin, gallocatechin, and three dimeric proanthocyanidins. The dimeric prodelphinidin epigallocatechin-(4β→8)-epigallocatechin (compound 6) showed the strongest DPPH radical scavenging activity, with IC50 1.7 μg/mL, 10 times more active than the positive control, BHT (IC50 17.3 µg/mL), followed by the new trimeric proanthocyanidin epigallocatechin-(4β→8)-epigallocatechin-(4β→8)-catechin with IC50 2.1 µg/mL. The crude extract exhibited high DPPH radical scavenging activity with IC50 15.5 µg/mL comparable with that of BHT. Discussion and conclusion: The results showed that all the isolated compounds from the tannin fraction exhibited potent free radical scavenging activities, which were higher than that of BHT, suggesting that the condensed tannins from G. biloba leaves strongly contribute to the overall antioxidant effects.

Flavan-3-ols and procyanidins from the bark of Salix purpurea

From a commercial aqueous ethanolic extract obtained from the bark of Salix purpurea L. the flavan-3-ols catechin, epicatechin, gallocatechin, catechin-3-O-(1-hydroxy-6-oxo-2-cyclohexene-1-carboxylic acid)-ester, the dimeric procyanidins B1, B3 and the trimeric procyanidins epicatechin-(4B-->8)-catechin-(4alpha-->8)-catechin and epicatechin-(4beta-->8)-epicatechin-(4beta-->8)-catechin were isolated. Structure elucidation was performed by NMR, CD, MS, degradation and optical rotation methods. A fraction containing higher oligomeric procyanidins was investigated by 13C NMR. Data indicate an average degree of oligomerization of 4 to 5 flavan-3-ol units with dihydroxylated B-rings and predominance of 2,3-cis-stereochemistry.

Proanthocyanidins and Bio Genetically Related Dihydroflavonols from cistus Incanus L.

In addition to known monomeric flavan-3-ols, the aerial parts of Cistus incanus L. ssp. tauricus (Cistaceae) have been shown to contain the novel (+)-gallocatechin-3-O-gallate and the rarely encountered (+)-catechin-3-O-rhamnoside. They are accompanied by the prodelphinidins gallocatechin-(4α → 8)-catechin, gallocatechin-(4α → 8)-gallocatechin, their (4α → 6)-regioisomers, the structurally related novel epigallocatechin-(4β→ 6)-catechin, epigallocatechin-(4β → 6)-gallocatechin, as well as a 3-O-gallate of the latter, and gallocatechin-(4α → 8)-gallocatechin-(4α → 8)-catechin. Differences in the chemical shifts of constituent ‘upper’ and ‘lower’ pyrogallol B-ring units are significant in defining the sequence of units in ‘mixed’ oligomers. The range of procyanidins comprised B-l, B-3, and the tentatively identified novel catechin-(4α → 8)-gallocatechin. Biogenetic implications based on the co-occurence of dihydroflavonols and the composition of the proanthocyanidin pool are important considerations.