• Natural Product Sciences
• /
• v.6 no.1
• /
• pp.1-4
• /
• 2000

Four biflavonoids were isolated from the leaves of Cephalotaxus koreana. Based on spectroscopic data, the compounds were identified as amentoflavone-7',7",4',4"'-tetramethyl ether, sciadopitysin, ginkgetin and bilobetin, respectively.

• Archives of Pharmacal Research
• /
• v.28 no.11
• /
• pp.1233-1235
• /
• 2005

Two new biflavonoids, 3'-hydroxyamentoflavone-7-O-methyl ether (1) and 3'-hydroxyamentoflavone (2), were isolated from the fruits of Aristolochia contorta Bge. Their structures were elucidated by HR-ESI-MS, 1D-, and 2D-NMR spectroscopy.

• Archives of Pharmacal Research
• /
• v.20 no.6
• /
• pp.533-538
• /
• 1997

Biflavonoid is one of unique classes of naturally-occurring bioflavonoid. Previously, certain biflavonoids were found to possess the inhibitory effects on phospholipase $A_2$ activity and lymphocytes $ proliferation^1$ suggesting their anti-inflammatory/immunoregulatory potential. In this study, effects of several biflavonoids on arachidonic acid release from rat peritoneal macrophages were investigated, because arachidonic acid released from the activated macrophages is one of the indices of inflammatory conditions. When resident peritoneal macrophages labeled with $[^{3}H]$arachidonic acid were activated by phorbol 12-myristate 13-acetate(PMA) or calcium ionophore, A23187, radioactivity released in the medium was increased approximately 4.1-7.3 fold after 120 min incubation compared to the spontaneous release in the control incubation. In this condition, biflavonoids (10 uM) such as ochnaflavone, ginkgetin and isoginkgetin, showed inhibition of arachidonate release from macrophages activated by PMA (32.5-40.0% inhibition) or A23187 (21.7-41.7% inhibition). Amentoflavone showed protection only against PMA-induced arachidonate release, while apigenin, a monomer of these biflavonoids, did not show the significant inhibition up to 10 uM. Staurosporin (1 uM), a protein kinase C inhibitor, showed an inhibitory effect only against PMA-induced arachidonate release (96.8% inhibition). Inhibition of arachidonate release from the activated macrophages may contribute to an anti-inflammatory potential of biflavonoids in vivo.

• Bulletin of the Korean Chemical Society
• /
• v.29 no.8
• /
• pp.1479-1484
• /
• 2008

Protein tyrosine phosphatase (PTP) 1B is the superfamily of PTPs and a negative regulator of multiple receptor tyrosine kinases (RTKs). Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a strategy for the treatment of type 2 diabetes and obesity. Recently, it has been reported that amentoflavone, a biflavonoid extracted from Selaginella tamariscina, inhibited PTP1B. In the present study, docking model between amentoflavone and PTP1B was determined using automated docking study. Based on this docking model and the interactions between the known inhibitors and PTP1B, we determined multiple pharmacophore maps which consisted of five features, two hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. Using receptor-oriented pharmacophore-based in silico screening, we searched the biflavonoid database including 40 naturally occurring biflavonoids. From these results, it can be proposed that two biflavonoids, sumaflavone and tetrahydroamentoflavone can be potent allosteric inhibitors, and the linkage at 5',8''-position of two flavones and a hydroxyl group at 4'-position are the critical factors for their allosteric inhibition. This study will be helpful to understand the mechanism of allosteric inhibition of PTP1B by biflavonoids and give insights to develop potent inhibitors of PTP1B.

• Biomolecules & Therapeutics
• /
• v.28 no.2
• /
• pp.145-151
• /
• 2020

Alzheimer's disease (AD) is a devastating neurodegenerative disease and a major cause of dementia in elderly individuals worldwide. Increased deposition of insoluble amyloid β (Aβ) fibrils in the brain is thought be a key neuropathological hallmark of AD. Many recent studies show that natural products such as polyphenolic flavonoids inhibit the formation of insoluble Aβ fibrils and/or destabilize β-sheet-rich Aβ fibrils to form non-cytotoxic aggregates. In the present study, we explored the structure-activity relationship of naturally-occurring biflavonoids on Aβ amyloidogenesis utilizing an in vitro thioflavin T assay with Aβ1-42 peptide which is prone to aggregate more rapidly to fibrils than Aβ1-40 peptide. Among the biflavonoids we tested, we found amentoflavone revealed the most potent effects on inhibiting Aβ1-42 fibrillization (IC₅₀: 0.26 µM), as well as on disassembling preformed Aβ1-42 fibrils (EC₅₀: 0.59 µM). Our structure-activity relationship study suggests that the hydroxyl groups of biflavonoid compounds play an essential role in their molecular interaction with the dynamic process of Aβ1-42 fibrillization. Our atomic force microscopic imaging analysis demonstrates that amentoflavone directly disrupts the fibrillar structure of preformed Aβ1-42 fibrils, resulting in conversion of those fibrils to amorphous Aβ1-42 aggregates. These results indicate that amentoflavone affords the most potent anti-amyloidogenic effects on both inhibition of Aβ1-42 fibrillization and disaggregation of preformed mature Aβ1-42 fibrils.

• Natural Product Sciences
• /
• v.6 no.4
• /
• pp.170-178
• /
• 2000

Flavonoids are natural polyphenolic compounds widely distributed in plant kingdom. Although many flavonoids were found to show anti-inflammatory activity in vitro and in vivo, the potency of anti-inflammatory activity was not enough for a clinical trial. Thus, a search for finding potential flavonoid molecules is continuing. In this review, in vivo anti-inflammatory activity of various flavonoid derivatives is summarized mainly based on the results obtained in authors' laboratories. Among them, several biflavonoids such as amentoflavone and ginkgetin were found to possess anti-inflammatory activity on animal models of acute/chronic inflammation comparable to nonsteroidal and steroidal anti-inflammatory drugs currently used. In respect of their action mechanisms, the effects on arachidonic acid metabolism and nitric oxide production were described. Some flavonoids directly inhibit cyclooxygenase and/or lipoxygenase. Biflavones such as ochnaflavone and ginkgetin are inhibitors of phospholipase $A_2$. In recent studies, certain flavonoids were also found to suppress cyclooxygenase-2 and inducible nitric oxide synthase expression induced by inflammatory stimuli. Therefore, it is suggested that anti-inflammatory activity of the certain flavonoids (mainly flavones, flavonols and biflavonoids) may be mediated by direct inhibition of arachidonic acid metabolizing enzymes as well as suppression of the enzyme expression involved in inflammatory responses.

• Korean Journal of Pharmacognosy
• /
• v.22 no.4
• /
• pp.207-210
• /
• 1991

From the chloroform and n-butanol extracts of Selaginella tamariscina, three biflavonoids were isolated by chromatographic separation. Structures of these compounds were determined as cryptomerin B, amentoflavone and isocryptomerin by spectroscopic analysis, and amentoflavone was further identified by comparison with the authentic sample. This is the first report of isolation of cryptomerin B from Selaginellaceae.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2007.11a
• /
• pp.67-73
• /
• 2007

There have been various inflammatory skin disorders in humans including atopic dermatitis, eczema and psoriasis. Although some drugs have been used for these disorders, there is an urgent need for safer and more effective topical anti-inflammatory agents. Plant flavonoids possess anti-inflammatory activity and some of them have multiple pharmacological mechanisms, inhibition of eicosanoid metabolizing enzymes, histamine release and/or down-regulation of pro inflammatory gene expression. These properties of flavonoids may be suitable for treating chronic skin inflammatory disorders. Especially, wogonin, some prenylated flavonoids and biflavonoids have a strong potential as new anti-inflammatory agents by topical application.

• Korean Journal of Pharmacognosy
• /
• v.26 no.1
• /
• pp.23-26
• /
• 1995

6-Hydroxykynurenic acid and ginkgolide B together with flavonol glycosides and biflavonoids were isolated from the yellow leaves of Ginkgo biloba and identified by means of spectroscopic methods. The correctness of $H{\"{o}}lzl's$ ${13}^C-NMR$ assignments for 6-hydroxykynurenic acid was confirmed by HMQC and HMBC techniques. Based on our present findings, it may be considered that the yellow Ginkgo leaves may contribute to be a source of high medicinal values.

• Natural Product Sciences
• /
• v.2 no.1
• /
• pp.1-8
• /
• 1996

Flavonoids are widely distributed polyphenol compounds in plant kingdom and known to possess varieties of biological/pharmacological activities in vitro and in vivo. A search for antiinflammatory/immunoregulatory flavonoids as potential therapeutic agents has been continued, since serious side effects of currently used nonsteroidal and steroidal antiinflammatory drugs limit their long term uses for the inflammatory disorders. In this reserch, various flavonids were isolated and tested for their in vivo antiinflammatory activity and in vitro inhibitory activity of lymphocyte proliferation. Using a mouse ear edema assay, it was found that certain flavones/flavonols possess mild antiinflammatory activity and a C-2,3-double bond might be essential. Isoflavones were less active. These flavonoids inhibited in vitro lymphocyte proliferation, relatively specific for T-cell proliferation $(IC_{50}=1-10\;{\mu}M)$ and the inhibition was reversible. We have also tested several biflavonoid derivatives, since we recently found that biflavones were phospholipase $A_2$ inhibitors. It was demonstrated that biflavones such as ochnaflavone and ginkgetin inhibited lymphocyte proliferation induced by both concanavaline A and lipopolysaccharide. The inhibition was irreversible in contrast to that of flavones/flavonols. And antiinflammatory activity of biflavonoids are discussed.