Nepodin

Biofactors. 2014 Jul-Aug;40(4):436-47.

Antidiabetic effect of nepodin, a component of Rumex roots, and its modes of action in vitro and in vivo.[Pubmed: 24756979 ]

Many active components derived from edible natural resources such as plant extracts have recently attracted attention for their potential use as functional foods or drugs for preventing and treating metabolic diseases such as diabetes.
METHODS AND RESULTS:
To obtain a novel modulator of glucose metabolism, we conducted screening of a small compound library in cultured L6 myotubes. We identified Nepodin that stimulated glucose uptake dose-dependently in differentiated L6 myotubes. The stimulatory effect of Nepodin on glucose uptake was abrogated by a 5'-adenosine monophosphate-activated protein kinase (AMPK) inhibitor. In addition, Nepodin stimulated the phosphorylation of AMPK. Nepodin also stimulated the translocation of GLUT4 to the plasma membrane in L6 myoblasts transfected with a Glut4 cDNA-coding vector and in differentiated L6 myotubes. In in vivo study, Nepodin suppressed the increases in fasting blood glucose levels and improved the glucose intolerance of C57BL/KsJ-db/db mice, a type 2 diabetic animal model. Nepodin rescued the impaired phosphorylation of AMPK in the skeletal muscle of db/db mice.
CONCLUSIONS:
These results suggest that Nepodin has an antidiabetic effect, which is at least partly mediated by stimulation of GLUT4 translocation via AMPK activation by Nepodin.

Arch Pharm Res. 2013 Apr;36(4):430-5.

Antimalarial activity of nepodin isolated from Rumex crispus.[Pubmed: 23440579 ]

The purpose of this study is to define the antimalarial activity of Rumex crispus.
METHODS AND RESULTS:
To identify an active compound that is isolated from R. crispus, bioassay-based chromatographic fractionation and purification is carried out from 70 % ethanol extract of R. crispus; then, an active compound, Nepodin, is identified by spectroscopic analysis. Anitmalarial activity is measured by PfNDH2 assay, cytotoxicity, and animal test. From NADH:quinone oxidoreductase enzyme (PfNDAH2) assay, Nepodin exhibited significant IC50 values that were 0.74 ± 0.07 and 0.79 ± 0.06 μg/ml against P. falciparum chloroquine-sensitive (3D7) and P. falciparum chloroquine-resistant (S20), respectively. Nepodin showed a potential selective inhibition (SI index: ratio of 50 % cytotoxic concentration to 50 % effective anti-plasmodial concentration) of 161.6 and 151.4 against P. falciparum 3D7 and P. falciparum S20. In the animal test, all groups of Nepodin treatment of 10, 50, and 250 mg/kg were active with a parasitemia suppression of 97.1 ± 3.3, 99.1 ± 3.7, and 99.1 ± 2.6 %, respectively. The survival time with Nepodin treatment was increased by 14.6 ± 2.5, 16.2 ± 1.5, and 19.8 ± 1.7 days at each dose, respectively.
CONCLUSIONS:
This study newly identified the plant R. crispus containing Nepodin, which is a potential antimalarial compound. It exhibited the inhibitory activity of PfNDH2 and prolonged the survival time on the group of Nepodin treatment; moreover, it inhibited the parasitemia in the animal test.

J Agric Food Chem. 2012 Oct 24;60(42):10415-9.

Isolation and identification of Flavobacterium columnare and Streptococcus iniae antibacterial compounds from the terrestrial plant Atraphaxis laetevirens.[Pubmed: 23030835 ]

Columnaris disease, enteric septicemia of catfish, and streptococcosis are common bacterial diseases of certain freshwater fish and are caused by Flavobacterium columnare , Edwardsiella ictaluri , and Streptococcus iniae , respectively.
METHODS AND RESULTS:
During the process of evaluating several species of plants to isolate and identify compounds with toxicity against these bacteria, a promising extract from the aerial parts of the terrestrial plant Atraphaxis laetevirens (Ledeb.) Jaub. et Spach (Polygonaceae Juss.) was selected for bioassay-guided fractionation using a rapid microplate bioassay. The active dichloromethane extract was subjected to liquid-liquid partitioning, and active fractions were further separated by normal-phase column chromatography and normal-phase high-performance liquid chromatography (HPLC). Nepodin (3) and emodin (4) were isolated from two fractions with strong toxicities against S. iniae .
CONCLUSIONS:
A chloroform fraction was further separated by normal-phase column chromatography to yield two active fractions against F. columnare , and these fractions contained chrysophanol (1), physcion (2), and Nepodin (3). Compound 1 had strong activity, and compound 3 had moderate activity against F. columnare , while compounds 2 and 4 were not toxic at the concentrations tested.

Eur J Med Chem. 2014 Jun 10;80:47-56.

Synthesis, biological evaluation, molecular docking and theoretical evaluation of ADMET properties of nepodin and chrysophanol derivatives as potential cyclooxygenase (COX-1, COX-2) inhibitors.[Pubmed: 24763362]

Nepodin and chrysophanol, isolated from Rumex nepalensis roots, showed significant cyclooxygenase (COX) inhibitory activity.
METHODS AND RESULTS:
To further optimize these lead molecules and study structure activity relationship (SAR), eighteen derivatives of Nepodin and nine derivatives of chrysophanol were synthesized and evaluated for COX-1 and COX-2 inhibitory potential. Among the synthesized compounds, four Nepodin (1f, 1g, 1h and 1i) and three chrysophanol (2e, 2f and 2h) derivatives displayed more pronounced COX-2 inhibition than their respective lead molecule. Further, compounds 1f, 1g, 2e and 2h exhibited better anti-inflammatory activity than ibuprofen in carrageenan-induced rat paw edema assay.
CONCLUSIONS:
Taking into account the in vitro and in vivo results, molecular docking and in silico prediction of ADMET properties of compounds were carried out respectively.