Chemical Composition, Antioxidant and Antiproliferative Activities of Taraxacum officinale Essential Oil.

Taraxacum officinale (TO) has been historically used for medicinal purposes due to its biological activity against specific disorders. To investigate the antioxidant and the antiproliferativepotential of TO essential oil in vitro and in vivo, the chemical composition of the essential oil was analyzed by GC-MS. The in vivo antioxidant capacity was assessed on liver and kidney homogenate samples from mice subjected to acetaminophen-induced oxidative stress and treated with TO essential oil (600 and 12,000 mg/kg BW) for 14 days. The in vitro scavenging activity was assayed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the reducing power methods. The cytotoxic effects against the HeLa cancer cell line were analyzed. The GC-MS analysis showed the presence of 34 compounds, 8 of which were identified as major constituents. The TO essential oil protected mice's liver and kidneys from acetaminophen-induced oxidative stress by enhancing antioxidant enzymes (catalase, superoxide dismutase, and glutathione) and lowering malondialdehyde levels. In vitro, the TO essential oil demonstrated low scavenging activity against DPPH (IC50 = 2.00 ± 0.05 mg/mL) and modest reducing power (EC50 = 0.963 ± 0.006 mg/mL). The growth of the HeLa cells was also reduced by the TO essential oil with an inhibition rate of 83.58% at 95 µg/mL. Current results reveal significant antioxidant and antiproliferative effects in a dose-dependent manner and suggest that Taraxacum officinale essential oil could be useful in formulations for cancer therapy.

Chemical Composition and Antioxidant Activity of Ammi visnaga L. Essential Oil.

The present study evaluated the chemical composition and the in vitro and in vivo antioxidant potential of Ammi visnaga L. essential oil to provide a scientific basis for the use of this plant in the traditional pharmacopoeia. Gas chromatography-mass spectrometry was used to identify the volatile constituents present of the oil. The in vitro antioxidant capacity was evaluated by the DPPH and the reducing power assays. For the in vivo tests, oral administration of Ammi visnaga L. oil (600 and 1200 mg/kg body weight) was performed in Swiss albino mice treated with acetaminophen (400 mg/kg). The toxic effect of acetaminophen and the action of the essential oil were measured by determining the levels of lipid peroxidation and antioxidant enzymes in liver and kidneys homogenates. The major components identified were butanoic acid, 2-methyl-, pentyl ester, (Z)-ß-ocimene, D-limonene, linalool, pulegone and lavandulyl-butyrate. The in vitro DPPH and reducing power assays showed moderate to low free radical scavenging activity and the antioxidant power was positively correlated with the polyphenols' concentration. In vivo, the Ammi visnaga L. essential oil showed a high antioxidant capacity at both concentrations (600 and 1200 mg/kg), effectively increasing the levels of reduced glutathione, superoxide dismutase, and catalase and significantly reducing the lipid peroxidation. The results obtained from this study suggest that Ammi visnaga L. could represent a source of molecules with antioxidant potential in the prevention of free radical-related diseases.

Structure-activity relationships of the ultrapotent vanilloid resiniferatoxin (RTX): The side chain benzylic methylene.

The side chain benzylic methylene is a critical element for the vanilloid activity of resiniferatoxin (2a, RTX), and introduction of branching, oxygen functions, or isosteric substitution at this center proved detrimental, with a decrease of potency of 2-3 orders of magnitude compared to the natural product. Conversely, only a modest erosion of activity was observed upon alpha-methylation and alpha-methylenation of the side chain. Surprisingly, introduction of an iodine atom in the guaiacyl moiety of the oxygen isoster 2h led to an unexpected and remarkable (>1000-fold) increase of potency, affording 2i, a compound that outperforms RTX in terms of vanilloid agonism and represents the first one-digit picomolar ligand of a TRP channel discovered to date.

Modulation of the transient receptor potential vanilloid channel TRPV4 by 4alpha-phorbol esters: a structure-activity study.

The mechanism of activation of the transient receptor potential vanilloid 4 (TRPV4) channel by 4alpha-phorbol esters was investigated by combining information from chemical modification of 4alpha-phorbol-didecanoate (4alpha-PDD, 2a), site-directed mutagenesis, Ca(2+) imaging, and electrophysiology. Binding of 4alpha-phorbol esters occurs in a loop in the TM3-TM4 domain of TRPV4 that is analogous to the capsaicin binding site of TRPV1, and the ester decoration of ring C and the A,B ring junction are critical for activity. The lipophilic ester groups on ring C serve mainly as a steering element, affecting the orientation of the diterpenoid core into the ligand binding pocket, while the nature of the A,B ring junction plays an essential role in the Ca(2+)-dependence of the TRPV4 response. Taken together, our results show that 4alpha-phorbol is a useful template to investigate the molecular details of TRPV4 activation by small molecules and obtain information for the rational design of structurally simpler ligands for this ion channel.

Denbinobin, a naturally occurring 1,4-phenanthrenequinone, inhibits HIV-1 replication through an NF-kappaB-dependent pathway.

Anthraquinones and structurally related compounds have been recently shown to exert antiviral activities and thus exhibit a therapeutic potential. In this study we report the isolation of the 1,4-phenanthrenequinone, denbinobin, from a variety of Cannabis sativa. Denbinobin does not affect the reverse transcription and integration steps of the viral cycle but prevents HIV-1 reactivation in Jurkat T cells activated by TNFalpha, mAbs anti-CD3/CD28 or PMA. In addition, denbinobin inhibits HIV-1-LTR activity at the level of transcription elongation and also TNFalpha-induced HIV-1-LTR transcriptional activity. We found that denbinobin prevents the binding of NF-kappaB to DNA and the phosphorylation and degradation of NF-kappaB inhibitory protein, IkappaBalpha, and inhibits the phosphorylation of the NF-kappaB p65 subunit in TNFalpha-stimulated cells. These results highlight the potential of the NF-kappaB transcription factor as a target for natural anti-HIV-1 compounds such as 1,4-phenanthrenequinones, which could serve as lead compounds for the development of an alternative therapeutic approach against AIDS.

A regiodivergent synthesis of ring a C-prenylflavones.

Capitalizing on the use of orthogonal protecting groups and the development of a modified Robinson flavone synthesis that avoids harsh acidic conditions, a regioselective synthesis of 6- and 8-prenylflavones from the same prenylated disilylated phloracetophenone (9) has been developed, targeting cannflavin B (1d), the COX-inhibiting principle of marijuana, and its unnatural isomer isocannflavin B (1e) as model compounds.

Structure-activity relationships of the ultrapotent vanilloid resiniferatoxin (RTX): the homovanillyl moiety.

Starting from ROPA (2), analogues of RTX (1a) modified on the acyl side chain were prepared and evaluated for vanilloid activity in HEK-293 cells over-expressing the human recombinant TRPV1. The ROPA motif provided an enhancement of potency sufficient to expand the range of vanillyl surrogates to structural elements (e.g., an unsubstituted phenyl ring) that afford inactive analogues in compounds from the capsaicin series.