• 3,5-DHBA
• HCAR1
• Whole-grain diet
• alkylresorcinols
• cancer
• neurogenesis

• Humans
• Whole Grains/chemistry
• Hydroxybenzoates/pharmacology
• Diet
• Dietary Fiber/pharmacology
• Neoplasms/metabolism
• Receptors, G-Protein-Coupled/metabolism
• Resorcinols/metabolism

The investigation of alkylresorcinols has drawn an increasing interest recently. Alkylresorcinols (ARs) are natural chemical compounds synthesized by bacteria, fungi, sponges, and higher plants, possessing a lipophilic polyphenol structures and a myriad of biological properties. Human takes ARs as a component of a whole grain diet (from whole grain rye, wheat, and barley products), and thus, alkylresorcinols are frequently used as whole grain intake markers. Besides, ARs are considered as promising bioregulators of metabolic and immune processes, as well as adjuvant therapeutic agents for antimicrobial and anticancer treatment. In this review, we attempted to systematize the accumulated information concerning ARs origin, metabolism, biological properties, and their effect on human health.

A bisresorcinol was isolated as the main constituent of Heliciopsis terminalis’s trunk (Proteaceae). Recently, resorcinol is applied as an active whitening agent in various cosmetic products. Because of the structural mimic to resorcinol, benefits of the bisresorcinol as an aging-enzyme antagonist were demonstrated in this study.

The bisresorcinol was purified from the crude ethanolic extract of H. terminalis’s trunk by solvent extraction and preparative chromatography, respectively. Inhibitory activity on collagenase, elastase, and tyrosinase of the compound was investigated by using a different spectroscopic technique. Molecular docking was carried out to predict possible interactions of the substance around the enzyme active sites.

The IC₅₀ values on collagenase of the bisresorcinol and caffeic acid were 156.7 ± 0.7 and 308.9 ± 1.6 µmole L⁻¹, respectively. For elastase activity, the IC₅₀ of 33.2 ± 0.5 and 34.3 ± 0.3 µmole L⁻¹ was respectively determined for the bisresorcinol and ursolic acid. The bisresorcinol was inhibitory to tyrosinase by exhibiting the IC₅₀ of 22.8 µmole L⁻¹, and that of 78.4 µmole L⁻¹ was present for β-arbutin. The bisresorcinol bound to collagenase, elastase, and tyrosinase with the respective binding energies of −5.89, −5.69, and −6.57 kcal mol⁻¹. These binding energies were in the same ranges of tested inhibitors. The aromatic phenol groups in the structure were responsible for principle as well as supporting binding interactions with enzymes. Hydrogen binding due to hydroxyl groups and π-related attractive forces from an aromatic ring(s) provided binding versatility to bisresorcinol.

The bisresorcinol purified from H. terminalis might be useful for inclusion in cosmetic products as an aging-enzyme antagonist.

• Anti-aging property
• Bisresorcinol
• Collagenase
• Elastase
• Enzyme inhibition
• Heliciopsis terminalis
• Molecular docking
• Tyrosinase

Leishmaniasis is a vector-borne disease caused by the protozoan parasite Leishmania found in tropical and sub-tropical areas, affecting 12 million people around the world. Only few treatments are available against this disease and all of them present issues of toxicity and/or resistance. In this context, the development of new antileishmanial drugs specifically directed against a therapeutic target appears to be a promising strategy. The GDP-Mannose Pyrophosphorylase (GDP-MP) has been previously shown to be an attractive therapeutic target in Leishmania. In this study, a chemical library of 5000 compounds was screened on both L. infantum (LiGDP-MP) and human (hGDP-MP) GDP-MPs. From this screening, oncostemonol D was found to be active on both GDP-MPs at the micromolar level. Ten alkyl-resorcinol derivatives, of which oncostemonols E and J (2 and 3) were described for the first time from nature, were then evaluated on both enzymes as well as on L. infantum axenic and intramacrophage amastigotes. From this evaluation, compounds 1 and 3 inhibited both GDP-MPs at the micromolar level, and compound 9 displayed a three-times lower IC₅₀ on LiGDP-MP, at 11 µM, than on hGDP-MP. As they displayed mild activities on the parasite, these compounds need to be further pharmacomodulated in order to improve their affinity and specificity to the target as well as their antileishmanial activity.

• GDP-Mannose pyrophosphorylase
• Leishmania
• alkyl-resorcinol
• natural products
• therapeutic target

• Glucosides/chemistry
• Glucosides/isolation & purification
• Magnetic Resonance Spectroscopy
• Plant Leaves/chemistry
• Proteaceae/chemistry
• Resorcinols/chemistry

• Alcohols/analysis
• Aldehydes/analysis
• Alkanes/analysis
• Fatty Acids/analysis
• Gas Chromatography-Mass Spectrometry/methods
• Molecular Structure
• Plant Leaves/chemistry
• Resorcinols/analysis
• Secale/chemistry
• Secale/growth & development
• Stereoisomerism
• Steroids/analysis
• Surface Properties
• Waxes/chemistry
• Waxes/isolation & purification

AIM: To study the mechanism of cytotoxicity of a new active 5-alkyl resorcinol [1, 3-dihydroxy-5- (tridec-4’, 7’-dienyl) benzene] isolated from Lithraea molleoides leaves on liver tumor cells.

METHODS: Human hepatocarcinoma cell lines (HepG2 and Hep3B) in culture were treated with inhibitory concentrations, 50% of the compound, for 24 h. The induction of apoptosis was detected in treated cells by analysis of DNA fragmentation, DNA content, and acridine orange and propidium iodide staining.

RESULTS: After 24 h of 5-alkyl resorcinol treatment, both cell lines showed: (1) the typical morphological alterations of apoptosis; (2) DNA fragmentation, detected by laddering and appearance of a subG0 population by flow cytometry; and (3) condensed and fragmented nuclei by acridine orange-propidium iodide staining.

CONCLUSION: Based on the results, this compound exerts its cytotoxic effect in both hepatocellular cell lines through apoptotic cell death. For Hep3B, cells with mutated p53 and Fas, apoptosis would proceed by p53- or Fas-independent pathways.

• Lithraea molleoides
• Cytotoxic activity
• Alkyl resorcinol
• Apoptosis
• Hepatoma

• Anacardiaceae/chemistry
• Apoptosis/drug effects
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/pathology
• Cell Line, Tumor
• Cell Nucleus/drug effects
• Cell Nucleus/pathology
• Cytotoxins/analysis
• Cytotoxins/pharmacology
• Cytotoxins/therapeutic use
• DNA Fragmentation/drug effects
• DNA, Neoplasm/drug effects
• Fas-Associated Death Domain Protein/genetics
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/pathology
• Mutation
• Plant Extracts/analysis
• Plant Extracts/therapeutic use
• Plant Leaves/chemistry
• Resorcinols/pharmacology
• Resting Phase, Cell Cycle/drug effects
• Tumor Suppressor Protein p53/genetics

• Anacardiaceae
• Antineoplastic Agents, Phytogenic/administration & dosage
• Antineoplastic Agents, Phytogenic/pharmacology
• Antineoplastic Agents, Phytogenic/therapeutic use
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/pathology
• Cell Line, Tumor/drug effects
• Humans
• Phytotherapy
• Plant Extracts/administration & dosage
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use
• Plant Leaves
• Resorcinols/administration & dosage
• Resorcinols/pharmacology
• Resorcinols/therapeutic use