Therapeutic Potential of 4-Hexylresorcinol in Preserving Testicular Function in Streptozotocin-Induced Diabetic Rats.

It is known that many diabetic patients experience testicular atrophy. This study sought to investigate the effect of 4-hexylresorcinol (4HR) on testicular function in rats with streptozotocin (STZ)-induced diabetes, focusing on testicular weight, sperm motility, histological alterations, and serum testosterone levels to understand the efficacy of 4HR on testes. Our findings reveal that 4HR treatment significantly improves testicular health in diabetic rats. Notably, the STZ group exhibited a testicular weight of 1.22 ± 0.48 g, whereas the STZ/4HR group showed a significantly enhanced weight of 1.91 ± 0.26 g (p < 0.001), aligning closely with the control group's weight of 1.99 ± 0.17 g and the 4HR group's weight of 2.05 ± 0.24 g, indicating no significant difference between control and 4HR groups (p > 0.05). Furthermore, the STZ/4HR group demonstrated significantly improved sperm motility compared to the STZ group, with apoptotic indicators notably reduced in the STZ/4HR group relative to the STZ group (p < 0.05). These results underscore the therapeutic potential of 4HR for maintaining testicular function under diabetic conditions.

Superior even skin tone and anti-ageing benefit of a combination of 4-hexylresorcinol and niacinamide.

OBJECTIVES: To demonstrate the synergistic effect of 4-hexylresorcinol (4-HR) with niacinamide in boosting anti-melanogenic efficacy in vitro and establish the in vivo efficacy and safety of the combination in a human trial. METHODS: Primary human epidermal melanocytes and 3D pigmented skin equivalents were treated with 4-HR, niacinamide, and their combinations for their effect on pigmentation. This was followed by a randomized, double-blind, split-face clinical study in Chinese subjects, and effects on skin tone, hyperpigmentation, fine lines and wrinkles, hydration, and skin firmness were measured for a 12-week study period. RESULTS: In vitro tyrosinase enzyme activity studies showed that 4-HR is one of the most potent tyrosinase inhibitors. The combination of 4-HR and niacinamide showed a synergistic reduction in melanin production in cultured melanocytes and lightened the 3D skin equivalent model. In vitro as well as in the human trial, the combination of 4-HR and niacinamide showed significantly improved efficacy over niacinamide alone on hyperpigmentation spots as measured by L*, the visual appearance of fine lines and wrinkles in crow's feet and perioral area and skin firmness, with no product-related adverse events. CONCLUSIONS: A formulation containing a combination of 4-HR and niacinamide delivered superior skin tone and anti-ageing benefits significantly better than niacinamide alone with no adverse events. This study demonstrates that a product designed to affect multiple pathways of melanogenesis, inflammation, and ageing may provide an additional treatment option, beyond hydroquinone and retinoids, for hyperpigmentation and ageing.

OBJECTIFS: Démontrer l'effet synergique du 4-hexylrésorcinol (4-HR) associé au niacinamide pour stimuler in vitro l'efficacité antimélanogène, et établir l'efficacité et la sécurité d'emploi in vivo de cette association dans un essai chez l'homme. MÉTHODES: Des mélanocytes épidermiques humains primaires et des équivalents cutanés pigmentés en 3D ont été traités avec du 4-HR, du niacinamide et leurs combinaisons pour leur effet sur la pigmentation. Ceci a été suivi d'une étude clinique randomisée, en double aveugle en hémi-visage chez des sujets chinois, et les effets sur le teint, l'hyperpigmentation, les rides et ridules, l'hydratation et la fermeté de la peau ont été mesurés pendant une durée d'étude de 12 semaines. RÉSULTATS: Les études in vitro sur l'activité enzymatique de la tyrosinase ont montré que le 4-HR est l'un des inhibiteurs de la tyrosinase les plus puissants. L'association du 4-HR et du niacinamide a montré une réduction synergique de la production de mélanine dans les mélanocytes de culture et donné de la luminosité au modèle cutané 3D équivalent. Également in vitro avec l'étude chez l'homme, l'association du 4-HR et du niacinamide a fait ressortir une efficacité significativement plus élevée qu'avec le niacinamide seul sur les taches d'hyperpigmentation mesurées par L*, l'aspect visuel des rides et ridules des pattes d'oie et de la zone périorale, et la fermeté de la peau, sans événements indésirables liés au produit. CONCLUSIONS: Une formulation contenant une association de 4-HR et de niacinamide a permis d'obtenir un teint et un effet anti-âge nettement supérieurs à ceux du niacinamide seul, sans événements indésirables. Cette étude démontre qu'un produit conçu pour toucher plusieurs voies de mélanogenèse, d'inflammation et de vieillissement peut constituer une nouvelle option thérapeutique, au-delà de l'hydroquinone et des rétinoïdes, pour l'hyperpigmentation et le vieillissement.

The use of 4-Hexylresorcinol as antibiotic adjuvant.

Ever decreasing efficiency of antibiotic treatment due to growing antibiotic resistance of pathogenic bacteria is a critical issue in clinical practice. The two generally accepted major approaches to this problem are the search for new antibiotics and the development of antibiotic adjuvants to enhance the antimicrobial activity of known compounds. It was therefore the aim of the present study to test whether alkylresorcinols, a class of phenolic lipids, can be used as adjuvants to potentiate the effect of various classes of antibiotics. Alkylresorcinols were combined with 12 clinically used antibiotics. Growth-inhibiting activity against a broad range of pro- and eukaryotic microorganisms was determined. Test organisms did comprise 10 bacterial and 2 fungal collection strains, including E. coli and S. aureus, and clinical isolates of K. pneumoniae. The highest adjuvant activity was observed in the case of 4-hexylresorcinol (4-HR), a natural compound found in plants with antimicrobial activity. 50% of the minimal inhibitory concentration (MIC) of 4-HR caused an up to 50-fold decrease in the MIC of antibiotics of various classes. Application of 4-HR as an adjuvant revealed its efficiency against germination of bacterial dormant forms (spores) and prevented formation of antibiotic-tolerant persister cells. Using an in vivo mouse model of K. pneumoniae-induced sepsis, we could demonstrate that the combination of 4-HR and polymyxin was highly effective. 75% of animals were free of infection after treatment as compared to none of the animals receiving the antibiotic alone. We conclude that alkylresorcinols such as 4-HR can be used as an adjuvant to increase the efficiency of several known antibiotics. We suggest that by this approach the risk for development of genetically determined antibiotic resistance can be minimized due to the multimodal mode of action of 4-HR.

Bactericidal activity of hexylresorcinol lozenges against oropharyngeal organisms associated with acute sore throat.

OBJECTIVE: For the majority of people with acute sore throat, over-the-counter treatments represent the primary option for symptomatic relief. This study evaluated the in vitro bactericidal activity of lozenges containing the antiseptic hexylresorcinol against five bacteria associated with acute sore throat: Staphylococcus aureus, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae and Fusobacterium necrophorum. RESULTS: Hexylresorcinol 2.4 mg lozenges were dissolved into 5 mL of artificial saliva medium. Inoculum cultures were prepared in triplicate for each test organism to give an approximate population of 108 colony-forming units (cfu)/mL. Bactericidal activity was measured by log reduction in cfu. Greater than 3log10 reductions in cfu were observed at 1 min after dissolved hexylresorcinol lozenges were added to S. aureus (log10 reduction cfu/mL ± standard deviation, 3.3 ± 0.2), M. catarrhalis (4.7 ± 0.4), H. influenzae (5.8 ± 0.4) and F. necrophorum (4.5 ± 0.2) and by 5 min for S. pyogenes (4.3 ± 0.4). Hexylresorcinol lozenges achieved a > 99.9% reduction in cfu against all tested organisms within 5 min, which is consistent with the duration for a lozenge to dissolve in the mouth. In conclusion, in vitro data indicate that hexylresorcinol lozenges offer rapid bactericidal activity against organisms implicated in acute sore throat.

Inhibition of foreign body giant cell formation by 4- hexylresorcinol through suppression of diacylglycerol kinase delta gene expression.

Grafted macromolecules often induce granuloma formation with foreign body giant cell (FBGC) infiltration, and this is the main reason for graft failure. Diacylglycerol kinase (DAGK) is an important intracellular mediator of FBGC formation in macrophages. In this study, 4-hexylresorcinol (4HR) inhibited DAGKδ in a macrophage cell line (RAW264.7 cells). As a result of DAGK-δ inhibition by 4HR, FBGC formation was significantly inhibited in RAW264.7 cells. Silk fibroin is a well-known natural macromolecule, and when it is grafted into bone defects, it results in granuloma formation with massive FBGC formation. 4HR-incorporating silk graft materials displayed significant reduction of granuloma formation and increases in the extent of new bone formation in a rabbit calvarial defect model. In conclusion, 4HR could inhibit foreign body reaction via a DAGK-mediated pathway.

Silk fibroin and 4-hexylresorcinol incorporation membrane for guided bone regeneration.

The objective of this study was to demonstrate that a silk fibroin (SF) and 4-hexylresorcinol (4-HR) incorporation membrane could be used for a guided bone regeneration technique. Fourier transform infrared measurements were obtained to determine change of physical property of SF membrane by 4-HR incorporation. Two peri-implant defects, 3.0 × 5.0 mm (width × length), were prepared on the lateral side of the implant hole in the tibia of New Zealand white rabbits (n = 8). The peri-implant defect was left unfilled in the control group. Silk fibroin + 4-HR membrane was applied to the peri-implant defect in the experimental group. The 8 animals were killed at 8 weeks after implantation. Subsequently, removal torque test and histomorphometric evaluation were done. Fourier transform infrared spectroscopy showed no specific chemical interaction between 4-HR and SF. In the histomorphometric analysis, the mean bone regeneration was 18.3 ± 1.9 mm(2) in the experimental group and 9.3 ± 0.9 mm(2) in the control group (P = 0.004). In conclusion, the SF and 4-HR incorporation membrane successfully regenerated bone in the rabbit tibia peri-implant bone defect model.

4-Hexylresorcinol as inhibitor of shrimp melanosis: efficacy and residues studies; evaluation of possible toxic effect in a human intestinal in vitro model (Caco-2); preliminary safety assessment.

Studies were performed on the efficacy, residues and in vitro enterocyte toxicity of 4-hexylresorcinol (4-HR), which could be utilized as an inhibitor of shrimp melanosis (black spot). Mediterranean sea shrimp (Parapaeneus longirostris) were treated with solutions of 4-HR in sea-water, at three different concentrations, 25, 50 or 100 mg/kg of shrimp, to test its antioxidative property. As a comparison a group of shrimp was treated with sodium metabisulphite (1 g/kg), while another group was left untreated. 4-HR showed a marked ability to inhibit or slow down melanosis (black spot) in shrimp; the most effective concentration was 100 mg/kg within an optimum period of 7 days but with effects up to the tenth day. During the first 5 days, 4-HR residues in the edible part of the shrimp showed a fast decrease in all three groups, going from initial average values of 20 mg/kg at 0 time, to 0.9 in the group treated at 25 mg/kg; from 42 to 1.8 mg/kg in the group at 50 mg/kg and from 85 to 1.9 mg/kg in the group at 100 mg/kg. In vitro studies on enterocyte-like Caco-2 cells did not indicate any cytotoxic effect up to a concentration of 50 micrograms/ml. Moreover, no inhibition of protein synthesis was observed, which lends further support to the absence of significant damage to the intestinal mucosa induced by 4-HR. The available database on 4-HR pharmacology and toxicology is inadequate to determine even a provisional ADI. There is negative evidence of carcinogenesis and no significant untoward effects were observed in humans when it was used as an anthelmintic. However, it is not possible to determine a NOEL for non-genotoxic effects. 4-HR could become an interesting alternative to the use of sulphites to prevent black spot. However, a more complete database is needed to achieve a regulatory evaluation.

The treatment of Fasciolopsis buski infection in children: a comparison of thiabendazole, mebendazole, levamisole, pyrantel pamoate, hexylresorcinol and tetrachloroethylene.

Four relatively new broad spectrum anthelmintics (thiabendazole, mebendazole, levamisole and pyrantel pamoate) were compared with two older anthelmintics, (tetrachloroethylene and hexylresorcinol) to treat heavy Fasciolopis buski infections in 17 children aged 4-13 years in hospital. Tetrachloroethylene was the most effective drug in these 17 children and another 49. Large numbers of worms were expelled and faecal egg counts were markedly reduced (99%). The mean number of worms per child was 122 with a range of 7 to 818. All the other anthelmintics tested were ineffective; no worms or only a few were expelled after treatment. However, the oral administration of tetrachloroethylene and hexylresorcinol were associated with severe anaphylactic reactions which were prevented by prior treatment with antihistamines.

Chronic diarrhea in returing travelers: intestinal parasitic infection with the fluke Metagonimus yokogawai.

An unusual intestinal infection with the parasite Metagonimus yokogawai was acquired by an American traveling in the Orient. Diarrhea began abroad, and recurred at intervals until she was seen 1 1/2 years later. Stool examinations resulted in the recovery of small operculated ova characteristic of intestinal or biliary fluke infection. Treatment with hexylresorcinol failed to eradicate the infection, but subsequent use of tetrachloroethylene was successful and facilitated recovery of adult parasites, leading to the specific diagnosis of metagonimiasis. Metagonimiasis and related intestinal fluke infections should be considered as a possible cause of persistent diarrhea in travelers returning from endemic areas abroad.

In vitro antiplaque effects of antiseptic phenols.

Several phenols known to be antiseptics were tested in vitro for their ability to adsorb to saliva-coated enamel and subsequently inhibit plaque formation. 3,5,4'-tribromosalicylanilide was found to be effective against growth and plaque formation of A viscosus, A naeslundii, S mutans and S sanguis. Dibromsalicil was effective against A viscosus. The other phenols (hexylresorcinol, thymol, phenylphenol and zinc phenolsulfonate) did not inhibit in vitro growth or plaque formation.