Potential Topical Agent Research Articles

Can l-ascorbic acid and trans-resveratrol protect HaCaT cells from fine particulate matter toxicity?

Continuous exposure of human skin to air pollution can result in a range of undesirable skin conditions. In our recent study, UV and visible light were found to increase cytotoxicity of fine particulate matter (PM2.5 ) against human keratinocytes. Since it is impossible to avoid exposure of human skin to PM2.5 , effective strategies are needed to reduce their damaging effects. l-ascorbic acid and resveratrol were tested as potential topical agents against pollution-related skin impairment. Although these agents were previously found to ameliorate PM-dependent damage, the effect of light and seasonal variation of particles were not previously studied. EPR spin-trapping, DPPH assay, and singlet oxygen phosphorescence were used to determine the scavenging activities of the antioxidants. MTT, JC-10 and iodometric assays were used to analyze the effect on PM2.5 -induced cytotoxicity, mitochondrial damage and oxidation of lipids. Live-cell imaging was employed to examine wound-healing properties of cells. Light-induced, PM2.5 -mediated oxidative damage was examined by immunofluorescent staining. Both antioxidants effectively scavenged free radicals and singlet oxygen produced by PM2.5 , reduced cell death and prevented oxidative damage to HaCaT cells. l-ascorbic acid and resveratrol, especially when applied in combination, can protect HaCaT cells against the dark and light induced toxicity of PM2.5 .

The Efficacy of Platelet-Rich Fibrin in the Management of Chronic Nonhealing Ulcers of the Lower Limb.

IntroductionNonhealing ulcers have a huge burden on the patient, by having high morbidity in terms of chronic pain, partial or complete loss of function, mental health issues, and social isolation, and can have a massive financial burden on the patient. Various novel therapies have been developed to treat nonhealing ulcers. Platelet-rich fibrin (PRF) has been developed in the recent era initially in the dental world for treating oral ulcers. Now, the role of PRF is strongly established in treating nonhealing ulcers. PRF has an aggregate of a myriad of growth factors and cytokines that stimulate healing of the wounds. In this study, we have compared the efficacy of PRF in treating nonhealing ulcers of the lower limb against normal saline dressings.Aims and objectivesThis study aims to determine the efficacy of platelet-rich fibrin over normal saline dressings in the treatment of nonhealing ulcers of the lower limb by comparing the percentage reduction in the surface area of wounds after treatment in both groups.MethodsFifty patients with nonhealing ulcers were selected and randomly divided into two groups with 25 patients in each group. Cases were treated with PRF dressings weekly for a period of six weeks. Controls were treated with normal saline dressings weekly for a period of six weeks. The percentage reduction in the size of the ulcer after treatment was recorded in both groups and compared. Patients of age 18-60 with nonhealing ulcers of the lower limb of >12 weeks duration have been included in the study. Patients having wounds with active infection, wound size > 35 cm2, uncontrolled diabetes, peripheral vascular disease with Ankle-Brachial Index < 0.9, osteomyelitis of the underlying bone, and immunocompromised state, and patients on antiplatelet drugs have been excluded from the study.ResultsThe mean age of the patients included in the study was 42.88 ± 2.73 years. The mean initial surface of the wound​​​ was 14.95 ± 3.08 cm2 among cases and 13.28 ± 2.83 cm2 among controls. The mean surface area of the wound after six weeks was 1.59 ± 0.78 cm2 among cases and 11.08 ± 2.74 cm2 among controls. The mean percentage reduction in the wound size after six weeks of treatment was 89.3% among cases and is significantly higher than in the normal saline group (16.5%) (Mdn = 14.63, U = 23, p < 0.00001).ConclusionPlatelet-rich fibrin is an emerging potential topical agent for the treatment of nonhealing ulcers of the lower limbs and is more effective than normal saline dressings and also has the advantage of being cost-effective.

Antiplanktonic and Antibiofilm Activity of Rheum palmatum against Streptococcus oralis and Porphyromonas gingivalis.

Periodontitis and peri-implantitis are inflammatory conditions with a high global prevalence. Oral pathogens such as Porphyromonas gingivalis play a crucial role in the development of dysbiotic biofilms associated with both diseases. The aim of our study was to identify plant-derived substances which mainly inhibit the growth of “disease promoting bacteria”, by comparing the effect of Rheum palmatum root extract against P. gingivalis and the commensal species Streptococcus oralis. Antiplanktonic activity was determined by measuring optical density and metabolic activity. Antibiofilm activity was quantified using metabolic activity assays and live/dead fluorescence staining combined with confocal laser scanning microscopy. At concentrations of 3.9 mg/L, R. palmatum root extract selectively inhibited planktonic growth of the oral pathogen P. gingivalis, while not inhibiting growth of S. oralis. Selective effects also occurred in mature biofilms, as P. gingivalis was significantly more stressed and inhibited than S. oralis. Our studies show that low concentrations of R. palmatum root extract specifically inhibit P. gingivalis growth, and offer a promising approach for the development of a potential topical agent to prevent alterations in the microbiome due to overgrowth of pathogenic P. gingivalis.

Innovative Treatment Using Salmon Skin Extract as Topical Application for Traumatic Oral Ulcer Healing: Animal Models

Salmon skin extract contains high proline and hydroxyproline, and has been suggested as a potential topical agent for traumatic oral ulcer healing. The aim of this study was to evaluate the effect of salmon skin extract as traumatic oral ulcer healing. A total of 32 Wistar rats (200 g to 250 g) were distributed into four groups. Group 1 served as the control group (no treatment), Group 2 was topically treated with salmon skin extract agent 4%, Group 3 was topically treated with salmon skin extract agent 5%, and Group 4 was topically treated with salmon skin extract agent 6%. Traumatic ulcers at lip mucosa were performed in all rats and 0.1 ml salmon skin extract was applied on the ulcer twice daily for seven days. The animals were euthanised on the last day of treatment. Biopsy specimens were taken from the lip mucosa in all rats for epithelial thickness evaluation and the study for number of fibroblasts by histological analysis. Significant increase in epithelial thickness and the number of fibroblasts (p &gt; 0.05) was observed in salmon skin extract treatment groups as compared to the control group. Salmon skin extract 6% treatment group had the highest epithelial thickness and the number of fibroblasts amongst the study groups. Salmon skin extract promises an innovative topical application treatment for traumatic oral ulcer healing. Salmon skin extract 6% was the most effective concentration for traumatic oral ulcer healing.

Water extract of medicinal ink (WEMI) attenuates lipopolysaccharide-induced NO production of Raw264.7 cells via downregulating JAK2/STAT3-mediated iNOS expression

Ethnopharmacological relevanceMedicinal ink is used as a traditional topical medicine for treating inflammatory diseases via detoxification, relieving pain, hemostasis, and reducing swelling. However, the effect of medicinal ink on the inhibition of inflammatory responses and the underlying molecular mechanism remain unclear. Aim of the studyThe present study aimed to investigate the anti-inflammatory function of water extract of medical ink (WEMI) and elucidate its active mechanisms. Materials and methodsCell viability was assessed using crystal violet staining assay. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Nitric oxide (NO) production was measured by Griess assay. The activation of inflammatory signaling molecules stimulated by lipopolysaccharide (LPS) was evaluated by assessing levels of inducible nitric oxide synthase (iNOS), phosphorylated Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) using Western blot assay. ResultsWater extract of medical ink (WEMI) did not present cytotoxic effect on murine macrophage Raw264.7 cells. High dosage of WEMI slightly rescued LPS-suppressed cell viability of Raw264.7 cells. WEMI did not induce NO production or IL-6 secretion, though WEMI significantly induced secretion of TNF-α on Raw264.7 cells not stimulated with LPS. On the other hand, LPS effectively stimulated inflammation on Raw264.7 cells; however, WEMI dramatically reduced LPS-induced NO production. WEMI alleviated LPS-stimulated IL-6 secretion but did not affect the content of TNF-α. In addition, WEMI effectively reduced expression of iNOS by abolishing LPS-mediated phosphorylation of JAK2 and STAT3 but not TLR4-mediated NF-κB and MAPK molecules. ConclusionsOur findings suggest that WEMI targets of the JAK2/STAT3-mediated iNOS expression play a key role in alleviating LPS-induced inflammatory responses in RAW264.7 macrophages. Therefore, medicinal ink may be a potential topical agent for treating fasciitis or synovitis via regulating the immune system.

An Efficient Microwave-Mediated Synthesis of Hexavalent Sialic Acid Sulfoglycodendrimers as Potential Anti-HIV Agents.

A series of four sialic acid-containing hexavalent sulfoglycodendrimers (SGDs) were synthesized in excellent yields using an efficient strategy involving multiple microwave-mediated reactions. Four sugars, sialic acid, and the dimer through tetramer of α-2→8-linked oligosialic acid were added to an aminooxy-terminated hexavalent dendrimer core using a chemoselective oxime-forming reaction. This method resulted in substantial improvements in reaction time and product yields over previous methods. These multivalent glycopolymers were designed as potential topical agents for preventing the sexual transmission of HIV-1. While inactive against HIV-1, the SGDs were also not cytotoxic, opening a pathway for the further development of anti-HIV SGDs.

Phytosphingosine Derivatives Ameliorate Skin Inflammation by Inhibiting NF-κB and JAK/STAT Signaling in Keratincoytes and Mice

Phytosphingosine is abundant in plants and fungi and is found in mammalian epidermis, including the stratum corneum. Phytosphingosine and its derivatives N-acetyl phytosphingosine and tetraacetyl phytosphingosine are part of the natural defense system of the body. However, these molecules exhibit strong toxicities at high concentrations. We synthesized phytosphingosine derivatives, mYG-II-6 ((Z)-4-oxo-4-(((2S,3S,4R)-1,3,4-trihydroxyoctadecan-2-yl)amino)but-2-enoic acid) and fYG-II-6 ((E)-4-oxo-4-(((2S,3S,4R)-1,3,4-trihydroxyoctadecan-2-yl)amino)but-2-enoic acid), to increase efficacy and decrease toxicity, and the biological activities of the derivatives in the inflammatory response were examined. Both YG-II-6 compounds effectively suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammatory skin damage and inflammatory response in a mouse model. In addition, topical application of fYG-II-6 suppressed ear swelling and psoriasiform dermatitis in the ears of IL-23-injected mice. Anti-inflammatory and antipsoriatic activities of the phytosphingosine derivatives inhibited NF-κB, JAK/signal transducer and activator of transcription (JAK/STAT), and mitogen-activated protein kinase (MAPK) signaling. Finally, the YG-II-6 compounds induced programmed cell death in keratinocytes and mouse skin and were less toxic than phytosphingosine. Our study demonstrated that the phytosphingosine-derived YG-II-6 compounds have much stronger biological potencies than the lead compounds. The YG-II-6 compounds ameliorated inflammatory skin damage. Thus, YG-II-6 compounds are potential topical agents for treating chronic inflammatory skin diseases, such as psoriasis.

Synthesis and biological evaluation of amino-pyridines as androgen receptor antagonists for stimulating hair growth and reducing sebum production

A series of amino-pyridines were synthesized and evaluated for androgen antagonist activities. Among these compounds, ( R)-(+)-6-[methyl-(1-phenyl-ethyl)-amino]-4-trifluoromethyl-nicotinonitrile was the most active example of this class. This compound displayed potent androgen receptor antagonist activity as well as favorable pharmacokinetic characteristics for a potential topical agent. It also demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model.

Semisynthetic derivatives of purpuromycin as potential topical agents for vaginal infections.

Purpuromycin (1) is an antibiotic with a broad spectrum of antimicrobial activity, encompassing bacteria, fungi, and protozoa, particularly those involved in vaginal infections. With the aim of enhancing the solubility and reducing the serum binding, a chemical program of modifications was undertaken on the natural compound, and a new interesting series of derivatives at the naphthoquinone system was synthesized and evaluated as potential topical agents for vaginal infections. In particular three semisynthetic derivatives, 7'-amino (8a), 7'-methylamino (8b), 7'-ethylamino (8c), of 7'-demethoxypurpuromycin seemed to be the most promising. They were tested for in vitro activity against three of the most important vaginal pathogens and showed activity similar to that of purpuromycin against Candida isolates while they were significantly more active against Trichomonas vaginalis and Gardnerella vaginalis, which are cultured in media containing blood or serum. This is probably due to the fact that the activity of the derivatives is less antagonized by these supplements than that of purpuromycin.

Use of antimicrobial susceptibility testing for epidemiology and the selection of oral, parenteral and topical regimens for control of CAPD-associated Staphylococcus aureus infection.

Staphylococcus aureus is an important cause of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Using standard broth microdilution and disk diffusion methodology, we evaluated the in vitro activity of selected antimicrobial agents against S. aureus strains isolated from CAPD patients to assess candidate regimens for 1) topical agent control of colonization, 2) oral chemotherapy of CAPD infectious complications, and 3) parenteral treatment of serious CAPD-associated staphylococcal infections. A total of 34 isolates (31 patients) of S. aureus were available for testing, including 29 isolates (29 patients) from pericatheter skin, four isolates (four patients) from the nares, and one isolate from an episode of peritonitis. Six of the isolates were oxacillin-resistant (ORSA). The antimicrobial agents tested by broth microdilution included 17 different quinolones, 10 cephalosporins, six glycopeptides, two aminoglycosides, and imipenem. A total of eight potential topical agents, including the antistaphylococcal agent mupirocin, were tested by disk diffusion. All of the quinolones, with the exception of nalidixic acid (MIC90 greater than 16 micrograms/ml), had excellent activity against both ORSA and oxacillin-susceptible S. aureus (OSSA) with the most active agent being WIN57273 (MIC90 less than or equal to 0.015 microgram/ml). Imipenem and the cephalosporins, with the exception of cefixime, ceftazidime, and E-1040, possessed good activity against OSSA. None of the beta-lactam agents tested were active against ORSA. Likewise, the aminoglycosides, amikacin and gentamicin, exhibited good activity against OSSA strains but no activity against ORSA strains. All glycopeptides tested demonstrated excellent activity against ORSA strains. Of the topical antimicrobial agents tested only bacitracin, mupirocin, and nitrofurantoin were active against all OSSA and ORSA strains tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Responsiveness of experimental surgical-wound infections to topical chemotherapy.

Topical agents freshly formulated in a cream base vehicle as well as commercial topical preparations were used to evaluate in mice the responsiveness of experimental surgical wounds infected with Staphylococcus aureus or Pseudomonas aeruginosa to chemotherapy. The responsiveness of the infections to therapy or the efficacy of a topical agent was assessed primarily by means of wound counts of the infecting organism before and after the employment of an immediate (prophylactic) or delayed (therapeutic) treatment regimen. From tests of several concentrations of an agent formulated in the vehicle, a median effective dose could be determined. In the case of the lethal P. aeruginosa infection, a median protective dose could be determined. Both infections were found to be quite susceptible to treatment with those topical agents that demonstrated good activity in vitro against the test organisms. The results of the investigation indicated that the model infections were suitable for the screening of potential topical agents in vivo.