An experimental study of the wound healing effect of ophthalmic drug films with 6-methyl-3-(thietan-3-yl)uracil and methyluracil

Purpose: to study experimentally the wound-healing effect of ophthalmic drug films (ODF) with 6-methyl-3-(thietan-3-yl) uracil and methyluracil. Material and methods. The study involved 17 Chinchilla rabbits (34 eyes), whose corneas were histomorphologically studied after an experimental chemical acid burn and treatment. ODF with 6-methyl-3-(thietan-3-yl)uracil were deposited in the right eyes of 15 rabbits (15 eyes), and ODF with methyluracil — in the left eyes of these rabbits. Two rabbits served as control: their right eyes were left without wound healing therapy, while the left eyes received dexpanthenol 5 % gel (corneregel) 4 times a day. All animals were monitored daily for 21 days. The morphological changes in the cornea were recorded on the 2nd, 7th, 14th and 21st days after the experimental chemical burn.Results. The course of reparative processes of the chemical burns of the cornea was found to be different depending on the drugs used. Our results show that the ODF with methyluracil led to the resorption of the edema and the turbidity, as well as to a total closure of the desquamation sites of the corneal epithelium on the 7th day. With the ODF containing 6-methyl-3-(thietan-3-yl) uracil, the effect was achieved on the 14th day. In contrast to the control, ODF enhanced the growth and reproduction of cells, rapidly improved the trophism, and stimulated the regeneration process in damaged corneal tissues. ODFs produced no toxic reactions, such as destruction of the collagen framework, maceration, pronounced edema, and hyperemia. On the 21st day of observation, the microscopic picture of rabbit cornea showed the usual normal structure. Conclusion. ODF therapy with methyluracil and 6-methyl-3-(thietan-3-yl)uracil leads to accelerated centripetal epithelialization of corneal erosion, more structured and histologically correct restoration of the epithelial-stromal layer.

Ethnopharmacological Survey and Comparative Study of the Healing Activity of Moroccan Thyme Honey and Its Mixture with Selected Essential Oils on Two Types of Wounds on Albino Rabbits

Wound healing consists of several continuous phases involving various cells and chemical intermediates. As a rich source of nutrition elements, honey has proved to have potential benefits in the treatment of various diseases. The present study was designed to investigate the healing effect of a honey mixture with selected essential oils on chemical and thermal wound models in rabbits. Dressing mixtures of Thymus vulgaris honey with three essential oils (Origanum vulgare, Rosmarinus officinalis, and Thymus vulgaris) were prepared and applied daily in the treatment groups. These essential oils were rich in phytochemicals and had significant antibacterial activity against four selected ATCC bacterial strains. Madecasol ointment was used as a standard control. The healing effect of the mixtures was evaluated by measuring wound surface area and comparing healing time. The results showed that the healing rate in the treatment groups was significantly higher than that of the untreated group and standard group. The best healing effect for burns was seen in the mixture of honey and Thymus vulgaris essential oil, which had wound closure rates of 85.21% and 82.14% in thermal- and chemical-induced burns, respectively, and showed the shortest healing time (14 days) in comparison to other groups. Therefore, it can be concluded that honey mixtures have significant beneficial effects on skin wound healing and, thus, they may be used as a healing agent in different types of wounds in humans after specific clinical trials.

High Efficiency In Vitro Wound Healing of Dictyophora indusiata Extracts via Anti-Inflammatory and Collagen Stimulating (MMP-2 Inhibition) Mechanisms

Dictyophora indusiata or Phallus indusiatus is widely used as not only traditional medicine, functional foods, but also, skin care agents. Biological activities of the fruiting body from D. indusiata were widely reported, while the studies on the application of immature bamboo mushroom extracts were limited especially in the wound healing effect. Wound healing process composed of 4 stages including hemostasis, inflammation, proliferation, and remodelling. This study divided the egg stage of bamboo mushroom into 3 parts: peel and green mixture (PGW), core (CW), and whole mushroom (WW). Then, aqueous extracts were investigated for their nucleotide sequencing, biological compound contents, and wound healing effect. The anti-inflammatory determination via the levels of cytokine releasing from macrophages, and the collagen stimulation activity on fibroblasts by matrix metalloproteinase-2 (MMP-2) inhibitory activity were determined to serve for the wound healing process promotion in the stage 2–4 (wound inflammation, proliferation, and remodelling of the skin). All D. indusiata extracts showed good antioxidant potential, significantly anti-inflammatory activity in the decreasing of the nitric oxide (NO), interleukin-1 (IL-1), interleukin-1 (IL-6), and tumour necrosis factor-α (TNF-α) secretion from macrophage cells (p < 0.05), and the effective collagen stimulation via MMP-2 inhibition. In particular, CW extract containing high content of catechin (68.761 ± 0.010 mg/g extract) which could significantly suppress NO secretion (0.06 ± 0.02 µmol/L) better than the standard anti-inflammatory drug diclofenac (0.12 ± 0.02 µmol/L) and their MMP-2 inhibition (41.33 ± 9.44%) was comparable to L-ascorbic acid (50.65 ± 2.53%). These findings support that CW of D. indusiata could be an essential natural active ingredient for skin wound healing pharmaceutical products.

Evaluation of Wound Healing Potential of Novel Hydrogel Based on Ocimum basilicum and Trifolium pratense Extracts

Plants are an inexhaustible source of compounds with different medicinal properties, suitable as alternative options for the prevention and treatment of various pathologies. They are safe, effective and economical. In this paper, a combined extract made of Ocimum basilicum and Trifolium pratense extracts (EOT) was used for the first time to demonstrate its healing effect on dermal pathologies. To evaluate the wound healing effect of EOT, a novel gel formulation was prepared and subsequently tested in vitro (using the scratch test assay) and in vivo (on an animal model). The in vitro tests demonstrated the complete recovery of the dermal fibroblast monolayer when treated with EOT in a concentration of 50 µg/mL. In vivo results using a hydrogel formulation based on EOT demonstrated improved wound contraction time and complete healing after 13 days of treatment. Moreover, a clinical case of Psoriasis vulgaris was presented, in which one week of treatment led to the significant improvement of the patient’s health. In conclusion, the topical use of the novel gel formulation containing EOT is a successful therapeutic alternative in the treatment of dermal diseases.

Phytochemical Screening of Himatanthus sucuuba (Spruce) Woodson (Apocynaceae) Latex, In Vitro Cytotoxicity and Incision Wound Repair in Mice

Himatanthus sucuuba, also known as “Bellaco caspi”, is a medicinal plant whose latex, stem bark, and leaves possess phenolic acids, lupeol, β-dihydro-plumbericinic acid, plumericin, and plumeride, among other components. Some of these have been linked to such biological activities as antiulcer, anti-inflammatory, and wound healing. The aim of this study was to determine the phytochemical compounds of H. sucuuba latex, as well as its in vitro cytotoxicity and wound healing effect in mice. Latex was collected in the province of Iquitos, Peru. Phytochemical analysis was carried out with UPLC-ESI-MS/MS. The cytotoxicity was evaluated on two colon tumor cell lines (SW480 and SW620) and non-malignant cells (human keratinocytes, HaCaT, and Chinese hamster ovary, CHO-K1). The mice were distributed into two groups, as follows: Group I—control (n = 10; without treatment); II—(n = 10) H. sucuuba latex; wounds were induced with a scalpel in the dorsal–cervical area and treatments were applied topically twice a day on the incision for 10 days. Molecular docking was carried out on the glycogen synthase kinase 3β protein. Twenty-four chemical compounds were determined, mainly flavonoid-type compounds. Latex did not have a cytotoxic effect on tumor cells with IC50 values of more than 500 µg/mL. The latex had a regenerative effect on wounds in mice. Acacetin-7-O-neohesperidoside had the best docking score of -9.9 kcal/mol. In conclusion, H. sucuuba latex had a wound healing effect in mice, as confirmed by histological study. However, a non-cytotoxic effect was observed on colon tumor cells SW480 and SW620.

Development and Evaluation of the Wound Healing Effect of a Novel Topical Cream Formula Based on Ginkgo biloba Extract on Wounds in Diabetic Rats

Despite advances in diabetes care, impaired diabetic wound healing remains a significant clinical problem. The present study was aimed at developing a novel cream based on Ginkgo biloba extract and investigating its wound healing effect on full-thickness wounds in diabetic rats. The topical formulated oil-in-water emulsion-based cream contains Ginkgo biloba aqueous extract in an amount of about 1% to 5% as an active agent. The prepared formula was subjected to physicochemical assessment and pharmacotechnical characterization. Eighteen alloxan-induced diabetic rats completing full-thickness excisional skin wounds were randomly divided into three groups topically treated with either a normal saline (control group), the reference drug (“Cytol Centella cream®”), and cream based on the Ginkgo biloba extract. The response to treatment was assessed by macroscopic, qualitative, and quantitative histopathological analysis. The prepared formula showed good physicochemical properties. The rheological behavior of the prepared cream followed a non-Newtonian pseudoplastic pattern at different storage temperatures. The cream, which is a macroemulsion with uniform size distribution, remained stable for 6 months. Skin tolerance studies confirmed the compatibility of the cream with the skin. During the experimental trial, the cream based on the Ginkgo biloba-treated group showed significant improvements over the control and reference groups for both general wound appearance and healing dynamics. This increased rate of closure of wounds in diabetic rats was associated with increased collagen synthesis. Our findings showed that the cream could be a promising and innovative topical treatment with Ginkgo biloba extract for the management of acute diabetic wounds.