Table 6.

Scientific evidence of Opuntia spp. on the healing of skin wounds.

Type of Study	Objective and Characteristics	Results and Conclusion	Ref
In vitro	As mentioned, OFI flowers are used for various medicinal purposes. Therefore, the healing activity (excision wound model in rats) and antioxidant activity (Trolox equivalent antioxidant capacity and DPPH assay) of mucilaginous and methanolic extracts of its flowers were studied.	After 13 days of treatment with both extracts, a beneficial effect on skin repair was observed, evaluated by the acceleration of the phases of contraction and remodeling of the wound. Histopathological studies of the granulation tissue indicated that the dermis was properly corrected and that the mucilage extract was more effective. In addition, it was confirmed that the extracts showed a significant antioxidant capacity.	[113]
In vivo	After isolating, washing, drying and cold pressing PPFs seeds from OFI, their oil was obtained to determine the effect of cicatrization of skin wounds and its antimicrobial potential against 4 bacterial strains and 3 fungi. The skin wounds of three experimental groups of rats were topically treated once a day with the oil, observing the healing process and calculating the percentage of wound contraction. At the same time, a histological study was performed on skin biopsies.	At the end of the study, it was shown that the oil exerted a good wound-cicatrization effect, preventing skin infections (especially against E. cloacae, and A. niger) and reducing the re-epithelialization phase. It is suggested to increase the studies to confirm the capacity of the oil in the promotion of the cicatrization process.	[124]
In vivo	The purpose of this study was to investigate the effect of spraying an extract of O. stricta on wounds on the ventral surface of rabbit ears. After the wounds healed, hypertrophic scar tissue was obtained and histological analysis was performed. Using immunohistochemistry and real-time quantitative polymerase chain reaction, the expression of type I and III collagen and matrix metalloproteinase-1 (MMP-1) was evaluated.	The results indicated: a) the expression of type I collagen in the animals treated with the extract was lower than in the control group, unlike type III collagen that gradually increased, b) the scar that was less prominent and expression of MMP- 1 decreased with the application of the extract. In conclusion, the extract decreased the formation of hypertrophic scars by inhibiting type I collagen, and increasing type III collagen and MMP-1.	[138]
In vivo	Despite advances in modern medicine, to date there is no effective natural treatment for second-degree burns. Therefore, the healing efficacy of oil extracted from PPFs on partial-thickness burns induced by fractional CO2 laser in rats was evaluated. All the burns were measured and treated topically for 7 days. The response to treatment was determined by macroscopic, histological and biochemical parameters.	The oil showed improvements in the general appearance of the wound and in the formation of scabs; besides, it significantly decreased the healing time. The histological evaluation confirmed that the oil has comparatively good healing properties and favors collagen content. This is scientific evidence of the efficacy of PPF oils on partial thickness burns.	[139]
In vitro	The purpose of the research was to compare the effects of OFI and Milk Thistle (MT) (Silybum marianum L.) on adult keratinocytes (HaCaT) functioning in basal conditions or in the presence of mechanical damage (wounded cells). Natural compounds were tested on HaCaT in monoculture and triculture configurations. In three-culture models, HaCaTs were treated with conditioned media obtained by co-cultures of normal human dermal fibroblasts and human dermal microvascular endothelial cells.	After determining cell viability, mechanisms of EOx (cytokine release and lipid peroxidation), cell remodeling (modulation of metalloproteinases), and migratory potential of HaCaT (in vitro wound healing assay); OFI and MT were found to favor migratory properties of HaCaT under both physiological conditions and mechanical damage. In addition, the response to EOx was modulated. The conclusion was that OFI and MT are good alternatives in skin repair.	[140]
In vivo	This last study investigated the potential of opuntiol, isolated from OFI, against UVA radiation-mediated inflammation and skin photoaging in mice. The animals were shaved and exposed to UVA rays (dose of 10 J/cm2/day) for ten days. One hour before each exposure, opuntiol (50 mg/kg) was applied topically.	Opuntiol pretreatment prevented UVA-linked clinical macroscopic skin lesions and histological changes in the mouse skin. In addition, opuntiol prevented dermal collagen fiber loss and collagen I and III breakdown in animal skin. Opuntiol was found to inhibit UVA-induced activation of iNOS, TNF-α, COX-2 MMP-2, and MMP-9. In conclusion, opuntiol exerted skin protection to the photoaging response associated with UVA radiation by reducing inflammatory responses and activating MAPK.	[141]
In vitro	O. humifusa (OHF) is considered a possible candidate to design cosmetic formulations that prevent the harmful effects of Particulate Matter (PM). Unfortunately, its high viscosity does not allow its adequate use in these formulations. Therefore, the effect of a high-power microwave treatment on an O. humifusa extract (MA-OHF) was investigated.	The results indicated that MA-OHE showed reasonable viscosity and outstanding anti-inflammatory activity to suppress PM-induced ROS production. In addition, COX-2 and MMP-9 expression was decreased in HaCaT keratinocytes. It is suggested that MA-OHE may be a suitable natural cosmetic ingredient to prevent PM-induced skin oxidative stress and inflammation.	[142]
In vivo	Considering that delayed wound healing represents a common health hazard, we compared the wound cicatrization activity of OFI seed oil and an auto-nanoemulsifying drug delivery system (OFI-SNEDDS) formulation in a full-thickness skin excision rat model. The OFI-SNEDDS formulation was prepared using a droplet size of 50.02 nm and applied directly to the animals.	The results showed that the formula exhibited healing activities superior to the oil, which was confirmed by histopathological examinations. In addition, OFI-SNEDDS presented greater antioxidant and anti-inflammatory capacity and improved angiogenesis (a phenomenon that was demonstrated by increasing the expression of vascular endothelial growth factor). The conclusion was that OFI has wound healing properties that are enhanced by the self-emulsion of the oil in nanodroplets. This is probably attributed to its anti-inflammatory, procollagenous and angiogenic properties.	[143]
In vitro	In this study, chitosan-based wound dressings loaded with an OFI extract were prepared. Chitosan (Ch) was crosslinked with a low molecular weight diepoxy-poly(ethylene glycol) (PEG), and hydrogel films with different Ch/PEG composition and OFI content were prepared. Using FTIR spectroscopy (Fourier transform infrared spectroscopy) the appearance of the crosslinking reaction was determined.	The analyses suggested that ionic interactions between Ch and OFI occur. The swelling characteristics, the water vapor transmission rate and the release kinetics showed that these films are suitable for their application. Finally, a scratch test on a keratinocyte monolayer showed that the rate of cell migration in the presence of OFI-loaded samples is approximately 3 times higher compared to unloaded films, confirming its restorative activity.	[144]