Table 2.

In vivo studies on animal models—a mixture of preparations.

Composition of the Mixture	Animal Model	Burn Wound	Treatment Schedule *	Results	Ref.
Allium sativum (bulbs; squeezed juice)Euphorbia honey	Wistar albino rats, either sex	Thermal burn—metal plate, heated in boiling water for 10 min, applied for 20 s	Once a day until healed E: Euphorbia honey or a mixture of Euphorbia honey and Allium sativum juice (amount and concentration not given) S: Betadine solution or 1% SSD cream	The shortest time needed for complete epithelisation and wound closure was noted for the group treated with the mixture, 1% SSD cream, and then for the group treated with Euphorbia honey. The longest time was recorded in the group treated with betadine. In the histological examination, the group treated with the mixture was characterised by a thicker layer of epidermis and skin than the other groups. There were no differences between the groups in the interdigitation index and the orientation of collagen fibres.	[100]
Aloe vera leaves Vitis vinifera leaves 30% (v/v) methanolic extracts	Wistar albino rats, male	Second-degree thermal burn—metal plate heated in boiling water for 5 min, applied for 10 s	Twice a day for 21 days E: the combination of leaf extracts in a ratio of 1.5%:1.5% in Eucerin S: 1% SSD cream C: Eucerin NC: w/o treatment	The wound area of the experimental group after 7, 14 and 21 days was significantly smaller than the wounds of the control groups but comparable to the standard group. It has been observed that treatment with the composition has better healing effects than treatment with the individual components. Compared to the control and standard groups, the experimental group showed a higher degree of tissue maturation and organisation and re-epithelialisation, a fully formed epidermis, more hair follicles, sebaceous glands, fibroblasts and capillaries, and a decrease in neutrophil and macrophage infiltration.	[47]
Arctocarpus heterophyllus, fruits Murraya koenigii leaves Nerium indicum, leaves Punica granatum, bark 70% (v/v) ethanolic extracts	albino rats, either sex	Third-degree chemical burn—sulphuric acid, applied for 10 s	Once a day until healed E: 10% or 15% of the combination of extracts (1:1:1:1) in ointment base or base gel S: Povidone-iodine C: ointment base or base gel NC: w/o treatment	The period of epithelialisation in the experimental groups with the basic ointment, the basic gel, and the standard group was significantly shorter than in the corresponding control groups. In addition, it was shorter than in the groups treated with single components. Hydroxyproline level and tensile strength were higher in the experimental and standard groups than in the controls. In the histopathological analysis, better wound healing parameters were observed in the experimental groups with base ointment than with base gel.	[101]
Azadirachta indica leaves Tridax procumbens leaves Honey 90% (v/v) ethanolic leaf extracts	Wistar albino rats, male	Second-degree thermal burn—hot molten wax (80 °C), applied until solidified	Once a day for 15 days E: herbal gel (unspecified concentration) S: 1% SSD cream C: base gel	The degree of wound closure after 15 days was 89.35 ± 0.4155, 90.43 ± 0.7691 and 68.58 ± 0.7791%, and the period of epithelisation was 26.32 ± 2.22, 25.20 ± 2.10 and 38.36 ± 1.77 days in the experimental, standard and control groups, respectively. The results obtained in the experimental group were as good as in the standard group and significantly better than in the control group. Moreover, the formulation has been shown to have synergistic activity in wound healing as the results obtained are better than those of the single components of the formulation.	[50]
Calendula officinalis Rosa damascena Beeswax	Wistar albino rats, male	Second and third-degree thermal burn—metal plate heated in boiling water for 5 min, applied for 10 or 30 s	Once a day for 40 days E: commercial herbal ointment Robacin® (the exact composition is not given) S: 1% SSD cream or Aloe vera cream	In the second-degree burn group treated with herbal ointment, wound healing was significantly fastest for the first two weeks and comparable to the standard groups. In the third-degree burn group, wound closure was the fastest in the experimental group. In both burns (second and third degree), a much smaller extent of angiogenesis and fibrosis was observed in the experimental group than in the standard groups. In third-degree burns, epithelialisation in the experimental group was as good as in the Aloe vera cream treatment.	[102]
Cannabis sativa Juglans regia Pistacia atlantica Sesamum indicum cold pressed oils	albino mice, male	Third-degree thermal burn—boiling water (100 °C), applied for 10 s	Twice a day for 21 days E: the combination of sesame oil (60%), pistachio oil (20%), hemp oil (12%) and walnut oil (8%) S: 1% SSD cream NC: w/o treatment	The degree of wound closure was 99.5 ± 0.8, 78.0 ± 4.0 and 88.4 ± 2.5% in the experimental, standard and control groups. The differences between the groups were statistically significant. In the experimental, standard and control groups, the time to complete epithelisation was 20.5 ± 1.37, 26.33 ± 0.81 and 25.5 ± 0.83 days. It was significantly shorter in the group treated with the oil composition.	[103]
Centella asiatica, herb, 70% (v/v) ethanolic extract Papaya latex, dried and powdered	albino mice, male	Chemical burn—50% phenol solution, applied for 30 s	Once a day for 10 days E: C. asiatica and papaya latex in a ratio of 1%:1%, 0.5%:1.5% and 1.5%:0.5% in a base gel S: Bioplacenton® jelly (neomycin + placenta extract) C: base gel	Complete wound closure was achieved after 6 days in the experimental group in the ratio of 1:1 and in the standard group. After 7 days, it was achieved in the groups in the ratio of 1.5:0.5 and 0.5:1.5. After 10 days, in the control group, the wound closure was only 75.34 ± 20.709%. The combination of C. asiatica and papaya latex showed a synergistic effect on wound healing, as in the case of the components used alone. Complete wound closure was observed after 8 days.	[56]
Cucurbita moschata Sesamum indicum oils	BALB/c albino mice, male	Third-degree thermal burn—coin heated for 3 min with a spirit lamp, applied for 8 s	Once a day for 28 days E: the combination of oils (1:1) NC: w/o treatment	In the experimental groups, wound healing was significantly better than in the negative control and the groups treated separately with sesame oil and pumpkin oil. In addition, a significantly higher level of total antioxidant power and a lower level of malondialdehyde were obtained than in the other groups.	[62]
Malva sylvestris, leaves, aqueous extract Rosa damascena, petal powder, sesame oil extract Solanum nigrum, leaves, aqueous extract	Wistar albino rats, male	Second-degree thermal burn—electrical heater heated to 110 °C, applied for 10 s	Once a day for 14 days E: herbal ointment (5% of each aqueous extract and 33% of oily extract in base ointment) S: 1% SSD cream C: base ointment NC: without treatment	After 14 days of treatment, the wound closure was the highest in the group treated with herbal ointment and amounted to 87.0 ± 2.1%. The remaining groups were 70.8 ± 3.5, 57.0 ± 5.3 and 32.2 ± 1.6% in the standard, control, and negative control groups. Compared to the other groups, the histopathological analysis in the experimental group showed a significant improvement in wound healing with complete re-epithelialisation, well-formed granulation tissue and mild infiltration of inflammatory cells. In addition, advanced neovascularisation, and irregular distribution of myofibroblasts, fibroblasts and collagen fibres were present.	[104]
Momordica charantia, fruits Piper nigrum, fruits Pongamia glabra, leaves aqueous extracts	albino rats, either sex	Third-degree chemical burn—sulphuric acid, applied for 10 s	Once a day for 21 days E: 10% or 15% of the combination of extract (1:1:1) in the ointment base S: Povidone-iodine ointment C: ointment base NC: w/o treatment	The period of epithelialisation was 14.97 ± 0.256, 14.77 ± 0.207 and 15.5 ± 0.315 days in the group treated with 10% ointment, 15% ointment and standard, respectively, and was significantly shorter in these groups than in the control groups, where it was 18.18 ± 0.345 and 18.88 ± 0.259 days in the control and negative control groups, respectively. Hydroxyproline levels and tensile strength were significantly higher in experimental and standard groups compared to controls. In the histopathological analysis in the experimental and standard groups, better wound healing, fewer inflammatory cells, a thicker layer of granulation tissue and epidermis, and more dermal fibrosis were observed than in control.	[105]
Rhododendron macrophyllum Thymus serpyllum	Wistar albino rats, male	Second and third-degree thermal burn—metal plate heated in boiling water for 5 min, applied for 10 or 30 s	Once a day for 40 days E: commercial herbal ointment Rimojen® (the exact composition is not given) S: 1% SSD cream or Aloe vera cream	In both the second and third-degree burn groups, wounds treated with herbal ointment healed much more slowly than those treated with Aloe vera cream and 1% silver sulfadiazine cream.	[102]
Sesamum indicum oil Camphora Honey	Wistar albino rats, male	Second-degree thermal burn—hot metal plate, applied for 10 s	Once a day for 28 days E: herbal ointment (the exact composition is not given) C: Vaseline	The percentage of wound healing from day 7 was higher for the group treated with herbal ointment than Vaseline. Moreover, neovascularisation was higher in the group treated with herbal ointment than in the control group.	[106]

* C—control group; E—experimental groups; NC—negative control group; S—standard/positive control group; SSD—silver sulfadiazine; w/o—without.