Evaluation of wound healing potential of pomegranate (Punica granatum) whole fruit extract on skin burn wound in rats (Rattus norvegicus)

Abstract

Objective: This research was conducted to study the wound healing process of whole fruit pomegranate extract ( punica granatum ) standardized with 40% ellagic acid ointment for deep second-degree burn wound of skin in the rat ( Rattus norvegicus ). Materials and Methods: Powder of standardized pomegranate extract (SPE) with 40% ellagic acid was processed to become ointments. Twenty-five male rats, weighed 150–180 gm at 3 months of age, were randomly divided into five groups. After anesthetized, stainless circle plate with 1 cm of diameter in 85°C was contacted firmly toward right gluteal of rat skins for 5 sec in order to create deep second-degree burn wound. Control groups consist of (T0) cream base and (T1) 1% silver sulfadiazine. Treatment groups consist of (T2) 2.5% SPE, (T3) 5% SPE, and (T4) 10% SPE. Histopathological preparation used hematoxylin-eosin stained skin samples. Histological observations were performed using the optics microscope against collagen, the number of polymorphonuclear cell (PMN) infiltration, the degree of angiogenesis, and re-epithelization. The results were statistically compared between groups. Results: Microscopic observation on the wound healing process on the collagen, PMN infiltration, angiogenesis, and re-epithelization showed that topical administration of 10% SPE in burns gives the best result. This is characterized by a high density of collagen with a good arrangement, which is accompanied by a complete and mature epithelium, low number of inflammatory cells, and angiogenesis. This may be caused by the compounds in the pomegranate extract, which have the antioxidant, anti-inflammatory, and anti-bacterial effects. Conclusion: This study reveals that 10% SPE accelerates the healing of deep second-degree burn wound. Thus, pomegranate standardized with 40% ellagic acid is a promising herb for the healing of burn wound of skin.

A Review of the Potential Benefits of Plants Producing Berries in Skin Disorders

“…The most frequently exploited plant material for In Vivo studies was the peel from fruit, extracted by maceration with combined polar solvents like ethanol:water or methanol:water, namely more organic solvent than water (at least a ratio of 70:30). Lukiswanto et al [ 52 ] and Yuniarti et al [ 53 ] obtained the healing activity, respectively, in the models of hot plate-induced burn and linear incision, with similar concentrations of corresponding ellagic acid (4% and 3% of the ointment, about 20–15 mg/kg referring to 0.5 g of topical application). Mo et al [ 54 ] paralleled the effect of pomegranate peel extract (5%) and the relative amount of pure ellagic acid (0.65%, close to 3.25 mg/kg) on excision, incision, and burn model.…”

“…The mechanism of action was partially explained—despite the analogue use of whole fruit extracts, standardized on ellagic acid amount (40%), Lukiswanto et al [ 52 ] and Yuniarti et al [ 53 ] observed the increase in collagen deposition but also divergent effects on polymorphonuclear (PMN) cells infiltration and angiogenesis. However, Mo et al [ 54 ] attributed the increase in hydroxyproline content and collagen deposition to the extract, but not to ellagic acid; granulation and inflammation were absent in the treated tissue, even when ellagic acid was used alone, thus supporting the observations of Lukiswanto et al [ 52 ] about impaired angiogenesis and PMN infiltration. In addition to the anti-inflammatory activity, ellagic acid (0.65%) counteracts the expression of myeloperoxidase in damaged tissue (−53%), leading to antioxidant activity [ 54 ].…”

“…Considering the average weight of Wistar rats (180 g) and a standard application of ointment (0.5 g) on the wounded area, it is possible to estimate a range of 28–280 mg/kg of extract in the other experiments. The poor characterization was a notable weak point of all the studies, since only four authors reported partial analytical data—Mo et al [ 54 ], Lukiswanto et al [ 52 ], and Yuniarti et al [ 53 ] standardized the amount of ellagic acid, which was 13% for the first paper and 40% for the other two, while Hayouni et al [ 55 ] carried out a qualitative characterization of the ellagitannins punicalagin A and B, ellagic acid and anthocyanins (delphinidin and pelargonidin glucosides).…”

Evaluation of the In Vitro Oral Wound Healing Effects of Pomegranate (Punica granatum) Rind Extract and Punicalagin, in Combination with Zn (II)

“…In light of its folklore medicinal status, crude pomegranate extracts and its constituent compounds, such as punicalagin, have received much biomedical attention given the considerable evidence supporting their efficacy against a wide range of diseases and conditions, ascribed to its various anticancer, antimicrobial, anti-inflammatory and antioxidant bioactivities [ 16 ]. Although numerous studies have previously endorsed the beneficial effects of PRE and punicalagin and advocated their application in the treatment of impaired wound healing responses in skin [ 19 , 20 , 21 , 22 , 23 , 24 ], a clinical area which has largely been overlook from a wound healing viewpoint are the potential abilities of PRE and punicalagin within the oral cavity, when tissue damage is commonly caused by periodontal disease and trauma. Indeed, periodontal diseases, comprising gingivitis and periodontitis, are regarded as being the most common disease of mankind, leading to huge economic burdens for healthcare providers worldwide [ 37 ].…”

“…The fruit exocarp (rind) is particularly abundant in hydrolysable tannins, in particular punicalagin, which is a large (mw 1,084.71 g/mol) molecule comprised of gallagic acid and ellagic acid linked via a glucose moiety ( Figure 1 ) [ 18 , 19 ]. These compounds have been attributed as being the primary sources of bioactivity responsible for the desirable medicinal properties of pomegranate, including their dermal wound healing efficacies [ 19 , 20 , 21 , 22 , 23 , 24 ]. Indeed, from our previous work, pomegranate rind extract (PRE) and punicalagin itself have been shown to exhibit potent anti-inflammatory, antimicrobial and antiviral activities, which can be further potentiated by combination with Zn (II) ions [ 25 , 26 , 27 , 28 ].…”