Burn Healing Plants in Iranian Traditional Medicine

Research Journal of Pharmacognosy (RJP) 2(1), 2015: 53-68 Received: Aug 2014 Accepted: Sep 2014

Review article

Burn healing plants in Iranian Traditional Medicine

Sh. Fahimi1, H. Hajimehdipoor1*, M. Abdollahi2, S.A. Mortazavi3

1Traditional Medicine and Materia Medica Research Center and Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. 3Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract Burns are known as one of the most common forms of injury with devastating consequences. Despite the discovery of several antiseptics, burn wound healing has still remained a challenge to modern medicine. Herbal products seem to possess moderate efficacy with no or less toxicity and are less expensive compared to synthetic drugs. Burn is a well-known disorder in Iranian Traditional Medicine (ITM). Iranian physicians have divided burns into various types based on the cause and recommended treatment for each type. According to ITM references, herbal therapy was the major treatment prescribed by Iranian physicians for burns. In the present study, seven ancient Iranian medical texts were screened for the herbs with burn healing effects along with their applied dosage forms. The medicinal herbs were listed and scored based on the frequency of their repetition. Moreover, the best scientific name that was suitable for each plant as well as surveying modern studies about their biological effects has been carried out. In our investigation eighteen plants with seven topical application categories have been obtained as the most frequent herbs for burn healing in ITM. Modern studies have revealed that these plants have shown some biological activities such as anti- inflammatory, antimicrobial and antioxidant effects which might establish the relationship between the mentioned activities and burn wound healing property. This list can provide a suitable resource for future researches in the field of burn treatment.

Keywords: anti-bacterial, anti-inflammatory, antioxidant, burn healing, Iranian Traditional Medicine

Introduction Burns are one of the most common and procedures and prolonged period of rehabilitation devastating forms of trauma, with outcomes [2, 3]. Burn is defined as tissue injury caused by spanning the spectrum from physical heat, chemicals, electricity, radiation, etc. [4]. impairments and disabilities to emotional and Thermal burn and related injuries have remained mental consequences [1, 2]. Burn management a major cause of death and disability [5]. entails significant duration of hospital stay, According to the depth, burn wounds are expensive medication, multiple operative classified as first degree (superficial), second

Fahimi Sh. et al. degree (partial thickness) and third degree (full- treatment. The aim of the first stage was thickness). Burn wound healing is a complicated prevention of blistering by cooling and non- process including inﬂammation due to disruption irritant agents. However, extra cooling should of blood vessels and extravasation of blood have been avoided due to the heat retention constituents, re-epithelialization that begins which might lead to tissue decomposition. In this several hours after injury, formation of situation, oils were usually useful to remove the granulation tissue, neovascularization, migration heat. In the second stage, if the blister had been and mitogenic stimulation of endothelial cells formed, detergent and desiccant medications with and finally wound contraction as a result of moderate hot and cold temperament were interaction between cells, extracellular matrix recommended. Generally, low fat desiccant and cytokines. Severe burn wounds need to be products were preferred for wet wounds, treated as soon as possible since any delay can whereas, wet temperament preparations or oils postpone the healing process or result in infection and waxes were considered as suitable [4]. This makes burn care expensive and every medications for dry wounds [6,7]. Moreover, effort should be made to provide a shorter different dosage forms have been used in ITM for treatment period for the burnt patients [3]. burn healing. The aim of the present study has Although small burns are not usually life been introducing some medicinal plants and their threatening, they need the same attention as large dosage forms used in ITM for burn healing. burns, in order to achieve functional and cosmetic outcome. Most of the early treatments Methods include topical application of medicaments, Seven ITM texts including al-Qanun fi al -Tibb mainly to prevent infections [5]. Healing of burn (Avicenna) [7], Al Havi (Rhazes) [8], Al-abniah wounds still remains a challenge to modern An Haghayegh el-adviah (Heravi) [9], al-jāmi li- medicine, though many antiseptics have been mufradāt al-adwiyawa al-aghdhiy (Ibn al-Baitar) discovered [3]. It may be due to the fact that most [10], Ekhtiarat-e-Badiee (Ansari) [11], Tohfat-ul- of the available products have antimicrobial momenin (Mo,men tonekaboni) [12] and activity rather than wound healing effect, as well Makhzan-ul-Adviah (Aghili Shirazi) [13] were as their probable negative performance and studied. The traditional word of “hargh” was toxicity as in the case of silver sulfadiazine on considered as the keyword for extracting the ﬁbroblasts [4]. Improving the methods of wound plants with healing effect in all kinds of burns. healing and tissue repair offers enormous First al-Qanun fi al –Tibb, the main text of ITM, opportunities to enhance the quality of life for was screened using the keyword and the burn trauma and burn patients. It may also help to healing property of the selected plants was reduce health care costs. Nowadays, many drugs checked in the rest of ITM texts to find the most with natural sources have been retrieved from frequently used plants. In addition to the traditional medical systems [5]. In Iranian temperament and used part, different dosage Traditional Medicine (ITM), plants have been forms of the chosen plants, applied to burns, have used to combat various diseases and pathological been studied. So, the description of the used conditions. Burn is a well-known disorder in ITM dosage forms has been investigated [14]. and several traditional prescriptions have been Afterwards, traditional names of the selected recommended for burn healing. According to plants were matched to the scientific names using ITM manuscripts, topical preparations have been botanical text references [15-17]. In the next step, considered as the main treatment for burns, a substantial search has been performed in though in some cases, phlebotomy was scientific databases such as ‘‘Google Scholar’’ prescribed. ITM scholars believed that there were and ‘‘pubmed’’ to find the plant biological two stages which should be noticed in burn activities concerning burn healing effect. For this

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Burn healing plants in Iranian Traditional Medicine purpose, the scientific plant names in The antioxidant potential of different fractions of combination with the key terms including "burn L. inermis has been demonstrated through DPPH healing", "wound healing", “antioxidant”, “anti- and β-carotene-linoleic acid assays as well [21]. inflammatory and “antibacterial" were used The anti-inflammation effects of the plant leaves separately and in vivo, in vitro and clinical trials have been established in a manner that butanol regarding to the search terms have been screened. and chloroform fractions exhibited more potent anti-inflammatory effect than aqueous fraction, Results and Discussion dose dependently [22]. Searching ITM references revealed eighteen plants as the most frequently used herbs for burn Hypericum perforatum L. healing which have been listed in table 1. These The healing properties of H. perforatum ointment plants have been ordered according to their have been evaluated and the histopathological repetition in the references along with their results, along with the wound contraction rate traditional names, family, temperament, used and period of epithelialization, have parts, dosage forms and biological effects. The demonstrated the healing effect of H. perforatum plant parts which had been used for burn healing ointment in linear incisions, circular excisions consisted of leaves, flowers, fruits, seeds, seed and thermal burn wounds [23]. Moreover, a oil, roots, bulbs, barks and gum resins while clinical research has shown that applying a leaves appeared to be the most used parts among specific H. perforatum ointment (Gol-Daru others. According to table 1, most of the herbs company) three times a day for 16 days has have hot and dry temperament (>66%) while significantly improved wound healing and has dryness is the prominent characteristic of the reduced scar formation compared to placebo [24]. majority of burn healing plants introduced by The ethanol extract of the plant has demonstrated Iranian scholars (>83%). Different types of anti- inflammatory effects in carrageenan induced dosage forms used in ITM for burn healing have pedal edema and cotton pellet induced granuloma been summarized in table 2. All of the mentioned model [25]. A flavonoid-rich extract of H. dosage forms were used topically. Among them perforatum L. has exhibited antioxidant activity “Dohn”, “Marham”, Qeirooti” and “Zemad” as an effective scavenger in quenching DPPH and (with oily base) could be suitable for dry wounds, superoxide radicals [26]. The available literature whereas, “Tela”, “Natool”, “Zaroor” and indicates that different extracts and preparations “Zemad” (without oily base) were useful for wet of H. perforatum possess more burns. In addition to the summarized biological antibacterial activity against gram-positive than effects in table 1, the results of in vitro/in vivo gram-negative bacteria in in vivo and in vitro tests or clinical trials performed on the plants and tests [27]. the probable mechanisms have been mentioned as follows: Myrtus communis L. Joursaraei et al. have demonstrated that M. Lawsonia inermis L. communis extract could increase The inhibitory effects of chloroform and aqueous revascularization and the number of fibroblasts in extracts of L. inermis leaves on the growth of second degree burn wounds in rats [28]. microorganisms that are involved in burn Myrtucommulone, a nonprenylated infections has been proven [18]. The animals acylphloroglucinol constituent in the leaves of M. treated with ethanol extract of the plant leaves communis, has exerted potent in vivo anti- showed reduction in the wound area, therefore, inflammatory effects [29]. In addition to the topical formulation of ethanol extract could be protecting effect of M. communis fruits against successfully used for the wound healing [19,20]. gastric ulcer, the antioxidant activity of the plant

Table 1. The most frequent herbs in ITM for burn healing

et al. Sh. Fahimi Traditional No. phonetics Scientific name Family Temperament Part used Dosage form Biological effectsa name

B [19, 20] , C [22], D 1 Henna /hennɑ:/ Lawsonia inermis L. Lythraceae Cold and dry Leaf Natool [21], E [18]

A [23] Hypericum 2 Hiofariqun /hɪu:fɑ:rɪɢu:n/ Hypericaceae Hot and dry Leaf Zemad B [23, 24] , C [25], D perforatum L. [26], E [27] Dohn, Marham, Qeirooti, A [28] 3 Ass /ɑ:s/ Myrtus communis L. Myrtaceae Cold and dry Leaf/fruit Zaroor, Zemad (with B [30], C [29], D [30], olive oil) E [31] B [32, 33], C [33, 34], Malva sylvestris L. Natool, Zemad (with D [35], E [36] 4 Khobbazi /xoʊbbɑ:zi: / Malvaceae Cold and wet Leaf Malva neglecta olive oil) B [37], C [39], D [38], Wallr. E [40] A [41] Hot and dry 5 Zaitoon /zæjtu:n/ Olea europaea L. Oleaceae Fruit Zemad B [42] , C [44], D [43], (ripe fruits) E [45] A [46] 6 Semsem /semsem/ Sesamum indicum L. Pedaliaceae Hot and wet Seed/seed oil Zemad B [46], C [48] , D [47]

Iris sp. Iridaceae Natool, Zemad (with C [50], D [49] 7 Sousan /su:sæn/ Hot and dry Leaf/ bulb Dohn,ul, vard)b Lilium candidum L. Liliaceae C [52], D [51, 52] B [53], C [53], D [54], 8 Sanoubar /sænoʊbær/ Pinus pinea L. Pinaceae Hot and dry Bark/leaf Tela, Zaroor E [54]

9 Selgh /selɢ/ Beta vulgaris L. Amaranthaceae Hot and dry Leaf Tela C [56], D [55], E [57]

10 Ghalioon /ɢɑ:li:u:n/ Galium verum L. Rubiaceae Hot and dry Flower Zemad D [58]

Loban /loʊbɑ:n/ Boswellia carteri Oleogum C [60], D [59], E [61, 11 Burseraceae Hot and dry Zemad (with oily base) (kondor) (/koʊndoʊr/) Birdw. resin 62]

Table 1. The most frequent herbs in ITM for burn healing (Continued)

Traditional No. phonetics Scientific name Family Temperament Part used Dosage form Biological effectsa name Arnebia A [32, 63, 64] euchroma B [65], C [64, 67], D (Royle) Marham, Qeirooti (with Abou [66], E [68] 12 /æbu:χælsɑ:/ I.M.Johnst. Boraginaceae Hot and dry Root olive oil), Tela (with khalsa Dohn,ul, vard) A [69] Alkanna tinctoria B [69, 70], C [73], D Taush Medicine Traditional Iranian in plants healing Burn [71, 72], E [74] Convolvulus Dry and Natool, Qeirooti Zemad 13 Leblub /leblʌb/ Convolvulaceae Leaf D [75], E [76] arvensis L. hot/coldc (with Dohn,ul, vard)

Narcissus tazetta 14 Narjes /nærdʒes/ Amaryllidaceae Hot and dry Bulb Zemad (with honey) E [77] L.

Indigofera C [78], D [79], E [80, 15 Nil /nɪl/ Leguminosae Hot and dry Leaf Zemad (with honey) tinctoria L. 81]

Ocimum B [82], C [84], D [83], basilicum L. Tela (with rosewater), E [85] 16 Zaimeran /zæjmerɑ:n/ Lamiaceae Hot and dry Leaf Ocimum Zemad B [86], D [87], E [86] minimum L.

Qeirooti (with olive oil), C [88, 89], D [90], E 17 Quesus /ɢesu:s/ Hedera helix L. Araliaceae Hot Flower/leaf Zemad [91]

Quasab ,o, Acorus calamus Zemad (with Dohn,ul, B [92], C [92, 93], D 18 /ɢæsæboʊzæri:re/ Acoraceae Hot and dry _d zarirah L. vard) [94-96], E [93, 97]

aA: burn healing effect; B: wound healing effect; C: anti-inflammatory effect; D: antioxidant effect; E: antibacterial effect bDohn,ul, vard : the oily extract of Rosa damascena petals cThere were different ideas about hot and cold temperament of this plant dNot mentioned in ITM references.

Fahimi Sh. et al. has been revealed by in vitro studies [30]. Also, the aqueous leaf extract of M. communis has have shown strong antioxidant activity and demonstrated an excellent antibacterial activity reducing power by scavenging the superoxide against Pseudomonas aeruginosa [31]. anion, hydrogen peroxide and free radicals as well as metal chelating property compared to Table 2. Dosage forms used for burns in ITM natural and synthetic standard antioxidants such No. Dosage form Description as BHA, BHT and α-tocopherol [38]. The anti- A dosage form prepared by extraction of the oily constituents of plant by direct compression inflammatory effects of the plant extracts have 1 Dohn (/dohn/) or indirectly by using other oils especially been shown by Vogl et al. through in vitro almond, sesame or olive oil. A topical preparation consisted of an oil or wax studies [39]. Besides, the ethanol extract of M. Marham 2 or mixture of them especially applied for (/mærhæm/) neglecta flowers has exhibited considerable injuries and some swellings. inhibitory effect against Staphylococcus The decoction form of plant material (with or Natool (/næt without filtration) poured lukewarmly on the epidermidis (MIC: 5 mg/mL) [40]. 3 u:l/) target organ where may be surrounded by a paste. Qeirooti A combination of oils and waxes with or Olea europaea L. 4 (/ɢeiru:ti/) without medicinal plants. During an in vivo study on full-thickness burns A low viscose topical dosage form of the plant 5 Tela (/telɑ:/) material which frequently applied on the body. conducted by Edraki et al., the rats treated with Zaroor Dried fine plant powder which sprinkled on the 6 sea buckthorn/olive oil mixture have revealed (/zæru:r/) target organ. A soft and viscose topical preparation which more developed re-epithelialization and Zemad 7 may have oils and waxes and usually dressed (/zemɑ:d/) continuous basement membrane with a mature on the location. granulation tissue and have shown faster wound contraction with no infection [41]. The wound Malva sylvestris L. healing activity of the leaves and fruits of O. The wound healing activity of M. sylvestris has europaea has been studied in incision and been demonstrated in rat burn model by excision models in rodents [42]. In addition, the Pirbalouti et al. [32]. In another study, the diethyl prominent antioxidant properties of the fruit ether extract of M. sylvestris flowers have extracts of ten olive tree cultivars have been effectively stimulated wound contraction and demonstrated by ABTS+ method [43]. The anti- have shown increasing in well-organized bands inflammatory effect of O. europaea has been of collagen, more fibroblasts and few investigated and the n-hexane extract of the inflammatory cells in the full thickness wounds fruits have displayed 12.7–27.8% inhibition in of alloxan-induced diabetic rats [33]. Moreover, the carrageenan-induced hind paw edema model the ethanol extract of the plant leaves have at 400 mg/kg [44]. Besides, the aqueous fruit exerted inhibitory effect on croton oil-induced extract of O. europaea has shown an excellent ear edema in mice [34]. The antioxidant activity effect on S. aureus growth isolated from burn of M. sylvestris has been established by DPPH cases [45]. and β-carotene-linoleic acid assays [35]. The chloroform, ethanol and water extracts of the Sesamum indicum L. plant have been active against Staphylococcus The seeds and oil of S. indicum have shown aureus and P. aeruginosa [36]. significant reduction in period of epithelization Malva neglecta Wallr. and wound contraction in the excision and burn Aerial parts of M. neglecta have demonstrated wound models while in the incision wound model anti-ulcerogenic activity against the ethanol- a significant increase in the wound breaking induced gastric ulcers in rat model [37]. In in strength has been observed [46]. Free radical vitro studies, hydroalcoholic extract of the plant scavenging capacity of antioxidants from sesame

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Burn healing plants in Iranian Traditional Medicine extract has been studied in DPPH assay [47]. It method, which is based on the inhibition of acetic has been demonstrated that sesamin, a lipid- acid-induced increase in capillary permeability soluble lignin isolated from S. indicum, has [53]. In addition to scavenging effect towards down-regulated NF-κB activation induced by DPPH, the oil obtained from the nuts of P. pinea various inflammatory stimuli. In addition, displayed inhibitory potentials against the sesamin has inhibited the expression of protein isolated strains of S. aureus [54].

COX-2 closely linked with inflammation [48]. Beta vulgaris L.

The antioxidant capacity of a phenolic fraction Iris sp. obtained from B. vulgaris hydro alcoholic extract Evaluation of antioxidant effects of I. has been reported [55]. The aqueous leaves pseudopumila has demonstrated that in addition extract of the plant has shown significant anti- to the significant antiradical effect of the inflammatory activity using carrageenan induced methanol and chloroform extracts of the flowers rat paw edema method for acute inflammation through DPPH assay, the chloroform extract of and cotton pellet granuloma method for chronic rhizomes and the methanol extract of the flowers inflammation [56]. Moreover, the ethanol extract have shown the most considerable activity in obtained from the aerial parts of the plant has lipid peroxidation of liposomes [49]. Moreover, exhibited antibacterial effect against S. the methanol extract of I. pseudopumila has epidermidis and S. aureus. [57]. exhibited significant inhibitory effect on NO (an Galium verum L. inflammatory mediator) production in Lakić et al. have evaluated the antioxidant macrophages [50]. properties of methanol extract of G. verum in four different models and have demonstrated that Lilium candidum L. the extract expressed powerful scavenging The antioxidant capacity of L. candidum essential activity, reducing the DPPH and OH radical oil has been revealed by photo chemi formation and neutralizing H O , in a dose luminescence (PCL) method [51]. The anti- 2 2 dependent manner. The examined extract has also inflammatory and antioxidant effects of Pfaffia showed notable inhibition of lipid peroxidation paniculata/Ptychopetalum olacoides /Lilium candidum mixture has been measured by [58]. quantification of prostaglandin E , leukotriene 2 Boswellia carteri Birdw. B4, histamine, and superoxide dismutase levels in an in vitro model of human skin culture. The The essential oil of B. carteri has shown strong results have shown a dose-dependent decrease in antioxidant activity by inhibition of linoleic acid production of inflammatory mediators, peroxidation [59]. Among the pentacyclic concomitant to increased antioxidant enzyme triterpenes, some boswellic acids (obtained from levels under basal and lipopolysaccharide- Boswellia species) are mainly responsible for stimulated conditions [52]. many of the pharmacological effects which have been revealed to be effective in inhibition of Pinus pinea L. leukoteriene formation [60]. The antimicrobial Süntar et al. have demonstrated that the essential activity of the essential oil isolated from the oil obtained from the cones of P. pinea possessed oleogum resin of B. carteri has been wound healing activity in linear incision and demonstrated against various microorganisms circular excision wound models. Besides, the including fungi, gram-positive and gram-negative anti-inflammatory effect of the plant essential oil bacterial strains [61]. Moreover, binary mixture was significantly approved by the Whittle of the methanol extracts of B. carteri and

Fahimi Sh. et al. clarithromycine, has shown a potent synergistic root extract, has been demonstrated on second effect against P. aeruginosa and S. aureus [62]. intention wounds in dogs [69]. Moreover, several Arnebia euchroma (Royle) I.M.Johst. studies have revealed molecular and biological The burn healing activity of A. euchroma has properties of A/S that have improve wound been revealed by Ashkani-Esfahani et al. They healing [70]. It has been declared that the have shown that wound closure rate, fibroblast dichloromethane extract of A. tinctoria roots, population, volume density of collagen bundles, containing mainly alkannin esters, has and length density of vessels have been demonstrated satisfactory antioxidant activity significantly improved by [71]. Besides, non-aqueous solvents and olive oil carboxymethylcellulose (CMC) gels containing extracts of A. tinctoria roots with their A/S esters, A. euchroma hydroalcoholic extract at the have exhibited notable radical scavenging concentration of 10% and 20% in third-degree activity [72]. The efficient anti-inflammatory burn wounds in rats [63]. In another study, it was effect of these two natural products (A/S ) has also found that the leaves and the root extracts of been revealed in mouse paw edema [73]. A. euchroma had shown anti-inflammatory effect Moreover, Shikonin dyed silk exhibited on second degree burn wounds in rats [64]. bactericidal effect against S. aureus [74]. Moreover, in vivo healing effect of goat lipid containing A. euchroma root extract on burns has Convolvulus arvensis L. been demonstrated through increasing the rate of A phenolic rich fraction of C. arvensis leaves, , wound contraction and collagen turnover [32]. In has shown antioxidant property by DPPH radical another study, a significant wound healing scavenging and inhibiting the oxidation of β- activity has been observed with an ointment carotene assays [75]. In addition, the antibacterial containing n- hexane root extract of A. euchroma activity of the aqueous and alcohol extracts of the (1%) in incision and excision models in mice and plant has been demonstrated [76]. rats [65]. The antioxidant activity of the aqueous and methanol extracts of the plant roots has been Narcissus tazetta L. assessed by several methods while the latter The plant aerial parts have shown potential extract has shown to be more powerful in Trolox antimicrobial activity against P. aeruginosa [77]. equivalent antioxidant capacity and reducing power assays [66]. The anti-inflammatory Indigofera tinctoria L. activity of the petroleum ether, chloroform, The anti-inflammatory activity of the ethanol alcohol and aqueous extracts of A. extract of I. tinctoria leaves has been evaluated euchroma roots has been evaluated in another by sub-planter injection of carrageenan in Wister research, and the results have demonstrated the albino rats. In this study Tyagi et al. has shown prominent edema inhibition property of the that oral administration of the extract, has dose extracts against carrageenan-induced rat-paw dependently exhibited potent anti-inflammatory edema which were comparable to ibuprofen [67]. activity by reducing the induced paw edema [78]. Besides, the ethanol extract of A. euchroma roots By employing different in vitro assays such as has shown interesting minimum inhibitory reducing power, DPPH, ABTS, NO and OH concentration (8 μg/mL) against P. aeruginosa radical scavenging methods, the antioxidant [68]. properties of different extracts of I. tinctoria leaves have been evaluated. All extracts have Alkanna tinctoria Taush exhibited reducing power and strong peroxidation The significant healing effect of an ointment inhibition against linoleic acid emulsion system, containing alkannin and shikonin (A/S), two although the ethyl acetate extract was found to enantiomeric naphthoquinones from A. tinctoria possess more hydrogen donating ability and

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Burn healing plants in Iranian Traditional Medicine higher DPPH and NO scavenging activities [79]. “Dermo HdC ”, a bioproduct obtained from the In a study conducted by Selvakumar and leaves of H. helix, has inhibited IL6 and IL8 Karunakaran, I. tinctoria has shown higher secretion and has blocked the VEGF (Vascular antimicrobial activity against P. aeruginosa, S. Endothelial Growth Factor) which could stop the aureus and Bacillus subtilis compared to inflammation progression from acute to chronic penicillin and tetracycline [80]. Moreover, the stage [88]. Besides, the anti-inflammatory chloroform extract from the plant leaves has properties of the ethanol leaves extract of H. helix exhibited the broadest and highest antibacterial has been demonstrated using formalin-induced activity compared to the butanol and ethanol paw edema test in Swiss albino mice [89]. α- extracts [81]. hederin and hederasaponin-C, two saponins isolated from H. helix, have been investigated Ocimum basilicum L. using different antioxidant tests and have finally Using the excision wound model in rats, Salmah exhibited a strong total antioxidant activity [90]. et al. have reported that the wounds treated with The ethyl acetate extract of the plant has honey in combination with alcohol extract of O. exhibited the maximum inhibitory effect against basilicum have demostrated considerable signs of Staphylococcus aureus, S. epidermidis, dermal healing which has significantly healed Escherichia coli, and Bacillus subtilis [91]. earlier compared to those treated with honey alone [82]. The antioxidant property of O. Acorus calamus L. basilicum and its effect on nitric oxide (NO) Shi et al. have shown that in addition to the production in lipopolysaccharide-activated inhibitory effect on mRNA expressions of macrophages has been revealed [83]. Besides, O. inflammatory mediators, the aqueous extracts basilicum methanol extract has inhibited the pro- from the fresh roots and rhizomes of A. calamus inflammatory cytokines and mediators, which could significantly enhance the rate of skin accounts for the anti-inflammatory effects [84]. wound-healing in the excisional wounding test in Assessment of the antibacterial effects of the mice [92]. Moreover, the significant carrageenan plant has shown that the ethanol extract of O. induced anti-inflammatory property of the plant basilicum has been more effective against the aqueous extract has been proved by several pathogens such as S. aureus and P. aeruginosa studies [93]. It has been demonstrated that the when compared to the acetone extract [85]. ethanol extract of A. calamus has exhibited hepatoprotective and antioxidant activities Ocimum minimum L. against acetaminophen-induced liver injury in The essential oil extracted from the leaves of O. rats which are comparable to the standard drug, minimum has demonstrated anti-ulcerogenic silymarin [94]. In addition to the of ethanol activity in gastric ulcers induced by indomethacin extract of A. calamus rhizomes [95], the leaf and ethanol. Moreover, the essential oil has methanol extract has exhibited remarkable DPPH shown antibacterial activity against S. aureus radical-scavenging activity, ability of chelating using disc diffusion technique [86]. Lukmanul ferrous ions and reducing power, whereas the Hakkim et al. have revealed the antioxidant rhizome extract has displayed the strongest activity of the methanol leaves extract of Ocimum superoxide anion-scavenging activity as well as species including O. minimum using iron (III) radical scavenging ability [95,96]. Besides, the reduction, ß-carotene–linoleic acid bleaching, antioxidant activity of A. calamus leaves and DPPH and superoxide anion free radical rhizomes extracts were comparable to the scavenging assays [87]. standard antioxidants [96]. The alcohol extract and the essential oil of A. calamus have Hedera helix L. represented potent in vitro activity against some In a research performed by Dumitriu et al., pathogenic and nonpathogenic fungi, Gram

Fahimi Sh. et al. negative and Gram positive bacteria specially Modern studies have also shown that all of the against S. aureus [93]. In addition, the mentioned plants possessed at least one antibacterial effect of the plant leaf extract biological effect corresponding to burn healing against P. aeruginosa has been demonstrated activity while antioxidant property was the [97]. prominent characteristic of the burn healing herbs. Moreover, among the plants which have Conclusion been evaluated for wound healing effect, only Wound healing is a complicated process five plants including “Hiofariqun”, “Ass”, occurring in injured tissues to restore its “Zaitoon”, “Semsem” and “Abou khalsa” construction and return the damaged tissue to its demonstrated burn healing property. Hence, the normal situation as soon as possible [98]. The rest of the introduced herbs could be appropriate aim of the healing process is prevention of candidates for future burn healing studies and pathogens invasion, confirm the integrity of alternative medicaments for management of burn damaged tissue, and reconstruct the skin wounds. physiological function [99]. There are different factors involved in burn healing process; oxidants Acknowledgments are considered as inhibitory factors to wound The article was based on Ph.D. thesis of healing so, protecting the tissue from oxidative Traditional Pharmacy (Shirin Fahimi, No. 128), damage is the important role of antioxidants granted by School of Traditional Medicine, which leads to survival of ischemic skin flaps or Shahid Beheshti University of Medical Sciences, improvement of wound healing [100]. On the Tehran, Iran (No. 111). other hand, the excessive and unbalanced inflammation could delay healing and enhance Declaration of interest scarring which suggests a promising target for The authors declare that there is no conflict of future therapeutic interventions or even interest. The authors alone are responsible for the predisposed tissue to cancer development [101- content of the paper. 103]. Therefore, the anti-inflammatory compounds could act as effective agents in References wound healing [104]. Despite the natural [1] Ezzati A, Bayat M, Taheri S, Mohsenifar Z. progression of the burn healing process, Low-level laser therapy with pulsed infrared infections can delay the process by several laser accelerates third -degree burn healing mechanisms. Hence, infection is the major process in rats. J Reh Res Dev. 2009; 46(4): complication of burn injuries and antibacterial 543-554. agents play a critical role in the burn healing [2] Upadhyay NK, Kumar R, Siddiqui MS, process [102,104-107]. Plants have an extensive Gupta A. Mechanism of wound-healing potential for management and treatment of activity of Hippophae rhamnoides L. leaf wounds and burns with their antioxidant, anti- extract in experimental burns. Evid-Based inflammatory and antimicrobial activities due to Complemen Altern Med. 2011; 1-9. their phytochemical constituents such as [3] Khorasani G, Hosseinimehr SJ, Zamani P, alkaloids, essential oils, ﬂavonoids, tannins, Ghasemi M, Ahmadi A. The effect of Saffron terpenoids, saponins, fatty acids and phenolic (Crocus Sativus) extract for healing of compounds [4,106,108]. Low cost, availability second-degree burn wound in Rats. Keio J and fewer side effects are other advantages of Med. 2008; 57(4): 190-195. herbal remedies [4]. In the present investigation, [4] Bahramsoltani R, Farzaei MH, Rahimi R. we have introduced eighteen plants which were Medicinal plants and their natural the most frequent herbs in ITM for burn healing. components as future drugs for the treatment

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Burn healing plants in Iranian Traditional Medicine

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