In this morden age the incidence of accidents has steeply risen, which is mostly responsible for different types of wounds

THERAPEUTIC POTENTIAL OF PLANTS IN WOUND HEALING
Rajinder Raina, A.K. Srivastava, Shahid Prawez and Azad Ahmad
Division of Pharmacology and Toxicology, F.V.Sc. & A.H., SKUAST-J, R.S. Pura, Jammu Introduction
Wound is defined simply as the disruption of the cellular and anatomic continuity of a tissue (Bennet 1988). Wound may be produced by physical, chemical, thermal, microbial or immunological insult to the tissue. The process of wound healing consists of integrated cellular and biochemical events leading to reestablishment of structural and functional integrity with regain of strength of injured tissue. The events include coagulation, inflammation, formation of granulation tissue and tissue remodeling (Lynch 1987; Savant & Shah 1998). Clinically, one often encounters non-healing, under-healing or over healing. Therefore the aim of treating a wound is to either shorten the time required for healing or to minimize the undesired consequences (Myers et al 1980). Attention is directed towards discovering an agent, which will accelerate wound healing either when it is progressing normally (Brown et al., 1988a; Mather et al., 1989), or when it is suppressed by various agents like corticosteroids (Ehrlich & Hunt 1968), antineoplastics (Raju & Kulkarni 1986), non steroidal anti-inflammatory agents (Lee 1968 b). Medical treatment of wound includes administration of drugs either locally (topical) or systemically (oral or parenteral) in an attempt to aid wound repair (Savanth & Shah 1998; Rains & Mann 1988; Moy 1993). The topical agents used include antibiotics and antiseptics (Chulani 1996), desloughing agents (chemical debridement, e.g. Hydrogen peroxide, eusol and collagenase ointment) (Savanth & Mehta 1998), wound healing promoters (eg. Tretinoin, aloe vera extract, honey, comfrey, benzoyl peroxide, chamomilia extract, dexpanthenol, tetrachlordecaxide solution, clostebol acetate Various growth factors like platelet derived growth factor, macrophage derived growth factor, monocyte derived growth factor (Brown et al., 1988a; Mather et al., 1989) etc. are necessary for the initiation and promotion of wound healing. Many substances like tissue extracts (Udupa et al 1991; Ramesh et al., 1990), vitamins (Williams & Bissel 1944), minerals (Rao et al., 1988a) and a number of plant products (Dahanukar et al., 2000; Sharma et al., 1990; Udupa et al., 1991); have been reported by various workers, to possess prohealing effects. These approaches are being advocated in wound management as body’s repair kit (McAuliffe 1989). Consequently there exists a need for new agents which may be useful in proper wound management. In this direction a number of herbal products are being investigated. Herbal products for wound management
Herbal products have been used in wounds management for many years. A few plants/plant products with promising outcome are discussed here. Aloe vera
Aloe, native to Africa, is also known as “lily of the desert”, the plant of immortality; and the medicinal plant. The name was derived from the alloeh meaning “bitter” because of the bitter liquid found in the leaves. In 1500 B.C Egyptians recorded use of this herbal plant in treating burns, Extensive research has shown that the clear gel of it has a dramatic ability to heal wounds, ulcers, burns by putting a protective coating on the affected areas and speeding up the healing process. The plant contains 96% of water and rest is essential oil, aminoacids, minerals, vitamins, enzymes and glycoproteins. Various constituents of Aloe vara have been shown to have anti- inflammatory activity as well as to simulate wound healing (Penneys 1981). There are reports that Aloe vera gel applied topically could help heal radiation burns. However, a large modern, placebo controlled study did not find aloe effective in this regard (Williams et al., 1996). Some clinical reports suggest topical Aloe vera gel for healing minor burns (Visuthilosol Aloe vera, topical application of the gel is harmless and hypersensitive reactions to it are rare. In some severe burns, aloe gel may actually impede healing (Schmidt & Greenspoon 1991). Lantana camara
Lantana camara Linn (Fam-Verbenaceae) a shrub, native of tropical America and completely naturalized in many parts of India as an ornamental plant. The plant has wound healing, abortificient, antimalarial and anti-inflammatory properties (Kirtikar & Basu 1994; Chopra et al., 1956; Kurian 1995). The leaves of the plant are reported to be useful in the treatment of wounds, ulcers, bruises, sores etc. (Brando et al., 1985). In a recent study hydroalcoholic extract and fresh juice of leaves have favored wound contraction (Dash et al., 2001). The toxicities of the plant include nephrotoxicity, hepatotoxicity, photosensitization, dermatitis, intestinal haemorrhages (Adesina 1982; Sharma et al., 1992). In view of the alarming reports of the toxicity, the use of this plant in whole or any part thereof needs to be carefully regulated until the alarming toxic principles of the plant are properly identified and removed. St. John’s Wort
St. John’s wort is a bushy perennial plant with numerous yellow flowers. It is native to many parts of the world including Europe and the United States. It has a 2400 years history of safe and effective usage in many folk and herbal remedies. It is claimed to be useful in mental depression, anxiety, sleep disorders, menstrual cramping, sciatica and arthritis. The blossoms have been used in folk medicine to relieve ulcers, gastritis, diarrhea and nausea. Externally it is used on cuts as disinfectants and to relieve inflammation and promote healing. The tincture of Hypericum spp. given orally has a remarkable effect in lacerated and suppurated wounds, and play an important role in restoring tissue vitality (Fayazuddin 1981). Further studies have also confirmed Hypericum spp. tincture has pro-healing action (Rao et al., 1991), as evidenced by the increase in wound contraction rate and granulation tissue breaking strengths. In addition, epithelization phase was also enhanced. Tridax procumbens
The plant is a native of tropical America and naturalized in tropical Africa, Asia, Australia and India. Leaf of Tridax procumbens mainly contains crude protein 26%, crude fiber 17% soluble carbohydrate 39% calcium oxide 5% (Chadha 1976). The juice of the leaves of this plant is used by villagers to arrest bleeding from cuts and bruises in animals. It has been shown that its juice accelerates two phases of healing namely epithelization and collagenization; and retards scar formation and granulation (Diwan et al., 1982). From these observations it was postulated that Tridax procumbens perhaps have certain components with prohealing and some with antihealing properties. Tridax procumbens antagonized anti-epithelization and tensile strength depressing effect of dexamethasone (a known healing suppressant agent) without affecting anticontraction and antigranulation action of dexamethasone (Diwan et al., 1983). The effect of various extracts (whole plant extract, aqueous extract, butanol extract and ether fraction) of this plant has been studied in dead space wound model (Udupa et al., 1991). The authors have reported that whole plant extract has the greatest prohealing activity with increase in tensile strength and lysyl oxidase activity among the various extracts. Aqueous extract was also effective in increasing lysyl oxidase but to a lesser degree than whole plant extract. Further it has been shown that extract of leaves of this plant also promotes wound healing in both normal and immunocompromised (steroid treated) rats in dead space wound model. The plant increased not only lysyl oxidase but also, protein and nucleic acid content in the granulation tissue, probably as a result of increase in glycosamino glycan content (Udupa et al., 1998). Chromolaena odorata
Chromolaena odorata was first identified in central America and Vietnam. The aqueous extract and the decoction from leaves of this plant have been used throughout Vietnam for the treatment of soft tissue wounds and burn wounds. In clinical use it has been noted that aqueous extracts of Chromolaena odorata enhances hemostatis (Akah 1990) and stimulates granulation tissue and reepithelization (Lee 1995). The extract also inhibits wound contraction and the inhibition of contraction is reversible. This supports that suggestion that it might be of therapeutic value in minimizing post burn scar contracture and Hydnocarpus wightiana
The oil of Hydnocarpus spp. has been recognized for several years as anti-leprosy drug and as an anti-parasitic drug in the treatment of guinea worm infestation. There are reports that wounds in leprosy patients and in patients with diabetic ulcers and gangrene healed faster when the oil of Hydnocarpus spp. was given orally or administered tropically (Manjrekar 1996). Recently the wound healing effect of oil of Hydnocarpus spp. was studied with reference to collagenation and the strength of scar tissue (Oomen et al., 1999). The drug treated group showed a significant increase in strength of scar tissues in the incision wound model and also increased the strength of collagen tissue and hydroxyproline content in the dead space wound model. Hydnocarpus oil administered orally promoted epithelization, but not wound contraction (Oomen et al., 2000). External application of oil of Hydnocarpus spp. and its paste significantly shortened the epithelization period when compared to control group. Further it was suggested that this finding is useful clinically because the oil may act as adjuvant in healing of wounds and ulcer in Helianthus annus Linn.
An ornamental annual herb, with erect, rough and hairy stem, common in Indian Gardens in swampy areas. In traditional medicine the plant is used by tribals for inflammation of eyes, sores, dysuria, colic, bite of tigers and bone fractures (Jain & Tarafdar 1970). The seed oil contains high levels of lysine, arginine, aspartic and glutamic acids and tannins (Jain et al., 1974). The alcoholic extract of whole plant of H. annus applied in the form of an ointment on the excised wound of rat led to a significant reduction in total healing period. This has been confirmed by histology where earlier appearance of fibroblasts are seen. Further it is stated that H. annus has hastened repair process which is indicated by a high degree of accumulation and an early appearance of the mucopolysaccharide (Deshpande et al., 1965). Jasminum auriculatum
A small herb found in south India and the western peninsula. The alcohol free defatted extract of J. auriculatum leaves has been reported to contain lupeol and jasminol (Deshpande & Upadyaya 1967). J. auriculatum has been shown to be beneficial in wound healing. The juice of the leaves in the form of jelly, on local application to a linear uniform excised wound in rats was found to promote wound healing, as assessed by histological, biochemical and contraction rate studied (Deshpande et Further, it has been reported that the fresh juice of the leaves showed an increased and early gain of the tensile strength in the treated linear wounds in rats. The study indicated that collagenation contributed to improved tensile strength in the early phase of healing (Deshpande & Pathak 1965). Further studied on musculo-peritoneal wound on the abdomen of rats, with 2.5% leaves extract of the plant injected intramuscularly confirmed the prohealing property of leaves. The effect was more marked in case of skin wounds that in the musculoperitoneal wounds Deshpande & Pathak Ghee medicated with J. auriculatum, on topical application was found to accelerate the healing time of second degree burn wounds in rats by six days. The mucopolysaccharide accumulation was found to be significantly higher in group treated with medicated ghee. The acceleration of the healing time was approximately 20% with inmedicated ghee and 30% in medicates ghee Deshpande & Pathak 1966b). Ginkgo biloba
Ginkgo biloba (Salisburia aduantifolia) is also known as maiden hair tree. The genus ginkgo originated 200 million years ago and is considered as a living fossil (Kubitzki K. 1990; Hori et al., 1997). Extracts of leaves have been used therapeutically for centuries (Newall et al., 1996). The main constituent are flavonoids and terpene trilactones. Ginkgo biloba exhibits a variety of interesting pharmacological activities such as increase in blood fluidity, antioxidant, prohealing, membrane stabilizing and improvement in cognition (Clostrew 1986; Kleijin & Knipschild 1992; Bairy & Rao 2001). Ginkgo biloba has promoted epithelization without altering wound contraction. In case of dead space wounds Ginkgo biloba has increased granulation tissue breaking strength without altering However, it did significantly enhance the content of hydroxyl-proline of granulation tissue. Further it is reported that the prohealing action of the Ginkgo biloba is due to the presence of Septilin
A proprietary herbal preparation claimed to be helpful in Gram negative and Gram positive infections (Gadekar et al., 1986; Sharma SK et al., 1986). It consists of Balsamodendron mukul (guggul), extracts Maharasanadi kwath, extract Phyllanthus embica, extract Tinospora cordifolia, Rubia cordifolia, extract Glycyrrhiza glabra and shanka bhasma which are claimed to have wound healing promoting action. Septilin has promoted gain in tensile strength in incision wound model, but at the same time, did not modify the granulation phase of healing (Udupa et al., 1989). In case of excision wound Septilin promoted epothelization and wound contraction (Nandakarni & Nadakarni 1954). This may be due its effect on migration and mitosis of epithelial cells and promotion of contraction of myo-fibroblasts, the later being now recognized as responsible for wound contraction (Gibbiani et al., 1992). Centella asiatica
Centella asiatica (Brahmi) also known as “gotu kola”, is the main herb in Ayurveda for nervous system, it is used in the repair of nervous tissue from crushing trauma, such as spinal injury, neuromuscular disorders, and to increase general brain function and memory concentration. Used extensively in Asia for the treatment of leprosy, gotu kola heals a host of skin conditions, including Only the aqueous extract suspension in 5% propylene glycol of Centella asiatica as compared to other extracts (viz. alcoholic, petroleum ether, chloroform extract) promoted wound healing in experimentally induced open wounds on topical administration in rats as evidenced by the increase in collagen content and thickness of epithelium (Rao et al., 1996). Suguna et al 1998 also demonstrated that alcoholic extract (oral and topical) of Centella asiatica improved the rate of wound healing in rats. It has also been shown that topical administration of the aqueous extract increased cellular proliferation, promoted the collagen synthesis at the wound site as evidenced by the increase in DNA, protein, collagen content of granulation tissue and in tensile strength. The treated wound epithelized faster as compared to control. Among the various formulations (ointment, cream and gel) of aqueous extract, the process of healing was better with gel formulation (Kumar et al., 1998). It has also been demonstrated that active principles (Triterpens and asiaticoside) promote rapid wound healing (Maquart et al 1999; Sukla et al Cissus quandrangularis
Cissus quandrangularis (Asthishankala) found in hotter parts of India. It is also wide spread in the drier parts of Africa and Arabia. Powdered roots are used for fracture of bone. The effect of the total extract of the plant on the healing of cortisone treated fracture has been compared with that of anabolic steroid nandrolone. Total extract of the plant, on parenteral administration, was found to neutralized anti-anabolic effect of cortisone in healing fractures. The stimulatory effect of the total extract was found to be greater than that of anabolic steroid probably due to its vitamin content (Prasad & Udapa 1963). The total extract was found hasten fracture healing by reducing the total convalescence period by 33% in experimental rats and dogs and produced a quick recovery in animals. The up-take of calcium is quick which helps in early completion of calcification process and earlier remodeling phenomenon. The tensile strength studies showed an early gain, leading to a 90% gain of its normal strength at the end of six weeks in comparison to 60% gain in strength noted in controls (Udupa & Prasad 1964). The plant extract has been found to influence fracture healing indirectly. Its effect on organic and inorganic phase of bone repair in normal and some pathological conditions like alloxan diabetes and in endocrine response during fracture healing suggested that parenteral administration of drug acted directly on the testes and through pituitary to release the androgenic hormone in to The other evidence of its androgenic property was its ability to produce a positive nitrogen balance, increase in body weight and total weight of testis of animals. A potent anabolic steroid isolated form the plant showed a marked influence on the rate of fracture healing by influencing early ingeneration process of all the connective tissue involved in the healing and quick mineralization of the callus (Satyavathi et al., 1976). Recently it has been reported that methanolic extract of Cissus quandrangularis promoted the healing process of experimentally fractured radius-ulna of dogs as evidenced by radiologically and histopathological examinations. The treated group also exhibited a reduction in serum calcium levels as compared to saline control animals (Deka et al., 1994). Miscellaneous prohealers from plants
The effects of Azadirachata indica, Ocimum sanctum, and Begia odorata on infected experimental wounds in laboratory animalshave been reported. All these plants, notably Ocimum sanctum promote healing (Thaker & Anjaria 1986). Euphoribia nerrifolia (aqueous extract) when applied topically facilitated the healing of surgically produced cutaneous wounds in guinea pigs. It has increased the gain in tensile strength, DNA content and promoted epithelization (Rasik et al., 1996). Both crude betal nut extract and its polyphenols promoted healing of incision and dead space wounds (Padmaja et al., 1993). Alcoholic extract of Indigofera aspalathoids has anti-inflammatory, wound healing and analgesic effect (Bhaskar et al., 1982). Fresh leaves of Kalanchoea integra showed encouraging results in inflammatory wound healing (Yadav & Yadav 1985). Mango butter which is extracted from the seeds of Mangifera indica has a wound healing property. It is used as application for ulcerations, fissures of lips, hands and chapped skin. Anecdotal evidence, some clinical observations, some animal model studies and few randomized clinical trials support the efficacy of honey in managing wounds (Molan 1998; Molan Reference:
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