AMAZING ANTIMICROBIAL AND WOUND HEALING POTENTIAL OF ACACIA CATECHU BARK EXTRACTS- A REVIEW

Plants are not only the source of food, oxygen, and shelter, but the same are also a potential foundation of medicines. Many natural and plant-derived antimicrobial and wound healing compounds have been recognized. In the present review, we have studied the main bioactive components of Acacia catechu with their medicinal roles. Most of these bioactive components are secondary metabolites which are produced by plants as side products of certain physiological reactions and are of no use for the plant itself. These components have been reported for their medicinal properties. In this review, we have mentioned some antibacterial, antifungal, and wound healing properties of A. catechu with its known bioactive components. The aim of this review article is, to enlist the possible potent bioactive components of the plant, against pathogenic microbes that can replace the use of chemicals and synthetic antibiotics for the treatment of skin infections and other diseases.


INTRODUCTION
Over long ago both humans and animal are depend on plants for food and also for their primary health care. In all over the world, more than 30% of the plant species are in use for medicinal purposes [1]. Recent data revealed that more than Rs. 20,00,000 million/annum is spent in the world market for plant-derived drugs. Though India is rich in vegetation and medicinal plants, but the Indian contribution for the same is less than Rs. 20,000 million/year [2,3]. India has great diversity and origin of many crops and medicinal plants. In India, the importance of medicinal plants has already been highlighted by several workers [3][4][5].
During the searching of available literature on antimicrobial plants and their extracts we have found many treatments based on plant-derived oil, extract, fine powder, etc. In addition to this, the data also revealed that from the 19 th sanctuary to 21 st sanctuary the use of these natural products is increased to double [4,6]. Many numbers and categories of plant-based antimicrobial and anti-infectious compounds have been recognized. More common of them are essential oils, alkaloids, flavonoids, sesqui-terpene lactones and naphtoquinones, etc [5,[7][8][9]. The same has documented for wound healing activity of different parts of plant extracts with or without their mechanism of action [8,[10][11][12][13][14].
In this section we have focused on antimicrobial and wound healing activities of Acacia catechu wild bark extracts. A. catechu Wild is one of the remarkable medicinal plants having immense medicinal potential in almost all parts of its body [15]. From long it has been widely using in Ayurveda and other medical systems for many diseases, both as an external and oral ingredient [16,17]. A. catechu is abundantly spread throughout the greater part of India due to its more adaptability in different atmospheric conditions, though in the desert and most humid areas limited varieties are reported [15][16][17][18]. In India, the most common varieties seen are A. catechu namely, Catechu, Catechuoides, and Sundra. From which, the Catechu variety is most commonly used to obtain Katha [18,19]. Some common names of this plant in different languages are "black catechu" in English, "Kher" in Gujarati, "Khayera" in Bengali, "Katha" in Hindi, "Kachinamara" in Kannada, "Kath" in Kashmiri, "Kharira" in Assamese, "Karingali" in Malayalam, "Kharira in Marathi" "Kaviri" in Urdu, "Chanbe" in Telugu etc [17,19].
Already the different parts of the same has been reported to be effective against skin diseases, melancholia, conjunctivits, diabetes, haemaptysis, hepato-protective activity, catarrah, cough, pruritus, leprosy, body surface infection, leucoderma, colon diseases, helminthiasis, norexia, diarrhea, dysentery, foul ulcers and wound treatment, hemorrhages, fever, anemia, and pharyngodynia [16,[18][19][20]. Because of such vast medicinal values, the same is widely used in various drug formulations too. A. catechu also known as Katha in Hindi which is a dispensable ingredient of pan (betel leaf preparation) chewed in India and other countries [19,21].
It is useful pan due to its capability to cure throat infections and dental problems [20]. This plant is also known for its various pharmacological effects like anti-inflammatory, antioxidative, antipyretic, anticancer, anti-ulcer, etc [20][21][22]. In this review, we have mentioned the antimicrobial and wound healing activities of this plant with special reference to its bark extracts. Here, we have also mentioned the studied bio-active components associated with the above-given activities with their mechanism of action. For basic understanding, a brief classification of plants with its morphology has also been given here.

MORPHOLOGY OF A. CATECHU PLANT
A. catechu wild is a medium to the higher-sized deciduous tree. Its stem is usually straight in the beginning and becomes branched after attending a certain height. The stems are usually brown to grayish in color with think bark [17]. This plant has bipinnately compound, small leaves with 2-6 mm length and arrange in pairs of pinnae. These leaves are supported by a glandular rachis in pairs. Inland areas the plant showed cylindrical inflorescence in the winter season with axillary pedunculate spike [17,19,20]. Its flowers are actinomorphic to zygomorphic, 5-10 cm long, sessile, pentamerous, which exhibit creamy whitish to pale yellow color with a 1-1.5 mm long campanulate calyx. The corolla is normally 2.5-3 mm long. Stamens are abundant in number and arrange in the far exerted form from the corolla [22]. These are white to yellowish-white filaments, having bisexual configuration and with single superior carpel; pod is one chambered legume, glabrous oblong, 3-10 seeded, straight, flat and brown with a triangular beak at the apex, shiny, narrowed at the base [21,[23][24][25].

ANTIMICROBIAL ACTIVITIES OF A. CATECHU BARK
In vitro studies of A. catechu wild are reported to have a broad spectrum anti-microbial and anti-fungal activity [23,26]. In the last decade, a number studied have put data on the antibacterial activity of Acacia bark extract against some specific and some multi-drug resistant disease-causing bacteria [27][28][29]. Some recent scientific studies have revealed the antibacterial activity of different extracts of the heartwood of A. catechu and reported strong antibacterial and antifungal activities in different experimental models. In few in-vitro evaluations too, the same is found to be exhibiting the antibacterial activity against enteric pathogens [30,31]. In species-specific anti-bacterial assays both ethanolic and aqueous extracts of the heartwood of A. catechu were seen to be successfully effective against Salmonella typhi, Shigella flexneri, Escherichia coli, Klebsiella pneumonia, Vibrio cholera, Pseudomonas aeruginosa and Staphylococcus aureus, etc bacterial cells [32][33][34]. In the same, the ethanolic extract was observed to be more efficient than the aqueous extract of the same also more efficient than the standard used [27,29,32]. Though, molecular level studies on the anti-microbial action of given bark extract is meager. But in few in-vitro antimicrobial assays the same; the phytochemical analysis showed that the alkaloids and carbohydrate substances are major bioactive compound work against pathogenic bacterial cells [33][34][35]. In one other research methanolic extract of A. catechu bark reported for its toxic effects against Bacillus subtilis, S. aureus, S. typhi, E. coli, P. aeruginosa and Candida albicans species of microorganisms [36]. To find out the responsible components of organic plant's extracts were separated by thin layer chromatography (TLC) and plant extracts were purified by column chromatography and were identified by Gas chromatography-mass spectrometry analysis. The analysis confirmed the presence of terpene, for example, camphor (nearly 76%) and phytol (nearly 28%) that to relate with its antibacterial and antifungal properties [28,32,36,37].
Phytochemical investigation of A. catechu wild shows the presence of alkaloids, flavonoids, glycosides, carbohydrates, phenolic compounds, different types of terpenes, saponins, steroids, and tannins which may be responsible for its anti-microbial activity. Methanolic extract of A. catechu wild (bark) has been known for antibacterial efficacy against both Gram-positive and Gram-negative bacteria. The same has also found to be helpful against S. aureus infection [22,25,30,34,[38][39][40].

WOUND HEALING ACTIVITIES OF A. CATECHU
Wounds are actually disrupted by cellular or histological structures associated with loss of integrity and function. Though nature has given each living being the auto-power of regeneration, but sometimes severe damage in tissues and/or infection with some pathogen may cause deadly consequences [41]. In such cases, treatment with an anti-microbial agent     [38,[40][41][42][43][44]. The aqueous extract of A. catechu at 3-6% w/w has been reported to exhibit significant wound healing activity. Furthermore, a similar evaluation has been made with other varieties of Acacia stem bark. Here also some data showed that the wound healing potential is due to its bioactive components and were determined by preliminary phyto-chemical screening.
In addition to this, in a number of studies, the formulation and ointment prepared from stem bark extracts in mice, rats, guinea pigs and human were seen significantly effective against microbial infected wounds [40,[44][45][46][47].
Some workers have revealed the wound healing activity of combined therapy of hydroalcoholic extract of A. catechu and Gymnema sylvestere in albino mice and found this is occur due to free radical scavenging [48][49][50]. Though, the mechanism and phyto-constitute involved in healing are not studied well. In addition to this the individual and additive impact of these phytochemicals is still not documented enough [30,[51][52][53]. Though one study revealed that the results of TLC showed the presence of flavonoids may be the responsible factor for this. Similar results were obtained by other workers with combined treatment with Beeswax from Apis mellifera, A. catechu bark extract, the oil of Sesamum indicum and oil of Azadirachta indica [54][55][56][57]. This combination was seen to reduce inflammation at wounded area and seen to cure wound faster than single extract treatment in mice. The same researchers also showed that the anti-inflammatory and wound healing activity occur due to prostaglandin synthesis via cyclo-oxygenase pathway in animal models [49,52,[58][59][60].

BIOACTIVE COMPONENTS OF A. CATECHU
The term "phyto-chemical" is generally used to describe chemicals obtained from plants that may improve the health status of organisms, but are not essential nutrients [45,[61][62][63][64]. There are sufficient evidence to support the health benefits of the plant in the form of roots, stems, leaves, bark, and fruits [65]. Above mentioned activities of A. catechu bark extract were observed to be associated with the quality and quantity of secondary metabolites produced by plants [66,67]. These seem to exert definite physiological actions through either scavenging of disease-causing free radicals or by the destruction of infectious agents from the human body [68]. Plant-based drugs are complex mixtures of bioactive compounds. The information of the potential health benefits of individual phyto-chemical is linked to the information of the health effects of a drug that contains these phytochemical [69,70].

Tiwari and Tiwari
A. catechu extracts have also played a role in chemistry, with various names of chemicals as catechin, catechol, and catecholamine being derived from bark. A. catechu is already been reported for the presence of caprylic acid methyl ester in about higher concentrations. The same has also been good source of Lauric acid, methyl ester (nearly about 28%). It has very high concentration (nearly 43%) of 2-Ethyl-3-methyl-1-butene and nearly 11% Myristic acid methyl ester which are known efficient bioactive compounds [72,73]. Some researchers carried out phytochemical studies of A. catechu and found poriferasterol, poriferasterolacyl glucosides, gallic acid, phlobatannins, d-galactose, aldobiuronic acid, d-rhamnose, and l-arabinose, etc [18,36,73,74].

DISCUSSION
Today, there are more than 121 pure chemical substances extracted from about 130 species of higher, used in the modern pharmacopeias throughout the world. Out of these, 89 plants derived drugs, currently used in modern medicine, were originally discovered through the study of traditional cures and plants folk knowledge of indigenous people [27,[75][76][77][78]. Medicinal plants are valuable for human ailments because of the presence of phytochemicals, which are present in the form of secondary metabolites such as alkaloids, saponin, glycosides, lactones, steroids etc. Several medicinal plants and their products are still widely used by the traditional medical practitioners for curing various diseases in their day to day practice [76][77][78][79]. Though, thousands side effects of allopathic medicines have been documented till now and much more are coming in front, so the use of herbal medicines is safer, cheaper and easily available therapeutic agents [34,58,80]. A. catechu based treatment is one of them.
A. catechu wild has great importance in ayurvedic system of medicine due to its medicinal properties [81][82][83]. It is well known for its therapeutic uses in dermatological, cardiovascular and respiratory diseases. Further, due to the presence of great percentage of acidic compounds the same is also used to reduce pH that inhibits the growth of microbial cells [36,38,56,84]. Catechin Obtained from the same is known antioxidant and reported to exhibit In vivo antioxidant properties against free radical attack [67,73]. The bark of A. catechu is used as a potent wound healing medicine. The extract of the bark of the same has been reported to exhibit an astringent effect in different experimental models [37,45,78,80,85]. Furthermore, it also exhibits antimicrobial property which prevents the growth of microbes on wounds. From a dental perspective, when used externally as a powder, it cures bleeding gums. It is used with great benefit internally in the form of gargle to alleviate sore throat, halitosis and dental caries. The literature has shown that it is antimicrobial against several oral pathogens, namely Streptococcus and Lactobacillus species [40][41][42][43][44][45][46]67,86].
During the last several decades, natural products with antimicrobial effects were investigated in order to eliminate the use of synthetic antibiotics which cause the resistance of microorganisms and can exhibit side effects to human health. Plants extract from 157 families including, A. catechu have been reported to be active against microorganisms [43,64,68,71,[85][86][87]. More so, A. catechu willd has also been reported for the synthesis and secretion of various active secondary metabolites which are already known for significant medicinal values, these are phenolic compound those serve as essential oils and also have significant insecticidal and antimicrobial activities. Because of such potential the same are routinely used in some pharmaceuticals, alternative medicines and natural therapies [28,36,[52][53][54][55][56][87][88][89][90].

CONCLUSION
In conclusion, the bark extract of A. catechu with different solvents are seen to be effective against pathogenic microbial strains and same has also seen to effective to cure different physiological diseases like diabetes, cancer, ulcer, anemia, inflammation, leucoderma, colon problems etc. Here, we have also found that these protective effects of the same are correlated with the presence of bioactive components which are basically produced by plant as secondary metabolites. These finding revealed that the individual as well as formulation of the bark extract of A. catechu with other protective compounds may be a potent and natural way to cure wounds infections than artificial harmful chemicals. With limited and guided doses the same can also used to treat abdominal infections too in case of abdominal infections. Though, further studies are needed to demonstrate the actual mechanism of action of same at the molecular level.

AUTHORS CONTRIBUTION
I, Mrs. Archana Tiwari, assistant professor, Government P.G. College Damoh, District Damoh, Madhya Pradesh, India has done the above complete review work including data search, data collection, interpretation to conclude the whole work under the guidance and supervision of Professor (Dr.) Avinash Tiwari, Head, School of studies in Microbiology, Jiwaji University, Gwalior, (M.P.) India, under whom I am pursuing my present research work as Ph.D. candidate.

CONFLICTS OF INTERESTS
No conflict.

SOURCE OF FUNDING
Nil.