Biojournal of Science and Technology
Volume 4, ISSN:2410-9754, Article ID: m160001

Review Article

Antibacterial properties of Neem(Azadirachta indica): a mini review

Shaila Haque1, Sumaiya Farah Khan2, Laisa Ahmad Lisa2*

Date of Acceptance: 30/08/2016
Published in Online: 2016/09/18

1Department of Biochemistry, Primeasia University, Dhaka-1213 Bangladesh.

2Department of Microbiology, Jagannath University, Dhaka-1100, Bangladesh.

Address Correspond to:
Laisa Ahmad Lisa Department of Microbiology, Jagannath University, Dhaka-1100, Bangladesh E-mail: [email protected]

Academic editor: Dr. M. Hafizur Rahman

To Cite This Article:
Shaila Haque,Sumaiya Farah Khan,Laisa Ahmad Lisa*. Antibacterial properties of Neem(Azadirachta indica): a mini review. Biojournal of Science and Technology.Vol:4,2016

Download PDF | Citation Download | Views: [wpstatistics stat=pagevisits time=total]

Abstract

Neem (Azadirachta indica) had been well known for its medicinal values in the ancient Asian country like Bangladesh, India had probably been the most useful medicinal plant in South Asia.From leaf to root, each and every part of the neem tree has also been used in Bangladesh and neighboring countries for over two thousand years for their medicinal properties. Neem tree drew the attention of natural products chemists by Ayurveda. During the last five decades, considerable progress has been achieved regarding the biological activities and medicinal applications of neem. The current review describes the major biological activities, antibacterial properties of some of the neem compounds isolated, as well as some other environmental, clinical and medicinal applications.

Keywords:

Authors Link:
, ,

Content Section

The neem (Azadirachta indica) or margosa tree, also called Indian lilac, belongs to the Meliaceae (mahogany) family(Schmutterer 1990). Its origin is mainly in southern and southeastern Asia as it is commonly found in Bangladesh, India, Pakistan and Nepal but currently grows in tropical and subtropical areas of Africa, America, and Australia(Koul et al. 1990). Various parts of this plant such as leaves, barks, fruits, seeds and roots (Figure 1) contain compounds with proven anti-inflammatory, anti-pyretic, anti-histamine, anti-fungal, antibacterial, anti-ulcer, analgesic, anti-arrhythmic, anti-tubercular, anti-malarial, diuretic, spermicide, anti-arthritic, anti-protozoal, insect repellant, anti-feedant, anti-hormonal properties and anti-cancerous uses(Biswas et al. 2002, Kumar and Navaratnam 2013, Tiwari et al. 2014).That’s why neem is also referred to as “Village pharmacy”, “Tree of the 21st century” and “A tree for solving global problems” (Paul et al. 2011, Kumar and Navaratnam 2013).
Various photographs of A. indica showing (A) a whole tree, (B) flowers, (C) fruits, (D) Seeds, (E) twinges and (F) roots.

Figure 1.Various photographs of A. indica showing (A) a whole tree, (B) flowers, (C) fruits, (D) Seeds, (E) twinges and (F) roots.

Taxonomy of Azadirachta indica

De Jussieu (De Jussieu 1830) has described the neem tree as A. indica as early as in 1830 and its taxonomic position is as Table 1.

 Table 1: Taxonomic position of Azadirachta indica (neem).

Order Rutales
Suborder Rutinae
Family Meliaceae
Subfamily Melioideae
Tribe Melieae
Genus Azadirachta
Species indica

Morphology

Neem is a large evergreen tree that may grow up to 20meter in height. The leaves are alternate and the leaflets contain 8-19 leaves that may appear in March-April and they are bitter in taste (Puri 2003).

Although, in early daysthe neem has been introduced in many countries, mainly for afforestation and fuelwood production in dry areas including use as an avenue or shade tree and as a producer of natural pesticides; but in recent days the scientists are more interestedto this multi-beneficial plant, and thus many other important roles have been discovered.In this reviewthe active ingredients and the overall role of neem specially the antibacterial ones are summarized.

Biologically active compounds
Azadirachta indica has compound of variousconstituents that play role in diseasemanagement.Although more than 300 natural products have been isolated from different sections of this tree, with new compounds added to the list every year till now (Sharma et al. 2015), but a few of them have been studied for biological activity (Biswas et al. 2002). Among them some compounds are well-known for their beneficial bioactive actions like anti-inflammatory,antifungal,antibacterialetc. as shown in Table 2.

 Table 2. Some bioactive compounds from neem (Biswas et al. 2002).

Neem compound Source Biological activity
Nimbidin Seed oil Anti-inflammatory, Antiarthritic, Antipyretic, Hypoglycaemic, Antigastric ulcer, Spermicidal, Antifungal, Antibacterial, Diuretic
Nimbin Seed oil Spermicidal
Azadirachtin Seed Antimalarial
Mahmoodin Seed oil Antibacterial
Gallic acid, (–) epicatechin and catechin Bark Anti-inflammatory,Immunomodulatory

 

Polysaccharides GIa , GIb Bark Antitumour
Cyclic trisulphide and cyclic tetrasulphide Leaf Antifungal

Antibacterial properties
General studies
Werner Fabryet. al.(Fabry et al. 1998) in their study tested the extracts of Azadirachta indica (stem bark and leaves) against 105 strains of bacteria from seven genera (Staphylococcus, Enterococcus, Pseudomonas, Escherichia, Klebsiella, Salmonella, Mycobacterium). The minimum inhibitory concentration reached by 50% (MIC50%) and 90% (MIC90%) of the strains for the extracts of A. indica (stem bark) ranged from 0.25–2 mg/ml and from 0.5 to 2 mg/ml, respectively.Moreover extracts of the edible part (flowers) of A. indicaalso showed antibacterial activity against Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella infantis(Alzoreky and Nakahara 2003). Because of this crucial role of A. indica in antibacterial activity, further studies have been carried out and found that methanolic and acetone extracts were more effective against the bacteria compared to that of aqueous extract (Rajasekaran 2008, Singh et al. 2016).

Studies at molecular level demonstrate that A.indica contains chemical constituents of alkaloids, terpenoids tannins and flavonoids(Makkar et al. 2007)responsible to overcome microbial infection specially having antioxidant andantimicrobial biological activities(Scalbert and Williamson 2000, Manach et al. 2004). These chemicalsmight show the antibacterial activity having the ability tomake a complex with the bacterial cell walls. Inhibitory activity towards DNA topoisomerase enzyme II by azadiractin, a bioactive metabolite of neem(Scalbert 1991) might also involvein the antibacterial potential. Moreover, the Gram-positive bacterial strains were foundmore sensitivethan the Gram-negative ones(Sinaga et al. 2016).

Specific diseases
From a preliminary study it has been found that β-sitosterol, a phytochemical found in A. indica has a role in strengthening the immune system(Bumrela and Naik 2011). Hence, many people apply it on skin for treating wounds, burns (www.webmd.com) and for curing skin diseases (Pandey et al. 2014). The phytoconstituents, β-sitosterol along with β carotene in the methanol extract are also a well- known antibacterial agent functioning against a broad spectrum of bothGram negative and Gram positive bacteria, including S. aureus(Bumrela and Naik 2011).

A clinical treatment study using formulation of mucoadhesive dental gel containing Azadirachta indica leaf extract (25 mg/g) showed microbial evaluation of Streptococcus mutans and Lactobacilli species which was carried out to determine the total decrease in the salivary bacterial count (Pai et al. 2004). Enterococcus faecalis is the most commonly found bacteria in failed root canal. Sodium hypochlorite (NaOCl) and 2% chlorhexidine (CHX) are used as the root canals irrigants (Bazvand et al. 2014), whereas, constant increase in antibiotic resistant strains and side effects of chemical irrigants has led to the search for alternative herbal medicaments.Thus,Gonmode et al.(Bazvand et al. 2014), Hegde et al.(Hegde and Kesaria 2013), and Damre(Damre 2015) in their studies observed higher inhibition zone of E.faecalisculture by neem leaves extract compared to that of NaOCl.Further studies showed that the antibacterial activity of neem could be due to the presence of several active constituents like nimbidin, nimbin, nimbolide, gedunin, azadirachtin, mahmoodin, margolone and cyclictrisulphide (Biswas et al. 2002). Moreover, 10% nonabsorbable neem oil chip has antibacterial effect against Porphyromonas gingivalis, a periodontal pathogen (Vennila et al. 2016).

Antibacterial activity along with antisecretory and antihemorrhagic activity was found against the multi-drug-resistant Vibrio cholerae(serotypes O1, O139 and non-O1, non-O139), a causative agent of watery diarrhea such as cholera, from the methanol extract of neem leaf (Thakurta et al. 2007).

Recently, endophytic actinomycetes from Azadirachta indica have beenpaying attentionto explore the novel bioactive natural compounds that can be used to design new drugs replacing those against which pathogenic strains have rapidly acquired resistance(Verma et al. 2009). In recent years, more than seven newly defined antibiotic compounds were revealed from endophytic Streptomyces(Castillo et al. 2002, Pullen et al. 2002, Ezra et al. 2004). Some of them (e.g., Coronamycin) had remarkable activity against malarial parasites(Pullen et al. 2002, Ezra et al. 2004). This observationrecommends that endophytic actinomycetes offer promise for the discovery of unique natural products with pharmaceutical prospective.

Other environmental, clinical and medicinal applications
The whole neem plant is full of domestic, industrial and pharmaceutical values as shown in Table 3.

 Mainly owing to its various effects on insects, azadirachtin (AZ, a steroid-like tetranortriterpenoid (limonoid)) is considered the most important active ingredient in neem seed kernels (NSK)(Schmutterer 1990). It can act as a green corrosion (deterioration of materials by chemical processes) inhibitor against various metals, especially for mild steel, aluminum and tin (Sharma et al. 2015).

Table 3. Medicinal uses of different parts of neem (A. indica) tree (Paul et al. 2011).

Parts of Neem                       Treatable ailments
Bark Alternative and curative of fever, Analgesic
Twig Intestinal worms, spermatorrhoea, obstinate urinary disorder, diabetes, cough, asthma, piles, phantom tumor
Leaf Intestinal worms, anorexia, biliousness, skin ulcers, cancer, leprosy, eye problem, epistaxis
Flower Bile suppression, elimination of intestinal worms, phlegm
Fruit Intestinal worms, urinary disorder, epistaxis, piles,  phlegm, eye problem, diabetes, wounds, leprosy
Seed Intestinal worms, leprosy, cancer
Oil Intestinal worms, leprosy
Gum Ulcers, skin diseases, scabies, wounds

From various research articles it can be presumed that A. indica has chemopreventive and chemotherapeutic potential against various cancer models.For instance,(i) crude aqueous extracts of A. indica leaves and seeds inhibited the growth of Ehrlich ascites carcinoma cells or acting against the breast cancer cells(Amer et al. 2010), (ii) against gastrointestinal tract and associated cancers,a neem leaf glycoprotein (NLGP) was found effective (Goswami et al. 2010), and also working against (iii) OVCAR-5 ovary cancer cells (Sastry et al. 2006), (iv) ethanolic and aqueous extracts of neem leaf effective in case of hematological cancer reducing the viability of E6-1 leukemic cells (Roma et al. 2015), (v) ethyl acetate fraction of crude leaf extract showed modest antiproliferative effects against A-549 lung cancer cells (Jafari et al. 2013) and other compounds against prostate cancer, skin cancer, connective tissue cancers, paracetamol hepatotoxicity (Chattopadhyay 2003) and so on. The details of these effective compounds and possible mechanism of actions are reviewed earlier (Patel et al. 2016).IRAB, a fractionated neem-leaf extract was reported having activities against Malaria, HIV/AIDS and cancer has been developed into a drug and currently marketed in Nigeria as IRACAP® (Anyaehie 2009).

Several studies also showed that the neem seed can be used as a protein source in animal feed (Adjorlolo et al. 2016).Other than most non-leguminous tree leaves, neem leaves have higher crude protein concentration which coupled with a low level of fiber, making it suitable as a protein supplement for ruminants on poor quality diets. And, recent studies also showed that combined use of the natural antioxidant neem with other plant (e.g. curcumin) having antioxidant property may reduce the inhibitory effect of α-Linolenic acid towards MCF-7 breast cancer cells(Cheung et al. 2016).

Practical problems and safety evaluation
Despiteof versatile qualities of neem, it isrequired to be used with care as indiscriminate use of its extracts may cause unpleasant side effects.It may also be a reason for damage to liver and kidney that may result in jaundice and in low or no urine production, respectively. Moreover, it might also destroy red blood corpuscles (Haque et al. 2006).Furthermore, neurotoxicity might be caused in case of excessive use of neem(Paul et al. 2011).Another important concern about its use is its ability to interfere with the normal reproductive systems fostering infertility (Sinha et al. 1984, Lal et al. 1986, Khosla et al. 2000, Khillare and Shrivastav 2003).

Conclusion
It can be concluded that various components of A. indicaseems to act as promising agents against several diseases.Further studies should be conducted on its clinical as well as industrial, environmental and pharmaceutical applications.

Conflict of Interests
None to declare.

Reference

  1. LK Adjorlolo, EC Timpong-Jones, S Boadu and T Adogla-Bessa, 2016. Potential contribution of neem (Azadirachta indica) leaves to dry season feeding of ruminants in West Africa. Development 28: 5.
  2. NS Alzoreky and K Nakahara, 2003. Antibacterial activity of extracts from some edible plants commonly consumed in Asia. International journal of food microbiology 80(3): 223-230.
  3. Hassan Amer, Wafaa A Helmy and Hanan AA Taie, 2010. IN VITRO ANTITUMOR AND ANTIVIRAL ACTIVITIES OF SEEDS AND LEAVES NEEM (AZADIRACHTA INDICA) EXTRACTS. International Journal of Academic Research 2(2).
  4. U Anyaehie, 2009. Medicinal properties of fractionated acetone/water neem (Azadirachta indica) leaf extract from Nigeria: a review. Nigerian Journal of Physiological Sciences 24(2).
  5. Leila Bazvand, Mohammad Ghasem Aminozarbian, Alireza Farhad, Hamid Noormohammadi, Seyed Mohsen Hasheminia and Sina Mobasherizadeh, 2014. Antibacterial effect of triantibiotic mixture, chlorhexidine gel, and two natural materials Propolis and Aloe vera against Enterococcus faecalis: An ex vivo study. Dental research journal 11(4): 469.
  6. Kausik Biswas, Ishita Chattopadhyay, Ranajit K Banerjee and Uday Bandyopadhyay, 2002. Biological activities and medicinal properties of neem (Azadirachta indica). CURRENT SCIENCE-BANGALORE- 82(11): 1336-1345.
  7. Shrinivas B Bumrela and Suresh R Naik, 2011. Identification of?-carotene and?-sitosterol in methanolic extract of Dipteracanthus patulus (Jacq) nees and their role in antimicrobial and antioxidant activity. International Journal of Phytomedicine 3(2): 204.
  8. Uvidelio F Castillo, Gary A Strobel, Eugene J Ford, Wilford M Hess, Heidi Porter, James B Jensen, Heather Albert, Richard Robison, Margret AM Condron and David B Teplow, 2002. Munumbicins, wide-spectrum antibiotics produced by Streptomyces NRRL 30562, endophytic on Kennedia nigriscansa. Microbiology 148(9): 2675-2685.
  9. R_R Chattopadhyay, 2003. Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract: Part II. Journal of ethnopharmacology 89(2): 217-219.
  10. T Cheung, Poonam Singh-Nee Nigam and Richard Owusu-Apenten, 2016. Antioxidant Activity of Curcumin and Neem (Azadirachta indica) Powders: Combination Studies with ALA Using MCF-7 Breast Cancer Cells. Journal of Applied Life Sciences International 4(3): 1-12.
  11. Prajkta G Damre, 2015. Comparative Evaluation of Antimicrobial Activity Of herbal vs chemical Root Canal Irrigants against E. Faecalis-An in Vitro Study. International Journal 3(9): 1563-1572.
  12. Adrien De Jussieu, 1830. Mem. Mus. Hist. Nat. 19(220).
  13. David Ezra, Uvidelio F Castillo, Gary A Strobel, Wilford M Hess, Heidi Porter, James B Jensen, Margaret AM Condron, David B Teplow, Joseph Sears and Michelle Maranta, 2004. Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp.(MSU-2110) endophytic on Monstera sp. Microbiology 150(4): 785-793.
  14. Werner Fabry, Paul O Okemo and Rainer Ansorg, 1998. Antibacterial activity of East African medicinal plants. Journal of ethnopharmacology 60(1): 79-84.
  15. Shyamal Goswami, Anamika Bose, Koustav Sarkar, Soumyabrata Roy, Tathagata Chakraborty, Utpal Sanyal and Rathindranath Baral, 2010. Neem leaf glycoprotein matures myeloid derived dendritic cells and optimizes anti-tumor T cell functions. Vaccine 28(5): 1241-1252.
  16. Enamul Haque, Ishita Mandal, Smarajit Pal and Rathindranath Baral, 2006. Prophylactic dose of neem (Azadirachta indica) leaf preparation restricting murine tumor growth is nontoxic, hematostimulatory and immunostimulatory. Immunopharmacology and immunotoxicology 28(1): 33-50.
  17. Vibha Hegde and Dhaval P Kesaria, 2013. Comparative evaluation of antimicrobial activity of neem, propolis, turmeric, liquorice and sodium hypochlorite as root canal irrigants against E. Faecalis and C. Albicans–An in vitro study. Endodontology 25(2): 38-45.
  18. Samineh Jafari, Soodabeh Saeidnia, Homa Hajimehdipoor, Mohammad Reza Shams Ardekani, Mohammad Ali Faramarzi, Abbas Hadjiakhoondi and Mahnaz Khanavi, 2013. Cytotoxic evaluation of Melia azedarach in comparison with, Azadirachta indica and its phytochemical investigation. DARU Journal of Pharmaceutical Sciences 21(1): 1.
  19. B Khillare and TG Shrivastav, 2003. Spermicidal activity of Azadirachta indica (neem) leaf extract. Contraception 68(3): 225-229.
  20. P Khosla, Sangeetha Bhanwra, J Singh, S Seth and RK Srivastava, 2000. A study of hypoglycaemic effects of Azadirachta indica (Neem) in normal and alloxan diabetic rabbits. Indian Journal of Physiology and Pharmacology 44(1): 69-74.
  21. Opender Koul, Murray B Isman and CM Ketkar, 1990. Properties and uses of neem, Azadirachta indica. Canadian Journal of Botany 68(1): 1-11.
  22. Venugopalan Santhosh Kumar and Visweswaran Navaratnam, 2013. Neem (Azadirachta indica): Prehistory to contemporary medicinal uses to humankind. Asian Pacific journal of tropical biomedicine 3(7): 505-514.
  23. Ramesh Lal, A Sankaranarayanan, VS Mathur and PL Sharma, 1986. Antifertility effect of neem oil in female albino rats by the intravaginal & oral routes. The Indian journal of medical research 83: 89-92.
  24. Harinder PS Makkar, Perumal Siddhuraju and Klaus Becker (2007). Plant secondary metabolites, Humana Press.
  25. Claudine Manach, Augustin Scalbert, Christine Morand, Christian Rémésy and Liliana Jiménez, 2004. Polyphenols: food sources and bioavailability. The American journal of clinical nutrition 79(5): 727-747.
  26. M Raveendra Pai, Leelavathi D Acharya and N Udupa, 2004. Evaluation of antiplaque activity of Azadirachta indica leaf extract gel—a 6-week clinical study. Journal of ethnopharmacology 90(1): 99-103.
  27. Garima Pandey, KK Verma and Munna Singh, 2014. Evaluation of phytochemical, antibacterial and free radical scavenging properties of Azadirachta indica (neem) leaves. Int. J. Pharm. Pharm. Sci 6(2): 444-447.
  28. Shradha M Patel, Kalyan C Nagulapalli Venkata, Piyali Bhattacharyya, Gautam Sethi and Anupam Bishayee (2016). Potential of neem (Azadirachta indica L.) for prevention and treatment of oncologic diseases. Seminars in cancer biology, Elsevier.
  29. Rajkumar Paul, Murari Prasad and Nand K Sah, 2011. Anticancer biology of Azadirachta indica L (neem): a mini review. Cancer biology & therapy 12(6): 467-476.
  30. Christian Pullen, Petra Schmitz, Kristina Meurer, Daniel D v Bamberg, Stephanie Lohmann, Suzelei De Castro Franca, Ingrid Groth, Brigitte Schlegel, Ute Möllmann and Friedrich Gollmick, 2002. New and bioactive compounds from Streptomyces strains residing in the wood of Celastraceae. Planta 216(1): 162-167.
  31. Harbans Singh Puri (2003). Neem: the divine tree Azadirachta indica, CRC Press.
  32. C Rajasekaran, 2008. Investigations on antibacterial activity of leaf extracts of Azadirachta indica A. Juss (Meliaceae): a traditional medicinal plant of India. Ethnobotanical Leaflets 2008(1): 161.
  33. Alessia Roma, Pamela Ovadje, Matthew Steckle, Leah Nicoletti, Ammar Saleem and Siyaram Pandey, 2015. Selective Induction of Apoptosis by Azadarichta indica Leaf Extract by Targeting Oxidative Vulnerabilities in Human Cancer Cells. Journal of Pharmacy & Pharmaceutical Sciences 18(4): 729-746.
  34. BS Sastry, K Suresh Babu, T Hari Babu, S Chandrasekhar, PV Srinivas, AK Saxena and J Madhusudana Rao, 2006. Synthesis and biological activity of amide derivatives of nimbolide. Bioorganic & medicinal chemistry letters 16(16): 4391-4394.
  35. Augustin Scalbert, 1991. Antimicrobial properties of tannins. Phytochemistry 30(12): 3875-3883.
  36. Augustin Scalbert and Gary Williamson, 2000. Dietary intake and bioavailability of polyphenols. The Journal of nutrition 130(8): 2073S-2085S.
  37. Heinrich Schmutterer, 1990. Properties and potential of natural pesticides from the neem tree, Azadirachta indica. Annual review of entomology 35(1): 271-297.
  38. Sanjay K Sharma, Anjali Peter and Ime Bassey Obot, 2015. Potential of Azadirachta indica as a green corrosion inhibitor against mild steel, aluminum, and tin: a review. Journal of Analytical Science and Technology 6(1): 1.
  39. Melese Sinaga, Kumar Ganesan, Suresh Kumar P Nair and Sharmila Banu Gani, 2016. PRELIMINARY PHYTOCHEMICAL ANALYSIS AND IN VITRO ANTIBACTERIAL ACTIVITY OF BARK AND SEEDS OF ETHIOPIAN NEEM (AZADIRACHTA INDICA A. JUSS).
  40. Aditi Singh, Parul Tripathi, Apeksha Srivastava, S Marzia Ali and Lavie Rekhi, 2016. Antibacterial activity of six indigenous Indian plants: Acacia nilotica (Fabaceae), Albizia saman (Fabaceae), Azadirachta indica (Meliaceae), Carica papaya (Caricaceae), Cymbopogon citratus (Poaceae) and Mangifera indica (Anacardiaceae). African Journal of Biotechnology 15(16): 666-669.
  41. KC Sinha, SS Riar, RS Tiwary, AK Dhawan, J Bardham, Pauline Thomas, AK Kain and RK Jain, 1984. Neem oil as a vaginal contraceptive. Indian Journal of Medical Research 79: 131-136.
  42. Prarthana Thakurta, Poulami Bhowmik, Souryadeep Mukherjee, Tapas K Hajra, Amarendra Patra and Prasanta K Bag, 2007. Antibacterial, antisecretory and antihemorrhagic activity of Azadirachta indica used to treat cholera and diarrhea in India. Journal of ethnopharmacology 111(3): 607-612.
  43. Ruchi Tiwari, Amit Kumar Verma, Sandip Chakraborty, Kuldeep Dhama and Shoor Vir Singh, 2014. Neem (Azadirachta indica) and its potential for safeguarding health of animals and humans: A review. Journal of Biological Sciences 14(2): 110.
  44. K Vennila, S Elanchezhiyan and Sugumari Ilavarasu, 2016. Efficacy of 10% whole Azadirachta indica (neem) chip as an adjunct to scaling and root planning in chronic periodontitis: A clinical and microbiological study. Indian Journal of Dental Research 27(1): 15.
  45. Vijay C Verma, Surendra K Gond, Anuj Kumar, Ashish Mishra, Ravindra N Kharwar and Alan C Gange, 2009. Endophytic actinomycetes from Azadirachta indica A. Juss.: isolation, diversity, and anti-microbial activity. Microbial ecology 57(4): 749-756.