**3.2 Chlorhexidine**

Chlorhexidine is a strong base and is most stable in the form of its salts. The original salts were chlorhexidine acetate and hydrochloride, both of which are relatively poorly soluble in water (Foulkes, 1973). Hence, they have been replaced by chlorhexidine digluconate. It has a cationic molecular component that attaches to negatively charged cell membrane area and causes cell lysis. Chlorhexidine is a potent antiseptic, which is used as a mouth rinse and endodontic irrigant. The later application is based on its substantivity and long-lasting antimicrobial effect which arise from binding to hydroxyapatite. Aqueous solutions of 0.1 to 0.2% concentrations are recommended for that purpose, while 2% is the concentration of root canal irrigating solutions usually found in the endodontic literature (Zamany et al., 2003). It is commonly held that chlorhexidine would be less caustic than sodium hypochlorite (Spngberg et al., 1973). A 2% chlorhexidine solution is irritating to the skin (Foulkes, 1973). As with sodium hypochlorite, heating chlorhexidine of lesser concentration could increase its local efficacy in the root canal system while keeping the systemic toxicity low (Evanov et al., 2004). Despite its usefulness as a final irrigant, chlorhexidine cannot be advocated as the main irrigant in standard endodontic cases, because: (a) chlorhexidine is unable to dissolve necrotic tissue remnants (Naenni et al., 2004), and (b) chlorhexidine is less effective on Gram-negative than on Gram-positive bacteria (Hennessey,1973). In a randomized clinical trial on the reduction of intracanal microbiota by either 2.5% NaOCl or 0.2% chlorhexidine irrigation, it was found that hypochlorite was significantly more efficient than chlorhexidine in obtaining negative cultures (Ringel, 1982). Most important CHX disadvantage is its inability of to dissolve necrotic tissue remnants and chemically clean the canal system.

#### **3.3 Iodine potassium iodine**

Iodine potassium iodine is a traditional root canal disinfectant with wide-spectrum antimicrobial activity. It is used in concentrations ranging from 2% to 5%).The oxidizing agent of this substance, iodine, reacts with free sulfhydryl groups of bacterial enzymes cleaving the disulfide bonds. It was manifested that calcium hydroxide–resistant

Antibacterial Agents in Dental Treatments 341

if incorrect laser parameters are used . Since the introduction of the laser in endodontics in 1971, several lasers were used to eliminating bacteria from root canals. The erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser has highest absorption in water and high affinity to hydroxyapatite, which makes it suitable for use in root canal therapy(Yamazaki et al., 2001; Yavari et al.,2010). Lasers have the ability to clean and effectively disinfect root canals; including eliminating highly resistant species such as *Enterococcus faecalis* (Le Goff et al., 1999). PDT (photodynamic therapy) is a new antimicrobial strategy that involves the combination of a nontoxic photosensitizer and a light source (Demidova&Hamblin., 2004). The excited photosensitizer reacts with molecular oxygen to produce highly reactive oxygen species, which induce injury and death of microorganisms (Wainwright, 1998). It has been established that PS, which possess a pronounced cationic charge, can rapidly bind and penetrate bacterial cells, and, therefore, these compounds show a high degree of selectivity for killing microorganisms compared with host mammalian cells (Maisch et al., 2005). PDT has been studied as a promising approach to eradicate oral pathogenic bacteria (Wilson, 2004) that cause diseases such as periodontitis, peri-implantitis and caries (Walsh, 2003). When PDT followed conventional endodontic therapy, there was significantly more killing and less bacterial growth than was

Abou-Rass, M. & Oglesby, SW. (1981). The effects of temperature, concentration, and tissue

Almyroudi, A.; Mackenzie, D. McHugh, S. & Saunders, WP. (2002). .The effectiveness of

Austin, JH. & Taylor, HD. (2002). Behavior of hypochlorite and of chloramine-T solutions in

Baker, N.; Liewehr, F. Buxton, T. & Joyce, A. (2004). Antibacterial efficacy of calcium

Basmadjian-charles, Cl.; Farge, P. & Lebrun, T. (2002). Factors influencing the long-term result of endodontic trearment.*Int Dent J*,Vol.52,pp.81-90,ISSN1309-100X. Beltz, RE.; Torabinejad, M. & Pouresmail, M. (2003). Quantitative analysis of solubilizing

Bently, Cd. (1994). Evaluation spatter and aerosol contamination during dental procedure. *J* 

Brent, J. (2009). Fomepizole for ethylene glycol and methanol poisoning. *N. Engl. J.* 

Burkhart, NW. & Crawford, JJ. (1997). Critical steps after cleaning: removing debris after

Bystrom, A. & Sundqvist, G. (1985). The antibacterial action of sodium hypochlorite and

EDTA in 60 cases of endodontic therapy. *Int Endod J,Vol.*18,pp.35-40,ISSN1365-2591.

sonication. J Am Dent Assoc,Vol.128,pp.456-463,ISSN0002-8177.

type on the solvent ability of sodium hypochlorite. *J Endod*,Vol.7, pp.376-

various disinfectants used as endodontic intracanal medications: an in vitro study. *J* 

contact with necrotic and normal tissue in vivo. *J Exp Med,*No. 27,pp.627-

hydroxide, iodine potassium iodine, betadine and betadine scrub with and without surfactant against E.faecalis in vitro. *Oral Surg Oral Med Oral* 

action of MTAD, sodium hypochlorite, and EDTA on bovine pulp and dentin . *J* 

seen after endodontic therapy alone (Garcez et al., 2007).

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microorganisms could be eradicated with combination of IKI and CHX (Baker et al., 2004). It shows relatively low toxicity in experiments using tissue cultures. An obvious disadvantage of iodine is a possible allergic reaction in some patients (Siren et al., 2004).

#### **3.4 MTAD (Mixture of Tetracyclin, Acid, Detergent)**

Biopure MTAD was recently introduced in the market as an antibacterial root canal cleanser .MTAD is a mixture of 3% tetracycline isomer (doxycycline), and 4.25% acid (citric acid), and 0.5% detergent (Tween 80). This biocompatible intracanal irrigant is commercially available as a two-part mix (Torabinejad et al., 2005). One of the characteristic of this solution is a high binding affinity of the doxycycline to dentin (Beltz et al., 2003).In this irrigant, doxycycline hyclate is used instead of its free base, doxycycline monohydrate, to increase the water solubility of this broad-spectrum antibiotic. MTAD has been reported to be effective in removing the smear layer due to citric acid action (Torabinejad et al., 2003), eliminating microbes that are resistant to conventional endodontic irrigants and medications (Shabahang& Torabinejad, 2003) and providing sustained antimicrobial activity. With every new product we are always concerned about the cytotoxicity to the underlying tissue. MTAD was compared with commonly used irrigants and medications The results showed MTAD to be less cytotoxic than eugenol, 3 percent H2O2, Ca(OH)2 paste, 5.25 percent NaOCl, Peridex, and EDTA. It is more cytotoxic than NaOCl at 2.63 percent, 1.31 percent, and 0.66 percent concentrations (Zaung et al., 2003).

#### **3.5 Calcium hydroxide**

Residual bacteria in the root canal have been held responsible for failures (Sjugren et al., 1990). It is generally believed that the number of remaining bacteria can be controlled by placing an interappointment medication within the prepared canal (Chong&Pitt Ford, 1992; Rahimi et al.,2010). Calcium hydroxide,Ca(OH)2 is the most common interappointment medication used which requires disinfection period of 7 days (Sjugren et al., 1991). However, some microbes such as *Enterococcus faecalis* (George et al., 2005) and *Candida albicans* (Waltimo et al., 1999) are resistant to it. Therefore, alternative intracanal medications have been sought to improve the eradication of bacteria before obturation. Chlorhexidine gluconate is effective against strains resistant to calcium hydroxide (Delany et al., 1989). Recent studies have suggested that CHX could be used in combination with calcium hydroxide to improve antimicrobial efficacy against calcium hydroxide-resistant microbes (Almyroudi et al., 2002). The high pH of calcium hydroxide formulations (pH=12.5) alters the biologic properties of bacterial lipopolysaccharides in the cell walls of gram-negative species and inactivates membrane transport mechanisms, resulting in bacterial cell toxicity (Siqueira & Lopes, 1999). However, as stated above, *E. faecalis* has been reported to be resistant to this effect as a result of its ability to penetrate the dentinal tubules and adapt to changing environment (George et al., 2005).

#### **3.6 Laser irradiation and photodynamic therapy**

Novel approaches to disinfecting root canals have been proposed recently that include the use of high-power lasers (Walsh, 2003) as well as photodynamic therapy (PDT) (Hamblin& Hasan, 2004). High-power lasers function by dose-dependent heat generation, but, in addition to killing bacteria, they have the potential to cause collateral damage such as char dentine, ankylosis roots, cementum melting, and root resorption and periradicular necrosis

microorganisms could be eradicated with combination of IKI and CHX (Baker et al., 2004). It shows relatively low toxicity in experiments using tissue cultures. An obvious disadvantage

Biopure MTAD was recently introduced in the market as an antibacterial root canal cleanser .MTAD is a mixture of 3% tetracycline isomer (doxycycline), and 4.25% acid (citric acid), and 0.5% detergent (Tween 80). This biocompatible intracanal irrigant is commercially available as a two-part mix (Torabinejad et al., 2005). One of the characteristic of this solution is a high binding affinity of the doxycycline to dentin (Beltz et al., 2003).In this irrigant, doxycycline hyclate is used instead of its free base, doxycycline monohydrate, to increase the water solubility of this broad-spectrum antibiotic. MTAD has been reported to be effective in removing the smear layer due to citric acid action (Torabinejad et al., 2003), eliminating microbes that are resistant to conventional endodontic irrigants and medications (Shabahang& Torabinejad, 2003) and providing sustained antimicrobial activity. With every new product we are always concerned about the cytotoxicity to the underlying tissue. MTAD was compared with commonly used irrigants and medications The results showed MTAD to be less cytotoxic than eugenol, 3 percent H2O2, Ca(OH)2 paste, 5.25 percent NaOCl, Peridex, and EDTA. It is more cytotoxic than NaOCl at 2.63 percent, 1.31 percent,

Residual bacteria in the root canal have been held responsible for failures (Sjugren et al., 1990). It is generally believed that the number of remaining bacteria can be controlled by placing an interappointment medication within the prepared canal (Chong&Pitt Ford, 1992; Rahimi et al.,2010). Calcium hydroxide,Ca(OH)2 is the most common interappointment medication used which requires disinfection period of 7 days (Sjugren et al., 1991). However, some microbes such as *Enterococcus faecalis* (George et al., 2005) and *Candida albicans* (Waltimo et al., 1999) are resistant to it. Therefore, alternative intracanal medications have been sought to improve the eradication of bacteria before obturation. Chlorhexidine gluconate is effective against strains resistant to calcium hydroxide (Delany et al., 1989). Recent studies have suggested that CHX could be used in combination with calcium hydroxide to improve antimicrobial efficacy against calcium hydroxide-resistant microbes (Almyroudi et al., 2002). The high pH of calcium hydroxide formulations (pH=12.5) alters the biologic properties of bacterial lipopolysaccharides in the cell walls of gram-negative species and inactivates membrane transport mechanisms, resulting in bacterial cell toxicity (Siqueira & Lopes, 1999). However, as stated above, *E. faecalis* has been reported to be resistant to this effect as a result of its ability to penetrate the dentinal tubules and adapt to changing environment (George et al., 2005).

Novel approaches to disinfecting root canals have been proposed recently that include the use of high-power lasers (Walsh, 2003) as well as photodynamic therapy (PDT) (Hamblin& Hasan, 2004). High-power lasers function by dose-dependent heat generation, but, in addition to killing bacteria, they have the potential to cause collateral damage such as char dentine, ankylosis roots, cementum melting, and root resorption and periradicular necrosis

of iodine is a possible allergic reaction in some patients (Siren et al., 2004).

**3.4 MTAD (Mixture of Tetracyclin, Acid, Detergent)**

and 0.66 percent concentrations (Zaung et al., 2003).

**3.6 Laser irradiation and photodynamic therapy** 

**3.5 Calcium hydroxide**

if incorrect laser parameters are used . Since the introduction of the laser in endodontics in 1971, several lasers were used to eliminating bacteria from root canals. The erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser has highest absorption in water and high affinity to hydroxyapatite, which makes it suitable for use in root canal therapy(Yamazaki et al., 2001; Yavari et al.,2010). Lasers have the ability to clean and effectively disinfect root canals; including eliminating highly resistant species such as *Enterococcus faecalis* (Le Goff et al., 1999). PDT (photodynamic therapy) is a new antimicrobial strategy that involves the combination of a nontoxic photosensitizer and a light source (Demidova&Hamblin., 2004). The excited photosensitizer reacts with molecular oxygen to produce highly reactive oxygen species, which induce injury and death of microorganisms (Wainwright, 1998). It has been established that PS, which possess a pronounced cationic charge, can rapidly bind and penetrate bacterial cells, and, therefore, these compounds show a high degree of selectivity for killing microorganisms compared with host mammalian cells (Maisch et al., 2005). PDT has been studied as a promising approach to eradicate oral pathogenic bacteria (Wilson, 2004) that cause diseases such as periodontitis, peri-implantitis and caries (Walsh, 2003). When PDT followed conventional endodontic therapy, there was significantly more killing and less bacterial growth than was seen after endodontic therapy alone (Garcez et al., 2007).

#### **4. References**


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**17** 

*Malaysia* 

*Andrographis paniculata* **(Burm.f)** 

*1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, 2Department of Biomedical Science, Faculty of Allied Health Sciences,* 

*International Islamic University Malaysia, Kuantan, Pahang,* 

**Wall. ex Ness: A Potent Antibacterial Plant** 

Qamar Uddin Ahmed1, Othman Abd. Samah2,\* and Abubakar Sule2

Antibacterial agents of plant origin have vast therapeutic potential. They are valuable in the treatment of infectious diseases while simultaneously extenuating many of the side effects that are often associated with synthetic antibacterial agents. The beneficial medicinal effects of plant materials typically result from the combinations of secondary metabolites such as alkaloids, steroids, tannins, phenol compounds, flavonoids and resins fatty acids gums which are capable of producing definite physiological action on body (Paul *et al*., 2006). Nowadays, multiple drug resistance has developed due to indiscriminate use of commercial antimicrobial drugs commonly used in the treatment of infectious disease. In addition to this problem, antibiotics are sometimes associated with adverse side effects on the host including hypersensitivity, immune-suppression and allergic reactions. This situation forced scientists to search for new antimicrobial substances. Giving the alarming incidence of antibiotic resistance in bacteria of medical importance, there is a constant need for new and effective therapeutic agents. Therefore, there is a need to develop alternative antimicrobial drugs for the treatment of infectious diseases from medicinal plants. Biodiversity is a precious source for modern biotechnology. It is a source which potentially holds innovative and sustainable solutions to a broad range of important problems for modern society. Improved cooperation between the natural product chemists and the microbiologists is a productive step to speed up the process of evaluating these potentialities. Moreover, microbiologists and natural product chemists in tropical countries, with the richest flora and fauna placed right at their door step have a very central position. They are essential for building up international scientific cooperation, with the objective of expanding our understanding of biological and biochemical diversity, and based on this bringing forward more biological solutions. The entire process is built on a principle of fairness and equity in sharing of the benefits and respecting the State's sovereign right to its own resources. After figuring out the chemical structures of secondary metabolites, it is considered crucial to know how useful these molecules might be in terms of medicinal properties. During the past 40 years, numerous novel compounds have been isolated from different plants and marine organisms and many of these have been reported to have core biological activities, some of which are of interest from the point of view of potential drug

**1. Introduction** 

development (Lene, 1996; Gerald, 2001).

