Herbal Sealers in Endodontics – A Systematic Review

Manoj Chandak*1, Pradnya Nikhade1, Rakhi Chandak2, Pavan Bajaj3, Kajol Relan1, Pooja Chandak1, Chanchal Rathi1, Madhulika Chandak1 1Department of Conservative Dentistry and Endodontics, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Medical Sciences (DU), Sawangi (Meghe), Wardha, Maharashtra, India 2Department of Oral Medicine and Radiology, SDKS Dental College and Hospital, Hingna, Nagpur, Maharashtra, India 3Department of Periodontology, Department of Conservative Dentistry and Endodontics, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Medical Sciences (DU), Sawangi (Meghe), Wardha, Maharashtra, India


INTRODUCTION
Root canal infections usually occur due to many micro-organisms, among which most frequent are the obligatory anaerobes. One of the predominantly found microbes is Candida albicans that requires special attention. They commonly occur in long-standing periapical infection. They also occur in retreatment cases. Another main microorganism commonly occurring in the bio ilm is Enterococcus faecalis (Schirrmeister et al., 2009). Both micro-organisms have a unique feature of surviv-ing harsh conditions. They can modify their occurrence according to the environment. This is mainly because of their physicochemical properties and bio ilm formation (Waltimo et al., 2004).
Endodontic therapy aims for disinfection as well as cleanliness of the canal. The primary objective of this therapy is to make the root canals free from microbes and debris that are mainly responsible for pulp and periapical infection. This can be achieved by chemical treatment of the root canal system. This treatment comprises of biomechanical preparation, irrigation and interappointment medicaments (Sundqvist et al., 1998). Complete disinfection of the root canal and creating favourable conditions are required for periapical healing (Chandak et al., 2017). However large proportions of the root canal remain untouched during instrumentation leading to the catastrophe of the root canal treatment. Irrigation helps in proper disinfection as well as eradication of infected micro-organism. Various irritants are used, such as NaOCl, Chlorhexidine, hydrogen peroxide, ethylenediaminetetraacetic acid (EDTA), citric acid etc (Zehnder, 2006). However, these irrigants may have several disadvantages.
Propolis is an effective anti-in lammatory, antioxidant, antimicrobial agent. This is due to the presence of phenolic compounds. Also, there are lavonoids and other aromatic compounds. It is a brownish resinous element. It is collected from plants and is used to keep the environment sterile (Kandaswamy et al., 2010).
Indian Neem is also named as Azadirachta Indica, and it has anti-adherence property. Due to this bacterial cell adhesion is transformed. It affects the colonizing property of bacteria. It is also a good antioxidant. It shows antimicrobial activity against E.faecalis and C.albicans (Chandak et al., 2018).
Morinda Citrifolia Juice (MCJ) is derivative from Morinda Citrifolia which is a fruit-bearing tree of the coffee family. It has a chelating ability. It removes the smear layer effectively. It also has antimicrobial activity against anaerobic bacteria that is E. faecalis and C. albicans (Jainkittivong et al., 2009).
Green tea extracts and garlic extracts are also effectively used in endodontics. They have antimicrobial, antioxidant, and anti-in lammatory property.
Many in-vitro and ex-vivo studies have been carried out to analyze the effectiveness of these herbal medicaments against Candida Albicans infection in root canals.

Research Question
Whether using herbal sealers is an effective treatment against Candida albicans in case of retreatment of Root canals ??
Procedure "Using the PRISMA guidelines statement, this systematic review was conducted. Reviewing all the abstracts and all texts, the studies are carefully chosen according to the inclusion and exclusion criteria and are reported below. None of the manuscript authors was contacted during this process. Disagreements between authors were evaluated, and the studies were eliminated through discussion among researchers until a consensus was reached."

Search strategy
"Two independent researchers conducted searches in PubMed/Medline, Web of Science, and Scopus to identify studies published in English without restriction on year of publication." The keywords used were "herbal sealers", "herbal irrigants", "Candida albicans ", "Triphala" and "propolis", " Morinda Citrofolia juice", " Green tea and garlic extracts".
The search details were herbal medicaments (all ields) AND ((Triphala OR Propolis OR Morinda Citrofolia juice OR Green tea extract OR Garlic extract)) AND ((ef icacy against Candida albicans in root canal infection)).

Criteria for Inclusion and Exclusion
Included were "The inclusion criteria for this review included studies published in English without restrictions on the year of publication and studies which evaluated and compared the ef icacy of Triphala, Propolis, Morinda Citrofolia juice, green tea extract, garlic extract against Candida albicans in root canal infection.
The types of studies were in vitro and ex vivo studies using human cells, prospective studies, retrospective studies."

Excluded were
"Studies that resulted in cytotoxicity of sealers, in vivo studies were excluded."

Criteria for selection of the studies
"First, studies were selected by analysis of the titles. If the title indicated inclusion, the abstract was evaluated carefully, and articles considered eligible for review (or in case of doubt) were selected for reading. Due to the lack of randomized clinical trials and prospective and retrospective studies, this review included in vitro studies and ex vivo studies using human root canals. For this reason, the patient -intervention -comparison-outcome (PICO) system was adapted: population (studies that evaluated human root canals), intervention (evaluation of herbal medicaments ), comparison (comparison of the Triphala, Propolis, Morinda Citrofolia juice, Green tea extract, Garlic extract), and outcomes ( which medicament is effective against candida Albicans in root canal infection)."

RESULTS
"The preliminary screening of the retrieved studies was conducted using titles and abstracts. The corresponding full text was read when the results were unclear. The authors independently evaluated the studies and discussed the results until a decision was reached by consensus. Among the 15 studies, ive studies were screened for inclusion." One exvivo study, four in vitro studies included in the study. Figure 1 summarises the details and results of the search strategy.

DISCUSSION
Root canal treatment aims at eradication of microbes from the root canal. It also aims at prevention of microbial recontamination in the treated root canal. Micro-organisms commonly occurring in the Endodontic reinfection are Candida albicans and Enterococcus faecalis. Therefore the elimination of these microbes is essential for successful root canal therapy. Commercially various irrigants and medicaments are used for treatment. They are Sodium hypochlorite, Chlorhexidine, EDTA etc. however, there are some drawbacks. Herbal extracts have been tried for their antibacterial and antifungal properties. Hence this study aims at analyzing the ef icacy of various herbal extracts against Candida albicans in infected root canals.
As mentioned in Table 1, Raghavendra and Balsaraf (2014) did in vitro study to assess the antifungal ef icacy of Azadirachta indica (Neem), 3% NaOCl, 2% CHX. The zones of inhibition were noted of the three materials. A statistically signi icant difference was not found amid the zone of inhibition of neem leaf extract and 3% NaOCl. However statistically significant difference was found amid neem leaf extract and 3% NaOCl with 2% CHX. Antimicrobial potential of the neem is better. This is found to be specially related to gingivitis and periodontitis (Vinothkumar et al., 2013). Neem can be used as an endodontic irrigant. This is attributed to its biocompatibility and antioxidant property. Neem does not cause severe injuries in the oral cavity which may occur due to sodium hypochlorite accidents. Bacterial and fungal adhesion is prevented by neem. It is due to its anti-adherence activity. Neem has constituents called Nimbidin and nimbolide (Jainkittivong et al., 2009). These are responsible for antibacterial and antifungal properties. This causes bacterial and fungal cell wall lysis (Prabhakar et al., 2010). Results attained from this study was neem extract was ef icacious against C. Albicans. Hence the author concluded that the Effectiveness of neem leaf extract was comparable to 3 % sodium hypochlorite.
As mentioned in Table 1, Jose et al. (2015) performed an in vitro study to evaluate and compare the ef icacy of herbal medicaments such as green tea extract, garlic extract and neem extract comparable to the ef icacy of sodium hypochlorite against Candida albicans in root canal infection (Sundaram et al., 2016). They measured the zones of inhibition. Mean diameter of 4.2 cm for candida Albicans was found in NaOCl. Mean diameter of inhibition for C. Albicans was 2.7 cm by green tea extract and 2.8 cm for garlic extract. He concluded that sodium hypochlorite was best among the four solutions. However, it was toxic when used injudiciously. Green tea extract showed better result against C. Albicans as compared to garlic extract and neem extract. But not as good as Sodium hypochlorite. Herbal medicaments are less tissue toxic as compared to sodium hypochlorite. Green tea polyphenols show antioxidant, anti-cariogenic, anti-in lammatory, probiotic and antimicrobial properties. It prevents bio ilm formation. Natural luoride is also present in green tea (Jainkittivong et al., 2009). It is helpful in the prevention of caries. The content Catechin, mainly epigallocatechin-3-gallate present in green tea, is bene icial. Garlic has minerals ( Selenium) and many sulphur compounds. The pungent odour and many of its medicinal effects are attributed to sulphur compounds. An unstable compound formed from Allicin present in garlic named allicin is responsible for inhibition of fungal growth (Amagase et al., 2001). This compound inhibits both sproutings of spores and development of hyphae. The allicin elic-

Figure 1: Prisma Flow Diagram
its antimicrobial effect due to its chemical reaction with the thiol group of various enzymes (Ankri and Mirelman, 1999). Hence the author concluded that green tea and garlic extract are effective against C. Albicans. Further research is necessary to conclude the Effectiveness of herbal extracts against C. Albicans.
As mentioned in Table 1, Jyothi and Gopal (2016) performed an in-vitro study comparing the antimicrobial ef icacy of 0.3% Propolis, 10% neem, 10% Triphala and 5% sodium hypochlorite on Candida albicans and Enterococcus faecalis bio ilm in root canal infection. The data obtained were analyzed digitally by colony count. Triphala and NaOCl showed no statistically signi icant difference. NaOCL, Triphala and neem showed no statistically signi icant difference. Propolis showed little antibacterial activity against C. Albicans. Triphala is effectively used in endodontics. Its ef icacy is comparable to sodium hypochlorite. It is as effective as sodium hypochlorite. Triphala has antimicrobial property because of its formulation that has three medicinal plants in equal portions. They are Terminalia bellerica, Terminalia chebula, Emblica of icinalis. These three combined results in additive/ synergistic effect (Pujar, 2011). Triphala also has antioxidant property. Ef icacy of Triphala can be partially due to this property. Propolis has good antimicrobial property. But is less as compared to Triphala and sodium hypochlorite. Propolis contains lavonoids and various esters of caffeine acid. The antimicrobial effect of propolis can be attributed to this. Propolis contains an unidenti ied, water-soluble, ultraviolet absorbing component. This hinders bacterial DNA dependent RNA polymerases (Simuth et al., 1986). Propolis have variable composition. Neem is another herbal extract showing good antimicrobial property similar to Triphala and sodium hypochlorite. Alkaloids, glycosides, lavonoids, steroids, anthraquinone and tannic acid are present resulting in its antimicrobial property. Hence the authors concluded that Triphala is effective against Candida albicans formed in the infected root canal. Further research is needed on herbal extracts to conclude their Effectiveness.
As mentioned in Table 1, Wijesinghe et al. (2018) performed an experiment evaluating and comparing the antimicrobial and anti-candida activity of Chlorhexidine gluconate, Triphala and Munamal pothu ( bark of Mimusops elengi). The results were calculated by testing the zones of inhibition. CHX had a zone of inhibition for all ten test strains of Candida species. Zone of inhibition by Triphala was Zone of inhibition was recorded against C. Albicans, C. tropicalis and C. parapropolis. Munamal pothu did not show any zone of inhibition against C. Albicans. Chlorhexidine gluconate is acceptably used in endodontics. It has an action against free-living planktonic cells. This showed its usefulness in the prevention of microbial colonization and viability. Yet using it for longer duration can show side effects, such as staining teeth, development of resistance, altering the taste sensation. Triphala possesses anti-in lammatory, antioxidant, antimicrobial activity against broad spectrum microbes (Gomes et al., 2013;Salam et al., 2015). Microbes include bacteria, yeasts, dermatophytes (Gomes et al., 2013). The active phytochemicals include tannic acid, chebulic acid and lavonoids that show activity against C. albicans (Jyothi and Gopal, 2016). Hence to conclude Chlorhexidine gluconate is a potent antifungal and antimicrobial agent against C. Albicans. Triphala is as potent as Chlorhexidine with lesser side effects.
As mentioned in Table 1, Sardana et al. (2018) performed an ex-vivo study exploring the role of Morinda citrifolia and Triphala juice against Candida albicans and Enterococcus faecalis present in root canal infection. The colony-forming unit was calculated for each sealer. The microbial count was reduced in CHX and Triphala. Chlorhexidine used in this study was found to be an ef icient antifungal agent as compared to an antibacterial agent. Morinda citrifolia juice (MCJ) is from the traditional folk medicinal plant used by Polynesians. Acubin, L-asperuloside, Alizarin, and some anthraquinones are present in MCJ are believed to express its antibacterial activity (Murray et al., 2008). MCJ was found effective in removing the smear layer, particularly when combined with EDTA. But it was not as ef icient as NaOCl and EDTA. MCJ is a biocompatible oxidant. Hence it did not cause grave injuries if extruded out (Jainkittivong et al., 2009). An Indian Ayurvedic herbal formulation -Triphala, consists of dried and powdered fruits of three medicinal plants. They are Terminalia bellerica (Bihara/belericmyrobalan), Terminalia chebula (Harad/chebulic myrobalan), and Emblica of icinalis (Amla/gooseberry). It has good antimicrobial activity. Triphala is also an excellent chelating agent. This is because the fruits are rich in citric acid. This results in an effective smear layer removal (Prabhakar et al., 2010). Hence the overall results showed that Triphala holds antibacterial ef icacy against E. faecalis. MCJ holds better antifungal ef icacy against C. albicans. Yet further studies are required to conclude the bene its of these herbal extracts.
Herbal sealers are safe, economical, readily available, biocompatible, have a good shelf life, are antioxidant, anti-in lammatory and have fewer chances of microbial resistance.

CONCLUSION
Candida albicans is conspicuously found microbe in failed root canal treatment. C. albicans cannot be eradicated with conventional root canal sealers. Hence the sealers having good biocompatibility and least microbial resistance is required for elimination of Candida albicans. Hence herbal sealers are an effective treatment against Candida albicans in case of retreatment.