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01.02.2021 | Original Article

Local delivery natural products to treat periodontitis: a systematic review and meta-analysis

verfasst von: Emerson Tavares de Sousa, Jaiza Samara Macena de Araújo, Andressa Cavalcanti Pires, Elis Janaina Lira dos Santos

Erschienen in: Clinical Oral Investigations | Ausgabe 7/2021

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Abstract

Objectives

This study aimed to answer the PICO question: in adults with periodontitis, does subgingival delivery of natural products (NP) after scaling and root planing (SRP) results in a better reduction of probing pocket depth (PPD) when compared with SRP alone or SRP plus placebo?

Material and methods

A search for trials was carried out in eight databases. Two independent investigators performed all steps of this review. PPD reduction, clinical attachment level (CAL) gain, gingival inflammation, and biofilm accumulation reduction were investigated. We conducted meta-analyses where data could be pooled.

Results

Searches yielded 4771 records, in which 27 trials fulfilled the eligibility. There was a large heterogeneity among trials (I² > 0.69, χ² < 0.000). Only four studies were at low risk of bias. The evidence quality was very low. The effectiveness of NP was demonstrated in a follow-up of 3–6 months considering PPD reduction (8 trials: 0.72 mm [95%CI: 0.23, 1.22]) and CAL gain (5 trials: 1.07 mm [95%CI: 0.36, 1.78]). A significant reduction in periodontal inflammation favors the use of NP. The biofilm accumulation reduction effect of NP was very weak or non-significant.

Conclusion

Although the high risk of bias and large heterogeneity of trials impose some restrictions on the validity of effect estimate, this review indicates that adjunctive NP better reduced the PPD when compared to SRP alone or SRP plus placebo in a follow-up of 3–6 months.

Clinical relevance

The evidence of non-responsive patients to conventional periodontal therapy highlights the need for therapeutic alternatives to treat periodontitis.

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Chapple ILC, Bouchard P, Cagetti MG, Campus G, Carra MC, Cocco F, Nibali L, Hujoel P, Laine ML, Lingström P, Manton DJ, Montero E, Pitts N, Rangé H, Schlueter N, Teughels W, Twetman S, van Loveren C, van der Weijden F, Vieira AR, Schulte AG (2017) Interaction of lifestyle, behaviour or systemic diseases with dental caries and periodontal diseases: consensus report of group 2 of the joint EFP/ORCA workshop on the boundaries between caries and periodontal diseases. J Clin Periodontol 44:S39–S51. https://doi.org/10.1111/jcpe.12685CrossRefPubMed

Smiley CJ, Tracy SL, Abt E et al (2015) Systematic review and meta-analysis on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts. J Am Dent Assoc 146:508-524.e5. https://doi.org/10.1016/j.adaj.2015.01.028CrossRef

Kinane DF, Stathopoulou PG, Papapanou PN (2017) Periodontal diseases. Nat Rev Dis Prim 3:17038. https://doi.org/10.1038/nrdp.2017.38CrossRefPubMed

Kumar PS, Leys EJ, Bryk JM, Martinez FJ, Moeschberger ML, Griffen AL (2006) Changes in periodontal health status are associated with bacterial community shifts as assessed by quantitative 16S cloning and sequencing. J Clin Microbiol 44:3665–3673. https://doi.org/10.1128/JCM.00317-06CrossRefPubMedPubMedCentral

Hanes PJ, Purvis JP (2003) Local anti-infective therapy: pharmacological agents. A systematic review. Ann Periodontol 8:79–98. https://doi.org/10.1902/annals.2003.8.1.79

Matesanz-Pérez P, García-Gargallo M, Figuero E, Bascones-Martínez A, Sanz M, Herrera D (2013) A systematic review on the effects of local antimicrobials as adjuncts to subgingival debridement, compared with subgingival debridement alone, in the treatment of chronic periodontitis. J Clin Periodontol 40:227–241. https://doi.org/10.1111/jcpe.12026CrossRefPubMed

Lazar V, Saviuc C-MC-M, Chifiriuc MC (2016) Periodontitis and periodontal disease - innovative strategies for reversing the chronic infectious and inflammatory condition by natural products. Curr Pharm Des 22:230–237. https://doi.org/10.2174/138161282202151221124307CrossRefPubMed

Mishra BB, Tiwari VK (2011) Natural products: an evolving role in future drug discovery. Eur J Med Chem 46:4769–4807. https://doi.org/10.1016/j.ejmech.2011.07.057CrossRefPubMed

Cragg GM, Newman DJ (2005) Biodiversity: a continuing source of novel drug leads. Pure Appl Chem 77:7–24. https://doi.org/10.1351/pac200577010007CrossRef

10.

Dias DA, Urban S, Roessner U (2012) A historical overview of natural products in drug discovery. Metabolites 2:303–336. https://doi.org/10.3390/metabo2020303CrossRefPubMedPubMedCentral

11.

Moro MG, Silveira Souto ML, Franco GCN, Holzhausen M, Pannuti CM (2018) Efficacy of local phytotherapy in the nonsurgical treatment of periodontal disease: a systematic review. J Periodontal Res 53:288–297. https://doi.org/10.1111/jre.12525CrossRefPubMed

12.

Saleem M, Nazir M, Ali MS, Hussain H, Lee YS, Riaz N, Jabbar A (2010) Antimicrobial natural products: an update on future antibiotic drug candidates. Nat Prod Rep 27:238–254. https://doi.org/10.1039/b916096eCrossRefPubMed

13.

Azab A, Nassar A, Azab AN (2016) Anti-inflammatory activity of natural products. Molecules 21. https://doi.org/10.3390/molecules21101321

14.

Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097CrossRefPubMedPubMedCentral

15.

Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M-I, Noel-Storr A, Rader T, Shokraneh F, Thomas JWL (2019) Chapter 4: searching for and selecting studies. In: JPT H, Thomas J, Chandler J, Cumpston M, Li T, Page MJWV (eds) Cochrane Handbook for Systematic Reviews of Interventions version 6.0

16.

Warad S, Kolar S, Kalburgi V, Kalburgi N (2013) Lemongrass essential oil gel as a local drug delivery agent for the treatment of periodontitis. Anc Sci Life 32:205–211. https://doi.org/10.4103/0257-7941.131973CrossRefPubMedPubMedCentral

17.

Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJWV (2020) No title. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJWV (eds) Cochrane handbook for systematic reviews of interventions version 6.1 (updated September 2020). Cochrane

18.

Follmann D, Elliott P, Suh I, Cutler J (1992) Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol 45:769–773. https://doi.org/10.1016/0895-4356(92)90054-qCrossRefPubMed

19.

Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernán MA, Hopewell S, Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ, Lasserson T, Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. https://doi.org/10.1136/bmj.l4898CrossRefPubMed

20.

Schünemann H, Brożek J, Guyatt G, Oxman A (2013) E GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013

21.

McMaster University (developed by Evidence Prime I (2015) GRADEpro GDT: GRADEpro Guideline Development Tool [Software]

22.

Borenstein M, Hedges LV, Julian PT, Higgins HRR (2009) Introduction to meta-analysis. Wiley, ChichesterCrossRef

23.

Chinn S (2000) A simple method for converting an odds ratio to effect size for use in meta-analysis. Stat Med 19:3127–3131. https://doi.org/10.1002/1097-0258(20001130)19:22<3127::aid-sim784>3.0.co;2-mCrossRefPubMed

24.

Suurmond R, van Rhee H, Hak T (2017) Introduction, comparison, and validation of meta-essentials: a free and simple tool for meta-analysis. Res Synth Methods 8:537–553. https://doi.org/10.1002/jrsm.1260CrossRefPubMedPubMedCentral

25.

Lesaffre E, Philstrom B, Needleman I, Worthington H (2009) The design and analysis of split-mouth studies: what statisticians and clinicians should know. Stat Med 28:3470–3482. https://doi.org/10.1002/sim.3634CrossRefPubMed

26.

Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560. https://doi.org/10.1136/bmj.327.7414.557CrossRefPubMedPubMedCentral

27.

Langan D, Higgins JPT, Jackson D, Bowden J, Veroniki AA, Kontopantelis E, Viechtbauer W, Simmonds M (2019) A comparison of heterogeneity variance estimators in simulated random-effects meta-analyses. Res Synth Methods 10:83–98. https://doi.org/10.1002/jrsm.1316CrossRefPubMed

28.

Hirasawa M, Takada K, Makimura M, Otake S (2002) Improvement of periodontal status by green tea catechin using a local delivery system: a clinical pilot study. J Periodontal Res 37:433–438. https://doi.org/10.1034/j.1600-0765.2002.01640.xCrossRefPubMed

29.

Gebaraa ECE, Pustiglioni AN, de Lima LAPA, Mayer MPA (2003) Propolis extract as an adjuvant to periodontal treatment. Oral Health Prev Dent 1:29–35. https://doi.org/10.3290/j.ohpd.a8218CrossRefPubMed

30.

Sastravaha G, Yotnuengnit P, Booncong P, Sangtherapitikul P (2003) Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts. A preliminary study J Int Acad Periodontol 5:106–115PubMed

31.

Funosas ER, Martínez AB, Pignolo M, Maestri L, Aromando RF, Scozzarro SM, Escovich L, Hermida PS (2005) Efectividad del té verde en el tratamiento de periodontitis crónica. Av Odontoestomatol 21:159–166. https://doi.org/10.4321/s0213-12852005000300005CrossRef

32.

Sastravaha G, Gassmann G, Sangtherapitikul P, Grimm WD (2005) Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts in supportive periodontal therapy. J Int Acad Periodontol 7:70–79PubMed

33.

Taweechaisupapong S, Intaranongpai K, Suwannarong W, Pitiphat W, Chatrchaiwiwatana S, Wara-aswapati N (2006) Clinical and microbiological effects of subgingival irrigation with Streblus asper leaf extract in chronic periodontitis. J Clin Dent 17:67–71PubMed

34.

Rassameemasmaung S, Sirikulsathean A, Amornchat C, Maungmingsook P, Rojanapanthu P, Gritsanaphan W (2008) Topical application of Garcinia mangostana L. pericarp gel as an adjunct to periodontal treatment. Complement Ther Med 16:262–267. https://doi.org/10.1016/j.ctim.2007.12.004CrossRefPubMed

35.

Patel PV, Patel A, Kumar S, Holmes JC (2012) Effect of subgingival application of topical ozonated olive oil in the treatment of chronic periodontitis: a randomized, controlled, double blind, clinical and microbiological study. Minerva Stomatol 61(9):381–398PubMed

36.

Gottumukkala SVS, Koneru S, Mannem S, Mandalapu N (2013) Effectiveness of sub gingival irrigation of an indigenous 1% curcumin solution on clinical and microbiological parameters in chronic periodontitis patients: a pilot randomized clinical trial. Contemp Clin Dent 4:186–191. https://doi.org/10.4103/0976-237x.114874CrossRefPubMedPubMedCentral

37.

Mahendra J, Mahendra L, Muthu J, John L, Romanos GE (2013) Clinical effects of subgingivally delivered spirulina gel in chronic periodontitis cases: a placebo controlled clinical trial. Journal of clinical and diagnostic research : JCDR 7(10):2330–2333. https://doi.org/10.7860/JCDR/2013/5793.3517CrossRefPubMedPubMedCentral

38.

Cheng Q, Gao W min, Cao B, et al (2014) Effects of Ginkgo biloba extract on periodontal pathogens and its clinical efficacy as adjuvant treatment. Chin J Integr Med 20:729–736. https://doi.org/10.1007/s11655-014-1824-4

39.

Rattanasuwan K, Rassameemasmaung S, Sangalungkarn V, Komoltri C (2014) Clinical effect of locally delivered gel containing green tea extract as an adjunct to non-surgical periodontal treatment. Odontology 104(1):89–97. https://doi.org/10.1007/s10266-014-0190-1CrossRefPubMed

40.

Sanghani NN, Shivaprasad BM, Savita S (2014) Health from the hive: Propolis as an adjuvant in the treatment of chronic periodontitis - a clinicomicrobiologic study. J Clin Diagnostic Res 8:ZC41–ZC44. https://doi.org/10.7860/JCDR/2014/8817.4856CrossRef

41.

Yaghini J, Shahabooei M, Aslani A, Zadeh MR, Kiani S, Naghsh N (2014) Efficacy of a local-drug delivery gel containing extracts of Quercus brantii and Coriandrum sativum as an adjunct to scaling and root planing in moderate chronic periodontitis patients. Journal of research in pharmacy practice 3(2):67–71. https://doi.org/10.4103/2279-042X.137076CrossRefPubMedPubMedCentral

42.

Nagasri M, Madhulatha M, Musalaiah SVVS et al (2015) Efficacy of curcumin as an adjunct to scaling and root planning in chronic periodontitis patients: a clinical and microbiological study. J Pharm Bioallied Sci 7:S554–S558. https://doi.org/10.4103/0975-7406.163537CrossRefPubMedPubMedCentral

43.

Sreedhar A, Sarkar I, Rajan P et al (2015) Comparative evaluation of the efficacy of curcumin gel with and without photo activation as an adjunct to scaling and root planing in the treatment of chronic periodontitis: a split mouth clinical and microbiological study. J Nat Sci Biol Med 6:S102–S109. https://doi.org/10.4103/0976-9668.166100CrossRefPubMedPubMedCentral

44.

Boyapati R, Gojja P, Chintalapani S, Nagubandi K, Ramisetti A, Salavadhi SS (2017) Efficacy of local drug delivery of Achyranthes aspera gel in the management of chronic periodontitis: a clinical study. J Indian Soc Periodontol 21:46–49. https://doi.org/10.4103/jisp.jisp_130_17CrossRefPubMedPubMedCentral

45.

Grover S, Tewari S, Sharma RK, Singh G, Yadav A, Naula SC (2016) Effect of subgingivally delivered 10% Emblica officinalis gel as an adjunct to scaling and root planing in the treatment of chronic periodontitis - a randomized placebo-controlled clinical trial. Phytother Res 30:956–962. https://doi.org/10.1002/ptr.5600CrossRefPubMed

46.

Singh HP, Muzammil SG et al (2016) Comparative study to evaluate the effectiveness of aloe vera and metronidazole in adjunct to scaling and root planing in periodontitis patients. J Int Oral Heal 8:374–377. https://doi.org/10.2047/jioh-08-03-14CrossRef

47.

Mahendra J, Mahendra L, Svedha P, Cherukuri S, Romanos GE (2017) Clinical and microbiological efficacy of 4% Garcinia mangostana L. pericarp gel as local drug delivery in the treatment of chronic periodontitis: a randomized, controlled clinical trial. Journal of investigative and clinical dentistry 8(4). https://doi.org/10.1111/jicd.12262, https://doi.org/10.1111/jicd.12262

48.

Ipshita S, Kurian IG, Dileep P, Kumar S, Singh P, Pradeep AR (2018) One percent alendronate and aloe vera gel local host modulating agents in chronic periodontitis patients with class II furcation defects: a randomized, controlled clinical trial. J Investig Clin Dent 9:e12334. https://doi.org/10.1111/jicd.12334CrossRefPubMed

49.

Kurian IG, Dileep P, Ipshita S, Pradeep AR (2018) Comparative evaluation of subgingivally-delivered 1% metformin and aloe vera gel in the treatment of intrabony defects in chronic periodontitis patients: a randomized, controlled clinical trial. J Investig Clin Dent 9:e12324. https://doi.org/10.1111/jicd.12324CrossRefPubMed

50.

Rayyan M, Terkawi T, Abdo H, Abdel Azim D, Khalaf A, AlKhouli Z, Meziad M, Alshamma'a M, Abu Naim H (2018) Efficacy of grape seed extract gel in the treatment of chronic periodontitis: a randomized clinical study. J Investig Clin Dent 9(2):e12318. https://doi.org/10.1111/jicd.12318CrossRefPubMed

51.

Jalaluddin M, Jayanti I, Gowdar IM, Roshan R, Varkey RR, Thirutheri A (2019) Antimicrobial activity of Curcuma longa L. extract on periodontal pathogens. Journal of pharmacy & bioallied sciences 11(Suppl 2):S203–S207. https://doi.org/10.4103/JPBS.JPBS_295_18CrossRef

52.

Pappu R, Varghese J, Koteshwara KB et al (2019) Evaluation of biodegradable gel containing flax seed extract (Linum usitatissimum) as a targeted drug delivery for management of chronic periodontitis. J Herb Med 15. https://doi.org/10.1016/j.hermed.2018.100254

53.

Nakao R, Senpuku H, Ohnishi M, Takai H, Ogata Y (2020) Effect of topical administration of propolis in chronic periodontitis. Odontology 108:704–714. https://doi.org/10.1007/s10266-020-00500-4CrossRefPubMed

54.

Lang NP, Bartold PM (2018) Periodontal health. J Clin Periodontol 45:S9–S16. https://doi.org/10.1111/jcpe.12936CrossRefPubMed

55.

Mark Bartold P, Van Dyke TE (2017) Host modulation: controlling the inflammation to control the infection. Periodontol 2000 75:317–329. https://doi.org/10.1111/prd.1216956

56.

Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Beglundh T, Sculean A, Tonetti MS; EFP Workshop Participants and Methodological Consultants. Treatment of stage I-III periodontitis-the EFP S3 level clinical practice guideline. J Clin Periodontol 2020 47:4–60. https://doi.org/10.1111/jcpe.13290

57.

Stoller NH, Johnson LR, Trapnell S, Harrold CQ, Garrett S (1998) The pharmacokinetic profile of a biodegradable controlled-release delivery system containing doxycycline compared to systemically delivered doxycycline in gingival crevicular fluid, saliva, and serum. J Periodontol 69:1085–1091. https://doi.org/10.1902/jop.1998.69.10.1085CrossRefPubMed

58.

Shifrovitch Y, Binderman I, Bahar H, Berdicevsky I, Zilberman M (2009) Metronidazole-loaded bioabsorbable films as local antibacterial treatment of infected periodontal pockets. J Periodontol 80:330–337. https://doi.org/10.1902/jop.2009.080216CrossRefPubMed

59.

Soskolne WA, Heasman PA, Stabholz A, Smart GJ, Palmer M, Flashner M, Newman HN (1997) Sustained local delivery of chlorhexidine in the treatment of periodontitis: a multi-center study. J Periodontol 68:32–38. https://doi.org/10.1902/jop.1997.68.1.32CrossRefPubMed

60.

Mombelli A (2018) Microbial colonization of the periodontal pocket and its significance for periodontal therapy. Periodontol 2000(76):85–96. https://doi.org/10.1111/prd.12147CrossRef

61.

Smaïl-Faugeron V, Fron-Chabouis H, Courson F, Durieux P (2014) Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study. BMC Med Res Methodol 14:64. https://doi.org/10.1186/1471-2288-14-64CrossRefPubMedPubMedCentral

62.

Muniz F, Langa G, Pimentel RP, Martins JR, Pereira DH, Rösing CK (2020) Comparison between hand and sonic/ ultrasonic instruments for periodontal treatment: systematic review with meta-analysis. Journal of the International Academy of Periodontology 22(4):187–204PubMed

63.

Pferschy-Wenzig E-M, Bauer R (2015) The relevance of pharmacognosy in pharmacological research on herbal medicinal products. Epilepsy Behav 52:344–362. https://doi.org/10.1016/j.yebeh.2015.05.037CrossRefPubMed

64.

Joshi D, Garg T, Goyal AK, Rath G (2016) Advanced drug delivery approaches against periodontitis. Drug Deliv 23:363–377. https://doi.org/10.3109/10717544.2014.935531CrossRefPubMed

Titel: Local delivery natural products to treat periodontitis: a systematic review and meta-analysis
verfasst von: Emerson Tavares de Sousa
Jaiza Samara Macena de Araújo
Andressa Cavalcanti Pires
Elis Janaina Lira dos Santos
Publikationsdatum: 01.02.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Oral Investigations / Ausgabe 7/2021
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-021-03774-2

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Local delivery natural products to treat periodontitis: a systematic review and meta-analysis