Therapeutic potential of Simarouba glauca in treatment of Oral diseases

 

Elizabeth C. Dony1, Mamatha G.S.2, Monika Srivastava3*

1Assistant Professor, Department of Oral Pathology and Microbiology,

Dr. D.Y. Patil Vidyapeeth’s, Dr. D.Y.Patil Dental College and Hospital, Pimpri, Pune -18.

2Professor, Department of Oral Pathology and Microbiology,

Dr. D.Y. Patil Vidyapeeth’s, Dr. D.Y. Patil Dental College and Hospital, Pimpri, Pune - 18.

3Assistant Professor, Department of Oral Pathology and Microbiology,

Dr. D.Y. Patil Vidyapeeth’s, Dr. D.Y. Patil Dental College and Hospital, Pimpri, Pune-18.

*Corresponding Author E-mail: drelizabethcdony@gmail.com, drmamatha78@gmail.com, monika.srivastav@dpu.edu.in

 

ABSTRACT:

Simarouba glauca is an evergreen, flowering tree belonging to family Simaroubaceae. It is commonly called as LaxmiTaru or Paradise Tree. Since ancient times it is widely used as a traditional medicinal plant and different parts of the plant are used for treatment of diseases like malaria, dysentery and cancer. Studies on Simarouba glauca, revealed the presence of several essential phytoconstituents of major pharmacological significance. These phytoconstituents are known to impart a wide range of medicinal properties like anti-cancerous, anti-inflammatory, anti- oxidative, anti-microbial and hemostatic properties to its plant extract.A group of triterpenes called quassinoids is by far the most active phytoconstituent present in Simarouba glauca. In recent years, there is an increase in its popularity as several studies showed its success in treatment of cancers including oral cancer. Also, there is a growing demand for natural products over synthetic drugs as it exhibits less side effects and develop less resistance during drug therapy. However, further in-vivo studies and clinical trials are needed to authenticate the efficiency and safety of Simarouba glauca plant extracts in humans. The purpose of this review is to summarize the therapeutic and medicinal properties of Simarouba glauca and to explore its potential applications in dentistry.

 

KEYWORDS: Simarouba glauca, Oral diseases, Oral cancer, Herbal, Dentistry.

 

 


INTRODUCTION: 

Oral diseases are one of the most serious public health issues and the most common chronic diseases afflicting the human population.1 World Health Organization (WHO) defines oral health as “A state of being free from chronic mouth pain, oral infection and sores, periodontal (gum) disease, tooth loss, oral ulcer, oral cancer.”2 Natural products are being constantly evaluated as an intriguing alternative to synthetic antimicrobials for the treatment of oral diseases due to its ease of availability and efficiency to overcome drug resistance during therapy.1

 

 

There is going to be a further increase in demand for natural products as they are thought to be safer and more cost effective than synthetic drugs for treatment of diseases.3 Moreover, many plant-derived chemicals are used as the basis for evidence-based pharmacological medications in modern medicine.4 For example, popular anticancer drugs like the vinca alkaloids i.e., vinblastine and vincristine are isolated from the medicinal plant Madagascar periwinkle. Hence, there have been a great interest in studying the extracts of traditional medicinal plants for identifying the source of the therapeutic effects and also for development of newer drugs.5 Simarouba glauca, commonly known as ‘Laxmitaru’ or ‘Paradise tree’ is one such traditional medicinal plant which is widely studied due to its well-established medicinal properties. It is quite popular since ancient times for its traditional use in treatment of malaria, cancer, dysentery, blood and gastric disorders and infectious diseases.6 Different parts of the plant like its leaves, bark and seeds are known for diverse pharmacological actions such as antimicrobial, hemostatic, antihelminthic, antiparasitic, antidysentric, antipyretic, and anticancerous effects.7 The present review emphasizes the therapeutic and medicinal potential of Simarouba glauca in treatment of oral diseases.

 

Simarouba glauca- Scientific Classification:

Kingdom: Plantae

Order:      Sapindales

Family:    Simaroubaceae

Genus:     Simarouba

Species:   Simarouba glauca8

 

Simarouba glauca belongs to the family Simaroubaceae.9 Derived from the Greek word ‘glaukos’ (bluish), the specific name glauca means covered with bloom and signifies its bluish green foliage.10 It is also commonly known as Aceituno, Simaba, Bitter wood tree or bitter ash.8,10 The bark extract of Simarouba glauca was widely used for treatment of dysentery and hence it was also called ‘dysentery-bark’.11

 

Ecology:

Simarouba glauca is indegenous to Florida in the United States, southern Florida, South America, and the Lesser Antilles. However, the tree well adapts to warm, humid and tropical regions with a temperature range of 10 to 50 °C.12 It easily thrives in areas of adequatelydrained soils (pH 5.5 to 8) with an annual rainfall of 250mm to 2500 mm.8

 

Description of The Plant:

Simarouba glauca, is an average sized evergreen tree with a larger circular crown and attains a height of 7-15 m. The diameter of its trunk varies from 50 to 80cm. The leaves are bright green in color, 20 to 50cm in length and pinnately compound with 3-21 leaflets. It produces yellow flowers and oval elongated fleshy fruits with sweet edible pulp.9 They are of two types based on the fruit color, one with greenish white fruit and the other with violet to almost black fruits.13 The seeds are1.5 to 2cm. in length, pinkish or yellowish in color after it ripens.9

 

Composition:

The therapeutic potential of Simarouba glauca is due to its phyto-constituents and the secondary metabolites synthesized by them. It includes alkaloids (quassinoids, quassin), glycosides, flavonoids, phenolic compounds, tannins, cardenolides, and saponins.14 Themain active constituent are the bitter compounds called quassinoids, which belong to a group of triterpene lactones.6

 

 

Simarouba glauca in Treatment of Oral Diseases:

Simarouba glauca as a potent root canal medicament:

Simarouba glauca when used as intracanal medicaments reduced Enterococcus faecalis from the root canal system.7 The presence of microorganisms such as Enterococcus faecalis (E. faecalis) after completion of root canal treatment, can lead totreatment failure.15 E. faecalisis a facultative anaerobic Gram positive bacterium present in root canal system and has been isolated in high numbers in endodontic failures.7 The various endurance and virulence factors of E. faecalissuch as its ability to compete with other microorganisms, invasion into deeper parts of dentinal tubules and survival even in a low nutrition state make it resistant to routinely used intracanal medicaments.7,15 The efficiency of Simarouba glauca as an intracanal medicament was comparable to that of metapex which is a drug of choice for eradication of E. faecalis present in dentinal tubules. The antimicrobial properties of Simarouba glauca can be due to the alkaloids which is a major phyto-constituent present in the plant. The alkaloids impart an alkaline pH to the plant extracts and can influence the growth and metabolism of E. faecalis. Hence Simarouba glauca when used as a naturalintracanal medicaments hold a promising result in the reduction of bacterial colonies within the root canal system.7

 

Anti-microbial potential of Simarouba glauca extracts:

Besides its significant antibacterial properties against several gram-negativeand gram-positive bacteria like E. faecalis, Simarouba glauca extracts showed significant anti-fungaland anti-viralproperties too.14,16,17

 

Ethanol leaf extract of Simarouba glauca was successful in hindering the growth of the test fungal strains of Candida albicans.17 Candida albicans along with other species included in the genus Candida, is known to cause candidiasis (candidosis) which is one of the most common opportunistic fungal infection of oral cavity.18 It is important to prevent superficial oral infections in order to improve one's quality of life and to avoid the development of a systemic fungal infection.19 In spite of the fact that, various effective antifungal agents are available to treat oral candidal infections, the success rate is less because isolates of Candida albicans may exhibit resistance to the drug during therapy.20 Hence, this anti-fungal property of Simarouba glauca should be further explored as it could prove useful to cope with the extensive complications related to antimicrobial drug resistance.

 

Bark water extracts of Simarouba glauca was found effectivein vitro against the herpes virus.14 The most common type of herpes simplex virus (HSV) infection is primary herpetic gingivostomatitis which is characterized by generalized gingivitis, vesicles and painful ulcerformation in and around the oral cavity.21 These in vitro results suggests that Simarouba glauca is a promising and effective potential source of anti-microbial drug.

 

Anti-cancer potential of Simarouba glauca extracts:

Oral cancer is the sixth most common type of cancer and it is commonly seen occurring on the lips, tongue, floor of mouth and other oral tissues.22 Oral squamous cell carcinoma (OSCC) or oral epidermoid carcinoma is the commonest type of oral cancer.The phytochemicals present in plants have less or no toxicity against healthy tissues and are thus ideal chemotherapeutic agents.23 The anti-cancer properties of Simarouba glauca includes cytotoxic, anti-proliferative, anti-apoptotic, anti-oxidative and anti-inflammatory6,24,25,26.27. Four alkaloids derivatives (canthin-6-one) isolated from the twigs of Simarouba glauca possessed cytotoxic activity against human oral epidermoid cancer.24 Quassinoids including glaucarubin, glaucarubinone, glaucarubol and glaucarubolone isolated from seed of Simarouba glauca also showed invitro cytotoxic activity against KB cells of human oral epidermoid carcinoma.10 Cytotoxicity was also exhibited by methanolic leaf extract of Simarouba glauca on squamous oral carcinoma cell line SCC9.25 Cytotoxic properties of quassinoids are linked to protein synthesis inhibition.28 Despite the significant role of chemotherapy in cancer treatment, its achievement is restricted by the development of multidrug resistance and serious adverse effects. Glaucarubinone, one of the major quassinoids from Simaroub aglauca not only enhanced the cytotoxicity of paclitaxel, an anticancer drug commonly used in treatment of oral cancers but also reversed the multidrug resistance caused by it in oral carcinoma KB cells. Glaucarubinone was also able to induce selective toxicity in oral cancer cells by sparing the normal cells which also makes it an ideal chemotherapeutic agent. Adding a second agent to the standard chemotherapy treatment would also reduce the dose and toxicity of individual anticancer drugs. These findings suggest that Glaucarubinone prove to be an effective subsidiary dietary supplement for oral cancer patients who are resistant to chemotherapeutic drugs.29

 

Anti-cancerous potential of Simarouba glauca was also demonstrated invitro in leukemia, pancreatic, colorectal, breast and lung cancer.6,26,30,31

 

Anti-oxidant potential of Simarouba glauca extracts:

The antioxidant property of Simarouba glauca, enables them to scavenge the free radicals and help to prevent cancer incidence.17 Antioxidants have the ability to suppress carcinogenesis in the oral cavity, lowering the risk of oral cancer and causing the reversal of premalignant lesions such as oral leukoplakia.32 Polyphenolic compounds present in Simarouba glauca, especially the flavonoids exert their anti-oxidative action by inhibition of membrane-bound enzymes such as the ATPase and phospholipase A2.33 When studied in squamous oral carcinoma cell line SCC9, this antioxidant property of Simarouba glauca leaf extract is believed to have synergistically enhanced its cytotoxic activity too.25

 

Anti-inflammatory potential of Simarouba glauca extracts:

Simarouba glauca exhibited notable anti-inflammatory activity due to presence of β-sitosterol and anti-oxidants such as phenols and flavonoids.34 Gingivitis and periodontitis are some of the commonly seen inflammatory diseases of the oral cavity.35 However, further studies have to be conducted to validate its efficiency in treatment of such oral inflammatory diseases.

 

CONCLUSION:

Simaroubaglauca was widely used for treatment of various diseases since ancient times. But its use in treatment of oral diseases was limited. From this review, it can be concluded that Simarouba glauca can be considered as a promising alternative to synthetic antimicrobials due to its lesser side effects, easy availability, low cost and its efficiency to overcome drug resistance during the therapy. Furthermore, it can be also used as an adjunct to modern day cancer treatment to improve anticancer therapeutic efficacy. However, more research is needed on its pharmacological and toxicological properties, and clinical efficiency to determine the commercial utility of Simarouba glauca.

 

REFERENCES:

1.      Shekar BR et al. Herbal extracts in oral health care-A review of the current scenario and its future needs. Pharmacognosy Reviews. 2015 Jul;9(18):87. doi: 10.4103/0973-7847.162101

2.      Thombre N, Thete M, Shimpi P. Review on role of herbs in management of oral diseases. Asian Journal of Pharmaceutical Research. 2020 Nov 26;10(4):321-6.doi: 10.5958/2231-5691.2020.00055.6

3.      Jadhav CA, Vikhe DN, Jadhav RS. Global and domestic market of herbal medicines: a review. Research Journal of Science and Technology. 2020 Oct 1;12(4):327-30.doi: 10.5958/2349-2988.2020.00049.2

4.      MatoleV.Brief Review on Herbal Medicines. Research Journal of Pharmacognosy and Phytochemistry. 2021; 13(2):101-2.

5.      Chauhan R, D'Souza HL, Shabnam RS, Abraham J. Phytochemical and cytotoxicity analysis of seeds and leaves of Adenantherapavonina. Research Journal of Pharmacy and Technology. 2015;8(2):198-203. doi:10.5958/0974-360X.2015.00036.0

6.      Jose Aet al. Anti-proliferative potential of phytochemical fractions isolated from Simaroubaglauca DC leaf. Heliyon. 2020 Apr 1;6(4):e03836.doi: 10.1016/j.heliyon.2020.e03836

7.      Varada SL et al. Antimicrobial Efficacy of Simaroubaglauca (Lakshmi Taru) Plant Extract against Enterococcus faecalis Biofilm: An in vitro Study. Conservative Dentistry and Endodontic Journal 2017;2(2):43-47.doi :10.5005/jp-journals-10048-0025

8.      Hussain MS et al. Pharmacological uses of simaroubaglauca: a review. Plant archives. 2021 Apr 20;21(1):648-655.doi: 10.51470/plantarchives.2021.v21.no1.090

9.      Abirami N et al. Plant Mediated Synthesis, Characterization of Zinc Oxide Nanoparticles using Simaroubaglauca and its Antibacterial Activities. Research Journal of Pharmacy and Technology. 2020;13(4):1819-24.doi: 10.5958/0974-360X.2020.00327.3

10.   Manasi PS, Gaikwad DK. A critical review on medicinally important oil yielding plant laxmitaru (Simaroubaglauca DC.). Journal of Pharmaceutical Sciences and Research. 2011 Apr 1;3(4):1195.

11.   Mugaranja KP, Kulal A. Alpha glucosidase inhibition activity of phenolic fraction from Simaroubaglauca: An in-vitro, in-silico and kinetic study. Heliyon. 2020 Jul 1;6(7):e04392.doi: 10.1016/j.heliyon.2020.e04392

12.   Gurupriya S et al. Qualitative and quantitative phytochemical analysis of Simaroubaglauca leaf extract. Int. J. Res. Appl. Sci. Eng. Technol. 2017;5(11):475-9. doi:10.22214/ijraset.2017.11074

13.   Dash AK et al. Some physical properties of simarouba fruit and kernel. International Agrophysics. 2008;22(1):111-6.

14.   Singh LR, Garg S. Medicinal Potential of LaxmiTaru (SimaroubaGlauca DC). Dev Sanskriti Interdisciplinary International Journal. 2021 Jul 31;18:40-5. doi:10.36018/dsiij.v18i.220

15.   Ismiyatin K, Mudjiono M, Kunarti S, Santoso ML, Hakiki D, Irsya W. Extracellular Polymeric Substance (EPS) Degradation of Enterococcus Faecalis biofilm after irradiation with 405nm diode laser. Research Journal of Pharmacy and Technology. 2021 Jul 1;14(7):3869-73.

16.   Lakshmi KS et al. In vitro antibacterial, antioxidant, haemolytic, thrombolytic activities and phytochemical analysis of Simaroubaglauca leaves extracts. International Journal of Pharmaceutical Sciences and Research (IJPSR). 2014;5(2):432-7.doi:10.13040/IJPSR.0975-8232.5(2).432-37

17.   Ramasamy SP et al. Broad-Spectrum Antimicrobial, Antioxidant, and Anticancer Studies of Leaf Extract of Simaroubaglauca DC in vitro. Antibiotics. 2022 Jan;11(1):59.doi:10.3390/antibiotics11010059

18.   Quindós G et al. Therapeutic tools for oral candidiasis: Current and new antifungal drugs. Medicina oral, patologia oral y cirugiabucal. 2019 Mar;24(2):e172.doi: 10.4317/medoral.22978.doi: 10.52711/0974-360x.2021.00671

19.   Charyulu RN, Devi P, Jose J, Shetty AV. Formulation and evaluation of mucoadhesive oral gel containing miconazole nitrate for oral candidiasis. Research Journal of Pharmacy and Technology. 2013 Nov 28;6(11):1251-7.

20.   Doddanna SJ et al. Antimicrobial activity of plant extracts on Candida albicans: An in vitro study. Indian Journal of Dental Research. 2013 Jul 1;24(4):401.doi: 10.4103/0970-9290.118358

21.   Mortazavi Het al. Diagnostic features of common oral ulcerative lesions: an updated decision tree. International journal of dentistry. 2016 Oct 3;2016. doi:10.1155/2016/7278925

22.   Sabira B, Alex F, Alex L, Manuel S, Sebastin S. Effectiveness of Structured Teaching Programme on knowledge regarding Oral cancer among adolescent boys in selected schools at Kollam. International Journal of Advances in Nursing Management. 2019;7(3):211-6.doi: 10.5958/2454-2652.2019.00049.0

23.   Lee TY, Tseng YH. The potential of phytochemicals in oral cancer prevention and therapy: a review of the evidence. Biomolecules. 2020 Aug;10(8):1150.doi:10.3390/biom10081150

24.   Rivero‐Cruz JF et al. Cytotoxic constituents of the twigs of Simaroubaglauca collected from a plot in Southern Florida. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2005 Feb;19(2):136-40. doi:10.1002/ptr.1642

25.   Umesh TG. In-vitro antioxidant potential, free radical scavenging and cytotoxic activity of Simarouba gluaca leaves. International Journal of Pharmacy and Pharmaceutical Sciences. 2015;7(2):411-6.

26.   Vikas B et al. The Apoptotic Properties of Leaf Extracts of Simaroubaglauca against Human Leukemic Cancer Cells. Asian Pacific Journal of Cancer Prevention: APJCP. 2021 Apr;22(4):1305. doi:10.31557/apjcp.2021.22.4.1305

27.   R A, Mishra B. Evaluation of anti-inflammatory and antidiabetic activity of Simaroubaglauca bark extract: an in vitro study. Asian Journal of Pharmaceutical and Clinical Research. 2020 May 22;74–8.doi:10.22159/ajpcr.2020.v13i8.37916

28.   Fukamiya N et al.  Structure–activity relationships of quassinoids for eukaryotic protein synthesis. Cancer Letters. 2005 Mar 18;220(1):37-48.doi: 10.1016/j.canlet.2004.04.023

29.   Karthikeyan S et al. Glaucarubinone sensitizes KB cells to paclitaxel by inhibiting ABC transporters via ROS-dependent and p53-mediated activation of apoptotic signaling pathways. Oncotarget. 2016 Jul 5;7(27):42353. doi:10.18632/oncotarget.9865

30.   Yeo D et al. Glaucarubinone and gemcitabine synergistically reduce pancreatic cancer growth via down-regulation of P21-activated kinases. Cancer Letters. 2014 May 1;346(2):264-72.doi:10.1016/j.canlet.2014.01.001

31.   Jose A et al. Tricaproin isolated from Simaroubaglauca inhibits the growth of human colorectal carcinoma cell lines by targeting class-1 histone deacetylases. Frontiers in Pharmacology. 2018 Mar 12;9:127. doi:10.3389/fphar.2018.00127

32.   Thirunavakarasu R.Antioxidants and Oral Cancer - A Review. Research Journal of Pharmacy and Technology. 2016; 9(8):1287-1290.doi: 10.5958/0974-360x.2016.00244.4

33.   Osagie-Eweka SD. Phytochemical analyses and comparative in vitro antioxidant studies of aqueous, methanol and ethanol stem bark extracts of Simaroubaglauca DC.(Paradise tree). African Journal of Plant Science. 2018 Jan 31;12(1):7-16. doi:10.5897/AJPS2017.1547

34.   Ariharasivakumar G et al. Evaluation of Leaf extracts of Simaroubaglauca on Experimentally Induced Inflammatory Bowel Diseases in Wistar rats. Research Journal of Pharmacy and Technology. 2020;13(4):1888-94.doi: 10.5958/0974-360X.2020.00340.6

35.   Kleinstein SE et al. Inflammatory networks linking oral microbiome with systemic health and disease. Journal of Dental Research. 2020 Sep;99(10):1131-9.doi: 10.1177/0022034520926126

 

 

 

 

 

 

Received on 02.04.2022            Modified on 04.07.2022

Accepted on 24.09.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2023; 16(6):2825-2828.

DOI: 10.52711/0974-360X.2023.00465