Aim: To compare the effectiveness of Noni and Bilberry in treating chronic periodontitis.

Materials and methods: The current study is a double-masked, randomized clinical trial. A total of forty patients of age 20 to 55 years were assigned randomly into two groups. After phase-I therapy, In Group A, Morinda citrifolia (MC) (Noni – 1000 mg, Biotrex company) and in Group B, Vaccinium myrtillus L (Bilberry – Biotrex)– 275mg was given adjunctively. In both groups, gingival index (GI), plaque index (PI), clinical parameters such as periodontal probing depth (PPD) and clinical attachment level (CAL), and bone biomarker C-terminal telopeptide (serum β-CTX) were evaluated at baseline and after six months.

Results: The results of the current trial showed that all subjects from the two groups had a significant decrease in the GI, PI, and clinical parameters like PPD and CAL compared from baseline to three months. There was a significant reduction in serum β-CTX levels after phase I therapy in chronic periodontitis subjects after host modulation with Noni and Bilberry. In both the groups, a positive correlation was shown between the clinical parameters and serum c levels. However, there was a statistically significant decrease in the serum β-CTX levels in the group treated with noni compared with the bilberry group.

Conclusion: Morinda citrifolia (Noni) had shown significant effect compared to Vaccinium myrtillus L(bilberry) in treating chronic periodontitis. The beneficial effect of noni is most probably a result of its well-known anti-inflammatory activity.

Keywords: Noni, Morinda citrifolia, Vaccinium myrtillus L, Bilberry HMT, β-CTX, C – terminal telopeptide, NSPT.

Periodontitis is one of the most common diseases that causes gradual deterioration of the tooth supporting tissues due to bacterial infection. It is characterized by the irreversible loss of connective tissue attachment and supporting alveolar bone [1]. Periodontal regeneration materials and techniques are meant to rebuild the damaged tissue by the new periodontal ligament, cementum, and bone formation by a network of biological phenomena [2]. Allogeneic, xenogeneic and alloplastic bone graft materials pose a risk of contamination and allergy during the graft placement or healing process. The use of natural materials in dentistry is only beginning to pick up momentum. For decades, herbal products have also been used in periodontology as mouthwashes, toothpastes, and as restorative materials [3].

Morinda citrifolia, usually referred to as Indian Mulberry, is the scientific name of the commercially accessible noni. Rubiaceae, or the coffee family, includes M. citrifolia [4]. Noni has recently gained notoriety due to its antibacterial, antiviral, antifungal, anticancer, antituberculosis, analgesic, and immunological properties [5]. Due to its impressive therapeutic benefits, Morinda citrifolia (noni) has long been regarded as a significant medicinal plant. More recently, it has been included as a plant of interest in dentistry. Scopoletin, octanoic acid, potassium, vitamin C, terpenoids, alkaloids, β-sitosterol, carotene, vitamin A, flavone glycosides, linoleic acid, amino acids, calcium, and phosphorus are among the substances found in the noni plant that are pertinent for human health [14].

Noni’s phytochemical constituents may have a potential role in the stimulation of osteogenic differentiation and matrix mineralization. Components of noni that have been found to stimulate bone formation include vitamin C, triterpenes, and flavonoids. Triterpenes were shown to promote proliferation, protein synthesis, and ALP activity through TGF-β. Flavonoids were shown to promote the osteogenic differentiation of human bone marrow-derived mesenchymal stem cell.

Vaccinium myrtillus L, usually referred to as the blueberry, is the biological name for the commercially accessible bilberry. The active ingredients present in bilberries include phenolic, hydroxycinnamic, anthocyanins (ACN’S), tannins, flavanols, quinonins, coumarins, stilbenoids, terpenoids, and other organic acids [6]. In bilberries, anthocyanins make up about 90% of the total amount of phenolic compounds in the fruit. Anthocyanins are a class of water- soluble natural pigments that are found in colourful plants and belong to flavonoid compounds. More than 635 ACNs have been identified based on the number and position of the hydroxyl and methoxy groups. Anthocyanins, water-soluble red and blue flavonoid pigments, are powerful antioxidant substances that can mitigate lipid peroxidation and the harmful effects of ROS, in vitro. Anthocyanins found in blueberries can aid in lowering the risk of redundant inflammation in this aspect [9]. ACN’s beneficial benefits on human health as an antioxidant, anti- inflammatory agent, and anti-apoptotic agent are extensively proven [8].

Noble biomarkers of bone resorption include pyridine cross-links. The most often researched collagen-degrading compounds include pyridinoline (hydroxylysl pyridinoline, or Pyr), deoxypyridinoline (lysyl pyridinoline, or Dpy), N-telopeptides, and C-telopeptides. In order to stabilise collagen fibrils deposited in the ECM, mature cross-links develop by lysyl oxidase on lysine and hydroxylysine residues in the N- and C-terminal regions [12]. Type I collagen cross-linked C-terminal telopeptide (β-CTX fragment) is a newer addition to serum markers of bone resorption. β-CTX, a carboxy-terminal telopeptide, is exceptional because it originates from the breakdown of mature collagen and is thus an accurate indicator of the resorption process [13].

The purpose of this study was to evaluate the benefit of adjunctive herbal medicines, noni and bilberry, after the introduction of proper oral hygiene and thorough full-mouth scaling and root planing.

For the study, 40 systemically healthy adults with chronic periodontitis who were receiving treatment at St. Joseph Dental College and Hospital, and were in the age range of 20 to 55 years, with twenty or more natural teeth, bilaterally symmetrical occlusion, and had localised suprabony periodontal pockets measuring 4-6 mm, were selected. Women who are pregnant, people with systemic diseases, people with deleterious habits like drinking, smoking, or using tobacco, people with aggressive periodontitis, and people who have recently received either surgical or nonsurgical periodontal therapy or antimicrobial therapy were excluded from the study. Periodontal parameters including gingival index (GI), plaque index (PI), probing pocket depth (PPD), clinical attachment level (CAL), and bone density were measured at baseline and 6 months. At baseline & 6 months, serum samples from both groups were taken for c-terminal telopeptide analysis.

The groups were treated as follows:

Group-A: consists of 20 Patients with Chronic Periodontitis. Initially, scaling and root planing was done, and an adjuvant prescription of Morinda citrifolia (Noni1000mg- Biotrex nutraceuticals) tablets – 1 tablet once a day for around five months – was provided.

Group-B: consists of 20 Patients with Chronic Periodontitis Initially, scaling and root planing was done, and an adjuvant prescription of Vaccinium myrtillus L (Bilberry275mg- Biotrex nutraceuticals) tablets – 1 tablet once a day for around five months – was provided.

Biochemical analysis:

Sampling from Blood: A venipuncture was used to draw 2 ml of blood from the antecubital fossa. Serum was centrifuged from the blood and kept at -20°C for further examination. An automated electro-chemiluminescent sandwich antibody assay (ECLIA) that is available commercially was used to measure the carboxy-terminal cross-linking telopeptide of type I collagen.

Statistical analysis:

Statistical analysis of the data using Statistical Package for the Social Sciences (SPSS) software 20 was performed. To test the mean changes in scores at different time points within each study group Student’s T test was employed.

On intragroup comparison of the GI, PI, PD, CAL & C-terminal telopeptide results at follow-up after six months, were compared between the two groups, they gave a P- value of 0.001, which was statistically significant.

On intergroup comparison of the GI, PI, PD, CAL & C-terminal telopeptide results at follow-up after six months, were compared between the two groups, they gave a P- value of 0.07,0.16,0.44 ,0.14 & 0.681 respectively, which was statistically insignificant.

The effectiveness of periodontal therapy is directly correlated with its capacity to reduce the prevalence and/or levels of one or more harmful bacterial species. This study’s objective is to report the effects of noni and bilberry capsules on periodontal clinical outcome and serum β-CTX in periodontitis patients. Our hypothesis was that taking bilberry and noni capsules along with scaling and root planing may bring down serum β-CTX levels and periodontal clinical parameters. All subjects received oral prophylaxis to maintain homogeneous baseline data for the two groups. Quercetin, Kaempferol and Coumarins (scopoletin), which have antioxidant and anti- inflammatory qualities, are among the flavonoids found in noni. According to Rosa Tundis et al, it’s the iridoids that deserve special attention since they have antinociceptive and anti-inflammatory action, antioxidant potential, and metabolic benefits [15].

Following SRP, Noni has dramatically decreased clinical attachment levels and probing depths. The fruit of the noni contains scopoletin, which can boost macrophage function and activity while simultaneously raising leukocyte. More successfully preventing the bacteria that cause gingivitis disease may be made possible by scopoletin’s impact   on   macrophages. Yufri Aldi et al, in his study stated that the production of IL-4 and IL-10, which promote the proliferation and differentiation of T cells into Th1 cells that can release cytokines that affect the proliferation and differentiation of monocytes and leukocytes, can also be reduced by scopoletin [7]. Gingival index scores had shown reduction in gingival inflammation at baseline and at 6 months (See Table 1; Graph 1)

Table 1: Intergroup Comparison of mean GI and PI scores at baseline and 6 months using independent sample t-test

Graph – 1

the probing pocket depth reduced at 6-month interval and there was a statistically significant gain in relative attachment level scores from baseline to 6-month interval (See Table 2; Graph 2) and the results were correlated with the study done by Blessy Shin Sabu et al [4].

Table 2: Intergroup Comparison of mean PD and CAL scores at baseline and 6 months using independent sample t-test

Graph – 2

After using M. citrifolia extract, there was a substantial decrease in gingival inflammation as a result of its anti-inflammatory action through inhibiting matrix metalloproteinase, as suggested by Masuda et al., and antibacterial activity against oral microorganisms including periodontopathogens. As suggested by Sharmila Hussain et al, the bone marrow-derived stem cells ability to initiate differentiation and proliferate as well as differentiate into osteoblasts is improved by noni extract’s action on human periodontal ligament cells [16].

Blueberries (Vaccinium myrtillus) contain various anthocyanins, such as delphinidin and  cyanidine glycosides, a bioactive molecule that improves inflammatory conditions and thus gum health. Increased osteoclastogenesis and reduced osteoclast apoptosis are the causes of the rise in bone resorption. According to Luka Dudaric et al, indirectly, ROS may stimulate osteoblast/osteoclast coupling and subsequent osteoclast differentiation through RANK ligand (RANKL), or directly by stimulating signalling associated with osteoclast differentiation and receptor activator of nuclear factor (NF)-B (RANK) [10].

Gingival index scores had shown reduction in gingival inflammation at baseline and at 6 months, the probing pocket depth reduced at 6-month interval and there was a statistically significant gain in relative attachment level scores from baseline to 6-month interval and the results were correlated with the studies done by Aakriti Sharma et al [9]. Numerous ACNs may encourage mesenchymal stem cells to differentiate into osteoblasts or may prevent osteoclastogenesis. Investigations were made on how most ACNs affect osteoclast differentiation.

The c-Fos pathway, the NF-B pathway, the JNK pathway, the Ca2+ pathway, and the ROS pathway are four important pathways in osteoclastogenesis. For these routes to work, they must also interact with one another. RANK signal-mediated osteoclast formation is also significantly influenced by three subfamilies of mitogen-activated protein kinases (MAPKs): P38, ERK1/2, and JNK (Zhai et al., 2014. A crucial transcription factor and a key target gene in most pathways controlling osteoclast differentiation is nuclear factor of activated T cells 1 (NFATc1). By controlling osteoblasts and osteoclasts, the flavonoid delphinidin [2-(3,4,5- trihydroxyphenyl) chromenylium-3,5,7- triol] found in abundance in berries has a protective effect against bone loss and helped in significant reduction in serum β-CTX levels after HMT with Bilberry [17]. The anti-oxidant flavonoids kaempferol, quercitin, rutin, and iridoids with anti- inflammatory and anti-nociceptive effect are abundant in the extracts of noni and helped in significant reduction in serum β-CTX levels (See Table 3; Graph 3) after HMT with Noni [11].

Table 3: Intergroup Comparison of mean Serum β-CTX scores at baseline and 6 months using      independent sample t-test

Graph – 3

Patients in this trial with chronic periodontitis who received host modulation with noni and bilberry after phase I therapy had considerable reduction in clinical parameters and blood

levels of β -CTX compared to baseline. However, on intra group comparison, the serum β-CTX levels in the noni group were statistically significantly lower than those in the bilberry group.

One limitation of this study is the evaluation’s small sample size.