Abstract
Background:
The aim of this study was to assess and compare the efficacy of curcuminoid gel as an adjuvant to scaling and root planing (SRP) in chronic periodontitis patients.
Materials and Methods:
Thirty subjects participated in this randomized controlled study. The control sites received SRP alone, while the experimental sites received curcuminoid gel as a local drug delivery in addition to SRP. Clinical parameters such as the Gingival Index, Oral Hygiene Index-Simplified, probing pocket depth, and clinical attachment level were assessed at baseline and 3-month posttreatment. In both control and test sites, prostaglandin E2 (PGE2) levels in gingival crevicular fluid (GCF) were assessed at baseline and 45 days posttreatment.
Results:
Parametric tests of significance were used for statistical analysis. Results revealed a statistically significant difference between the groups in both clinical and biochemical parameters.
Conclusion:
In treating moderate chronic periodontitis, the adjunctive use of curcuminoid gel significantly improved clinical outcomes compared to SRP alone. Following the procedure, the PGE2 level in GCF was substantially lower in the test sites than in the control sites. Controlled release mechanisms lessen inflammation and prevent recolonization for an extended period. Given the limitations of the study, curcuminoid gel may be utilized in addition to nonsurgical periodontal treatment.
Keywords: Curcuminoid gel, periodontitis, prostaglandin E2
INTRODUCTION
Plaque biofilm is a source of the inflammatory process that eventually results in the loss of periodontal attachment and tooth loss.[1] Strict oral hygiene maintenance and mechanical tooth debridement are common treatments for periodontal disease. However, thorough mechanical debridement of regions with deep periodontal pockets is difficult to accomplish. Systemic antibiotics have been used as adjuvant treatment due to the microbial etiology of periodontitis.[2] Local drug delivery systems were developed to overcome the drawbacks of systemic antibiotic therapy, which include the development of resistant bacteria, hypersensitivity reaction, organ toxicity, inadequate drug concentration at the pocket site, rapid decline of drug levels, frequent dosing, patient noncompliance, and the need for high dosages to achieve the desired concentration in the gingival crevicular fluid (GCF).[3]
Since the disease is confined to the periodontium, the best course of treatment seems to be local drug delivery within the periodontal pocket. The pocket facilitates the easy installation of the drug delivery system and acts as an integrated reservoir. The GCF serves as a medium for drug release and diffusion within the pocket. High concentrations of drugs can also be maintained in the GCF for extended durations.[4]
Commercially available medications used include tetracyclines,[5] doxycycline,[6,7] minocycline,[8] metronidazole,[9] and chlorhexidine;[10] however, they are expensive. It is also clear that continuous usage of synthetic medicines leads to pharmaceutical pollution.[11] Hence, it is high time for professionals from the fields of drug discovery, pharmaceutics, and health care to bring out alternate means to reduce the pollution. Plant-derived substitutes are viable options for addressing pollution concerns. Using phytomolecules as medicines is not a new concept in health care.
Curcuminoid is a widespread antimicrobial agent in Indian traditional medicine. Curcuma longa’s rhizome, turmeric, is a more palatable and practical alternative. Curcuminoids include a group of compounds such as curcumin, dimethoxy curcumin, and bisdemethoxycurcumin, derived from the Zingiberaceae family.[12] These compounds exhibit anti-inflammatory, antioxidant, antibacterial, hepatoprotective, immunostimulant, antiseptic, antimutagenic, and wound-healing properties.[13]
The purpose of the study was to evaluate the effectiveness of curcuminoid gel as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis.
MATERIALS AND METHODS
Thirty patients aged 25–60 years, diagnosed with localized or generalized chronic periodontitis and having at least two nonadjacent sites with pocket depths of 4–6 mm in different quadrants of the mouth were included in this randomized controlled study. Patients with systemic disorders, pregnant and lactating women, smokers, betel nut chewers, mobile teeth, furcation or angular defects, and periodontal pockets more than 7 mm were excluded. Prior to the procedure, all patients provided written informed consent.
A mouth mirror, explorer, and University of North Carolina (UNC-15) probe were used to measure clinical data. The selected sites were randomly assigned as control or experimental in a split-mouth design. Parameters noted included the Oral Hygiene Index-Simplified (OHI-S), Gingival Index, probing pocket depth (PPD), clinical attachment level (CAL), and prostaglandin E2 (PGE2) levels in GCF. Both at baseline and 3 months after the procedure, the clinical parameters were documented. PGE2, a biochemical marker, was measured at baseline and 45 days posttreatment.[14,15]
Thirty experimental sites received SRP followed by the placement of 2% curcuminoid gel as local drug delivery, while 30 control sites received only SRP. SRP was performed using Gracey curettes in a single-sitting protocol. A periodontal dressing (GC Coe-Pak) was applied to retain the drug and prevent contamination. Patients were recalled after a week for dressing removal. A syringe with a blunt-ended 23-gauge cannula, similar in size to a periodontal probe, was used to place the gel [Figures 1–6].
Figure 1.
Baseline probing pocket depth showing 6 mm of probing depth
Figure 6.
Postopervative probing pocket depth showing 3 mm of probing depth
Figure 2.
Gingival crevicular fluid collection for prostaglandin E2 analysis
Figure 3.
Scaling and root planing
Figure 4.
Curcuminoid gel placement as local drug delivery
Figure 5.
Periodontal dressing given postoperatively
The curcuminoid gel formulation used in the study was patented (ref no.: 202441044122; date: 14.06.2024, Indian Patent Office). Curcuminoids which are present in turmeric rhizome are extracted and crystallized in the purest possible form. The names of different curcuminoids and their molecular structures are as follows: curcumin, demethoxycurcumin, and bisdemethoxycurcumin [Figure 7].
Figure 7.
Molecular structure of curcuminoids
The above molecules are isolated from turmeric by a solvent extraction process by following steps: the flakes of dried turmeric were soaked in ethyl acetate for about 3 h. Ethyl acetate dissolves curcuminoids present in the turmeric. Ethyl acetate containing curcuminoids is drained from the vessel through a filter. Then, the ethyl acetate solution is concentrated to get crystals of curcuminoids, which are filtered, dried, and used for the formulation.
Powdered crystals of curcuminoids were dissolved in polysorbate. The concentration of curcuminoids in this formulation is 8% w/w. The formulation was tested for all necessary parameters as per global regulations, and on confirming that the formulation met all the requirements, it was used in the study.
According to the results of a thin-layer chromatographic analysis, the curcuminoids lot utilized to prepare the gel is 96.78% w/w pure and free of any foreign contaminants [Figure 8].
Figure 8.
Thin-layer chromatographic examination of curcuminoids
Microcapillary pipettes (Kimble Chase Life Science Capillary Tube-USA) were utilized in the collection of GCF samples, and they were stored at −80°C. The PGE2 levels in collected GCF were analyzed using enzyme-linked immunosorbent assay (ELISA). This sandwich ELISA kit is designed to detect PGE2 levels quantitatively and accurately. Human PGE2 antibody has been precoated on the ELISA kit. When the GCF sample is added, the PGE2 attaches itself to the coated antibodies on the wells. Subsequently, the PGE2 in the GCF sample binds to the biotinylated Human PGE2 that has been introduced. Next comes the addition of streptavidin-horseradish peroxidase (HRP), which attaches itself to the biotinylated PGE2 antibody. In the washing process, unbound streptavidin-HRP is removed after incubation. Subsequently, color appears with the amount of Human PGE2 when a substrate solution is introduced. At 450 nm, absorbance is measured after the addition of an acidic stop solution to terminate the process.
RESULTS
Sixty sites were treated – 30 as control and 30 as experimental sites (curcuminoid gel). Following the procedure, PGE2 levels, CAL, PPD, Gingival Index, and OHI-S show significant improvement in both groups [Tables 1, 2 and Graphs 1, 2]. However, statistically significant values were observed in the experimental sites when compared with the control group [Table 3]. In comparison to baseline data, Graph 3 demonstrates a statistically significant decrease in PGE2 levels in GCF postoperatively.
Table 1.
Intragroup comparison of probing pocket depth, clinical attachment level, Gingival Index, Oral Hygiene Index-Simplified, and prostaglandin E2 levels in gingival crevicular fluid at baseline and 3 months in the control group
| Control group | n | Mean | SD | SE | Paired t | P |
|---|---|---|---|---|---|---|
| PPD | ||||||
| Baseline | 30 | 5.60 | 0.498 | 0.091 | 16.86 | 0.001** |
| 3rd month | 30 | 3.27 | 0.640 | 0.117 | ||
| CAL | ||||||
| Baseline | 30 | 3.53 | 0.507 | 0.093 | 16.55 | 0.001** |
| 3rd month | 30 | 1.60 | 0.675 | 0.123 | ||
| Gingival Index | ||||||
| Baseline | 30 | 2.00 | 0.001** | 0.001** | 23.03 | 0.001** |
| 3rd month | 30 | 0.93 | 0.254 | 0.046 | ||
| Oral Hygiene Index-Simplified | ||||||
| Baseline | 30 | 1.73 | 0.394 | 0.072 | 23.58 | 0.001** |
| 3rd month | 30 | 0.46 | 0.234 | 0.043 | ||
| PGE2 levels in GCF (nanogram/L) | ||||||
| Baseline | 30 | 221.32 | 6.599 | 1.205 | 54.06 | 0.001** |
| Postoperative | 30 | 126.70 | 5.825 | 1.064 |
**Significant at 1% (highly significant). P –Probability value; n – Total number; SD – Standard deviation; SE – Standard error; PGE2 – Prostaglandin E2; CAL – Clinical attachment level; PPD – Probing pocket depth; GCF – Gingival crevicular fluid
Table 2.
Intragroup comparison of probing pocket depth, clinical attachment level, Gingival Index, Oral Hygiene Index-Simplified, and prostaglandin E2 levels in gingival crevicular fluid at baseline and 3 months in the test group
| Test group | n | Mean | SD | SE | Paired t | P |
|---|---|---|---|---|---|---|
| PPD | ||||||
| Baseline | 30 | 5.23 | 0.568 | 0.104 | 26.66 | 0.001** |
| 3rd month | 30 | 2.47 | 0.629 | 0.115 | ||
| CAL | ||||||
| Baseline | 30 | 3.20 | 0.551 | 0.101 | 24.08 | 0.001** |
| 3rd month | 30 | 0.53 | 0.681 | 0.124 | ||
| Gingival Index | ||||||
| Baseline | 30 | 2.00 | 0.001** | 0.001** | 15.58 | 0.001** |
| 3rd month | 30 | 0.57 | 0.504 | 0.092 | ||
| Oral Hygiene Index-Simplified | ||||||
| Baseline | 30 | 1.74 | 0.384 | 0.070 | 26.54 | 0.001** |
| 3rd month | 30 | 0.51 | 0.227 | 0.042 | ||
| PGE2 levels in GCF (nanogram/l) | ||||||
| Baseline | 30 | 221.44 | 7.174 | 1.310 | 47.35 | 0.001** |
| Postoperative | 30 | 120.41 | 9.915 | 1.810 |
**Significant at 1% (highly significant). P – Probability value; n – Total number; SD – Standard deviation; SE – Standard error, PGE2 – Prostaglandin E2; CAL – Clinical attachment level; PPD – Probing pocket depth; GCF – Gingival crevicular fluid
Graph 1.
Intragroup comparison of clinical parameters and prostaglandin E2 levels in gingival crevicular fluid at baseline and 3 months in the control group. PGE2 – Prostaglandin E2, CAL – Clinical attachment level, OHI-S – Oral Hygiene Index-Simplified, GI – Gingival Index
Graph 2.
Intragroup comparison of clinical parameters and prostaglandin E2 levels in gingival crevicular fluid at baseline and 3 months in the test group. PGE2 – Prostaglandin E2, CAL – Clinical attachment level, OHI-S – Oral Hygiene Index-Simplified, GI – Gingival Index
Table 3.
Intergroup comparison of probing pocket depth, clinical attachment level, Gingival Index, Oral Hygiene Index-Simplified, and prostaglandin E2 levels in gingival crevicular fluid at baseline and 3 months in the control and test group
| Group | n | Mean | SD | SE | Paired t | P |
|---|---|---|---|---|---|---|
| PPD–baseline | ||||||
| Control | 30 | 5.60 | 0.498 | 0.091 | 2.66 | 0.010** |
| Test | 30 | 5.23 | 0.568 | 0.104 | ||
| PPD 3rd month | ||||||
| Control | 30 | 3.27 | 0.640 | 0.117 | 4.88 | 0.001** |
| Test | 30 | 2.47 | 0.629 | 0.115 | ||
| CAL–baseline | ||||||
| Control | 30 | 3.53 | 0.507 | 0.093 | 2.44 | 0.018* |
| Test | 30 | 3.20 | 0.551 | 0.101 | ||
| CAL–3rd month | ||||||
| Control | 30 | 1.60 | 0.675 | 0.123 | 6.09 | 0.001** |
| Test | 30 | 0.53 | 0.681 | 0.124 | ||
| Gingival Index – baseline | ||||||
| Control | 30 | 2.00 | 0.000a | 0.001** | - | - |
| Test | 30 | 2.00 | 0.000a | 0.001** | ||
| Gingival Index – 3rd month | ||||||
| Control | 30 | 0.93 | 0.254 | 0.046 | 3.56 | 0.001** |
| Test | 30 | 0.57 | 0.504 | 0.092 | ||
| Oral Hygiene Index-Simplified – baseline | ||||||
| Control | 30 | 1.73 | 0.394 | 0.072 | 0.166 | 0.869 |
| Test | 30 | 1.74 | 0.384 | 0.070 | ||
| Oral Hygiene Index-Simplified – 3rd month | ||||||
| Control | 30 | 0.46 | 0.234 | 0.043 | 0.839 | 0.405 |
| Test | 30 | 0.51 | 0.227 | 0.042 | ||
| Baseline PGE2 levels in GCF | ||||||
| Control | 30 | 221.32 | 6.599 | 1.205 | 0.066 | 0.948 |
| Test | 30 | 221.44 | 7.174 | 1.310 | ||
| Postoperative PGE2 levels in GCF | ||||||
| Control | 30 | 126.70 | 5.825 | 1.064 | 3.00 | 0.004** |
| Test | 30 | 120.41 | 9.915 | 1.810 |
*Significant at 5%; **Significant at 1% (highly significant); aVery low P value. n – Total number, SD – Standard deviation, SE – Standard error; P – Probability value; PGE2 – Prostaglandin E2; CAL – Clinical attachment level; PPD – Probing pocket depth; GCF – Gingival crevicular fluid
Graph 3.
Intragroup comparison of prostaglandin E2 levels in gingival crevicular fluid in the control and test groups. GCF – Gingival crevicular fluid
DISCUSSION
As far as the literature is evident, no research has been published on the use of curcuminoid gel for local drug delivery. Drug delivery systems currently provide a variety of natural formulations, including tulsi, eucalyptus extract, aloe vera, bloodroot, chamomile, green tea, catechin, and turmeric, as a result of growing interest and knowledge of the therapeutic benefits of natural commodities.[16]
Curcuminoid’s desired preventative or potential therapeutic characteristics have also been linked to its advantageous antioxidant, anti-inflammatory, antibacterial, and chemopreventive capabilities. The most plausible mechanism by which curcuminoids reduce inflammation is by its ability to inhibit cyclooxygenase-2 (COX-2), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS). Key enzymes such as COX-2, LOX, and iNOS control inflammatory reactions.
Along with clinical parameters, biochemical parameters like PGE2 levels help in assessing the disease severity. PGE2 is also one of the key proteinases present in GCF that affects the periodontium and is involved in tissue breakdown in chronic periodontitis. Increased levels of PGE2 in GCF show an association with periodontal diseases and serve to be a potential biomarker.
PGE2 induces vasodilation and increases capillary permeability, leading to clinical manifestations as gingival redness, edema, and inhibition of collagen production and bone resorption. The majority of the inflammatory and periodontal destructive changes that occur in periodontal disease may theoretically only be brought on by the presence and direct actions of PGE2.
The purpose of this study was to assess the effectiveness of curcuminoid gel in treating patients with chronic periodontitis as an adjunct to SRP. In this study, 30 sites were treated with SRP alone, and 30 sites were treated with SRP and curcuminoid gel. At baseline and 45 days after the procedure, GCF was obtained for PGE2 analysis. Using the ELISA, PGE2 was analyzed. The findings demonstrated a significant clinical improvement in the 3-month evaluation from baseline for clinical parameters such as Oral Hygiene Index, Gingival Index, CAL, and PPD. In addition, PGE2 levels in GCF were reduced following the procedure.
Behal et al. found that applying turmeric gel as a local drug administration strategy comparably improved clinical measure. The clinical and microbiological effectiveness of locally administered 1% curcumin gel as a supplement to SRP in the management of chronic periodontitis was investigated by Bhatia et al., and the study’s findings demonstrated a substantial improvement in clinical parameters.[17,18]
All of the study participants thought the experimental material was satisfactory and comfortable. The absence of tooth discoloration, ulcer formation, dryness or pain, or burning sensation indicated appropriate biological acceptance.
Results of the study show that a novel local drug used in conjunction with SRP effectively eliminates local irritants and improves the parameters such as the Gingival Index, OHI-S, PPD, CAL, and PGE2 levels in GCF. The method of local administration of the drug used in this study is simple to use and intuitive. Due to its syringe compatibility, it is simple to slide into the pocket. Furthermore, the bioadhesive property of curcuminoid gel allows for better retention and is well accepted, with no adverse effects on biology.
Evaluation of clinical indicators at baseline, 3 months later, and the GCF were conducted in the current study. The study does not include microbiological sampling to determine the bacterial count before and following treatment to assess the severity of the disease. Additional long-term monitoring is required to assess the effectiveness of curcuminoid gel as a therapeutic adjuvant.
Obtaining GCF samples without contaminating them with saliva is challenging. Results showed that when curcuminoid gel was used as an adjuvant to nonsurgical periodontal treatment, clinical indicators significantly improved, and PGE2 levels decreased after treatment. However, these findings were limited to the current experiment.
CONCLUSION
In treating moderate chronic periodontitis, the adjunctive use of curcuminoid gel significantly improves clinical outcome as compared to SRP alone. Controlled release mechanisms lessen inflammation and keep infections from recolonizing for an extended amount of time.
Therefore, given the study’s limitations, administering curcuminoid gel as an adjuvant to traditional nonsurgical therapy may be preferred. More long-term monitoring and a microbiological culture investigation are needed to determine how well the curcuminoid gel works as an adjuvant treatment for patients with chronic periodontitis.
Conflicts of interest
There are no conflicts of interest.
Acknowledgement
I express my gratitude to Dr. Siva Shanmugam for his assistance in formulating the gel containing curcuminoids.
Funding Statement
Nil.
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