Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti-inflammatory activity through the suppression of numerous cell signalling pathways including NF-κB, STAT3, Nrf2, ROS and COX-2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials.

Linked Articles
This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc

https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.13621

Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases

This review highlights recent advances towards non-invasive and continuous glucose monitoring devices, with a particular focus placed on monitoring glucose concentrations in alternative physiological fluids to blood.

Glucose Sensing for Diabetes Monitoring: Recent Developments.

Improving the safety efficacy ratio of existing drugs is a current challenge to be addressed rather than the development of novel drugs which involve much expense and time. The efficacy of drugs is affected by a number of factors such as their low aqueous solubility, unequal absorption along the gastrointestinal (GI) tract, risk of degradation in the acidic milieu of the stomach, low permeation of the drugs in the upper GI tract, systematic side effects, etc. This review aims to enlighten readers on the role of pH sensitive hydrogels in drug delivery, their mechanism of action, swelling, and drug release as a function of pH change along the GI tract. The basis for the selection of materials, their structural features, physical and chemical properties, the presence of ionic pendant groups, and the influence of their pKa and pKb values on the ionization, consequent swelling, and targeted drug release are also highlighted.

https://www.mdpi.com/2073-4360/9/4/137/pdf

pH Sensitive Hydrogels in Drug Delivery: Brief History, Properties, Swelling, and Release Mechanism, Material Selection and Applications

Background
Dental plaque associated gingivitis is a reversible inflammatory condition caused by accumulation and persistence of microbial biofilms (dental plaque) on the teeth. It is characterised by redness and swelling of the gingivae (gums) and a tendency for the gingivae to bleed easily. In susceptible individuals, gingivitis may lead to periodontitis and loss of the soft tissue and bony support for the tooth. It is thought that chlorhexidine mouthrinse may reduce the build-up of plaque thereby reducing gingivitis.

Objectives
To assess the effectiveness of chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for the control of gingivitis and plaque compared to mechanical oral hygiene procedures alone or mechanical oral hygiene procedures plus placebo/control mouthrinse. Mechanical oral hygiene procedures were toothbrushing with/without the use of dental floss or interdental cleaning aids and could include professional tooth cleaning/periodontal treatment.

To determine whether the effect of chlorhexidine mouthrinse is influenced by chlorhexidine concentration, or frequency of rinsing (once/day versus twice/day).

To report and describe any adverse effects associated with chlorhexidine mouthrinse use from included trials.

Search methods
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 28 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 28 September 2016); MEDLINE Ovid (1946 to 28 September 2016); Embase Ovid (1980 to 28 September 2016); and CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 28 September 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.

Selection criteria
We included randomised controlled trials assessing the effects of chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for at least 4 weeks on gingivitis in children and adults. Mechanical oral hygiene procedures were toothbrushing with/without use of dental floss or interdental cleaning aids and could include professional tooth cleaning/periodontal treatment. We included trials where participants had gingivitis or periodontitis, where participants were healthy and where some or all participants had medical conditions or special care needs.

Data collection and analysis
Two review authors independently screened the search results extracted data and assessed the risk of bias of the included studies. We attempted to contact study authors for missing data or clarification where feasible. For continuous outcomes, we used means and standard deviations to obtain the mean difference (MD) and 95% confidence interval (CI). We combined MDs where studies used the same scale and standardised mean differences (SMDs) where studies used different scales. For dichotomous outcomes, we reported risk ratios (RR) and 95% CIs. Due to anticipated heterogeneity we used random-effects models for all meta-analyses.

Main results
We included 51 studies that analysed a total of 5345 participants. One study was assessed as being at unclear risk of bias, with the remaining 50 being at high risk of bias, however, this did not affect the quality assessments for gingivitis and plaque as we believe that further research is very unlikely to change our confidence in the estimate of effect.

Gingivitis

After 4 to 6 weeks of use, chlorhexidine mouthrinse reduced gingivitis (Gingival Index (GI) 0 to 3 scale) by 0.21 (95% CI 0.11 to 0.31) compared to placebo, control or no mouthrinse (10 trials, 805 participants with mild gingival inflammation (mean score 1 on the GI scale) analysed, high-quality evidence). A similar effect size was found for reducing gingivitis at 6 months. There were insufficient data to determine the reduction in gingivitis associated with chlorhexidine mouthrinse use in individuals with mean GI scores of 1.1 to 3 (moderate or severe levels of gingival inflammation).

Plaque

Plaque was measured by different indices and the SMD at 4 to 6 weeks was 1.45 (95% CI 1.00 to 1.90) standard deviations lower in the chlorhexidine group (12 trials, 950 participants analysed, high-quality evidence), indicating a large reduction in plaque. A similar large reduction was found for chlorhexidine mouthrinse use at 6 months.

Extrinsic tooth staining

There was a large increase in extrinsic tooth staining in participants using chlorhexidine mouthrinse at 4 to 6 weeks. The SMD was 1.07 (95% CI 0.80 to 1.34) standard deviations higher (eight trials, 415 participants analysed, moderate-quality evidence) in the chlorhexidine mouthrinse group. There was also a large increase in extrinsic tooth staining in participants using chlorhexidine mouthrinse at 7 to 12 weeks and 6 months.

Calculus

Results for the effect of chlorhexidine mouthrinse on calculus formation were inconclusive.

Effect of concentration and frequency of rinsing

There were insufficient data to determine whether there was a difference in effect for either chlorhexidine concentration or frequency of rinsing.

Other adverse effects

The adverse effects most commonly reported in the included studies were taste disturbance/alteration (reported in 11 studies), effects on the oral mucosa including soreness, irritation, mild desquamation and mucosal ulceration/erosions (reported in 13 studies) and a general burning sensation or a burning tongue or both (reported in nine studies).

Authors' conclusions
There is high-quality evidence from studies that reported the Loe and Silness Gingival Index of a reduction in gingivitis in individuals with mild gingival inflammation on average (mean score of 1 on the 0 to 3 GI scale) that was not considered to be clinically relevant. There is high-quality evidence of a large reduction in dental plaque with chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for 4 to 6 weeks and 6 months. There is no evidence that one concentration of chlorhexidine rinse is more effective than another. There is insufficient evidence to determine the reduction in gingivitis associated with chlorhexidine mouthrinse use in individuals with mean GI scores of 1.1 to 3 indicating moderate or severe levels of gingival inflammation. Rinsing with chlorhexidine mouthrinse for 4 weeks or longer causes extrinsic tooth staining. In addition, other adverse effects such as calculus build up, transient taste disturbance and effects on the oral mucosa were reported in the included studies.

/pdf/chlorhexidine-mouthrinse-as-an-adjunctive-treatment-for-cfe5n9a1rm.pdf

Chlorhexidine mouthrinse as an adjunctive treatment for gingival health.

Curcumin is a naturally occurring polyphenolic compound present in rhizome of Curcuma longa belonging to the family zingiberaceae. Growing experimental evidence revealed that curcumin exhibit multitarget biological implications signifying its crucial role in health and disease. The current review highlights the recent progress and mechanisms underlying the wide range of pharmacological effects of curcumin against numerous diseases like neuronal, cardiovascular, metabolic, kidney, endocrine, skin, respiratory, infectious, gastrointestinal diseases and cancer. The ability of curcumin to modulate the functions of multiple signal transductions are linked with attenuation of acute and chronic diseases. Numerous preclinical and clinical studies have revealed that curcumin modulates several molecules in cell signal transduction pathway including PI3K, Akt, mTOR, ERK5, AP-1, TGF-β, Wnt, β-catenin, Shh, PAK1, Rac1, STAT3, PPARγ, EBPα, NLRP3 inflammasome, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4 and MyD-88. Curcumin has a potential to prevent and/or manage various diseases due to its anti-inflammatory, anti-oxidant and anti-apoptotic properties with an excellent safety profile. In contrast, the anti-cancer effects of curcumin are reflected due to induction of growth arrest and apoptosis in various premalignant and malignant cells. This review also carefully emphasized the pharmacokinetics of curcumin and its interaction with other drugs. Clinical studies have shown that curcumin is safe at the doses of 12 g/day but exhibits poor systemic bioavailability. The use of adjuvant like piperine, liposomal curcumin, curcumin nanoparticles and curcumin phospholipid complex has shown enhanced bioavailability and therapeutic potential. Further studies are warranted to prove the potential of curcumin against various ailments.

Cellular and molecular mechanisms of curcumin in prevention and treatment of disease

Objectives: Saliva contains a variety of host defense factors It influences calculus formation and periodontal disease Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease Study Design: The study population consisted of 300 patients They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis The randomized unstimulated saliva from each patient was collected and pH was tested Data was analyzed statistically using analysis of variance technique Results: The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group ( P = 0001) whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group ( P = 0001) Conclusion: These results indicate a significant change in the pH depending on the severity of the periodontal condition The salivary pH shows significant changes and thus relevance to the severity of periodontal disease Salivary pH may thus be used as a quick chairside diagnostic biomarker

Salivary pH: A diagnostic biomarker.

Purpose To evaluate the efficacy of curcumin mouthwash as an adjunct to scaling and root planing in the treatment of chronic gingivitis and to compare curcumin to chlorhexidine in terms of its anti-inflammatory and anti-microbial properties. Materials and methods Thirty patients aged 20-40 years with generalised chronic gingivitis were included in the study. They were randomly divided into 3 groups of 10 each. In group 1, patients underwent scaling and root planing followed by chlorhexidine mouthwash (SRP/CHX Gr-1); in group 2, patients underwent scaling and root planing followed by curcumin mouthwash (SRP/CUR Gr-2); in group 3, patients underwent only scaling and root planing (SRP Gr-3). Gingival and plaque indices were recorded at baseline (day 0) and 7, 14 and 21 days. Differences between the groups were statistically analysed. Results The clinical parameters showed improvement in all the three groups compared to baseline. When compared to the scaling and root planing group (Gr-3), both curcumin and chlorhexidine groups were found to have statistically significantly better results (P 0.05). Conclusion Curcumin is comparable to chlorhexidine as an anti-inflammatory mouthwash. Thus, it can be considered as an effective adjunct to mechanical periodontal therapy.

Efficacy of curcumin in the treatment of chronic gingivitis: a pilot study.

Purpose To compare the efficacy of alcohol-free chlorhexidine mouthrinse to chlorhexidine with alcohol and a placebo (water) in controlling plaque and reducing gingival inflammation in patients with gingivitis. Materials and methods This was a single-blind, parallel-group study with 30 gingivitis patients in whom the plaque index (Silness and Loe) and gingival index (Loe and Silness) were recorded prior to treatment with 0.2% chlorhexidine mouthrinse with alcohol (group I, n = 10; CHX-A), 0.2% chlorhexidine mouthrinse without alcohol (group II, n = 10; CHXNA) or a placebo (water) (group II, n = 10; P). The plaque and gingival indices were recorded again at days 14 and 28 after the start of treatment. Results There were significant differences in plaque and gingival indices with both chlorhexidine rinses compared to the placebo. The gingival index showed a greater clinical change in group II (CHX-NA) than in group I (CHX-A). Conclusion The alcohol-free rinse was as effective as the one containing alcohol in controlling plaque and reducing gingival inflammation. Therefore, its use can be recommended in all periodontal patients, but especially in those for whom the use of alcohol may lead to side effects.

Efficacy of chlorhexidine mouthrinses with and without alcohol - a clinical study.

Objective: The objective of this study is to evaluate and compare surgical stripping and neodymium-doped: yttrium, aluminum garnet (Nd:YAG) laser techniques for gingival depigmentation and to evaluate their effect on repigmentation. Background data: Gingival depigmentation is often associated with repigmentation. Recurrence of pigmentation differs according to different treatment modalities. Materials and methods: In this study, 40 maxillary sites from 20 patients presenting bilateral melanin gingival hyperpigmentation were selected. Contralateral quadrants in the maxilla were randomly assigned to receive Nd:YAG laser at 3 W, 30 mJ per pulse, with contact mode, and with a handpiece with a 300 μm diameter optic fiber and surgical stripping. Plaque index, Dummett Oral Pigmentation Index (DOPI), Hedin melanin index, size of pigmented area, time interval and extent of repigmentation, time taken for each of the procedures, assessment of pain, intraoperative bleeding index, and patient preference were ...

Comparison of Nd:YAG Laser and Surgical Stripping for Treatment of Gingival Hyperpigmentation: A Clinical Trial.

Background: Chlorhexidine (CHX) is considered as a gold standard of antimicrobial rinses. Various herbal oral rinses are available in the market. However, little is known of its effectiveness. Aim: The aim of this study was to evaluate the clinical changes after the usage of herbal oral rinse and 0.12% CHX. Subjects and Methods: In a randomized clinical trial, 76 patients with dental plaque-induced gingivitis were assigned to Group I (Herbal Oral Rinse - Hiora ; ) and 76 patients with dental plaque-induced gingivitis to Group II (0.12% Chlorhexidine-Peridex ; ). Gingival index and Plaque index scores were recorded at baseline and 21 days after scaling. Results: Intragroup comparison in both groups showed that plaque index and gingival index scores were statistically significant after 21 days as compared to baseline. Intergroup comparison showed that plaque index scores and gingival index scores were statistically significant in Group II as compared to Group I. Conclusion: When herbal oral rinse was compared to 0.12% CHX, 0.12% CHX mouth rinse effectively reduced the clinical symptoms of plaque-induced gingivitis.

Sangeeta Muglikar

Papers

Salivary pH: A diagnostic biomarker.

Efficacy of curcumin in the treatment of chronic gingivitis: a pilot study.

Efficacy of chlorhexidine mouthrinses with and without alcohol - a clinical study.

Comparison of Nd:YAG Laser and Surgical Stripping for Treatment of Gingival Hyperpigmentation: A Clinical Trial.

The comparative effects of 0.12% chlorhexidine and herbal oral rinse on dental plaque-induced gingivitis: A randomized clinical trial.