The commensal oral bacteria are responsible for the initiation and propagation of the disease through the process of dysbiosis, or microbial imbalance. The disease proceeds cyclically with periods of activity and quiescence until therapeutic action is taken, or the tooth and surrounding structures are destroyed by the disease process that may result in the loss of the tooth. As periodontal disease progresses from gingivitis to periodontitis, a greater number of anaerobic organisms colonize deeper periodontal pockets, such as Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, which triggers the host inflammatory response. This response includes the production and dissemination of C-reactive protein (CRP), a biomarker of inflammation, as well as various neutrophil and macrophage compounds such as tumor necrosis factor-alpha (TNF-a), matrix metalloproteinases (MMPs), and interleukins (IL-1 and IL-8). An elevated serum CRP level suggests that the inflammation arising as a result of periodontitis may correlate with cardiovascular pathology. Additionally, smoking creates an increasingly favorable environment for the growth of periodontal pathogens, thus furthering the disease process.

In recent meta-analysis, published articles on the effect of saffron supplementation on three inflammatory biomarkers (CRP, TNF-α, and IL-6) were evaluated. Combining eight eligible trials, it was demonstrated that saffron supplementation did not have a significant effect on serum levels of the three inflammatory biomarkers. However, in the subgroup analysis, saffron was found to significantly reduce CRP and TNF-α serum concentrations

Periodontitis, a common inflammatory dis ease, affects the teeth-supporting tissues. In this complex disease, dental biofilm interacts with inflammatory immune system, which may lead to an imbalance between bacterial invasion and the intensity of the host immune response. Scaling and root planning (SRP) is a common major meth od used as the gold standard for periodontal treatment. However, SRP alone has limited effects on some bacterial species and does not remove subgingival bacteria completely. This may be related to the fact that some species may exist in soft tissue, dentinal tubules, or root surface irregularities, which are associated with the treatment failure.

Therefore, to help the healing process, both chemical and herbal therapeutic mouthwashes were added to the treatment. In this way, herbs such as turmeric with its potent anti-inflammatory active ingredient, curcumin, or ginger have been used as adjunctive treatment for periodontitis along with SRP. In traditional Persian medicine, saffron and its extracts are used to improve digestion, increase appetite, relaxation, and treat liver diseases, spasm, toothache, rhinitis, pharyngitis, insomnia, depression, cough, asthma, bronchitis, fever, nausea, scarlet fever, urinary tract infections, cardiovascular disorders, and even cancers and immune system modulation. According to the modern studies, saffron has antioxidant, anti-inflammatory, anticoagulant, antibacterial and analgesic effects.

In recent years, herbal plants have received increasing attention considering their roles in health and disease. Saffron (Crocus sativus, L.) is an example of herbs, commonly used as a flavoring agent in food preparation. Saffron contains high amounts of carotenoid pigments (crocin, crocetin, α-carotene, lycopene, and zeaxanthin), monoterpene aldehydes (picrocrocin and safranal), monoterpenoids (crocusatines), isophorones, and flavonoids, which could contribute to its wide range of biological properties. A number of investigations have shown that saffron possesses anti-oxidant, anti-tumor, anti-genotoxic, and hypotensive properties. In addition, a growing number of studies have suggested that saffron possesses anti-inflammatory properties too.

However, clinical studies are very limited about the use of saffron in the field of oral diseases. A laboratory study reported that ethyl acetate extract of saffron has strong antimicrobial effects against various microorganisms such as both gram-positive (g+) and gram-negative (g-) bacteria, but it is obvious that alcoholic compounds themselves may have an antibacterial effect, so to avoid errors, the investigators chose the aqueous type from two types of alcoholic and aqueous extracts.

Considering the anti-inflammatory effect of saffron and due to the dissatisfaction of some patients with the taste of conventional mouthwashes, especially the gold standard chlorhexidine, this study was conducted to investigate the effect of mouthwash containing saffron aqueous extract on periodontal indices of patients with moderate to severe generalized periodontitis.

Inclusion Criteria:

• - Both genders, aged above 18 years.
• All patients must have a periodontal disease.
• Patients must be able to make reliable decision or communications.

Exclusion Criteria:

• - Smoking, Alcohol.
• Vulnerable groups such as pregnant females, prisoners, mentally and physically handicapped individuals.
• Known hypersensitivity or severe adverse effects to the treatment drugs or to any ingredient of their preparation.

The clinical outcome assessor (A.A) will not be aware of which treatment will be being administered, thus yielding a single-blind controlled study.