Chemistry, metabolism and pharmacology of carcinogenic alkaloids present in areca nut and factors affecting their concentration.

Memory, one of the most vital aspects of the human brain, is necessary for the effective survival of an individual. 'Memory' can be defined in various ways but in an overall view, memory is the retention of the information that the brain grasps. Different factors are responsible for the disbalance in the brain's hippocampus region and the acetylcholine level, which masters the memory and cognitive functions. Plants are a source of pharmacologically potent drug molecules of high efficacy. Recently herbal medicine has evolved rapidly, gaining great acceptance worldwide due to their natural origin and fewer side effects. In this review, the authors have discussed the mechanisms and pharmacological action of herbal bioactive compounds to boost memory. Moreover, this review presents an update of different herbs and natural products that could act as memory enhancers and how they can be potentially utilized in the near future for the treatment of severe brain disorders. In addition, the authors also discuss the differences in biological activity of the same herb and emphasize the requirement for a higher standardization in cultivation methods and plant processing. The demand for further studies evaluating the interactions of herbal drugs is mentioned.

Herbal drugs and natural bioactive products as potential therapeutics: A review on pro-cognitives and brain boosters perspectives.

Betel quid (BQ) chewing increased the risk of oral cancer and oral submucous fibrosis (OSMF), an oral premalignant disorder (OPMD) with malignant transformation potential. BQ components such as areca nut (AN), trauma by coarse AN fiber, catechin, copper, alkaloids, stimulated reactive oxygen species (ROS), inflammation and cytotoxicity are suggested to be the contributing factors. They may induce tissue inflammation, proliferation of fibroblasts and collagen deposition, myofibroblast differentiation and contraction, collagen cross-links and inhibit collagen phagocytosis, finally leading to the development of OSMF and oral cancer. These events are mediated by BQ components-induced changes of extracellular matrix (ECM) turnover via regulation of TGF-β1, plasminogen activator inhibitor-1 (PAI-1), cystatin, lysyl oxidase (LOX) and tissue inhibitors of metalloproteinases (TIMPs) and metalloproteinases (MMPs). Genetic susceptibility is also involved in these disease processes. Further understanding the molecular mechanisms of BQ-induced OSMF and oral cancer can be helpful for future disease prevention and treatment.

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Genetic Susceptibility and Protein Expression of Extracellular Matrix Turnover-Related Genes in Oral Submucous Fibrosis.

Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-β) pathway has a pivotal role in the pathogenesis of fibrosis in several organs, including the salivary glands. Among the TGF-β superfamily members, TGF-β1 and 2 are pro-fibrotic ligands, whereas TGF-β3 and some bone morphogenetic proteins (BMPs) are anti-fibrotic ligands. TGF-β1 is thought to be associated with the pro-fibrotic pathogenesis of sialadenitis, post-radiation salivary gland dysfunction, and Sjogren's syndrome. Potential therapeutic strategies that target multiple levels in the TGF-β pathway are under preclinical and clinical research for fibrosis. Despite the anti-fibrotic effect of BMPs, their in vivo delivery poses a challenge in terms of adequate clinical efficacy. In this article, we will review the relevance of TGF-β signaling in salivary gland fibrosis and advances of potential therapeutic options in the field.

https://www.mdpi.com/1422-0067/21/23/9138/pdf

TGF-β Pathway in Salivary Gland Fibrosis

Signaling pathways promoting epithelial mesenchymal transition in oral submucous fibrosis and oral squamous cell carcinoma.

Background and objectives: Oral Submucous Fibrosis (OSF) is a potentially malignant oral disorder which leads to fibrosis of the oral mucosa and has a high rate of malignant transformation. The consumption of various forms of areca nut is causatively linked to the condition. The constituents of areca nut activate several pro-fibrotic cytokines, chiefly transforming growth factor-β1, β2, which leads to an increased deposition and decreased degradation of extracellular matrix and collagen. TGF-β1, β2 probably represent the major pathway in the deposition of collagen fibres in this condition. The present study aims to identify and correlate the expressions of TGF-β1 and TGF-β2 immunohistochemically on paraffin sections of various stages of OSF. A comparison was also made between normal oral mucosa and scar tissue and OSF to judge the mode, extent and type of expression of TGF β1, β2. Methods: The expression of TGF-β1 antibody (8A11, NovusBio, USA) and TGF-β2 antibody (TB21, NovusBio, USA) was detected immunohistochemically on paraffin sections of 58 and 70 cases of OSF respectively, 10 cases of normal oral mucosal tissue and 4 cases of scar tissue. A mapping of the positivity of the two cytokines was done using JenOptik camera and ProReg image analysis software. The results were statistically analysed using one way ANOVA and students "t" test. Results: Expression of TGF-β1 and TGF-β2 was more in OSF as compared with normal oral mucosa, scar/keloid tissue showing highest values. Positivity for both the markers was seen in epithelium, around the blood vessels, in areas of inflammatory infiltrate, fibroblasts and in muscles. TGF-β1 expression was higher and more intense than that of TGF-β2 in all the cases. TGF-β2 was restricted in its expression to submucosal area with minimal involvement of the epithelium and the deeper muscle tissue. Conclusion: TGF-β1 is the most prominent cytokine in the fibrotic pathway and TGF-β2 plays a contributory role.

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Transforming growth factor-β1 and TGF-β2 act synergistically in the fibrotic pathway in oral submucous fibrosis: An immunohistochemical observation.

Background: Areca nut and its commercial preparations such as pan masala have been causatively linked in the disorder oral submucous fibrosis (OSF). Arecoline, major alkaloid of areca nut, is involved in stimulating fibrosis through transforming growth factor beta pathway. Areca consumed in various forms and with additives alters the arecoline content of the nut. Aims: Estimation of levels of arecoline in various areca nut preparations consumed in the country (raw, boiled, and roasted) along with commercially prepared sample of areca nut (pan masala). Materials and Methods: Estimation and validation were performed by high-performance thin-layer chromatography system (CAMAG® Muttenz, Switzerland). Four samples of 5 g each of raw, roasted, boiled, and pan masala containing areca nuts were assessed. Pure arecoline was used for validation as a control. Three runs of each with interand intra-day validations were carried out as per established protocols. Results: Raw areca nut contains the highest concentration of arecoline (1.15 ± 0.008) followed by pan masala preparations (0.94 ± 0.006), least content in boiled areca nut (0.79 ± 0.009), while roasted variety exhibited an intermediate level (0.85 ± 0.007). Conclusions: Alteration of contents of the areca nut has great implications in its capacity to induce the potentially malignant disorder of OSF. The use of raw areca nuts in commercial preparations and well-known observations of greater incidence of the development of OSF and probable malignant transformation with these forms is probably related to their arecoline content.

Venkatesh Viswanath Kamath

Papers

Transforming growth factor-β1 and TGF-β2 act synergistically in the fibrotic pathway in oral submucous fibrosis: An immunohistochemical observation.

Estimation of arecoline content of various forms of areca nut preparations by high-pressure thin-layer chromatography