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Stem cells are a well-known autologous pluripotent cell source, having excellent potential to develop into specialized cells, such as brain, skin, and bone marrow cells. The oral cavity is reported to be a rich source of multiple types of oral stem cells, including the dental pulp, mucosal soft tissues, periodontal ligament, and apical papilla. Oral stem cells were useful for both the regeneration of soft tissue components in the dental pulp and mineralized structure regeneration, such as bone or dentin, and can be a viable substitute for traditionally used bone marrow stem cells. In recent years, several studies have reported that plant extracts or compounds promoted the proliferation, differentiation, and survival of different oral stem cells. This review is carried out by following the PRISMA guidelines and focusing mainly on the effects of bioactive compounds on oral stem cell-mediated dental, bone, and neural regeneration. It is observed that in recent years studies were mainly focused on the utilization of oral stem cell-mediated regeneration of bone or dental mesenchymal cells, however, the utility of bioactive compounds on oral stem cell-mediated regeneration requires additional assessment beyond in vitro and in vivo studies, and requires more randomized clinical trials and case studies.

Periodontal diseases are caused mainly by inflammation of the gums and bones surrounding the teeth or by dysbiosis of the oral microbiome, and the Global Burden of Disease study (2019) reported that periodontal disease affects 20–50% of the global population. In recent years, more preference has been given to natural therapies compared to synthetic drugs in the treatment of periodontal disease, and several oral care products, such as toothpaste, mouthwash, and dentifrices, have been developed comprising honeybee products, such as propolis, honey, royal jelly, and purified bee venom. In this study, we systematically reviewed the literature on the treatment of periodontitis using honeybee products. A literature search was performed using various databases, including PubMed, Web of Science, ScienceDirect, Scopus, clinicaltrials.gov, and Google Scholar. A total of 31 studies were reviewed using eligibility criteria published between January 2016 and December 2021. In vitro, in vivo, and clinical studies (randomized clinical trials) were included. Based on the results of these studies, honeybee products, such as propolis and purified bee venom, were concluded to be effective and safe for use in the treatment of periodontitis mainly due to their antimicrobial and anti-inflammatory activities. However, to obtain reliable results from randomized clinical trials assessing the effectiveness of honeybee products in periodontal treatment with long-term follow-up, a broader sample size and assessment of various clinical parameters are needed.