New Drug Therapy with Natural Compound Shows Promise Against Periodontal Diseases

A translational study from the lab of Dr. Esra Sahingur shows “senotherapy” drug combination was effective in lab-dish and animal models.

PHILADELPHIA – Periodontal diseases, commonly known as gingivitis and periodontitis, remain a significant global health challenge, affecting nearly 60% of adults aged 65 and older and contributing to substantial medical, psychological, and financial burdens. Driven by a deregulated immune response to oral bacteria, chronic inflammation can not only lead to gum tissue destruction and tooth loss but also is linked to numerous systemic conditions.

Researchers at Penn Dental Medicine discovered in a previous clinical study that the chronic gum inflammation can promote an aging-related condition called “senescence,” even in younger tissues. Senescent cells, which have permanently ceased to divide in response to stress, secrete inflammatory molecules that increase tissue damage, impair healing, and accelerate disease severity.

Now, a new translational study by the same research team reveals that targeting senescent cell burden could be an effective strategy for managing periodontal disease and promoting oral health.

In a paper recently published in the Journal of Dental Research (April 2025), the researchers showed that an anti-senescence therapy or “senotherapy,” consisting of an enzyme inhibitor called dasatinib and a natural flavonoid plant compound called quercetin, reduced markers of senescence and associated periodontal inflammation and bone loss in lab-dish and animal models.

“Our findings suggest that senotherapy offers a promising approach to preserving periodontal health,” says Dr. Esra Sahingur of Penn Dental Medicine. “Periodontitis is more than a bacterial infection—it’s driven by immune and metabolic dysfunction, cellular aging, and inflammation. By targeting inflammation and senescent cells, we may disrupt chronic disease cycle and unlock new preventive and therapeutic possibilities for oral and systemic health.”

Cellular senescence drives periodontal disease by promoting inflammation, cellular and metabolic dysfunction and impaired healing. The model illustrates senescent cell accumulation and its effects on the periodontium. Senotherapeutics may counter these effects by reducing senescent cells and modulating their secretory profile, thereby improving tissue health and clinical outcomes.

Cells exposed to stressors like inflammation, oxidative stress, and microbial toxins can enter a senescent state, ceasing to divide and losing normal function. These cells also release molecules that fuel further inflammation and senescence in surrounding tissues. Senotherapies, which target senescent cells by eliminating them or suppressing their harmful effects, are gaining attention for a host of potential clinical applications, and now periodontal diseases as well.

In their new study, Sahingur and her team used the dasatinib-quercetin (DQ) combination, a senotherapy that has shown an ability to reduce senescent cell numbers and senescence markers in other clinical contexts.

In lab-dish experiments, the team exposed gum cells called keratinocytes to periodontitis-associated bacteria, which induced a senescence-like molecular signature. Treatment with DQ significantly weakened this signature—as did quercetin alone comparably.

The results extended to a live animal model as well. In aging mice, which exhibit features of senescence as they age, DQ treatment significantly decreased senescence markers and senescence-associated inflammatory mediators in gum tissues, restoring them to levels observed in young, non-senescent gums. Importantly, the DQ supplements also prevented much of the loss of alveolar bone—the bone in which teeth are rooted—suggesting that senotherapy could help preserve the structural integrity of the periodontium.

“These results are consistent with our previous studies and a growing body of research that shows the powerful role of natural compounds, like quercetin, in promoting oral and systemic health,” says Sahingur.

Sahingur and her team now hope to initiate an early-stage clinical trial to assess the effects of quercetin—a widely available and safe over-the-counter supplement—on biological and clinical markers in patients with gum diseases. She says that future clinical trials might also investigate the benefits of adding dasatinib, which is currently used in leukemia, at lower doses and intermittently to determine its safety and efficacy in periodontal applications.

The figure demonstrates that quercetin, alone or with dasatinib, reduces nuclear envelope damage in gingival keratinocytes. The image showing intact lamin-B1 staining in the healthy cells was featured as the cover illustration for the Journal of Dental Research April 2025 issue.

“Our hope is that these initial clinical trials will provide proof-of-concept for leveraging the therapeutic potential of natural products- either as standalone agents or in combination regimens—as host modulatory strategies to enhance clinical outcomes in the management of periodontitis,” Sahingur says. “If successful, this could lay the foundation for more targeted and effective treatments and delivery options, particularly for patients at high risk of severe periodontal diseases, such as the elderly, diabetics, and immunocompromised.”

The study included multiple students from different programs, including undergraduate students at the Penn Center for Undergraduate Research and Fellowships, dental students from Penn Dental Medicine’s summer research program, and a graduate student from Penn Dental Medicine’s DScD program.

Sahingur is an associate professor in the Department of Periodontics and Associate Dean of Graduate Studies and Student Research at Penn Dental Medicine

Other authors are K. Rattanaprukskul, X.-J. Xia, M. Hysa, M. Jiang, M. Hung, and S.F. Suslavich.

The research was supported in part by the National Institute of Dental and Craniofacial Research (R01DE025037 and R01DE027374).