Ninjin'yoeito enhances saliva secretion in aged mice via nutritional, immune, anti-inflammatory, and anti-aging effects

OBJECTIVES: This study aimed to evaluate the effects of long-term administration of Ninjin'yoeito, a traditional Japanese Kampo medicine, on age-related salivary hypofunction in mice. METHODS: Male senescence-accelerated mice (SAMP1) were divided into two groups and fed either a control diet, or a diet containing 3 % Ninjin'yoeito extract for four months. Salivary gland function was assessed by measuring the flow rate after muscarinic stimulation of the submandibular glands perfused ex vivo. Additional analysis included histological and immunohistochemical evaluations, blood tests, and real-time PCR to investigate gland morphology, immune cell profiles, gene expression, and inflammation/aging markers. RESULTS: Long-term Ninjin'yoeito administration significantly increased salivary secretion after stimulation and decreased the number of vacuoles in acinar cells as compared to the controls. Ninjin'yoeito improved the plasma albumin levels and increased the lymphocyte ratio in the white blood cell count. Furthermore, real-time PCR revealed decreased levels of inflammatory cytokine and senescence-associated genes. No significant changes were detected in the expression or localization of the main salivary secretion-related channels, such as transmembrane protein 16A and aquaporin 5. CONCLUSIONS: Ninjin'yoeito enhances salivary secretion from the submandibular glands of aged mice by improving nutritional status, modulating immune function, suppressing chronic inflammation, and attenuating cellular aging. These results suggest that Ninjin'yoeito has potential applications as a complementary therapy for age-related dry mouth.