Maoto, a traditional Japanese medicine, controls acute systemic inflammation induced by polyI:C administration through noradrenergic function

• Published in: Gene Vol. 806; p. 145921
• Main Authors: Ogura, Keisuke, Kadota, Ayumi, Nakayama, Akiko, Kanno, Hitomi, Tahara, Yoshio, Nishi, Akinori
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.01.2022
• Subjects: Administration, Oral; Adrenergic beta-Antagonists - pharmacology; Adrenergic receptor; Animals; Anti-Inflammatory Agents - pharmacology; Cytokine; Disease Models, Animal; Ephedrine - pharmacology; Gene Expression Regulation; Inflammation - prevention & control; Injections, Intraperitoneal; Interleukin-10 - agonists; Interleukin-10 - genetics; Interleukin-10 - immunology; Japan; Male; Maoto; Medicine, Kampo - methods; Mice; Mice, Inbred BALB C; Mice, Nude; Plant Extracts - pharmacology; Poly I-C - administration & dosage; Poly I-C - antagonists & inhibitors; Receptors, Adrenergic, beta - genetics; Receptors, Adrenergic, beta - immunology; Signal Transduction; Systemic inflammation; T cell; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Japan; Maoto; Adrenergic receptor; T cell; Systemic inflammation; Cytokine
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2021.145921

•Maoto and its constituent ephedrine inhibited systemic inflammatory responses.•The anti-inflammatory effects of maoto were T-cell-independent.•Maoto increased IL-10 levels independent of its anti-inflammatory effects.•Maoto did not act directly on inflammatory cells.•Maoto exerted its anti-inflammatory effects via β-adrenergic receptors. Maoto, a traditional Japanese medicine (Kampo), is widely used to treat upper respiratory tract infections, including influenza virus infection. Although maoto is known to inhibit pro-inflammatory responses in a rodent model of acute inflammation, its underlying mechanism remains to be determined. In this study, we investigated the involvement of immune responses and noradrenergic function in the inhibitory action of maoto. In a mouse model of polyI:C-induced acute inflammation, maoto was administered orally in conjunction with intraperitoneal injection of PolyI:C (6 mg/kg), and blood was collected after 2 h for measurement of plasma cytokines by ELISA. Maoto significantly decreased PolyI:C-induced TNF-α levels and increased IL-10 production. Neither pretreatment with IL-10 neutralizing antibodies nor T-cell deficiency using nude mice modified the inhibitory effect of maoto, indicating that the anti-inflammatory effects of maoto are independent of IL-10 and T cells. Furthermore, the inhibitory effects of maoto on PolyI:C-induced TNF-α production were not observed in ex vivo splenocytes, suggesting that maoto does not act directly on inflammatory cells. Lastly, pretreatment with a β-adrenergic receptor antagonist partially cancelled the anti-inflammatory effects of maoto. Collectively, these results suggest that maoto mediates its anti-inflammatory effects via β-adrenergic receptors in vivo.