Cinnamon plays a key role in the anti-obesity action of Hachimijiogan by ameliorating leptin resistance in the hypothalamus

OBJECTIVES: Hachimijiogan (MIX8), a traditional herbal formulation comprising eight crude drugs, is used clinically to alleviate symptoms associated with cold conditions. Although anti-obesity effects have been suggested, the bioactive constituents and underlying mechanisms remain poorly understood. Thus, we aimed to identify the key bioactive components responsible for the anti-obesity effects of MIX8 and elucidate the underlying mechanisms. METHODS: Modified MIX8 formulations lacking processed aconite root (PAR) (MIX7) or PAR and cinnamon (MIX6) were administered to diet-induced obese C57BL/6J mice. Body weight, fat mass, insulin sensitivity, hepatic lipid accumulation, and circulating leptin levels were evaluated. To assess the underlying mechanisms, a leptin challenge test was conducted following cinnamon extract administration. KEY FINDINGS: MIX7 suppressed weight gain, adipocyte hypertrophy, systemic insulin resistance, hepatic steatosis, and hyperleptinemia. MIX6 failed to suppress weight gain, implicating cinnamon as having anti-obesity activity. Cinnamon extract enhanced the acute anorexigenic response to leptin and restored hypothalamic leptin signalling, indicating the reversal of central leptin resistance. CONCLUSIONS: Cinnamon is an essential component of MIX8 that mediates its anti-obesity effects by restoring central leptin sensitivity. The present study provides mechanistic insights into the pharmacological basis of MIX8, supporting the preventive potential of cinnamon in managing diet-induced obesity.