Agastache rugosa, a traditional Asian herbal medicine, is primarily used for digestive problems; yet, its cognitive benefits remain unexplored. This study evaluated the anti-amnesic effects of A. rugosa extract (ARE) on scopolamine (SCO)-induced memory impairment in mice. Mice received 100 or 200 mg/kg ARE orally for 5 days, followed by SCO injection. The ARE demonstrated significant antioxidant (DPPH IC₅₀: 75.3 µg/mL) and anti-inflammatory effects (NO reduction). Furthermore, the ARE significantly improved memory performance in the passive avoidance test (escape latency: 157.2 s vs. 536.9 s), the novel object recognition test (novel object preference: 47.6% vs. 66.3%) and the Morris water maze (time spent in the target quadrant: 30.0% vs. 45.1%). The ARE reduced hippocampal acetylcholinesterase activity (1.8-fold vs. 1.1-fold) while increasing choline acetyltransferase (0.4-fold vs. 1.0-fold) and muscarinic acetylcholine receptor subtype I (0.3-fold vs. 1.6-fold) expression. The ARE improved hippocampal neurogenesis via doublecortin- (0.4-fold vs. 1.1-fold) and KI-67-positive (6.3 vs. 12.0) cells. Therefore, the ARE exerts protective effects against cognitive decline through cholinergic system modulation and antioxidant activity, supporting its potential use as a cognitive enhancer.

Citrus fruits are widely distributed in East Asia, and tea made from citrus peels has demonstrated health benefits, such as a reduction in fever, inflammation, and high blood pressure. However, citrus leaves have not been evaluated extensively for their possible health benefits. In this study, the α-glucosidase-inhibitory activity of Jeju citrus hot-water (CW) and ethyl alcohol (CE) extracts, along with hesperidin (HP) (a bioactive compound in citrus leaf extracts), was investigated, and furthermore, their effect on postprandial blood glucose reduction in an animal model was determined. The hesperidin contents of CW and CE were 15.80 ± 0.18 and 39.17 ± 0.07 mg/g-extract, respectively. Hesperidin inhibited α-glucosidase (IC₅₀, 4.39), sucrase (0.50), and CE (2.62) and demonstrated higher α-glucosidase inhibitory activity when compared to CW (4.99 mg/mL). When using an SD rat model, during sucrose and starch loading tests with CE (p < 0.01) and HP (p < 0.01), a significant postprandial blood glucose reduction effect was observed when compared to the control. The maximum blood glucose levels (Cmax) of the CE administration group decreased by about 15% (from 229.3 ± 14.5 to 194.0 ± 7.4, p < 0.01) and 11% (from 225.1 ± 13.8 to 201.1 ± 7.2 hr·mg/dL, p < 0.05) in the sucrose and starch loading tests, respectively. Our findings suggest that citrus leaf extracts standardized to hesperidin may reduce postprandial blood glucose levels through the observed inhibitory effect against sucrase, which results in delayed carbohydrate absorption. Our findings provide a biochemical rationale for further evaluating the benefits of citrus leaves.

Polymethoxyflavones (PMFs) are flavonoid compounds present in citrus plants that are proposed to be advantageous to human health. However, the advantageous effects of PMFs in the context of renal dysfunction are unclear. In this study, we made a PMF-rich fraction (PRF) from the leaves of Citrus sunki Hort ex. Tanaka and identified its components using liquid chromatography and mass spectrometry. We then investigated the effect of PRF—comprising 9 types of PMF—on renal dysfunction induced by unilateral ureteral obstruction (UUO) in mice. Animals were divided into four experimental groups ( n = 7 per group): I) sham-operated group (Sham); II) UUO group (UUO); III) UUO + Enalapril 0.1 mg/1 mL (UUO + Enap); IV) UUO + PRF 100 mg/kg/day (UUO + PRF). All mice were orally administered with the drugs once a day from 7 days before UUO to 1 week after UUO. After the experiments were over, serum and tissues were taken for biochemical and histological analysis. PRF promoted the recovery of body weight in the background of UUO. Biochemical and histological analysis revealed that PRF ameliorated UUO-induced renal dysfunction and moderately reversed inflammation and tubulointerstitial fibrosis. Further, PRF inhibited the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), transforming growth factor-β (TGF-β), collagen I (Col-I), and collagen IV (Col-IV). These results suggest that PRF improves UUO-induced renal dysfunction by regulating the expression of inflammatory and fibrotic response-related genes.