Kai-Xin-San Inhibits Tau Pathology and Neuronal Apoptosis in Aged SAMP8 Mice.

Alzheimer's disease (AD) is an age-related neurological disorder. Currently, there is no effective cure for AD due to its complexity in pathogenesis. In light of the complex pathogenesis of AD, the traditional Chinese medicine (TCM) formula Kai-Xin-San (KXS), which was used for amnesia treatment, has been proved to improve cognitive function in AD animal models. However, the active ingredients and the mechanism of KXS have not yet been clearly elucidated. In this study, network pharmacology analysis predicts that KXS yields 168 candidate compounds acting on 863 potential targets, 30 of which are associated with AD. Enrichment analysis revealed that the therapeutic mechanisms of KXS for AD are associated with the inhibition of Tau protein hyperphosphorylation, inflammation, and apoptosis. Therefore, we chose 7-month-old senescence-accelerated mouse prone 8 (SAMP8) mice as AD mouse model, which harbors the behavioral and pathological hallmarks of AD. Subsequently, the potential underlying action mechanisms of KXS on AD predicted by the network pharmacology analyses were experimentally validated in SAMP8 mice after intragastric administration of KXS for 3 months. We observed that KXS upregulated AKT phosphorylation, suppressed GSK3ß and CDK5 activation, and inhibited the TLR4/MyD88/NF-κB signaling pathway to attenuate Tau hyperphosphorylation and neuroinflammation, thus suppressing neuronal apoptosis and improving the cognitive impairment of aged SAMP8 mice. Taken together, our findings reveal a multi-component and multi-target therapeutic mechanism of KXS for attenuating the progression of AD, contributing to the future development of TCM modernization, including KXS, and broader clinical application.

Comparison of the anti-ulcer activity between the crude and bran-processed Atractylodes lancea in the rat model of gastric ulcer induced by acetic acid.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Atractylodes lancea (AL, Compositae, Chinese name: Cangzhu; Japanese name: Sou-ju-tsu) has been used traditionally for the treatment of various diseases such as digestive disorders, rheumatic diseases, and influenza in China, Korea and Japan. The crude AL and AL bran-processed are both listed in the Chinese Pharmacopoeia. However, the differences between the effects of the crude and AL bran-processed on gastric ulcer were poorly understood, and the mechanisms for the treatment of gastric ulcer were not clear. This study aimed at comparing the anti-ulcer effects between the crude AL and AL processed in acetic acid induced model in rats and evaluating the mechanisms of action involved in the anti-ulcer properties of AL. MATERIALS AND METHODS: The model of gastric ulcer was imitated by acetic acid in rats, and AL was gavaged. The serum and gastric tissues were collected. The levels of epidermal growth factor (EGF), trefoil factor2 (TFF2), tumor necrosis factor-α (TNF-α), interleukin 6, 8 (IL-6, 8) and prostaglandin E2 (PGE2) in serum and gastric tissues were determined by the double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of EGF, TFF2, TNF-α, and IL-8 in stomach were analyzed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, histopathological changes were evaluated by hematoxylin and eosin (HE) stain. The protein expressions of EGF, TFF2, TNF-α, and IL-8 were examined by immunohistochemistry in stomach. RESULTS: The results demonstrated that the damage of gastric tissue was obviously alleviated and the productions of TNF-α, IL-8, IL-6, and PGE2 and the mRNA expressions of TNF-α, and IL-8 were notably inhibited. Furthermore, the productions of EGF and TFF2 and the mRNA expressions of EGF and TFF2 were significantly stimulated by both crude AL and AL processed in a dose-dependent manner. Compared with the crude AL, the processed AL was more effective. CONCLUSION: The AL processed had more satisfactory effects in treatment of gastric-ulcer than the crude AL. The anti-ulcer effects of AL could be attributed to the anti-inflammatory properties via down-regulating TNF-α, IL-8, IL-6 and PGE2 and to the gastroprotective effects via up-regulating EGF and TFF2.