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[Display omitted] Alzheimer's disease (AD) is a progressive brain disorder, and one of the most common causes of dementia and amnesia. Due to the complex pathogenesis of AD, the underlying mechanisms remain unclear. Although scientists have made increasing efforts to develop drugs for AD, no effective therapeutic agents have been found. Natural products and their constituents have shown promise for treating neurodegenerative diseases, including AD. Thus, in-depth study of medical plants, and the main active ingredients thereof against AD, is necessary to devise therapeutic agents. In this study, N2a/APP cells and SAMP8 mice were employed as in vitro and in vivo models of AD. Multiple molecular biological methods were used to investigate the potential therapeutic actions of oxyphylla A, and the underlying mechanisms. Results showed that oxyphylla A, a novel compound extracted from Alpinia oxyphylla, could reduce the expression levels of amyloid precursor protein (APP) and amyloid beta (Aβ) proteins, and attenuate cognitive decline in SAMP8 mice. Further investigation of the underlying mechanisms showed that oxyphylla A exerted an antioxidative effect through the Akt-GSK3β and Nrf2-Keap1-HO-1 pathways. Conclusions. Taken together, our results suggest a new horizon for the discovery of therapeutic agents for AD. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) and fatigue are two common diseases endangering human life and health that may interact and reinforce one another. Myocardial infarction survivors frequently experience fatigue, and acute myocardial infarction (AMI) is one of the most common cardiovascular diseases that cause fatigue-induced sudden death. Sheng Mai Yin (SMY), a Chinese medicine prescription, is traditionally used for the treatment of diabetes and cardiovascular disease, and has been demonstrated to reduce fatigue and safeguard cardiac function. This study aims to investigate the effects and underlying mechanisms of SMY in treating fatigue and AMI. The pharmacological mechanisms of SMY in treating fatigue and AMI were predicted by bioinformatics and network pharmacology methods. After administering SMY at high, medium and low doses, the swimming time to exhaustion, hemoglobin level, serological parameters and hypoxia tolerance time were detected in C57BL/6N mice, and the left ventricular ejection fractions (LVEF), left ventricular fractional shortening (LVFS), grasp strength, cardiac histopathology, serological parameters and the expression of PINK1 and Parkin proteins were examined in Wistar rats. 371 core targets for SMY and 282 disease targets for fatigue and AMI were obtained using bioinformatics and network pharmacology methods. Enrichment analysis of target genes revealed that SMY might interfere with fatigue and AMI through biological processes such as mitochondrial autophagy, apoptosis, and oxidative stress. For in vivo experiments, SMY showed significant anti-fatigue and hypoxia tolerance effects in mice; It also improved the cardiac function and grasp strength, decreased their cardiac index, myocardial injury and fibrosis degree, and induced serological parameters levels and the expression of PTEN-induced putative kinase 1 (PINK1) and Parkin proteins in myocardium, suggesting that SMY may exert cardioprotective effects in a joint rat model of fatigue and AMI by inhibiting excessive mitochondrial autophagy. This study revealed the anti-fatigue, anti-hypoxia and cardioprotective effects of SMY in a joint model of fatigue-AMI, and the pharmacological mechanism may be related to the inhibition of mitochondrial autophagy in cardiomyocytes through the PINK1/Parkin pathway. The discoveries may provide new ideas for the mechanism study of traditional Chinese medicine, especially complex prescriptions, in treating fatigue and AMI. [Display omitted] • Fatigue and acute myocardial infarction may be related to apoptotic process. • Sheng Mai Yin reduced fatigue, hypoxia and heart damage in mice and rats. • Sheng Mai Yin may suppress PINK1 and Parkin expression in the mitochondrial autophagy of myocardium. [ABSTRACT FROM AUTHOR]

Puerarin, a bioactive natural C -glycoside isoflavonoid isolated from Pueraria lobata (Willd.) Ohwi, possesses many potential health benefits. However, the in vivo metabolic fates of puerarin have not been comprehensively clarified yet. In this study, an efficient strategy based on UHPLC-LTQ-Orbitrap mass spectrometer in both positive and negative ion modes was developed to profile and characterize puerarin metabolites in rat urine and plasma. Meanwhile, post-acquisition data-mining methods including high-resolution extracted ion chromatogram (HREIC) and multiple mass defect filtering (MMDF) were utilized to screen potential puerarin metabolites from HR-ESI–MS 1 stage. The mass fragmentation behaviors of five reference standards, including puerarin, daidzin, daidzein, genistin, and genistein, were comprehensively studied for construction of diagnostic product ions (DPIs), which could be employed to implement rapid identification of puerarin metabolites. Finally, a total of 66 metabolites (prototype compound included) were tentatively or positively identified based on standard substances, chromatographic retention times, accurate mass measurement, and corresponding Clog P values. Our results demonstrated that puerarin underwent multiple in vivo metabolic reactions including methylation, hydroxylation, dehydroxylation, hydrogenation, deglycosylation, glycosylation, sulfonation, glucuronidation, and their complicated reactions. In conclusion, the newly discovered puerarin metabolites significantly expanded the understanding on its pharmacological effects and built the foundation for further toxicity and safety studies. [ABSTRACT FROM AUTHOR]

Structural modification of active natural compounds which were originated from Traditional Chinese Medicine (TCM) have showed great advantages in the development of new drugs. In TCM, "Huangqin - Huanglian" is a classic "medicine couple" that has been used to treat intestinal diseases for thousands of years, while baicalin and berberine are the major active compounds of Huangqin and Huanglian respectively. Based on this "medicine couple", we designed and synthesized a new baicalin and berberine hybrid compound (BBH). Its molecular structure was confirmed by spectroscopy. The antibacterial activity of BBH was detected in vitro. Results indicated that the new hybrid compound exhibited the best antibacterial activity for proteobacteria as compared with its original synthetic materials (baicalin and berberine). In vivo, the effect of BBH on ulcerative colitis was also investigated. BBH treatment significantly ameliorated the disease symptoms and prevented the colon damage of ulcerative colitis. Furthermore, BBH showed a significant anti-inflammatory effect through regulating activities of SOD, MPO and expressions of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in colon tissue. Data also suggested that BBH was more superior than baicalin and berberine in ameliorating colonic damage. This indicated that the new hybrid compound BBH showed enhanced efficacy in treating ulcerative colitis. [ABSTRACT FROM AUTHOR]

• Chaihu Shugan San showed multi-target mechanisms on the treatment of Alzheimer's disease based on network pharmacology. • Chaihu Shugan San protected neural cells against Aβ-induced cell death through Akt signaling pathway. • Network pharmacology analysis was an effective approach to predict the pharmacological mechanisms of traditional medicines. Chaihu Shugan San (CSS) is a well-known herbal formula used to nourish liver and blood, promote blood circulation and Qi flow in Traditional Chinese Medicine. Modern pharmacological studies and clinical uses showed that CSS could ameliorate cognitive dysfunction of Alzheimer's disease (AD). The present study aimed to elucidate the multi-target mechanisms of CSS on AD using network pharmacology analysis and verify its effect by biological experiments. Firstly, a total of 152 active compounds in CSS, 520 predicted biological targets and 160 AD-related targets were identified. Subsequently, the networks including herb-compound-target network, AD-target network, and CSS potential target-AD target network were constructed. 60 key targets highly responsible for the beneficial effect of CSS on AD were identified by central network topological analysis. They were significantly characterized as nuclear or cytoplasmic proteins with molecular function of protein binding. They were also enriched in various biological processes through PI3K-Akt signaling pathway, MAPK signaling pathway and HIF signaling pathway by GO function and KEGG pathway enrichment analysis. Pretreatment with CSS ameliorated Aβ-induced neural cell death and reduced the number of apoptotic cells in differentiated PC12 cells. Moreover, increased phosphorylation of Akt accompanied with decreased Bax expression was found after CSS pretreatment, suggesting that Akt signaling pathway was involved in the protective effect of CSS against neural cells death. The present study systematically revealed the multi-target mechanisms of CSS on AD using network pharmacology approach, as well as validated the protective effect of CSS against Aβ-induced neural cells death through Akt signaling pathway. It provided indications for further mechanistic studies and also for the development of CSS as a potential treatment for AD patients. [ABSTRACT FROM AUTHOR]

Inflammatory disorders result from abnormal immune response and their incidence has increased recently. Thus, there is an urgent need to discover new treatments for inflammatory disorders. In recent years, the natural products contained in Chinese herbs have attracted much attention worldwide owing to their anti-inflammatory effects. Paeoniflorin (PF) is a bioactive compound purified from the Chinese herb Paeonia lactiflora and reports have recently emerged suggesting the great potential of P. lactiflora as an agent to counter inflammatory disorders. The anti-inflammatory effects of PF have been revealed by in vitro studies and in vivo animal experiments of different inflammatory disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and asthma. This review systematically describes the recent progress of studies on the mechanism of PF and its therapeutic potential in inflammatory disorders. Image 1 [ABSTRACT FROM AUTHOR]