Yi Zheng

Walnut peptide Lys-Gly-His-Leu-Phe-Pro-Asn (KG-7) is a food-derived bioactive peptide with a high antioxidant capacity. We systematically evaluated the ameliorative effects of KG-7 on scopolamine-induced memory deficits in mice and its intestinal absorption mechanisms through integrating motion behavior analysis, molecular biochemistry research, and fluorescence imaging technology. Morris water maze tests revealed that KG-7 significantly improved the behavioral performance of these mice. Further mechanistic investigations demonstrated that KG-7 restored cholinergic function by reducing acetylcholinesterase activity and increasing acetylcholine levels. Hematoxylin-eosin staining and hippocampal immunohistochemistry confirmed that KG-7 alleviated neuronal damage by downregulating Hes1 overexpression, clarifying its behavioral improvement mechanism. In vitro fluorescence imaging showed that KG-7 reached peak accumulation in brain tissue 8 h post-administration, confirming its brain delivery. To elucidate the absorption mechanism, immunohistochemistry and immunofluorescence revealed that KG-7 markedly reduced the expression of efflux transporter P-gp in the small intestine, thereby diminishing efflux activity, while weakened tight junction (Occludin, ZO-1) fluorescence indicated activation of the paracellular pathway. Western blot analysis confirmed that KG-7 enhanced paracellular absorption efficiency and reduced intestinal efflux by downregulating ZO-1, Occludin, and efflux transporters (P-gp, BCRP, and LRP1) alongside upregulating Claudin-2 expression. These findings provide a foundation for exploring walnut peptides that enhance memory and optimize absorption.

The aim of this study was to investigate the aqueous two-phase extraction (ATPE), in vitro antioxidant, and in vivo renal protective effects of polysaccharides from spores of Cordyceps cicadae (CCSPs). The optimal ATPE parameters were as follows: an extraction temperature of 61 °C, an ammonium sulfate concentration of 18%, an ethanol concentration of 40%, a liquid-to-material ratio of 33 mL/g, and an extraction time of 60 min. Under these parameters, the CCSPs yield was 6.96 ± 0.11% (n = 3), which was consistent with the predicted yield (6.92%). Among the three purified polysaccharide fractions, CCSP-2 displayed stronger scavenging activities against DPPH radicals and hydroxyl radicals, reducing power and ferrous-ion-chelating ability to a greater extent than CCSP-1 and CCSP-3. CCSP-2 exhibited its protective effect in lipopolysaccharide (LPS)-induced septic acute kidney injury (AKI) mice by significantly alleviating renal edema; reducing 24 h urine protein, blood urea nitrogen (BUN), and serum creatinine (SCr); inhibiting the release of serum proinflammatory cytokines; boosting the activities of antioxidant enzymes; and reducing the levels of oxidative damage products. These results suggest that CCSP-2 exerted its protective effect against LPS-induced septic AKI in mice through anti-inflammatory and antioxidant pathways.

This study investigated the purification, preliminary structure and in vivo immunomodulatory activities of polysaccharides from the spores of Cordyceps cicadae (CCSP). The crude CCSP was purified by diethylaminoethyl (DEAE)-cellulose and Sephadex G-100 chromatography, affording CCSP-1, CCSP-2 and CCSP-3 with molecular weights of 1.79 × 10⁶, 5.74 × 10⁴ and 7.93 × 10³ Da, respectively. CCSP-2 consisted of mannose and glucose, while CCSP-1 and CCSP-3 are composed of three and four monosaccharides with different molar ratios, respectively. CCSP-2 exhibited its ameliorative effects in cyclophosphamide-induced immunosuppressed mice through significantly increasing spleen and thymus indices, enhancing macrophage phagocytic activity, stimulating splenocyte proliferation, improving natural killer (NK) cytotoxicity, improving bone marrow suppression, regulating the secretion of cytokines and immunoglobulins, and modulating antioxidant enzyme system. These results indicate that CCSP-2 might be exploited as a promising natural immunomodulator.

Hypothermia is an important protective strategy against global cerebral ischemia following cardiac arrest. However, the mechanisms of hypothermia underlying the changes in different regions and connections of the brain have not been fully elucidated. This study aims to identify the metabolic nodes and connection integrity of specific brain regions in rats with global cerebral ischemia that are most affected by hypothermia treatment. ¹⁸F-fluorodeoxyglucose positron emission tomography was used to quantitatively determine glucose metabolism in different brain regions in a rat model of global cerebral ischemia established at 31–33°C. Diffusion tensor imaging was also used to reconstruct and explore the brain connections involved. The results showed that, compared with the model rats established at 37–37.5°C, the rat models of global cerebral ischemia established at 31–33°C had smaller hypometabolic regions in the thalamus and primary sensory areas and sustained no obvious thalamic injury. Hypothermia selectively preserved the integrity of the anterior forebrain mesocircuit, exhibiting protective effects on the brain during the global cerebral ischemia. The study was approved by the Institutional Animal Care and Use Committee at Capital Medical University (approval No. XW-AD318-97-019) on December 15, 2019.

Trametes orientalis polysaccharide (TOP-2) could alleviate PM _2.5 -induced lung injury in mice via its antioxidant and anti-inflammatory activities.

Ultrasonic-microwave assisted extraction (UMAE) of Trametes orientalis polysaccharides was optimized by response surface methodology. Hepatoprotective effects of a purified T. orientalis polysaccharide (TOP-2) were evaluated by alcohol-induced liver injury model mice. The optimal UMAE parameters were indicated as below: ratio of water to raw material 28 mL/g, microwave power 114 W, extraction time 11 min. The polysaccharides yield was 7.52 ± 0.12%, which was well consistent with the predicted value of 7.54%. Pre-treatment with TOP-2 effectively increased the liver index and spleen index in alcohol-treated mice. The elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of mice after alcohol exposure were inhibited by TOP-2 administration. The liver tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels have decreased significantly as a result of alcohol exposure, while pre-treatment with TOP-2 could mitigate these consequences. Furthermore, pre-treatment with TOP-2 could efficiently boost the superoxidase dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, and observably constrain the malondialdehyde (MDA) level. The findings suggest that TOP-2 might be useful for alleviating the alcohol-induced hepatotoxicity via its antioxidant and anti-inflammatory potential.

We recently described a novel series of aminopyridopyrazinones as PDE5 inhibitors. Efforts toward optimization of this series culminated in the identification of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, which possessed an excellent potency and selectivity profile and demonstrated robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. Furthermore, this compound is brain penetrant and will be a useful agent for evaluating the therapeutic potential of central inhibition of PDE5. This compound has recently entered clinical trials.