Cistanche tubulosa alleviates ischemic stroke-induced blood-brain barrier damage by modulating microglia-mediated neuroinflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke (IS) has both high morbidity and mortality. Previous research conducted by our group demonstrated that the bioactive ingredients of the traditional medicinal and edible plant Cistanche tubulosa (Schenk) Wight (CT) have various pharmacological effects in treating nervous system diseases. However, the effect of CT on the blood-brain barrier (BBB) after IS are still unknown. AIM OF THE STUDY: This study aimed to identify CT's curative effect on IS and explore its underlying mechanism. MATERIALS AND METHODS: IS injury was established in a rat model of middle cerebral artery occlusion (MCAO). Gavage administration of CT at dosages of 50, 100, and 200 mg/kg/day was carried out for seven consecutive days. Network pharmacology was used for predicting the pathways and potential targets of CT against IS, and subsequent studies confirmed the relevant targets. RESULTS: According to the results, both neurological dysfunction and BBB disruption were exacerbated in the MCAO group. Moreover, CT improved BBB integrity and neurological function and protected against cerebral ischemia injury. Network pharmacology revealed that IS might involve neuroinflammation mediated by microglia. Extensive follow-up studies verified that MCAO caused IS by stimulating the production of inflammatory factors and microglial infiltration. CT was found to influence neuroinflammation via microglial M1-M2 polarization. CONCLUSION: These findings suggested that CT may regulate microglia-mediated neuroinflammation by reducing MCAO-induced IS. The results provide theoretical and experimental evidence for the efficacy of CT therapy and novel concepts for the prevention and treatment of cerebral ischemic injuries.

Microbiome-metabolomics analysis reveals the potential effect of verbascoside in alleviating cognitive impairment in db/db mice.

Cognitive impairment is the main central nervous system complication of diabetes, affecting the quality of life of patients. Herba Cistanche is a homologous plant widely used as a health food and therapeutic drug. Verbascoside, a signature component of Herba Cistanche, has anti-diabetic and neuroprotective effects. However, it is quickly metabolized by the gut microbiota, and the mechanism of its neuroprotection and improvement of learning and memory remains unclear. We investigated the effectiveness and potential mechanisms of verbascoside on cognitive dysfunction in db/db mice using a 16S rRNA microbiome and serum metabolomics approach. We found that 12-week treatment with verbascoside significantly inhibited insulin resistance, reduced blood glucose and lipids, and improved cognitive deficits. In addition, verbascoside increased the gut microbiota diversity, improved intestinal dysbiosis, attenuated intestinal barrier disruption, reduced the levels of inflammatory factors, regulated the expression of the metabolites associated with cognitive function, and enhanced the central insulin sensitivity and hippocampal synaptogenesis signaling. We revealed that verbascoside induced the enrichment of Alistipes, Roseburia, and Intestinimonas in the gut, suppressed the abundance of Escherichia-Shigella, increased the serum levels of gamma-aminobutyric acid, L-glutamic acid, and L-lysine, and decreased taurine expression. Finally, a strong association between gut microbes, serum metabolites, and cognitive performance affected by verbascoside was observed. Our research suggests that alterations in gut microbes/metabolites are involved in the development of diabetic cognitive dysfunction, which is alleviated by verbascoside in the db/db mice through restructuring the gut microbiota composition, ameliorating diabetic metabolic disorders, and attenuating pathological brain damage.

Effects of Phenylethanoid Glycosides Extracted from Herba Cistanches on the Learning and Memory of the APP/PSI Transgenic Mice with Alzheimer's Disease.

BACKGROUND: To investigate the effects of phenylethanoid glycosides (PhGs) extracted from Herba Cistanches on the behavioral and cognition capacity of the APP/PSI transgenic mice with Alzheimer's disease (AD). METHODS: AD mice were randomly divided into the control group, model group, donepezil group, PhG groups, and verbascose group, respectively. Three weeks later, the animals were subject to behavioral and cognition evaluation by the nesting test, Morris water maze test, and step-down test. RESULTS: The cognition capacity in these groups showed a significant increase compared with that in the model group. The step-down test indicated that the errors induced by the memory decrease in the PhG groups and verbascose group showed a significant decrease compared with those in the model group (P < 0.05). CONCLUSIONS: PhGs attenuated the cognitive dysfunction features of the APP/PSI transgenic gene. Besides, PhGs were the active components for the anti-AD activity of H. Cistanches.

Combination of Systems Pharmacology and Experimental Evaluation to Explore the Mechanism of Synergistic Action of Frankincense-Myrrh in the Treatment of Cerebrovascular Diseases.

Frankincense-Myrrh is a classic drug pair that promotes blood circulation, and eliminates blood stasis. The combination of the two drugs has a definite clinical effect on the treatment of cerebrovascular diseases (CBVDs), but its mechanism of action and compatibility have not been elucidated. In this study, the bioactive components, core targets, and possible synergistic mechanisms of Frankincense-Myrrh in the treatment of CBVDs are explored through systems pharmacology combined with in vivo and in vitro experiments. Comparing target genes of components in Frankincense and Myrrh with CBVD-related genes, common genes were identified; 15 core target genes of Frankincense-Myrrh for the treatment of CBVDs were then identified using protein-protein interaction (PPI) analysis. It was also predicted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis that the molecular mechanism of Frankincense-Myrrh action on CBVDs was mainly related to the regulation of neurotrophic factors and inflammatory responses. Frankincense-Myrrh significantly improved neurological function, decreased infarct volume, alleviated histopathological damage, inhibited microglial expression, and promoted the expression of neurons in middle cerebral artery occlusion (MCAO)-induced rats. The results of this study not only provide important theoretical support and experimental basis for the synergistic effect of Frankincense-Myrrh, but also provide new ideas for the prevention and treatment of cerebral ischemic injuries.

Improved Interface Stability and Room-Temperature Performance of Solid-State Lithium Batteries by Integrating Cathode/Electrolyte and Graphite Coating.

Poor interface stability is a crucial problem hindering the electrochemical performance of solid-state lithium batteries. In this work, a novel approach for interface stability was proposed to integrate the cathode/solid electrolyte by forming an electrolyte buffer layer on the rough surface of the cathode and coating a layer of graphite on the side of the electrolyte facing the lithium anode. This hybrid structure significantly improves the integration and the interface stability of the electrode/electrolyte. The interfacial resistance was dramatically reduced, the stability of the plating/stripping of Li metal was enhanced, and the growth of lithium dendrites was also inhibited due to the formation of the LiC6 transition layer. The obtained solid-state lithium battery shows enhanced rate performance at room temperature from 0.5 to 4 C and stable cycling performance at 1 C with a retention capacity of 100 mAh g-1 after 200 cycles. This integrated electrode/electrolyte design approach is expected to be widely used to improve interfacial stability and room-temperature electrochemical performance of solid-state batteries.

Neuroprotective effects of phenylethanoid glycosides in an in vitro model of Alzheimer's disease.

The present study aimed to investigate the neuroprotective effects of phenylethanol glycosides (PhGs) on H2O2- and ß-amyloid peptide (Aß)1-42-induced injury of PC12 cells as an in vitro model of Alzheimer's disease (AD). The optimal induction conditions were established through screening of various incubation times and concentrations. PC12 cells were treated with 0.5 µM Aß1-42 and H2O2 in the presence of PhGs for 24 h and the cell viability was then evaluated by an MTT assay; lactate dehydrogenase (LDH) release and malondialdehyde (MDA) content were also measured. The optimal conditions for establishing the AD model were the treatment of PC12 cells with 0.5 µM Aß1-42 for 48 h, or with 25 µM H2O2 dissolved in DMEM with PBS. PhGs at concentrations of 5, 25 and 50 µg/ml increased the viability and decreased LDH and MDA release by PC12 cells injured with Aß1-42 or H2O2. In conclusion, the model of Aß1-42- and H2O2-induced PC12 cell injury was successfully established. PhGs were shown to have a significant neuroprotective effect against Aß1-42- or H2O2-induced cell injury.

Hepatoprotective effects of Gentianella turkestanerum extracts on acute liver injury induced by carbon tetrachloride in mice.

Objective: To investigate the contents of secoiridoid compounds (i.e. sweroside, swertiamarin and gentiopicrin) from Gentianella turkestanerum extracts, and the potential effects of G. turkestanerum extracts against carbon tetrachloride (CCl4) induced liver injury in mice. Methods: The contents of swertiamarin, gentiopicroside and sweroside from different G. turkestanerum extracts were determined with high performance liquid chromatography (HPLC). CCl4 was used to induce acute liver injury in mice. The serum aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), total bilirubin (TB), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione transferase (GSH) and catalase (CAT) were measured. HE staining was performed to investigate the pathological changes of liver. Results: Iridoid glycoside showed the highest content in the product extracted by butanol (designated as GBA), but lower in the products extracted by ethyl acetate and water designated as GEA and GW, respectively. All G. turkestanerum extracts showed protective effects against CCl4 induced acute liver injury in mice, among which GBA showed the maximal protective effects. G. turkestanerum extracts induced significant decrease in the serum ALT, AST, ALP and TB compared with those in the mice with acute lung injury (P < 0.01). Obvious increase was noticed in serum TP (P < 0.01). Moreover, such effects presented in a dose-dependent manner. Compared with the control group, the MDA was significantly elevated in the model group (P < 0.01), while significant decrease was observed in the levels of SOD, GSH and CAT in model group compared with the control group (P < 0.01). Whereas, such phenomenon was completely reversed by G. turkestanerum extracts in a dose-dependent manner. Conclusion:G. turkestanerum showed protective effects against CCl4 induced acute liver injury in mice.

Preparation and evaluation of microemulsion­based transdermal delivery of Cistanche tubulosa phenylethanoid glycosides.

The primary aim of the present study was to develop a novel microemulsion (ME) formulation to deliver phenylethanoid glycoside (PG) for use in skin lighteners and sunscreens. The oil phase was selected on the basis of drug solubility, while the surfactant and cosurfactant were screened and selected on the basis of their solubilizing capacity and the efficiency with which they formed MEs. Pseudoternary phase diagrams were constructed to evaluate ME regions and five formulations of oil­in­water MEs were selected as vehicles. In vitro skin permeation experiments were performed to optimize the ME formulation and to evaluate its permeability in comparison to that of saline solution. The physicochemical properties of the optimized ME and the permeating ability of PG delivered by this ME were also investigated. The optimized ME formulation was composed of isopropyl myristate (7%, w/w), Cremorphor EL (21%, w/w), propylene glycol (7%, w/w) and water (65%, w/w). The cumulative amount of PG that permeated through excised mouse skin when carried by ME was ~1.68 times that when PG was carried by saline solution only. The cumulative amount of PG in the microemulsion (4149.650±37.3 µg·cm­2) was significantly greater than that of PG in the saline solution (2288.63±20.9 µg·cm­2). Furthermore, the permeability coefficient indicated that optimized microemulsion was a more efficient carrier for transdermal delivery of PG than the control solution (8.87±0.49 cm/hx10­3 vs. 5.41±0.12 cm/hx10­3). Taken together, the permeating ability of ME­carried PG was significantly increased compared with saline solution.