Metabolome and microbiome analyses of the anti-fatigue mechanism of Acanthopanax senticosus leaves.

Acanthopanax senticosus leaves, widely used as a vegetable and tea, are reported to be beneficial in treating neurological disorders. At present, their anti-fatigue effect remains to be established. In this study, we analyzed the composition of the extracts from A. senticosus leaves and confirmed their antioxidant and anti-inflammatory properties at the cellular level. In mice subjected to exhaustive running on a treadmill, supplementation with A. senticosus leaf extracts enhanced exercise performance and alleviated fatigue via the reversal of exercise-induced 5-HT elevation, metabolic waste accumulation, organ damage, and glucose metabolism-related gene expression. The collective findings from microbiome and metabolomic analyses indicate that A. senticosus leaf extracts increase α-diversity, regulate microbial composition, and reverse exercise-mediated disruption of carbohydrate, creatine, amino acid, and trimethylamine metabolism. This study provides preliminary evidence for the utility of A. senticosus leaves as a promising anti-fatigue food and offers insights into the underlying mechanism.

Cardio-Oncology: Mechanisms, Drug Combinations, and Reverse Cardio-Oncology.

Chemotherapy, radiotherapy, targeted therapy, and immunotherapy have brought hope to cancer patients. With the prolongation of survival of cancer patients and increased clinical experience, cancer-therapy-induced cardiovascular toxicity has attracted attention. The adverse effects of cancer therapy that can lead to life-threatening or induce long-term morbidity require rational approaches to prevention and treatment, which requires deeper understanding of the molecular biology underpinning the disease. In addition to the drugs used widely for cardio-protection, traditional Chinese medicine (TCM) formulations are also efficacious and can be expected to achieve "personalized treatment" from multiple perspectives. Moreover, the increased prevalence of cancer in patients with cardiovascular disease has spurred the development of "reverse cardio-oncology", which underscores the urgency of collaboration between cardiologists and oncologists. This review summarizes the mechanisms by which cancer therapy induces cardiovascular toxicity, the combination of antineoplastic and cardioprotective drugs, and recent advances in reverse cardio-oncology.

Litchi chinensis seed prevents obesity and modulates the gut microbiota and mycobiota compositions in high-fat diet-induced obese zebrafish.

Obesity continues to be a global public health challenge. Litchi chinensis seed is rich in bioactive ingredients with pharmacological effects, such as hypoglycemic activity and anti-oxidation. This study aimed to assess the potential anti-obesity effects of L. chinensis seed and the changes of gut microbiota and mycobiota compositions in obese zebrafish induced by a high-fat diet. The anti-obesity effects were supplemented and validated in high-fat diet-induced obese mice. In this study, various chemical components of L. chinensis seed water and ethanol extracts were detected using UHPLC-QE-MS, and both extracts showed strong in vitro antioxidant activities. Network pharmacology analysis showed the potential of the extracts to improve obesity. Litchi chinensis seed powder, water and ethanol extracts decreased the weight of obese zebrafish, improved lipid accumulation and lipid metabolism, regulated appetite, and inhibited cell apoptosis and inflammation of the liver and intestine. They showed similar effects in obese mice, and also reduced the weight of fat tissues, regulated insulin resistance and glucose metabolism, and improved the intestinal barrier. Additionally, L. chinensis seed modulated the compositions of gut microbiota and mycobiota in zebrafish, with the regulation of the proportion of bacteria that produce short-chain fatty acids or affect intestine health, including Cetobacterium, Trichococcus, Aeromonas, Staphylococcus, and Micrococcaceae, and the proportion of fungi that produce mycotoxins or have special metabolic capacities, including Penicillium, Candida, Rhodotorula, and Trichoderma. Spearman's correlation analysis revealed the potential link between zebrafish obesity parameters, gut bacteria and fungi. Overall, these findings indicated that L. chinensis seed effectively improved obesity.

[Oral absorption of asiatic acid nanoparticles modified with PEG].

A solvent diffusion method was used to prepare pegylated asiatic acid (AA) loaded nanostructured lipid carriers (p-AA-NLC), and the ligated intestinal circulation model was established to observe the absorption and distribution in small intestine. The concentration of AA in bile after oral administration of p-AA-NLC was detected by HPLC in healthy SD rats to indirectly evaluate the oral absorption promoting effect of PEG-modified namoparticles. The results showed that the penetration of p-AA-NLC was enhanced significantly and the transport capacity was increased greatly in small intestinal after PEG modification. As compared with the normal nanoparticles (AA-NLC), the Cmax of the drug excretion was increased by 76%, the time to reach the peak (tmax ) was decreased and the elimination half-life t1/2 was doubled in the rats after oral administration of p-AA-NLC, and the AUC0→t was 1.5 times of the AA-NLC group, indicating that the oral bioavailability of AA-NLC was significantly improved by hydrophilic modification of PEG.

A novel doxorubicin loaded folic acid conjugated PAMAM modified with borneol, a nature dual-functional product of reducing PAMAM toxicity and boosting BBB penetration.

Effective targeting drug delivery system for glioma treatment is still greatly challenged by the existence of the blood-brain barrier (BBB) and the intracranial overspreading of anti-tumor drug. Herein, we presented a dual-functional glioma targeting delivery of doxorubicin based on the PAMAM G5 dendrimer, modified with folic acid (FA) to target tumor cell, also borneol (BO), a well known safe material derived from traditional Chinese medicine, to facilitate the BBB permeability and reduce the toxicity of naked PAMAM. The intracranial transportation and glioma targeting ability were evaluated on the BBB model and C6 glioma cells in vitro. Also, pharmacokinetics and biodistribution were studied on C6 glioma-bearing rats in vivo. It indeed reduced the cytotoxicity of PAMAM against both HBMEC and C6 cells by coupling BO on the surface, while efficiently boosted BBB permeability with the improvement of transportation ratio by 2 folds to the BO-unmodified conjugates. Furthermore, conjugated FA increased total uptake amount by C6 cells leading to strong inhibition with the 3-fold lower IC50 value than FA-unmodified DOX conjugate. In comparison with DOX solution, FA-BO-PAMAM/DOX exhibited significantly prolonged half-life time and increased area under the curve and improved DOX accumulation in brain tumor. The tumor growth inhibition, in vivo, was significantly increased up to 57.4%. The median survival time of xenograft rats after administering FA-BO-PAMAM/DOX (28days) was significantly prolonged compared to free DOX (18days, P<0.05) or other controls. In conclusion, this strategy of novel targeting nanocarrier provides a promising method to increase the drug accumulation in the tumor site for therapy of glioma.

[Response surface method for optimization of asiatic acid nanoparticles modified with PEG and its enhancing effects on intestinal absorption].

A solvent diffusion method was used to prepare pegylated asiatic acid (AA) loaded nanostructured lipid carriers (p-AA-NLC). Then central composite design-response surface method was used to obtain optimum condition for preparation technology of p-AA-NLC, where PEG/lipid ratio was 8.0% and AA/lipid ratio was 22.0%. Under the optimum condition, the system had particle size of (111.2±2.9) nm, Zeta potential of (-37.1±0.9) mV, drug loading of (15.4±0.2)% and entrapment efficiency greater than 90%. The deviations between observed values and predicated values were all below 5%, indicating that the established model had a good predictability. Meanwhile, a low-speed single pass perfusion model of rat in situ was set up to estimate the absorption kinetics of p-AA-NLC in small intestine, where the effective permeability (Peff), absorption rate constant (Ka) and other parameters were used to evaluate the drug absorption. It turned out that Peff and Ka in p-AA-NLC group were significantly higher than those in unmodified group (P<0.05), indicating that asiatic acid loaded nanostructured lipid carriers (AA-NLC) could enhance the effects on intestinal absorption after being modified with hydrophilic PEG.

[Effect of suyu capsule on behavior and injury of hippocampal neurons in depression model mice].

OBJECTIVE: To observe the effect of Suyu capsule on behavior, injury of hippocampal neurons and Ca2+ ion in hippocampal synaptic in the depression model mice. METHOD: Sixty male Kunming mice were randomly divided into 5 groups, the control group, the model group and three Suyu capsule groups (the doses were 22.8, 11.4, 5.7 g x kg(-1) respectively). The model was established by separation and chronic unpredictable mild stimulation. The increased weight and crossing score, rearing score were measured by open-field and sweet water consumption of mice. Cone cell and configuration of neuron in CA1, CA3 region of hippocampus were observed by Nissl. The concentration of hippocampal synaptic Ca2+ ion was detected by fluorimetry. RESULT: Comparing with the mice of control, the increased weight was slowered ( P < 0.01), the scores of rearing and crossing were decreased (P < 0.01), sweet water consumption were decreased too (P < 0.01), numbers of cone cell in CA3 region of hippocampus were decreased obviously (P < 0.01), and Ca2+ ion in hippocampal synaptic was increased obviously. Comparing with the mice of model, Suyu capsule (22.8 g kg(-1)) could increase the increased weight on the 14th and 21 st day obviously (P < 0.05); Suyu capsule (22.8 g x kg(-1)) could increase the scores of crossing obviously (P < 0.05), Suyu capsule (22.8, 11.4 g x kg(-1)) could increase the scores of rearing obviously (P < 0.01, P < 0.05); Suyu capsule (22.8, 11.4, 5.8 g x kg(-1)) could increase sweet water consumption obviously (P < 0.01, P < 0.05, P < 0.05; Suyu capsule (22.8, 11.4, 5.8 g x kg(-1)) could increase numbers of cone cell in CA3 region of hippocampus obviously (P < 0.01, P < 0.05, P < 0.05); Suyu capsule (22.8, 11.4, 5.8 g x kg(-1)) decreased Ca2+ ion in hippocampal synaptic with dose-effect relationship (P < 0.01, P < 0.01, P < 0.05). CONCLUSION: Suyu capsule can improve all the symptoms of the depression model mice and protect injury of hippocampal neurons in the depression model mice. The possible mechanism of action is to restrict Ca2+ ion overfreight.