Identification of potential inhibitors targeting Ebola virus VP35 protein: a computational strategy.

Ebola virus (EBOV) poses a severe threat as a highly infectious pathogen, causing devastating hemorrhagic fever in both humans and animals. The EBOV virus VP35 protein plays a crucial role in viral replication and exhibits the ability to suppress the host interferon cascade, leading to immune system depletion. As a potential drug target, VP35 protein inhibition holds promise for combating EBOV. To discover new drug candidates, we employed a computer-aided drug design approach, focusing on compounds capable of inhibiting VP35 protein replication. In this connection, a pharmacophore model was generated using molecular interactions between the VP35 protein and its inhibitor. ZINC and Cambridge database were screened using validated pharmacophore model. Further the compounds were filtered based on Lipinski's rule of five and subjected to MD simulation and relative binding free energy calculation. Six compounds manifest a significant docking score and strong binding interaction towards VP35 protein. MD simulations further confirmed the remarkable stability of these six complexes. Relative binding free energy calculations also showed significant ΔG value in the range of -132.3 and -49.3 kcal/mol. This study paves the way for further optimization of these compounds as potential inhibitors of VP35, facilitating subsequent experimental in vitro studies.Communicated by Ramaswamy H. Sarma.

Exploring the underlying mechanisms of obesity and diabetes and the potential of Traditional Chinese Medicine: an overview of the literature.

Obesity and diabetes are closely related metabolic disorders that have become major public health concerns worldwide. Over the past few decades, numerous studies have explored the underlying mechanisms of these disorders and identified various risk factors, including genetics, lifestyle, and dietary habits. Traditional Chinese Medicine (TCM) has been increasingly recognized for its potential to manage obesity and diabetes. Weight loss is difficult to sustain, and several diabetic therapies, such as sulfonylureas, thiazolidinediones, and insulin, might make it harder to lose weight. While lifestyle changes should be the primary approach for people interested in lowering weight, drugs are also worth investigating. Since some of the newer glucose-lowering medications that cause weight loss, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), are additionally utilized or are under consideration for use as anti-obesity drugs, the frontier between glucose-lowering medication and weight loss drugs appears to be shifting. This review provides an overview of the literature on the underlying mechanisms of obesity and diabetes and the prospect of TCM in their management. We discuss the various TCM interventions, including acupuncture, herbal medicine, and dietary therapy, and their effects on metabolic health. We also highlight the potential of TCM in regulating gut microbiota, reducing inflammation, and improving insulin sensitivity. The findings suggest that TCM may provide a promising approach to preventing and managing obesity and diabetes. However, further well-designed studies are needed to confirm the efficacy and safety of TCM interventions and to elucidate their underlying mechanisms of action.

Protective effect of Gastrodia elata blume ameliorates simulated weightlessness-induced cognitive impairment in mice.

During the long-term orbital flight, exposure to microgravity negatively affects the astronauts' development of cognition, characterized by learning and memory decline. Gastrodia elata Blume (GEB) has a significant protective effect on cognitive impairment and has been used in Asia for centuries as a functional product. A previous study demonstrated that GEB could improve memory loss in mice caused by circadian rhythm disorders. However, the effects of GEB on cognitive dysfunction caused by weightless environments have not been investigated. In this study, mice received daily treatment with GEB (0.5, 1 g·kg-1d-1, i.g) and Huperzine A(Hup, 0.1 mg·kg-1d-1, i.g) orally until the end of the behavioral test (New object recognition test (NORT). Malondialdehyde (MDA) and nitric oxide (NO) levels were detected by kits, and expression of brain-derived neurotrophic factor (BDNF), protein kinase B (AKT), phosphorylated Akt (P-AKT), synaptophysin (SYN) and postsynaptic density 95(PSD95) in hippocampus were detected by western blotting. The results show that administration of GEB (0.5, 1 g·kg-1d-1, i.g) and Hup (0.1 mg·kg-1d-1, i.g) remarkably reverse HLS-induced learning and behavioral memory disorders, which were associated with significant changes in MDA and NO levels. Additionally, the protein expressions of BDNF, P-AKT/AKT, SYN, and PSD95 were significantly increased in the hippocampus. In summary, our findings will improve the reference for developing GEB as a functional product that improves memory decline.

Baihe Jizihuang Tang Ameliorates Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior: Integrating Network Pharmacology and Brain-Gut Axis Evaluation.

Baihe Jizihuang Tang (BHT) is a traditional Chinese medicine (TCM) prescription, which can also be used as a nutritional food with medicinal value. Herein, we aimed to clarify the antidepressive effects and molecular mechanism of BHT. Network pharmacological analysis; chronic unpredictable mild stress (CUMS) rat model assessment; behavioral tests; analysis of hippocampal neurotransmitter levels, hippocampal pathological structure, and hypothalamic-pituitary-adrenal (HPA) axis; western blot analysis; 16s RNA sequencing; ultraperformance liquid chromatography (UPLC)/mass spectrometry (MS); and high-performance liquid chromatography (HPLC)/ultraviolet (UV) analysis were used. We found 8 potentially active components and 12 targets from the database. KEGG analysis suggested that BHT significantly affected BDNF/tyrosine receptor kinase B levels, glutamate binding, synaptic transmission based on neurotransmitter signal, and the response to glucocorticoid signaling pathways. Consistently, 7 chemical components were identified using UPLC/quadrupole time-of-flight/MS; among them, regalosides A, B, C, and E were unique components of lily of TCM, and their content in BHT was significantly different: regaloside A > B > E > C. BHT could nourish hippocampal neurons, affect neurotransmitter metabolism, reduce HPA axis hyperactivity, improve deficits in hippocampal tissue structure, and change depressive behavior. Moreover, BHT regulated BDNF expression in the hippocampus and improved intestinal flora deficits in CUMS rats by changing the content of Bifidobacterium, Rothia, Glutamicibacter, and Lactobacillus at the genus level. Collectively, BHT attenuated CUMS-induced depression-like behavior by regulating BDNF and intestinal flora disorder through the brain-gut axis. Therefore, including BHT in the medication list may constitute a potential strategy for preventing depression.

Effects of different drying methods on the chemical constituents of Lilium lancifolium Thunb. based on UHPLC-MS analysis and antidepressant activity of the main chemical component regaloside A.

The Lilium lancifolium Thunb. is a herb with multiple functions in both medicine and food in China, and its extracts have shown antidepressant effects. In this study, fresh bulbs of Lilium lancifolium Thunb. were processed to study the effects of different drying processes on changes in its main chemical components. We found that different drying methods can affect the chemical constituents of the herb. Among these components, Regaloside A has been found as the characteristic component. Here, Cell Counting Kit-8 assay, and Western blotting were used to evaluate the neuroprotective antidepressant effects of Regaloside A. The results showed the cell survival rate was improved, the phosphorylation levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphatidylinositol 3 kinase, protein kinase B, and mammalian target of rapamycin were increased after Regaloside A treatment. In general, different drying methods have a significant influence on the chemical composition of the herb, and Regaloside A may be the main chemical component of the herb. It can alleviate the damage of corticosterone in SH-SY5Y cells, and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling mediated by brain-derived neurotrophic factor/tyrosine kinase receptor B may play an important role in the neuroprotective antidepressant effects of Regaloside A.

Meranzin hydrate exhibits anti-depressive and prokinetic-like effects through regulation of the shared α2-adrenoceptor in the brain-gut axis of rats in the forced swimming test.

BACKGROUND: In recent years, the brain-gut axis theory has received increasing attention in studies of depression. However, most studies separately address potential antidepressant and prokinetic treatments. Investigations of drugs that could potentially treat comorbid depression and gastrointestinal (GI) dysfunction via a common mechanism of action have not yet been performed in detail. AIM: To find a common mechanism of action of our patented drug, meranzin hydrate (MH), in the antidepressant and prokinetic treatment. METHODS: The forced swimming test (FST) model of depression, plasma ghrelin measurement, and in vivo and in vitro measurements of GI motility were used. RESULTS: 1. Administration of MH (9 mg/kg) decreased the immobility time during the FST after acute treatment; this effect was inhibited by the alpha 2-adrenoceptor antagonist, yohimbine, but not by the alpha 1-adrenoceptor antagonist, prazosin. 2. After chronic treatment, the immobility time of rats during the FST was decreased significantly by MH (2.25 mg/kg). 3. MH (9 mg/kg) increased plasma ghrelin levels in rats subjected to the FST; this increase was enhanced by the ghrelin receptor agonist, GHRP-6. 4. MH (9 mg/kg) also promoted gastric emptying and intestinal transit in rats with or without FST. 5. In vitro, MH (10 µM) increased jejunal contractions in rats subjected to the FST; this effect was inhibited by yohimbine. Furthermore, the inhibitory effect of yohimbine was partly reversed by the ghrelin receptor agonist, GHRP-6. CONCLUSION: Our study revealed that MH from natural resources exhibits antidepressive and prokinetic-like effects through the regulation of the common mediator, the alpha 2-adrenoceptor.

[Observation on therapeutic effect of moxibustion and exercise for children with short stature of deficience of the kidney essence].

OBJECTIVE: To observe the therapeutic effect of moxibustion and exercise comprehensive scheme intervention for children with short stature of deficience of the kidney essence. METHODS: Twenty four cases of children in 12 to 14 years old were selected, 12 male and 12 female, they were treated with comprehensive therapy of exercise therapy and moxibustion. Running and jumping were selected as main exercise therapy, it became a suitable exercise amount when the heart rate reach to 150 to 170 times per minute, thrice each week, 35 to 45 minutes each time. After exercises they were treated with moxibustion, Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36), Dazhu (BL 11), Xuanzhong (GB 39), Geshu (BL 17) etc. were selected. After treatment for half a year, the changes of the body height, body weight, bone age(BA), growth hormone (GH), testosterone (T) and estradiol (E2) were compared before and after treatment. RESULTS: The body height and bone age of the boys and girls were significantly higher than those before treatment (all P<0.05), the growth of body height was more than 4 cm, the growth of bone age was more than 0.5 years old in half a year; the testosterone of all children was significantly increased (all P<0.05), and there were no significant differences in body weight, GH and E2 compared to those before treatment (all P>0.05). CONCLUSION: Moxbustion and exercise comprehensive scheme can effectively improve the children with short stature of deficience of the kidney essence, the mechanism is related to the improving of the testosterone level.