Danggui Buxue decoction ameliorates mitochondrial biogenesis and cognitive deficits through upregulating histone H4 lysine 12 acetylation in APP/PS1 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue decoction (DBD) is a classic herbal decoction consisting of Astragali Radix (AR) and Angelica Sinensis Radix (ASR) with a 5:1 wt ratio, which can supplement 'blood' and 'qi' (vital energy) for the treatment of clinical diseases. According to Traditional Chinese Medicine (TCM) theory, dementia is induced by Blood deficiency and Qi weakness, which causes a decline in cognition. However, the underlying mechanisms of DBD improving cognition deficits in neurodegenerative disease are no clear. AIM OF THE STUDY: This study aims at revealing the underlying mechanisms of DBD plays a protective role in the cognitive deficits and pathology process of Alzheimer's disease (AD). MATERIALS AND METHODS: The APP/PS1 (Mo/HuAPP695swe/PS1-dE9) double transgenic mice were adopted as an experimental model of AD. Qualitative and quantitative analysis of 3 compounds in DBT was analyzed by HPLC. Morris water maze test, Golgi staining and electrophysiology assays were used to evaluate the effects of DBD on cognitive function and synaptic plasticity in APP/PS1 mice. Western blot, immunofluorescence and Thioflavin S staining were used for the pathological evaluation of AD. Monitoring the level of ATP, mitochondrial membrane potential, SOD and MDA to evaluate the mitochondrial function, and with the usage of qPCR and CHIP for the changes of histone post-translational modification. RESULTS: In the current study, we found that DBD could effectively attenuate memory impairments and enhance long-term potentiation (LTP) with concurrent increased expression of memory-associated proteins. DBD markedly decreased Aß accumulation in APP/PS1 mice by decreasing the phosphorylation of APP at the Thr668 level but not APP, PS1 or BACE1. Further studies demonstrated that DBD restored mitochondrial biogenesis deficits and mitochondrial dysfunction. Finally, the restored mitochondrial biogenesis and cognitive deficits are under HADC2-mediated histone H4 lysine 12 (H4K12) acetylation at the peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) and N-methyl-D-aspartate receptor type 2B (GluN2B) promoters. CONCLUSIONS: These findings reveal that DBD could ameliorate mitochondrial biogenesis and cognitive deficits by improving H4K12 acetylation. DBD might be a promising complementary drug candidate for AD treatment.

The underlying mechanisms of anti-hepatitis B effects of formula Le-Cao-Shi and its single herbs by network pharmacology and gut microbiota analysis.

Formula Le-Cao-Shi (LCS), a traditional Chinese medicine (TCM), has been used as folk remedy for treating hepatitis B for a long time. In our previous study, the anti-hepatitis B effects of LCS have been verified. In the present study, the anti-hepatitis B activities of LCS and its three single herbs were investigated in vitro by HepG2.2.15 cellular model, and the mechanisms against hepatitis B were deciphered via network pharmacology and gut microbiota analysis. By network pharmacology method, twelve key compounds that played a vital role in LCS were filtered from 213 ingredients. The targets RORA, CDK2, RELA, AKT1, IKBKG, PRKCß and CASP3 were directly related to hepatitis B pathway, which indicated that LCS could exert anti-hepatitis B effect by co-regulating cell cycle and inflammatory pathways. The interactions between candidate compounds and target proteins that were directly involved in hepatitis B pathway were validated by molecular docking simulation and RT-PCR. By gut microbiota analysis, it was revealed that LCS could alter the disordered microbial composition in the infected ducks towards normal, especially the restoration of three key strains, namely Streptococcus alactolyticus, Enterococcus cecorum and Bacteroides fragilis. The above findings could provide a scientific basis for further development and utilization of LCS against hepatitis B.

[TCMATCOV--a bioinformatics platform to predict efficacy of TCM against COVID-19].

There is urgent need to discover effective traditional Chinese medicine(TCM) for treating coronavirus disease 2019(COVID-19). The development of a bioinformatic tool is beneficial to predict the efficacy of TCM against COVID-19. Here we deve-loped a prediction platform TCMATCOV to predict the efficacy of the anti-coronavirus pneumonia effect of TCM, based on the interaction network imitating the disease network of COVID-19. This COVID-19 network model was constructed by protein-protein interactions of differentially expressed genes in mouse pneumonia caused by SARS-CoV and cytokines specifically up-regulated by COVID-19. TCMATCOV adopted quantitative evaluation algorithm of disease network disturbance after multi-target drug attack to predict potential drug effects. Based on the TCMATCOV platform, 106 TCM were calculated and predicted. Among them, the TCM with a high disturbance score account for a high proportion of the classic anti-COVID-19 prescriptions used by clinicians, suggesting that TCMATCOV has a good prediction ability to discover the effective TCM. The five flavors of Chinese medicine with a disturbance score greater than 1 are mainly spicy and bitter. The main meridian of these TCM is lung, heart, spleen, liver, and stomach meridian. The TCM related with QI and warm TCM have higher disturbance score. As a prediction tool for anti-COVID-19 TCM prescription, TCMATCOV platform possesses the potential to discovery possible effective TCM against COVID-19.

Gastrodin protects against chronic inflammatory pain by inhibiting spinal synaptic potentiation.

Tissue injury is known to produce inflammation and pain. Synaptic potentiation between peripheral nociceptors and spinal lamina I neurons has been proposed to serve as a trigger for chronic inflammatory pain. Gastrodin is a main bioactive constituent of the traditional Chinese herbal medicine Gastrodia elata Blume, which has been widely used as an analgesic since ancient times. However, its underlying cellular mechanisms have remained elusive. The present study demonstrated for the first time that gastrodin exhibits an analgesic effect at the spinal level on spontaneous pain, mechanical and thermal pain hypersensitivity induced by peripheral inflammation, which is not dependent on opioid receptors and without tolerance. This analgesia by gastrodin is at least in part mediated by depressing spinal synaptic potentiation via blockade of acid-sensing ion channels. Further studies with miniature EPSCs and paired-pulse ratio analysis revealed the presynaptic origin of the action of gastrodin, which involves a decrease in transmitter release probability. In contrast, neither basal nociception nor basal synaptic transmission was altered. This study revealed a dramatic analgesic action of gastrodin on inflammatory pain and uncovered a novel spinal mechanism that could underlie the analgesia by gastrodin, pointing the way to a new analgesic for treating chronic inflammatory pain.

Radical resection of 202 pediatric craniopharyngiomas with special reference to the surgical approaches and hypothalamic protection.

OBJECTIVE: The goal of this study was to disclose the appropriate surgical approaches to radically removing pediatric craniopharyngiomas with optimal hypothalamic protection. METHODS: In 202 patients undergoing primary surgery from April 1997 to December 2002, eight approaches were used to remove craniopharyngiomas in the sellar region and the third ventricle. Among the eight approaches, the transcallosal-interseptal-interforniceal approach was used in 89 cases, the unilateral transfrontal interhemispheric approach in 68 cases, the pterional approach in 20 cases, and the other five approaches in 25 cases. Active preventive and therapeutic measurements of hypothalamic dysfunction were adopted pre- and postoperatively. RESULTS: Of the 202 cases, 184 tumors were totally or nearly totally removed (91.1%); 89 cases were resected with the transcallosal-interseptal-interforniceal approach with a total and subtotal removal rate of 92.1%, and 68 cases were removed with the unilateral transfrontal interhemispheric approach with a total and subtotal removal rate of 95.6%. Two patients died (0.9%). The major postoperative complications included diabetes insipidus in 81.7% of the cases, permanent diabetes insipidus in 11.4%, electrolyte disorder in 74.8%, and seizures in 9.4%. The 5-year survival rate was 68.2%. CONCLUSIONS: Appropriate approaches with direct tumor exposure should be determined in order to remove the craniopharyngioma as much as possible, while at the same time carefully protecting the anteroinferolateral wall of the third ventricle (hypothalamus). Active measurements to manage blood sodium disorder and seizures could help to ensure the safety of the operation.

[Transcallosal interforniceal approach for removing the medial type of thalamic gliomas].

OBJECTIVE: To report an approach for removing the medial type of thalamic gliomas. METHODS: Eight cases of medial type of thalamic gliomas, 4 males and 4 females, aged 22 (14 approximately 53), underwent resection of the tumor by transcallosal interforniceal approach: right frontal craniotomy, along the cerebral midline natural cleft to reach the third ventricle. RESULTS: By using microsurgical skill, subtotal removal of the tumors was achieved in 5 cases and partial removal was achieved in 3 cases with satisfactory postoperative effects. CONCLUSIONS: Keeping the fornix, thalamus, midbrain, and internal cerebral vein intact with few complication and good outcome, transcallosal interforniceal approach is an ideal way to resect the medial type of thalamic gliomas.

Pediatric craniopharyngiomas: clinicomorphological study of 189 cases.

OBJECTIVE: To understand the pathological changes in pediatric craniopharyngiomas in order to determine the diagnosis and operative strategy and to prevent damage to the hypothalamus. METHODS: A total of 189 cases of pediatric craniopharyngiomas from 1990 to 1998 were reviewed and analyzed based on computerized tomography scans, magnetic resonance imaging and operations. RESULTS: Of the 189 cases, 187 (98.9%) were cystic tumors and calcification could be seen in 176 cases (93.1%). Two cases were solid tumors (1.1%), and calcification occurred in only 1 of these. There was a gliosis layer between the wall of the tumor and the hypothalamus. CONCLUSION: Cystic changes and calcification are the pathological features of pediatric craniopharyngiomas. There are some special relationships between the tumors and stalk. This is the basis for the total removal of pediatric craniopharyngiomas.