[Research progress in role of autophagy in diabetic wound healing and traditional Chinese medicine intervention].

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.

[Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention].

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

Network pharmacology and experimental study of phenolic acids in salvia miltiorrhiza bung in preventing ischemic stroke.

At present, the preventive effect of ischemic stroke is not ideal, and the preventive drugs are limited. Danshen, the dried root of Salvia miltiorrhiza Bge, is a common medicinal herb in Traditional Chinese Medicine, which has been used for the treatment of cardiovascular diseases for many years. Phenolic Acids extracted from danshen, which showed multiple biological activities, have been developed as an injection for the treatment of ischemic stroke. However, its preventive effect on ischemic stroke has not been fully reported. The current study aimed to identify the potential active phenolic acids for the prevention of ischemic stroke and explore its mechanism using network pharmacology and experimental analyses. The targets of phenolic acids and ischemic stroke were obtained from public databases. Network pharmacology predicted that 35 kinds of phenolic acids had 201 core targets with ischemic stroke. The core prevention targets of ischemic stroke include IL-6, AKT1, VEGFA, etc. The signaling pathways involved in core targets include AGE-RAGE signaling pathway, HIF-1 signaling pathway, and cAMP signaling pathways, etc. Then, the antiplatelet effect of phenolic acids was screened by in vitro antiplatelet experiment. Our results showed that phenolic acids have a good inhibitory effect on ADP-induced platelet aggregation and salvianolic acid A had a good antiplatelet effect. We further demonstrated that SAA preventive administration reduced neurobehavioral scores, decreased infarct size, and protected tight junction proteins in autologous thrombus stroke model. These studies not only shed light on the potential mechanisms of phenolic acids active components on ischemic stroke, but also provided theoretical and experimental information for the development of new medicines from Danshen for the prevention of ischemic stroke. In addition, our results suggest that SAA has the potential to be a candidate for ischemic stroke prevention drug.

Evaluation and Identification of the Neuroprotective Compounds of Xiaoxuming Decoction by Machine Learning: A Novel Mode to Explore the Combination Rules in Traditional Chinese Medicine Prescription.

Xiaoxuming decoction (XXMD), a classic traditional Chinese medicine (TCM) prescription, has been used as a therapeutic in the treatment of stroke in clinical practice for over 1200 years. However, the pharmacological mechanisms of XXMD have not yet been elucidated. The purpose of this study was to develop neuroprotective models for identifying neuroprotective compounds in XXMD against hypoxia-induced and H2O2-induced brain cell damage. In this study, a phenotype-based classification method was designed by machine learning to identify neuroprotective compounds and to clarify the compatibility of XXMD components. Four different single classifiers (AB, kNN, CT, and RF) and molecular fingerprint descriptors were used to construct stacked naïve Bayesian models. Among them, the RF algorithm had a better performance with an average MCC value of 0.725±0.014 and 0.774±0.042 from 5-fold cross-validation and test set, respectively. The probability values calculated by four models were then integrated into a stacked Bayesian model. In total, two optimal models, s-NB-1-LPFP6 and s-NB-2-LPFP6, were obtained. The two validated optimal models revealed Matthews correlation coefficients (MCC) of 0.968 and 0.993 for 5-fold cross-validation and of 0.874 and 0.959 for the test set, respectively. Furthermore, the two models were used for virtual screening experiments to identify neuroprotective compounds in XXMD. Ten representative compounds with potential therapeutic effects against the two phenotypes were selected for further cell-based assays. Among the selected compounds, two compounds significantly inhibited H2O2-induced and Na2S2O4-induced neurotoxicity simultaneously. Together, our findings suggested that machine learning algorithms such as combination Bayesian models were feasible to predict neuroprotective compounds and to preliminarily demonstrate the pharmacological mechanisms of TCM.

Inhibition of FOXO3a/BIM signaling pathway contributes to the protective effect of salvianolic acid A against cerebral ischemia/reperfusion injury.

Salvianolic acid A (SalA) is an effective compound extracted from traditional Chinese medicine Salvia miltiorrhiza Bunge. The Forkhead box O3a (FOXO3a) signaling pathway plays crucial roles in the modulation of ischemia-induced cell apoptosis. However, no information about the regulatory effect of SalA on FoxO3a is available. To explore the anti-cerebral ischemia effect and clarify the therapeutic mechanism of SalA, SH-SY5Y cells and Sprague-Dawley rats were applied, which were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively. The involved pathway was identified using the specific inhibitor LY294002. Results showed that SalA concentration-dependently inhibited OGD/R injury triggered cell viability loss. SalA reduced cerebral infarction, lowered brain edema, improved neurological function, and inhibited neuron apoptosis in MCAO/R rats, which were attenuated by the treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) specific inhibitor LY294002. SalA time- and concentration-dependently upregulated the phosphorylation levels of protein kinase B (AKT) and its downstream protein FOXO3a. Moreover, the nuclear translocation of FOXO3a was inhibited by SalA both in vivo and in vitro, which was also reversed by LY294002. The above results indicated that SalA fought against ischemia/reperfusion damage at least partially via the AKT/FOXO3a/BIM pathway.

[Preparation and characterization of chitosan coated puerarin liposomes].

OBJECTIVE: To prepare chitosan coated puerarin liposomes and investigate their physicochemical properties. METHODS: Puerarin liposomes were prepared by reverse phase evaporation technique and then coated with chitosan. Using encapsulation efficiency as index of examination and designing an orthogonal experiment, the optimal formulation of liposomes was determined. The physicochemical properties of uncoatd and chitosan coated puerarin liposomes were investigated, respectively. RESULTS: Uncoated and chitosan coated puerarin liposomes were spherelike and smooth. The mean particles size of uncoated and coated liposomes were 217. 3nm and 632. 6nm, respectively. The Zeta potential were -14.44 mV and +35.61 mV, respectively. The encapsulating efficency was 50. 6% and 51.1%, respectively. CONCLUSION: Puerarin liposomes can be prepared by reverse phase evaporation technique successfully. The chitosan coated purarin liposomes ware spherelike and smooth.