Active components and mechanisms of total flavonoids from Rhizoma Drynariae in enhancing cranial bone regeneration: An investigation employing serum pharmacochemistry and network pharmacology approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Drynariae, as the dried rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., is a traditional Chinese medicine for treating the injury and bone broken of falling and beating. Total flavonoids is considered as the major and effective compounds for the therapeutic efficacy of Rhizoma Drynariae. AIM OF THE STUDY: To explore the effect of total flavonoids from Rhizoma Drynariae (TFRD) on bone regeneration and the underlying mechanisms. MATERIALS AND METHODS: The effect of TFRD in various doses on bone reconstruction in cranial bone defect rats was explored in vivo. The active ingredients in TFRD-medicated serum were characterized by serum pharmacochemistry and integrated by network pharmacology analysis and target prediction. To elucidate the underlying mechanism of TFRD on bone regeneration, experimental validation in vitro was executed to assess the influence of different concentrations of TFRD-medicated serum on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). RESULTS: Micro-CT, histological examination, immunohistochemical analysis, and ELSA demonstrated that administration of TFRD could promote bone reconstruction in a rat cranial defect model. We identified 27 active components of TFRD using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Results from CCK8, ALP, and Alizarin Red S staining revealed that TFRD-medicated serum notably enhanced BMSCs proliferation and osteogenic differentiation. qRT-PCR and Western blot harvested results consistent with those predicted by network pharmacology, providing further evidence that TFRD activated the TGF-ß signaling pathway to benefit bone regeneration. CONCLUSION: The active components of TFRD modulate the TGF-ß signaling pathway to facilitate osteogenesis, thereby repairing cranial bone defects.

Bilobalide protects astrocytes from oxygen and glucose deprivation-induced oxidative injury by upregulating manganese superoxide dismutase.

Bilobalide (BB), a constituent of the Ginkgo biloba extract, is a neuroprotective agent with multiple mechanisms of action. To further explore the potential therapeutic effects of BB in stroke, we investigated its effects on primary astrocytes using the oxygen and glucose deprivation-reoxygenation (OGD-R) model. Cell viability was measured by lactate dehydrogenase release assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell death was measured by annexin 5 conjgated with fluorescein isothiocyanate (V-FITC) assay, and reactive oxygen species (ROS) production was measured by 2',7'-Dichlorodihydrofluorescein Diacetate (DCFH-DA) probe. Manganese superoxide dismutase (MnSOD) expression was measured by western blot and immunofluorescence. Mitochondrial membrane potential was monitored using JC-1 staining. Our results show that OGD-R downregulated MnSOD and impaired mitochondrial function, which further enhanced ROS production in primary astrocytes. As a result, cell viability was compromised, and cell death increased. BB treatment protected astrocytes from those injuries mainly by restoring MnSOD level as MnSOD inhibitor abolished the effects of BB. In conclusion, we demonstrated that OGD-R induced astrocytic injury, but BB increased the expression of MnSOD, the ROS scavenger, to reverse the exacerbated astrocytic injury.

Xuebijing in the treatment of patients with sepsis.

BACKGROUND: There are more than 18 million patients diagnosed with sepsis every year. In China, Xuebijing (XBJ) injection is a traditional medicine that is widely used in the treatment of sepsis. However, the efficacy of XBJ in treatment of randomized controlled trials (RCTs) remains unclear. This meta-analysis was to evaluate the clinical efficacy of XBJ based on randomized case-control studies. METHODS: PubMed, Cochrane, Embase, Wanfang, CNKI, and WeiPu (VIP) databases were searched to identify all the relative randomized case-control. The latest research was done in June, 2016. Relative risks (RR), weighted mean difference (WMD) along with 95% confidence interval (95%CI) were used to analyze the main outcomes. Statistical analysis was performed using STATA 10.0 (TX, USA). The qualities of the involved articles were accessed by the Jadad scale. RESULTS: Forty-nine randomized case-control studies met the inclusion and exclusion criteria, with 1861 patients in the control group and 2023 patients in the XBJ group. Compared with the conventional therapy, XBJ injection could significantly reduce the APACHE-IIscore (WMD: -3.70, 95%CI: -4.31-[-3.09]), PCT (WMD: -1.26µg/L, 95%CI: -1.63µg/L-[-0.88µg/L]), WBC (WMD: -1.48×109/L, 95%CI: -2.03×109/L-[-0.94×109/L]), CRP (WMD: -24.38mg/L, 95%CI:-30.49mg/L-[-18.26mg/L]), NEU (WMD: -4.68, 95%CI: -8.32-[-1.04]), T0(WMD: -0.50, 95%CI: -0.92-[-0.07]). The 28-day mortality of the XBJ group was significantly lower than the control group (RR: 0.51; 95%CI: 0.44-0.59). CONCLUSION: XBJ injection has a significant clinical efficacy in the therapy of patients with sepsis. However, there is a need for more randomized, lager-sample size, high-quality, and multicenter studies to confirm the extract efficacy of XBJ injection.