Atrophy patterns in hippocampal subregions and their relationship with cognitive function in fibromyalgia patients with mild cognitive impairment.

Objectives: Fibromyalgia (FM) has been associated with decreased hippocampal volume; however, the atrophy patterns of hippocampal subregions have not yet been identified. We therefore aimed to evaluate the volumes of hippocampal subregions in FM patients with mild cognitive impairment (MCI), and to explore the relationship between different subregional alterations and cognitive function. Methods: The study included 35 FM patients (21 with MCI and 14 without MCI) and 35 healthy subjects. All subjects performed the Montreal Cognitive Assessment (MoCA) to assess cognitive function. FreeSurfer V.7.3.2 was used to calculate hippocampal subregion volumes. We then compared hippocampal subregion volumes between the groups, and analyzed the relationship between hippocampal subregion volume and cognitive function using a partial correlation analysis method. Results: Compared with the healthy subjects, FM patients with MCI had smaller hippocampal volumes in the left and right CA1 head, Molecular layer head, GC-DG head, and CA4 head, and in the left Presubiculum head. Poorer executive function, naming ability, and attention were associated with left CA1 head and left Molecular layer head atrophy. By contrast, hippocampal subregion volumes in the FM patients without MCI were slightly larger than or similar to those in the healthy subjects, and were not significantly correlated with cognitive function. Conclusion: Smaller volumes of left CA1 head and left Molecular layer head were associated with poorer executive function, naming ability, and attention in FM patients with MCI. However, these results were not observed in the FM patients without MCI. These findings suggest that the hippocampal subregions of FM patients might present compensatory mechanisms before cognitive decline occurs.

Total flavone of Abelmoschl manihot L. medic exhibits protective effect against hind-limb ischemia in rat model.

Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from Chinese herb Abelmoschus manihot L. Medic. TFA has shown neuroprotective effect against cerebral ischemia injury in rats and rabbits. However, the effects of TFA on hind-limb ischemia and the underlying mechanisms remain unclear. Therefore, in the present study, we used a rat hind-limb ischemia model to investigate protective effect of TFA against limb ischemia injury. The rat model of hind-limb ischemia was established. Treatment groups received TFA at two different doses (160 and 40mg/kg) daily for 10 days. Sham operated control group and model group received saline. At the end the rats were sacrificed, hindlimb tissues were stained with Haematoxylin-Eosin and Masson's trichrome. RNA and protein were extracted from tissues for PCR and Western blot analysis. The results showed that TFA reduced lower limb ischemic injury, recovered tissue volume and diminished fibrosis and muscle degeneration. Mechanistically, we showed that TFA increased the expression of anti-apoptotic factor such as Bcl-2 and survivin, decreased the expression of pro-apoptotic factor such as Caspase 3, Bax and Bak and inhibited the activation of caspase 3 and 9. In summary, this study proves new evidence that TFA protects hind-limb against ischemia injury by inhibiting apoptosis and could be a promising therapeutic agent for acute lower extremity ischemia.

Total Flavones of Abelmoschus manihot Exhibits Pro-Angiogenic Activity by Activating the VEGF-A/VEGFR2-PI3K/Akt Signaling Axis.

Angiogenesis is a process of new blood vessel formation from pre-existing vessels. Vascular endothelial growth factor-A (VEGF-A) binds to VEGF receptor-2 (VEGFR2) and thus activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway play a central role in angiogenesis. Total flavones of Abelmoschus manihot (TFA), the major active component of the traditional Chinese herb Abelmoschus manihot, display novel pro-angiogenic activity. However, little information concerning its underlying mechanism is available. Here we investigate the pro-angiogenesis of TFA with the aim of understanding its mechanism of action. Human umbilical vein endothelial cells (HUVECs) and the chick chorioallantoic membrane (CAM) model were used to evaluate pro-angiogenesis of TFA using cell viability, wounding healing, transwell invasion, tube formation, RT-qPCR and Western blot methods. LY294002, a PI3K inhibitor, was used to interfere with PI3K/Akt pathway signal for assessing the underlying mechanism. Results in vitro indicated TFA obviously promoted HUVECs proliferation, migration, invasion and tube formation. Furthermore, TFA markedly augmented PI3K and Akt phosphorylation and up-regulated VEGF-A and VEGFR2 expression in HUVECs. However, pre-treatment with LY294002 not only markedly attenuated TFA-induced cells proliferation, migration, invasion and tube formation, but also significantly abolished TFA-induced VEGF-A and VEGFR2 over-expression as well as PI3K and Akt phosphorylation. Experiments in CAM model showed TFA significantly promoted the formation of branched blood vessels and was dramatically suppressed by LY294002. Taken together, TFA promoted angiogenesis both in vitro and in vivo which, however, were counteracted by LY294002, suggesting at least in part, TFA exhibits pro-angiogenic activity by activating the VEGF-A/VEGFR2-PI3K/Akt signaling axis.

Total flavones of abelmoschus manihot enhances angiogenic ability both in vitro and in vivo.

Angiogenesis is a process of new blood vessel formation from pre-existing vessels. It is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. Total flavones of Abelmoschus manihot (TFA) are the major constituents of the traditional Chinese herb Abelmoschus manihot L. Medic. The aim of this study is to investigate the effect of TFA on angiogenic ability using human umbilical vein endothelial cells (HUVECs) in vitro and chick chorioallantoic membrane (CAM) in vivo. HUVECs were treated with TFA at different concentrations. Cell viability, cell cycle progression, cell apoptosis, cell migration and tubular formation were investigated. The expression of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, VEGFR-2) was examined by immunohistochemistry to identify mechanism of action of TFA. CAM model was used to evaluate the effect of TFA on angiogenesis in vivo. Our results showed that TFA promoted HUVECs proliferation in a dose- and time-dependent manner. It increased HUVECs migratory ability and the number of tubular structure, promoted vessel formation in HUVECs culture and CAM model. Furthermore, TFA treatment resulted in a decrease in cell apoptosis and enhanced the expression of VEGF and KDR. Taken together, TFA, as the major active component isolated from the traditional Chinese herb Abelmoschus manihot L. Medic, could enhance angiogenic ability of HUVECs in vitro and CAM in vivo. TFA may be used in the treatment of wound healing and ischemic/reperfusion injuries.

The cardioprotective effect of total flavonoids on myocardial ischemia/reperfusion in rats.

The flowers of Abelmoschus manihot (L.) Medic is a traditional Chinese medicine used for the treatment of ischemic diseases. The present study is to investigate whether total flavones (TA) of extracted from Abelmoschus manihot L. Medic has the potential cardioprotective effect on myocardial ischemia/reperfusion (I/R) damage in rats. The index of myocardial injury, inflammatory biomarkers and NLRP3-related parameters were measured, respectively. The results demonstrated that compared to I/R group, TA reduced myocardial infarction area, declined serum creatinine kinase (CK), lactate dehydrogenase (LDH) levels, attenuated serum interleukin-6 (IL-6), IL-1ß and tumour necrosis factor (TNF-α) production. Moreover, TA markedly enhanced the activities of superoxide dismutase (SOD) and reduced the amounts of malondialdehyde (MDA) in I/R rats. In addition, TA reduced myocardial I/R induced injury in rats by inhibiting NLRPR3 inflammasome. Thus, it is assumed that TA could significantly improve myocardial I/R injury in rats partially through suppressing NLRP3 activtion.