The mechanism of interactions between flavan-3-ols against a-glucosidase and their in vivo antihyperglycemic effects.

Catechin and epicatechin are flavan-3-ols, with (+)-catechin (C) and (-)-epicatechin (EC) being the most common optical isomers found in nature. In this study, we found that C and EC showed notable inhibitory activity against a-glucosidase (AGH), and that both inhibition activities reversible and competitive. Additionally, we observed that C and EC quenched the intrinsic fluorescence of AGH through a static quenching mechanism, and that the electrostatic force was the predominant driving factor in the binding reaction. Molecular docking studies indicated that the benzene-ring-4'-hydroxyphenyl construct on flavan-3-ol plays an important role in AGH inhibition, and that the inhibition increases along with increased binding of amino acid residues at this site. Furthermore, C and EC inhibited glucose absorption in everted intestine sleeves in vitro and suppressed increases in postprandial blood glucose levels in vivo. Our results suggest that C and EC are useful to protect against hyperglycemia through inhibiting the activity of a-glucosidase.

Vanillic acid alleviates palmitic acid-induced oxidative stress in human umbilical vein endothelial cells via Adenosine Monophosphate-Activated Protein Kinase signaling pathway.

Vanillic acid (VA), one of the phenolic acids metabolized by anthocyanidins, can modulate vascular reactivity by reducing the superoxide. We investigated that VA alleviated fatty acid-induced oxidative stress and clarified its potential mechanisms in human umbilical vein endothelial cells (HUVECs). Our results showed that VA reduced the production of reactive oxygen species and malondialdehyde levels. It also restored mitochondrial membrane potential and enhanced the activities of antioxidant enzymes. In addition, VA promoted the expression of p-Nrf2 and HO-1 through LKB1/AMPK signaling pathway, as well as the level of SIRT1 and PGC-1α. Moreover, compound C reduced the effect of VA on the enhancement of p-Nrf2 and HO-1. These results indicated that AMPK was an important target molecule of VA in the process of alleviating oxidative stress in HUVECs, providing a new potential evidence for vascular protection of anthocyanin in vitro. PRACTICAL APPLICATIONS: As a phenolic derivative and phase II metabolite of anthocyanins in vivo, VA can be found in various edible plants and fruits. This study revealed that VA improved oxidative stress in endothelial cells stimulated by palmitic acid by activating AMPK and its downstream proteins. VA could be a potential functional material for the protection of diabetic vascular complications.

[Expression of macrophage inflammatory protein-1alpha, a disintegrin-like and metalloproteinase 8 and 12, and CD68 protein in giant cell lesions of jaw and giant cell tumors of long bone].

OBJECTIVE: To detect the expression of macrophage inflammatory protein-1alpha (MIP-1alpha), a disintegrin-like and metalloproteinase (ADAM) 8 and 12 and CD68 protein in giant cell lesions of jaw and giant cell tumors of long bone, and to study their effects on the histogenesis of giant cells in such lesions. METHODS: MIP-1alpha, ADAM8, ADAM12 and CD68 were detected by immunohistochemistry in 24 paraffin-embedded specimens of central giant cell lesions of jaw and giant cell tumors respectively. RESULTS: MIP-1alpha positive signal was located in blood vessels and bone. ADAM8, ADAM12 and CD68 positive signals were located in the cell membrane and cytoplasm of all multinucleated giant cells and some round mononuclear cells in the lesions. In addition, some spindle mononuclear stromal cells were positive for ADAM12 in both lesions. CONCLUSION: Multinucleated giant cells probably originate from CD68-postive round mononuclear cells, which are recruited from monocyte-macrophage system by chemokines, such as MIP-1alpha, followed by cell fusion mediated by ADAM8 and ADAM12.

[Gene mutation and expression of SH-3BP-2 in cherubism].

OBJECTIVE: To detect the mutation and expression of SH-3BP-2 in Chinese patients of cherubism and to investigate the possible relationship of gene mutation and multinucleated giant cells in lesions. METHODS: Genomic DNA was extracted from paraffin-imbedded tissues and peripheral blood samples of 10 cases of cherubism (6 familial cherubism and 4 sporadic cherubism). SH-3BP-2 mutations were detected by PCR-direct sequencing. The nature of multinucleated giant cells in lesions was detected by enzyme histochemical staining and immunohistochemical staining using paraffin-imbedded tissues sections. The SH-3BP-2 protein was detected by immunohistochemical staining. RESULTS: Three missense mutations (G1520A, G1505A, G1505C) in exon 9 of SH-3BP-2 were identified which led to 3 transitions (Gly420Glu, Arg415Gln, Arg415Pro). There were no abnormalities in exon 3 of SH-3BP-2 except 1 case which had not PCR products. The protein SH-3BP-2, the calcitonin receptor and the tartrate-resistant acid phosphatase were detected in the cytoplasm of all multinucleated giant cells and parts of monokaryon matrix cells in 8 paraffin-imbedded samples. CONCLUSIONS: The SH-3BP-2 mutation may participate in the differentiation and maturation of osteoclast-like cells in the lesion of cherubism.

[Expression of receptor activator of NF-kappa B ligand and osteoprotegerin protein in the giant cell lesions of jaw].

OBJECTIVE: To detect the expression of RANKL and OPG protein in the giant cell lesions of jaw and to study the mechanism of this lesion. METHODS: RANKL and OPG were detected by immunohistochemistry (SP) in 24 paraffin-embedded and 2 frozen specimens of central giant cell lesion of jaw. RESULTS: RANKL signals were strongly positive in the vascular epithelial cells. They also could be found in fibrous stroma, bone matrix, and stromal spindle cells, even in some cytomembrane of multinucleated giant cells. OPG was detected in multinucleated giant cells and a fraction of round mononuclear cells. CONCLUSIONS: Active vascular epithelial cells are contributed to the formation of multinucleated giant cells through regulating RANKL, and RANKL could play its role by paracrine and autocrine, which might be inhibited by OPG.

[Expression of a disintegrin-like and metalloproteinase protein 8 and 12 in the giant cell lesions of jaw].

OBJECTIVE: To detect the expression of a disintegrin-like and metalloproteinase (ADAM) 8 and 12 gene in the giant cell lesions of jaw and to study their effects on the histogenesis of cells in these lesions. METHODS: ADAM8 and ADAM12 was detected by immunohistochemistry (SP) in 40 paraffin-embedded specimens of central giant cell lesions of jaw, 10 peripheral giant cell lesions, 9 cherubisms, 6 aneurysmal bone cysts. RESULTS: ADAM8 and ADAM12 were positive in the cytomembrane and cytoplasm of all multinucleated giant cells and some round mononuclear cells of the lesions; ADAM12 was positive for some spindle mononuclear stromal cells in central and peripheral giant cell lesions. CONCLUSIONS: Multinucleated giant cells probably originated from the fusion of the round mononuclear cells, and ADAM8 and ADAM12 were involved in this process. In addition, ADAM12 might play a role in the maturation of spindle mononuclear stromal cells.

[The beneficial effect of genistein on mandible bone metabolism in ovariectomized rats].

OBJECTIVE: To detect the effect of genistein on mandible metabolism in ovariectomized rats. METHODS: Forty 12 week-old female SD rats were randomly assigned to four groups: (1) sham operated; (2) ovariectomized; (3) ovariectomized and treated with estradiol; (4) ovariectomized and received genistein, 45 mg/kg body weight per day. After 12 weeks, bone mineral density (BMD), serum level of alkaline phosphatase (ALP), acid phosphatase (ACP), osteocalcin, IL-1beta, TNF-alpha, IL-6 and calcitonin (CT) were evaluated. In addition, the serum estradiol and the weight of uteri were also examined to indicate the side effect of genistein to the uteri. RESULTS: Ovariectomized animals had a significant decrease in BMD, and increased serum level of ALP, ACP, IL-1beta and osteocalcin compared with sham rats. After treated with genistein, BMD and the serum level of ALP, ACP, osteocalcin increased significantly, while the serum level of IL-1beta and TNF-alpha decreased. Especially, the increase of ALP and osteocalcin was higher than that of estradiol-treated animal. Additionally, the uterus weight index and the serum estradiol in genistein-treated rats were lower significantly than those of estradiol-treated rats. CONCLUSIONS: Genistein can improve the mandible bone metabolism as well as its effect on femur through the promotion of bone formation and the prevention of bone resorption with slight side effect. Genistein provides an additional viable way to therapy for osteoporosis in the jaw bones.

[Clinicopathologic study of a family cherubism].

OBJECTIVE: To investigate the clinicopathologic features of familial cherubism and its differentiation from other giant cell lesions in jaws and the results of surgical treatments with a long-term follow-up. METHODS: Four cases of familial cherubism were reviewed and their clinical and radiographic features, histopathologic appearance, biochemical markers and surgical treatments analysed. RESULTS: Clinically, cherubism was characterized by bilateral painless swelling of jaws, mandibular deformity was common. Radiographs showed multilocular radiolucencies with sclerotic thickening border. Histopathologically, numerous randomly distributed multinucleated giant cells and vascular spaces within a fibrous connective tissue stroma with or without eosinophilic collagen perivascular cuffing were shown. The lesion regressed without treatment in 1 cases. Curettage was performed in 3 cases with good results. CONCLUSIONS: Cherubism can be diagnosed according to its typical clinical and radiographical features with a positive family history. It might regress without treatment. But surgery intervention is suggested to improve physiological function and to solve the psychologic problem of the patients.