Chrysanthemum coronarium L. Extract Attenuates Homocysteine-Induced Vascular Inflammation in Vascular Smooth Muscle Cells.

Hyperhomocysteinemia is a main risk factor for phenotypic modulation of vascular smooth muscle cells (VSMCs) and atherosclerosis. Phenotypic switching and proliferation of VSMCs are related to the progression of vascular inflammation. Chrysanthemum coronarium L. is a leafy vegetable with various biological functions, such as antioxidative, anti-inflammatory, and antiproliferative effects. In this study, we aimed to identify the mechanisms underlying the therapeutic and preventive effects of C. coronarium L. extract (CC) in regulating homocysteine (Hcy)-induced vascular inflammation in human aortic VSMCs. CC did not exhibit cytotoxicity and inhibited Hcy-stimulated VSMC proliferation and migration. In addition, CC promoted Hcy-induced expression of VSMC contractile phenotype proteins, including alpha-smooth muscle actin, calponin, and smooth muscle 22α. CC also decreased Hcy-induced accumulation of reactive oxygen species and expression of inflammatory markers nicotinamide adenine dinucleotide phosphate oxidase-4 and soluble epoxide hydrolase. These results showed that CC attenuates Hcy-induced inflammatory responses, highlighting its potential as a therapeutic or preventive target for Hcy-induced vascular inflammation.

Effect of Menaquinone-4 on Receptor Activator of Nuclear Factor κB Ligand-Induced Osteoclast Differentiation and Ovariectomy-Induced Bone Loss.

Osteoporosis is a progressive metabolic disease characterized by decreased bone mineral density and increased fracture risk. Previous studies have shown that higher intake of vitamin K (VK) correlates with a reduced risk of osteoporosis. However, the effect of menaquinone-4 (MK-4), a specific form of VK, still remains obscure. Therefore, in this study, we investigated the effects of MK-4 on osteoclast differentiation by differentiating RAW 264.7 cells into osteoclasts with the help of receptor activator of nuclear factor-kappa B ligand (RANKL), assessed the mRNA expression of osteoclast-specific genes, and studied the effects of MK-4 in vivo in ovariectomized mice, a postmenopausal osteoporosis murine model. MK-4 inhibited osteoclast differentiation, decreased the mRNA expression of nuclear factor of activated T cells c1 (NFATc1), osteoclast-associated receptor (OSCAR), and cathepsin K (CTSK), and inhibited bone loss in ovariectomized mice. The findings strongly suggest that MK-4 is a therapeutic alternative for postmenopausal osteoporosis.

Preventive Effects of Chrysanthemum coronarium L. Extract on Bone Metabolism In Vitro and In Vivo.

Osteoporosis is characterized by decreased bone mass and bone microarchitectural failure, leading to an enhanced risk of bone fractures. Chrysanthemum coronarium L. (CC) is a natural plant with powerful antioxidant activity. This study investigated the antiosteoporotic effects of CC extracts in in vitro cell cultures and in vivo bone loss animal models. CC stimulated osteoblast differentiation and mineralized bone formation by osteoblasts by increasing the expression of bone formation markers (alkaline phosphatase, osteoprotegerin, and osteoprotegerin/receptor activator nuclear factor-κB ligand ratio) in the murine preosteoblastic cell line MC3T3-E1. Additionally, CC was found to inhibit osteoclast differentiation by downregulating bone resorption markers (tartrate-resistant acid phosphatase, cathepsin K, dendritic cell-specific transmembrane protein, and calcitonin receptor) in the murine macrophage-like cell line RAW264.7. CC prevented ovariectomy-induced bone loss, preserved trabecular microarchitecture, and improved serum bone turnover markers in an osteoporotic mouse model. These findings suggest that CC extract may be considered as a natural therapeutic or preventive agent for osteoporotic bone loss.

Amaranthus mangostanus Inhibits the Differentiation of Osteoclasts and Prevents Ovariectomy-Induced Bone Loss.

Bone homeostasis is dynamically balanced between bone forming osteoblasts and bone resorbing osteoclasts. Osteoclasts play an important role in bone destruction and osteoporosis, and they are derived from monocyte/macrophages in response to macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). Amaranthus mangostanus L. (AM) is a plant with powerful antioxidant and other biological activities including anti-inflammatory, antidiabetic, and antihyperlipidemic effects. However, its effects on bone health are unknown. In this study, we explored whether AM could affect RANK-mediated osteoclastogenesis. AM significantly suppressed RANKL-induced osteoclast differentiation and expression of osteoclast-specific genes, TRAP, cathepsin K, NF-activated T-cells (NFATc1), and Dc-stamp in RAW 264.7 cells. Moreover, AM significantly inhibited extracellular signal-regulated kinase (ERK), Akt, and NF-κB signaling pathways in RAW 264.7 cells. In addition, AM preserved ovariectomy-induced bone loss in mice. Taken together, our results suggest that AM might be a potential candidate for the treatment of postmenopausal osteoporosis.

Peanut shell extract inhibits the development of dextran sulfate sodium (DSS)-induced colitis.

Inflammatory bowel diseases (IBD) induce inflammation in the colon and small intestine. IBD include ulcerative colitis and Crohn's disease, with such common symptoms as severe diarrhea, fever, and blood in the stool. In the current study, we explored the ability of peanut shell extract (PSE) to alleviate IBD in an experimental colonic inflammation model. Colitis was induced by orally administered dextran sulfate sodium (DSS) in mice. Peanut shell extract was prepared using a method of aqueous ethanol. DSS treatment reduced the colon length and mouse body weight, and aggravated disease condition compared with untreated control mice. Oral administration of 400 mg/kg PSE alleviated colon shortening, body weight loss, DAI, and colon injury score in DSS-induced colitis. These physiological improvements were validated by reduced levels of proinflammatory cytokines and infiltrating macrophage accumulation in the inflamed colon in the PSE administered group. These observations suggest that PSE may be developed as an alternative natural extract for the prevention or treatment of IBD.

Melandrii Herba Extract Attenuates H2O2-Induced Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells and Scopolamine-Induced Memory Impairment in Mice.

Oxidative stress plays a significant role in the etiology of a variety of neurodegenerative diseases. In this study, we found that Melandrii Herba extract (ME) attenuated oxidative-induced damage in cells. Mechanistically, ME exhibited protection from H2O2-induced neurotoxicity via caspase-3 inactivation, Bcl-2 downregulation, Bax upregulation, and MAPK activation (ERK 1/2, JNK 1/2, and p38 MAPK) in vitro. Moreover, our in vivo data showed that ME was able to attenuate scopolamine-induced cognitive impairment. These results provide in vitro and in vivo evidence that ME exhibits neuroprotective properties against oxidative stress, which suggests that ME is worthy of further investigation as a complementary, or even as an alternative, product for preventing and treating neurodegenerative disorders.

Luteolin ameliorates cisplatin-induced acute kidney injury in mice by regulation of p53-dependent renal tubular apoptosis.

BACKGROUND: Cisplatin chemotherapy often causes acute kidney injury in cancer patients. The causative mechanisms of cisplatin-induced acute kidney injury include renal inflammation, activation of p53 tumour suppressor protein and tubular apoptosis. Luteolin, a flavone found in medicinal herbs and plants, has been reported to exhibit anti-inflammatory, antioxidant and anticarcinogenic activities. The purpose of this study was to investigate the anti-apoptotic effect of luteolin on cisplatin-induced acute kidney injury and the molecular mechanism. METHODS: C57BL/6 mice were treated with cisplatin (20 mg/kg) with or without treatment with luteolin (50 mg/kg for 3 days). Renal function, histological changes, degree of oxidative stress and tubular apoptosis were examined. The effects of luteolin on cisplatin-induced expression of renal p53, PUMA-α and Bcl-2 family proteins were evaluated. RESULTS: Treatment of mice with cisplatin resulted in renal damage, showing an increase in blood urea nitrogen and creatinine levels, tubular damage, oxidative stress and apoptosis. Treatment of cisplatin-treated mice with luteolin significantly improved renal dysfunction, reducing tubular cell damage, oxidative stress and apoptosis. Examination of molecules involving apoptosis of the kidney revealed that treatment of cisplatin increased the levels of p53 and its phosphorylation, PUMA-α, Bax and caspase-3 activity that were significantly decreased by treatment with luteolin. CONCLUSION: These results indicate that cisplatin induces acute kidney injury by regulation of p53-dependent renal tubular apoptosis and that luteolin ameliorates the cisplatin-mediated nephrotoxicity through down-regulation of p53-dependent apoptotic pathway in the kidney.

Gymnema montanum H. protects against alloxan-induced oxidative stress and apoptosis in pancreatic beta-cells.

The present study evaluated the molecular mechanism of antidiabetic property of G. montanum leaf extract (GLEt) against alloxan-induced apoptotic cell death in rat insulinoma cells (RINm5F). The pre-treatment of GLEt (5 microg and 10 microg/ml) resulted in significant decrease in intracellular Ca(2+) concentration, nitric oxide (NO) production along with increase in mitochondrial membrane potential in alloxan (7mM/ml) treated cells. Further GLEt reduced apoptosis by inhibiting the release of cytochrome c and subsequent cleavage of PARP and caspase-3. The immunochemical staining of 8-hydroxydeoxyguanosine (8-OHdG) also evidenced the suppression of oxidative stress by GLEt. The cell cycle analysis, annexin-V labelling assay and TUNEL assay showed the suppression of apoptosis by the treatment of GLEt. Moreover, GLEt significantly increased the cellular antioxidant levels and decreased the lipid peroxides in alloxan-treated RINm5F cells. Taken together, these findings suggest that G. montanum protects pancreatic beta-cells against reactive oxygen species (ROS) by counteracting with mitochondrial membrane permeability and inhibition of the apoptotic pathway.