akebia-saponin-d and Disease-Models--Animal

Glucocorticoid hormones are implicated in the pathogenesis of Alzheimer's disease (AD) and other diseases including diabetes, hyperlipidemia, and osteoporosis. Akebia saponin D (ASD) possesses numerous pharmacological activities, including as an anti-AD, anti-hyperlipidemia, anti-diabetes, and anti-osteoporosis agent. The anti-AD effect of ASD is possibly through its regulation of glucocorticoid levels.. The present study was undertaken to investigate the neuroprotective effects of ASD on Aβ. The AD rat model was established by an intracerebroventricular injection of Aβ. Compared with the control group, AD rats displayed significant spatial learning and reference memory impairments, serious anxiety disorders, obvious hypertrophy of adrenal gland, elevated corticosterone and ACTH levels in the plasma, and increased 11β-HSD1 activity in liver and groin fat pad. ASD could significantly ameliorate the memory deficits and anxiety symptoms, markedly reduce the viscera coefficient of adrenal gland, observably decrease corticosterone and ACTH concentrations, and showed no effect on the activity of 11β-HSD1.. These results indicate that ASD might exert a significant neuroprotective effect on cognitive impairment, driven in part by reducing systemic corticosterone level by down-regulation of the hypothalamic-pituitary-adrenal (HPA) axis.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adipose Tissue; Adrenal Glands; Alzheimer Disease; Amyloid beta-Peptides; Animals; Anxiety; Corticosterone; Disease Models, Animal; Hypertrophy; Hypothalamo-Hypophyseal System; Liver; Male; Maze Learning; Memory Disorders; Models, Biological; Peptide Fragments; Pituitary-Adrenal System; Rats, Sprague-Dawley; Saponins; Viscera

Asperosaponin VI (ASA VI), a natural compound isolated from the well-known traditional Chinese herb Radix Dipsaci, has an important role in promoting osteoblast formation. However, its effects on osteoblasts in the context of osteoporosis is unknown. This study aimed to investigate the effects and mechanism of ASA VI action on the proliferation and osteogenic differentiation of bone marrow stromal cells isolated from the ovariectomized rats (OVX rBMSCs). The toxicity of ASA VI and its effects on the proliferation of OVX rBMSCs were measured using a CCK-8 assay. Various osteogenic differentiation markers were also analyzed, such as ALP activity, calcified nodule formation, and the expression of osteogenic genes, i.e., ALP, OCN, COL 1 and RUNX2. The results indicated that ASA VI promoted the proliferation of OVX rBMSCs and enhanced ALP activity and calcified nodule formation. In addition, while ASA VI enhanced the expression of ALP, OCN, Col 1 and RUNX2, treatment with LY294002 reduced all of these osteogenic effects and reduced the p-AKT levels induced by ASA VI. These results suggest that ASA VI promotes the osteogenic differentiation of OVX rBMSCs by acting on the phosphatidylinositol-3 kinase/AKT signaling pathway.

Topics: Animals; Bone Marrow; Cell Differentiation; Disease Models, Animal; Drugs, Chinese Herbal; Gene Expression Regulation, Developmental; Humans; Oncogene Protein v-akt; Osteogenesis; Osteoporosis; Phosphatidylinositol 3-Kinases; Ranunculaceae; Rats; Saponins; Signal Transduction; Stromal Cells

The aim of the study was to determine the effects of Asperosaponin VI (ASA VI), a triterpene saponin isolated from Dipsacus asper Wall, on chronic myocardial infarction (MI) and possible mechanisms in rats. MI was induced by permanent ligation of the left coronary artery. Twenty-four hours after MI, the rats were administered the extract by gavage (once a day). Six weeks after MI/sham surgery, cardiac dysfunction, infarct size (IS), cardiac fibrosis, hydroxyproline concentration, the oxidative stress parameter and inflammation mediators were examined. The results indicated that ASA VI improved left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dP/dt, heart weight/body weight, right ventricular weight/body weight and lung weight/body weight (P<0.01, P<0.05). These were accompanied by the attenuation of cardiac fibrosis, IS and hydroxyproline concentration (P<0.01, P<0.05). ASA VI could decrease the levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), but increase IL-10 content (P<0.01, P<0.05). Furthermore, it also could raise the activities of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but reduce malonyldialdehyde (MDA) level (P<0.01, P<0.05). The results indicated that ASA VI improved cardiac function and myocardial fibrosis from myocardial ischemia injury, and this cardioprotection might be attributed to reduce oxidative stress and regulate inflammation mediators.

Topics: Administration, Oral; Animals; Body Weight; Disease Models, Animal; Fibrosis; Interleukin-10; Interleukin-6; Male; Myocardial Infarction; Organ Size; Oxidative Stress; Rats; Rats, Sprague-Dawley; Saponins; Tumor Necrosis Factor-alpha

Cholinergic deficit is one of the most remarkable symptoms and plays an important role in Alzheimer's disease. In the present study, the protective effects of Akebia saponin D (ASD) on learning and memory impairments induced by excitatory neurotoxin ibotenic acid injection were examined in vivo. Our findings suggest that ASD (90 mg/kg, p.o.) would exert a rescue effect on rats both in behavioral performances in Morris water maze and Y maze and cholinergic functions detected by chemical methods. We further investigated in the hippocampus and found ASD could regulate apoptosis-related proteins expression following ibotenic acid injection. Additionally, mitogen-activated protein kinase (MAPK) family phosphorylations were inhibited after ASD treatment, implicating that the MAPK signaling pathway could be involved in the mechanism underlying neuroprotection of ASD against ibotenic acid-induced excitotoxicity.

Topics: Acetylcholine; Acetylcholinesterase; Animals; Apoptosis; Brain; Choline O-Acetyltransferase; Cognition Disorders; Disease Models, Animal; Hippocampus; Humans; Ibotenic Acid; Male; MAP Kinase Signaling System; Maze Learning; Memory; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Saponins

Neuroinflammatory responses caused by amyloid β(Aβ) play an important role in the pathogenesis of Alzheimer's disease (AD). Aβ is known to be directly responsible for the activation of glial cells and induction of apoptosis. Akebia Saponin D (ASD) is extracted from a traditional herbal medicine Dipsacus asper Wall, which has been shown to protect against ibotenic acid-induced cognitive deficits and cell death in rats. In this study, we investigated the in vivo protective effect of ASD on learning and memory impairment induced by bilateral intracerebroventricular injections of Aβ1-42 using Morris water and Y-maze task. Furthermore, the anti-inflammatory activity and neuroprotective effect of ASD was examined with methods of histochemistry and biochemistry. These data showed that oral gavage with ASD at doses of 30, 90 and 270 mg/kg for 4 weeks exerted an improved effect on cognitive impairment. Subsequently, the ASD inhibited the activation of glial cells and the expression of tumor necrosis factor (TNF)-α, interleukin-1 beta (IL-1β) and cyclooxygenase-2 (COX-2) in rat brain. Moreover, ASD afforded beneficial actions on inhibitions of Akt and IκB kinase (IKK) phosphorylations, as well as nuclear factor κB (NF-κB) activation induced by Aβ1-42. These results suggest that ASD may be a potential agent for suppressing both Alzheimer's disease-related neuroinflammation and memory system dysfunction.

Topics: Amyloid beta-Peptides; Animals; Cognition Disorders; Cytokines; Disease Models, Animal; Drug Administration Routes; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hippocampus; Inflammation; Male; Maze Learning; NF-kappa B p52 Subunit; Oncogene Protein v-akt; Peptide Fragments; Phosphorylation; Rats; Rats, Sprague-Dawley; Saponins; Signal Transduction

A novel topical paste used for fracture healing (FH), consisting of the extracts of six herbs, Radix Dipsaci, Ramulus Sambucus Williamsii, Rhizoma Notoginseng, Flos Carthami, Rhizoma Rhei and Fructus Gardeniae, was developed according to the classical theory of traditional Chinese medicine. This study aimed to determine the effectiveness of this formula, and some of its important chemical components in the promotion of fracture healing. The transdermal transport of FH was also examined.. The osteogenic, angiogenic and nitric oxide suppressing effects of FH and its important chemical marker components were assessed by using osteoblastosacroma UMR-106 cells, human umbilical vein endothelial cells (HUVEC) and murine macrophage RAW264.7 cells, respectively. The bone healing effects of the FH paste and its transdermal absorption were determined using a rabbit fracture model. The callus sizes, bone specific alkaline phosphatase levels and biomechanical properties of the healed bone were assessed.. FH significantly increased the cell proliferation in UMR-106 and HUVEC cells and inhibited the nitric oxide production in murine macrophage in dose-dependent manner. Its important chemical components asperosaponin VI, ginsenoside Rg1 and emodin were shown to be acting positively in the respective in vitro studies. FH paste significantly improved the bone healing in the rabbit fracture model, as was indicated by the increases in callus size at weeks 2-5, and the elevations in bone specific alkaline phosphatase activities at weeks 5-6. The analysis using LC/MS/MS also showed the presence of important chemical marker components of the FH formula in the plasma after 8 weeks of topical treatment.. This study presents the first scientific evidence of the efficacy of a herbal paste in the promotion of fracture healing. There were evidences of transdermal transport of the chemical components, control the inflammation through nitric oxide inhibition, promotion of angiogenesis, and bone healing in the in vitro tests, as well as in the experimental animal.

Topics: Administration, Cutaneous; Alkaline Phosphatase; Animals; Bony Callus; Cell Line; Cell Proliferation; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Emodin; Endothelial Cells; Endothelium, Vascular; Fracture Healing; Ginsenosides; Humans; Macrophages; Magnoliopsida; Male; Mice; Nitric Oxide; Osteogenesis; Phytotherapy; Rabbits; Saponins; Skin Absorption; Tibial Fractures; Umbilical Veins