onjisaponin-b and Cognition-Disorders

In this study, we investigated the potential effect of onjisaponin B (OB) on aging rats induced by D-gal (D-galactose). Sub-acute aging model was established in rats by the subcutaneous injection of D-gal (120 mg/kg) for 42 days, accompanied with OB (10, 20 mg/kg, p.o.) or normal saline intervention for 28 days since the 14th day after the beginning of D-gal stimulation. Morris water maze test and step-down passive avoidance test were conducted to evaluate the cognitive function of the rats. The superoxidase dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GSH-px) contents in hippocampus were measured by according kits, respectively. And the hippocampus levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were assayed by enzyme-linked immunosorbent assay (ELISA). Furthermore, the expressions of SOD1, MDA5, GSH, GSH-px, NF-кB pathway were present by western blot. It revealed that administration of OB was able to significantly attenuate the D-gal-induced changes in the hippocampus, ranging from cognitive capacity, oxidative stress to inflammation response. In a nutshell, our data provided evidence that OB could contribute to the restoration of cognitive ability by improving the antioxidant and anti-inflammatory capacity in D-gal induced aging rats.

Topics: Aging; Animals; Avoidance Learning; Cognition Disorders; Disease Models, Animal; Galactose; Glutathione Peroxidase; Hippocampus; Interleukin-1beta; Interleukin-6; Male; Malondialdehyde; Maze Learning; NF-kappa B; Rats, Sprague-Dawley; Saponins; Superoxide Dismutase; Triterpenes; Tumor Necrosis Factor-alpha

The purpose of the present study was to investigate the effects of Onjisaponin B (OB) in lipopolysaccharide (LPS)-induced cognitive deficits.. The rats were divided into four groups: sham group, LPS group (the model group), LPS + OB (1 mg/kg) group and LPS + OB (2 mg/kg) group. OB was treated three days before surgery and thereafter continuously for 7 days. Three days later, rats were intracerebroventricularly injected with LPS. The levels of inflammatory cytokines and the capability of free radical scavenging in serum and hippocampus were determined after the LPS challenge. PC12 cells were divided into control group, LPS group (the model group), LPS + OB (10 µM) group, LPS + OB (20 µM) group, LPS + OB (40 µM) group, LPS + OB (2 mg/kg) + nicotinamide group. The cell viability was measured by MTT assay. The protein expressions of Sirt1, p-AMPK, AMPK, Nrf-2, HO-1, Bcl-2, Bax, caspase-9, caspase-3, p-IκBα, IκBα, p-NF-κBp65 and NF-κBp65 were detected by western blot analysis.. As a result, OB administration effectively relived the cognitive impairment, reduced the contents of IL-1β, IL-6, TNF-α, MDA and restored SOD activities of SOD in serum and hippocampus of LPS-induced rats. Furthermore, OB treatment improved cell viability, ameliorated the alterations of IL-1β, IL-6, TNF-α, MDA and SOD in the supernatant of LPS-induced PC12 cells. Of note, the expressions of Sirt1, Nrf-2, HO-1, Bcl-2 and p-AMPK were downregulated, while Bax, caspase-9, caspase-3 and the phosphorylations of IκBα and NF-κBp65 in the LPS-stimulated hippocampus and PC12 cells were increased attributed to the LPS stimulation. Nevertheless, the conditions were significantly attenuated by OB treatment. In the LPS-induced PC12 cell, nicotinamide, a SIRT1 inhibitor, abrogated the beneficial effects of OB, as indicated by the antioxidant, anti-inflammatory and anti-apoptosis signaling.. Based on the above evidence, our results demonstrated that OB was a potential therapeutic candidate for LPS-induced cognitive deficits.

Topics: Animals; Cognition Disorders; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Hippocampus; Lipopolysaccharides; Maze Learning; Neurons; Neuroprotective Agents; PC12 Cells; Rats; Rats, Sprague-Dawley; Saponins; Signal Transduction; Sirtuin 1; Superoxide Dismutase; Thiazolidinediones; Triterpenes

Decline of cognitive function is the hallmark of Alzheimer's disease (AD), regardless of the pathological mechanism. Traditional Chinese medicine has been used to combat cognitive impairments and has been shown to improve learning and memory. Radix Polygalae (RAPO) is a typical and widely used herbal medicine. In this study, we aimed to follow the β-amyloid (Aβ) reduction activity to identify active constituent(s) of RAPO. We found that Onjisaponin B of RAPO functioned as RAPO to suppress Aβ production without direct inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and γ-secretase activities. Our mechanistic study showed that Onjisaponin B promoted the degradation of amyloid precursor protein (APP). Further, oral administration of Onjisaponin B ameliorated Aβ pathology and behavioral defects in APP/PS1 mice. Taken together, our results indicate that Onjisaponin B is effective against AD, providing a new therapeutic agent for further drug discovery.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Cell Line; Cognition Disorders; Disease Models, Animal; Drugs, Chinese Herbal; Enzyme Activation; Humans; Medicine, Chinese Traditional; Mice; Mice, Transgenic; Nootropic Agents; Proteolysis; Saponins; Substrate Specificity; Triterpenes