ginsenoside-rg5 and Disease-Models--Animal

As the most common sleep disorder, insomnia seriously affects people's everyday lives. Phytochemicals have been shown to have excellent sleep-promoting effects. Therefore, this study was designed to investigate whether Rg5 and Rk1 extracted from ginseng had sleep-promoting effects and to explore their potential mechanisms. The results showed that Rg5 and Rk1 could significantly lessen the locomotor activity of mice and promote the sleep quality index, including increasing the amount of sleep in a pentobarbital sodium experiment with a threshold dose. In parallel, Rg5 and Rk1 could significantly shorten the sleep latency of mice and prolong the sleep time of mice. Furthermore, Rg5 and Rk1 augmented the GABA/Glu ratio, up-regulating the expression of the GABAA receptor and the GABAB receptor, whereas the GABAA receptor antagonist picrotoxin could antagonize the sleep quality of Rg5/Rk1. In addition, 5-HTP, the precursor of 5-HT, could enhance the sleep effect of Rg5 and Rk1 in mice, and both Rg5 and Rk1 could up-regulate the expression of 5-HT1A. These results were also confirmed by the detection of GABA and 5-HT in mouse cecum content. In conclusion, ginsenoside Rg5/Rk1 can exert sedative and hypnotic effects by affecting the GABA nervous system and the serotonin nervous system.

Topics: Animals; Disease Models, Animal; Ginsenosides; Male; Panax; Phytotherapy; Plant Oils; Rats; Rats, Wistar; Receptors, GABA-A; Signal Transduction; Sleep; Sleep Initiation and Maintenance Disorders; Up-Regulation

Breast cancer is the most frequently diagnosed cancer and has become the main cause of cancer-related death among women worldwide. Traditional chemotherapy for breast cancer has serious side effects for patients, such as the first-line drug docetaxel. Ginsenoside Rg5, a rare ginsenoside and the main ingredient extracted from fine black ginseng, has been proved to have anti-breast cancer efficacy in vitro. Here, the in vivo anti-breast cancer efficacy, side effects and potential molecular mechanisms of Rg5 were investigated on a BALB/c nude mouse model of human breast cancer. The tumor growth inhibition rate of high dose Rg5 (20 mg kg-1) was 71.4 ± 9.4%, similar to that of the positive control docetaxel (72.0 ± 9.1%). Compared to docetaxel, Rg5 showed fewer side effects in the treatment of breast cancer. Treatment with Rg5 induced apoptosis and autophagy in breast cancer tissues. Rg5 was proved to induce caspase-dependent apoptosis via the activation of the extrinsic death receptor and intrinsic mitochondrial signaling pathways. The autophagy induction was related to the formation of an autophagosome and accumulation of LC3BII, P62 and critical Atg proteins. Further studies showed that Rg5 in a dose-dependent manner induced apoptosis and autophagy through the inhibition of the PI3K/Akt signaling pathway as indicated by the reduced phosphorylation level of PI3K and Akt. Taken together, Rg5 could be a novel and promising clinical antitumor drug targeting breast cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; Autophagy; Autophagy-Related Proteins; Breast Neoplasms; Disease Models, Animal; Docetaxel; Female; Gene Expression Regulation; Ginsenosides; Humans; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Panax; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction; Xenograft Model Antitumor Assays

This study investigated the effect of ginsenoside‑Rg5 on the degradation of articular cartilage in osteoarthritis rat model and on induction of chondrocyte apoptosis. Osteoarthritis rat model was prepared by ligament transection and medial meniscus resection. The rats were then treated with different doses (1, 2, 5, 10 and 15 µM) of ginsenoside‑Rg5 for 48 h. The results from histopathological analysis revealed a significant (P=0.005) prevention of cartilage degradation in OA rat model by ginsenoside‑Rg5 treatment at 15 µM. Ginsenoside‑Rg5 treatment prevented the disintegration of synovial membrane to a significant (P=0.005) extent. The proportion of apoptotic cells in the knee joints was reduced to 7% by ginsenoside‑Rg5 treatment after one month compared to the control. Treatment of the rats with ginsenoside‑Rg5 caused increase in the levels of proteoglycan, collagen and type II collagen by 5-, 3- and 4-fold compared to the control group. Immunohistochemistry revealed that the level of MMP-13 was reduced to 45% and that of TIMP‑1 was increased by 67% on treatment with ginsenoside‑Rg5. The levels of interleukin-1β, tumor necrosis factor-α, nitric oxide and inducible nitric oxide synthetase were reduced by 67, 54, 32 ad 49%, respectively after one month of treatment with 15 mg/kg dose of ginsenoside‑Rg5. The expression was increased to 67 and 52% for BMP-2 and TGF-β1, respectively on treatment with ginsenoside‑Rg5. Thus ginsenoside‑Rg5 prevents cartilage degradation in the OA rats and inhibits cartilage apoptosis, therefore it can be used for osteoarthritis treatment.

Topics: Animals; Apoptosis; Blotting, Western; Cartilage, Articular; Cells, Cultured; Chondrocytes; Disease Models, Animal; Flow Cytometry; Ginsenosides; Knee Joint; Male; Matrix Metalloproteinase 13; Osteoarthritis; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tissue Inhibitor of Metalloproteinase-1

Neuroinflammatory responses play a crucial role in the pathogenesis of Alzheimer's disease (AD). Ginsenoside Rg5 (Rg5), an abundant natural compound in Panax ginseng, has been found to be beneficial in treating AD. In the present study, we demonstrated that Rg5 improved cognitive dysfunction and attenuated neuroinflammatory responses in streptozotocin (STZ)-induced memory impaired rats. Cognitive deficits were ameliorated with Rg5 (5, 10 and 20mg/kg) treatment in a dose-dependent manner together with decreased levels of inflammatory cytokines TNF-α and IL-1β (P<0.05) in brains of STZ rats. Acetylcholinesterase (AChE) activity was also significantly reduced by Rg5 whereas choline acetyltransferase (ChAT) activity was remarkably increased in the cortex and hippocampus of STZ-induced AD rats (P<0.05). In addition, Congo red and immunohistochemistry staining results showed that Rg5 alleviated Aβ deposition but enhanced the expressions of insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) in the hippocampus and cerebral cortex (P<0.05). Western blot analysis also demonstrated that Rg5 increased remarkably BDNF and IGF-1 expressions whereas decreased significantly Aβ deposits (P<0.05). Furthermore, it was observed that the expressions of COX-2 and iNOS were significantly up-regulated in STZ-induced AD rats and down-regulated strongly (P<0.05) by Rg5 compared with control rats. These data demonstrated that STZ-induced learning and memory impairments in rats could be improved by Rg5, which was associated with attenuating neuroinflammatory responses. Our findings suggested that Rg5 could be a beneficial agent for the treatment of AD.

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents; Behavior, Animal; Choline O-Acetyltransferase; Cognition Disorders; Disease Models, Animal; Ginsenosides; Interleukin-1beta; Male; Maze Learning; Memory; Neuroprotective Agents; Rats; Rats, Wistar; Streptozocin; Tumor Necrosis Factor-alpha