Rb1 Treatment Research Articles

Antidepressant Effects of Ginsenosides from Panax notoginseng

Ginsenosides Rg1, Rb1, R1, Rd, and Re are major constituents of Panax notoginseng, a famous traditional Chinese medicinal herb, which has both stimulative and inhibitory effects on the central nervous system (CNS). The monoamine hypothesis proposes that depression is a result of the depletion of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) in addition to the activation of monoamine oxidase in the CNS. The purpose of this study was to determine whether P. notoginseng Saponin (PNS) has an antidepressant activity. We investigated the antidepressant-like activities of Rg1, Rb1, R1, Rd, and Re in mice, using two animal models of depression. In addition, we analyzed the neurochemicals by the chronic unpredictable mild stress test. Our results showed that Rb1, Rd, and Re treatment at 10 mg kg−1 significantly reduced the duration of immobility in both the tail suspension and forced swimming tests. Rb1, Rd, and Re increases in 5-HT and NE levels at 10 mg kg−1 in both the frontal cortex and hippocampus. Dopamine levels increased in the hippocampus and the striatum. Moreover, 5-hydroxyindoleacetic acid (5-HIAA) levels were found increased in the hippocampus. These findings suggest that the antidepressant effects of Rb1, Rd, and Re may be related to the increase in 5-HT and NE in the CNS, and through the alterations in the synthesis or metabolism of dopamine.

Anti-neuroinflammation effect of ginsenoside Rbl in a rat model of Alzheimer disease

The present work explored the anti-neuroinflammation effects of Ginseng Rb1 in a rat model of Alzheimer disease produced by ventricle injection of Aβ1-42. Aβ1-42 injection induces loss of learning and memory behavior of rats in Morris water maze, which could be reversed with Rb1 treatment. Further, Rb1 reversed the changes in several direct or indirect neuroinflammation markers in the hippocampus, suggesting that this could be a potential underlying mechanism and a way to develop anti-aging drugs.

Ginsenoside RB1 Reduces Neurologic Damage, is Anti-Apoptotic, and Down-Regulates p53 and BAX in Subarachnoid Hemorrhage

Stroke is the second leading cause of death worldwide and the number one cause of adult disability in the United States and Europe. A subtype of stroke, subarachnoid hemorrhage (SAH), accounts for 7% of all strokes each year and claims one of the highest mortalities and morbidities. Many therapeutic interventions have been used to treat brain injury following SAH but none have reached the level of effectiveness needed to clinically reduce mortality. Ginsenoside Rb1 (GRb1), a major component of the Chinese traditional medicine Panax Ginseng, has been shown to reduce ischemic brain injury and myocardial injury via anti-apoptotic pathways. In the present study, we investigated the use of GRb1 on SAH induced brain injury in rats. Four groups were used: sham, vehicle (SAH), low dose treatment (SAH+ 5mg/kg GRb1), and high dose treatment (SAH+ 20mg/kg GRb1). Post assessment included wall thickness and mean cross-section area of basilar artery were measured for evaluating cerebral vasospasm, Evans blue extravasations to assess blood brain barrier (BBB) permeability, immunohistochemistry and Western Blot analysis looking for specific pro-apoptotic markers, and tunnel staining for cell death assessment. In addition, mortality, neurological function and brain edema were investigated. The results showed that high dose GRb1 treatment significantly enlarged mean cross-sectional area and decreased wall thickness of basilar artery, reduced neurological deficits, brain edema, BBB disruption, and TUNEL positive cell expression. Same time, we found that the proteins expression of P53, Bax and Caspase-3 were significantly reduced, whereas the expression of bcl-2 was up-regulated in Rb1 treatment. The results of this study suggest that GRb1 could relieve cerebral vasospasm and potentially provide neuroprotection in SAH victims. The underlying mechanisms may be partly related to inhibition of P53 and Bax dependent proapoptosis pathway. More studies will be needed to confirm these results and determine its potential as a long term agent.

Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction

To investigate the possible protective effect and mechanism of ginsenoside Rb1 against oxidative damage and renal interstitial fibrosis on rats with unilateral ureteral obstruction (UUO). In total, 80 male rats were randomly divided into 4 groups, 20 in each group: the sham operated group (SOR), UUO group, UUO with ginsenoside Rb1 treatment group (treated with intraperitoneal injection of 50 mg/ kg daily) and UUO with Losartan treatment group (as the positive control, treated with 20 mg/kg by gastrogavage per day). The rats were randomly sacrificed on day 3, 7 and 14 after surgery, respectively. The histopathologic changes of renal interstitial tissues were observed with Masson staining. The mRNA of transforming growth factor beta 1 (TGF-beta 1), collagen I and fibronectin were reversed transcribed and quantified by Real-time PCR. Enzyme-linked immunosorbent assay was used to quantitatively detect TGF-beta 1 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. P47phox protein expression was assessed by immunohistochemistry and Western blot analysis. In the UUO model, the obstructed kidney showed typical features of progressive renal tubulointerstitial fibrosis, and the levels of TGF-beta1, collagen I and fibronectin increased (P<0.05). As compared with the UUO group, ginsennoside Rb1 significantly inhibited the interstitial fibrosis including tubular injury and collagen deposition, and decreased the levels of TGF-beta1 (P<0.05). Ginsenoside Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative stress (P<0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox, a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P<0.05). Ginsenoside Rb1 can obviously inhibit renal interstitial fibrosis in rats with UUO, its mechanism possibly via against the oxidative damage and suppressing TGF-beta1 expression.

Ginsenoside Rb1 as a suppressor in central modulation of feeding in the rat.

Ginsenosides, the main component of Panax ginseng root, have been reported to show several pharmacological actions on the peripheral metabolism of glucose and lipid and on endocrine secretion. In the present study, the effects of ginsenoside Rb1 on feeding behavior and endogenous chemical substances were investigated in the normal (N) diet and high-fat (HF) diet rats. The male 4-week-old SD rats were randomly divided into N diet and HF diet group. After 5 weeks, each group was subdivided into N diet-Rb1 and HF diet-Rb1 group. The anti-obesity effects of Rb1 were estimated through analyses of changes in body weight, food intake, body fat mass, serum leptin, serum nitric oxide (NO), and hypothalamic appetitive peptides (neuropeptide Y:NPY, cholecystokinin:CCK), and locomotor activity. Administration of Rb1 (10 mg/kg, i.p., 3 weeks) in the HF diet group reduced the body weight, total food intake, fat contents, serum leptin and NO to level equals or below the N diet group. In the hypothalamus, especially paraventricular nucleus, the expression of orexigenic NPY was decreased and the expression of anorexigenic CCK was increased by Rb1 treatment compared with that of the HF diet group. Rb1-treated group in the HF diet from 1 week after treatment increased locomotor activity relative to HF diet group, but significant difference was not found among groups for the other experimental periods. The Rb1 may be useful agent for the control obesity via the implication in the peripheral and central appetitive modulators.

Ginsenoside-Rb1 Prevents HIV protease inhibitor ritonavir-induced vasomotor dysfunction

Introduction. We previously reported that ritonavir (RTV), one of the clinically used HIV protease inhibitors, can cause endothelial injury by increasing oxidative stress. The objective of this study was to determine whether an active ingredient of Panax ginseng, Ginsenoside-Rb1 (Rb1), could prevent coronary arteries from RTV-induced vasomotor dysfunction. Methods. Porcine coronary arteries were cut into 5-mm rings and incubated with RTV (15 μM) or/and Rb1 (1 or 10 mg/L) for 24 h. Vasomotor function was studied with a myograph tension system in response to U46619 (contraction) and bradykinin (relaxation). The mRNA and protein levels of endothelial nitric oxide synthase (eNOS) were determined by real-time PCR and Western blot, respectively. Superoxide anion levels were determined by lucigenin-enhanced chemiluminescence. Results. In response to U46619, the control vessels showed a vessel tension of 168 mN, while RTV-treated vessels had 41 mN, showing a 76% reduction ( P < 0.001, n = 8). The combination of RTV and Rb1 (1 or 10 mg/L) showed a vessel tension of 76 or 90 mN, respectively. In response to bradykinin, the control vessel rings relaxed by 70%, while RTV-treated vessels only relaxed by 29%, which showed a 59% reduction ( P < 0.001). Rb1 (1 or 10 mg/L) plus RTV showed 46 or 58% of vasorelaxation, respectively. The eNOS mRNA expression was decreased by 77% in RTV-treated vessels over controls ( P < 0.05). Western blot and immunohistochemistry also showed a decrease of eNOS protein levels in RTV-treated vessels. Superoxide anion levels in the RTV-treated group was increased by 47% over controls ( P < 0.05). Rb1 treatment (1 and 10 mg/L) significantly inhibited RTV-induced down regulation of eNOS and overproduction of superoxide anion. Conclusions. HIV protease inhibitor RTV significantly decreases vessel contractivity and endothelium-dependent vasorelaxation in porcine coronary arteries. It also decreases eNOS and increases superoxide anion production. Ginsenoside-Rb1 effectively inhibited RTV-induced endothelial dysfunction and oxidative stress in this model.