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September 2011

Active-oxygen scavenging activity of traditional nourishing-tonic herbal medicines and active constituents of Rhodiola sacra.

The active-oxygen scavenging activity of 70 traditional herbal medicines used in China and Japan as nourishing tonics were evaluated by electron spin resonance (ESR) technique, in order to evaluate their effectiveness for anti-aging and to search for new active-oxygen scavengers from natural resources. Most of the 70 herbal medicines showed scavenging activity with various intensities. Areca catechu (methanol extract), Dendrobium plicatile (methanol extract), Juglans regia (water extract), Paeonia lactiflora (methanol extract), Psychotria serpens (water and methanol extracts), Rhodiola sacra (water and methanol extracts) and Uncaria rhynchophylla (water extract) especially showed strong scavenging activity against superoxide anion radical (*O2-), while J. regia (water and methanol extracts), Morus alba (water extract) and Schisandra chinensis (water extract) revealed strong scavenging activity against hydroxyl radical (HO*). In addition, the active-oxygen scavenging activities of 19 compounds isolated from R. sacra were also examined, and hydroquinone (1), caffeic acid (3), protocatechuic acid (6), gallic acid (7), (-)-epigallocatechin 3-O-gallate (8), 3-O-galloylepigallocatechin-(4beta-->8)-epigallocatechin+ ++ 3-O-gallate (10), heterodendrin (17) and gallic acid 4-O-beta-D-glucopyranoside (19) were found to show mild or strong inhibitory activity against superoxide anion radical (*O2-), while 4-hydroxybenzoic acid (2), 3, 4-hydroxycinnamic acid (4), 6-8 and 19 inhibited hydroxyl radical (OH*). These active-oxygen scavengers may contribute, to different extents, to their anti-aging action.

J Ethnopharmacol. 1999 Oct;67(1):111-9

Rhodiola: a promising anti-aging Chinese herb.

Using the fruit fly, Drosophila melanogaster, we investigated the effects of Rhodiola on life-span. Rhodiola is a plant root used in traditional Chinese medicine that may increase an organism’s resistance to stress. It has been proposed that Rhodiola can extend longevity and improve health span by alleviating oxidative stress. Rhodiola supplied every other day at 30 mg/mL significantly increased the lifespan of Drosophila melanogaster. When comparing the distribution of deaths between Rhodiola-supplemented and control flies, Rhodiola-fed flies exhibited decelerated aging. Although the observed extension in lifespan was associated with statistically insignificant reductions in fecundity, correcting for a possible dietary restriction effect still did not eliminate the difference between supplemented and control flies, nor does the effect of Rhodiola depend on dietary manipulation, strongly suggesting that Rhodiola is not a mere dietary restriction mimetic. Although this study does not reveal the causal mechanism behind the effect of Rhodiola, it does suggest that the supplement is worthy of continued investigation, unlike the other Chinese herbals, Lu Duo Wei (LDW), Bu Zhong Yi Qi Tang (BZYQT), San Zhi Pian (SZP, Three Imperial Mushrooms), Hong Jing Tian (Rhodiola) that were evaluated in this study.

Rejuvenation Res. 2007 Dec;10(4):587-602

The cardioprotective and antiadrenergic activity of an extract of Rhodiola rosea in stress.

The course of administration of Rhodiola rosea extract was studied for effects on the pattern of stress-induced cardiac damage which was assessed by 99mTc-pyrophosphate accumulation in the heart. Rhodiola rosea was found to prevent stress-induced cardiac damage. Simultaneously, myocardial catecholamines and cAMP levels were measured. Rhodiola rosea was ascertained to prevent both stress-induced catecholamine release and higher cAMP levels in the myocardium. Moreover, the adaptogen prevented lower adrenal catecholamines during stress. The findings suggest that the antistressor and cardioprotective effects of Rhodiola rosea are associated with limited adrenergic effect on the heart.

Eksp Klin Farmakol. 1994 Nov-Dec;57(6):61-3

Cardioprotective and antiarrhythmic properties of Rhodiolae roseae preparations.

It is established that the chronic administration of Rhodiola rosea extract (RRE) in a single daily dose of 1 ml/kg (p.o.) during 8 days increased the resistance of myocardium with respect to the cardiotoxic action of isoproterenol and the arrhythmogenic action of epinephrine in rats. Pretreatment with RRE prevented the stressor cardiac damages, as measured by 99mTc-pyrophosphate accumulation in the heart. The cardioprotective action of RRE was maximum after 5-day administration. The antiarrhythmic effect of the adaptogen was maximum after 8-day administration. It was found that p-tyrosol also exhibited antiarrhythmic and cardioprotective properties. Pretreatment with RRE decreased the infarction size/risk area ratio during the coronary artery occlusion and reperfusion in vivo. The chronic administration of RRE increased th e tolerance of the isolated perfused rat heart to the pathogenic action of global ischemia and reperfusion. Pretreatment with RRE not only prevented the occurrence of arrhythmias, but also abolished cardiac electrical instability in rats with postinfarction cardiac sclerosis. It has been found that the chronic administration of RRE (1 ml/kg, p.o., over 8 days) increased the level beta-endorphin in rat blood plasma and the content of leu-enkephalin in myocardial tissue. Naloxone (2 mg/kg) abolished cardioprotective and antiarrhythmic effect of the adaptogen. It was suggested that both RRE effects depend on the occupancy of opioid receptors by endogenous opioid peptides. It has been found that the sympathetic nervous system is involved in the development of antiarrhythmic effect of RRE, while HSP-70 is not involved in the cardioprotective and antiarrhythmic effect of adaptogen. It is concluded that the mechanism of cardioprotective and antiarrhythmic action of RRE needs further investigation.

Eksp Klin Farmakol. 2007 Sep-Oct;70(5):59-67

Bioactive constituents from Chinese natural medicines. XXVI. Chemical structures and hepatoprotective effects of constituents from roots of Rhodiola sachalinensis.

The methanolic extract from the roots of Rhodiola sachalinensis was found to show a protective effect on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes. From the methanolic extract, five new glycosides, two monoterpene glycosides, two flavonol bisdesmosides, and a cyanogenic glycoside, were isolated together with 34 known compounds. The structures of new constituents were elucidated on the basis of chemical and physicochemical evidence. In addition, the principal constituents, sachalosides III and IV, rhodiosin, and trans-caffeic acid, displayed hepatoprotective effects.

Chem Pharm Bull (Tokyo). 2007 Oct;55(10):1505-11

Hepatoprotective phenolic constituents of Rhodiola sachalinensis on tacrine-induced cytotoxicity in Hep G2 cells.

Two hepatoprotective phenolic compounds, kaempferol (2) and salidroside (4), were isolated from the roots of Rhodiola sachalinensis together with two inactive compounds cinnamyl alcohol (1) and daucosterol (3) based on the hepatoprotective activity against tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. The EC(50) values of compounds 2 and 4 were 33.5 and 51.3 micro m, respectively. Silybin as a positive control showed an EC(50) value of 68.4 micro m.

Phytother Res. 2003 May;17(5):563-5

Anti-inflammatory activity of Rhodiola rosea—”a second-generation adaptogen”.

Rhodiola rosea (golden root), a unique phytoadaptogen grown in high-altitude regions has gained attention for its various therapeutic properties. In India, this plant is found in the Himalayan belt and has not been completely explored for its beneficial health effects. The present study was undertaken to evaluate the anti-inflammatory efficacy of the tincture extract of Rhodiola rosea roots (RTE). The anti-inflammatory activity was determined through carrageenan-induced paw oedema, formaldehyde-induced arthritis and nystatin-induced paw oedema in rat model. The tincture extract exhibited inhibitory effect against acute and subacute inflammation at a dose of 250 mg/kg body weight. Inhibition of nystatin-induced oedema was also observed in a dose-dependent manner. The in vitro inhibitory effects of the tincture extract from R. rosea roots was evaluated against the enzymes relating to inflammation. The enzymes include cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and Phospholipase A2 (PLA2). The extract showed varying inhibitory activities against these enzymes depending on the concentrations. A potent inhibition was observed against Cox-2 and PLA2. Inhibition of nystatin induced oedema and phospholipase A2 suggested that membrane stabilization could be the most probable mechanism of action of RTE in anti-inflammation. The findings in this study may provide the use of R. rosea root extract in the treatment of inflammatory conditions.

Phytother Res. 2009 Aug;23(8):1099-102

Aqueous extract of Rhodiola imbricata rhizome stimulates proinflammatory mediators via phosphorylated IkappaB and transcription factor nuclear factor-kappaB.

Modulation of immune response to alleviate diseases has long since been of interest. Plant extracts have been widely investigated for their possible immunomodulatory properties. We have evaluated the immunomodulatory activity of aqueous extract of Rhodiola rhizome in human peripheral blood mononuclear cells (PBMCs) and mouse macrophage cell line RAW 264.7. The Rhodiola extract was found to stimulate production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in human PBMCs as well as RAW 264.7 cell line. It also increased production of nitric oxide synergistically in combination with lipopolysaccharide (LPS) in RAW 264.7. Rhodiola at 250 microg/ml increased the p-IkappaB expression in human PBMCs. Aqueous extract of Rhodiola (250 microg/ml) also activated the nuclear translocation of NF-kappaB in human PBMCs, which is comparable to the positive stimulant LPS. Thus, our present study suggests that Rhodiola most likely activates proinflammatory mediators via phosphorylated inhibitory kB and transcription factor NF-kB. Our study demonstrates immunostimulatory potential of aqueous extract of Rhodiola rhizome, that can be used for upregulation of immune response in patients with inadequate functioning of the immune system.

Immunopharmacol Immunotoxicol. 2006;28(2):201-12

Adjuvant effect of aqueous extract of Rhodiola imbricata rhizome on the immune responses to tetanus toxoid and ovalbumin in rats.

In the present study we have evaluated the immunopotentiating activity of Rhodiola aqueous extract (RAE) in rats. The efficacy of RAE was determined by using strong antigen tetanus toxoid (TT) and weak antigen Ovalbumin (OVA). The dynamic changes in humoral and cell-mediated immune response were measured. The results indicated that the TT specific immunoglobulin levels were significantly enhanced by RAE and were at par with complete Freund’s adjuvant (CFA). The level of OVA induced antibody response was also enhanced by RAE. It was observed that TT and OVA in combination with CFA or RAE could evoke a significant delayed type hypersensitivity (DTH) response, confirming its potential to generate strong cell-mediated immunity (CMI). The anti-inflammatory or immunosuppressive effect of RAE was evaluated in adjuvant-induced arthritis model (AIA). RAE could not suppress the swelling response. Therefore, this study suggests that RAE has adjuvant/immunopotentiating activity in terms of humoral as well as cell-mediated immune response against strong antigen like TT and weak antigen like OVA.

Immunopharmacol Immunotoxicol. 2010 Mar;32(1):141-6

The in vitro and in vivo antiviral effects of salidroside from Rhodiola rosea L. against coxsackievirus B3.

The aim of this study was to investigate the antiviral effects of salidroside, a major component of Rhodiola rosea L. First, the antiviral effects of salidroside against coxsackievirus B3 (CVB3) were determined in vitro and in vivo. Then, the effect of salidroside on the mRNA expression of some important cytokines was measured in hearts of infected BALB/c mice by RT-PCR. Salidroside exhibited obvious antiviral effects both in in vitro and in vivo experiments. Salidroside was found to modulate the mRNA expression of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2). In conclusion, salidroside possesses antiviral activities against CVB3 and it may represent a potential therapeutic agent for viral myocarditis.

Phytomedicine. 2009 Mar;16(2-3):146-55.

Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities.

Five flavonols (3, 5, and 9-11) were isolated from Rhodiola rosea, and compared with commercially available flavonoids (1, 2, 4, 6-8, and 12-14) to facilitate analysis of their structure-activity relationship (SAR). All compounds (1-14) showed neuraminidase inhibitory activities with IC(50) values ranging from 0.8 to 56.9 microM. The in vitro anti-influenza virus activities of flavonoids 1-6, 8-12, and 14 were evaluated using two influenza viral strains, H1N1 (A/PR/8/34) and H9N2 (A/Chicken/Korea/MS96/96), testing their ability to reduce virus-induced cytopathic effect (CPE) in MDCK cells. We found that the activity of these compounds ranged from 30.2 to 99.1 microM against H1N1- and 18.5 to 133.6 microM against H9N2-induced CPE. Of compounds 1-14, gossypetin (6) exhibited the most potent inhibitory activity, with IC(50) values of 0.8 and 2.6 microM on neuraminidases from Clostridium perfringens and recombinant influenza virus A (rvH1N1), respectively. In contrast, kaempferol (3) exhibited the highest activity against two influenza viruses, H1N1 and H9N2 with EC(50) values of 30.2 and 18.5 microM, respectively. Activity depended on the position and number of hydroxy groups on the flavonoids backbone. In kinetic studies, all isolated compounds behaved as noncompetitive inhibitors.

Bioorg Med Chem. 2009 Oct 1;17(19):6816-23

Activity of compounds from Chinese herbal medicine Rhodiola kirilowii (Regel) Maxim against HCV NS3 serine protease.

Treatment of the chronic hepatitis C virus (HCV) infection is an unmet medical need, and the HCV NS3 serine protease (NS3-SP) has been used as an attractive target of antiviral screening against HCV. To find naturally chemical entities as lead compounds from which novel anti-HCV agents could be developed, bioassay-guided fractionation and isolation were performed on a crude ethanol extract from rhizomes of the Chinese medicinal herb Rhodiola kirilowii (Regel) Maxim using column chromatography (CC) techniques and in vitro inhibitory activity against HCV NS3-SP. The partition of the extract between water and different organic solvents led to the isolation and identification of 12 compounds in the ethyl acetate part which proved to be the most active. These compounds were tested for in vitro activity against HCV NS3-SP, among which four (-)-Epicatechin derivatives: 3,3’-Digalloylproprodelphinidin B2 (Rhodisin, 1); 3,3’-Digalloylprocyanidin B2 (2); (-)-Epigallocatechin-3-O-gallate (EGCG, 3); and (-)-Epicatechin-3-O-gallate (4, ECG) represented the most potent ones with IC(50) of 0.77, 0.91, 8.51, and 18.55 microM, respectively. Salidroside, the commonly known compounds, together with the other compounds showed no activity up to 100.0 microM. Methylation and acylation of the hydroxyl groups of 1-4 caused a decrease of activity. Cell viability and secreted alkaline phosphatase (SEAP) activity assays with 1-4 revealed little if any toxicity. These nonpeptide inhibitors of HCV NS3-SP might serve as potential candidate anti-HCV agents.

Antiviral Res. 2007 Oct;76(1):86-92

Chemical constituents and anti-tuberculosis activity of root of Rhodiola kirilowii.

The chemical constituents of Rhodiola kirilowii were separated and purified by repeated column chromatography on silica gel, RP - 18, Sephadex LH -20 and semi-preparative HPLC. Each compound was characterized by spectroscopic and physical data. Twelve compounds have been purified and identified to be beta-sitosterol (1), tyrosol (2), trans-hydroxycinnamic acid (3), geranyl beta-glucopyranoside (4), neryl beta-glucopyranoside (5), hexyl beta-glucopyranoside (6), gallic acid (7), (-) -epigallocatechin gallate (8), rhodiolgin (9), isolariciresinol-9-O-beta-glucopyranoside (10), rhodiooctanoside (11), and sacranoside B (12). Among them, compounds 3, 6, 9-12 were isolated from Rhodiola kirilowii for the first time; Compounds 4 and 5 were obtained for the first time from the genus Rhodiola. The in vitro activities against Macobacterium tuberculosis (ATCC 27294) of its extracts and pure components were evaluated by testing their MIC (minimal inhibitory concentration) and MBC (minimal bactericidal concentration). The 80% (a. q.) EtOH extract, EtOAc-soluble extract, compounds 7 and 8 exhibited in-vitro inhibitory and bactericidal activities against Macobacterium tuberculosis in different extent.

Zhongguo Zhong Yao Za Zhi. 2008 Jul;33(13):1561-5

Bioactive compounds from Rhodiola rosea (Crassulaceae).

The methanol extract of the underground part of Rhodiola rosea was found to show inhibitory activity against Staphylococcus aureus. Bioactivity-guided fractionation of a 95% ethanol extract from the stems of R. rosea led to the isolation of five compounds: gossypetin-7-O-L-rhamnopyranoside (1), rhodioflavonoside (2), gallic acid (3), trans-p-hydroxycinnamic acid (4) and p-tyrosol (5). Their structures were elucidated by UV, IR, MS and NMR data, as well as by comparison with those of the literature. Compounds 1 and 2 were evaluated for their antibacterial and antiprostate cancer cell activities. Compounds 1 and 2 exhibited activity against Staphylococcus aureus with minimum inhibitory concentrations of 50 microg/mL and 100 microg/mL, respectively. Cytotoxicity studies of 1 and 2 also displayed activity against the prostate cancer cell line with IC(50) values of 50 microg/mL and 80 microg/mL, respectively.

Phytother Res. 2005 Sep;19(9):740-3

Neuroprotective effects of constituents of the oriental crude drugs, Rhodiola sacra, R. sachalinensis and Tokaku-joki-to, against beta-amyloid toxicity, oxidative stress and apoptosis.

We tested the constituents of two Rhodiola plants, Rhodiola sacra S. H. Fu and R. sachalinensis A. BOR, and an Oriental crude drug, Tokaku-joki-to, for their neuroprotective effects. Of the 58 compounds tested, six had considerable protective effects against beta-amyloid-induced death of B103 neuronal cells in vitro. These six compounds also showed protective effects against staurosporine-induced cell death, and two of the six compounds protected neurons from H2O2-induced cell death. These results suggest that some of the tested compounds protect neurons from beta-amyloid toxicity based on antiapoptotic and antioxidative activity.

Biol Pharm Bull. 2002 Aug;25(8):1101-4