Rosea Root Extract Research Articles

Phytochemical profile and anti-inflammatory activity of a commercially available Rhodiola rosea root extract

Rhodiola rosea roots and rhizomes hold an important place in the folk medicines of Russia, Scandinavia, Mongolia, and China as a health supplement for stimulating the nervous system, enhancing physical and mental performances, and nowadays they constitute the active ingredient in many popular commercial preparations sold worldwide as food additives, pharmaceutical remedies, and drinks. This study was aimed at providing a detailed phytochemical characterization of the Rhodiola 5%, a commercially available extract of R. rosea roots, and resulted in the characterization of 18 secondary metabolites, including 13 polyphenols and 6 terpenoids, and in the discovery of the new rhodiosidin (5), the first R. rosea metabolite to show both terpenoid and cinnamoyl moieties. The 5-lipoxygenase inhibiting activity of the main components was characterized and disclosed that rosiridin (6), kenposide A and rosavins are mainly responsible for this activity of the extract.

Insights into the direct anti-influenza virus mode of action of Rhodiola rosea

Background: The anti-influenza A virus activities and contents of previously isolated most active flavonoids (rhodiosin and tricin) from a standardized hydro-ethanolic R. rosea root and rhizome extract (SHR-5®), did not fully explain the efficacy of SHR-5®. Moreover, the mode of antiviral action of SHR-5® is unknown.Purpose: To determine the anti-influenza viral principle of SHR-5® we evaluated i) the combined anti-influenza virus effect of rhodiosin and tricin, ii) the impact of its tannin-enriched fraction (TE), iii) its antiviral spectrum and mode of action, and iv) its propensity for resistance development in vitro.Methods: The combined anti-influenza virus effect of rhodiosin and tricin and the impact of TE were investigated with cytopathic effect (CPE)-inhibition assays in MDCK cells. A tannin-depleted fraction (TD) and TE were prepared by polyamide column chromatography and dereplicated by LC-MS. Plaque-reduction assays provided insights into the anti-influenza virus profile, the mode of action, and the propensity for resistance development of SHR-5®.Results: Our results i) did not reveal synergistic anti-influenza A virus effects of rhodiosin and tricin, but ii) proved a strong impact of TE mainly composed of prodelphinidin gallate oligomers. iii) TE inhibited the plaque-production of influenza virus A(H1N1)pdm09, A(H3N2), and B (Victoria and Yamagata) isolates (including isolates resistant to neuraminidase and/or M2 ion channel inhibitors) with 50% inhibitory concentration values between 0.12 - 0.53 µg/ml similar to SHR-5®. Mechanistic studies proved a virucidal activity, inhibition of viral adsorption, viral neuraminidase activity, and virus spread by SHR-5® and TE. iv) No resistance development was observed in vitro.Conclusion: For the first time a comprehensive analysis of the anti-influenza virus profile of a hydro-ethanolic R. rosea extract (SHR-5®) was assessed in vitro. The results demonstrating broad-spectrum multiple direct anti-influenza virus activities, and a lack of resistance development to SHR-5® together with its known augmentation of host defense, support its potential role as an adaptogen against influenza virus infection.

High-performance Countercurrent Chromatography to Access Rhodiola rosea Influenza Virus Inhibiting Constituents.

In a cytopathic effect inhibition assay, a standardized Rhodiola rosea root and rhizome extract, also known as roseroot extract (SHR-5), exerted distinct anti-influenza A virus activity against HK/68 (H3N2) (IC50 of 2.8 µg/mL) without being cytotoxic. For fast and efficient isolation and identification of the extract's bioactive constituents, a high-performance countercurrent chromatographic separation method was developed. It resulted in a three-stage gradient elution program using a mobile phase solvent system composed of ethyl acetate/n-butanol/water (1 : 4 : 5 → 2 : 3 : 5 → 3 : 2 : 5) in the reversed-phase mode. The elaborated high-performance countercurrent chromatographic method allowed for fractionation of the complex roseroot extract in a single chromatographic step in a way that only one additional orthogonal isolation/purification step per fraction yielded 12 isolated constituents. They cover a broad polarity range and belong to different structural classes, namely, the phenylethanoid tyrosol and its glucoside salidroside, the cinnamyl alcohol glycosides rosavin, rosarin, and rosin as well as gallic acid, the cyanogenic glucoside lotaustralin, the monoterpene glucosides rosiridin and kenposide A, and the flavonoids tricin, tricin-5-O-β-D-glucopyranoside, and rhodiosin. The most promising anti-influenza activities were determined for rhodiosin, tricin, and tricin-5-O-β-D-glucopyranoside with IC50 values of 7.9, 13, and 15 µM, respectively. The herein established high-performance countercurrent chromatographic protocol enables fast and scalable access to major as well as minor roseroot constituents. This is of particular relevance for extract standardization, quality control, and further in-depth pharmacological investigations of the metabolites of this popular traditional herbal remedy.

Plumbagin Suppresses Pulmonary Fibrosis via Inhibition of p300 Histone Acetyltransferase Activity.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis similar to that of malignancy. The causes of IPF are not clearly known, and there is no effective therapy to date. In this study, the natural compound plumbagin, which was isolated from Plumbago rosea root extract, was screened for p300 inhibitory activity. Plumbagin specifically inhibited the activity of p300 toward histone acetyltransferases. Plumbagin treatment significantly suppressed transforming growth factor-β-induced profibrotic target-gene expression and proliferation of fibroblast cell lines. Moreover, plumbagin significantly inhibited bleomycin-induced pulmonary fibrosis in mice. Taken together, these data demonstrate the inhibitory effects of plumbagin on lung fibrosis and its promise as a therapeutic agent for IPF.

The effect of rhodiola rosea root extract on stress-induced ovarian damage, infertility and reproductive disorders in female rats

The effect of rhodiola rosea root extract on stress-induced ovarian damage, infertility and reproductive disorders in female rats

Removing Disperse red 60 and Reactive blue 19 dyes removal by using Alcea rosea root mucilage as a natural coagulant

In terms of health, dyes have carcinogenic, mutagenic and toxic properties and can have adverse effects on health and the environment. Therefore, sewage containing to dyes must be purified before being discharged into the environment. The current study aimed to investigate the effectiveness of Alcea rosea root extract in Disperse red 60 and Reactive blue 19 dyes removal from synthetic sewage. In this study, the effect of different indices including pH (5–11), Alcea rosea concentration (50–300 mg/L) and initial dye concentration (10–80 mg/L) was investigated. During the tests, the coagulant was stirred with rapid mixing at a speed of 250 rpm for 2 min. In the following, the speed (30–60 rpm) and the time (10–25 min) were used for slow mixing and after mixing the effect of settling time (10–60 min) and temperature (20–70) on removal efficiency of Disperse and Reactive dyes was investigated. The results showed that the maximum of removal efficiency of Disperse and Reactive dyes in optimum conditions including (pH = 11, coagulant concentration = 200 and 250 mg/L, dye concentration 40 and 20 mg/L, speed 60 rpm, during 15 min with settling time 60 min and temperature 60 °C obtained 86% and 68%, respectively. According to the result, the Alcea rosea coagulant has the best ability in removing dyes from aqueous solutions and sewage, especially Disperse dyes. Disperse dye is much eliminated in the coagulation process due to its lower solubility, higher suspending materials and less required solved chemical oxygen demand to the total chemical oxygen demand (SCOD/TCOD).

Rhodiola rosea root extract has antipsychotic-like effects in rodent models of sensorimotor gating

Ethnopharmacological relevanceThe plant arctic root (Rhodiola rosea, L.) is growing in northern regions of Europe, Asia and North America. Extracts of R. rosea are used in traditional medicine for various conditions related to nervous system function. According to scientific studies from the last decades, the plant might have potential for use in the treatment of memory impairments, stress and depression, but reports concerning other neuropsychiatric disorders are scarce. Aim of the studyIn this context, our study aimed to examine potential antipsychotic-like effects of R. rosea root extract. Materials and methodsWe tested the effects of R. rosea root extract on prepulse inhibition in rats and mice. Prepulse inhibition is an established operational measure of sensorimotor gating, which is impaired in schizophrenia and other psychotic disorders. ResultsR. rosea root extract increased prepulse inhibition in rats and mice. Interestingly, the R. rosea extract had stronger effects in those individual animals that had low baseline levels of prepulse inhibition. Therefore, we performed further experiments in which we pharmacologically induced a prepulse inhibition deficit by two different psychostimulants, either the dopamine D2 receptor agonist apomorphine or the NMDA receptor antagonist dizocilpine (MK-801). Pre-treatment with the R. rosea extract significantly restored both, apomorphine- and dizocilpine-induced prepulse inhibition deficits. ConclusionsThe present study demonstrates that R. rosea extract robustly reverses prepulse inhibition deficits in rodents. This suggests antipsychotic-like effects of R. rosea extract. Future studies should focus on the pharmacological mechanisms underlying these effects.

Rhodiola rosea, a protective antioxidant for intense physical exercise: An in vitro study

In physiological conditions, the response to oxidative stress induced by strenuous physical training, is not always efficient. Furthermore, a weak muscle fiber antioxidant system can contribute to muscle wasting during ageing and pathological conditions. Natural antioxidant supplements could counteract the effects of oxidative stress. An in vitro model of exercise allowed us to mimic intense or moderate exercise by electrically stimulating cultured mouse myotubes with high- and/or low-frequency pulses; the resulting ROS production was then monitored. The herbal supplement Rhodiola rosea aqueous extract was characterized in terms of its polyphenol content and used to test for antioxidant activity against ROS, produced during muscle contraction. Our results showed that Rhodiola rosea extract reduced the oxidative stress produced by muscle contraction and brought values of ROS production back to physiological levels. We suggest that Rhodiola rosea root extract could exert a protective antioxidant role during intense physical exercise.

Rhaponticum carthamoides and Rhodiola rosea plant extracts: the right combination between both to get the optimal effect on muscle de novo protein synthesis and performance gain

We previously reported in C2C12 myotubes that a Rhaponticum carthamoides root extract (RCE) was able to significantly stimulate protein synthesis and induce an activation of the Akt/mTOR signalling pathway (induction of Akt and S6K1 phospohrylations), that a Rhodiola rosea root extract (RRE) had also the capacity to induce protein synthesis and to inhibit myostatin gene expression and that the combination of both exhibited inhibition of atrogin gene expression (unpublished). Therefore, we aimed to investigate the effects of RCE or RRE alone or combinations of both on acute muscle protein synthesis stimulation and on performance gain following a 4-week resistance training program in adult rats. Acutely, rats were trained on a ladder making 3 repetitions of 10 climbs with a load that successively reached 0%, 50% and 75% of their body mass and were fed (oral gavage) just after training with either placebo, whey protein (910 mg/kg bw) as a positive control, RRE (43 mg/kg bw), RCE (43 mg/kg) and different doses of a 50:50 combination of both (87, 43, 22 or 9 mg/kg bw). RCE alone but not RRE was able to significantly stimulate protein synthesis as measured by western blot quantitative analysis of puromycin incorporation in the flexor digitorum profondus (FDP) and in comparison to placebo (200% versus 100% for RCE and placebo group respectively). Any doses of the combination was significantly superior to RRE alone (300% versus 150%) or RCE alone (300% versus 200%) and also significantly superior to whey proteins (300% versus 150%). The same results were obtained in the biceps and deltoid muscles. In the second part of the study rats followed a 4-week progressive resistance training program while consuming RRE alone (22 mg/kg), RCE alone (22 mg/kg) and different ratio and doses of the combination (50:50 ratio: 43, 22 or 9 mg/kg bw; 83 RCE:17 RRE ratio: 26 mg/kg; 76 RCE:24 RRE ratio: 28 mg/kg; 70 RCE:30 RRE ratio: 15 mg/kg. Training sessions (19) consisted in one set of 10 repetitions with 2 minutes rest between trials and 5 minutes between each set, were held five times a week with initial load fixed at 50% of the rat body weight and increased progressively until 200% after 4 weeks. Maximal repetition was determined as the maximum weight carried up the exercise ladder by the rats in one climb and performance gain was calculated as delta power (post versus pre resistance training). As shown in Figure 1, RCE alone but not RRE was able to significantly increase performance gain in comparison to placebo after 4 weeks of resistance training (0.66±0.08 versus 0.39±0.08 W respectively, + 65%, p<0.05). A synergistic effect on performance gain was detected for the 50:50 combination but interestingly, the combination ratio 70:30 warranted the best improvement of performance gain with the lower daily dosage (15 mg/kg bw) in comparison to placebo (0.62±0.08 versus 0.39±0.08 W respectively, + 59%, p<0.05). These results clearly demonstrated synergy of the combination of extracts on protein synthesis stimulation in the FDP, deltoid and biceps muscles following acute resistance exercise and an improvement of performance gain following a 4-week resistance training program. Those effects are currently investigated in recreationally active men and histological analysis of muscle fibers are under investigations in rats to understand what could drive the effect on performance.

Evaluation of molecular chaperons Hsp72 and neuropeptide Y as characteristic markers of adaptogenic activity of plant extracts

We have previously demonstrated that ADAPT-232, a fixed combination of adaptogenic substances derived from Eleutherococcus senticosus root extract, Schisandra chinensis berry extract, Rhodiola rosea root extract stimulated the expression and release of neuropeptide Y (NPY) and molecular chaperone Hsp72 from isolated human neurolgia cells. Both of these mediators of stress response are known to play an important role in regulation of neuroendocrine system and immune response. We further demonstrated that ADAPT-232 induced release of Hsp70 is mediated by NPY, suggesting an existence of NPY-mediated pathway of activation of Hsp72 release into the blood circulation system. The objective of this study was to determine whether this pathway is common for adaptogens and whether NPY and/or Hsp72 can be considered as necessary specific biomarkers for adaptogenic activity. The release of NPY and Hsp72 from neuroglia cells in response to treatment with various plant extracts (n=23) including selected validated adaptogens, partly validated adaptogens, claimed but negligibly validated adaptogens and some other plant extracts affecting neuroendocrine and immune systems but never considered as adaptogens was measured using high throughput ELISA techniques. We demonstrated that adaptogens, e.g. R. rosea, S. chinensis and E. senticosus stimulate both NPY and Hsp70 release from neuroblastoma cells, while tonics and stimulants have no significant effect on NPY in this in vitro test. In the groups of partly validated adaptogens the effect of Panax ginseng and Withania somnifera was not statistically significant both on NPY and Hsp70 release, while the activating effect of Bryonia alba and Rhaponticum cartamoides was significant only on Hsp70. In contrast, all tested non-adaptogens, such as antiinflammatoty plant extracts Matricaria recutita, Pelargonium sidoides, Hedera helix and Vitis vinifera significantly inhibit Hsp70 release and have no influence on NPY release from neuroblastoma cells. These experiments were further validated using primary human neurons and confirmed that adaptogens activate the release of both NPY and Hsp70, while tested non adaptogens were inactive in NPY assay and inhibit the release of Hsp70. Taken together, our data demonstrates for the first time that neuropeptide Y and heat shock protein Hsp70 can be used as molecular biomarkers for adaptogenic activity.

A Rhodiola Rosea Root Extract Protects Skeletal Muscle Cells Against Chemically Induced Oxidative Stress by Modulating Heat Shock Protein 70 (HSP70) Expression

Rhodiola rosea is a perennial plant in the Crassulaceae family, recently postulated to exert its adaptogenic functions partially by modulating the expression of molecular factors such as heat shock proteins (HSP). The aim of this study was to analyze the efficacy of a Rhodiola rosea extract (Rhodiolife) in protecting murine skeletal muscle cells (C2 C12 myotubes) from chemically induced oxidative stress and to establish whether modulation of HSP70 expression is observed. C2 C12 cells treated with Rhodiolife did not experience any loss of viability (p > 0.05) at concentrations of 1-100 µg/mL for up to 24 h. In control cultures, viability decreased 25% following exposure to 2 mM H2 O2 (1 h). However, no significant decrease in viability in cells pre-treated with extract at concentrations as low as 1 µg/mL was observed. HSP70 mRNA levels were up-regulated two-fold in cell cultures treated with Rhodiolife (10 µg/mL), and expression was further enhanced by exposure to H2 O2 (six-fold, p < 0.05). HSP70 protein levels were maintained in pre-treated cell cultures compared to controls but was significantly lower (-50%) in cells lacking treatment exposed to H2 O2 . The present results indicate that Rhodiolife protects C2 C12 myotubes against peroxide-induced oxidative stress through the modulation of the molecular chaperone HSP70.

Adaptogens Stimulate Neuropeptide Y and Hsp72 Expression and Release in Neuroglia Cells

The beneficial stress–protective effect of adaptogens is related to the regulation of homeostasis via mechanisms of action associated with the hypothalamic–pituitary–adrenal axis and the regulation of key mediators of the stress response, such as molecular chaperones, stress-activated c-Jun N-terminal protein kinase, forkhead box O transcription factor, cortisol, and nitric oxide (NO). However, it still remains unclear what the primary upstream targets are in response to stimulation by adaptogens. The present study addresses this gap in our knowledge and suggests that an important target for adaptogen mediated stress–protective effector functions is the stress hormone neuropeptide Y (NPY). We demonstrated that ADAPT-232, a fixed combination of adaptogens Eleutherococcus senticosus root extract, Schisandra chinensis berry extract, Rhodiola rosea root extract SHR-5, and its active constituent salidroside, stimulated the expression of NPY and 72 kDa heat shock protein (Hsp72) in isolated human neuroglia cells. The central role of NPY was validated in experiments in which pre-treatment of human neuroglia cells with NPY-siRNA and HSF1-siRNA resulted in the significant suppression of ADAPT-232-induced NPY and Hsp72 release. Taken together our studies suggest that the stimulation and release of the stress hormones, NPY and Hsp72, into systemic circulation is an innate defense response against mild stressors (ADAPT-232), which increase tolerance and adaptation to stress.

Alcea rosea root extract as a preventive and curative agent in ethylene glycol-induced urolithiasis in rats

Introduction:Alcea rosea L. is used in Asian folk medicine as a remedy for a wide range of ailments. The aim of the present study was to investigate the effect of hydroalcoholic extract of Alcea rosea roots on ethylene glycol-induced kidney calculi in rats.Materials and Methods:Male Wistar rats were randomly divided into control, ethylene glycol (EG), curative and preventive groups. Control group received tap drinking water for 28 days. Ethylene glycol (EG), curative and preventive groups received 1% ethylene glycol for induction of calcium oxalate (CaOx) calculus formation; preventive and curative subjects also received the hydroalcoholic extract of Alcea rosea roots in drinking water at dose of 170 mg/kg, since day 0 or day 14, respectively. Urinary oxalate concentration was measured by spectrophotometer on days 0, 14 and 28. On day 28, the kidneys were removed and examined histopathologically under light microscopy for counting the calcium oxalate deposits in 50 microscopic fields.Results:In both preventive and curative protocols, treatment of rats with hydroalcoholic extract of Alcea rosea roots significantly reduced the number of kidney calcium oxalate deposits compared to ethylene glycol group. Administration of Alcea rosea extract also reduced the elevated urinary oxalate due to ethylene glycol.Conclusion:Alcea rosea showed a beneficial effect in preventing and eliminating calcium oxalate deposition in the rat kidney. This effect is possibly due to diuretic and anti-inflammatory effects or presence of mucilaginous polysaccharides in the plant. It may also be related to lowering of urinary concentration of stone-forming constituents.

Inhibition of Lysine Acetyltransferase KAT3B/p300 Activity by a Naturally Occurring Hydroxynaphthoquinone, Plumbagin

Lysine acetyltransferases (KATs), p300 (KAT3B), and its close homologue CREB-binding protein (KAT3A) are probably the most widely studied KATs with well documented roles in various cellular processes. Hence, the dysfunction of p300 may result in the dysregulation of gene expression leading to the manifestation of many disorders. The acetyltransferase activity of p300/CREB-binding protein is therefore considered as a target for new generation therapeutics. We describe here a natural compound, plumbagin (RTK1), isolated from Plumbago rosea root extract, that inhibits histone acetyltransferase activity potently in vivo. Interestingly, RTK1 specifically inhibits the p300-mediated acetylation of p53 but not the acetylation by another acetyltransferase, p300/CREB-binding protein -associated factor, PCAF, in vivo. RTK1 inhibits p300 histone acetyltransferase activity in a noncompetitive manner. Docking studies and site-directed mutagenesis of the p300 histone acetyltransferase domain suggest that a single hydroxyl group of RTK1 makes a hydrogen bond with the lysine 1358 residue of this domain. In agreement with this, we found that indeed the hydroxyl group-substituted plumbagin derivatives lost the acetyltransferase inhibitory activity. This study describes for the first time the chemical entity (hydroxyl group) required for the inhibition of acetyltransferase activity.

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.

Decrease of cyclophosphamide haematotoxicity by Rhodiola rosea root extract in mice with Ehrlich and Lewis transplantable tumours

BIOLOGICAL RESPONSE MODIFIERS may decrease haematotoxicity during cancer chemotherapy [l]. Many such modifiers are of natural origin [2]. One such is Rhodiolu rosea root extract (RRRE), used in Siberian folk medicine for many diseases, including cancer [3]. Our aim was to study the effect of RRRE on neoplastic and normal haemapoietic cell precursors of mice with Ehrlich ascites tumour (EAT) and Lewis lung carcinoma (3LL) treated with cyclophosphamide 100 mg/kg. RRRE 0.5 ml/kg was given orally daily from 2-8 days after EAT and 3LL transplantation (7 doses). We evaluated the numbers of leucocytes and myelokariocytes, weight of tumours and extent of metastases in mice with 3LL, and relative number of viable EAT cells. Neoplastic (0.3 x 10’) and haemapoietic (0.5 x 106) elements were placed in diffusion chambers and implanted intraperitoneally in syngenaic mice [4]. Colonies were counted on the 5 th day. Cyclophosphamide suppressed the growth of both tumours to 31-39% (P < 0.05) and extent of metastases of 3LL to 18%. Corresponding figures for RRRE were 19-27% and 16% (P < 0.05). However, while cyclophosphamide inhibited the numbers of leucocytes and myelokariocytes to 40-50% (P < 0.05) and 20-25%, respectively, RRRE had no effect on these indices. In combination, RRRE increased by 36% the antimetastatic activity of cyclophosphamide (P < 0.05) and enhanced the number of leucocytes and myelokariocytes by 30% (P < 0.05) and 16-18%, respectively. Cyclophosphamide inhibited the proliferation of all the clonogenic cells assessed (Table 1); RRRE inhibited only tumour cells. The combination resulted in summation of these effects, and complete abrogation of the haematotoxicity of cyclophosphamide. The results indicate that RRRE selectively inhibited the proliferation of tumour-disseminating elements, enhanced the antimetastatic and antitumour activities of cyclophosphamide, and decreased its haematotoxicity. This effect could be linked to different actions of RRRE on the clonogenic elements of both tissues.