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Attenuation of Long-Term Rhodiola rosea Supplementation on Exhaustive Swimming-Evoked Oxidative Stress in the Rat



Rhodiola rosea improves exercise endurance and fatigue. We hypothesized that ingredients in Rhodiola rosea may increase antioxidant capability against swimming induced oxidative stress. In this study, we have identified the Rhodiola rosea ingredients, p-tyrosol, salidroside, rosin, rosavin and rosarin by high performance liquid chromatography-mass spectrometer and evaluated their O2(-)*, H2O2, and HOCl scavenging activities by a chemiluminescence analyzer. We next explored the effect and mechanism of Rhodiola rosea on 90-min swimming-induced oxidative stress in male Wistar rats fed with three doses of Rhodiola rosea extracts in drinking water (5, 25, 125 mg/day/rat) for 4 weeks. Our results showed that the 4 major ingredients (salidroside, rosin, rosavin and rosarin) from Rhodiola rosea extracts scavenged O2(-)*, H2O2, and HOCl activity in a dose-dependent manner. The ninety-min swimming exercise increased the O2(-)* production in the order: liver > skeletal muscle > blood, indicating that liver is the most sensitive target organ. The level of plasma malonedialdehyde, a lipid peroxidation product, was also increased after exercise. Treatment of 4 weeks of Rhodiola rosea extracts significantly inhibited swimming exercise-enhanced O2(-)* production in the blood, liver and skeletal muscle and plasma malonedialdehyde concentration. The expression in Mn-superoxide dismutase Cu/Zn-superoxide dismutase, and catalase in livers were all enhanced after 4 weeks of Rhodiola rosea supplementation especially at the dose of 125 mg/day/rat. Treatment of Rhodiola rosea extracts for 4 weeks significantly increased swimming performance. In conclusion, treatment of Rhodiola rosea extracts for 4 weeks could reduce swimming-enhanced oxidative stress possibly via the reactive oxygen species scavenging capability and the enhancement of the antioxidant defense mechanisms.
Corresponding author: Dr. Chiang-Ting Chien, No. 7 Chung-Sun South Road, Department of Medical Research, National Taiwan University
Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, ROC. Tel: +886-2-23123456 ext. 5720, Fax: +886-2-
23947927, E-mail:
Received: April 28, 2008; Revised: February 11, 2009; Accepted: February 13, 2009.
2009 by The Chinese Physiological Society. ISSN : 0304-4920.
Chinese Journal of Physiology 52(5): 316-324, 2009
DOI: 10.4077/CJP.2009.AMH029
Attenuation of Long-Term Rhodiola rosea
Supplementation on Exhaustive
Swimming-Evoked Oxidative Stress in the Rat
Shih-Chung Huang1, Fang-Tsai Lee2, Tz-Yin Kuo3, 4, Joan-Hwa Yang3,
and Chiang-Ting Chien4
1Departments of Cardiology and
2Orthopaedic Surgery, Kuang-Tien General Hospital, Taichung
3Department of Food Science, Nutrition, and Nutraceutical Biotechnology,
Shih-Chien University College of Human Ecology, Taipei
4Department of Medical Research, National Taiwan University Hospital and National Taiwan
University College of Medicine, Taipei, Taiwan, Republic of China
Rhodiola rosea improves exercise endurance and fatigue. We hypothesized that ingredients in
Rhodiola rosea may increase antioxidant capability against swimming induced oxidative stress. In this
study, we have identified the Rhodiola rosea ingredients, p-tyrosol, salidroside, rosin, rosavin and
rosarin by high performance liquid chromatography-mass spectrometer and evaluated their O2–., H2O2,
and HOCl scavenging activities by a chemiluminescence analyzer. We next explored the effect and
mechanism of Rhodiola rosea on 90-min swimming-induced oxidative stress in male Wistar rats fed with
three doses of Rhodiola rosea extracts in drinking water (5, 25, 125 mg/day/rat) for 4 weeks. Our results
showed that the 4 major ingredients (salidroside, rosin, rosavin and rosarin) from Rhodiola rosea
extracts scavenged O2–., H2O2, and HOCl activity in a dose-dependent manner. The ninety-min
swimming exercise increased the O2–. production in the order: liver > skeletal muscle > blood, indicating
that liver is the most sensitive target organ. The level of plasma malonedialdehyde, a lipid peroxidation
product, was also increased after exercise. Treatment of 4 weeks of Rhodiola rosea extracts significantly
inhibited swimming exercise-enhanced O2–. production in the blood, liver and skeletal muscle and
plasma malonedialdehyde concentration. The expression in Mn-superoxide dismutase Cu/Zn-superoxide
dismutase, and catalase in livers were all enhanced after 4 weeks of Rhodiola rosea supplementation
especially at the dose of 125 mg/day/rat. Treatment of Rhodiola rosea extracts for 4 weeks significantly
increased swimming performance. In conclusion, treatment of Rhodiola rosea extracts for 4 weeks could
reduce swimming-enhanced oxidative stress possibly via the reactive oxygen species scavenging capability
and the enhancement of the antioxidant defense mechanisms.
Key Words: Rhodiola rosea, exercise, oxidative stress, reactive oxygen species, rat
Rhodiola rosea (Golden Root, Roseroot) is a
plant in the Crassulaceae family growing in the
mountainous and arctic regions of North America,
Europe, and Asia. Rhodiola rosea can combat fatigue
Rhodiola rosea Supplementation Attenuates Oxidative Stress 317
by its several unique ingredients (5, 10). Among
these, p-tyrosol, salidroside, rosin, rosavin and rosarin
are the major active components of Rhodiola rosea
with adaptogenic characteristics (5) for improvement
of cognitive function (35) and endurance performance
(1, 12, 35), reduction of mental fatigue (10, 36), anti-
diabetic effect (22) and reactive oxygen species (ROS)
production (2, 13, 20, 21).
Physical exercise is characterized by an increase
in O2 uptake and consumption and induced stressors
such as elevations of body temperature, the formation
of reactive oxygen species (ROS), and a decrease in
glycogen (3, 25, 26). In extreme conditions such as
ischemia/reperfusion or exhaustive exercise, the
increased ROS can oxidize macromolecules con-
tributing to abnormal signal transduction or cellular
dysfunction, impairment of both enzymic and non-
enzymic antioxidant defense systems of target tissues
and trigger erythrocyte hemolysis (4) and the cascade
of apoptosis, autophagy and necrosis (7, 8, 26, 30-
33). Exhaustive exercise enhances xanthine oxidase
activities of plasma and skeletal muscle, muscular
myeloperoxidase activity and malondialdehyde
concentrations of plasma and tissues (25). Exhaustive
exercise leads to oxidative damage in the liver in-
cluding rough endoplasmic reticulum fragmentation
and dilatation, glycogen depletion, and mitochondrial
enlargement (34, 37). Therefore, exhaustive exercise-
enhanced oxidative stress may impair liver, kidney,
skeletal muscle and other tissues by different degrees
of ROS production. It has been speculated that in-
creased antioxidant/oxidative damage-repairing
enzyme activities, increased resistance to oxidative
stress and lower levels of oxidative damage may
protect oxidative stress-related cardiovascular, kidney,
liver and neuronal damages (8, 33, 41). The long-
term effects of Rhodiola rosea supplementation on
exhaustive exercise-induced oxidative stress have not
clearly been demonstrated. The purpose of the current
study was to identify the active components in the
Rhodiola rosea extract and to examine the long-term
effect and mechanism of Rhodiola rosea supplemen-
tation on ROS production and oxidized biomarkers in
the liver, skeletal muscle and blood after exhaustive
Materials and Methods
Rhodiola rosea and High Performance Liquid
Chromatography-Mass Spectrometry (HPLC-MS)
Dry powders from water extraction of roots of
Rhodiola rosea L. was purchased from Numen Biotech
(Taipei, Taiwan, ROC). In brief, fresh original habitats
of Rhodiola rosea rhizomes from Siberia were thorough-
ly washed with water, shade-dried for 4 weeks, and
powdered using a mixer grinder. A known quantity of
the dried powdered material was soaked in distilled
water for 24 h at 35-42°C and macerated thoroughly
with the help of a mortar and pestle. The mixture
was filtered through Whatman filter paper No. 1, con-
densed using a rotary evaporator and lyophilized.
A model Agilent 1,100 with vacuum degasser,
binary pump, autosampler and thermostatic column
holder was used. The LC separation was performed
using a ZORBAX 300SB-C18 3.5 µm, 1.0 × 150 mm.
The temperature of the column oven was 35°C and the
injection volume was 1 µl. The eluent flow-rate was
0.08 ml/min. The gradient conditions were initially
90% A (aqueous phase with distilled water produced
by Mill-Q, 18.2 M)-5% B (acetonitrile)-5% C
(methanol), changed linearly to 76% A-12% B-12%
C in 16 min. After gradient elution, the column was
washed for 1 min with acetonitrile and equilibrated
for 5 min under the initial conditions leading to a total
time of 25 min for one analysis. All HPLC-MS ex-
periments were performed using a mass spectrometer
(Esquire 3000+, Bruker Daltonik GmbH, Bremen,
Germany) equipped with a positive spray ionization
source in the full-scan mode over the m/z range 100-
600. Nitrogen was used as the drying gas at a flow-
rate of 8 l/min. The dry air temperature was 310°C at
20 psi pressure. For calibration of the HPLC-MS
method with ESI and the eluent system, eight
concentration levels of standard were prepared for
obtaining the calibration curves. We used salidroside,
rosin, rosarin and rosavin for standards (Sigma, St.
Louis, MO, USA). Standard solutions were prepared
in 6% methanol containing 400 ng/ml internal
standard. For all standards, the concentration levels
prepared were 0.5, 2, 5, 20, 50, 200, 500 and 2000
ng/ml. Calibration curves were constructed by plotting
responses of the standard compounds relative to
responses of the internal standard (measured in
triplicate for each concentration) against the con-
centration of standard compounds. Ten mg of the
Rhodiola rosea extracts was dissolved in methanol
and stirred after supersonic vibration for 15 min. The
supernatant was filtered after 0.45 µm and was
analyzed by HPLC-MS. The data were presented in
the Fig. 1. Rhodiola rosea extract contains three
cinnamyl alcohol-vicianosides, rosavin, rosin, and
rosarin, that are specific to this species (14, 15).
Animals and Swimming Model
Male Wistar rats (200-250 g) were housed at the
Experimental Animal Center, National Taiwan
University, at a constant temperature and with a
consistent light cycle (light from 07:00 to 18:00
o’clock). Food and water were provided ad libitum.
All surgical and experimental procedures were
318 Huang, Lee, Kuo, Yang and Chien
approved by the National Taiwan University College
of Medicine and College of Public Health Institu-
tional Animal Care and Use Committee in accordance
with the guidelines of the National Science Council
of Republic of China (NSC 1997).
All the animals were divided into four groups
for oral administration of 0, 5, 25 and 125 mg/day
Rhodiola rosea extracts for 4 weeks. Before the com-
mencement of an experiment, all animals were
familiarized to swimming for 10 min/day for 3 days.
At the indicated time, rats fasted overnight for 8 h
(from 12:00 PM to 8:00 AM) in a 90-min swimming
exercise test were measured (6). The swimming
exercise in free style was carried out in a circular
plastic barrel (diameter, 20 cm; depth, 30 cm) filled
with water maintained at a temperature of 24 ± 1°C.
The rats swam in the circular plastic barrel for 90 min.
After 90 min of swimming challenge, the rats were
killed with an overdose of sodium pentobarbital
intraperitoneally (90 mg/kg body weight) and the
liver, skeletal muscle and blood were removed.
Changes of Lucigenin- and Luminol-Enhanced
Chemiluminescence Counts (CL)
The antioxidant activities of 5 major ingredients
(tyrosol, salidroside, rosin, rosarin and rosavin) and
Rhodiola rosea extracts on xanthine (0.75 mg kg-1,
dissolved in 0.01 N NaOH) and xanthine oxidase (24.
8 mU kg-1) enhanced O2–., 0.03% H2O2 induced H2O2
Fig. 1. A. Structures of four compounds. B. Standards and Rhodiola rosea extract extracted chromatograms from HPLC-MS experi-
ment (full-scan mode) with positive ESI and eluent system.
Sample (0.1 mg/ml)
(0.4 µg/ml) Rosin
EIC 379 +Al
EIC 323 +Al
EIC 451 +Al
EIC 451 +Al
EIC 319 +Al
EIC 323 +Al
Time [min]
Rhodiola rosea Supplementation Attenuates Oxidative Stress 319
activity, and % HOCl induced HOCl activity were
ROS levels were measured using a CL analyzing
system (CLD-110, Tohoku Electronic Industrial,
Sendai, Japan) as previously described (7). The
system contained a photon detector (Model CLD-
110), a CL counter (Model CLC-10), a water circulator
(Model CH-200) and a 32-bit IBM personal computer
system. A cooler circulator was connected to the
model CLD-110 photon detector to keep the tem-
perature at 5°C. Under these conditions, radiant
energy as low as 10-15 W could be detected.
CL was measured in an completely dark chamber
of the CL analyzing system. We demonstrated that
using the CL-emitting substance lucigenin (N,N’-
dimethyldiacridinium, Sigma, St. Louis, MO, USA)
for O2–. or luminol (5-amino-2,3-dihydro-1,4-
phthalazinedione, Sigma, St. Louis, MO, USA) for
H2O2 or HOCl to enhance the CL counts provided
similar data to those reported in our previous in vivo
study (7). The lucigenin-enhanced CL method
provides a reliable assay for superoxide. After 100 s,
1.0 ml of 0.1 mM lucigenin in PBS (pH = 7.4) was
mixed with the tested sample. CL in the tested sample
was measured continuously for a total of 600 s. The
assay was performed in duplicate for each sample,
and the results are expressed as CL counts (10 s)-1.
The total amount of CL in 600 s was calculated by
integrating the area under the curve. The means ±
S.E.M. CL level for each sample was calculated.
We used 1 ml blood samples and 0.2 g homoge-
nized liver and leg skeletal muscle to measure
ROS levels. The analysis of lipid peroxidation,
malondialdehyde (MDA), concentrations of plasma
samples was assessed colorimetrically at 586 nm
using a commercial kit (Calbiochem 437634;
Calbiochem-Novabiochem, La Jolla, CA, USA) as
previously described (40). Concentration was ex-
pressed in µM in plasma and in µmol/mg protein in
tissue samples.
Effect of Rhodiola rosea Extract on MnSOD, Cu/Zn
SOD, Catalase Protein Expression
Protein concentration was determined by a
BioRad Protein Assay (BioRad Laboratories,
Hercules, CA, USA). Ten g of protein was electro-
phoresed as described below. The expression of
MnSOD, Cu/Zn SOD and catalase in liver tissues was
evaluated by western immunoblotting and densito-
metry as described (41). Briefly, total proteins were
homogenized with a prechilled mortar and pestle
in an extraction buffer of 10 mM Tris-HCl (pH 7.6),
140 mM NaCl, 1 mM phenylmethyl sulfonyl fluoride,
1% Nonidet P-40, 0.5% deoxycholate, 2% β-
mercaptoethanol, 10 µg/ml pepstatin A and 10 µg/ml
aprotinin. The mixtures were homogenized com-
pletely by vortexing and kept at 4°C for 30 min. The
homogenate was centrifuged at 12,000 g for 12 min at
4°C, the supernatant was collected, and protein
concentrations were determined by the BioRad Pro-
tein Assay (BioRad Laboratoriess Hercules, CA,
The polyclonal anti-MnSOD (Stressgen
Bioreagents Limited, Victoria, Canada) rabbit anti-
human Cu/Zn SOD (Stress Marq Biosciences Inc.,
Victoria, Canada) and catalase (Chemicon Interna-
tional Inc., Temecular, CA, USA) antibodies, and the
monoclonal mouse anti-mouse β-actin (Sigma, Saint
Louis, MI, USA) were used at 1:1000 dilutions. All
of these antibodies cross-reacted with the respective
rat antigens (29).
Statistical Analysis
All values were expressed as means ± standard
error mean (SEM). Differences within groups were
evaluated by paired t-test. One-way analysis of
variance was used for establishing differences among
groups. Intergroup comparisons were made by
Duncan’s multiple-range test. A chi-square test was
performed in the hepatic antioxidant expression.
Differences were regarded as significant if P < 0.05
was attained.
Ingredient Analysis of Rhodiola rosea Extract
In the present study, the structures of four
standard components including salidroside, rosin,
rosarin and rosavin are demonstrated in Fig. 1A. The
original diagram obtained from the four standard
components (upper panel) and the samples of Rhodiola
rosea extract (lower panel) was analyzed by HPLC-
MS (Fig. 1B). Rhodiola rosea ingredient was analyzed
by HPLC-MS as shown in Table 1. By the use of our
techniques, Rhodiola rosea extract was shown to
contain four major components including salidroside,
rosin, rosarin and rosavin. Among these four com-
ponents, the salidroside content was the highest (13128
ppm). Our data verified that the Rhodiola rosea
extract in this study contains approximately 1.3%
salidroside, 0.4% rosin, 0.4% rosarin and 1% rosavin,
but did not contain p-tyrosol in our HPLC-MS analysis.
Rhodiola rosea extract supplementation was provided
to the rat in drinking water in a dose-dependent
manner. Table 1 shows the level of the four com-
ponents in the three dosages of Rhodiola rosea extract
supplementation. The salidroside, rosin, rosarin and
rosavin contents were dose-dependently increased
with the Rhodiola rosea extract dose.
320 Huang, Lee, Kuo, Yang and Chien
Antioxidant Activity of the Rhodiola rosea Extract
We first compared the antioxidant activities of
O2–., H2O2, HOCl of five ingredients, p-tyrosol,
salidroside, rosin, rosavin and rosarin, of the Rhodiola
rosea extract in 2, 20 and 200 µg/ml. As shown in Fig.
2, p-tyrosol, salidroside, rosin, rosavin and rosarin
significantly (P < 0.05) inhibited xanthine- and
xanthine oxidase-induced O2–. levels at 2, 20 and
200 µg/ml. The inhibited O2–. ability was most
prominent in p-tyrosol and rosavin at 200 µg/ml.
Also, p-tyrosol, salidroside, rosin, rosavin and rosarin
significantly (P < 0.05) inhibited H2O2 and HOCl
activities (Fig. 2) at 2, 20 and 200 µg/ml. The in-
hibited H2O2 ability was most prominent in p-tyrosol
and rosin at 200 µg/ml. The inhibited HOCl ability
was most prominent in p-tyrosol at 200 µg/ml.
The second part of study was to explore the
antioxidant activity in different dosages of Rhodiola
rosea extract with serial dilutions at 0, 0.2, 1, 5, 25
and 125 mg/mL. Rhodiola rosea extract significantly
reduced xanthine- and xanthine oxidase-induced O2–.,
H2O2, and HOCl activities in a dose-dependent manner
(Fig. 3).
To explore the effect of 90-min exhaustive swim-
ming exercise on blood and tissue ROS production,
we investigated lucigenin-dependent O2–. chemilu-
minescence counts in the blood and in homogenized
liver and skeletal muscle. As shown in Fig. 4, after
90-min swimming, the level of lucigenin-dependent
O2–. chemiluminescence counts was significantly (P <
0.05) increased in blood, liver and skeletal muscle.
The enhancement in O2–. production was in an order of
liver > skeletal muscle > blood. The plasma level of
malonedialdehyde, a lipid peroxidation product, was
also significantly (P < 0.05) increased.
Long-term Rhodiola rosea extract supplemen-
tation at different dosages for 4 weeks significantly
decreased the swimming exercise-enhanced O2–.
chemiluminescence counts in blood, liver and skeletal
Table 1. Aqueous concentrations of Rhodiola rosea extracts as determined by HPLC-MS
Salidroside (µg) Rosin (µg) Rosarin (µg) Rosavin (µg)
R0 (0 mg) 0 ±00±00±00±0
R5 (5 mg) 71 ±520±221±352±6
R25 (25 mg) 334 ±39 87 ±10 85 ±9 247 ±32
R125 (125 mg) 1,645 ±169 416 ±61 382 ±42 1,187 ±155
Fig. 2. Different dosages of five standards displaying O2–., H2O2
and HOCl scavenging activities in a dose-dependent
manner. The sample concentration was 2-200 µg/ml.
Each data point was tested for four times. *P < 0.05
when compared to the control value.
% of O
-. inhibition
140 2 µg
20 µg
200 µg
Control salidroside tyrosol rosarin rosin rosavin
% of H
Control salidroside tyrosol rosarin rosin rosavin
% of HOCl inhibition
Control salidroside tyrosol rosarin rosin rosavin
Fig. 3. The antioxidant activity against O2–., H2O2 and HOCl
in different dosages of Rhodiola rosea extract with
serial dilutions at 0 (R0), 0.2 (R0.2), 1 (R1), 5 (R5), 25
(R25) and 125 (R125) mg/ml. *P < 0.05 when com-
pared to the control value.
% of ROS inhibition
100 O
Control R0.2 R1 R5 R25 R125
Rhodiola rosea Supplementation Attenuates Oxidative Stress 321
muscle. The increased plasma malonedialdehyde
level induced by swimming was also depressed by
long-term Rhodiola rosea extract supplementation
(Fig. 4).
Chronic Rhodiola rosea Treatment Enhanced Hepatic
Antioxidant Enzymes Expression
We explored whether 4 weeks of Rhodiola rosea
extract supplementation affected expression of
antioxidant enzymes in the rat liver. As shown in Fig.
5, Mn SOD, Cu/Zn SOD and catalase were all ex-
pressed in the liver of R0 group. After 90 min of
swimming exercise, the expression of Cu/Zn SOD,
but not Mn SOD and catalase, was significantly
decreased in the R0 group. Four weeks of administra-
tion of the Rhodiola rosea extract at 25 and 125 mg
enhanced hepatic Mn SOD and Cu/Zn SOD expression
before the exhaustive swimming exercise. Catalase
expression was mildly enhanced at the dosage of
125 mg of Rhodiola rosea extract for four weeks.
Four weeks of Rhodiola rosea extract supplemen-
tation attenuated the depression of Cu/Zn SOD after
exhaustive swimming.
Rhodiola rosea Extract Supplementation Increased
Exercise Performance
After 4 weeks of Rhodiola rosea extract supple-
mentation at different dosages, 5% weight-loaded
swimming was used to evaluate the exercise perfor-
mance by the swimming time to fatigue. Treatment
of four weeks of the Rhodiola rosea extract at 5, 25
and 125 mg significantly (P < 0.05) increased the
swimming performance by 18.8%, 46.8% and 59.3%
(n = 5 each).
In the present study, we described a HPLC-MS
technique to identify and quantify 4 major components,
salidroside, rosin, rosarin and rosavin, in the Rhodiola
rosea extract. The application of HPLC for deter-
mining hydrophilic extracts from Rhodiola rosea and
Rodiola quadrifida has led to the identification of
cinnamic alcohol, chlorogenic acid, rhodiooctanoside,
rosiridin, rosavin and the phenolic compounds
salidroside, rhodiolin and viridoside (20, 24, 38).
Fig. 4. Antioxidant effects by different dosages of Rhodiola
rosea extract against the O2–. level in blood, liver and
muscle, and plasma MDA in the rats subjected to 90-min
swimming exercise that significantly increased the
oxidative stress. The animals were fed Rhodiola rosea
extract at 0 (R0), 5 (R5), 25 (R25) and 125 (R125) mg/ml
in the drinking water for 4 weeks. *P < 0.05 when
compared to the control value.
Fig. 5. Effects of different dosages of Rhodiola rosea extract
supplement and swimming test on MnSOD, Cu/Zn SOD
and catalase expression in the rat livers. R0, no Rhodiola
rosea extract supplement; R5, 5 mg/ml; R25, 25 mg/ml;
R125, 125 mg/ml. *P < 0.05 when compared to the
control value of R0 group.
Plasma MDA
Blood O
(counts/10 s)
Control n = 8 each
Swimming n = 8 each
Liver O
(counts/10 s)
Muscle O
(counts/10 s)
R0 R5 R25 R125
R5R0 R125R25
Control Swim Control Swim Control Swim Control Swim
322 Huang, Lee, Kuo, Yang and Chien
Our technique did not detect p-tyrosol in our Rhodiola
rosea extract.
It is frequently stated, but poorly demonstrated,
that exercise could have adverse effects related to
inflammatory response, ROS production and accu-
mulation of oxidative damage in several organs (3,
11, 16, 19, 33). Unlike the skeletal muscle, liver con-
tains high levels of xanthine dehydrogenase; during
exercise, xanthine dehydrogenase is converted to
xanthine oxidase generating ROS and oxidative
damage (31). In the present study, we found that 90-
min exhaustive swimming exercise increased O2–.
production in an order liver > skeletal muscle > blood
indicating that liver is the most sensitive target organ.
This result is agreement with a previous report with
nuclear 8-hydroxydeoxyguanosine as the oxidative
stress; the report showed that the nuclear 8-hydrox-
ydeoxyguanosine content increased in liver, not in
skeletal muscle and brain (33). The increased blood
ROS after exhaustive exercise may contribute to the
enhanced level of plasma malonedialdehyde, a lipid
peroxidation product, found in our analysis. Increased
blood ROS including O2–., H2O2 or HOCl may induce
oxidation of phospholipid bilayers in the erythrocytes,
increase phosphotidylcholine hydroperoxide and
malonedialdehyde accumulation in the erythrocyte
membrane and consequently contributes to hemoly-
sis (13, 17, 18).
Therefore, an increased activity in the antioxi-
dant defense mechanism or a decrease in oxidative
stress may protect organs against oxidative damages.
Exhaustive exercise on the treadmill resulted in
significant increases in lipid peroxidation of skeletal
muscle, liver and kidney inrats, and this was prevented
by superoxide dismutase derivatives (30, 31). Previous
studies have indicated that Rhodiola rosea extracts
containing specific ingredients may have beneficial
effects in enhancing exercise performance (1, 12, 23,
35) and in reducing ROS levels (2, 13, 21), but the
major active component has not clearly been demon-
strated. It has been reported that some Rhodiola
species did not have antioxidant effects on hypoxemia
and oxidative stress (39). The chemical composition
and physiological properties of Rhodiola species are
to a degree species-dependent although overlaps in
constituents and physiological properties do exist in
many Rhodiola species (20, 27, 28). Rhodiola rosea
contains a range of biologically active substances
including organic acids, flavonoids, tannins and phe-
nolic glycosides. The stimulating and adaptogenic
properties of Rhodiola rosea were originally attributed
to two compounds isolated from its roots identified as
p-tyrosol and the phenolic glycoside salidroside found
in all studied species of Rhodiola (9). However, other
active glycosides, including rosavin, rosin and rosarin,
have not been found in the Rhodiola species examined
(20). Because of this variation within the Rhodiola
genus, verification of Rhodiola rosea by HPLC is
dependent on the content of the rosavin, rosin and
rosarin rather than salidroside and p-tyrosol (9, 14,
15, 20). Based on a comparative analysis, the most
uniquely active chemical constituents are rosavin
(the most active), rosin, rosarin, salidroside and its
aglycon, p-tyrosol. In our data and in a previous
study, p-tyrosol, salidroside, rosavin, rosin, and rosarin
are all antioxidant substances (13, 20, 21, 42, 43),
especially in p-tyrosol. In the present study, we have
clearly identified that Rhodiola rosea extracts used
in our study contained rosavin, rosin and rosarin, but
did not contain p-tyrosol as analyzed by our HPLC-
MS technique. A previous study has indicated that
Rhodiola rosea roots contain 1.3 to 11.1 mg/g salidro-
side and 0.3 to 2.2 mg/g p-tyrosol (20). Our HPLC-
MS data show that 13 mg/g salidroside, 3.3 mg/g
rosin, 3.1 mg/g rosarin and 9.5 mg/g rosavin are
found in our Rhodiola rosea extracts. We therefore
suggest that high contents of rosin, rosarin and ro-
savin may exert a more efficient potential than p-
tyrosol (not detected or too low in our Rhodiola
rosea extract) in the reduction of swimming-induced
oxidative stress.
Our results also showed that four weeks of
Rhodiola rosea extract supplementation can up-
regulate Mn SOD and Cu/Zn SOD protein expression
in the rat liver. Although we did not know the detailed
mechanisms involving Rhodiola rosea-enhanced
antioxidant protein expression, direct scavenging ROS
activity and enhancement of several antioxidant
proteins of Rhodiola rosea extract may have provided
hepatic protection against exhaustive exercise- induced
oxidative stress in the liver. In the present study, we
have clearly indicated that p-tyrosol, salidroside, rosin,
rosarin and rosavin or the Rhodiola rosea extract
can significantly and dose-dependently decreased
O2–., H2O2 and HOCl activity in vitro. In addition,
chronic Rhodiola rosea extract supplement signifi-
cantly and dose-dependently reduced swimming
exercise-enhanced plasma malonedialdehyde con-
centrations and O2–. levels in the liver, skeletal muscle
and blood. In the present study, we evaluated all the
responses after Rhodiola rosea extract supplemen-
tation. We did not determine the responses after
terminating the supplementation. However, we suggest
that upregulation of several antioxidant proteins in the
liver may persist for several days until these proteins
are degraded. This potential effect requires further
investigation for the mode and kinetics of possible
medicinal applications of the Rhodiola rosea extract.
This work was supported in part by the National
Rhodiola rosea Supplementation Attenuates Oxidative Stress 323
Science Council of the Republic of China (NSC96-
2320-B002-007) to Dr. Chien CT and in part by the
Kuan-Tien General Hospital Research Funds to Dr.
Lee FT.
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... The functional claim of Rhodiola dietary supplements mentioned in the consolidated list of Article 13 Health Claims of the European Food Safety Authority (EFSA) is that it "contributes to optimal mental and cognitive activity". Rhodiola contains a range of biologically active substances, including organic acids, flavonoids, tannins and high amounts of rosavins (rosin, rosavin, rosarian), which are Rhodiola-specific glycosides, and salidroside, which are present in all species of Rhodiola [7]. Rhodiola is used to improve cognitive function and endurance performance, reduce mental fatigue and reactive oxygen species (ROS) production, and exert antidiabetic effects [7]. ...
... Rhodiola contains a range of biologically active substances, including organic acids, flavonoids, tannins and high amounts of rosavins (rosin, rosavin, rosarian), which are Rhodiola-specific glycosides, and salidroside, which are present in all species of Rhodiola [7]. Rhodiola is used to improve cognitive function and endurance performance, reduce mental fatigue and reactive oxygen species (ROS) production, and exert antidiabetic effects [7]. Interestingly, it has been shown that Rhodiola exhibits antidepressant, adaptogenic, anxiolytic-like, and stimulating effects in mice [8]. ...
... The molecular mechanisms underlying the effects of Rhodiola are currently unknown, although it has been hypothesized that it enhances the activity of monoamines and opioid peptides [9]. Thus, Rhodiola could improve the consumption of substrates, enhancing lipid oxidation and sparing glycogen [7]. ...
Full-text available
Background Owing to its strength-building and adaptogenic properties, Rhaponticum carthamoides ( Rha ) has been commonly used by elite Soviet and Russian athletes. Rhodiola rosea ( Rho ) is known to reduce physical and mental fatigue and improve endurance performance. However, the association of these two nutritional supplements with resistance exercise performance has never been tested. Resistance exercise is still the best way to stimulate protein synthesis and induce chronic muscle adaptations. The aim of this study was to investigate the acute and chronic effects of resistance exercise coupled with Rha and Rho supplementation on protein synthesis, muscle phenotype, and physical performance. Methods For the acute study, fifty-six rats were assigned to either a trained control group or one of the groups treated with specific doses of Rha and/or Rho . Each rats performed a single bout of climbing resistance exercise. The supplements were administered immediately after exercise by oral gavage. Protein synthesis was measured via puromycin incorporation. For the chronic study, forty rats were assigned to either the control group or one of the groups treated with doses adjusted from the acute study results. The rats were trained five times per week for 4 weeks with the same bout of climbing resistance exercise with additionals loads. Rha + Rho supplement was administered immediately after each training by oral gavage. Results The findings of the acute study indicated that Rha and Rha + Rho supplementation after resistance exercise stimulated protein synthesis more than resistance exercise alone ( p < 0.05). After 4 weeks of training, the mean power performance was increased in the Rha + Rho and Rha -alone groups ( p < 0.05) without any significant supplementation effect on muscle weight or fiber cross-sectional area. A tendency towards an increase in type I/ type II fiber ratio was observed in Rha/Rho -treated groups compared to that in the trained control group. Conclusion Rhodiola and Rhaponticum supplementation after resistance exercise could synergistically improve protein synthesis, muscle phenotype and physical performance.
... Les mécanismes moléculaires qui sous-tendent les effets de Rhodiola Rosea sont actuellement peu connus, cette plante pourrait améliorer la consommation de substrats, augmenter l'oxydation des lipides et épargner le glycogène (Kelly et al., 2001). Rhodiola Rosea contient une gamme de substances biologiquement actives, notamment des flavonoïdes, des tanins des rosavines (rosavine, rosin), et du salidroside (Huang et al., 2009). Le salidroside (p-hydroxyphénéthyl-b-d-glucoside) est l'un des principaux tyrosols présent dans la plante Rhodiola Rosea et l'un des composants les plus actifs. ...
... Selon l'Autorité européenne de sécurité des aliments (EFSA) « Rhodiola contribue à une activité mentale et cognitive optimale ». Le Rhodiola rosea est utilisée pour améliorer la fonction cognitive et les performances d'endurance, réduire la fatigue mentale et exercer des effets antidiabétiques(Huang et al., 2009).Au cours de l'Etude 1 nous avons montré qu'une supplémentation aigue avec la combinaison d'extraits de plantes chez le rat jeune associée à un exercice en résistance entraînait une augmentation de synthèse protéique chez trois muscles actifs (Flexor Digitorum Profundus (FDP), deltoïde et biceps), significativement supérieure au groupe exercice. Cette augmentation significative concernait les groupes supplémentés avec la combinaison des deux extraits. ...
Le développement de nouveaux produits d’extraits végétaux est actuellement une stratégie importante dans le domaine de l’amélioration de la performance sportive et des stratégies de prévention nutritionnelles du déconditionnement musculaire au cours du vieillissement. Actuellement, l’exercice physique essentiellement basé sur des exercices aérobies à intensité moyenne reste la stratégie de prévention du déconditionnement musculaire au cours du vieillissement la plus efficace. Cependant, seulement 50 % des adultes de plus de 65 ans respectent les prescriptions concernant la pratique d'activité physique de type aérobie par manque de temps. Ceci suggère qu’il y aurait une plus grande participation à des modalités d'exercice nécessitant moins de temps de pratique mais entraînant des effets similaires. Au cours de ce travail de thèse nous avons donc exploré dans une première étude les effets ergogéniques d’une combinaison d’extraits de plantes (Rhaponticum carthamoides et Rhodiola Rosea) dans un modèle d'exercice en résistance chez le rat jeune. Nos résultats ont principalement montré que cette combinaison d’extraits végétaux permettait d’accroitre les performances physiques en réponse à un entrainement en résistance en comparaison au même entrainement seul. Nos résultats ont montré que ceci pourrait passer par des effets anaboliques de nos extraits végétaux. Sur la base de ces résultats, nous avons analysé par une approche molécule candidate deux principes actifs (la 20 hydroxyecdysone et le salidroside) qui pourraient médier ces effets. Dans le même temps, nous avons mis au point un exercice intermittent à haute intensité (HIIT) permettant d’observer une augmentation aigüe de la synthèse protéique. L’objectif était d’associer cet exercice à un des principes actifs contenus dans nos extraits végétaux en tant que stratégie de prévention du déconditionnement musculaire lié au vieillissement. Suite à des mises au point expérimentales, nous avons finalement testé chez des souris vieillissantes une stratégie de prévention basée sur un entrainement HIIT associé à une supplémentation en salidroside. Nos principaux résultats ont montré que cette stratégie était efficace pour maintenir les qualités aérobies, la force de préhension et limiter la prise de masse grasse. Ces résultats pourraient s’expliquer en partie par une meilleure vascularisation ainsi que des modifications du métabolisme aérobie. En conclusion, ces travaux de thèses contribuent à l’avancée des connaissances concernant le potentiel anabolisant des extraits de plantes Rhaponticum carthamoides et Rhodiola Rosea sur les stratégies de prévention du déconditionnement musculaire.
... Clinical studies have indicated beneficial effects of Rhodiola rosea extracts (including the WS®1375 extract) in stress and fatigue management as well as in building resilience [5][6][7][8][9][10][11][12][13]. RRE has also shown antioxidant, antiinflammatory, and neuroprotective effects in animal [14][15][16][17] and cellular models [18]. Phytochemically, extracts of Rhodiola rosea roots and rhizomes contain mainly six classes of compounds: flavonoids, phenolic acids, phenylethanoloids, phenylpropanoids, monoterpenes, and triterpenes. ...
... Our study is the first evaluating the effect of the whole extract on mRNA BDNF levels. Of note, increased BDNF mRNA expression does not necessarily lead to increased BDNF protein levels because the mRNA could possibly not be translated into the respective protein that is necessary for the 14 Oxidative Medicine and Cellular Longevity induction of neurite outgrowth and synaptic plasticity. BDNF is synthetized as a preform that includes a prosegment and the mature BDNF. ...
Full-text available
Background: Sustained stress with the overproduction of corticosteroids has been shown to increase reactive oxygen species (ROS) leading to an oxidative stress state. Mitochondria are the main generators of ROS and are directly and detrimentally affected by their overproduction. Neurons depend almost solely on ATP produced by mitochondria in order to satisfy their energy needs and to form synapses, while stress has been proven to alter synaptic plasticity. Emerging evidence underpins that Rhodiola rosea, an adaptogenic plant rich in polyphenols, exerts antioxidant, antistress, and neuroprotective effects. Methods: In this study, the effect of Rhodiola rosea extract (RRE) WS®1375 on neuronal ROS regulation, bioenergetics, and neurite outgrowth, as well as its potential modulatory effect on the brain derived neurotrophic factor (BDNF) pathway, was evaluated in the human neuroblastoma SH-SY5Y and the murine hippocampal HT22 cell lines. Stress was induced using the corticosteroid dexamethasone. Results: RRE increased bioenergetics as well as cell viability and scavenged ROS with a similar efficacy in both cells lines and counteracted the respective corticosteroid-induced dysregulation. The effect of RRE, both under dexamethasone-stress and under normal conditions, resulted in biphasic U-shape and inverted U-shape dose response curves, a characteristic feature of adaptogenic plant extracts. Additionally, RRE treatment promoted neurite outgrowth and induced an increase in BDNF levels. Conclusion: These findings indicate that RRE may constitute a candidate for the prevention of stress-induced pathophysiological processes as well as oxidative stress. Therefore, it could be employed against stress-associated mental disorders potentially leading to the development of a condition-specific supplementation.
... 2) увеличение активности стресс-активируемых протеинкиназ -JNK1 (c-Jun N-terminalproteinkinase 1), AMPK (АМФзависимая протеинкиназа), которые фосфорилируют белки, участвующие в окислительном метаболизме [10,26,27]; ...
... Л и т е р а т у р а (пп. [3][4][5]7,[10][11][12][13][17][18][19][20]22,23,[26][27][28][29][30] ...
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1 ФГБНУ «Научно-исследовательский институт комплексных проблем гигиены и профессиональных заболеваний», 654041, Новокузнецк; 2 Новокузнецкий институт (филиал) ФГБОУ ВО «Кемеровский государственный университет», 654041, Новокузнецк; 3 ГБУЗ «Новокузнецкий клинический онкологический диспансер», 654041, Новокузнецк Введение. Фтор и его соединения являются производственным загрязнителем, вызывающим при длительном поступлении в организм развитие хронической фтористой интоксикации (ХФИ). Показано, что при ХФИ наблюдаются нарушения в обменных процессах и морфологические изменения в различных органах. Поэтому поиск органопротекторной профилактики и коррекции повреждений, вызываемых ХФИ, остаётся актуаль-ным в гигиене и медицине труда. Перспективным направлением является оценка возможности профилак-тики и коррекции повреждений при ХФИ с помощью средств растительного происхождения, обладающих адаптогенным действием, одним из которых является Rhodiola rosea L. Цель исследования. В эксперименте оценить эффективность органопротекторной профилактики хрониче-ской фтористой интоксикации адаптогенным препаратом, содержащим Rhodiola rosea L. Материал и методы. Работа проведена на белых крысах-самцах массой 200-250 г. Животные в количестве 45 были разделены на группы по 15 особей: контрольные крысы; крысы с хроническим воздействием фтори-да натрия (NaF) в течение 12 нед; крысы, получавшие раствор NaF с одновременным введением экстракта Rhodiola rosea L. Проводили определение биохимических параметров метаболизма в сыворотке крови и ги-стологические исследования органов-печени и почек. Результаты. Показано, что применение адаптогенного препарата, содержащего Rhodiola rosea L., для про-филактики повреждений, вызываемых хроническим воздействием соединений фтора на организм, является эффективным, поскольку: нормализует окислительный метаболизм в тканях; сокращает выраженность де-генеративных, дистрофических и некротических изменений в печени и почках; восстанавливает синтетиче-скую и детоксикационную функции печени, а также сохраняет гомеостатическую функцию почек. Заключение. Применение адаптогенного препарата, содержащего Rhodiola rosea L., для профилактики по-вреждений, вызываемых хроническим воздействием соединений фтора на организм, является эффективным. К л ю ч е в ы е с л о в а : хроническая фтористая интоксикация; профилактика; адаптоген Rhodiola rosea L.; мета-болизм; морфология; печень; почки. Для цитирования: Михайлова Н.Н., Жукова А.Г., Горохова Л.Г., Бугаева М.С., Ядыкина Т.К., Киселева А.В. Оценка эффективно-сти профилактики хронической фтористой интоксикации адаптогеном Rhodiola rosea L. Гигиена и санитария. 2019; 98(7): 744-747. Финансирование. Исследование не имело спонсорской поддержки. Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов. Участие авторов: редактирование, утверждение окончательного варианта статьи-Михайлова Н.Н.; концепция и дизайн иссле-дования, написание и редактирование текста, ответственность за целостность всех частей статьи-Жукова А.Г.; сбор и обработка экспериментального материала-Горохова Л.Г., Бугаева М.С.; статистическая обработка данных-Ядыкина Т.К., Киселева А.В. Поступила Introduction. Fluorine and its compounds are industrial pollutants that cause the development of chronic fluorine intoxication (CFI) during long-term intake. It has been shown that in CFI there are disturbances in metabolic processes and morphological changes in various organs. Therefore, the search for organ protective prevention and correction of damage caused by CFI remains relevant in occupational health and medicine. The perspective direction is the assessment of the possibility of prevention and correction of CFI related disorders by means of the remedies of plant origin possessing adaptogenic action, one of which is Rhodiola Rosea L. The objective of the research. To evaluate the effectiveness of organ protective prevention of chronic fluoride intoxication with an adaptogenic drug-containing Rhodiola Rosea L in the experiment conditions Material and methods. The work was carried out on 45 white male rats weighing 200-250 g. Animals were divided into groups of 15 animals: control rats; rats with chronic exposure to sodium fluoride (NaF) for 12 weeks; rats who received NaF solution while administering of Rhodiola Rosea L. extract. Determination of biochemical indices of metabolism in blood serum and histologic studies of the organs (liver and kidneys) were performed. Results. The use of an adaptogenic drug-containing Rhodiola Rosea L. was shown to be effective in preventing the disorders caused by chronic exposure to fluorine compounds, since it normalizes oxidative metabolism in tissues, reduces the manifestation of degenerative, dystrophic and necrotic changes in the liver and kidneys, restores the synthetic and detoxication functions of the liver, and also preserves the homeostatic function of the kidneys.
... Sport is an area that interferes more and more with that of plant extracts and various plant products, given their multiple health benefits. Thus, the antioxidative actions of some plants and plant-derived compounds on physical exertion are already demonstrated (Avakian et al., 1984;Abidov et al., 2003;Huang et al., 2009;Jówko et al., 2011;Jurcău & Jurcău, 2017). Also, different plant extracts have been shown to have beneficial effects in increasing endurance (Murase et al., 2006;Lee et al., 2009;Panossian, 2013; and performance (Yang et al., 2018;Jurcău et al., 2019) and reduce physical fatigue (Kimura & Sumiyoshi, 2004;Khanum et al., 2005;Yang et al., 2018;Jurcău et al., 2019). ...
... Thus, adaptogens (Panossian et al., 2018) and plants with an adaptogenic role represent an important resource for modulating stress in general and physical exertion stress, in particular. In this sense, there are studies that have shown the modulation of physical stress with Eleutherococcus senticosus (Kimura & Sumiyoshi, 2004), Rhodiola rosea (Huang et al., 2009), Schisandra chinensis (Panossian, 2013;Jurcău et al., 2019) and Ginseng (Yang et al., 2018;. ...
Ethnopharmacological relevance Panax ginseng C.A. Mey (PG) is famous for “Qi-tonifying” effect, which has a medicinal history of more than 2 millennia. Modern pharmacology has confirmed that the “Qi-tonifying” effect of PG may be closely related to its pharmacological properties such as anti-oxidation, antineoplastic and treatment of cardiovascular disease. As one of the earliest cells affected by oxidative stress, RBCs are widely used in the diagnosis of diseases. Ginseng polysaccharide (GPS), is one of the major active components of PG, which plays an important role in resisting oxidative stress, affecting energy metabolism and other effects. However, the molecular mechanism explaining the “Qi-tonifying” effect of GPS from the perspective of RBCs oxidative damage has not been reported. Aim of the study This study aimed to investigate the protective effect of GPS on oxidatively damaged RBCs using in vitro and in vivo models and explore the molecular mechanisms from the perspective of glycolysis and gluconeogenesis pathways. To provides a theoretical basis for the future research of antioxidant drugs. Materials and methods Established three different in vitro and in vivo research models: an in vitro model of RBCs exposed to hydrogen peroxide (H2O2) (40 mM), an in vivo model of RBCs from rats subjected to exhaustive swimming, and an in vitro model of BRL-3A cells exposed to H2O2 (25 μM). All three models were also tested in the presence of different concentrations of GPS. Results The findings showed that GPS was the most potent antagonist of H2O2-induced hemolysis and redox inbalance in RBCs. In exhaustive exercise rats, GPS ameliorated RBVs hemolysis, including reducing whole-blood viscosity (WBV), improving deformability, oxygen-carrying and -releasing capacities, which was related to the enhancing of antioxidant capacity. Moreover, GPS promoted RBCs glycolysis in rats with exhaustive exercise by recovering the activities of glycolysis-related enzymes and increasing band 3 protein expression, thereby regulating the imbalance of energy metabolism caused by oxidative stress. Furthermore, we demonstrated that GPS improved antioxidant defense system, enhanced energy metabolism, and regulated gluconeogenesis via activating PPAR gamma co-activator 1 alpha (PGC-1α) pathway in H2O2-exposed BRL-3A cells. Mechanistically, GPS promoted glycolysis and protected RBCs from oxidative injury was partly dependent on the regulation of gluconeogenesis, as inhibition of gluconeogenesis by metformin (Met) attenuates the regulation of antioxidant enzymes and key enzymes of glycolytic by GPS in exhaustive exercise rats. Conclusion This study demonstrates that GPS protects RBCs from oxidative stress damage by promoting RBCs glycolysis and liver gluconeogenesis pathways. These results may contribute to the study of new RBCs treatments to boost antioxidant capacity and protect RBCs against oxidative stress.
Inflammation and oxidative stress caused by fine particulate matter (PM2.5) increase the incidence and mortality rates of respiratory disorders. Rosavin is the main chemical component of Rhodiola plants, which exerts anti‐oxidative and antiinflammatory effects. In this research, the potential therapeutic effect of rosavin was investigated by the PM2.5‐induced lung injury rat model. Rats were instilled with PM2.5 (7.5 mg/kg) suspension intratracheally, while rosavin (50 mg/kg, 100 mg/kg) was delivered by intraperitoneal injection before the PM2.5 injection. It was observed that rosavin could prevent lung injury caused by PM2.5. PM2.5 showed obvious ferroptosis‐related ultrastructural alterations, which were significantly corrected by rosavin. The pretreatment with rosavin downregulated the levels of tissue iron, malondialdehyde, and 4‐hydroxynonenal, and increased the levels of glutathione. The expression of nuclear factor E2‐related factor 2 (Nrf2) was upregulated by rosavin, together with other ferroptosis‐related proteins. RSL3, a specific ferroptosis agonist, reversed the beneficial impact of rosavin. The network pharmacology approach predicted the activation of rosavin on the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) signaling pathway. LY294002, a potent PI3K inhibitor, decreased the upregulation of Nrf2 induced by rosavin. In conclusion, rosavin prevented lung injury induced by PM2.5 stimulation and suppressed ferroptosis via upregulating PI3K/Akt/Nrf2 signaling pathway.
Bioactive constituents from Rhodiola rosea L. (RRL) exhibit multiple pharmacological effects on diverse diseases. However, whether they are suitable for the treatment of radiation‐induced intestinal injury (RIII) remains unclear. This study aims to investigate their roles and mechanisms in the RIII rat model. The radioprotective effects of the 4 bioactive constituents of RRL (salidroside, herbacetin, rosavin and arbutin) were evaluated by the cell viability of irradiated IEC‐6 cells. Intestinal tissues were collected for histological analysis, localized inflammation and oxidative stress assessments. Our work showed that salidroside, rosavin and arbutin improved the cell viability of the irradiated IEC‐6 cells, with the highest improvement in 12.5 μM rosavin group. The rosavin treatment significantly improved survival rate and intestinal damage in irradiated rats by modulating the inflammatory response and oxidative stress. Our work indicated that rosavin may be the optimal constituent of RRL for RIII treatment, providing an attractive candidate for radioprotection.
Over the past three decades, the knowledge gained about the mechanisms that underpin the potential use of Rhodiola in stress- and ageing-associated disorders has increased, and provided a universal framework for studies that focused on the use of Rhodiola in preventing or curing metabolic diseases. Of particular interest is the emerging role of Rhodiola in the maintenance of energy homeostasis. Moreover, over the last two decades, great efforts have been undertaken to unravel the underlying mechanisms of action of Rhodiola in the treatment of metabolic disorders. Extracts of Rhodiola and salidroside, the most abundant active compound in Rhodiola, are suggested to provide a beneficial effect in mental, behavioral, and metabolic disorders. Both in vivo and ex vivo studies, Rhodiola extracts and salidroside ameliorate metabolic disorders when administered acutely or prior to 2 experimental injury. The mechanism involved includes multi-target effects by modulating various synergistic pathways that control oxidative stress, inflammation, mitochondria, autophagy, and cell death, as well as AMPK signaling that is associated with possible beneficial effects on metabolic disorders. However, evidence-based data supporting the effectiveness of Rhodiola or salidroside in treating metabolic disorders is limited. Therefore, a comprehensive review of available trials showing putative treatment strategies of metabolic disorders that include both clinical effective perspectives and fundamental molecular mechanisms is warranted. This review highlights studies that focus on the potential role of Rhodiola extracts and salidroside in type 2 diabetes and atherosclerosis, the two most common metabolic diseases.
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Rhodiola rosea L., also known as "golden root" or "roseroot" belongs to the plant family Crassulaceae.1 R. rosea grows primarily in dry sandy ground at high altitudes in the arctic areas of Europe and Asia.2 The plant reaches a height of 12 to 30 inches (70cm) and produces yellow blossoms. It is a perennial with a thick rhizome, fragrant when cut. The Greek physician, Dioscorides, first recorded medicinal applications of rodia riza in 77 C.E. in De Materia Medica.3 Linnaeus renamed it Rhodiola rosea, referring to the rose-like attar (fragrance) of the fresh cut rootstock.4 For centuries, R. rosea has been used in the traditional medicine of Russia, Scandinavia, and other countries. Between 1725 and 1960, various medicinal applications of R. rosea appeared in the scientific literature of Sweden, Norway, France, Germany, the Soviet Union, and Iceland.2,4-12 Since 1960, more than 180 pharmacological, phytochemical, and clinical studies have been published. Although R. rosea has been extensively studied as an adaptogen with various health-promoting effects, its properties remain largely unknown in the West. In part this may be due to the fact that the bulk of research has been published in Slavic and Scandinavian languages. This review provides an introduction to some of the traditional uses of R. rosea, its phytochemistry, scientific studies exploring its diverse physiological effects, and its current and future medical applications.
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We report a two- to three-fold increase in free radical (R•) concentrations of muscle and liver following exercise to exhaustion. Exhaustive exercise also resulted in decreased mitochondrial respiratory control, loss of sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER) integrity, and increased levels of lipid peroxidation products. Free radical concentrations, lipid peroxidation, and SR, ER, and mitochondrial damage were similar in exercise exhausted control animals and non-exercised vitamin E deficient animals, suggesting the possibility of a common R• dependent damage process. In agreement with previous work showing that exercise endurance capacity is largely determined by the functional mitochondrial content of muscle (1–4), vitamin E deficient animals endurance was 40% lower than that of controls. The results suggest that R• induced damage may provide a stimulus to the mitochondrial biogenesis which results from endurance training.
Rhodiola rosea (rose root) belonging to the family Crassulaceae is a popular medicinal plant in Russia, Scandinavia, and many other countries. Extracts of the roots of this plant have been found to favorably affect a number of physiological functions including neurotransmitter levels, central nervous system activity, and cardiovascular function. It is being used to stimulate the nervous system, decrease depression, enhance work performance, eliminate fatigue, and prevent high-altitude sickness. Most of these effects have been ascribed to constituents such as salidroside (rhodioloside), rosavins, and p-tyrosol. It has also been found to be a strong antioxidant and anticarcinogen due to the presence of several phenolic compounds. Adaptogens are plant extracts that allow an organism to counteract adverse physical, chemical, and biological stressors by generating nonspecific resistance. Adaptogens are known to increase the availability of energy during the day, reduce stressed feelings, increase endurance, and increase mental alertness. This multipurpose medicinal plant (R. rosea), with adaptogenic properties that increase the body's nonspecific resistance and normalize functions, has been traditionally grown and used in Russia and Mongolia. Due to increasing consumer demands toward natural health products and the growing interests in the secondary metabolites of plants and their application in biotechnology and therapy, much focus has been put on the rose root and its medical properties. The rose root imparts normalizing influences on adverse physical, chemical, and biological disturbances but is otherwise innocuous. In India, the plant has been growing wild in the high altitudes of the Himalayas. The Defence Research and Development Organization in India has taken on the responsibilities of its conservation, as well as the development of multiple management practices and the development of health foods, supplements, and nutraceuticals in India.
To prevent oxidative tissue damage induced by strenuous exercise in the liver and kidney superoxide dismutase derivative (SM-SOD), which circulated bound to albumin with a half-life of 6 h, was injected intraperitoneally into rats. Exhausting treadmill running caused a significant increase in the activities of xanthine oxidase (XO), and glutathione peroxidase (GPX) in addition to concentrations of thiobarbituric acid-reactive substances (TBARS) in hepatic tissue immediately after running. There was a definite increase in the immunoreactive content of mitochondrial superoxide dismutase (Mn-SOD) 1 day after the running. Meanwhile, the TBARS concentration in the kidney was markedly elevated 3 days after running. The activities of GPX, and catalase in the kidney increased significantly immediately and on days 1 and 3 following the test. The immunoreactive content of Mn-SOD also increased 1 day after running. The exercise induced no significant changes in immunoreactive Cu, Zn-SOD content in either tissue. The administration of SM-SOD provided effective protection against lipid peroxidation, and significantly attenuated the alterations in XO and all the anti-oxidant enzymes, measured. In summary, the present data would suggest that exhausting exercise may induce XO-derived oxidative damage in the liver, while the increase in lipid peroxidation in the kidney might be the result of washout-dependent accumulation of peroxidised metabolites. We found that the administration of SM-SOD provided excellent protection against exercise-induced oxidative stress in both liver and kidney.
Exercise can induce short-term increases in the sensitivity and responsiveness of skeletal muscle glucose transport to insulin. The purpose of this study was to determine the effect of carbohydrate deprivation on the persistence of increased insulin sensitivity and responsiveness after a bout of exercise. Three hours after a bout of exercise, epitrochlearis muscles from carbohydrate-deprived (fat fed) rats showed a 25% greater increase in 3-O-methylglucose (3-MG) transport in response to a maximal insulin stimulus compared with muscles of nonexercised rats; this increase in insulin responsiveness had reversed 18 h postexercise. Muscles of rats fed carbohydrate showed no increase in insulin responsiveness 3 h after exercise. The effect of 60 microU/ml of insulin on 3-MG transport was approximately twofold greater in muscles studied 3 h after exercise than in nonexercised controls regardless of dietary carbohydrate intake. This increase in insulin sensitivity was lost within 18 h in carbohydrate-fed rats but persisted for at least 48 h in carbohydrate-deprived rats. Muscle glycogen increased approximately 41 mumol/g in the rats fed carbohydrate for 18 h, and only approximately 14.5 mumol/g in the rats fed fat for 48 h, after exercise. The persistent increase in insulin sensitivity after exercise in carbohydrate-deprived rats was unrelated to caloric intake, as muscles of fasted and fat-fed rats behaved similarly.
Because the amounts of lipid peroxides in the blood are rather small, a sensitive assay method is needed. For this purpose, the most appropriate among several reactions for detecting lipid peroxides is the thiobarbituric acid (TBA) reaction because of its sensitivity. TBA reaction with lipid peroxides gives a red-colored pigment. Malondialdehyde also gives the same product upon reaction with TBA. Because this product is fluorescent, a sensitive assay can be made by fluorometry. Results show that lipid peroxides can be measured by TBA reaction with fluorometry. Elimination of TBA-reacting substances other than lipid peroxides is necessary for the measurement of lipid peroxides in serum. The elimination procedure must be simple to avoid artifact due to the peroxidation during the procedure. One of the best procedures is to isolate lipids by precipitating them along with serum protein with the phosphotungstic acid–sulfuric acid system. By this procedure, water-soluble substances, which react with TBA to yield the same product as lipid peroxides, are removed. It was anticipated that platelet aggregation, if it occurs during the drawing of the blood, would liberate the TBA-reacting substances, and the effect of the aggregation was found to be eliminated by treatment with phosphotungstic acid–sulfuric acid system.
An ultrastructural, morphologic and histochemical study was made on the livers of rats exposed to eight different acute stressors: fasting, cortisol injecions, reserpine injections, restraint, spinal cord transection, immersion in hot water, exposure to cold and forced muscular exercise in a revolving drum. After 48 hours of exposure to stress, electron microscopy of the liver revealed rough endoplasmic reticulum fragmentation and dilatation, glycogen depletion, and mitochondrial enlargment. The most striking change, however, was an increase in the number and size of autophagic vacuoles which were limited by single or multiple membranes. A cytochemical study revealed that in the former case, the vacuolar membranes did not show a glucose-6-phosphatase positive reaction, whereas they did in the latter case. The vacuoles contained acid phosphatase positive material as well as organelles in various stages of degradation. Following exposure to most of the stressors, a marked increase of plasma corticosterone was noted, with a lowered rectal temperature and the appearance of the typical stress triad (adrenal hypertrophy, thymicolymphatic involution and gastrointestinal ulcers). The severity of the morphologic changes appeared to parallel the degree of hypothermia caused by the stressor. The results suggest that autophagy in the liver may be an adaptive response to stressors at the subcellular level.
A superoxide dismutase derivative (SM-SOD) that circulates and is bound to albumin with a half-life of 6 h was injected intraperitoneally into rats before exhaustive treadmill running to study its antioxidant scavenging capacity in the plasma and soleus and tibialis muscles. The exercise induced a marked increase in xanthine oxidase activity in plasma and an increase in thiobarbituric acid-reactive substances in the plasma as well as in the soleus and tibialis muscles of nonadministered rats immediately after the exercise. The immunoreactive content and activity of both SOD isoenzymes (Cu,Zn-SOD and Mn-SOD) of the nonadministered rats increased in the soleus and tibialis muscles immediately after running. SM-SOD treatment definitely attenuated the degree of the increase in thiobarbituric acid-reactive substances and xanthine oxidase in all samples examined immediately after exercise. Glutathione peroxidase activity significantly increased in the soleus muscle of nonadministered rats 1 day after running, whereas catalase activity remained unchanged throughout the experimental period. These results suggest that a single bout of exhaustive exercise induces oxidative stress in skeletal muscle of rats and that this oxidative stress can be attenuated by exogenous SM-SOD.