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Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebo-controlled trial

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Rationale: We hypothesized that valerian root might prevent cognitive dysfunction in coronary artery bypass graft (CABG) surgery patients through stimulating serotonin receptors and anti-inflammatory activity. Objectives: The aim of this study was to evaluate the effect of Valeriana officinalis root extract on prevention of early postoperative cognitive dysfunction after on-pump CABG surgery. Methods: In a randomized, double-blind, placebo-controlled trial, 61 patients, aged between 30 and 70 years, scheduled for elective CABG surgery using cardiopulmonary bypass (CPB), were recruited into the study. Patients were randomly divided into two groups who received either one valerian capsule containing 530 mg of valerian root extract (1,060 mg/daily) or placebo capsule each 12 h for 8 weeks, respectively. For all patients, cognitive brain function was evaluated before the surgery and at 10-day and 2-month follow-up by Mini Mental State Examination (MMSE) test. Results: Mean MMSE score decreased from 27.03 ± 2.02 in the preoperative period to 26.52 ± 1.82 at the 10th day and then increased to 27.45 ± 1.36 at the 60th day in the valerian group. Conversely, its variation was reduced significantly after 60 days in the placebo group, 27.37 ± 1.87 at the baseline to 24 ± 1.91 at the 10th day, and consequently slightly increased to 24.83 ± 1.66 at the 60th day. Valerian prophylaxis reduced odds of cognitive dysfunction compared to placebo group (OR = 0.108, 95 % CI 0.022-0.545). Conclusion: We concluded that, based on this study, the cognitive state of patients in the valerian group was better than that in the placebo group after CABG; therefore, it seems that the use of V. officinalis root extract may prevent early postoperative cognitive dysfunction after on-pump CABG surgery.
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Psychopharmacology
ISSN 0033-3158
Volume 232
Number 5
Psychopharmacology (2015)
232:843-850
DOI 10.1007/s00213-014-3716-x
Can Valeriana officinalis root extract
prevent early postoperative cognitive
dysfunction after CABG surgery? A
randomized, double-blind, placebo-
controlled trial
Soghra Hassani, Abbas Alipour, Hadi
Darvishi Khezri, Abolfazl Firouzian,
Amir Emami Zeydi, Afshin Gholipour
Baradari, et al.
1 23
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ORIGINAL INVESTIGATION
Can Valeriana officinalis root extract prevent early postoperative
cognitive dysfunction after CABG surgery? A randomized,
double-blind, placebo-controlled trial
Soghra Hassani &Abbas Alipour &Hadi Darvishi Khezri &Abolfazl Firouzian &
Amir Emami Zeydi &Afshin Gholipour Baradari &Rahman Ghafari &
Wali-all ah Habibi &Homeyra Tahmasebi &Fatemeh Alipour &Pooneh Ebrahim Zadeh
Received: 25 December 2013 / Accepted: 8 August 2014 /Published online: 31 August 2014
#Springer-Verlag Berlin Heidelberg 2014
Abstract
Rationale We hypothesized that valerian root might prevent
cognitive dysfunction in coronary artery bypass graft (CABG)
surgery patients through stimulating serotonin receptors and
anti-inflammatory activity.
Objectives The aim of this study was to evaluate the effect of
Valeriana officinalis root extract on prevention of early postop-
erative cognitive dysfunction after on-pump CABG surgery.
Methods In a randomized, double-blind, placebo-controlled
trial, 61 patients, aged between 30 and 70 years, scheduled for
elective CABG surgery using cardiopulmonary bypass (CPB),
were recruited into the study. Patients were randomly divided
into two groups who received either one valerian capsule
containing 530 mg of valerian root extract (1,060 mg/daily)
or placebo capsule each 12 h for 8 weeks, respectively. For all
patients, cognitive brain function was evaluated before the
surgery and at 10-day and 2-month follow-up by Mini
Mental State Examination (MMSE) test.
Results Mean MMSE score decreased from 27.03±2.02 in
the preoperative periodto 26.52± 1.82 at the 10th day and then
increased to 27.45±1.36 at the 60th day in the valerian group.
Conversely, its variation was reduced significantly after
60 days in the placebo group, 27.37±1.87 at the baseline to
24± 1.91 at the 10th day, and consequently slightly increased
to 24.83±1.66 at the 60th day. Valerian prophylaxis reduced
odds of cognitive dysfunction compared to placebo group
(OR= 0.108, 95 % CI 0.0220.545).
Conclusion We concluded that, based on this study, the cog-
nitive state of patients in the valerian group was better than
that in the placebo group after CABG; therefore, it seems that
the use of V. officinalis root extract may prevent early postop-
erative cognitive dysfunction after on-pump CABG surgery.
Keywords Valeriana officinalis .Cognition disorder .
Coronary artery bypass grafting
Introduction
Coronary artery bypass graft (CABG) surgery is one of the
most commonly performed surgical procedures worldwide
(Farhoudi et al. 2010). Since the introduction of cardiopulmo-
nary bypass (CPB) in the early 1950s, the neurological con-
sequence of cardiac surgery has been an important issue
(Arrowsmith et al. 2000). Cognitive dysfunction is the most
S. Hassani :H. Darvishi Khezri (*):H. Tahmasebi
Department of Nursing, Faculty of Medicine, Islamic Azad
University, 7th km of Sea Road (Farah Abaad), Firoozkande,
Sari, Iran
e-mail: hadidarvishi@iausari.ac.ir
A. Alipour
Department of Epidemiology, Faculty of Medicine, Mazandaran
University of Medical Sciences, Sari, Iran
A. Firouzian :A. Gholipour Baradari
Department of Anesthesiology, Faculty of Medicine, Mazandaran
University of Medical Sciences, Sari, Iran
A. Emami Zeydi
Department of Nursing, Faculty of Nursing and Midwifery,
Mazandaran University of Medical Sciences, Sari, Iran
A. Emami Zeydi
PhD Student in Nursing, School of Nursing and Midwifery, Mashhad
University of Medical Sciences, Mashhad, Iran
R. Ghafari :W.<a. Habibi
Department of Cardiac Surgery, Faculty of Medicine, Mazandaran
University of Medical Sciences, Sari, Iran
F. A lip our :P. Ebrahim Zadeh
ICU, Mazandaran University of Medical Sciences, Sari, Iran
Psychopharmacology (2015) 232:843850
DOI 10.1007/s00213-014-3716-x
Author's personal copy
common complication after cardiac surgery with the approx-
imate reported incidence of 2080 % (Kilo et al. 2001). This
complication is associated with increased mortality (Spiegel
et al. 2011), longer hospital stay (Slater et al. 2009), increased
hospital costs (Plaschke et al. 2010), reduced patient recovery
(Slater et al. 2009), increased risk of dementia (Petersen et al.
2001), and long-period care (Bilotta et al. 2011).
Cognitive dysfunction presume to be the result of physio-
logical disturbances caused by the CPB (Farhoudi et al. 2010;
VanHartenetal.2012). Brain damage caused by acute inflam-
mation and decreased serotonin neurotransmitter are the caus-
ative mechanisms of cognitive dysfunction in patients under-
going on-pump cardiac surgery (Baumgartner 2007;Figueroa-
Ramos et al. 2009). This condition has led to the development
of pharmacological neuroprotective strategies in these patients
(Gilmore and Wolfe 2013). Pharmacologic prophylactic treat-
ment (e.g., cholinesterase inhibitors and antipsychotics) has
been suggested as a means to prevent cognitive dysfunction
in selected patients and high-risk settings (e.g., older patients,
postoperation, and after stroke) (Gilmore and Wolfe 2013;
Oldenbeuving et al. 2008). A meta-analysis stated that preop-
erative, low-dose, and short-term administration of haloperidol
or risperidone may modestly decrease delirium incidencebut
not durationin high-incidence samples who require intensive
care unit (ICU) support (Gilmore and Wolfe 2013). Some other
studies have not demonstrated a decrease in the incidence of
cognitive dysfunction in patients receiving pharmacologic pro-
phylactic (such as haloperidol, donepezil (Sampson et al. 2007),
citicoline (Bcpp et al. 2009), and rivastigmine) (Gamberini et al.
2009; Kalisvaart et al. 2005;Pisanietal.2010).
Valerian root, an herbal product consisting of the root of
Valeriana officinalis L., is widely available on the market as a
traditional medicine (Taibi et al. 2009). The root of V. officinalis
have been used in the treatment of sleep disorders, anxiety,
myalgia, and epilepsy (Bent et al. 2006;Sudatietal.2013).
Many studies have shown the anti-inflammatory properties
(Jacobo-Herrera et al. 2006;Patočka and Jakl 2010), stimulatory
effects on serotonin (5-HT) and acetylcholine (ACh) receptors
(Dietz et al. 2005;Patočka and Jakl 2010), and reduction of
sleep disturbance properties of valerian (Bent et al. 2006).
Considering that several studies showed the role of inflam-
mation (Gorelick 2010;Pengetal.2013), sleep disruption
(Inouye et al. 1999;Sveinsson1975), and decrease in the ACh
and 5-HT neurotransmitters (Figueroa-Ramos et al. 2009)in
occurrence of postoperative cognitive dysfunction, we hy-
pothesized that valerian probably can decrease the incidence
of cognitive dysfunction through stimulating ACh and 5-HT
receptors (Dietz et al. 2005; Patočka and Jakl 2010) and anti-
inflammatory properties (Jacobo-Herrera et al. 2006;Patočka
and Jakl 2010), with reduction of sleep disturbance (Bent et al.
2006). Currently, two studies confirmed effects of valerian
root on cognitive dysfunction improvement in mice (Nam
et al. 2013;Wangetal.2014). According to the safety,
accessibility, and inexpensiveness of V. officinalis (Bent
et al. 2006; Gooneratne 2008) and to test this hypothesis and
also due to the lack of clinical evidence regarding the effect of
valerian on cogitative dysfunction after cardiac surgery, this
study was conducted for the first time with aim to investigate
the effect of valerian root extract on the prevention of postop-
erative cognitive dysfunction in patients undergoing CABG
surgery.
Materials and methods
Participants
After approval of the study in the Ethics Committee of the
Islamic Azad University, and obtaining written informed con-
sent from the patients, 61 adult patients of both sexes, aged
3070 years, who are candidates for elective CABG surgery
using CPB, were enrolled in this study. Exclusion criteria
included the following: CABG surgery with no CPB, concur-
rency with other cardiac surgeries (e.g., valve replacement),
reoperation, history of cerebrovascular disease, alcoholism,
known mental illness, use of psychotherapeutic drugs in the
last 3 months, hepatic failure (SGPT and SGOT more than
75 IU/L), severe pulmonary insufficiency, acute renal failure
(creatinine 2 mg/dL), previous heart surgeries, heart failure
(ejection fraction less than 30 %), deafness, blindness, inabil-
ity to speak, and sensitivity to valerian. Also, patients with pH
less than 7.25 or serum base excess (BE) of less than
6 mmol/L and coagulopathy (prolonged PT, a PTT, or both)
were excluded from the study.
Study design
A randomized, double-blinded, placebo-controlled trial was
conducted in the Cardiothoracic Surgery and ICU units at
Mazandaran Heart Center, a university teaching hospital
affiliated to Mazandaran University of Medical Sciences.
The trial protocol was registered at the Iranian Clinical
Trials Registry (IRCT201311104190N2; www.irct.ir)and
performed in accordance with the Declaration of Helsinki
and its subsequent revisions. Patients were informed of
their right to withdraw from the trial at any time. The
study was performed between March and September 2013.
Valerian root extract
Val e ri an ( V. officinalis, Valerianaceae) is a resistant perennial
flowering plant, with heads of pink or white flowers. The roots
of species belonging to the genus Va l e ri an a are used in
traditional medicine of many cultures. This genus consists of
over 250 species with many more subspecies. V. officinalis L.
is the official species used in Europe and Asia. Valerian, in
844 Psychopharmacology (2015) 232:843850
Author's personal copy
pharmacology and herbal medicine, is the name of supple-
ment prepared from roots of the plant. Extract of the root is
often sold in the form of capsules (Circosta et al. 2007). In this
study, valerian capsules made in Goldaru Company, Isfahan,
Iran, were used. Each capsule contains 530 mg dried root of
V. officinalis (IRC; 1228022753).
Intervention
History taking and physical examination on the patients were
conducted by an anesthesiologist, who was blinded to the
study, a day before the surgery. Patients who fulfilled the
inclusion criteria were randomly allocated into two groups
of experimental (taking valerian) and control (taking pla-
cebo) by a nurse who was unaware of the study groups,
according to numbers generated by the computer-generated
list. The experimental group received valerian capsules
containing 530 mg V. officinalis root extract, every 12 h.
The placebo group, however, received placebo capsule
every 12 h. The preparation of placebo capsules is as that
of the valerian capsules manufactured by Goldaru
Company, Isfahan, Iran. First, the contents of valerian
capsules were removed, and then the capsules were filled
with fixed amount of wheat flour for all randomized
patients who received placebo. Hence, placebo capsules
were identical to valerian capsules in shape, size, texture,
color, taste, and odor. Intake of the valerian and placebo
began 1 day before the surgery and continued 60 days
after the surgery. Valerian or placebo was administered
orally 3 h after extubation.
Anesthesia and operation conditions
All patients were premedicated with promethazine, midazo-
lam, and morphine, 3060 min before surgery by an anesthe-
siologist who was blinded to the study. Anesthesia in all
patients was based on moderate doses of fentanyl (20 to
30 μg/kg) and midazolam (0.05 to 0.15 mg/kg), supplemented
with isoflurane (<1 %) or propofol (2.5 to 4.0 mg/kg/h) during
CPB. The CPB circuit included a roller pump (Stockert
Instruments, Munich, Germany), a hollow-fiber membrane
oxygenator (Medtronic Inc., Minneapolis, MN, USA), and a
34-μm screen arterial filter (Medtronic Inc.).
Neurocognitive test
The Mini Mental State Examination (MMSE) (standardized
mental status interview) for screening of cognitive dysfunc-
tion was used in this study (Rudolph et al. 2006). Validity and
reliability of the Persian version of the MMSE score (Folstein
test) is confirmed, and it is used widely in research studies to
evaluate cognitive function in several studies (Farhoudi et al.
2010; Ghafari et al. 2012). The five areas of the test were as
follows: orientation (10 scores), registration (3 scores), atten-
tion and calculation (5 scores), recall (3 scores), and language
and praxis (9 scores), with a maximum score of 30 points. Any
score greater than or equal to 25 points is efficiently normal.
The scores lower than this can indicate severe (9 scores),
moderate (1020 scores), or mild (2124 scores) cognitive
dysfunction (Ghafari et al. 2012; Mungas 1991). The
neurocognitive tests were administered three times: once
the day before, at 10 days, and 2 months after the surgery
(Ghafari et al. 2012). Assessments were completed by an
experienced psychometrician who was blinded to the treat-
ment group assignments. The time of the neurocognitive
test and assessment was also the same (in the morning)
for all patients.
Statistical analysis
We used the Shapiro-Wilk test to test whether data were
normally distributed. Descriptive baseline characteristic com-
parisons for the two groups (valerian and placebo) were
tabulated as median (inter-quartile range) or as percentages.
Comparisons between the two groups for categorical data
were statistically analyzed using chi-square or Fishersexact
test, and for continuous data, the MannWhitney Utest was
used. The primary efficacy data on MMSE were examined
using intention-to-treat analysis. General linear model (GLM)
scores of MMSE between two groups were compared by
repeated measurement ANOVA test. Time of evaluation was
considered as the within-subject factor, and intervention state
(valerian and placebo) as the between-subject factor. The group
time (interaction term) was considered as group differences
(between valerian and placebo groups) in their response
over time. We tested Mauchleys sphericity test for com-
pound symmetry assumption. Additionally, we used a
generalized estimating equation (GEE) model to estimate
the differences in values of MMSE state (binary variable)
at each time point between the two groups and also the
time trend after treatment. A pvalue of 0.05 or less was
considered statistically significant, and a pvalue of less
than 0.1 was considered marginally statistically significant.
Data were analyzed using IBM SPSS statistics version 16
and STATA version 10.
Results
Participants
A total of 86 patients who were referred for CABG surgery to
our hospital were screened during the study period. Of these,
three patients did not meet the inclusion criteria and seven
patients declined to participate in the study. From 76 patients
Psychopharmacology (2015) 232:843850 845
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who were allocated in the two groups, 7 and 8 patients
were lost to follow-up during the study period in case and
control group, respectively. In total, 61 patients completed
the present study and data from all these patients were
analyzed (Fig. 1).
Basic demographic and clinical characteristics of patients
in the two groups are presented in Table 1.
Results show that differences of lowest NPT during CPB,
lowest pO
2
during operation (mm Hg), and duration of oper-
ation between groups are significant (p<0.05), but were not
significant in the other factors (p>0.05).
Outcomes
MMSE score and cognitive dysfunction
Table 2shows the mean and SD values of the preoperation
and postoperation MMSE parameters of each group. As
shown in Table 2, there is a marginal statistically signifi-
cant time trend (within-subject differences or time effect)
for recall domain of MMSE (p<0.1), and there is no
statistically significant time trend for overall MMSE and
other domains (p>0.05). There is statistically significant
differences in the values of MMSE and all domains except
language and praxis between groups (between-subject
differences or group effect) (p<0.1). The following were
identified that contrary to the MMSE and all domain trends
in the intervention group was stable; the placebo group
showed a statistically significant downward trend (group
time interaction or interaction effect) (p<0.05) except for
attention and calculation domain of MMSE where this
difference was not statistically significant (no interaction
effect) (p>0.1).
After adjusting of other variables, GEE model revealed that
valerian prophylaxis reduced odds of cognitive dysfunction
compare to placebo group (estimate: 2.22, OR=0.108, 95 %
CI 0.0220.545).
Discussion
Cognitive dysfunction and neuroinflammation are associated
with cardiac surgery after CPB (Scott et al. 2014;VanHarten
et al. 2012). We evaluated the effectiveness of valerian
root extract on the prevention of postoperative cognitive
dysfunction in patients undergoing CABG surgery. The
major finding of this study was that the patients who
received valerian had significantly lower incidence of the
cognitive dysfunction as well as greater improvement in
their cognitive function during the 8 weeks after CABG
surgery compared to the other group that received placebo.
Any score greater than or equal to 25 points (out of 30) is
normal. The scores lower than this indicate cognitive
dysfunction. MMSE score had relatively a stable or rising
trend after 2 months in patients receiving valerian, but it is
considerably reduced in the placebo group at the end of
study.
To the best of our knowledge, there are no clinical
trials which evaluate preventive effects of valerian root
on cognitive dysfunctions in vivo. Recently, the results
of the two studies showed that V. officinalis could
improve cognition dysfunction in vitro (Nam et al. 2013;
Wang et al. 2014).
Wang et al. suggest that valerian could protect the brain
neurons and ameliorate amyloid-beta-induced cognitive dys-
function by enhancing the cerebral cholinergic function, hence
Fig. 1 CONSORT diagram of
patientsrandomization,
intervention, and analysis
846 Psychopharmacology (2015) 232:843850
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increasing the secretion of ACh and enhancing the choline
acetyltransferase (ChAT) activity (Wang et al. 2014). Nam
et al. investigated the effects of extract from valerian root in
adult and aged mice. Study results indicate that valerian root
extract (100 mg/kg) and valerenic acid enhance cognitive
function, promote cell proliferation and neuroblast differenti-
ation, and decrease serum corticosterone and lipid peroxida-
tion in aged mice (Nam et al. 2013).
Inflammation may be an important mechanism causing
cognitive dysfunction (Gorelick 2010). Peng et al., in a me-
ta-analysis, provided evidence that cognitive dysfunction is
indeed associated with the concentrations of peripheral
inflammatory markers, especially interleukin-6 and S-100β
(Peng et al. 2013).
Considering that acute inflammation and decreased seroto-
nin neurotransmitter resulting from abnormal tryptophan me-
tabolism are the two mechanisms of developing cognitive
dysfunction in these patients (Baumgartner 2007;Figueroa-
Ramos et al. 2009), likely, valerenic acid contained in valerian
through stimulating serotonin receptors and inhibiting of in-
flammatory factor NF-kB (Jacobo-Herrera et al. 2006;
Patočka and Jakl 2010) result in decrease the incidence of
cognitive dysfunction in patients, and this led us to assume
that the prophylactic effect shown by valerian on cognitive
Tabl e 1 Basic demographic and clinical characteristics of patients in both groups
Variable Valerian group
(n=31)
Placebo group
(n=30)
Pvalue
Age (years) 66 (6268) 66 (63.769) 0.54
Sex (M/F) 17/14 19/11 0.34
BMI (kg/m
2
) 31.2 (28.333.1) 30.3 (28.533.1) 0.58
Literate 13 (41.9 %) 13 (43.3 %) 0.91
Smoker 6 (19.4 %) 4 (13.3 %) 0.73
HTN 30 (96.8 %) 28 (93.3 %) 0.61
a
COPD 6 (19.4 %) 3 (10 %) 0.47
a
Carotid stenosis 1 (3.2 %) 1 (3.3 %) >0.99
a
LVEF ( % ) 45 (40 50) 45 (4046.2) 0.09
Preoperative hospital stay (days) 2 (23) 2 (22) 0.11
Postoperative hospital stay (days) 5 (55) 5 (45.25) 0.83
ICU stay (day) 2 (23) 2 (22) 0.11
Duration of operation (h) 3 (34) 3.77 (3.354.0) 0.01
Duration of MV in ICU (h) 6 (68) 6.73 (5.78) 0.49
Duration of intubation in ICU (h) 7 (68) 6.38 (5.838) 0.32
Duration of CPB (min) 60 (5462) 60 (53.765.0) 0.46
Duration of aortic crassclamping (min) 38 (3248) 40 (3545) 0.74
Lowest NPT during CPB (°C) 30 (2931) 29 (2930) 0.02
Lowest HB during CPB (g/dL) 6 (67) 6 (67) 0.29
Lowest MAP during CPB (mmHg) 60 (5060) 58.5 (5565) 0.31
Lowest SpO
2
during operation (%) 98 (9899) 97 (9799) 0.15
Lowest pO
2
during operation (mmHg) 179 (170192) 166.0 (159180) 0.01
Blood transfusion during operation 1 (12) 1 (12) 0.09
Patients receiving prolong inotrope (>12 h) 1 (3.2 %) 2 (6.7 %) 0.61
a
Patients requiring IABP 4 (12.9 %) 1 (3.3 %) 0.35
a
Postoperative dysrhythmia AF
VT
VF
8 (25.8 %) 9 (30 %) 0.72
2 (6.5 %) 3 (10 %) 0.67
a
1 (3.2 %) 3 (10 %) 0.29
a
Data are expressed as the median (inter-quartile range) or as number (percentages)
BMI body mass index, HTN hypertension, COPD chronic obstructive pulmonary disease, LVEF left ventricular ejection fraction, MV mechanical
ventilation, ICU intensive care unit, CPB cardiopulmonary bypass, NPT nasopharyngeal temperature, HB hemoglobin, MAP mean arterial pressure,
SpO
2
saturation of peripheral oxygen, pO
2
partial pressure of oxygen, IABP intra-aortic balloon pump, AF atrial fibrillation, VT ventricular tachycardia, s
ventricular fibrillation
a
Fishersexacttest
Psychopharmacology (2015) 232:843850 847
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dysfunction is most likely to result from anti-inflammatory
actions and neuroprotective effects (Baumgartner 2007;
Figueroa-Ramos et al. 2009;Wangetal.2014). Although,
more research is still needed in this regard.
Sleep disruption is another potential risk factor for cogni-
tive dysfunction in cardiac surgical patients (Sveinsson 1975).
The relationship between sleep deprivation and cognitive
dysfunction has been studied in a many studies (Fulda and
Schulz 2001; Yildizeli et al. 2005).
The available evidence indicates that valerian root
might improve sleep quality without producing side effects
(Bent et al. 2006; Taavoni et al. 2011). V. officinalis is
effective in reducing insomnia associated with oxidative
stress (Sudati et al. 2009).
Therefore, other possible explanations for the effectiveness
of valerian root extract in reducing postoperative cognitive
dysfunction in our study may be that valerian through
improvement of sleep quality leads to a reduction in cog-
nitive dysfunction.
The result of our study showed that the cognitive state of
patients in the valerian group was better than in the placebo
group at the 10 days after CABG; therefore, it seems that the
use of V. officinalis root extract can prevent early postopera-
tive cognitive dysfunction after on-pump CABG surgery.
Moreover, since valerian has anticoronaryspastic, antihyper-
tensive, and antibronchospastic (Circosta et al. 2007;Murti
et al. 2011) properties, its application is reinforced in patients
undergoing heart surgery.
This study, however, has some limitations. One limitation
of the present study was that we only evaluate the patients
cognitive function in the morning and did not evaluate
it at the evening. Also, we only used MMSE as a
subjective measurement of cognitive function and did
not utilize several different screenings for diagnosis of
cognitive dysfunctions, which indicates the need for
further research. In addition, the study was not large
enough to completely prove a benefit from valerian for
cognitive dysfunction prophylaxis after CABG. In conclusion,
the present study provides evidence for V. officinalis root
extract as a prophylactic strategy in the prevention of cogni-
tive dysfunction after CABG surgery. However, further robust
randomized, blinded studies with large sample sizes are
required in this field.
Acknowledgments The authors wish to thank the staff of Mazandaran
Heart Center, Mazandaran, Sari, Iran, and the patients at the Fatemeh
Zahra Hospital, Division of Cardiac Surgery, and ICU Open Heart
for their kind and efficient collaboration. The financial support of
Research Deputy of Islamic Azad University is gratefully acknowl-
edged. We are grateful to Dr. Farzaneh Tabassomi for doing
neurocognitive test.
Conflict of interest All authors declare no conflicts of interest; no
conflict of interest exists for any of the authors associated with the
manuscript and there was no source of extra institutional commercial
funding, and the entire study was performed without external funding.
The funding organization had no role in the design and conduct of the
study, and in the collection, analysis, and interpretation of the data.
Tabl e 2 MMSE score at baseline, 10 days, and 60 days follow-up in both groups
Variable Time F Statistic
Baseline
(mean ± SD)
After operation
10th day
(Mean ± SD)
After operation
60th day
(mean ± SD)
Time Group Time* Group
Total MM SE sco re
(030)
Valerian 27.03±2.02 26.52±1.82 27.45±1.36 0.41 6.72
b
42.28
a
Placebo 27.3 1.87 24± 1.91 24.83±1.66
Orientation
(010)
Valerian 9.55±0.81 9.55±0.77 9.87±0.34 0.43 2.99
c
7.41
a
Placebo 9.8 ± 0.41 9.1±0.68 9.7±0.47
Registration
(03)
Valerian 0 3±0 0 0.07 31.59
a
21.82
a
Placebo 3±0 2.33±0.48 2.5±0.5
Attention and calculation
(05)
Valerian 4.48±0.77 4.13±1.18 4.42±0.76 1.76 1.39 2.36
Placebo 4.33±0.88 3.73±0.94 3.8±0.96
Recall
(03)
Valerian 2.52±0.67 2.68±0.48 2.71±0.46 2.95
c
8.84
a
22.15
a
Placebo 2.57±0.57 2±0.45 2.03±0.49
Language and praxis
(09)
Valerian 7.42±1.2 7.16±1.04 7.42±1.03 0.29 0.19 4.23
b
Placebo 7.63±1.03 6.8±1 6.8±0.92
*Interaction between time and group
a
Significance level less than 0.01
b
Significance level less than 0.05
c
Significance level less than 0.1
848 Psychopharmacology (2015) 232:843850
Author's personal copy
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... 7 It reduces cerebral metabolic rate as well as the inflammatory response and apoptosis. 8 Several studies investigated the effect of hypothermia on cognitive deficit among patients with CABG and they did not find any advantage of hypothermia over normothermia for improving cognitive deficit, 4,[9][10][11][12][13][14] resulting in ambiguity in terms of the role of temperature management during CPB surgery. Therefore, clinical practice guideline of temperature management advised that arterial outlet blood temperature should be limited to below 37°C to avoid cerebral hyperthermia. ...
... In harmony with other reviews on the association of hypothermia and POCD, 4,9,[12][13][14] our meta-analysis showed that a wide range of hypothermia (28-34°C) does not reduce POCD after CABG surgery. However, there is no statistically significant difference between the 2 groups, risk ratio for very early (1.004), early (0.968) and late (0.887), showing that the trend is compatible with that reported by Brown et al. 6 They demonstrated that there is a rapid decline in the embolic load as time from surgery increases (particularly in the first few days after surgery). ...
... A meta-analysis reported comparing off-pump compared to on-pump CABG does not show any significant effect on POCD. 14,39 There are several limitations of this meta-analysis. Studies have been conducted from 1994 to 2007; therefore, it was impossible to contact all the authors for additional data. ...
Article
Full-text available
There is controversy about whether hypothermia during coronary artery bypass grafting (CABG) surgery is effective in reducing postoperative cognitive deficit (POCD). The objective of this study was to determine the effect of hypothermia on POCD and to undertake a meta-regression to determine whether moderator variables mediate the relationship between hypothermia and POCD. We searched the Web of Science, PubMed database, Scopus, and the Cochrane Library database (up to June 2017), and systematically reviewed a list of retrieved articles. Our final review includes only randomized controlled trials (RCTs) that compared administration of hypothermia (34°C). Statistical analysis of the risk ratio (RR) and corresponding 95% confidence interval (95% CI) was used to report the overall effect. Mantel-Haenszel risk ratio (MH RR) and corresponding 95% CI was used to report the overall effect and meta-regression analysis. Eight RCTs were included in this study, with a total of 1,474 patients. The POCD occurred in 36.06% of all cases. A wide range of hypothermia (28-34°C) did not reduce the occurrence of POCD (RR = 0.983 (95% CI = 0.881-1.143); Z = -0.304; P = 0.761; I2 = 38%). Shorter CPB time reduced the occurrence of POCD (MH log risk ratio = -0.011 (95% CI = -0.021--0.0008); Z = -2.123; P = 0.033). Postoperative cognitive deficit is a common event among CABG patients. Contrary to deep hypothermia, mild hypothermia was significantly effective in reducing the risk of POCD. The neuroprotective effect of hypothermia on POCD may be attenuated by prolonged cardiopulmonary bypass (CPB) time.
... Healthful eating patterns such as the Mediterranean diet, have been shown to offer protective effects on brain function, such as memory and cognitive processes [5,6]. A growing number of data indicates that native Mediterranean herbs and spices are within those components of the Mediterranean diet involved in memory and cognitive enhancement [7][8][9][10][11][12]. ...
Article
Full-text available
Background Several findings suggest neuroinflammation as a contributing factor for the onset of psychiatric disorders such as Alzheimer’s disease, depression, and anxiety. There is increasing evidence pointing out that the Mediterranean diet influences brain and behavior. Mediterranean herbs and spices have been shown to be within those components of the Mediterranean diet involved in cognitive enhancement. Thus, we investigated the influence of Mediterranean natural extracts (MNE), Rosemary extract (RE) and Glycyrrhiza glabra root extract (GGRE), on cognitive behavior. Results Adult zebrafish were exposed to RE or GGRE (100 and 250 mg/L) treatments. Both MNE improved memory retention during the T-maze test, although no improvements were observed during the novel object preference. Similarly, chronic administration of RE (150 mg/Kg) and GGRE (150 mg/Kg) improved, respectively, spatial and retention memory, as assessed by the Morris Water Maze (MWM), and the Elevated Plus Maze (EPM) in healthy male rats. However, no improvements were observed during the novel object recognition. Finally, male, and female rats were chronically treated with lipopolysaccharide [(LPS) 300 ug/kg] and orally administered with RE. Interestingly, RE reversed LPS-induced cognitive deficit during the MWM and EPM in female rats. Conclusions We found that MNE improved cognition in both zebrafish and rats. Moreover, MNE rescued LPS-induced cognitive impairment in a gender-specific manner. Therefore, our study supports the view that zebrafish represent a valuable preclinical model for drug discovery in neuroscience. These findings contribute to an exciting and growing body of research suggesting that MNE may play an important role in the prevention of cognitive impairment.
... Valerian can be continued as it appears to be a safe supplement that may protect against cognitive dysfunction in the perioperative period. 134 Consider continuing lavender extract and hops as there is no convincing evidence that they can cause significant interactions with other CNS depressants. ...
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The widespread use of complementary products poses a challenge to clinicians in the perioperative period and may increase perioperative risk. Because dietary supplements are regulated differently from traditional pharmaceuticals and guidance is often lacking, the Society for Perioperative Assessment and Quality Improvement convened a group of experts to review available literature and create a set of consensus recommendations for the perioperative management of these supplements. Using a modified Delphi method, the authors developed recommendations for perioperative management of 83 dietary supplements. We have made our recommendations to discontinue or continue a dietary supplement based on the principle that without a demonstrated benefit, or with a demonstrated lack of harm, there is little downside in temporarily discontinuing an herbal supplement before surgery. Discussion with patients in the preoperative visit is a crucial time to educate patients as well as gather vital information. Patients should be specifically asked about use of dietary supplements and cannabinoids, as many will not volunteer this information. The preoperative clinic visit provides the best opportunity to educate patients about the perioperative management of various supplements as this visit is typically scheduled at least 2 weeks before the planned procedure.
... Valerian root (Valeriana officinalis), an herbal supplement, is used for its anxiolytic and sedative properties and is being explored as an agent to improve cognitive function. 1,2 It is available over the counter as a tea or as a dietary supplement, in doses ranging from 350 mg to 1000 mg. The extract of valerian root, valerenic acid, is thought to work as an anxiolytic by serving as an allosteric modulator of gamma-aminobutyric acid type A (GABA-A), specifically binding to the loreclezole binding site of the beta subunit. ...
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Background: Valerian root is an herbal supplement used for its anxiolytic and sedative properties. Its extract is thought to serve as an allosteric modulator of gamma-aminobutyric acid A, which can cause delirium due to its influence on the nervous system’s inhibitory tone and its effect on the sleep-wake cycle. Objective: This report presents a patient who developed delirium secondary to withdrawal from valerian root. Conclusion: This report emphasizes the importance of screening for use and abstinence of herbal supplements when delirium develops, as herbal supplement withdrawal can be an uncommon and overlooked etiology of delirium.
Chapter
Valerian (Valeriana officinalis) is a perennial flowering plant native to Europe and Asia that has had widespread use for insomnia since 400 BCE. Valerian is also used for anxiety, often in combination with other herbal products with which it has the strongest evidence. It may be beneficial for premenstrual syndrome, dysmenorrhea, menopause, postoperative cognitive impairment, restless legs syndrome, anxiety, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder (with lemon balm). In vitro, valerian shows antioxidant, cytoprotective, and neuroprotective effects. In animal research, valerian has shown antihypertensive, anxiolytic, antidepressant, and antispasmodic effects. This chapter examines some of the scientific research conducted on valerian, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of valerian’s use in treating genitourinary, neurological, psychiatric, and infectious disorders. Finally, the chapter presents a list of valerian’s Active Constituents, different Commonly Used Preparations and Dosages, and a Section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
Article
Valeriana officinalis L. (Caprifoliaceae family) has been traditionally used to treat mild nervous tension and sleep problems. The basis of these activities are mainly attributed to valerenic acid through the modulation of the GABA receptor. Moreover, V. officinalis is claimed to have other biological activities such as cardiovascular benefits, anticancer, antimicrobial and spasmolytic. The current review aims to update the biological and pharmacological studies (in vitro, in vivo and clinical trials) of V. officinalis and its major secondary metabolites in order to guide future research. Databases PubMed, Science Direct and Scopus were used for literature search including original papers written in English and published between 2014 and 2020. There have been identified 33 articles which met inclusion criteria. Most of these works were performed with V. officinalis extracts and only a few papers (in vitro and in vivo studies) evaluated the activity of isolated compounds (valerenic acid and volvalerenal acid K). In vitro studies focused on studying antioxidant and neuroprotective activity. In vivo studies and clinical trials mainly investigated activities on the nervous system (anticonvulsant activity, antidepressant, cognitive problems, anxiety and sleep disorders). Just few studies were focused on other different activities, highlight effects on symptoms of premenstrual and postmenopausal syndromes. Valeriana officinalis continues to be one of the medicinal plants most used by today's society for its therapeutic properties and whose biological and pharmacological activities continue to arouse great scientific interest as evidenced in recent publications. This review shows scientific evidence on traditional uses of V. officinalis on nervous system.
Article
Objective To assess the effect of valerian root extract on the sleep quality of patients after coronary artery bypass graft (CABG) surgery.Methods The patients who participated in this triple-blind clinical trial were selected by permuted block randomization. The participants were assigned to the valerian (n=36) and placebo (n=36) groups. The valerian group received 530 mg of valerian capsules for 30 nights after CABG surgery, and the placebo group received 530 mg of the placebo capsules containing wheat flour. The Pittsburgh Sleep Quality Index (PSQI), the prothrombin time (PT) and partial thromboplastin time (PTT) were assessed on four occasions, including the baseline, the 3rd, 14th and 30th days following intervention.ResultsThe odds ratio of worsened sleep quality significantly varied over time (the interaction of time and group) in the valerian group compared to the placebo group in various dimensions including total sleep quality (P=0.001), sleep latency (P<0.01), sleep duration (P=0.020), sleep efficiency (P=0.001) and daytime dysfunction (P=0.025). No significant difference was observed in the alterations of the odds ratio of PT in the two groups over time. (P=0.371).Conclusion The consumption of oral valerian root extract over 30 nights could significantly improve the patients' sleep quality safely after CABG surgery.
Preprint
Full-text available
Background: Several findings suggest neuroinflammation as a contributing factor for the onset of psychiatric disorders such as Alzheimer’s disease, depression, and anxiety. There is increasing evidence pointing out that the Mediterranean diet influences brain and behavior. Mediterranean herbs and spices have been shown to be within those components of the Mediterranean diet involved in cognitive enhancement. Thus, we investigated the influence of Mediterranean natural extracts (MNE), Rosemary extract (RE) and Glycyrrhiza glabra root extract (GGRE), on cognitive behavior. Results: Adult zebrafish were exposed to RE or GGRE (100 and 250 mg/L) treatments. Both MNE improved memory retention during the T-maze test, although no improvements were observed during the novel object preference. Similarly, chronic administration of RE (150 mg/Kg) and GGRE (150 mg/Kg) improved, respectively, spatial and retention memory, as assessed by the Morris Water Maze (MWM), and the Elevated Plus Maze (EPM) in healthy male rats. However, no improvements were observed during the novel object recognition. Finally, male, and female rats were chronically treated with lipopolysaccharide [(LPS) 300 ug/kg] and orally administered with RE. Interestingly, RE reversed LPS-induced cognitive deficit during the MWM and EPM in female rats. Conclusions: We found that MNE improved cognition in both zebrafish and rats. Moreover, MNE rescued LPS-induced cognitive impairment in a gender-specific manner. Therefore, our study supports the view that zebrafish represent a valuable preclinical model for drug discovery in neuroscience. These findings contribute to an exciting and growing body of research suggesting that MNE may play an important role in the prevention of cognitive impairment.
Article
Full-text available
Sleep problems are widely prevalent and associated with various comorbidities including anxiety. Valerian ( Valeriana officinalis L.) is a popular herbal medicine used as a sleep aid, however the outcomes of previous clinical studies are inconsistent. This study was conducted to update and re-evaluate the available data in order to understand the reason behind the inconsistent outcomes and to provide a broader view of the use of valerian for associated disorders. PubMed, ScienceDirect, and Cochrane Library were searched to retrieve publications relevant to the effectiveness of valerian as a treatment of sleep problems and associated disorders. A total of 60 studies (n=6,894) were included in this review, and meta-analyses were performed to evaluate the effectiveness to improve subjective sleep quality (10 studies, n=1,065) and to reduce anxiety (8 studies, n=535). Results suggested that inconsistent outcomes were possibly due to the variable quality of herbal extracts and that more reliable effects could be expected from the whole root/rhizome. In addition, therapeutic benefits could be optimized when it was combined with appropriate herbal partners. There were no severe adverse events associated with valerian intake in subjects aged between 7 and 80 years. In conclusion, valerian could be a safe and effective herb to promote sleep and prevent associated disorders. However, due to the presence of multiple active constituents and relatively unstable nature of some of the active constituents, it may be necessary to revise the quality control processes, including standardization methods and shelf life.
Article
Full-text available
Valerian is used to treat sleeping disorders, restlessness and anxiety, but it seems only to work when taken over long periods (several weeks). Some studies have demonstrated that valerian extracts interact with the GABA and benzodiazepine receptors. Valerian is also used traditionally to treat gastrointestinal pain and spastic colitis. There are no long term safety studies. Valerian contains over 150 chemical constituents and many of them are physiologically active, mainly pyridine alkaloids, some organic acids and terpenes, especially the so called valepotriates, esterified iridoid-monoterpenes. As valepotriates may be potential mutagens, valerian should only be used after consultation with a physician. Valerian medication is sometimes recommended as first line treatment when the benefit-risk relation requires it and is often indicated as transition medication during the discontinuation processes involving bromazepam, clonazepam and diazepam, among others.
Article
Full-text available
Postoperative cognitive dysfunction (POCD) is common following cardiac and non-cardiac surgery, but the pathogenic mechanisms remain unknown. Many studies suggest that an inflammatory response is a key contributor to POCD. The current meta-analysis shows that the levels of peripheral inflammatory markers are associated with POCD. An online search was performed to identify peer-reviewed studies without language restriction that measured peripheral inflammatory markers of patients with and without POCD, using PubMed, ScienceDirect, SinoMed and the National Knowledge Infrastructure database. Extracted data were analyzed with STATA (version 12).The standardized mean difference (SMD) and the 95% confidence interval (95%CI) were calculated for each outcome using a random effect model. Tests of heterogeneity assessment of bias, and meta-regression were performed in the meta-analysis. A total of 13 studies that measured the concentrations of peripheral inflammatory markers were included. The current meta-analysis found significantly higher concentrations of S-100β(SMD[95%CI]) (1.377 [0.423, 2.331], p-value < 0.001, N [POCD/non-POCD] =178/391, 7 studies), and interleukin(IL)-6 (SMD[95%CI]) (1.614 [0.603,2.624], p-value < 0.001, N[POCD/non-POCD] = 91/99, 5 studies), but not of neuron specific enolase, interleukin-1β, or tumor necrosis factor-α , in POCD compared with patients without POCD. In meta-regression analyses, a significant positive association was found between the SMD and the preoperative interleukin-6 peripheral blood concentration in patients with POCD (Coef.= 0.0587, p-value=0.038, 5 studies). This study shows that POCD is indeed correlated with the concentrations of peripheral inflammatory markers, particularly interleukin-6 and S-100β.
Article
The present review describes the morphological, phytochemical and pharmacology aspects of Valeriana officinalis (Valerianaceae). Valeriana officinalis is a hardy perennial flowering plant. Valerian is native to Europe and Asia and has naturalized in eastern North America. Native to Europe and parts of Asia, valerian has been introduced into North America. The major modern and historical uses for valerian are as a sedative and anxiolytic, but it is also used to treat "nervous stomach". It significantly improves subjectively recalled sleep quality compared to placebo and shows a favorable adverse effect profile compared with other commonly prescribed sedative hypnotics and anxiolytics. Historically, the herb used for its sedative/hypnotic, anxiolytic, other neurological condition, cardiovascular properties. So, in this article we are going to discuss about its benefits and an overview of phytochemical and pharmacological profiles.
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Cognitive deterioration can reliably be measured after procedures requiring anesthesia and surgery. Cardiac surgery has had the spotlight because of the high reported incidence of postoperative cognitive dysfunction in early studies, but such effects occur after other surgical procedures as well. "Early" postoperative cognitive dysfunction should be considered as a different phenomenon, relating to acute pharmacological, physiological, and stress-related recovery. The focus should be on what is affecting patients at 3 months, 12 months, and 5 years later. Like with many other aspects of perioperative risk, a significant element is the patient's preoperative cognitive status. We now know that up to one-third of overtly "normal" elective cardiac surgical patients enter surgery with some degree of pre-existing cognitive impairment or, when applying psychogeriatric measures, mild cognitive impairment. The latter is a known prodrome or early stage of the amyloid associated Alzheimer's disease dementia. Inflammatory responses during cardiac surgery have been recognized for years, but our understanding of the complexity of systemic inflammatory response has grown significantly with the ability to assay neurohumoral markers such as interleukins. The blood-brain barrier is made vulnerable by both pre-existing disorders (mild cognitive impairment/amyloid; vascular disease) and by the inflammatory response to surgery and cardiopulmonary bypass. Inflammation affecting the brain at this time may set in motion accelerated neurological and hence cognitive decline that, despite an initial recovery and even functional improvement, may proceed to further long-term decline at an accelerated rate in susceptible individuals. Clinical data are emerging from longer-term studies to support this concern, but evidence for effective preventive or therapeutic strategies is limited.
Article
Ethnophamacological relevance: Valeriana amurensis, a perennial medicinal herb, has been widely used as anxiolytic, antidepressant, antispasmodic, and sedative in traditional Chinese medicines (TCMs). Moreover, it has been used to treat dementia in Mongolia preparations. In our previous study, we reported that AD-effective fraction of Valeriana amurensis (AD-EFV) has protective effect on Aβ-induced toxicity in PC12 cells. Up to now, however, the therapeutic effect of Valeriana amurensis on Alzheimer disease (AD) has not been explored. This study was designed to determine whether the AD-EFV could improve the Amyloid-beta (Aβ)-induced cognitive deficit and to explore the mechanism of AD-EFV improves cognitive deficit in intact animals. Materials and methods: The constituents of AD-EFV were isolated with silica gel, octadecyl silica gel (ODS) column chromatography (CC) and preparative HPLC. The structures of compounds were determined by detailed NMR and ESI-MS data analyses. AD mice model was established by injecting A(β1-42) (1 μL, 200 μmol) into the bilateral ventricle. Cognitive performance was evaluated by the Morris water maze (MWM) test. The level of cerebral acetylcholine (ACh), the activities of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) were investigated using Enzyme-linked immunoassay (ELISA) kits. Brain sections were processed and neuronal apoptosis in hippocampus were evaluated by Hematoxylin and Eosin (HE), Nissl, and Tunel stainings. The analyses of p-ERK/ERK and Bcl-2/Bax protein expression by western blot assay were used to explore the anti-neuronal apoptosis mechanism of AD-EFV. Results: Seventeen compounds (15 lignans and two iridoids) were isolated from AD-EFV. A significant improvement in cognitive function was observed in administrated AD-EFV AD model mice. AD-EFV increased the ACh level by enhancing the ChAT activity but has no effect on AChE activity in the cerebral cortex and hippocampus in mice. Moreover, the histological injury in hippocampus CA1 induced by A(β1-42) was inhibited following administration of the AD-EFV. As well as the expression ratios of Bcl-2 to Bax and p-ERK to ERK were increased significantly in the mice which were administrated AD-EFV. Conclusion: These findings suggest that AD-EFV could ameliorate Aβ induced cognitive dysfunction through two underlying mechanisms: AD-EFV enhances the cerebral cholinergic function by increasing the secretion of ACh and enhancing the ChAT activity, and AD-EFV protects the brain neurons from Aβ induced apoptosis via activating the p-ERK and Bcl-2 signaling and suppressing the Bax pathways. Besides, the main constituents of AD-EFV are lignans which might be responsible for the AD-activity of Valeriana amurensis.
Article
In this study, we investigated the potential protective effects of Valeriana officinalis (V. officinalis) against the toxicity induced by rotenone in Drosophila melanogaster (D. melanogaster). Adult wild-type flies were concomitantly exposed to rotenone (500μM) and V. officinalis aqueous extract (10mg/mL) in the food during 7 days. Rotenone-fed flies had a worse performance in the negative geotaxis assay (i.e. climbing capability) and open-field test (i.e. mobility time) as well as a higher incidence of mortality when compared to control group. V. officinalis treatment offered protection against these detrimental effects of rotenone. In contrast, the decreased number of crossings observed in the flies exposed to rotenone was not modified by V. officinalis. Rotenone toxicity was also associated with a marked decrease on the total-thiol content in the homogenates and cell viability of flies, which were reduced by V. officinalis treatment. Indeed, rotenone exposure caused a significant increase in the mRNA expression of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and also in the tyrosine hydroxylase gene (TH). The expression of SOD and CAT mRNAs were normalized by V. officinalis treatment. Our results suggest that V. officinalis extract was effective in reducing the toxicity induced by rotenone in D. melonogaster as well as confirm the utility of this model to investigate potential therapeutic strategies on movement disorders, including Parkinson disease (PD).
Article
Objective: The objective was to examine whether prophylactic treatment with antipsychotics can decrease the incidence and severity of postsurgical delirium. Method: A meta-analysis of existing trials comparing delirium incidence between patients given prophylactic antipsychotic and placebo was performed. Secondary outcomes were total hospital days, total days of delirium and severity. Pooled odds ratios (ORs) and mean differences were calculated using a random-effects model. Results: Five randomized placebo-controlled trials comprising a total of 1491 patients were included. In the pooled analysis, prophylactic antipsychotic administration showed a reduction in delirium incidence (OR: 0.42; 95% confidence interval (CI): 0.24, 0.74). Among the studies reporting other outcomes, patients receiving antipsychotics prophylactically showed no differences in total hospital days (0.1; 95% CI: -0.73, 0.94), days of delirium (-1.17; 95% CI: -5.22, 2.88) or delirium severity (-1.02; 95% CI: -6.81, 4.76). Conclusions: Prophylactic antipsychotic treatment in surgical patients modestly decreases the incidence of delirium, but not the length of hospital stay, duration of delirium or its severity. Given the modest protective effect of antipsychotics and their potential adverse reactions, there is insufficient evidence to support its universal use as a preventive agent, though potential benefit may be seen in populations at high risk of developing delirium.