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Metadata of the article that will be visualized in

OnlineFirst
ArticleTitle

On Gelsemium and Complementary and Alternative Medicine (CAM) in Anxiety and Experimental
Neurology

Article Sub-Title
Article CopyRight

The Author(s)
(This will be the copyright line in the final PDF)

Journal Name

Neurology and Therapy

Corresponding Author

Family Name

Chirumbolo

Particle
Given Name

Salvatore

Suffix

Schedule

Division

Department of Medicine

Organization

Univerity of Verona

Address

LURM Est Policlinico GB Rossi, Piazzale AL Scuro 10, Verona, 37134,

Italy

Email

salvatore.chirumbolo@univr.it

Received

12 November 2014

Revised
Accepted

Abstract

A recent discussion expanded the debate about the experimental research on Gelsemium in anxiety. Herbal
medicine is widely used in anxiety and mood disorders, often with contradictory evidence, although some
authors are yet prompted to promote their full introduction in pharmacology as a promising therapy.
Complementary and alternative medicine (CAM) in anxiety is particularly appreciated by individual
healthcare, but deserves further investigation, as many critical issues have been recently raised. Comments
about the ability of negligible doses of Gelsemium hydroalcoholic extracts to affect gene expression were
recently reported.

Keywords (separated by '-')

Gelsemium - Gelsemine - GABA receptors - Behaviour - Anxiety

Footnote Information

Neurol Ther
DOI 10.1007/s40120-014-0025-6

Salvatore Chirumbolo

6
7
8

To view enhanced content go to www.neurologytherapy-open.com

Received: November 12, 2014
 The Author(s) 2014. This article is published with open access at Springerlink.com

ABSTRACT

10
11

A recent discussion expanded the debate about

12
13

anxiety. Herbal medicine is widely used in

anxiety and mood disorders, often with

14

contradictory
evidence,
although
some
authors are yet prompted to promote their full

therapy. Complementary and alternative

medicine (CAM) in anxiety is particularly

19

appreciated by individual healthcare, but

deserves further investigation, as many critical

OR

17
18
20
21

issues have been recently raised. Comments

about the ability of negligible doses of
Gelsemium hydroalcoholic extracts to affect

24
25

gene expression were recently reported.

UN
C

22
23

Gelsemine;

26

Keywords: Gelsemium;

27
28

receptors; Behaviour; Anxiety

A1
A2
A3
A4
A5

29

Herbal medicine is widely used in anxiety and

contradictory

31
32

evidence [1], although some authors are yet

prompted to promote their full introduction in

33
34

pharmacology as a promising therapy [2, 3].

Complementary and alternative medicine

35

mood

CT

introduction in pharmacology as a promising

RE

15
16

the experimental research on Gelsemium in

GELSEMIUM IN ANXIETY:
INTRODUCTION

ED

PR
OO
F

On Gelsemium and Complementary and Alternative

Medicine (CAM) in Anxiety and Experimental
Neurology

Author Proof

COMMENTARY

GABA

S. Chirumbolo (&)
Department of Medicine, Univerity of Verona,
LURM Est Policlinico GB Rossi, Piazzale AL Scuro 10,
37134 Verona, Italy
e-mail: salvatore.chirumbolo@univr.it

disorders,

often

(CAM) in anxiety is particularly appreciated by

36
37

individual healthcare [4], but deserves further

investigation, as many critical issues have been

38
39

recently raised. [5, 6]. As a matter of fact, a

recent discussion expanded the debate about

40

the experimental research on Gelsemium in

41
42

anxiety [711]. This Commentary tries to

elucidate major issues causing this debate by

43
44

addressing the numerous aspects raised in

comments published elsewhere in the literature.

45

The anxiolytic property of Gelsemium plant

46
47

has been extensively reviewed [1114]. Raw

alcoholic extracts from Gelsemium sempervirens

48
49

showed the ability to modify the response of

mice in behavioural tests and reduce anxiety

50

[15]. In this research, the anxiolytic property

51
52

related to Gelsemium extracts has been quite

exclusively associated with the alkaloid

53
54

gelsemine [13, 15, 16]; yet, Gelsemium plants

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with

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Neurol Ther

contain many further alkaloids with anxiolytic

of possible active principles, its ethanol content

potential [12], thus suggesting that the anti-

would be within the range 0.51.0 mM [18], an

97
98

58
59

anxiety activity of Gelsemium sempervirens may

come indifferently from gelsemine, koumine, or

occurrence that raised comments about the

active molecule in the observed and reported

99
100

60

gelsevirine or a complex mixture of several

active alkaloids [13]. Actually, plants from the

effects [15, 1821]. These issues prompted this

author to address the debate about Gelsemium in

101

genus Gelsemium are considered a source of

the following step-points.

102
103

63
64

potential anxiolytic substances [12]. This means

that experimental neuroscience based on the

This article is based on previously conducted

studies, and does not involve any new studies of

104
105

65

possible use of Gelsemium as a CAM therapy for

anxiety shows many difficulties in highlighting

human or animal subjects performed by the

author.

106

GELSEMIUM IN ANXIETY: ACTIVE

PRINCIPLES, SOLVENT,
AND MECHANISM OF ACTION

108
109

Alcoholic raw extracts from plants contain

111

alkaloids and other molecules that may

interfere with a plain interpretation of the

112

a single active principle accounting for the

68
69

presumptive evidence of efficacy observed in

in vitro and animal models. The current debate

70
71

on Gelsemium and anxiety includes the many

issues exemplified in Table 1, where bias,

72

comments,

73
74

thoroughly summarized. A comprehensive

neuropharmacology of Gelsemium should take

75
76

into consideration any aspect coming from

issues described within the reported table.

77

Most of articles dealing with Gelsemium in

anxiety pertain to CAM therapy. A Pubmed/

to

comments

are

Medline search of the MESH term Gelsemium

allowed us to retrieve 121 papers from 1945 to
date, of which 83 dealt with Gelsemium in

82

herbal medicine and CAM. The excellent

journal Psychopharmacology published at least

83
84

OR

80
81

two papers about Gelsemium in homeopathy

85
86

[15, 17], showing either a cataleptogenic or

anxiolytic action by Gelsemium 30cH, i.e. a

87

theoretical gelsemine concentration less than

6 9 10-60 mol/L [15]. In this circumstance, it

88
89

should be quite difficult to associate any

90
91

neurologic effect whatsoever with any active

molecule present in serially diluted extracts

92

from
the
Gelsemium
plant.
Moreover,
comments were raised about the presence of

93
94
95
96

107

110

pharmacology of active principles, due to the

113
114

complex interaction, either synergistic or

competitive,
existing
between
different

115
116

substances in the raw mixture [11].

Particularly, gelsemine has been recently

117

CT

replies

RE

78
79

and

ED

66
67

UN
C

Author Proof

61
62

PR
OO
F

56
57

neuro-

118
119

pharmacological mechanism related with

anxiety. It modulates anxiety in laboratory

120
121

animals at a sub-micromolar dose range, and

in fact, gelsemine doses from 10-6 to 10-10 M

122

associated

with

well-defined

induce an anxiolytic action in rats in the

123
124

elevated plus-maze test [13]. Gelsemine is a

Gelsemium derived alkaloid sharing a chemical

125
126

and functional kinship with strychnine [22]. In

rat spinal cords, gelsemine showed an additive

127

effect with glycine in increasing the production

128
129

of the neurosteroid allopregnenolone (3a,5atetraidroprogesterone or 3a-idrossi-5a-pregnan-

130
131

ponderable, significant moles of ethanol added

20-one, 3a,5a-THP), which in turn should

increase anxiety, due to an increased

132
133

as a co-solvent with water [9, 10, 18, 19]. While

a Gelsemium 30CH might have negligible traces

hippocampal expression of a4bd GABAA

receptors [23, 24]. 3a,5a-THP is a positive

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Neurol Ther

Table 1 Fundamental issues in the research about Gelsemium and anxiety

Issues and bias

References (A) Comments

and (B) replies
in:

Active principles

Gelsemine (3-ethenyl-1-methyl-2,3,3a,7,8,8a-hexahydro1 h,5 h-spiro[3,8,5-(ethane[1, 1, 2]triyl)oxepino[4,5b]pyrrole-4,30 -indol]-20 (10 h)-one) was the only active
principle described in the behavioural research

PR
OO
F

Topic

[15, 21,
40]

A [9]

B [10]

Author Proof

BIAS 1. Gelsemium plant extracts contain other alkaloids

with anxiolytic activity (e.g. koumine, gelsevirine)

BIAS 2. The anxiolytic activity of Gelsemium alcoholic

extracts was not further dissected in order to identify one or
more coworking active principles;

ED

BIAS 3. Gelsemine was supposed to be the only active

principle working in Gelsemium extracts on the simple basis of
previous in vitro pharmacological evidence
BIAS 4. Adverse effects not evaluated

Gelsemium extracts were used as a 30 % EtOH/water mixture [1416,

and further diluted with EtOH and water to have test samples 20, 21]

CT

Solvent and test

samples

A [8, 9, 18]
B [10, 19]

RE

BIAS 5. Refs [.] started from a raw EtOH/H2O Gelsemium

extract containing 30 % alcohol (*50 mM EtOH), then a
1:100 dilution into water with 30 % EtOH and a 1.100
dilution into water (1:10,000) followed. Final dilution
contained *500 lM EtOH, still biologically active

Experimental setting
(a): animal model

OR

BIAS 6. Ethanol is effective on gene expression at molar

concentrations as low as 250 lM
Animal models: mouse

[15, 16]

BIAS 7. Behavioural tests were performed on mice and

in vitro confirmatory cellular tests on humans

A [8, 9]
B [10]

UN
C

BIAS 8. Behavioural tests performed did not include specific

tests on anxiety, depression, sedation
BIAS 9. Operators treating animals performed behavioural
tests

Experimental setting
(b): in vitro cell
model

In vitro cell model: human neuroblastoma cell line

[20, 21]

BIAS 10. Criticism in gene expression performing and

interpretation

B [19]

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Neurol Ther

Table 1 continued
Issues and bias

References (A) Comments

and (B) replies
in:

Pharmacological
interpretation

Associated exclusively with gelsemine and considering the

allopregnenolone/GABAR pathway

PR
OO
F

Topic

[15]

A [8, 18]

B [19]

BIAS 11. The anxiolytic activity of Gelsemium may derive

from other alkaloids besides gelsemine

Author Proof

BIAS 12. Gelsemine can be anxiolytic through a GlyR/

GlyT1-mediated mechanism
Dilutions and ponderal chemistry. Solvents

ED

BIAS 13. Pharmacological interpretation may be hindered by

diluted test solutions with negligible amounts of active
principles
BIAS 14. Ethanol amount is much more higher than any
Gelsemium derived active principles in tested solutions besides
Gelsemium 2CH
Statistics with pooling data

[15]

CT

Statistics

BIAS 15. Pooling data projected to retrieve positive

evaluation of the mechanism

A [8]
B [10]

136

RE

BIAS 16. Blinded confounders with the same operator in

treating and performing test with animals
modulator of GABAA receptors and may cause
anxiogenic and adverse mood effects in

GABA relationship with anxiolytic effects.

Interestingly, recent reports on the effect of

particular

hydroalcoholic

153

Gelsemium

154
155

139
140

withdrawal [25]. The effect of 3a,5a-THP on

GABAA receptors is particularly complex in

sempervirens on mouse behaviour showed a

marked insensitivity of mice to diazepam [26].

156
157

141

neuroscience and depends on the many

factors related to chronic stress, the expression

In this circumstance, criticism was raised about

setting and evaluation of mice stress response in

158

level of the GABA receptor a4 subunit, the

behavioural tests [8, 9]. Furthermore, other

159
160

144
145

direction of chloride-mediated ionic fluxes

created by these target receptors, leading also

alkaloids contained in Gelsemium plants, such

as koumine, have been associated with a 3a,5a-

161
162

146

to a downregulation or dampening in the

benzodiazepine ability to modulate this

THP/GABA receptor signaling [26].

Yet, the anxiolytic activity exerted by

mechanism [8, 25]. This should suggest that,

Gelsemium might be caused by many further

164
165

149
150

at least in animal models, the anxiolytic action

attributed to gelsemine may be actually caused

mechanisms.
Many
Gelsemium-derived
alkaloids, such as kuomine and gelsenicine

166
167

151

by other mechanisms, and more caution is

requested about a presumptive 3a,5a-THP/

[26, 27] exert a nociceptive effect. Particularly,

gelsemine acts on chronic pain through the

168

147
148

152

involving

OR

142
143

circumstances

steroid

UN
C

137
138

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from

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Neurol Ther

170
171

activation of spinal a3 glycin receptors (GlyR)

around

[22]. This should suggest that the anxiolytic

be outbred or random-bred. Popular stocks of

212
213

172
173

activity associated with Gelsemium may not

directly come from GlyR activation, but most

such mice in the US include CD-1 (Charles

River Breeding Laboratories), Swiss Webster

214
215

174

probably from the contribution of activated

GlyR on the anziolytic activity of glycine

(Taconic Farms), and ICR, and NIH Swiss (both

from Harlan SpragueDawley). Outbred mice

216

transporter inhibitors [28]. Therefore, it is very

are used for the same reasons as F1 hybrids

217
218

177
178

difficult to highlight the neurological

mechanism by which Gelsemium exerts its

they exhibit hybrid vigor with long life spans,

high disease resistance, early fertility, large and

219
220

179

anxiolytic activity, when Gelsemium extract is

used within a micromolar-millimolar range.

frequent litters, low neonatal mortality, rapid

growth, and large size. However, unlike

221

world

are

considered

to

PR
OO
F

180
181

Furthermore, Gelsemium contains a lot of

F1 hybrids,

genetically

222
223

182
183

molecules with sedative, anti-depressant

activity [8], for which it is very difficult to

undefined. Nevertheless, outbred mice are

bought and used in large numbers simply

224
225

184
185

ascertain an anxiolytic activity only by widely

used, not properly suited behavioural tests [8, 9,

because they are less expensive than any of

the genetically defined strains. These animals

226
227

186

15]. In this perspective, other components

are

tests.

228

187
188

contained in Gelsemium-derived test solutions

such as ethanol, may be significantly involved

Behavioural tests most commonly used, such

as the light dark box test (LDBT) or open field

229
230

189
190

[8]. Describing a comprehensible overview of

the anxiolytic activity of Gelsemium extracts, is

test (OFT), should evaluate time spent at light,

without hiding into a small pitch dark hole or

231
232

191

walking on the centre of an empty arena, as a

measure of stress lacking or anxiety absence for

233

192
193

hampered also by the recent observation that

flavonoids, which are present in the Gelsemium

plant, may exert an anxiolytic action [29].

tested animals [15], yet these tests are used also

234
235

194
195

Furthermore,
the
involvement
of
the
GABAergic system in anxiety models is yet

to evaluate sedation, fear-related stress and

depression [9] and are much less specifically

236
237

196

controversial, because anxiogenic/anxiolytic

activity on GABAergic systems may be

used for anxiety research than others [8].

Test solutions of Gelsemium alcoholic

238

modulated by different types of orexins [30].

extracts were made by diluting 1:100 solutions

239
240

199
200

This strongly suggests that the interpretation of

Gelsemium anxiolytic activity by involving a

starting from a raw material containing 30 % or

about
50 mM
ethanol
[15,
20,
21].

241
242

201

single, defined
reductive.

Concentration
of
gelsemine,
a
major
component of Gelsemium extract, was

243

202
203

ED

outbred

widely

used

mice

for

are

behavioural

CT

RE

OR

197
198

UN
C

Author Proof

175
176

the

mechanism

[15]

may

be

A recent behavioural research on ICR-CD1

calculated as low as 6.5 9 10

-4

M in the fresh

244
245

204
205

mice used an hydroalcoholic extract of

Gelsemium sempervirens, which was serially

hydroalcoholic raw extract, then diluted 1:100

(6.5 9 10-6 M) in 30 % ethanol (49.93 mmol/L)

246
247

206

diluted to reach negligible concentrations of

potentially bio-active molecules [15]. ICR-CD1

and significant evidence reported for tested

solutions
containing
an
estimated

248

207
208

mice are not particularly suited for behavioural

concentration of 6.5 9 10

M gelsemine and

249
250

209
210

tests compared to the more considered

C57BL6 J mouse [31]. A large number of the

4.99 9 10-4 M ethanol [15, 20, 21]. While the

final concentration of ethanol (EtOH) at the so-

251
252

211

laboratory mice sold and used by investigators

called Gelsemium 2CH should be as low as

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254
255

5 9 10-6

6.5 9 10-8 M as 2CH means a final dilution

hydroalcoholic

Gelsemium

295
296

256
257

1:10,000, the authors made 1CH (1:100) in 30 %

ethanol (50.5 mM EtOH) and 2CH into water

downregulated the expression of 49/56 [21] or

45/55 [20] genes in SH-SYS5 neuroblastoma.

297
298

258

(0.505 mM EtOH, i.e. 5.05 9 10-4 M EtOH) [15,

20, 21]. Therefore, in Gelsemium 2CH, the ratio

Published comments addressed the issue that

the effect observed on gene expression might be

299

EtOH/gelsemine was about 10,000:1 [15, 20].

brought up by EtOH carry-over in the test

300
301

261
262

Because any further dilution was made with this

approach, this ratio was particularly higher for

solution, due to the predominant presence of

EtOH respect to any molecule of the starting

302
303

263

EtOH with respect to Gelsemium at 9CH and

even more at 30CH. Comments raised about

Gelsemium extract [18]. No gene particularly

involved in the neurological mechanism

304

this

which

underlying the molecular action of Gelsemium

305
306

266
267

suggested a preponderant role from ethanol

respect to Gelsemium components in modifying

alkaloids was up- or downregulated in the

experimental research [18, 20, 21].

307
308

268
269

mice behaviour in a LDBT and OFT [15], also

highlighted why the evidence was scarcely

270

reproducible [9, 32]. The authors claimed their

271
272

results as promising and explained Gelsemium

ability to reduce anxiety in mice by an

273
274

anxiolytic effect attributed to gelsemine and

3a,5a-THP [15]. In their paper, the minimal

275

effective concentration of gelsemine, estimated

by the iterative dilution process from 6.5 9 10-4

disproportion,

as

6 nM gelsemine [20]. In both papers, a diluted

extract

of

PR
OO
F

alkaloid/ethanol

calculated

ED

gelsemine

GELSEMIUM IN ANXIETY: FURTHER

COMMENTS AND CONCLUSIVE
REMARKS

CT

264
265

and

309
310
311
312

of Gelsemium hydroalcoholic extracts to affect

gene expression were recently reported [18]. In

313
314
315

M, was much lower the concentration reported

an attempt to highlight possible conclusive

remarks on the research about Gelsemium, I

278
279

in recent studies [13, 15].

The same research group recently showed

will introduce these fundamental concerns.

1. A more general observation of these studies

280

that diluted hydroalcoholic extracts of

Gelsemium
were
able
to
affect
gene

showed that Gelsemium extract did not

undergo a thorough chemical analysis of

transcription in human neuroblastoma models

its

authors

320
321

283
284

[1921]. They reported the same gelsemine

concentration previously shown [20] and a

attributed any result to the exclusive effect

of gelsemine [15, 20, 21]. Gelsemium

322
323

285

slight reduction in a
expression model on

microarray gene
human SH-SY5Y

sempervirens extracts contain alkaloids with

an in toto anxiolytic activity, yet a chemical

324

neuroblastoma cell line with an estimated

definition of these components needs to be

325
326

288
289

concentration of gelsemine as low as

6.5 9 10-9 M, hence within ranges previously

performed [14]. Other oxindole alkaloids

contained in Gelsemium extracts besides

327
328

290

reported for rats [13, 21]. A cognate paper,

published in a niche journal in CAM research,

gelsemine exhibit a neurotropic action

[12]. New alkaloids are being discovered

329

confirmed the effect of this gelsemine dosage,

and

between

330
331

but highlighted also a significant effect, though

slight, with doses decisively much lower than

Gelsemium alkaloids and their metabolites

may affect significantly the biological

332
333

281
282

286
287

291
292
293
294

OR

276
277

RE

Comments about the ability of negligible doses

UN
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Author Proof

259
260

composition,

complex

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many

interaction

316
317
318
319

Neurol Ther

response of an organism to plant extracts

toxicity [37, 38], so EtOH in test solutions

376

335
336

[33, 34].
Tested solutions contain a sizable molar

cannot be excluded from any comment

about Gelsemium effect. The authors

377
378

fraction of ethanol, with respect to

Gelsemium extract [13, 18]. The analytical

incubated SH-SY5Y cells with Gelsemium

hydroalcoholic extracts for 24 h [20, 21];

379

evaluation of gelsemine reported in [21]

ethanol itself may exhibit an activity on

380
381

340
341

should refer to the calculation indicated in

[15], as the authors did not perform and

neuroblastoma cells at the estimated

concentration of this research for that

382
383

342

subsequently describe the concentration of

gelsemine in the alcoholic raw extract used

time course [39].

While the gross bulk of evidence in this

384

337

343
344

3.

research regards effects with micromolar-

345
346

19]. According to this assumption, a

Gelsemium
hydroalcoholic
extract

nanomolar concentrations of Gelsemium

alkaloids [12], the lowest doses should

387
388

347
348

containing
gelsemine

as low as 6.5 9 10-22 M

and 5.0 9 10-4 M ethanol

raise criticism for an intrinsic difficulty in

chemical analysis and for ethanol-related

389
390

349

downregulated

bias. The molar mass of ethanol solvent in

391

350
351

bombesin-like receptor 3 (BRS3) and

gastrin-releasing peptide receptor (GRPR)

tested solutions approaching a theoretical

concentration of active principles lower

392
393

352
353

genes in SH-SY5Y cells [20]. Aside from the

consideration about which genes are

than 1 attomole/L, is at least 16 orders of

magnitude higher. As ethanol is a bioactive

394
395

354

possibly expressed by neuroblastoma in a

genomic microarray and how much they

molecule at relatively low doses [18], its

activity on gene expression may be highly

396

are involved in a behavioural mechanism

complex and unpredictable, both in treated

397
398

357
358

[18], Gelsemium hydroalcoholic extracts

appeared to fundamentally affect genes

and control cells, so hindering a reliable

statistical evaluation of the assay system.

399
400

359

involved in olfactory and tumor-related

mechanism [20, 35, 36], while changes in

Some authors recently reported that

Perhaps we need to remind that normally,

401

of

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expression

RE

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356

the

ED

for the experiment on gene expression [18,

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386

4.

when one performs a study of doseresponse

402
403

362
363

involved in anxiety were not reported [18,

19] This evidence apparently discourages

and the concentration in the highest dose

and the dilution factor are known, there is

404
405

364

the promising role of Gelsemium used in

CAM in modulating genes associated with

no way to determine the concentration of

substances in all successive dilutions [19].

406

neuroscience and mood disorders. This

This suggests that the way Gelsemium in

407
408

apparently aspecific activity by even

nanomolar concentrations of gelsemine in

CAM approaches mood disorders and

anxiety needs this standpoint to be

409
410

Gelsemium might be related also to effects

coming from other Gelsemium components,

addressed and further elucidated.

411

365
366
367
368
369
370
371

OR

genes related to neurological mechanism

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361

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339

2.

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334

their complex interaction or even to

372
373

alcoholic solvent, past reports have

outlined a role for bombesin-like peptides

374

in the neurological control of ethanol

CONCLUSIONS

412

While increasing evidence reports the

anxiolytic activity of Gelsemium [16, 11, 13,

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14], research on its active principles needs

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418

anti-depressant,
sedative,
anxiolytic,
neurotropic, nociceptive, and mood modifier

419

molecules represents the herbal potential of the

Gelsemium plant. In this respect, CAMs using

2.

Mills PJ, Farag NH, Newton RP, Parry BL. Effects of a

traditional herbal supplement on anxiety in
patients with generalized anxiety disorder. J Clin
Psychopharmacol. 2002;22(4):4434.

452
453
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should

reappraise

3.

Qureshi NA, Al-Bedah AM. Mood disorders and

complementary and alternative medicine: a
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2013;9:63958.

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Bazzan AJ, Zabrecky G, Monti DA, Newberg AB.

Current evidence regarding the management of
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Chirumbolo S. Plant-derived extracts in the

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9.

experimental

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comments and bias about the pharmacological

interpretation of Gelsemium activity.

426

ACKNOWLEDGMENTS

427

No funding or sponsorship was received for this

428
429

study or publication of this article. The named

author meets the ICMJE criteria for authorship

430

for this manuscript, takes responsibility for the

integrity of the work as a whole, and has given

6.

CT

reports about test setting and molecular

models, in order to reduce misinterpretations,

ED

Gelsemium

422
423

431
432

450
451

further investigation. A complex panoply of

final approval for the version to be published.

Conflict of interest. Salvatore Chirumbolo

declares no conflict of interest.

435

Compliance with ethics guidelines. This

436
437

article is based on previously conducted

studies, and does not involve any new studies

438
439

of human or animal subjects performed by the

author.

Chirumbolo S. Gelsemine and Gelsemium

sempervirens L. extracts in animal behavioral test:
comments and related biases. Front Neurol.
2011;2:31.

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440

Open Access. This article is distributed

under the terms of the Creative Commons

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behavioral models. Front Neurol. 2011;12(2):56.

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Attribution

11. Jin GL, Su YP, Liu M, Xu Y, Yang J, Liao KJ, Yu CX.

Medicinal plants of the genus Gelsemium
(Gelsemiaceae, Gentianales)a review of their
phytochemistry, pharmacology, toxicology and
traditional
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Noncommercial

License

which

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permits any noncommercial use, distribution,

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original author(s) and the source are credited.

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