Introduction:Bryophyllum pinnatum is widely used in folk medicine. It has neuropharmacological, anti-inflammatory, immunomodulatory, antidiabetic, hepatoprotective, and nephroprotective effects, among others. It also acts on uterine contractility. It is prescribed by practitioners of anthroposophic medicine for preterm labor, insomnia, and emotional disorders, and has other potential uses in obstetrics. As all drugs currently used in preterm labor have side effects, new tocolytic agents remain an area of active research. Objective: To evaluate the effect of B. pinnatum mother tincture (MT) on albino rats and their offspring throughout pregnancy from a biochemical and histological standpoint. Methods: Longitudinal, prospective, randomized controlled bioassay. This is the second stage of a trial that investigated 60 animals distributed across six equal groups: controls C1 and C2, which received 1 and 25 times the vehicle dose (30% ethanol), B1 and B2 (1- and 25-fold doses of B. pinnatum MT), and B3 and B4 (which received 50- and 100-fold doses of B. pinnatum concentrate). At this stage, blood chemistry parameters (glucose, alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, and blood urea nitrogen) were measured in dams, as well as histological aspects of dam liver, kidney, placenta, and uterine tissue and fetal liver, kidney, heart, and brain. Results: No differences were found between group B1 (therapeutic dose) and its control C1 in relation to glucose, AST, ALT, and creatinine. Group B2 exhibited lower glucose levels than groups C1, B3, and B4. There was no difference in AST across groups. Groups B3 and B4 exhibited higher ALT levels than groups C1 and B1. Groups B1–B4 exhibited higher urea nitrogen levels than group C1. Creatinine levels were higher in groups B2 and B3 than group C1. On morphological evaluation, fatty infiltration of the liver was observed in the alcoholic vehicle control groups (C1 and C2). Conclusions: Daily administration of B. pinnatum at therapeutic doses (group B1) to pregnant albino rats appears to be safe, with reduced glucose at dose B2, elevated ALT at doses B3 and B4, and increased urea at doses B1 to B4 and creatinine at B2 and B3, but never exceeding the normal reference range. It was not associated with histological changes in specimens of the maternal or fetal structures of interest.

1.
Correa
M
.
Dicionário de plantas úteis do Brasil
.
Rio de Janeiro
:
Ministério da Agricultura
;
1984
.
2.
Bueno
RS
.
Grande Dicionário Etimológico-prosódico da Língua Portuguesa.
Santos: Brasília;
1974
.
3.
Gwehenberger
B
,
Rist
L
,
Huch
R
,
von Mandach
U
.
Effect of Bryophyllum pinnatum versus fenoterol on uterine contractility
.
Eur J Obstet Gynecol Reprod Biol
.
2004
Apr
;
113
(
2
):
164
71
.
[PubMed]
0301-2115
4.
Ojewole
JA
.
Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum pinnatum (Crassulaceae) leaf aqueous extract
.
J Ethnopharmacol
.
2005
May
;
99
(
1
):
13
9
.
[PubMed]
0378-8741
5.
Siddiqui
S
,
Faizi
S
,
Siddiqui
BS
,
Sultana
N
.
Triterpenoids and phenanthrenes from leaves of Bryophyllum pinnatum
.
Phytochemistry
.
1989
;
28
(
9
):
2433
8
. 0031-9422
6.
Yamagishi
T
,
Haruna
M
,
Yan
XZ
,
Chang
JJ
,
Lee
KH
.
Antitumor agents, 110. Bryophyllin B, a novel potent cytotoxic bufadienolide from Bryophyllum pinnatum
.
J Nat Prod
.
1989
Sep-Oct
;
52
(
5
):
1071
9
.
[PubMed]
0163-3864
7.
Pereira
KM
,
Grecco
SS
,
Figueiredo
CR
,
Hosomi
JK
,
Nakamura
MU
,
Lago
JH
.
Chemical composition and cytotoxicity of Kalanchoe pinnata Leaves extracts prepared using accelerated system extraction (ASE)
.
Nat Prod Commun
.
2018
;
13
(
2
):
163
6
. 1934-578X
8.
Pal
S
,
Nag Chaudhuri
AK
.
Studies on the anti-ulcer activity of a Bryophyllum pinnatum leaf extract in experimental animals
.
J Ethnopharmacol
.
1991
May-Jun
;
33
(
1-2
):
97
102
.
[PubMed]
0378-8741
9.
Nassis
CZ
,
Haebisch
EM
,
Giesbrecht
AM
.
Antihistamine activity of Bryophyllum calycinum
.
Braz J Med Biol Res
.
1992
;
25
(
9
):
929
36
.
[PubMed]
0100-879X
10.
Pal
S
,
Sen
T
,
Chaudhuri
AK
.
Neuropsychopharmacological profile of the methanolic fraction of Bryophyllum pinnatum leaf extract
.
J Pharm Pharmacol
.
1999
Mar
;
51
(
3
):
313
8
.
[PubMed]
0022-3573
11.
Akinpelu
DA
.
Antimicrobial activity of Bryophyllum pinnatum leaves
.
Fitoterapia
.
2000
Apr
;
71
(
2
):
193
4
.
[PubMed]
0367-326X
12.
Yadav
NP
,
Dixit
VK
.
Hepatoprotective activity of leaves of Kalanchoe pinnata Pers
.
J Ethnopharmacol
.
2003
Jun
;
86
(
2-3
):
197
202
.
[PubMed]
0378-8741
13.
Yemitan
OK
,
Salahdeen
HM
.
Neurosedative and muscle relaxant activities of aqueous extract of Bryophyllum pinnatum
.
Fitoterapia
.
2005
Mar
;
76
(
2
):
187
93
.
[PubMed]
0367-326X
14.
Cruz
EA
,
Da-Silva
SA
,
Muzitano
MF
,
Silva
PM
,
Costa
SS
,
Rossi-Bergmann
B
.
Immunomodulatory pretreatment with Kalanchoe pinnata extract and its quercitrin flavonoid effectively protects mice against fatal anaphylactic shock
.
Int Immunopharmacol
.
2008
Dec
;
8
(
12
):
1616
21
.
[PubMed]
1567-5769
15.
Berkman
ND
,
Thorp
JM
 Jr
,
Lohr
KN
,
Carey
TS
,
Hartmann
KE
,
Gavin
NI
, et al.
Tocolytic treatment for the management of preterm labor: a review of the evidence
.
Am J Obstet Gynecol
.
2003
Jun
;
188
(
6
):
1648
59
.
[PubMed]
0002-9378
16.
Simhan
HN
,
Caritis
SN
.
Prevention of preterm delivery
.
N Engl J Med
.
2007
Aug
;
357
(
5
):
477
87
.
[PubMed]
1533-4406
17.
Hamre
HJ
,
Witt
CM
,
Glockmann
A
,
Ziegler
R
,
Willich
SN
,
Kiene
H
.
Anthroposophic medical therapy in chronic disease: a four-year prospective cohort study
.
BMC Complement Altern Med
.
2007
Apr
;
7
(
1
):
10
.
[PubMed]
1472-6882
18.
Bryophyllum
R
. São Paulo: Weleda do Brasil;
2008
.
19.
Hosomi
JK
,
Ghelman
R
,
Quintino
MP
,
de Souza
E
,
Nakamura
MU
,
Moron
AF
.
Effects of chronic Bryophyllum pinnatum administration on Wistar rat pregnancy
.
Forsch Komplement Med
.
2014
;
21
(
3
):
184
9
.
[PubMed]
1661-4127
20.
HBA
.
H 5 Production Methods. German Homeopathic Pharmacopoeia
.
Stuttgart
:
MedPharm
;
2007
.
21.
Ministério da Saúde (Brasil)
.
A Fitoterapia no SUS e o Programa de Pesquisa de Plantas Medicinais da Central de Mediciamentos
.
Brasília
:
Ministério da Saúde
;
2006
.
148
pp.
22.
Patil
SB
,
Dongare
VR
,
Kulkarni
CR
,
Joglekar
MM
,
Arvindekar
AU
.
Antidiabetic activity of Kalanchoe pinnata in streptozotocin-induced diabetic rats by glucose independent insulin secretagogue action
.
Pharm Biol
.
2013
Nov
;
51
(
11
):
1411
8
.
[PubMed]
1744-5116
23.
Menon
N
,
Sparks
J
,
Omoruyi
F
.
Hypoglycemic and hypocholesterolemic activities of the aqueous preparation of Kalanchoe pinnata leaves in streptozotocin-induced diabetic rats
.
Asian Pac J Trop Biomed
.
2015
;
5
(
1
):
3
9
. 2221-1691
24.
Aoki
C
,
Hartati
S
,
Sasnti
MR
, Lydwina, Firdaus R, Hanafi M, et al.
Isolation and identification of substances with anti-hepatitis C virus activities from Kalanchoe pinnata
.
Int J Pharm Pharm Sci
.
2014
;
6
(
2
):
211
5
.0975-1491
25.
Harlalka
GV
,
Patil
CR
,
Patil
MR
.
Protective effect of Kalanchoe pinnata pers. (Crassulaceae) on gentamicin-induced nephrotoxicity in rats
.
Indian J Pharmacol
.
2007
;
39
(
4
):
201
5
. 0253-7613
26.
Indriyanti
N
,
Garmana
AN
,
Setiawan
F
.
Repairing effects of aqueous extract of Kalanchoe pinnata (Lmk) Pers. on lupus nephritis mice
.
Pharmacogn J
.
2018
;
10
(
3
):
548
52
. 0975-3575
27.
Boone
L
,
Meyer
D
,
Cusick
P
,
Ennulat
D
,
Bolliger
AP
,
Everds
N
, et al.
Selection and interpretation of clinical pathology indicators of hepatic injury in preclinical studies
.
Vet Clin Pathol
.
2005
Sep
;
34
(
3
):
182
8
.
[PubMed]
0275-6382
28.
Griffin
BR
,
Faubel
S
,
Edelstein
CL
.
Biomarkers of Drug-Induced Kidney Toxicity
.
Ther Drug Monit
.
2019
Apr
;
41
(
2
):
213
26
.
[PubMed]
1536-3694
29.
Simões-Wüst
AP
,
Grãos
M
,
Duarte
CB
,
Brenneisen
R
,
Hamburger
M
,
Mennet
M
, et al.
Juice of Bryophyllum pinnatum (Lam.) inhibits oxytocin-induced increase of the intracellular calcium concentration in human myometrial cells
.
Phytomedicine
.
2010
Oct
;
17
(
12
):
980
6
.
[PubMed]
1618-095X
30.
Wächter
R
,
Brenneisen
R
,
Hamburger
M
,
Mennet
M
,
Schnelle
M
,
Worel
AM
, et al.
Leaf press juice from Bryophyllum pinnatum (Lamarck) Oken induces myometrial relaxation
.
Phytomedicine
.
2011
Dec
;
19
(
1
):
74
82
.
[PubMed]
1618-095X
31.
McKenzie
RA
,
Dunster
PJ
.
Hearts and flowers: bryophyllum poisoning of cattle
.
Aust Vet J
.
1986
Jul
;
63
(
7
):
222
7
.
[PubMed]
0005-0423
32.
McKenzie
RA
,
Franke
FP
,
Dunster
PJ
.
The toxicity to cattle and bufadienolide content of six Bryophyllum species
.
Aust Vet J
.
1987
Oct
;
64
(
10
):
298
301
.
[PubMed]
0005-0423
33.
Reppas
GP
.
Bryophyllum pinnatum poisoning of cattle
.
Aust Vet J
.
1995
Nov
;
72
(
11
):
425
7
.
[PubMed]
0005-0423
34.
Mora-Pérez
A
,
Hernández-Medel
MR
.
Anticonvulsant activity of methanolic extract from Kalanchoe pinnata Lam. stems and roots in mice: A comparison to diazepam
.
Neurologia
.
2016
Apr
;
31
(
3
):
161
8
.
[PubMed]
0213-4853
35.
Stalikas
CD
.
Extraction, separation, and detection methods for phenolic acids and flavonoids
.
J Sep Sci
.
2007
Dec
;
30
(
18
):
3268
95
.
[PubMed]
1615-9306
36.
Biesaga
M
.
Influence of extraction methods on stability of flavonoids
.
J Chromatogr A
.
2011
May
;
1218
(
18
):
2505
12
.
[PubMed]
1873-3778
37.
Muzitano
MF
,
Bergonzi
MC
,
De Melo
GO
,
Lage
CL
,
Bilia
AR
,
Vincieri
FF
, et al.
Influence of cultivation conditions, season of collection and extraction method on the content of antileishmanial flavonoids from Kalanchoe pinnata
.
J Ethnopharmacol
.
2011
Jan
;
133
(
1
):
132
7
.
[PubMed]
1872-7573
38.
Gagnier
JJ
,
Boon
H
,
Rochon
P
,
Moher
D
,
Barnes
J
,
Bombardier
C
;
CONSORT Group
.
Recommendations for reporting randomized controlled trials of herbal interventions: explanation and elaboration
.
J Clin Epidemiol
.
2006
Nov
;
59
(
11
):
1134
49
.
[PubMed]
0895-4356
39.
Gagnier
JJ
,
Boon
H
,
Rochon
P
,
Moher
D
,
Barnes
J
,
Bombardier
C
;
CONSORT Group
.
Reporting randomized, controlled trials of herbal interventions: an elaborated CONSORT statement
.
Ann Intern Med
.
2006
Mar
;
144
(
5
):
364
7
.
[PubMed]
1539-3704
40.
Kim
WR
,
Flamm
SL
,
Di Bisceglie
AM
,
Bodenheimer
HC
;
Public Policy Committee of the American Association for the Study of Liver Disease
.
Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease
.
Hepatology
.
2008
Apr
;
47
(
4
):
1363
70
.
[PubMed]
1527-3350
41.
Minuk
GY
.
Canadian Association of Gastroenterology Practice Guidelines: evaluation of abnormal liver enzyme tests
.
Can J Gastroenterol
.
1998
Sep
;
12
(
6
):
417
21
.
[PubMed]
0835-7900
42.
Travlos
GS
,
Morris
RW
,
Elwell
MR
,
Duke
A
,
Rosenblum
S
,
Thompson
MB
.
Frequency and relationships of clinical chemistry and liver and kidney histopathology findings in 13-week toxicity studies in rats
.
Toxicology
.
1996
Jan
;
107
(
1
):
17
29
.
[PubMed]
0300-483X
43.
Torres-Santos
EC
,
Da Silva
SA
,
Costa
SS
,
Santos
AP
,
Almeida
AP
,
Rossi-Bergmann
B
.
Toxicological analysis and effectiveness of oral Kalanchoe pinnata on a human case of cutaneous leishmaniasis
.
Phytother Res
.
2003
Aug
;
17
(
7
):
801
3
.
[PubMed]
0951-418X
44.
Simões-Wüst
AP
,
Lapaire
O
,
Hösli
I
,
Wächter
R
,
Fürer
K
,
Schnelle
M
, et al.
Two Randomised Clinical Trials on the Use of Bryophyllum pinnatum in Preterm Labour: Results after Early Discontinuation
.
Complement Med Res
.
2018
;
25
(
4
):
269
73
.
[PubMed]
2504-2106
45.
Plangger
N
,
Rist
L
,
Zimmermann
R
,
von Mandach
U
.
Intravenous tocolysis with Bryophyllum pinnatum is better tolerated than beta-agonist application
.
Eur J Obstet Gynecol Reprod Biol
.
2006
Feb
;
124
(
2
):
168
72
.
[PubMed]
0301-2115
46.
Lambrigger-Steiner
C
,
Simões-Wüst
AP
,
Kuck
A
,
Fürer
K
,
Hamburger
M
,
von Mandach
U
.
Sleep quality in pregnancy during treatment with Bryophyllum pinnatum: an observational study
.
Phytomedicine
.
2014
Apr
;
21
(
5
):
753
7
.
[PubMed]
1618-095X
47.
Kechagias
S
,
Ernersson
A
,
Dahlqvist
O
,
Lundberg
P
,
Lindström
T
,
Nystrom
FH
;
Fast Food Study Group
.
Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects
.
Gut
.
2008
May
;
57
(
5
):
649
54
.
[PubMed]
1468-3288
48.
Boehm
O
,
Zur
B
,
Koch
A
,
Tran
N
,
Freyenhagen
R
,
Hartmann
M
, et al.
Clinical chemistry reference database for Wistar rats and C57/BL6 mice
.
Biol Chem
.
2007
May
;
388
(
5
):
547
54
.
[PubMed]
1431-6730
49.
Spinelli
MO
,
Godoy
CM
,
Motta
MC
,
Cruz
RJ
,
Junqueira
MS
,
Bortolatto
J
.
Perfil bioquímico dos animais de laboratório do biotério da Faculdade de Medicina da USP
.
R Soc Bras Ci Anim Lab.
2012
;
1
(
1
):
76
81
.
50.
Shukla
AB
,
Mandavia
DR
,
Barvaliya
MJ
,
Baxi
SN
,
Tripathi
CR
.
Evaluation of anti-urolithiatic effect of aqueous extract of Bryophyllum pinnatum (Lam.) leaves using ethylene glycol-induced renal calculi
.
Avicenna J Phytomed
.
2014
May
;
4
(
3
):
151
9
.
[PubMed]
2228-7930
51.
Yadav
M
,
Gulkari
VD
,
Wanjari
MM
.
Bryophyllum pinnatum Leaf Extracts Prevent Formation of Renal Calculi in Lithiatic Rats
.
Anc Sci Life
.
2016
Oct-Dec
;
36
(
2
):
90
7
.
[PubMed]
0257-7941
52.
Ponnappa
BC
,
Rubin
E
.
Modeling alcohol’s effects on organs in animal models
.
Alcohol Res Health
.
2000
;
24
(
2
):
93
104
.
[PubMed]
1535-7414
53.
Thibaut
F
,
Chagraoui
A
,
Buckley
L
,
Gressier
F
,
Labad
J
,
Lamy
S
, et al.
WFSBP * and IAWMH ** Guidelines for the treatment of alcohol use disorders in pregnant women
.
World J Biol Psychiatry
.
2019
Jan
;
20
(
1
):
17
50
.
[PubMed]
1814-1412
54.
Fürer
K
,
Simões-Wüst
AP
,
von Mandach
U
,
Hamburger
M
,
Potterat
O
.
Bryophyllum pinnatum and Related Species Used in Anthroposophic Medicine: Constituents, Pharmacological Activities, and Clinical Efficacy
.
Planta Med
.
2016
Jul
;
82
(
11-12
):
930
41
.
[PubMed]
1439-0221
55.
Santos
S
,
Haslinger
C
,
Mennet
M
,
von Mandach
U
,
Hamburger
M
,
Simões-Wüst
AP
.
Bryophyllum pinnatum enhances the inhibitory effect of atosiban and nifedipine on human myometrial contractility: an in vitro study
.
BMC Complement Altern Med
.
2019
Nov
;
19
(
1
):
292
.
[PubMed]
1472-6882
56.
Santos
S
,
Haslinger
C
,
Klaic
K
,
Faleschini
MT
,
Mennet
M
,
Potterat
O
, et al.
A Bufadienolide-Enriched Fraction of Bryophyllum pinnatum Inhibits Human Myometrial Contractility In Vitro
.
Planta Med
.
2019
Mar
;
85
(
5
):
385
93
.
[PubMed]
1439-0221
57.
Fürer
K
,
Simões-Wüst
AP
,
Winkler
A
,
Amsler
N
,
Schnelle
M
,
von Mandach
U
.
[The Application of Bryophyllum pinnatum Preparations in Obstetrics and Gynaecology – a Multicenter, Prospective Observational Study]
.
Forsch Komplement Med
.
2015
;
22
(
4
):
231
6
.1661-4119
58.
Betschart
C
,
von Mandach
U
,
Seifert
B
,
Scheiner
D
,
Perucchini
D
,
Fink
D
, et al.
Randomized, double-blind placebo-controlled trial with Bryophyllum pinnatum versus placebo for the treatment of overactive bladder in postmenopausal women
.
Phytomedicine
.
2013
Feb
;
20
(
3-4
):
351
8
.
[PubMed]
1618-095X
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