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VOLUME
Vol.05 Issue03 2025
PAGE NO.
46-53
10.37547/ijmscr/Volume05Issue03-09
The study of acute toxity and efficacy evaluation of
bioactive compounds for constipation
Nufuzakhan Adilova
Tashkent Medical Academy, Tashkent, Uzbekistan
Malika Foziljonova
Pharmaceutical Education and Research Institute, Tashkent, Uzbekistan
Zilola Abdujalilova
Pharmaceutical Education and Research Institute, Tashkent, Uzbekistan
Abdusattor Tojiboyev
Tashkent Medical Academy, Tashkent, Uzbekistan
Jasurbek Kholmatov
Tashkent Medical Academy, Tashkent, Uzbekistan
Received:
29 January 2025;
Accepted:
28 February 2025;
Published:
31 March 2025
Abstract:
Constipation is a prevalent gastrointestinal disorder that significantly impacts patients' quality of life.
The present study aims to evaluate the acute toxicity and efficacy of selected bioactive compounds for the
treatment of constipation. Acute toxicity was assessed using standardized in vivo models to determine the safety
profile of the bioactive compounds. The therapeutic efficacy was evaluated through pharmacodynamic and
biochemical analyses, focusing on bowel motility, stool frequency, and intestinal microbiota modulation.
Preliminary findings suggest that the tested compounds exhibit favorable safety margins and potent laxative
effects, potentially offering a novel approach for constipation management. Further clinical studies are required
to validate their long-term safety and effectiveness.
Keywords:
Garcinia cambogia, senna, chitosan, green coffee, constipation, bioactive compounds, acute toxicity,
subchronic toxicity,white mice.
Introduction:
The World Health Organisation is
currently facing a global problem with the increasing
number of pathological conditions in the human div
due to metabolic disorders. Bioactive substances
derived from natural plants have become a popular
treatment for improving metabolism in the human
div. As we know, in recent years, the number of types
of drugs derived from bioactive substances obtained
from plants has increased in the pharmaceutical
market. The primary reason for this is the widespread
awareness of the long-term health benefits of natural
ingredients by consumers. As demand for plant-derived
medicines grows worldwide, many countries are
increasingly concentrating on producing new types of
plant-based medicines.
Senna (Cassia angustifolia) is a plant of the bean family.
This branched shrub, which is abundant throughout
southern India, can reach a height of 1.8 m. Extracts of
this plant are used in folk medicine to treat some
gastrointestinal
disorders.
hydroxyanthrazine
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glycosides, also known as sennosids, have been
reported to stimulate the peristalsis of the colon and
change the absorption and secretion of the colon
resulting in fluid accumulation and excretion.b
Researchers 2 have suggested that a normal daily dose
of senna for adults consists of two tablets containing 18
mg of sennoside per 90 mg tablet. Other studies 4 have
shown that sennosids cause diarrhea due to changes in
the intestinal tract. The laxative effect of this natural
product is due to its anthraquinone glycosides.
[1,2,3,4,5]
Garcinia cambogia extract is quite promising for the
correction of serum and tissue cortisol levels. It is
known that the fruit of Garcinia cambogia includes
organic acids, benzophenones, pectins, polyphenolic
compounds,
xanthocymol
and
isooxantocimol,
cambonine, kamboginol, carbohydrates, molds and
other biologically active substances; The content of
hydroxylic acid in fruits reaches 65%. Numerous studies
have shown that Garcinia cambogia drugs can prevent
obesity, having hypolipidemic, antidiabetic, anti-
inflammatory and antioxidant activity. [6,7,8].
Chitosan is a natural cationic polysaccharide obtained
by the deacetylation of chitin [9]. The chemical reaction
occurs as a result of the substitution of parts of the N-
aceti
c groups in chitin, which are β
- (1-4)-2-amino-2-
deoxy-D-
glycopyranose and β
- (1-4)-Acetamide-2-
deoxy-D-glicopyranosis [10]. Chitosan demonstrates
good biocompatibility, biodegradability, permeability,
low cell toxicity [ 11 ,12], anti-inflammatory, analgesic
and blood-stopping action [13,14]. In addition, chitosan
exhibits antibacterial activity by interacting protonated
amino groups with the negative charges of bacterial cell
membrane and cell wall [ 15 ,16] and binding to
bacterial DNA, which avoids transcription and gene
translation. These properties secrete chitosan among
other biomaterials in wound healing [17, 18]. The
antibacterial activity of chitosan can be improved by
chemical modification of its structure, such as inclusion
of amino groups [19, 20, 21, 22].
The composition of compounds in the following ratio
was considered as a bioactive additive against
constipation:
Composition of biologically active substance No. 1:
• Garcinia Cambodia –
400 mg
• Chitosan –
150 mg
• Senna –
50 mg
• Green coffe
e
–
10 mg
Composition of biologically active substance 2:
• Garcinia Cambodia –
350mg
• Chitosan –
200 mg
• Senna –
40 mg
• Green coffee –
20 mg
Composition of biologically active substance 3:
• Garcinia Cambodia –
450 mg
• Chitosan –
100 mg
• Senna –
55 mg
• Green coffee –
5 mg
Composition of biologically active substance 4:
• Garcinia Cambodia –
400 mg
• Chitosan –
100 mg
• Senna –
70 mg
• Green coffee –
40 mg
METHODS
The study of acute toxic interaction described in the
literature with the general method adopted, disposable
into the stomach by sending special zond and toxic
studied by determining the class was [23].
Type and number of animals: 72 white sterile male mice
weighing 19-21 g, quarantined for 14 days, were used
in the experiment.
Preparation of aqueous solutions: 12.2% aqueous
solution of tested biologically active substances (1
capsule + 5 ml H2O) was prepared for acute toxicity
study and determination of LD50.
The laxative effect of biologically active substances 1, 2,
3, 4 was studied on 24 white rats with a mass of 190-
210 g.
RESULTS
The following information was obtained for
biologically active substance №1:
1-group (dose 2440 mg/kg): biologically active
substances for a day on the slopes remained active
after being introduced, if it did not track changes in
conduct. The usual mode of wool and skin,
o'zgarishlarsiz, denial of food and water, not a day,
diarrhea in mice were observed during the four slopes
of the death did not take place. On the second day and
the next tracking and pathological changes in
physiological indicators during the period in the
conduct of the slopes aredi. Stay on track by those
behind the normal growth and development water and
feed consumption ofdi. The slopes of the death of 14
days for the quality isadi.
2-group (dose 3660 mg/kg): substance is active after
being introduced for a day on the slopes, track changes
in the conduct did not. The usual mode of wool and
skin, no changes, diarrhea were observed for 3 days,
food and wateris to reject, the slopes of death did not
take place. On the fourth day and the next tracking and
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pathological changes in physiological indicators during
the period in the conduct of the slopes aredi. Stay on
track by those behind the normal growth and
development water and feed consumption ofdi. The
slopes of death for 14 days did not monitor the quality.
Table № 1shows that mice did not die within 14 days.
Biologically active substances №1 of acute toxic
Table 1
Number of animals
Biologically active substance №1
Size
Sending way
Results
mg/kg
ml
1
2440
0.4
os
0/6
2
3660
0,6
os
0/6
3
4880
0.8
os
0/6
LD
50
>4880 mg/kg
Group 3 was treated with a biologically active
substance (dose 4880 mg/kg) which caused short-term
flaccidity and immobility in mice, but it disappeared
after 60-90 minutes. 3-4 hours prior to the first day of
the experiment, the animals did not consume any food
or water. All animals had diarrhea for 3 days, despite
the active behavior and normal physiological
indicators. For the fourth day and period of
observation, no changes in behavior and other
physiological
indicators
were
observed,
mice
consumed food and water willingly, their reactions to
light and sound exposure remained normal, no mouse
death was observed for 14 days.
The following information is gathered for substance
№2.
The biologically active substance administered to mice
in Group 1 (2440 mg/kg dose) remained active for 24
hours without any behavioral changes observed. The
wool and skin were in a normal condition without any
changes, food and water were not denied, and four
mice had diarrhea for one day, but they did not die. No
pathological changes in the mice' behavior or
physiological indicators were observed during the
second day and throughout the observation period.
Normal water and food consumption did not cause
growth and development delays. There were no mice
deaths within 14 days.
Group 2 (dose 3660 mg/kg): mice were active within
24 hours of administration, no behavioural changes
were observed. The condition of the wool and skin was
normal without any changes. For three days, there was
diarrhea, but food and water were not refused, and
mice did not die. The behavioral and physiological
indicators of mice did not change on the fourth day and
during the observation period. The absence of normal
water and food intake, growth, and developmental
delays was observed. Table № 2 shows that mice did
not die within 14 days.
Biologically active substances №2 of acute toxic
Table 2
Number of animals
Biologically
active substances №2
Size
Sending way
Results
mg/kg
ml
1
2440
0.4
os
0/6
2
3660
0,6
os
0/6
3
4880
0.8
os
0/6
LD
50
>4880 mg/kg
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Group 3 was given a biologically active substance (dose
4880 mg/kg) which caused short-term flaccidity and
immobility in the mice, but it disappeared within 60 to
120 minutes. Before the first day of the experiment, the
animals did not eat or drink for 4-5 hours. All animals
had diarrhea for 3 days, despite the active behavior and
normal physiological indicators. For the fourth day and
during the observation period, no changes in behavior
and other physiological indicators of mice were
observed, mice willingly ate food and water, their
reactions to light and sound exposure remained
normal, no mouse death was observed for 14 days.
The following information is gathered for substance
№3.
Group 1 (2440 mg/kg dose): Mice maintained activity
for 24 hours after administering the biologically active
substance, no behavioural changes were observed. The
condition of the wool and skin was normal, without
changes, food and water were not refused, four mice
had diarrhea for one day, there was no mouse death.
During the second day and throughout the observation
period, no pathological changes in the behavior and
physiological indicators of the mice were observed.
Normal water and food consumption, growth and
development delays were not observed. There was no
death of mice within 14 days.
Group 2 (dose 3660 mg/kg): mice were active within 24
hours of administration, no behavioural changes were
observed. The condition of the wool and skin was
normal, without changes, for 3 days there was
diarrhea, food and water were not refused, mice did
not die. Pathological changes in the behavior and
physiological indicators of mice for the fourth day and
during the observation period were not detected.
Normal water and food intake, growth and
development delays were not observed. Mortality of
mice within 14 days was not observed.
Group 3 (dose 4880 mg/kg): Following the
administration of a biologically active substance, the
mice exhibited temporary flaccidity and immobility,
which resolved within 60 to 90 minutes. Prior to the
commencement of the experiment, the animals
refrained from consuming food and water for a
duration of 2 to 4 hours. Their behavior was
characterized as active, and physiological parameters
remained within normal ranges; however, all subjects
experienced diarrhea for a period of 4 days. By the
fourth day and throughout the subsequent observation
period, no alterations in behavior or other physiological
parameters were noted. The mice resumed normal
feeding and drinking habits, their responses to light and
sound stimuli remained unaffected, and no fatalities
were recorded over the 14-day observation period.
Table 1 indicates that the mice survived for a duration
of 14 days without any fatalities
Biologically active substances №3 of acute toxic
Table 3
Number of animals
Biologically
active substances №3
Size
Sending way
Results
mg/kg
ml
1
2440
0.4
os
0/6
2
3660
0,6
os
0/6
3
4880
0.8
os
0/6
LD
50
>4880 mg/kg
The following information is gathered for substance
№4.
In Group 1, which received a dosage of 2440 mg/kg, the
mice exhibited sustained activity for a full 24 hours
following the administration of the biologically active
substance, with no notable behavioral alterations
recorded. The condition of their fur and skin remained
normal, and there were no changes in their eating or
drinking habits. Although four mice experienced
diarrhea for a single day, there were no fatalities.
Throughout the second day and the entire observation
period, no pathological changes in behavior or
physiological parameters were noted. Additionally,
there were no delays in food and water consumption,
growth, or development, and no mouse deaths
occurred over the 14-day period.
In Group 2, which was administered a dose of 3660
mg/kg, the mice displayed activity for 24 hours post-
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administration, with no behavioral changes detected.
Their fur and skin condition remained stable, and they
did not refuse food or water. Diarrhea was observed in
the mice for a duration of three days, yet there were no
instances of mortality. No pathological changes in
behavior or physiological indicators were identified by
the fourth day or throughout the observation period.
Furthermore, normal consumption of food and water
was maintained, and there were no delays in growth or
development, with no recorded deaths among the mice
after 14 days.
In Group 3 (dose 4880 mg/kg), the administration of a
biologically active substance resulted in a temporary
state of flaccidity and immobility in the mice, which
resolved within 60 to 90 minutes. Prior to the
commencement of the experiment, the animals
refrained from consuming food and water for a
duration of 3 to 4 hours. During the initial phase, the
mice exhibited active behavior, and their physiological
parameters remained within normal limits; however,
all subjects experienced diarrhea for a period of three
days. From the fourth day onward and throughout the
observation period, no alterations in behavior or other
physiological parameters were noted. The mice
resumed normal consumption of food and water, and
their responses to light and sound stimuli remained
unaffected. Notably, there were no recorded fatalities
among the mice over the 14-day observation period.
These findings indicate that the acute toxic dose of the
biologically active substance exceeds the LD50
threshold of 4880 mg/kg. Table 4 indicates that the
mice survived for a duration of 14 days without any
fatalities.
Biologically active substances №4 of acute toxic
Table 4
Number of animals
Biologically
active substances №4
Size
Sending way
Results
mg/kg
ml
1
2440
0.4
os
0/6
2
3660
0,6
os
0/6
3
4880
0.8
os
0/6
LD
50
>4880 mg/kg
Efficiencies evaluation
Research on the laxative effects of biologically active
substance-1 indicated that the stool mass was elevated
by 1.92 times relative to the control group. Meanwhile,
animals treated with biologically active substance-2
showed a 1.73-fold increase in stool mass. Additionally,
those receiving biologically active substance-3
experienced a 1.6 times increase. In the fourth group,
the content of the biologically active substance was
found to have increased by 1.4 times. These findings
are summarized in table 5.
Laxative activity of the analysed biologically active substances 1, 2, 3, 4
Table 5
Weight, g
Dose
Feces of the mass, g,
mg/kg
1 l/100g
Control group + purified water
1
189,3± 3.7
-
2
1,91 ± 0,14
Biologically active substance-1
2
186,6 ± 6.7
140
2
3,68± 0,3
R<0.05 up to
Biologically active substance-2
3
185,3 ± 4,9
140
2
3,31
±
0,34
R<0.05 up to
Biological active ingredients-3
4
187 ± 5,4
140
2
3
±
0,27
R<0.05 up to
Biologically active substance-4
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5
189,8 ± 6.1
140
2
2,68
±
0,36
R<0.05 up to
The experimental animals were categorized into five
groups, each consisting of six individuals. The
administration of biologically active substances
occurred in the following sequence:
Control group: A single oral dose of 2 ml of purified
water was provided;
Experimental group: A single oral dose of 50 mg/kg of a
1.0% solution of biologically active substance-1
(Uzbekistan) was administered;
Experimental group: A single oral dose of 50 mg/kg of a
1.0% solution of biologically active substance-2
(Uzbekistan) was administered;
Experimental group: A single oral dose of 50 mg/kg of a
1.0% solution of biologically active substance-3
(Uzbekistan) was administered;
Experimental group: A single oral dose of 50 mg/kg of
a 1.0% solution of biologically active substance-4
(Uzbekistan) was administered.
The experimental animals in each group were housed
in specialized containers, and fecal samples were
collected twice, with an interval of eight hours. The
weight of the fecal mass was determined by calculating
the difference between the weight of the empty
container and that of the container filled with feces.
The results obtained were analyzed using the
"STATISTICA" software in accordance with Student's
paired t-test
DISCUSSION
The acute toxicity experiment of the biologically active
substance 1,2,3,4 was conducted in four series. In the
first series, white mice were divided into 3 groups of 6
individuals. The mice in each group were fed 12.2% of
the biologically active solution into their stomachs as
follows:
1 group (6 mice) - per os 2440 mg/kg (0.4 ml);
Group 2 (6 mice) - per os 3660 mg/kg (0.6 ml);
Group 3 (6 mice) - at os4880 mg/kg (0.8 ml).
In the second series, the mice in each group were
injected with 12.2% of a biologically active solution into
their stomachs as follows:
1 group (6 mice) - per os 2440 mg/kg (0.4 ml);
Group 2 (6 mice) - per os 3660 mg/kg (0.6 ml);
Group 3 (6 mice) - at os4880 mg/kg (0.8 ml).
In the third series, mice in each group were fed 12.2%
aqueous solution of biologically active substance 3 into
the stomach as follows:
1 group (6 mice) - per os 2440 mg/kg (0.4 ml);
Group 2 (6 mice) - per os 3660 mg/kg (0.6 ml);
Group 3 (6 mice) - per os 4880 mg/kg (0.8 ml).
In the fourth series, the mice in each group were
injected with 12.2% of the aqueous solution of a
biologically active substance into their stomachs as
follows:
Group 1 (6 mice) - per os 2440 mg/kg (0.4 ml);
Group 2 (6 mice) - per os 3660 mg/kg (0.6 ml);
Group 3 (6 mice) - per os 4880 mg/kg (0.8 ml).
Observation: on the first day of the experiment animals
in the experimental group were observed hourly, in
laboratory conditions, by appearance (state of
feathers, mucous membranes and so on). .k.; functional
state (survival in the experiment, general state,
coordination and death) and record of behavior. In the
following days and daily for 2 weeks under vivarium
conditions, changes in the general state and activity of
animals of all groups, behavior characteristics, pain
reactions, sound and light effects, frequency and depth
of breathing movements, heartbeat, feather and skin
condition, fecal mass quantity and consistency, urine,
div mass and other indicators.[24]
The experimental animals were categorized into five
groups, each consisting of six individuals. The
administration of biologically active substances
occurred in the following sequence:
Control group: A single oral dose of 2 ml of purified
water was provided;
Experimental group: A single oral dose of 50 mg/kg of a
1.0% solution of biologically active substance-1
(Uzbekistan) was administered;
Experimental group: A single oral dose of 50 mg/kg of a
1.0% solution of biologically active substance-2
(Uzbekistan) was administered;
Experimental group: A single oral dose of 50 mg/kg of a
1.0% solution of biologically active substance-3
(Uzbekistan) was administered;
Experimental group: A single oral dose of 50 mg/kg of a
1.0% solution of biologically active substance-4
(Uzbekistan) was administered.
The experimental animals in each group were housed
in specialized containers, and fecal samples were
collected twice, with an interval of eight hours. The
weight of the fecal mass was determined by calculating
the difference between the weight of the empty
container and that of the container filled with feces.
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
The results obtained were analyzed using the
"STATISTICA" software in accordance with Student's
paired t-test [25]
CONCLUSION
The analysis of the specific activities of biological active
substances numbered 1, 2, 3, and 4 has determined
that biological active substance No. 1 has a high degree
of intravascular activity. It is recommended to keep
using this substance as the primary laxative.
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