The Chronic and Acute Toxicity of Traditional Medicines Containing Terminalia chebula

Gerelmaa Enebish; Wang Song; Wei Cheng Xi; Anuujin Gantumur; Oyunbaatar Altanbayar; Hirofumi Shimomura; Battogtokh Chimeddorj; Batnairamdal Chuluun; Avarzed Amgalanbaatar

doi:10.3831/KPI.2023.26.1.18

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The Chronic and Acute Toxicity of Traditional Medicines Containing Terminalia chebula

ARONGQIQIGE^1,2, Gerelmaa Enebish¹, Wang Song³, Wei Cheng Xi³, Anuujin Gantumur¹, Oyunbaatar Altanbayar¹, Hirofumi Shimomura⁴, Battogtokh Chimeddorj¹, Batnairamdal Chuluun⁵, Avarzed Amgalanbaatar^6*

¹Department of Microbiology and Infection Prevention Control, School of Biomedicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
²Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
³Inner Mongolia Autonomous Region Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
⁴Department of Organoid Research, KBBM Ltd., Kyoto, Japan
⁵Department of Internal Medicine, International School of Mongolian Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
⁶International Cyber Education Center, Graduate School, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia

Correspondence to: Avarzed Amgalanbaatar
InternationalCyber Education Center, Graduate School, Mongolian National University of Medical Sciences, Zorig Street Sukhbaatar District, Ulaanbaatar 14210, Mongolia
Tel: +976-9916-4258
E-mail: avarzed@mnums.edu.mn

Received: May 13, 2022; Revised: May 21, 2022; Accepted: December 14, 2022

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

J Pharmacopuncture 2023; 26(1): 18-26

Published March 31, 2023 https://doi.org/10.3831/KPI.2023.26.1.18

Abstract

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Abstract
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION
ACKNOWLEDGMENT
CONFLICT OF INTEREST
References

Objectives: Terminalia chebula, the main ingredient of Altan Arur 5, has been used for many years in traditional medicine. This medicine is more effective than other drugs and is used to treat chronic gastritis and gastrointestinal disorders such as peptic ulcers and esophageal reflux. Other ingredients of Altan Arur 5 are Punica granatum (pomegranate), tulip seeds, black balm, and excreta of Trogopterus xanthipes. The main ingredients of T. chebula are antibacterial and analgesic in traditional medicine. Despite having been used for many years and although many studies have been conducted on the beneficial effects of this medicine and its ingredients, the toxicity of Altan Arur 5 has not yet been elucidated. Therefore, we aimed to study the toxicity of Altan Arur 5 to ensure that it is safe to use.
Methods: Acute and chronic toxicity of Altan Arur 5 were assessed in 10 Kunming mice and 8 Sprague-Dawley rats, respectively, in different doses. In the acute toxicity study, Altan Arur 5 was orally administered to Kunming mice in doses of 12 g/kg, 24 g/kg, and 48 g/kg for 14 days. In the chronic toxicity study, it was orally administered to Sprague-Dawley rats in doses of 1.25 g/kg, 2.5 g/kg, and 5 g/kg for 12 weeks.
Results: No significant differences were observed in the relative organ weights for mice treated with Altan Arur 5 compared with those in the control group. Furthermore, no macro- or microstructural changes were noted in the organs of any group.
Conclusion: Our toxicity testing revealed that the traditional medicine Altan Arur 5 has no toxic effects in vivo. Keywords: traditional

Keywords

traditional medicine, altan arur 5, acute toxicity, chronic toxicity, terminalia chebula, punica granatum

INTRODUCTION

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Abstract
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION
ACKNOWLEDGMENT
CONFLICT OF INTEREST
References

Most Asians have been using herbal medicines for many years. However, experimental studies on the herbs used in traditional medicine, especially pharmacodynamic studies, are lacking. Therefore, in vivo and in vitro studies are warranted to evaluate the possible risks, such as organ toxicity and cytotoxic effects; determine appropriate dosage levels; and avoid overdosing during treatment [1].

Herbal medicines used for patients with gastrointestinal disorders in Inner Mongolia, China, include Altan Arur 5, Fluorspar-21, White Pills, Fluorspar Ash, Buteelch-5, Anarbadmaa, and Khadangarid-13. Terminalia chebula, the main ingredient of Altan Arur 5, has been used for many years in traditional medicine. Altan Arur 5 is more effective than other medications and is used to treat chronic gastritis and gastrointestinal disorders, such as peptic ulcers and esophageal reflux [2, 3]. However, it is unknown whether Altan Arur 5 exerts toxic effects in vivo.

Other ingredients of Altan Arur 5 are Punica granatum (pomegranate), tulip seeds, black balm, and excreta of Trogopterus xanthipes. The main ingredient T. chebula is considered to be antibacterial [4, 5] and analgesic [6] in traditional medicine. Pomegranate contains a large number of tannins, which protect the mucous membranes of the stomach and duodenum and are important for wound healing and inflammation [7]. Saponins in tulip seeds prevent inflammation, promote regeneration of the gastric mucosa, protect the liver, and relieve pain [8]. The excreta of Trogopterus xanthipes have anti-inflammatory effects, inhibit gastric acid secretion, improve or regulate blood circulation in the gastric mucosa, and protect the gastric mucosa [9]. In recent years, T. chebula has been studied to inhibit the growth of Bacillus subtilis, Salmonella, Escherichia coli, Staphylococcus epidermidis, S. aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Shigella, and Candida albicans [4, 10-13]. In addition, Altan Arur 5 has antibacterial properties, and studies have investigated its antibacterial activity against Helicobacter pylori, a pathogenic and oncogenic bacterium in the stomach [14]. Pomegranate has medicinal properties, such as supporting digestive function, reducing inflammation, killing parasites, maintaining hemostasis, and exerting protective effects against murine malaria [15, 16].

However, reports on the toxicity or side effect profiles of Altan Arur 5 are lacking. Therefore, we aimed to investigate the acute and chronic toxicity of Altan Arur 5 tablets in mice and rats.

MATERIALS AND METHODS

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Abstract
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION
ACKNOWLEDGMENT
CONFLICT OF INTEREST
References

1. Chemicals

Altan Arur 5 tablets were obtained from the Mongolian Medicine Preparation Room of the Affiliated Hospital of Inner Mongolia University for Nationalities and powdered using a pulverizer. After the pulverization of Altan Arur 5, the powder was filtered through a 100-mesh sieve and dissolved in 0.5% sodium carboxymethylcellulose solution. Altan Arur 5 solution was prepared for each experiment and stored at room temperature.

2. Animals

Acute and chronic toxicities were assessed in 10 Kunming mice and 8 Sprague-Dawley (SD) rats in each group, respectively. Kunming mice and SD rats of specific pathogen-free grade, weighing 18-20 g and 180-200 g, respectively, were purchased from Changchun Yisi Experimental Animal Technology Co., Ltd. (animal license number: SCXK (Kyrgyzstan)-2018-0007). Experimental animals were housed in standardized conditions: accommodated in clean polypropylene cages and maintained in an air-conditioned animal house at 20 ± 2℃, 50-60% humidity, and under a 12 h light/dark cycle, with three or four animals accommodated per cage. The animal cages were cleaned, and the water supply and light were checked daily. The animals were housed in a specific pathogen-free animal house for at least 5 days before the experiments.

3. Acute toxicity tests

Kunming mice were randomly divided into a control and experimental (three doses [12 g/kg, 24 g/kg, and 48 g/kg]) groups, with 10 mice in each group. Before the experiments, the mice were fasted for 12 h and not provided water. The control group was administered distilled water, and the experimental groups were administered Altan Arur 5 dissolved in 0.5% sodium carboxymethylcellulose solution by oral gavage according to intragastric administration techniques. A single dose of Altan Arur 5 was 0.6 mL, which was administered twice a day in the experimental group. Drug toxicity was evaluated immediately after administration for 14 consecutive days to calculate the maximum dose; the dose is equivalent to a multiple of the clinical daily recommended dose.

Multiples of the maximum dose in mice were calculated using the following formula: Multiple of the maximum dose is equal to the maximum dose of each mouse (g) divided by the average weight of mice (g) multiplied by the average weight of a human (60,000 g) divided by the daily dose of humans (g) [17].

The animals were observed for 14 consecutive days for changes in weight, diet, appearance, behavior, secretion, excrement, and death. The dying and dead animals were grossly dissected in time, and other animals were grossly dissected after the end of the observation period. Histopathological examination of the liver, kidney, lung, spleen, and heart was performed to calculate the maximum dose; the dose was equivalent to multiples of clinical daily dosage.

4. Chronic toxicity tests

Thirty-two specific-pathogen–free male SD rats weighing approximately 180-200 g were used for the experiments. The rats were fed and observed for 1 week before the experiment, and those with no abnormalities were used as test animals. The rats were fasted for 12 h before drug administration and were not provided water. The rats were randomly divided into a control and administration groups, each consisting of eight rats. The control group was given distilled water, and the administration group was administered Altan Arur 5 at doses of 1.25 g/kg, 2.5 g/kg, and 5 g/kg [18], respectively, equivalent to 12.5 times, 25 times, and 50 times higher than the clinical dose, dissolved in 0.5% sodium carboxymethylcellulose solution and infused with gavage needle stomach administration, once a day by gavage (2 mL). During the experimental period, the body weight of rats was measured once a week, and the dosage was adjusted according to the new body weight. After administration for 12 weeks, blood was collected from the abdominal aorta of rats for biochemical analysis of chronic toxicity. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), direct bilirubin (DBIL), total bilirubin (TBIL), indirect bilirubin (IBIL), urea, troponin (TP), creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and creatinine kinase (CK) levels were measured using a biochemical automated system (Cobas C311, Roche, Switzerland).

5. Histopathological examination

At the end of the acute and chronic toxicity experiments, the rats and mice were euthanized. The heart, liver, lungs, spleen, and kidneys were removed, and organ weights and microstructural changes were measured. Autopsies were fixed in 10% formalin solution for 48 h. After fixation, the preparations were dehydrated using an alcohol series and cleared using a xylene series. After tissue processing for histopathology, the paraffin-embedded tissues were sectioned at a thickness of 5 mm using a microtome (Leica RM2235, Leica Instruments, Nussloch, Germany) with disposable metal microtome blades (Leica 819, Leica Instruments, Nussloch, Germany). Tissue preparations were stained with hematoxylin and eosin. Images were captured using a light microscope equipped with a camera (Olympus BH-40).

6. Statistical analysis

The results are expressed as mean ± standard deviation of the mean. Data collected from the chronic toxicity results were analyzed using one-way ANOVA within the control, low-, medium-, and high-dose groups, and t-tests within each group. p-values < 0.05 were considered significant. Statistical analysis was performed using SPSS (version 17.0; International Business Machines Corporation, New York, USA).

7. Ethical considerations

This animal study was performed according to the ethical approval of the Research Ethics Committee of Mongolian National University of Medical Sciences No. 2019/0-05, on April 19, 2019. All efforts were made to minimize the number of animals and their suffering. Toxicity testing was performed according to the WHO guidelines and OECD guideline for testing of chemicals, acute toxicity 420, chronic toxicity 452 (OECD 1981), and ARRIVE guidelines U.K. Animals (Scientific Procedures) Act, 1986.

RESULTS

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Abstract
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION
ACKNOWLEDGMENT
CONFLICT OF INTEREST
References

1. Acute toxicity

Acute toxicity was determined for 14 consecutive days during the intake of Altan Arur 5, and changes in animal weight, diet, appearance, behavior, secretions, excrement, death, etc., were evaluated. No mortality was observed in any group during the oral intake of Altan Arur 5, even in mice administered high doses of Altan Arur 5. Body weights increased gradually throughout the study period, and the increases were not significantly different between the control group and 12 g/kg, 24 g/kg, and 48 g/kg dose groups of Altan Arur 5 (p > 0.05). Water intake, food intake, and behavioral changes in the three dose groups were not significantly different from those in the control group. No significant differences were observed in the relative organ weights of mice treated with Altan Arur 5 compared with those in the control group. No macro- and microstructural changes were noted in the organs of all groups by pathological examination, such as the liver, kidney, lung, spleen, and heart, even at doses of 12 g/kg, 24 g/kg, and 48 g/kg (Table 1). Therefore, this study could not detect LD50 in the experiments.

Table 1 . Bodyweight and organ weights of the mice for experiment of acute toxicity.

Weight (gram)	Value	Groups				p value** (between groups)	f-ratio (between groups)

		Control (n-6)	12 g/kg (n-6)	24 g/kg (n-6)	48 g/kg (n-6)
Body	Mean	34.06	32.6	31.6	34.6	0.44	0.94
	STD	2.46	4.18	4.59	1.74
	p value*	-	0.88	0.61	0.99
Liver	Mean	2.1	1.88	1.9	2.24	0.01	4.53
	STD	0.17	0.29	0.14	0.15
	p value*	-	0.24	0.32	0.61
Kidney	Mean	0.44	0.44	0.44	0.46	0.97	0.07
	STD	0.05	0.15	0.08	0.05
	p value*	-	0.00	0.00	0.98
Spleen	Mean	0.16	0.18	0.24	0.2	0.02	4.37
	STD	0.05	0.04	0.05	0
	p value*	-	0.82	0.01	0.33
Lung	Mean	0.22	0.18	0.18	0.22	0.15	2
	STD	0.04	0.04	0.04	0.04
	p value*	-	0.33	0.33	0.00
Heart	Mean	0.12	0.14	0.14	0.2	0.01	4.5
	STD	0.04	0.05	0.05	0
	p value*	-	0.82	0.82	0.01

*p value was analyzed by one-way ANOVA test between control and each group, **p value was analyzed by one-way ANOVA test between groups. STD, standard deviation..

2. Chronic toxicity

Macroscopic examination of the main organs (liver, kidney, lung, heart, and spleen) of the experimental groups revealed no abnormal changes in the color, size, and organ weight compared with the organs of rats in the control group (Table 2). Body weights of the rats did not differ significantly between the groups (Table 3). No histological abnormalities were noted in the microscopic examination of the liver, kidney, lung, heart, and spleen compared with those of rats in the control group (Fig. 1).

Table 2 . Organ weights of the SD rats for experiment of chronic toxicity.

Weight (gram)	Value	Groups				p value** (between groups)	f-ratio (between groups)

		Control (n-8)	Low dose (n-7)	Medium dose (n-8)	High dose (n-6)
Liver	Mean	10.4	12.4	9.6	11.6	0.09	2.3
	STD	1.6	1.7	2.8	2.6
	p value*	-	0.30	0.93	0.71
Kidney	Mean	2.6	2.6	2.5	2.8	0.46	0.89
	STD	0.2	0.3	0.3	0.4
	p value*	-	0.99	0.87	0.79
Spleen	Mean	0.6	0.8	0.7	0.7	0.009	4.73
	STD	0.05	0.1	0.1	0.1
	p value*	-	0.006	0.57	0.40
Lung	Mean	1.3	1.6	1.4	1.4	0.11	2.17
	STD	0.2	0.3	0.2	0.3
	p value*	-	0.09	0.90	0.80
Heart	Mean	1.1	1.1	1.1	1.2	0.73	0.43
	STD	0.1	0.1	0.2	0.2
	p value*	-	0.99	0.92	0.95

*p value was analyzed by one-way ANOVA test between control and each group, **p value was analyzed by one-way ANOVA test between groups. STD, standard deviation..

Table 3 . Body weights of the SD rats for experiment of chronic toxicity.

Body weight (gram)	Value	Groups				p value** (between groups)	f-ratio (between groups)

		Control (n-8)	Low dose (n-7)	Medium dose (n-8)	High dose (n-6)
1 week	Mean	211.3	210.9	211.0	211.0	0.95	0.11
	STD	1.28	1.46	1.19	1.14
	p value*	-	0.94	0.98	0.98
1 month	Mean	332.5	297.9	295.8	311.4	0.04	3.31
	STD	9.96	34.17	29.23	25.64
	p value*	-	0.06	0.05	0.39
2 months	Mean	337.9	376.4	339.4	343.5	0.18	1.73
	STD	13.11	41.08	40.31	45.93
	p value*	-	0.20	0.99	0.99
3 months	Mean	366	423.7	374.3	410.5	0.14	2.02
	STD	22.51	51.98	69.5	57.07
	p value*	-	0.19	0.99	0.40

*p value was analyzed by one-way ANOVA test between control and each group, **p value was analyzed by one-way ANOVA test between groups. STD, standard deviation..

Figure 1.Histological section of major organs from the control and high dose of Altan Arur 5 groups (Hematoxylin-eosin staining, ×40). (a, b) histology of spleen; (c, d) histology of heart; (e, f) histology of kidney; (g, h) histology of lung; (i, j) histology of liver. Figures a, c, e, g and i were control group, figures b, d, f, h and j were high dose group. No significant changes were detected in all groups.

No significant changes were noted in the biochemical parameters for ALT, AST, ALP, BILD2, SBIL3, IBIL, UREAL, TP2, CKMB2, LDHI2, and CK2 levels of rats in the control and Altan Arur 5 administration groups, even at exposure to high doses of Altan Arur 5 (Table 4). No significant differences in biochemical parameters were observed among the four groups (low, medium, high dose, and control) using one-way ANOVA.

Table 4 . Biochemical analysis for chronic toxicity of Altan Arur 5 in rats.

Biochemical parameters** (mean)	Value	Groups				p value*** (between groups)	f-ratio (between groups)

		Control (n-8)	Low dose (n-7)	Medium dose (n-8)	High dose (n-6)
ALP	Mean	127.24	114.80	119.05	116.25	0.00	13.68
	STD	1.92	5.89	4.41	3.32
	p value*	-	0.00	0.00	0.00
ALT	Mean	49.79	39.77	41.91	51.43	0.32	1.22
	STD	16.71	8.71	9.15	18.48
	p value*	-	0.52	0.70	0.99
AST	Mean	150.41	134.51	154.40	150.58	0.43	0.95
	STD	17.06	20.09	31.50	25.96
	p value*	-	0.61	0.99	0.00
DBIL	Mean	0.91	0.93	1.05	–33.78	0.29	1.32
	STD	0.36	0.22	0.31	85.15
	p value*	-	0.00	0.00	0.33
TBIL	Mean	175.31	178.86	151.43	186.97	0.94	0.13
	STD	93.08	88.00	155.08	109.19
	p value*	-	0.99	0.98	0.99
IBIL	Mean	174.40	177.93	150.38	220.60	0.76	0.39
	STD	93.03	88.04	154.92	131.97
	p value*	-	0.99	0.98	0.88
Urea	Mean	5.83	6.41	6.66	21.97	0.20	1.65
	STD	0.67	1.39	0.95	34.32
	p value*	-	0.99	0.99	0.22
TP	Mean	83.15	78.41	84.23	85.32	0.49	0.83
	STD	4.16	11.65	6.88	11.32
	p value*	-	0.73	0.99	0.96
CK-MB	Mean	1,652.29	1,495.96	1,633.69	1,692.22	0.75	0.41
	STD	360.38	252.67	369.61	393.28
	p value*	-	0.83	0.99	0.99
LDH	Mean	2,128.88	2,212.43	2,262.88	2,190.83	0.93	0.14
	STD	372.70	354.55	522.23	319.87
	p value*	-	0.98	0.92	0.99
CK	Mean	991.13	825.86	1,214.38	1,553.00	0.05	2.92
	STD	233.99	193.75	595.44	697.67
	p value*	-	0.91	0.81	0.13

*p value was analyzed by one-way ANOVA test between control and each group, **Biochemical parameters- Alkaline phosphatase ALP, alanine aminotransferase ALT, aspartate aminotransferase AST, direct bilirubin DBIL, total bilirubin TBIL, indirect bilirubin IBIL, Urea, troponin TP, creatinine kinase-MB CK-MB, Lactate Dehydrogenase LDH and creatinine kinase CK, ***p value was analyzed by one-way ANOVA test between groups. STD, standard deviation..

Furthermore, examination of biochemical, macro, and microscopic characteristics reported no significant abnormalities in the rats. Thus, Altan Arur 5 may be a nontoxic, biologically active substance in herbal medicine.

DISCUSSION

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MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION
ACKNOWLEDGMENT
CONFLICT OF INTEREST
References

Altan Arur 5 contains five herbal ingredients, one of which is a fruit and the other three are herbs. Altan Arur 5 has been used to treat gastrointestinal diseases and in traditional medicine for many years. One of these five ingredients is myrobalan (international name: T. chebula), which is more effective in the treatment of bacterial infections and some kinds of pain, but it is not common in nature [6]. The next most common ingredient is pomegranate, which contains a high number of tannins and has good anti-inflammatory and mucosal protective properties [7]. Tulip seeds prevent inflammation, promote the regeneration of the gastric mucosa, protect the liver, and relieve pain. The excreta of Trogopterus xanthipes is known as the complex-toothed flying squirrel, which also has an anti-inflammatory effect, inhibits gastric acid secretion, improves blood circulation in the gastric mucosa, and protects the gastric mucosa [8, 9]. All five ingredients of Altan Arur 5 are the main ingredients in most medicines or are used directly in food, indicating that they are less likely to be toxic.

In their study, Sireeratawong et al. [19] found that dried fruits of T. chebula had no toxic effect on rats, even when orally administered at very high doses or at a single dose of 5,000 mg/kg body weight. No toxicity related to body weight, internal organ weight, general behaviors, and internal organs was noted in the rats, indicating no pathological abnormalities. The authors concluded that the aqueous extract of T. chebula is practically nontoxic after an acute exposure in rats [19]. In our study, Altan Arur 5 showed no toxic effects in mice and rats. Several studies on T. chebula have reported no toxic effects in rats and mice at doses of ≥ 5,000 kg; however, those studies could not determine the LD50 because the animals did not die even after oral administration of Altan Arur 5 at > 5,000 mg/kg body weight [20-25]. These findings indicate that T. chebula has no toxic effects on animals such as mice and rats.

In a previous study, the LD50 was determined as 731 mg/kg in mice after the intraperitoneal administration of Punica granatum hydroalcoholic extract [26]. Mehru et al. [27] reported that the P. granatum peel extract had an LD50 of > 1 mg/mL, tested using a brine shrimp assay. Tripathi et al. [28] found that administration of 0.5, 1.9, and 7.5 mg/kg of pomegranate peel extract to BALB/c mice did not cause death. Furthermore, no animals showed behavioral changes, toxic signs or symptoms, or pathological abnormalities. In a study by Patel et al. [29], the LD50 of the extract after oral administration to rats and mice was found to be > 5 g/kg body weight. These studies indicate that the extract of P. granatum does not have a toxic effect on animals.

A previous study found that the LD50 was 2.57 g/kg in BALB/c mice and that the essential oil could only be considered moderately toxic [30]. Bounihi et al. studied the acute toxicity of Melissa officinalis essential oil in mice and found that its LD50 value is > 2 g/kg, and no significant changes were noted in animal behavior, general appearance, or any signs of toxicity after a 2 g/kg administration [31].

The toxicity of tulip seeds was not comparable to that reported in other studies because of the lack of research on this ingredient. In this study, we reported novel findings on the acute and chronic toxicity of Altan Arur 5 in mice and rats; therefore, it cannot be effectively compared with findings from other studies. The LD50 could not be determined in the rats because even when Altan Arur 5 was administered at doses 50 times higher than the clinical dose, no significant changes in clinical findings were noted, even after administration for 3 months. Furthermore, a blood chemical examination performed to evaluate any toxic effects on the liver and kidneys reported minor changes that remained within the normal range. Pathological examinations performed to further confirm damage to the organs or tissues also revealed no macroscopic or microscopic changes in any of the treated rats. These results suggest that oral administration of Altan Arur 5 in rats does not produce acute or chronic toxicity.

CONCLUSION

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References

The lack of adverse effects of the Altan Arur 5 extract following its administration in mice and rats suggests that this herbal medicine is safe in vivo. However, we could not determine whether this medicine affects humans. Therefore, further studies should be conducted in this area.

ACKNOWLEDGMENT

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ACKNOWLEDGMENT
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We are grateful for the collaboration of the Department of Microbiology and Infection Prevention Control, School of Biomedicine, MNUMS and Inner Mongolia Autonomous Region Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Inner Mongolia University for Nationalities.

CONFLICT OF INTEREST

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The authors declare that there are no conflicts of interest regarding the publication of this paper.

References

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References

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