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. 2022 Jul 12;14(7):475.
doi: 10.3390/toxins14070475.

Evaluation of Acute and Subacute Toxicity and LC-MS/MS Compositional Alkaloid Determination of the Hydroethanolic Extract of Dysphania ambrosioides (L.) Mosyakin and Clemants Flowers

Fahd Kandsi  1 , Fatima Zahra Lafdil  1 , Amine Elbouzidi  2 , Saliha Bouknana  1 , Achraf Miry  3 , Mohamed Addi  2 , Raffaele Conte  4 , Christophe Hano  5 , Nadia Gseyra  1
Affiliations

Evaluation of Acute and Subacute Toxicity and LC-MS/MS Compositional Alkaloid Determination of the Hydroethanolic Extract of Dysphania ambrosioides (L.) Mosyakin and Clemants Flowers

Fahd Kandsi et al. Toxins (Basel). .

Abstract

Dysphania ambrosioides (L.) Mosyakin and Clemants is a medicinal plant that has traditionally been used to cure a range of diseases. There has been no thorough investigation of the potential toxicity of this plant. The objective of this study is to assess the acute and subacute toxicity of D. ambrosioides hydroethanolic extract (DAHE), as well as it alkaloids composition, utilizing LC-MS/MS analysis. An in silico approach was applied to determine pharmacokinetic parameters and to predict the toxicity of D. ambrosioides identified alkaloids. A 14-day treatment with a single oral dose of 1-7 g/kg was carried out to investigate acute toxicity. DAHE was given orally at dosages of 5, 50, and 500 mg/kg for 15 days in the subacute toxicity investigation, and body weight and biochemical parameters were evaluated. Livers, kidneys, lungs, and heart were examined histologically. Chromatographic investigation revealed the existence of nine alkaloids, with N-formylnorgalanthamine being the most prevalent. The oral LD50 value of DAHE was found to be 5000 mg/kg in an acute toxicity study. No variations were observed with respect to food intake, water consumption, mortality, or body and organ weight in the subacute toxicity study. On the other hand, DAHE (500 mg/kg) significantly enhanced alanineaminotransferase, aspartate aminotransferase, and urea. Liver and kidney histological examinations revealed modest infiltration of hepatocyte trabeculae by inflammatory cells in the liver and slight alteration in the kidney histoarchitecture. According to our findings, DAHE exhibits low to moderate toxicity.

Keywords: ADMET analysis; Dysphania ambrosioides; LC-MS/MS; Mexican tea; acute toxicity; alkaloids; in silico; subacute toxicity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
BOILED-Egg predicting model for blood–brain barrier permeability and intestinal absorption of the molecules: (1) trisphaeridine, (2) galanthamine, (3) crinine, (4) demethylmaritidine, (5) anhydrolycorine, (6) nor-galanthamine, (7) N-formylnorgalanthamine, (8) peramine, and (9) ergovaline.
Figure 2
Figure 2
The effect of DAHE on the relative weight of organs in mice. The data are shown as mean ± standard error of the mean (six animals per group). ns: non-significant; no significant difference was found when comparing treated groups to the control group.
Figure 3
Figure 3
Changes in body weight in rats treated with DAHE during the 15-day subacute toxicity study. The results are presented as the mean ± SEM (n = 6). ns: non-significant.
Figure 4
Figure 4
Effect of subacute oral administration of DAHE on (A) AST (U/L) and (B) ALT in serum. Values are presented as the means ± SEM. When compared to the control group, there were significant differences. ns: non-significant, ∗∗ p < 0.01.
Figure 5
Figure 5
Total cholesterol (A) and triglycerides (B) after a subacute oral dose of DAHE. Data are presented as means and standard deviations (SEM). When compared to the control group, there were no significant differences. ns: non-significant.
Figure 6
Figure 6
The effect of oral administration of DAHE on uric acid (A), urea (B), and creatinine (C) in treated rats. Data are presented as mean ± SEM. When compared to the control group, there were significant differences. ns: non-significant, * p < 0.05 and *** p < 0.001.
Figure 7
Figure 7
Effect of subacute oral administration of DAHE on total protein (A), total bilirubin (B), and albumin (C) in rats. ns: non-significant.
Figure 8
Figure 8
Effect of subacute oral administration of DAHE on plasma glucose levels in rats. ns: non-significant.
Figure 9
Figure 9
Liver histopathology. Light micrographs of liver sections of different treatment groups. The treatment groups are represented by the numbers on the photos. (A) untreated rats, (B) rats treated with5 mg/kg DAHE, (C) rats treated with 50 mg/kg DAHE, and (D) rats treated with 500 mg/kg DAHE. Red arrows = inflammatory cells (granulocytes and lymphocytes).White scale bar = 1.03 mm.
Figure 10
Figure 10
Histopathology of the kidney. Light micrographs of liver slices of different treatment groups. The treatment groups are represented by the numbers on the photos. (A′) untreated rats, (B′) rats treated with 5 mg/kg DAHE, (C′) rats treated with 50 mg/kg DAHE, and (D′) rats treated with 500 mg/kg DAHE. Red arrow = decrease in glomerulus cells; Black star = expansion of the Bowman space. Black scale bar = 1.03 mm.
Figure 11
Figure 11
Histopathology of the heart. Light micrographs of heart slices of different treatment groups. The treatment groups are represented by the numbers on the photos. (A″) Untreated rats, (B″) rats given the DAHE (5 mg/kg), (C″) rats treated with the DAHE (50 mg/kg), and (D″) rats treated with the DAHE (500 mg/kg).Black scale bar = 1.03 mm.
Figure 12
Figure 12
Histopathology of the lung. Lung slice light micrographs of different treatment groups. The treatment groups are denoted by numbers on the photographs. (A‴), rats treated with 5 mg/kg DAHE, (B‴) control rats, (C‴) rats treated with 50 mg/kg DAHE, and (D‴) rats treated with 500 mg/kg DAHE. Black scale bar = 0.51 mm.
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