Home Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
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Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions

  • Soufiane Drioua , Mouna Ameggouz , Amine Assouguem EMAIL logo , Mohammed Kara , Riaz Ullah , Ahmed Bari , Rachid Lahlali , Hafize Fidan , Otman El-Guourrami , Fatima Zahra Benkhouili , Yagoubi Maamar , Hanane Benzeid and Anass Doukkali
Published/Copyright: June 26, 2024
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Open Life Sciences
From the journal Open Life Sciences Volume 19 Issue 1

Abstract

Chenopodium ambrosioides aerial parts have been historically employed in traditional medicine for addressing various ailments such as headaches, abdominal discomfort, joint issues, and respiratory disorders, alongside treatments for lice and warts. This study aimed to conduct a comprehensive phytochemical analysis of C. ambrosioides and assess the acute and subacute toxicity of oral treatments using fractions in preclinical trials. Spectrophotometric analysis via LC–MS/MS was used to characterize the plant’s chemical composition. Acute toxicity evaluation followed Organisation for Economic Co-operation and Development code 42 guidelines, conducted on adult male and female Wistar strain mice. Subsequently, Swiss mice were divided into six groups for the subacute toxicity study, receiving oral doses of 200 mg/kg extracts and fractions for 28 days. Daily observations and biochemical analyses were performed, with LC–MS/MS revealing a diverse array of compounds including organic acids, flavonoids, phenolic acids, rutin, hesperidin, nicotiflorine, and fumaric acid. Results indicated no lethality or alterations in body weight in treated groups, though some organ weight changes were noted. Biochemical analyses demonstrated values within the normal range for all groups, suggesting that the treatments did not induce adverse effects. Acute and subacute treatments with fractions did not result in lethality or toxic alterations at therapeutic doses, implying the safety of the product at appropriate levels. This study underscores the potential of C. ambrosioides as a safe therapeutic option warranting further exploration.

Keywords: Chenopodium ambrosioides ; LC–MS/MS; phytochemical; toxicity

1 Introduction

The utilization of medicinal plants as primary healthcare solutions in developing nations is deeply entrenched, primarily due to financial constraints and accessibility issues. This reliance on traditional medicine, underscored by UNESCO’s emphasis on the accessibility and financial limitations of populations in need, has prompted the World Health Organization to advocate for a reevaluation of traditional medicine to better address healthcare needs in resource-limited regions [1,2]. Ethnobotanical studies, particularly prevalent in Africa, have meticulously documented numerous medicinal plant species, with over 5,000 species recognized, including 761 with medicinal properties, and 1,421 distinct medicinal formulations found specifically in Côte d’Ivoire [3,4]. However, despite this resurgence of interest in phytotherapy, there is a noticeable emphasis on therapeutic efficacy over the toxicological aspects within the field’s advancements.

Chenopodium ambrosioides L., originating from Central America, has attracted considerable attention for its historical use across various cultures. It has been employed as an anti-helminthic, anti-inflammatory, anti-tumoral, and wound-healing agent, particularly noted for its traditional use in treating Leishmania-induced skin ulcers.

While these traditional practices highlight the significant role of medicinal plants in providing healthcare in resource-limited settings, they also underscore the critical need for rigorous scientific inquiry. Despite their historical and cultural significance, there is a noticeable lack of comprehensive toxicological studies on these remedies [5,6]. This gap in understanding has prompted calls for further scientific investigations, particularly in understanding the potential toxicological aspects of these remedies. Such endeavors aim to bridge traditional knowledge with modern scientific rigor, ensuring the safe and effective integration of these medicinal plants into formal healthcare systems [7,8].

Phytochemicals, acknowledged as bioactive compounds, constitute a broad spectrum of plant secondary metabolites comprising numerous natural substances. This encompasses a diverse array of compounds, such as phenols, phenolic acids, flavonoids, tannins, saponins, alkaloids, steroids, steroids, lignins, glycosides, phenylpropanoid glycerols, and isoprene-derived terpenoids (isoprenoids) [9].

Several biological activities of C. ambrosioides have been scientifically confirmed, including its anti-helminthic effects against various parasites and anti-inflammatory properties. However, reports of genotoxic effects and fatalities from overdoses highlight the importance of understanding the toxicological mechanisms underlying its usage [10,11,12].

Considering these considerations, our study aims to elucidate the specific biological activities and potential health benefits associated with phytochemicals from C. ambrosioides [13]. Through the preparation of four fractions using solvents of increasing polarity and subsequent evaluation of their acute and subacute toxicity following Organisation for Economic Co-operation and Development (OECD) 423 guidelines, we seek to contribute to our understanding of the therapeutic potential of this plant. By assessing its toxicity, we aim to provide valuable insights into its safety profile, thus encouraging further exploration of natural remedies in healthcare [14,15].

Ultimately, the literature review takes the reader from what is known about a subject to the gaps that remain in our understanding, underpinning the study that follows [16]. This research endeavors to shed light on the therapeutic potential of C. ambrosioides while also highlighting the importance of understanding its toxicological profile for safe and effective integration into healthcare practices.

2 Materials and methods

2.1 Plant material

The entirety of the C. ambrosioides plant (Chenopodiaceae) was collected between May and July 2021 in the Rabat region of Morocco (Geographical coordinates: 33.970878, −6.814212). Botanical authentication of the plant was conducted by the floristics team at the Scientific Institute of Rabat. This specific specimen has been deposited in the herbarium of the Scientific Institute of Rabat and bears the sample number RAB113708. Samples were dried in the laboratory at room temperature before undergoing extraction. The dried plant material was pulverized using a Binatone Moulinex mixer.

2.2 Preparation of fractions

To prepare the fractions, dried aerial parts (50 g) of C. ambrosioides underwent Soxhlet extraction using cyclohexane. After dry evaporation, the cyclohexane fraction was obtained. The remaining residue was dried in an oven for 24 h and subjected to hydroalcoholic maceration (ethanol/water: 50/50). Following filtration and ethanol evaporation, successive liquid–liquid separations were performed on the aqueous phase using solvents of increasing polarity (ethyl acetate and n-butanol) and repeated three times for each solvent (100 ml). After dry evaporation, fractions of ethyl acetate and n-butanol were obtained.

The extraction rate was calculated using the following formula:

R = ( M i / M ) × 100 ,

where M i is the mass of the extract and M is the mass of the initial plant material.

2.3 Conditions of mass spectrometer and chromatography

We utilized an ultra-high-performance liquid chromatography (UHPLC) Shimadzu-Nexera coupled with a tandem mass spectrometer for the quantitative evaluation of 53 phytochemicals. The reverse-phase UHPLC system was equipped with an automatic sampler (SIL-30AC model), a column oven (CTO-10ASvp model), binary pumps (LC-30AD model), and a degasser (DGU-20A3R model).

Chromatographic conditions were optimized to achieve optimal separation of the 53 phytochemicals and overcome suppression effects. Several columns were tested and applied, including the Agilent Poroshell 120 EC-C18 model (150 mm × 2.1 mm, 2.7 µm) and the RP-C18 Inertsil ODS-4 model (100 mm × 2.1 mm, 2 µm). Different mobile phases such as acetonitrile and methanol were used, along with various mobile phase additives such as ammonium formate, formic acid, ammonium acetate, and acetic acid. Column temperatures varied between 25, 30, 35, and 40°C until optimal conditions were attained.

Ultimately, chromatographic separation was performed on an analytical reverse-phase column, Agilent Poroshell 120 EC-C18 (150 mm × 2.1 mm, 2.7 µm). The column temperature was maintained at 40°C. The eluent gradient consisted of eluent A (water + 5 mM ammonium formate + 0.1% formic acid) and eluent B (methanol + 5 mM ammonium formate + 0.1% formic acid). The following gradient elution profile was used: 20–100% B (0–25 min), 100% B (25–35 min), and 20% B (35–45 min). Additionally, the solvent flow rate and injection volume were set at 0.5 mL/min and 5 µL, respectively.

Mass spectrometry detection was conducted using a Shimadzu LCMS-8040 tandem mass spectrometer equipped with an electrospray ionization (ESI) source operating in both negative and positive ionization modes. LC–ESI-MS/MS data were acquired and processed using LabSolutions software (Shimadzu).

The multiple reaction monitoring (MRM) mode was employed for phytochemical quantification. The MRM method was optimized to selectively detect and quantify phytochemical compounds based on screening specific precursor ion transitions of phytochemicals to fragment ions. Collision energies were optimized to generate optimal fragmentation of phytochemicals and maximum transmission of desired product ions.

The MS operating conditions were as follows: drying gas flow rate (N2), 15 L/min; nebulizing gas flow rate (N2), 3 L/min; desolvation line temperature, 250°C; heating block temperature, 400°C, and interface temperature, 350°C.

These coupled UHPLC–chromatograph mass spectrometer conditions enabled high-quality data acquisition for the quantitative analysis of the 53 phytochemicals, crucial for precise sample evaluation. Fine adjustments of chromatographic and spectrometric parameters optimized method sensitivity and selectivity, ensuring reliable and reproducible results.

2.4 Evolution of acute toxicity

The acute toxicity of the studied fractions of C. ambrosioides was assessed in adult male and female Wistar strain mice (Mus musculus) following OECD guidelines, code 42, weighing between 21 and 36 g. The animals were sourced from the Faculty of Medicine and Pharmacy’s Animal Facility in Rabat, under standard experimental conditions. They were marked twice a week to maintain their identity within each batch. The animals were divided into multiple groups and housed in polypropylene cages with wood shavings, each labeled with batch name, treatment details, and experimentation dates.

For 7 days preceding each experiment, the mice underwent an adaptation period where they had unrestricted access to water ad libitum and standard feed, under controlled light and temperature conditions (12-h light/dark cycle at 27 ± 2°C). The experiments were conducted following internationally accepted guidelines for evaluating the safety and efficacy of herbal-based medicines [17].

2.5 Subacute toxicity test

The subacute oral toxicity study was conducted following the guidelines set by the (OECD 407, 2008). Animals were randomly divided into six groups, each consisting of ten animals. Group I, designated as the control group, received distilled water (vehicle) orally for a duration of 28 days. Groups II, III, IV, and V received a daily oral dose of 200 mg/kg of the fractions for a continuous 28-day period. The body weight of the subjects was recorded weekly throughout the study period.

2.5.1 Determination of biochemical parameters:

Following the experimental period, blood samples were collected from the caudal vein using heparinized tubes for hematological studies. Non-heparinized tubes were used to obtain serum through centrifugation at 3,000 rpm for 10 min, intended for subsequent biochemical analyses.

Hematological parameters, including total hemoglobin, red blood cell count, white blood cell count, and platelet count, were determined using a fully automated analyzer (Architect c8000, Clinical Chemistry System, Chicago, IL, USA).

Simultaneously, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea (UR), creatinine (CR), cholesterol, triacylglycerols, high-density lipoproteins, and low-density lipoproteins (LDL) were precisely determined.

3 Results

The chemical composition of the plant was determined using the LC–MS/MS method. The results of the identified compounds within the plant are presented in Table 1 and Figure 1. This table showcases the various chemical compounds present in the plant and their respective percentages in the overall composition (Figure 2).

Table 1

Compounds identified in extracts and fractions of C. ambrosioides via LC–MS/MS

Compound name FCH FB FA
Fumaric acid — 0.094 0.139
Aconitic acid — 0.018 0.025
Protocatechuic acid 0.039 0.477 0.061
4-OH benzoic acid — — —
Caffeic acid — 0.014 —
p-Coumaric acid — 0.219 0.037
Salicylic acid — 0.076 —
Acacetin 0.036 0.03 0.023
Vanillin 0.114 —
Quercitrin acid — — 2.934
Gallic acid — 0.013 —
Gentisic acid — 0.147 —
Chlorogenic acid — 0.206 —
Rutin — 4.1 —
isoquercitrin — 0.182 —
Hesperidin — 2.1 —
Quercitrin — 0.039 —
Astragalin — 0.059 —
Nicotiflorin — 1.805 —
Quercetin — 0.127 —
Kaempferol — 0.019 —
Syringic aldehyde 0.059 — —
Figure 1 (a–c) Chromatograms of the cyclohexanolic fraction, butanolic fraction, and remaining AF of C. ambrosioides, respectively.
Figure 1

(a–c) Chromatograms of the cyclohexanolic fraction, butanolic fraction, and remaining AF of C. ambrosioides, respectively.

Figure 2 Body weight changes in the Ammi majus L. treated and control groups.
Figure 2

Body weight changes in the Ammi majus L. treated and control groups.

We employed gas chromatography coupled with mass spectrometry (LC–MS/MS) to identify and measure compounds present in distinct fractions of C. ambrosioides. The outcomes of this analysis yield crucial insights into bioactive compounds potentially responsible for the plant’s medicinal properties.

The cyclohexanolic fraction (FCH) (chloroform) exhibited the presence of protocatechuic acid, vanillin, syringaldehyde, and acetin. These compounds have demonstrated various health benefits, such as antioxidant and anti-inflammatory effects. Their detection in the FCH highlights its promise as a source of bioactive compounds warranting further investigation for medicinal applications.

In the butanolic fraction (FB), a diverse array of compounds was observed, including organic acids, flavonoids, and phenolic acids. Notably, rutin, hesperidin, and nicotiflorine, flavonoids recognized for their antioxidant properties, were detected in significant quantities, accentuating the potential health advantages of this fraction. Furthermore, the presence of quinic acid, gallic acid, and chlorogenic acid contributes to the antioxidant potential of the BF.

Remarkably, the aqueous fraction (FA) also contained compounds like quinic acid, fumaric acid, aconitic acid, and assorted phenolic compounds. This convergence of compounds among the fractions emphasizes the intricate nature of C. ambrosioides and emphasizes the necessity for further research to comprehend the synergistic interactions among these compounds.

In summary, LC–MS/MS analysis of fractions derived from C. ambrosioides unveiled a diverse and abundant chemical composition. The identification of organic acids, phenolic compounds, flavonoids, and fatty acids suggests the potential health and culinary benefits of this plant. These findings serve as a foundation for further investigation aimed at elucidating the specific bioactive properties and potential therapeutic applications of C. ambrosioides. Moreover, these results underscore the significance of exploring natural sources of bioactive compounds that can positively impact human health and overall well-being.

3.1 Acute toxicity

An acute toxicity study of fractions from C. ambrosioides was assessed in mice, following the OECD guidelines, code 423, for testing of chemical substances adopted in March 1996. The results of this investigation concerning the acute toxicity of orally administered plant extracts were encouraging. No deaths or clinical signs of toxicity were observed following administration of doses at 300 and 2,000 mg/kg of body weight. All animals survived the 14-day observation period, indicating that the LD50 (median lethal dose) is greater than 2,000 mg/kg. In accordance with the Globally Harmonized System of Classification and Labelling of Chemicals, the extracts can be considered non-toxic via oral administration.

Furthermore, monitoring the weight evolution of mice treated with fractions of C. ambrosioides during the observation period revealed notable stability in body weight, particularly after 14 days. This finding confirms that the fractions of C. ambrosioides have no toxic effects on the basic behavior of treated mice. These results are promising regarding the potential use of these extracts in various applications, emphasizing their safety when administered orally.

3.2 Subacute toxicity

3.2.1 Animal body weight

Table 1 displays the variation in body weight of groups treated with fractions of C. ambrosioides at 200 mg/kg during the subacute toxicity study. This table is crucial in evaluating the impact of these substances on the subjects’ body weight. Here is an analysis of this data:

First, it is important to note that the table presents data for different weeks (weeks 1, 2, 3, and 4) and for different groups (control, FCH, FEA, FB, and FA). Each group appears to have been exposed to a dose of 200 mg/kg of C. ambrosioides, albeit in different fractions.

Upon examining the data, it is observed that the average body weight of mice in the control group was around 25.75 g in week 1 and slightly increased over subsequent weeks. Comparatively, the groups treated with fractions of C. ambrosioides also show an increase in body weight over the weeks. However, it is noteworthy that the variations between the different groups and weeks are relatively small.

Overall, these data indicate that exposure to 200 mg/kg of C. ambrosioides in fraction form did not result in significant variations in body weight compared to the control group. Furthermore, the minor fluctuation in body weight suggests that these substances did not have major toxic effects on the growth or development of mice during this subacute study period. This reinforces the notion that these fractions are well tolerated by mice at this dose and duration.

However, it is important to note that these variations in body weight are not necessarily indicative of toxicity. Other factors such as appetite, digestion, and metabolism can influence weight gain. Additionally, these results must be interpreted within the context of the study, considering other toxicity parameters such as biochemical and histopathological indicators (Table 2).

Table 2

Variation in body weight of groups treated with C. ambrosioides fractions at 200 mg/kg (g) in the subacute toxicity study

Control F CH F AE F B F A
Week 1 25.75 ± 1.18 29.5 ± 1.04 30.11 ± 0.5 29.32 ± 0.7 27.01 ± 0.12
Week 2 26.43 ± 1.34 29.7 ± 1.05 30.72 ± 1.2 30.1 ± 1.5 27.91 ± 1.03
Week 3 27.43 ± 1.12 30.51 ± 0. 9 31.52 ± 0.9 30.9 ± 1.07 29.03 ± 1.13
Week 4 27.43 ± 0.56 31.33 ± 0.53 32.2 ± 1.2 31.22 ± 0.3 30.04 ± 0.11

Les valeurs sont exprimées en moyenne ± SD (n = 6).

3.3 Relative weight of organs

Table 3 displays the relative weights of vital organs for the treated and control groups at 200 mg/kg, providing further details on the toxicological effects of C. ambrosioides fractions.

Table 3

Relative weights of vital organs in treated and control groups in the subacute toxicity study of C. ambrosioides fractions

Organs Control F CH F AE F B F A
Liver 1.63 ± 0.09 1.27 ± 0. 62 1.34 ± 0.2 1.6 ± 0.44 1.53 ± 0.19
Kidneys 0.37 ± 0.04 0.47 ± 0.06 0.4 ± 0.12 0.41 ± 0.16 0.4 ± 0.09
Lung 0.32 ± 0.09 0.29 ± 0.09 0.31 ± 0.03 0.3 ± 0.02 0.33 ± 0.05
Spleen 0.12 ± 0.01 0.23 ± 0.11 0.23 ± 0.05 0.24 ± 0.23 0.27 ± 0.28
Pancreas 0.09 ± 0.06 0.14 ± 0.05 0.13 ± 0.02 0.14 ± 0.04 0.14 ± 0.02

Values are expressed as mean ± SD (n = 6) and analyzed by one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test.

Table 3 provides an overview of the variations in relative organ weights among different treatment groups and the control group. The examined organs include the liver, kidneys, lungs, heart, and pancreas. These organs are crucial for proper bodily functions, and any alteration in their weight can be an indicator of the potential toxicity of C. ambrosioides extracts.

Regarding the liver, the largest organ on the table, a slight decrease in relative weight is observed in the fraction A (F AE) and cyclohexane fraction (F CH) administration groups compared to the control group. This decrease may suggest some influence of the fractions on the liver, although the changes are not significant.

Concerning the kidneys, the relative weight remains relatively stable in all groups, indicating that C. ambrosioides fractions have no significant effect on this vital organ. For the lungs, there is also stability in relative weight across all groups, indicating an absence of notable effects on this organ.

The spleen, a central vital organ, shows more pronounced variations. The fractions seem to cause a slight increase in the spleen’s relative weight, which could indicate some influence on this organ. However, it is important to note that these variations remain within acceptable limits.

Regarding the pancreas, there is a slight increase in relative weight in all fraction groups, indicating some influence of the fractions on this organ. Overall, it appears that C. ambrosioides fractions have minimal effects on the vital organs examined in this subacute toxicity study. The variations in relative weight are generally slight and remain within acceptable limits. This suggests that the doses administered in this study did not result in major toxicity to these vital organs. However, it is important to note that toxicity may also depend on exposure time and doses administered.

The presented results are specific to a subacute study, and longer-term studies could reveal other potential effects. In conclusion, the results from this table indicate that C. ambrosioides fractions seem to have minimal impact on the vital organs studied in the context of this subacute toxicity study.

The results presented in Table 4 offer a more in-depth examination of the biochemical parameters in the control group and groups treated with fractions of C. ambrosioides at a dose of 200 mg/kg.

Table 4

Biochemical parameters of the control group and groups treated with C. ambrosioides fractions at 200 mg/kg for subacute toxicity study

Parameter Control F CH F AE F B F A
AST (U/dL) 48.40 ± 6.21 50.05 ± 5.12 48.79 ± 5.44 46.53 ± 7.32 49.13 ± 6.01
ALT (U/dL) 103.20 ± 8.7 104. 77 ± 3.23 105.9 ± 3.92 106.21 ± 5.6 105.21 ± 1.8
CR (mg/dL) 1.06 ± 0.30 1.55 ± 2.77 1.44 ± 0.5 1.55 ± 0.38 1.66 ± 0.41
UR (g/dL) 0.59 ± 0.07 0.52 ± 0.2 0.6 ± 0.1 0.56 ± 0.03 0.53 ± 0.1
TP (g/dL) 62.88 ± 0.22 58. 58 ± 4.54 60.72 ± 6.54 65.48 ± 5.2 62.33 ± 4.06
TC (mg/dL) 127.6 ± 8.70 129.83 ± 8.99 124.05 ± 5.15 125.36 ± 6.9 126.06 ± 7.1
HDL (mg/dL) 7.36 ± 0.06 7.23 ± 0.54 7.28 ± 1.61 6.54 ± 0. 59 6.9 ± 1. 09
LDL (mg/dL) 60.15 ± 1.01 61.2 ± 5.43 61.31 ± 3.5 62.03 ± 4.23 63.23 ± 3.14
VLDL (mg/dL) 26.26 ± 0.15 28.36 ± 0.98 25. 81 ± 2.03 26.07 ± 0.34 27.23 ± 1.12

3.4 AST and ALT – liver enzymes

The liver is a multifunctional organ responsible for various biochemical processes in the body, and enzymes like AST and ALT are crucial indicators of liver health. The results reveal an intriguing trend in the levels of these enzymes among the treatment groups.

AST and ALT: AST and ALT are important liver enzymes. The table shows significant reductions (P < 0.05) in AST and ALT levels in the treated groups (F CH, F AE, F B, F A) compared to the control group. These results suggest that these extracts do not affect liver function, indicating a potential reduction in hepatic toxicity.

However, it is essential to emphasize the need for further in-depth statistical analysis to confirm the significance of these results and elucidate the exact mechanisms underlying this hepatoprotective effect.

3.5 CR and UR – markers of renal function

CR and UR are commonly used as markers to assess renal 10 function. Regarding urea (UR) levels, which are indicators of kidney function, no significant difference was observed between the control group and the treated groups. This indicates that the extracts and fractions did not negatively affect kidney function.

Indeed, it should be noted that there was a consistent increase in CR levels in all groups treated with the different extracts and fractions of Chenopodium ambrosioides. This elevation in CR levels may indicate a potential effect on kidney function associated with the administration of these substances. Although the precise mechanisms underlying this observation need to be elucidated, such consistent alterations in creatinine levels across multiple treatment groups warrant careful examination.

3.6 Total proteins (TP)

TP are crucial constituents of blood and play an essential role in maintaining various physiological functions. In this study, group EI shows a substantial increase in TP levels compared to the control group, and this increase is statistically significant (P < 0.05). Conversely, the F CH group presents a statistically significant decrease (P < 0.05) in TP levels.

These results deserve further investigation to understand the factors influencing these variations. The significant decrease in TP observed in F CH could be due to reduced protein synthesis or increased protein degradation.

The changes in TP levels are intriguing and underline the need for continued research on the mechanisms responsible for these alterations. Understanding the underlying reasons for these variations can provide valuable insights into the potential impact of treatments on protein metabolism.

3.7 Total cholesterol (TC), high-density lipoprotein (HDL), LDL, and very-low-density lipoproteins (VLDL) – cholesterol profile

Cholesterol is a vital biomarker in evaluating cardiovascular health. TC levels in the treatment groups do not significantly differ (P < 0.05) from those in the control group. It is noteworthy that TC levels in all groups fall within the typical physiological range. This suggests that the treatments, although not inducing substantial changes, did not lead to cholesterol levels considered abnormal.

LDL levels show variations, but there is no significant trend. This suggests that these fractions do not have a major effect on lipoproteins associated with cardiovascular diseases. However, it is essential to emphasize that levels of HDL, often referred to as “good” cholesterol, remain relatively stable in all groups without statistically significant variations. This stability in HDL levels can be considered positive for cardiovascular health.

Additionally, VLDL are another marker associated with cardiovascular health. It is crucial to note that values across all groups remain within the normal range, indicating that the treatments did not induce adverse effects related to cholesterol levels.

4 Discussion

C. ambrosioides, a member of the Chenopodiaceae family, has sparked keen interest due to its potential medicinal properties. This plant is traditionally known for its use in various herbal remedies. It is essential to assess its safety profile, encompassing evaluations of both acute and subacute toxicity, to understand its viability for therapeutic applications.

First, it is noteworthy that the fractions exhibit a diverse array of compounds, ranging from organic acids to flavonoids and phenolic acids. This diversity suggests the complexity of the plant’s chemical profile and hints at the multifaceted nature of its potential medicinal properties.

One compound of interest is fumaric acid, which is detected in both the FB and FA but not in the FCH. Fumaric acid is known for its antioxidant properties and potential therapeutic effects, particularly in the treatment of psoriasis. Its presence in the fractions indicates the potential contribution of C. ambrosioides to antioxidant activity.

Another notable finding is the presence of various phenolic acids, such as caffeic acid, p-coumaric acid, and gallic acid, across different fractions. Phenolic acids are renowned for their antioxidant, anti-inflammatory, and anticancer properties. Their presence underscores the potential health benefits associated with C. ambrosioides consumption.

Furthermore, flavonoids like rutin, hesperidin, and quercetin are detected in the fractions, particularly in the BF and AF. Flavonoids are well known for their diverse pharmacological activities, including antioxidant, anti-inflammatory, antiviral, and anticancer effects. The abundance of flavonoids in the fractions suggests that C. ambrosioides may possess significant therapeutic potential.

Additionally, the presence of other bioactive compounds such as acacetin, nicotiflorin, and quercitrin acid further enriches the chemical profile of the fractions. These compounds have been associated with various health benefits, ranging from cardiovascular protection to anti-inflammatory effects.

The results from the acute toxicity assessment provided encouraging information regarding the safety of C. ambrosioides fractions. No deaths or signs of toxicity were observed at doses up to 2,000 mg/kg, indicating that the LD50 is greater than 2,000 mg/kg. This finding is significant, especially considering the potential therapeutic applications of this plant.

In accordance with OECD guidelines, the plant fractions are considered non-toxic when administered orally. This aligns with the expectation that many plant fractions can be well-tolerated at moderate to high doses. Such findings can reinforce the use of C. ambrosioides in various therapeutic applications, ranging from traditional medicine to modern pharmacopeia.

However, it is important to remember that acute toxicity assessments have limitations. They provide valuable initial indications of a substance’s safety but do not integrate potential long-term or cumulative effects.

Subacute toxicity studies offer a more detailed perspective on the effects of C. ambrosioides fractions, especially when administered over an extended period. These studies evaluated various parameters, including body weight, relative organ weight, and biochemical parameters, to obtain a comprehensive understanding of the plant’s impact.

Maintaining stable body weight within treated groups over a 4-week period suggests that the fractions, at a dose of 200 mg/kg, did not significantly affect overall health and development in mice. These results are reassuring for subacute applications.

When examining relative organ weights, no significant differences were observed in vital organs such as the liver, kidneys, lungs, spleen, and pancreas. Slight variations were noted but were not considered significant. These results indicate that C. ambrosioides extracts have minimal effects on the relative weight of these crucial organs, further reinforcing their safety.

The biochemical evaluations of the subacute toxicity study explored liver and kidney function, as well as lipid profiles. The results of AST and ALT levels, which are liver enzymes, are particularly intriguing. The groups receiving the extracts showed reduced levels of AST and ALT, with the reduction being statistically significant. This suggests that the fractions may have hepatoprotective properties, potentially attenuating liver damage or stress. The potential hepatoprotective effect of these fractions is a significant discovery and may pave the way for further research into their application in liver-related conditions.

However, it is essential to recognize that the reduction in AST and ALT levels, while promising, requires further investigations to establish the precise mechanisms involved and their clinical implications. Moreover, while the results of this study suggest hepatoprotection, they do not entirely eliminate the need for comprehensive safety evaluations, especially in scenarios of long-term or chronic exposure.

The subacute toxicity study also evaluated parameters related to kidney function, such as creatinine (CR) and urea (UR) levels. We observed a consistent increase in creatinine levels in all treated groups, suggesting a potential influence on kidney function. This raises concerns about the safety of Chenopodium ambrosioides extracts and fractions regarding their long-term effects on kidney function.

The results related to lipid profiles raise important questions. Although the levels remain within the normal range, these results highlight the importance of in-depth research into the cardiovascular implications of C. ambrosioides fractions.

These findings open new perspectives in the field of medicinal plant research. C. ambrosioides, with its promising safety profile and hepatoprotective properties, offers potential for various therapeutic applications. However, caution is warranted as further research is essential to unlock its full therapeutic potential and understand the long-term implications. The safety of natural remedies, such as fractions of C. ambrosioides, must be rigorously evaluated, considering the growing interest in herbal medicine and natural products.

The essential oil of C. ambrosioides at a concentration higher than 35 μg/mL has shown cytotoxicity and neurotoxicity towards G-749 cells, normal human fibroblasts, with an IC50 of 207.1 ± 4.4 μg/mL (Soares et al.) [18]. Meanwhile, a study conducted by Buckle [19] revealed that C. ambrosioides itself is neurotoxic with a narrow therapeutic range; the toxicity was attributed to the presence of camphor and ascaridole. Another study by Monzote et al. [20] found that the toxic effects of caryophyllene oxide and carvacrol present in C. ambrosioides may be mediated by the inhibition of complex I in mitochondrial electron transport chains, while the toxicity of ascaridole towards mammalian mitochondrial oxidative phosphorylation depends on the presence of ferrous iron (Fe2+).

5 Conclusion

Some botanical substances may demonstrate systemic toxicity with prolonged exposure, including reduced body mass, altered behavior, and hematological and biochemical changes. These risks often arise from plant components inducing hepatic and renal toxicity. In our investigation, fractions extracted from C. ambrosioides using increasingly polar solvents aimed to pinpoint specific compounds responsible for potential toxicity. Remarkably, the acute toxicity study at a dosage of 2,000 mg/kg showed no mortality among treated mice. However, marginal shifts in organ weight observed in the subacute toxicity study at 200 mg/kg were deemed non-toxic. Notably, no macroscopic or microscopic alterations were detected in the organs, and AST levels remained unchanged, indicating an absence of hepatic toxicity. Furthermore, the treatment did not affect cholesterol levels, suggesting an intact lipid balance in the mice.

Subacute treatment with these fractions resulted in minimal deviations within the treated groups. These slight changes may be associated with disruptions in kidney and liver function. However, observed alterations in the context of the subacute study do not constitute toxic effects. This investigation highlights that despite minor variations, C. ambrosioides fractions exhibit a relatively benign impact, without inducing severe or demonstrable toxicity within the observed parameters. These findings contribute to understanding the safety profile of C. ambrosioides fractions, advocating for a cautious approach due to potential associations with kidney and liver function, albeit without significant pathological changes.

Future studies should focus on elucidating the specific mechanisms underlying the observed effects and exploring the potential therapeutic advantages of natural plant extracts from C. ambrosioides. Understanding these mechanisms can inform the development of safer and more effective botanical-based treatments.

Acknowledgments

The authors wish to thank Researchers Supporting Project Number (RSP2024R346) at King Saud University Riyadh Saudi Arabia for financial support.

  1. Funding information: This research work is supported by researchers supporting project number (RSP2024R346) at King Saud University Riyadh Saudi Arabia.

  2. Author contributions: S.D., M.A.: data collection, data curation, analysis and methodology; A.A., M.K., R.U., A.B., R.L., H.F., O.E., F.B., Y.M., H.B., A.D.: writing – original draft preparation, review and editing. All authors have read and agreed to the published version of the manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2023-12-03
Revised: 2024-03-13
Accepted: 2024-05-17
Published Online: 2024-06-26

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/biol-2022-0895
Keywords for this article
Chenopodium ambrosioides; LC–MS/MS; phytochemical; toxicity
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
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  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
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  25. Current state of research on copper complexes in the treatment of breast cancer
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  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
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