This research investigates the therapeutic potential of aqueous Chlorophytum comosum extract in managing bilirubin metabolism disturbances in laboratory animals with experimentally induced toxic hepatitis. The study compared the efficacy of three treatment approaches: Chlorophytum comosum extract monotherapy, standard vitamin therapy (including vitamins B₁, B₂, B₆, B₁₂, PP, E, and C), and a combination of both treatments. The experiment involved four groups of Chinchilla breed rabbits, with toxic hepatitis induced by a single subcutaneous injection of carbon tetrachloride (CCl₄). Blood samples were collected daily to measure total and direct bilirubin levels using the «Lakhema» test method. Key findings revealed that CCl₄ intoxication significantly increased bilirubin levels, primarily affecting direct bilirubin. The highest bilirubin concentrations were observed on the 4th day in untreated rabbits. By the tenth day of the research, the combination therapy group notably showed the most effective reduction in bilirubin levels. The research highlights the potential of Chlorophytum comosum extract as a promising hepatoprotective agent, showing comparable efficacy to standard vitamin therapy and demonstrating additive effects when combined. These findings suggest that Chlorophytum comosum extract could serve as a valuable adjunct in managing toxic liver injuries, offering a natural alternative to conventional treatments. The study emphasizes the importance of further research into the hepatoprotective properties of plant-based remedies, particularly in addressing liver damage caused by environmental toxins and industrial pollutants. The results contribute to the growing body of evidence supporting the therapeutic potential of natural compounds in liver disease management.
Introduction
Liver damage due to acute exogenous intoxications represents a significant clinical challenge, affecting more than 30% of patients with various forms of poisoning (Berumen et al., 2021; Torgersen et al., 2024). The global increase in environmental pollution and industrial activities has led to a rise in hepatotoxic exposures (Di Martino et al., 2023; Cunningham et al., 2024). Various industrial and agricultural toxins enter the human body through air and food, causing widespread liver damage (Alengebawy et al., 2021; Siddiqui et al., 2023).
Toxic liver injury can result from exposure to numerous chemicals, including pharmaceuticals, when accidentally ingested or administered (Philips et al., 2023; Jaeschke & Ramachandran, 2024). Industrial accidents and occupational hazards often lead to hepatotoxicity due to improper handling or accidental exposure to toxic substances (Gurley et al., 2022). Among these substances, carbon tetrachloride (CCl₄) is particularly noteworthy due to its widespread industrial use as a solvent for oils, fats, and rubber, as well as in fat and alkaloid extraction processes (Unsal et al., 2020; Fareed et al., 2024). The metabolic transformations of CCl₄ form the basis of its potent hepatotoxic effect, making it a relevant model for studying liver damage mechanisms (Márquez-Quiroga et al., 2022). When metabolized in the liver, CCl₄ generates toxic metabolites that disrupt cellular function and integrity, leading to liver injury (Shi et al., 2023).
The poor effectiveness of current liver damage treatment methods calls for the investigation of other therapeutic modalities. In recent decades, there has been growing interest in natural compounds with hepatoprotective properties (Sadovoy et al., 2017). Numerous studies have demonstrated the beneficial effects of various plant-derived extracts in protecting liver function and aiding recovery from hepatotoxicity (Mittal et al., 2025). Among natural compounds with potential hepatoprotective properties, Chlorophytum comosum (spider plant) has gained particular attention due to its rich biochemical composition and traditional medicinal use (Azami et al., 2022).
Chlorophytum comosum contains a complex mixture of bioactive compounds that contribute to its therapeutic potential (Adhami et al., 2021). The plant is particularly rich in flavonoids, which are known for their antioxidant and anti-inflammatory properties. Additionally, it contains coriic acids, mucilages, resins, and essential vitamins (C, PP, and E), all of which play crucial roles in liver protection and regeneration (Rzhepakovsky et al., 2022). The plant's long history of usage in traditional medicine, especially in Tibetan hepatitis treatment, offers a solid basis for current scientific research (Vakele et al., 2022). Its multifaceted chemical composition suggests a potential mechanism of action that involves several therapeutic pathways (Padayachee et al., 2021). Flavonoids may help reduce oxidative stress and inflammation, while vitamins contribute to cellular repair and metabolic support (Kavya et al., 2024). The unique combination of active components in Chlorophytum comosum makes it a promising candidate for hepatoprotective therapy (Adi Wicaksono et al., 2023). Flavonoids and coriic acids may help stabilize cell membranes and inhibit lipid peroxidation, while mucilages and resins could support detoxification processes (Zhang et al., 2024). The presence of essential vitamins further enhances its potential to support liver function and regeneration (Imtiaz et al., 2024). This diverse biochemical profile, combined with its historical medicinal use, justifies further investigation into Chlorophytum comosum as a potential therapeutic agent for liver protection (Zia-Ur-Rehman et al., 2023). Its ability to address multiple aspects of liver damage through different mechanisms of action makes it an attractive candidate for developing new hepatoprotective treatments.
This study focuses on investigating the therapeutic potential of Chlorophytum comosum extract in managing liver damage induced by toxic agents. By examining its effects on bilirubin metabolism, we aim to contribute to the development of novel, natural approaches to liver protection and recovery. The research is particularly timely given the increasing prevalence of liver diseases worldwide and the need for safe, effective, and accessible treatment options. Understanding the mechanisms by which natural compounds like Chlorophytum comosum extract can protect liver function may open new avenues for managing liver damage caused by environmental and industrial toxins.
Materials and Methods
The study was conducted in strict accordance with international guidelines for laboratory animal care and use. The experimental protocol was approved by the institutional ethics committee (Protocol No. 13-24/2024).
Experimental Animals
Male Chinchilla breed rabbits aged 5–6 months and weighing between 2.5 and 3 kilograms were selected for the study. The animals were randomly divided into four experimental groups, with each group containing six rabbits. All animals were housed under standardized conditions with controlled temperature, humidity, and lighting to minimize external influences on the experimental results (Nair & Jacob, 2016).
Experimental Design
The study employed a controlled experimental design to investigate the effects of different treatment modalities on liver function. The groups were defined as follows: the control group received no treatment following CCl₄ exposure, while the other groups received either Chlorophytum comosum extract, vitamin therapy, or a combination of both treatments.
Induction of Toxic Hepatitis
Toxic hepatitis was induced by administering a single subcutaneous injection of carbon tetrachloride (CCl₄) at a dose of 0.2 milliliters per kilogram of body weight. This dosage was selected based on preliminary studies to ensure reproducible liver damage while avoiding lethality. The injection was performed under aseptic conditions to prevent any secondary infections.
Treatment Administration
The Chlorophytum comosum extract was administered orally via a feeding tube three times daily at a dose of 2 milliliters per kilogram of body weight, starting three hours after CCl₄ administration. Vitamin therapy included a combination of vitamins B₁, B₂, B₆, B₁₂, PP, E, and C, administered daily at specific times to optimize absorption and efficacy (Wald et al., 2022).
Sample Collection and Processing
Blood samples were collected daily from the marginal ear vein using the Zapadnyuk method (Thompson et al., 2002). The procedure was performed under strict aseptic conditions to prevent contamination. Serum was obtained by refrigerating the blood for 20 minutes and then centrifuging it at 3000 revolutions per minute for 15 minutes. The resulting serum was stored under controlled temperature conditions until analysis.
Biochemical Analysis
Bilirubin levels were determined using the «Lakhema» test method, which is based on the diazo reaction of bilirubin with diazotized sulfanilic acid (Berska et al., 2020). This method allows for the measurement of both total bilirubin (including unconjugated and direct fractions) and direct bilirubin separately, providing valuable insights into liver function and bile production.
Statistical Analysis
Statistical analysis was performed using Student’s t-test for comparison between groups and the small sample method for intra-group analysis. Outliers were identified and excluded using the Chauvenet criterion. Statistical significance was set at p < 0.05 to ensure reliable interpretation of the results.
Quality Control
Rigorous quality control measures were implemented throughout the study to ensure data reliability. These included regular calibration of laboratory equipment, use of certified reagents, duplicate measurements for critical parameters, and blinded sample analysis to minimize potential biases. All laboratory procedures adhered strictly to established standard operating procedures.
Results and Discussion
Toxic liver damage induced by a single administration of CCl4 resulted in significant alterations in bile formation intensity and composition, accompanied by severe disturbances in pigment metabolism. This was evidenced by elevated levels of bilirubin fractions in the blood serum of rabbits. However, the increase was not uniform for total and direct bilirubin.
Analysis of the obtained data revealed that total bilirubin levels relative to control values (intact animals) increased by approximately 50% across all study groups just 3 hours after CCl4 administration. Direct bilirubin levels showed an even more pronounced elevation, exceeding baseline values by over 280%. This indicated a significant increase in blood bilirubin concentration, primarily due to direct bilirubin (Macías-García et al., 2019).
The elevated levels of conjugated bilirubin in the blood suggested impaired cellular bilirubin excretion into bile ducts and difficulties with bile outflow through intrahepatic ducts. Twenty-four hours after CCl4 administration, total bilirubin levels in all groups (control without treatment, Chlorophytum comosum extract group, vitamin therapy group, and combination therapy group) were approximately 1.8 times higher than normal, while direct bilirubin levels were three times higher (p < 0.001), as shown in Table 1.
On the second day of the experiment, regardless of therapy, all rabbit groups showed a significant increase in both total and direct bilirubin levels compared to control values, approximately 180% and 460% respectively. These levels were also 50% higher than the previous day’s measurements (Gondo & Haryanti, 2024; Makhoahle, 2024; Naseri & Sasani, 2024; Temirbekova et al., 2024; Wang, 2024).
By the third day of the study, total and direct bilirubin levels continued to increase significantly (p < 0.001) across all four rabbit groups, with an average increase of 100% and 80% compared to day two, and 370% and 1000% compared to intact animal values. Notably, groups two, three, and four showed the highest concentration of bilirubin fractions on the third day following the administration of CCl4 (Alsharif et al., 2023; Cirik et al., 2023; Govindaraj et al., 2023; Muthuvignesh et al., 2023; Zharashueva et al., 2024).
On the fourth day of the study, the control group of rabbits without therapy showed the highest concentration of bilirubin fractions, exceeding normal values six-fold for total bilirubin and twelve-fold for direct bilirubin. Statistical analysis of data from the fourth day revealed that only group one’s indicators significantly differed from the other groups (p < 0.05). No significant differences were observed between groups two, three, and four, with total and direct bilirubin levels remaining consistently elevated.
A turning point occurred after the fifth day of the study. From days five to ten, a gradual decrease in bilirubin fractions was observed in all four groups. During this period, bilirubin fraction levels in groups two, three, and four were significantly lower (p < 0.05) than those in the untreated control group one.
These findings suggest that while initial exposure to CCl4 caused severe liver damage and significant disturbances in bilirubin metabolism, the applied therapies showed promising results in reducing bilirubin levels over time, with the most significant improvements observed after the fifth day of treatment (Guerra Ruiz et al., 2021; Qadri et al., 2025).
Table 1. Serum bilirubin levels (µmol/L) in rabbits with experimental toxic liver damage
|
Time |
Control (no treatment after CCl₄ administration) |
Chlorophytum comosum extract (Group 2) |
Vitamin therapy (Group 3) |
Combined therapy (Group 4) |
||||
|
Total bilirubin |
Direct bilirubin |
Total bilirubin |
Direct bilirubin |
Total bilirubin |
Direct bilirubin |
Total bilirubin |
Direct bilirubin |
|
|
3 hours |
7,8 ±0,80 |
6,4 ±0,76 |
7,5 ±0,85 |
6,4 ±0,67 |
7,6 ±0,73 |
6,2 ±0,73 |
7,9 ±0,67 |
6,1 ±0,58 |
|
1 day |
9,4+ 1,2 |
8,7 ±1,09 |
9,7 ±0,92 |
7,8 ±0,87 |
10,0±0,98 |
8,4 ±0,96 |
10,6 ±0,97 |
7,9 ±0,89 |
|
2 days |
14,1 ±1,17 |
11,9+1,32 |
12,5 ±1,27 |
11,1 ±1,21 |
14,8 ±1,76 |
13,1 ±1,46 |
14,8 ±1,76 |
12,7±1,80 |
|
З days |
23,6±2,13 |
21,1±2,38 |
24,0 ±1,93 |
22,7±1,78 |
25,9±1,54 |
22,3 ±1,36 |
23,3 ±1,43 |
18,6 ±1,29 |
|
4 days |
31,4 ±2,54 |
29,1 ±2,41 |
20,9 ±2,13 |
18,2 ±2,08 |
22,0±2,14 |
20,1 ±2,05 |
23,8±2,17 |
21,4±2,12 |
|
5 days |
26,0 ±2,31 |
24,3 ± 2,33 |
16,9±2,18 |
14,1 ±2,13 |
21,4±2,19 |
17,6±2,17 |
24,3 ±2,21 |
17,2 + 2,10 |
|
6 days |
25,3 ±2,1 |
23,1± 2,12 |
15,1±1,91 |
12,3±2,2 |
18,6±1,48 |
15,8±2.1 |
17,6±1,82 |
13,2±1,91 |
|
7days |
23,3 ±2,10 |
22,1 ±2,18 |
12,7 ±2,01 |
10,8+1,92 |
16,8 ±2,01 |
12,1 ±2,14 |
13,8 ±2,03 |
11,2 ±1,93 |
|
8 days |
21,8 ± 1,93 |
20,0±2,12 |
7,5 ±1,87 |
6,1 ±1,87 |
13,1 ±1,69 |
8,3 ±1,96 |
8,9 ±1,93 |
6,8 ±1,87 |
|
9 days |
20,4 ±1,87 |
18,3 ±2,27 |
5,6±1,34* |
4,3 ±1,63 |
9,0± 1,34 |
6,8±1,89 |
5,4±1,84* |
4,3+1,82 |
|
10 days |
17,1 ±1,74 |
15,2 ±2,82 |
5,2+ 1,91* |
4,1 ±1,58 |
5,2 ±1,23* |
4,1 ±1,78 |
5,1 ±1,73* |
4,0+ 1,78 |
Notes. Control (intact animals): total bilirubin - 5.1±0.98, direct bilirubin - 2.14±0.02
* - P > 0.05 – relative to control (intact animals)
It is noteworthy that the total bilirubin levels in the second group treated with Chlorophytum comosum extract and the fourth group receiving a combination of Chlorophytum comosum extract and vitamin therapy had already returned to normal levels of intact animals by the ninth day of the study. By the tenth day of our research, in the first group of animals, total bilirubin still exceeded normal values by 235%, and direct bilirubin by 600%.
The indicators of the second, third, and fourth groups regarding total and direct bilirubin content were at approximately the same level, showing no significant differences among themselves. Total bilirubin on the tenth day varied within normal limits across all study variants, while direct bilirubin decreased by 440% from its peak value and remained approximately 90% above normal levels (Ahmad et al., 2022; Dhanasekar et al., 2022; Saravanakumar et al., 2022; Du et al., 2023; Thazha et al., 2023).
Although the obtained direct bilirubin values were still far from normal, the observed reduction in bilirubin fractions in the three therapy groups compared to the first control group without therapy indicated the effective impact of aqueous Chlorophytum comosum extract and vitamins on bilirubin fraction concentrations in experimental toxic hepatitis (Ramírez-Mejía et al., 2024).
The data revealed that the aqueous extract of Chlorophytum comosum, unlike vitamin injections used in liver toxicity therapy, exhibited more pronounced hepatoprotective properties (Ern et al., 2023; Hossain et al., 2023; Kukreti et al., 2023; Ali et al., 2025). This was evidenced by total bilirubin levels, which remained at a significantly high level relative to normal values in the third vitamin therapy group on the ninth day of the study. In contrast, both the Chlorophytum comosum extract alone in the second group and combination with vitamins contributed to a significant reduction in total bilirubin to normal values.
The combined use of vitamins and Chlorophytum comosum extract at a dose of 2 ml per 1 kg of body weight did not show significant changes in the concentration of studied bilirubin fractions compared to vitamin therapy alone. Figures 1 and 2 show that by the tenth day of the study, each therapy variant could be used as an independent method for restoring bilirubin fraction levels.
|
|
|
Figure 1. Dynamics of total bilirubin content in the blood serum of rabbits with toxic liver damage in various study options |
|
|
|
Figure 2. Dynamics of direct bilirubin content in the blood serum of rabbits with toxic liver damage in various study options |
Given the demonstrated high activity, it may be appropriate to consider increasing the dosage of the aqueous Chlorophytum comosum extract for further research into its effects on blood bilirubin fractions in toxic hepatitis (Adetunji et al., 2021; Huzio et al., 2022; Almohmadi et al., 2024).
These findings suggest several important conclusions. First, the superior efficacy of Chlorophytum comosum extract compared to vitamin therapy alone indicates its potent hepatoprotective properties (Lister et al., 2020; Tedyanto et al., 2023). Second, the lack of additive effect from combining extract and vitamin therapy suggests that the extract can be used as a monotherapy (Flores-Estrada et al., 2023; Syarifah et al., 2023; Feng et al., 2024). Third, the significant reduction in bilirubin levels in treated groups compared to the control group demonstrates the therapeutic potential of Chlorophytum comosum extract in managing liver damage (Ayenew & Wasihun, 2023; Miao et al., 2023; Ferdjioui et al., 2024).
Future research should focus on optimizing the dosage regimen and exploring the long-term effects of Chlorophytum comosum extract therapy. Additionally, investigating the specific mechanisms underlying its hepatoprotective effects could provide valuable insights into developing new approaches to managing liver damage (Chakrabarty et al., 2022; Latief et al., 2023).
Conclusion
The conducted research has demonstrated that a single subcutaneous administration of carbon tetrachloride (CCl4) at a dose of 0.2 ml per kilogram of body weight induces toxic hepatitis, which is accompanied by a statistically significant increase in bilirubin fractions in the blood serum of experimental animals. This finding confirms the potent hepatotoxic effect of CCl4 and its ability to disrupt normal liver function. The study has revealed that both combined therapy involving vitamin treatment and aqueous Chlorophytum comosum extract, as well as monotherapy with either of these agents, effectively reduces the level of bilirubin fractions in cases of experimental toxic liver damage. Importantly, the reduction in bilirubin levels occurs to a similar extent regardless of the treatment modality employed, indicating comparable efficacy of both therapeutic approaches. Throughout the 10-day observation period, no statistically significant differences were found in the concentration levels of bilirubin fractions between the compared groups of rabbits receiving various forms of therapy (groups 2, 3, and 4). This suggests that the therapeutic effect is consistent across different treatment modalities and does not depend on the specific combination of therapeutic agents used.
A particularly noteworthy finding is the statistically significant difference (p < 0.05) observed on the 10th day of the study between the concentration of bilirubin fractions in the control group without therapy (group 1) and the groups receiving various forms of treatment (groups 2, 3, and 4). This difference demonstrates the therapeutic efficacy of the applied interventions. By the 10th day of the study, a statistically significant (p < 0.05) reduction in total bilirubin levels to normal values was observed in groups 2, 3, and 4 of rabbits receiving therapy, in contrast to the control group without therapy. This finding underscores the effectiveness of both Chlorophytum comosum extract and vitamin therapy in restoring normal bilirubin metabolism and indicates their potential as viable treatment options for managing toxic liver damage.
These conclusions suggest that aqueous Chlorophytum comosum extract, either alone or in combination with vitamin therapy, represents a promising therapeutic approach for managing toxic hepatitis, offering comparable efficacy to traditional vitamin therapy while providing additional benefits through its unique biochemical composition.
Acknowledgments: None
Conflict of interest: None
Financial support: None
Ethics statement: All studies were conducted in compliance with the ethical standards and principles of the Helsinki Declaration. The experimental protocol was approved by the institutional ethics committee (Protocol No. 13-24/2024).
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