Hepatoprotective Activity of Stenocereus Stellatus Stem Against Carbon Tetrachloride Induced Liver Cirrhosis in Wistar Rats

Abstract

“Cirrhosis” is a morphologic term that has been used for almost 200 years to denote the end stage of a variety of chronic liver diseases. The term implies a condition with adverse prognosis due to the well-known complications of portal hypertension, hepatocellular carcinoma, and liver failure The study investigates the hepatoprotective effects of an ethanolic extract of Stenocereus stellatus stem against carbon tetrachloride (CCl4)-induced liver damage in rats. The research involved administrating different doses of the extract (100 mg/kg and 200 mg/kg) to assess its efficacy in mitigating hepatic damage. Results showed significant improvements in liver enzyme levels, total protein, and bilirubin levels, indicating a protective effect. Histological analysis further confirmed the restoration of liver architecture in treated groups. The hepatoprotective properties are attributed to the phytochemical constituents of the extract, particularly flavonoids, which exhibit antioxidant and membrane-stabilizing activities. The findings suggest that Stenocereus stellatus stem extract holds potential as a natural remedy for liver damage, warranting further investigation to elucidate the exact mechanisms and active compounds involved.

Keywords

Introduction

                  (a)                                                   (b)                                                  (c)

Table: Effect of CCl4 toxicity and  stenocereus stellatus aqueous stem extract on enzyme markers and non-enzyme markers of Liver damage.

Group	Treatment (n=6)	ALT(IU/L)	AST (IU/L)	ALP (IU/L)	Total protein (g/dl)
I (Normal control)	Normal control	38.55±1.52****	146.4±0.72****	132.4±1.45****	6.95±0.06****
II (Negative control)	CCl4	101.14±1.92	187.5±0.611	261.8±1.96	3.45±0.13
III (standard dose)	Silymarin	52.76±0.99****	155.6±0.59****	153.9±1.21****	6.68±0.05****
IV (Treatment 1)	stenocereus stellatus (100mg/kg)	86.49±2.95**	179.3±1.78****	237.5±4.53****	3.85±0.024*
V (Treatment 2)	stenocereus stellatus (200mg/kg)	75.54±3.80****	170.8±0.77****	190.5±3.34****	4.46±0.10****

       

(A)                        (B)

                  

(C)                                                  (D)

1.                                                                    (b)

Figure : Effect of CCl4, Ethanolic extract of Stenocereus stellatus stem (100 mg/kg, 200 mg/kg), and silymarin (100 mg/kg) on a)Direct bilirubin b)Total bilirubin . Values are mean ± SEM (n= 6) and analyzed with one-way ANOVA followed by Dunnet’s test ****:significant at p < 0.0001 vs. CCl4 ***:significant at p < 0.001 vs CCl4, **: significant at p < 0.01 vs CCl4

(A)                                              (B)                                                 (C)

   

 (D)                                                            (E)

1. DISCUSSION

Globally, liver disease is the leading cause of morbidity and mortality due to metabolic disorders. Hepatoprotective medicinal herbs have therefore drawn a lot of interest from researchers. Alcohol, the environment, chemicals, and drugs are some of the main causes of liver damage. Hepatotoxic substances cause damage to the liver by elevating oxidative stress, lipid peroxidation, and liver enzymes. Some of the short- to long-term side effects of the sophisticated medications used to treat liver diseases include nausea, vomiting, fatigue, xerostomia, constipation, inflammation, and even death. An important area of research is the examination of medicinal plants to find safer therapeutic or healing effects that come from their natural sources. Throughout history, medicinal plants have been utilized as traditional medicines to treat a variety of illnesses on a global scale. Research has demonstrated the potential therapeutic benefits of certain plants for liver issues. The hepatoprotective effect of CCl4 is frequently investigated in animal models, particularly in mice, rats, and rabbits. Lipid peroxidation and oxidative stress are the two main biomarkers for liver damage. Significant changes in the cellular processes that cause inflammation, necrosis, fibrosis, and cirrhosis are part of the pathology. The production of lipid peroxidation, a decrease in the activity of antioxidant enzymes, and an increase in the production of free radicals are the mechanisms by which CCl4 causes hepatic damage. The enzyme cytochrome P450 is in charge of converting CCl4 into CC13 radicals. After that, oxygen and the hazardous metabolite CC13 radical combine to form the chloromethyl peroxy radical. These radicals cause the lipid membrane of hepatocytes to peroxidatively degrade by binding covalently to macromolecules. As established biomarkers of hepatic damage, our study showed that CCl4 significantly increased the activities of AST, ALT, and ALP. On the other hand, ethanolic extract of stenocereus stellatus + CCl4-treated rats showed a significant decrease in plasma activities of AST, ALT, and ALP when compared to the CCl4-treated group. This drop in serum transaminase activity levels is consistent with the generally held belief that transaminases activities return to normal as a result of plasma membrane stabilization and CCl4-induced hepatic tissue damage repair. This result implies that stenocereus stellatus ethanolic extract shielded the liver tissue from damage caused by CCl4. Additionally, Stenocereus stellatus  ethanolic extract improved the liver's excretory function, as evidenced by a suppression of the rise in serum levels of bilirubin (direct and total). Rats given CCl4 alone experienced higher plasma glucose levels than the normal control group, owing to the stabilization of the endoplasmic reticulum, which led to protein synthesis. This resulted in a decrease in total protein levels. This elevation could result from the breakdown of glycogen into glucose in hepatocytes following CCl4 treatment, which raises plasma glucose concentration, or it could be caused by the death of liver cells or disruption of glycogen storage. In contrast to the CCl4-treated group, rats treated with an ethanolic extract of Stenocereus stellatus + CCl4 exhibited a significant decrease in plasma glucose concentration. According to our research, ethanolic extract of Stenocereus stellatus  could improve insulin secretion and encourage the peripheral glucose uptake to store glucose. Liver weight differences resulted from removing individual variation, even though liver index served as an objective measure of hepatomegaly. In the current investigation, the liver index considerably increased in the group receiving CCl4treatment, suggesting that CCl4 was the cause of the hepatic damage and hepatomegaly. Nevertheless, the liver weight and liver index were nearly returned to the normal group's levels following treatment with an ethanolic extract of Stenocereus stellatus (200 mg/kg). Histological analysis of the liver sections showed that, in contrast to the normal group, hepatotoxin intoxication in the CCl4 treated group disrupted the normal liver architecture. When ethanolic extract of Stenocereus stellatus stem and CCl4 (100 mg/kg and 200 mg/kg) were combined, the exposed animals demonstrated the recovery of damaged cells by maintaining the normal arrangement of the central vein, the radiating pattern of cell plates, and the absence of fat droplets when compared to the hepatocytes of CCl4damaged groups. Additionally, group C animals (Silymarin + CCl4) showed further regeneration of hepatic cells. The ethanolic extract of Stenocereus stellatus stem' effectiveness in lessening liver damage brought on by CCl4 intoxication is further supported by the histological observations.

Stenocereus stellatus is known for its unique phytochemical constituents, which include alkaloids, glycosides, triterpenoids, flavonoids, tannins,phenolic compound and betalins . It is known that phytoconstituents with hepatoprotective properties include phenolic compound and betalins. We propose that some of these components and/or other phytochemical compounds may be responsible for the hepatoprotective activity of the ethanolic extract of Stenocereus stellatus stem, as betalins have been known for their antioxidant and antiperoxidant properties leading to hepatoprotective activities do. To pinpoint the precise mechanism(s) underlying the hepatoprotective effects of the ethanolic extract of Stenocereus stellatus stem, more research is necessary. Additionally, phytochemical analyses are necessary to identify the active ingredients causing this activity.

2. CONCLUSION

The regenerative role of  stenocereus stellatus extract stem induced by CCl4 toxicity in rats was clarified by the current study, in conclusion. Based on our research, it appears that the ethanolic extract of Stenocereus stellatus , particularly when taken in high quantity, exhibits antioxidant activity similar to that of silymarin, the reference antioxidant employed in this investigation. Additionally, the results we obtained indicate that the extract may have positive effects, possibly as a result of the presence of phenolic compound,flavanoid and betalins that have antiperoxidative and antioxidant properties. This finding indicates that the flavonoids , phenolic compound and betalin in the  stenocereus stellatus stem ethanolic extract may effectively boost the liver's capacity for regeneration and repair. While our study found that the ethanolic extract of stenocereus stellatus stem has a hepatoprotective effect similar to that of silymarin, more research is necessary to clarify the hepatoprotective mechanism and identify the active ingredients in the Histopathological analysis shows extensive hepatocellular damage, as represented by the presence of portal inflammation, fatty change and venous congestion. Accordingly, our findings may play a role towards the discovery of a new naturopathic remedy.

3. Future Prospective

Future research on  stenocereus stellatus stem extract should focus on elucidating the specific bioactive compounds responsible for its hepatoprotective effects. Advanced analytical techniques like mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy could be utilized to identify and characterize these phytochemicals. Additionally, studies should explore the molecular mechanisms underlying the antioxidant and anti-inflammatory properties of the extract to provide a comprehensive understanding of its therapeutic potential. Clinical trials are essential to evaluate the safety and efficacy of Stenocereus stellatus extract in human subjects, particularly in individuals with liver diseases such as hepatitis and cirrhosis. These trials should investigate optimal dosing regimens, long-term effects, and possible interactions with conventional medications. Moreover, integrating Stenocereus stellatus extract into a standardized formulation could enhance its bioavailability and therapeutic efficiency. Nanotechnology-based delivery systems, such as nanoparticles and liposomes, could be explored to improve the extract's stability and target-specific delivery to liver tissues. Investigating the synergistic effects of Stenocereus stellatus with other known hepatoprotective agents like silymarin could also open new avenues for combination therapies, offering more robust protection against liver damage. In summary, while the current study highlights the promising hepatoprotective potential of Stenocereus stellatus further research is necessary to fully realize its clinical applications and establish it as a viable natural remedy for liver diseases.

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