INTRODUCTION:

Constipation is a condition where feces are difficult to expel due to changes in the consistency of the stool, it becomes hard and large in size¹. Some conditions that can cause constipation include lack of fiber and water intake, structural abnormalities, metabolic disorders, enteric nervous system disorders, and consequences of the influence of the drugs consumed.

Generally constipation is considered a normal thing that occurs occasionally and does not result in system disruption body, but if left untreated and occurs repeatedly in a long period of time will result in serious gastrointestinal complications such as hemorrhoids, anal fissures, hematochezia, and rectal prolapse^2,3. One type of medication that can help facilitate constipation is a laxative drug^4,5.

Administration of laxatives as pharmacological therapy for constipation can be an option if non-pharmacological therapy such as increased consumption of fiber and water, avoid drugs that can cause constipation, as well as increasing physical activity are not successful in treating the constipation that occurs⁶. The types of laxatives commonly used for constipation are stool-forming laxatives, stimulant laxatives, as well as osmotic laxatives. Apart from coping constipation, the use of laxatives is also recommended to facilitate post-digestion surgery and to clean the digestive tract before certain medical procedures, such as bowel surgery or colonoscopy^7,8.

The laxative drugs to treat constipation were available widely and free access⁹. However, The use of laxative drugs have side effects that may appear due to wrong treatment such as nausea, vomiting, anorexia, hypokalemia, and irritation of the rectal mucosa¹⁰. Traditional medicine with medicinal plants is also popular with local people as one of the ways to treat many diseases including constipation, because it is proven to be safer, has more toxic effects few, and does not cause side effects compared to synthetic drugs^11,12,13. Cassia alata is one of medicinal plants used for the treatment of many diseases traditionally¹⁴. Cassia alata leaves were also reported to have various pharmacological activities such as anti-inflammatory, analgesic activity, antiviral, antibacterial, and antiplatelet-aggregating activity^{15,16,17,18,19}. Despite the several known effects of Cassia alata, this study needs more validation as a laxative compound.

MATERIAL AND METHODS:

Ethical Clearance:

All treatment procedures under guided Animal Ethics Committee, School of Veterinary Medicine and Biomedical Sciences (SVMBS), IPB University, Indonesia (Approval reference number: 154/KEH/SKE/XII/2023).

Plant material:

The Cassia alata leaves were collected and authenticated from Tropical Biopharmaca Research Centre, IPB University, Indonesia.

Extract preparation:

A total of 1kg of Cassia alata leaves samples are entered in the drying process by an oven at 40°C for two days. Samples were ground using a blender and weighed the dried simplicia. Simplicia is extracted using a single maceration method using a solvent 70% ethanol with a simplicia and solvent ratio of 1:10.

Animals:

The twenty four Sprague dawley male rats (200-250g) obtained by Laboratory Animal Management Unit, SVMBS, IPB University were used for screening of laxative activity. Animals were housed in standard environmental conditions and fed with standard rodent diet and water ad libitum. The rats were divided into six groups. Group one (K1) is normal control (given Tween-20 0,5%), group two (K2) is negative control (induce loperamide with no treatment), group three (K3) is positive control (induce loperamide, treated by bisacodyl), and the rest of group 4, 5, and 6 are treatment group which induce loperamide and treated by Cassia alata leaves extract 50mg/kg BW (P1), 100 mg/kg BW (P2) and 200mg/kg BW (P3).

Screening of laxative activity:

The screening of laxative activity used measurement of fecal parameters and gastrointestinal transit ratio. Fecal parameters include the defecation frequency and fecal weight which is calculated and evaluated during the treatment, while the gastrointestinal transit ratio used rats induced loperamide two times a day for two days, then rats fasted for 18hours. Once it finished, the treatments were given at doses respectively and rested 45 minutes to give 0, 5% norit suspension as a marker, then waited 25 minutes so that the gastrointestinal tract is stained. The rats were dissected by laparotomy, the pylorus of the stomach is protected to prevent the contents of the stomach and intestines from being expelled. The intestine is stretched to measure the total length of the intestine and the length of the intestine passed by the marker.

Statistical analysis:

The data obtained from the biological studies were reported as mean±Standard deviation (n = 4). Standard error mean and analysis of variance (ANOVA) at 5% level significance used for determining the statistical significance (P<0.05).

RESULTS AND DISCUSSION:

Constipation can be classified into two based on pathophysiology, namely constipation due to structural abnormalities and constipation functional. Constipation due to structural abnormalities caused by colonic obstruction or rectum, while functional constipation is related to disorders of colonic motility^20,21. This study is more related to evaluating the Cassia alata leaves extract treatment in the colonic motility aspect compared with bisacodyl as a laxative drug that is commonly used in the community. The fecal evaluation showed that the Cassia alata leaves extract dosage 100 mg/kg BW has a significant difference (p<0.05) in terms of increased defecation frequency and fecal weight compared with negative control, while the positive control has no significant value compared to treatment groups. The results of the fecal output percentage as a result of the laxative effect of Cassia alata leaves extract can be seen in table 1.

Table 1. Laxative activity of measuring fecal parameters of Cassia alata leaves extract

Groups	Defecation frequency (times)	Fecal weight (g)
Negative control (K1)	42,50±2,64^ab	9,47±1,14^a
Normal control (K2)	56,00±2,94^c	13,23±2,94^b
Positive control (K3)	65,50±1,29^d	10,79±1,65^ab
Dosage 50mg/kg BB (P1)	39,75±4,78^a	9,83±1,13^a
Dosage 100mg/kg BB (P2)	52,25±2,98^c	11,60±2,38^ab
Dosage 200 mg/kg BB (P3)	47,00±3,56^b	9,98±1,33^a

Note: numbers in the same column followed by different superscript letters indicate significant differences (p < 0.05)

As shown in table 1, the active compound content of Cassia alata might be responsible for the observed laxative activity. According to phytochemical tests conducted, ethanol extract of Cassia alata leaves contains secondary metabolite compounds such as alkaloids, glycosides, carbohydrates, anthraquinones, flavonoids, saponins, steroids, tannins and terpenoids^22,23,24. Anthraquinones are a class of stimulant laxatives that can have a direct effect on enterocytes, the enteric nervous system, and smooth muscle in the digestive tract²⁵. The previous study also showed that products containing anthraquinones are mainly used as laxatives²⁶.

Another method to test the effectiveness of laxatives is the intestinal transit ratio to determine one of the laxative mechanisms for increasing intestinal motility²⁷. The ability of the drug to increase intestinal motility can be seen from the increase in the percentage of intestinal length stained with the marker. Markers in the intestine will move more quickly if intestinal motility is increased, resulting in shorter transit times and longer marker trajectories²⁸. The percentage of intestinal length stained with markers showed that the Cassia alata leaves extract at doses of 100 and 200mg/kg was significantly different from the negative control group, while the dose of 50mg/kg BW was not significantly different. Even though Cassia alata leaves extracted at a dose of 200 mg/kgBW had a significant difference from the negative control group, the percentage exceeded the normal and positive control groups. This indicates that it is not a laxative effect that occurs, but rather a diarrheal effect because intestinal motility increases beyond the animal's normal physiology^29,30. Therefore, Cassia alata leaves extract at a dose of 100 mg/kg BW is the most effective dose as a laxative because it is able to increase the intestinal transit ratio close to normal and positive control. The results of percentage intestinal length showed in table 2.

Table 2. Laxative activity of measuring intestinal length percentage of Cassia alata leaves extract

Groups	Percentage of intestinal length stained with marker (%)
Negative control (K1)	47,13 ± 7,87^ab
Normal control (K2)	57,67 ± 8,67^bc
Positive control (K3)	52,61 ± 5,78^bc
Dosage 50 mg/kg BB (P1)	43,88 ± 1,94^a
Dosage 100 mg/kg BB (P2)	56,46 ± 3,04^bc
Dosage 200 mg/kg BB (P3)	63,03 ± 3,12^c

Different superscript letters indicate significant differences (p < 0.05)

Loperamide was used as a constipation inducing drug in this study because it is a μ-opioid receptor agonist and is commonly used to treat chronic diarrhea. As shown in table 2 (negative control), loperamide is able to reduce intestinal peristaltic movements and inhibit fluid and electrolyte secretion in the colon, thereby inhibiting intestinal transit time³¹. Bisacodyl is also used as a positive control because it is a type of stimulant laxative drug that is commonly used in the treatment of constipation. Based on this study, bisacodyl and Cassia alata leaves extract at dose 100 mg/kg BW works directly on the colon by increasing intestinal motility and accelerating transit time^32,33.

CONCLUSION:

This study revealed that Cassia alata leaves extract produce significant in fecal output and resulting in a short gastrointestinal transit ratio showing laxative activity, and the dose 50 mg/kgBB being more potent. Further studies are required to identify the actual chemical constituents of this plant which are responsible for laxative activity and the details of molecular mechanism Cassia alata is still needed to be explored as a laxative drug.

ACKNOWLEDGEMENT:

This study was supported by Riset Fundamental with reference number 422/IT.3.D10/PT.01.03/P/B/2023 from IPB University.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

REFERENCES:

1. Jani B. Marsicano E. Constipation: Evaluation and Management. Missouri Medicine. 2018; 115(3): 236–240.

2. Vageriya V. Sharma K. A Study to Evaluate the Effectiveness of Planned Teaching Program on Knowledge About the Prevention and Management of Constipation among the Mothers of Infants in Alur village, Hassan (Karnataka). Asian J. Nur. Edu. and Research. 2017; 7(2): 158-162. doi.org/10.5958/2349-2996.2017.00032.5

3. Benjamin SE. Drobatz KJ. Retrospective Evaluation of Risk Factors and Treatment Outcome Predictors in Cats Presenting to the Emergency Room for Constipation. J Feline Med Surg. 2020; 22(2):153-160.doi.org/10.1177/1098612X19832663

4. Werth BL. Christopher SA. Laxative use in the Community: A Literature Review. Journal of Clinical Medicine. 2021;10(1):143-156.doi.org/10.3390/jcm10010143

5. Patel M. Chauchan S. Patel V. Soni H. Trivedi V. Standardization of Proprietary Ayurvedic Laxative Tablet Formulation-Vasolex. Research J. Pharm. and Tech. 2022;15(1):5206-0.doi.org/10.52711/0974-360X.2022.00877

6. Rao SS. Rattanakovit K. Patcharatrakul T. Diagnosis and Management of Chronic Constipation in Adults. Nat. Rev. Gastroenterol. Hepatol. 2016;13:295–305.doi.org/10.1038/nrgastro.2016.53

7. Bassotti G. Battaglia E. Considerations for Laxatives in Terms of their Interactions with other Drugs. Expert Opinion on Drug Metabolism & Toxicology. 2023; 19(3):121-123.doi.org/10.1080/17425255.2023.2193326

8. Krishna KVVS. Kumar PA. Akhila P. Samitha N. Suryaveni PNSG. Kumari PH. Kumar PS. Evaluation of Laxative Activity of Panchachurnam: An Ayurvedic Poly Herbomineral Formulation. Res. J. Pharmacognosy and Phytochem. 2019;11(2): 93-96.doi.org/10.5958/0975-4385.2019.00017.7

9. Guerin A. Carson RT. Lewis B. Yin D. Kaminsky M. Wu E. The Economic Burden of Treatment Failure amongst Patients with Irritable Bowel Syndrome with Constipation or Chronic Constipation: A Retrospective Analysis of A Medicaid Population. J. Med. Econ. 2014;17:577–586.doi.org/10.3111/13696998.2014.919926

10. Motola G. Mazzeo F. Rinaldi B. Capuano A. Rossi S. Russo F. Vitelli MR et al Self-Prescribed Laxative Use: A Drug-Utilization Review. Adv. Ther. 2002;19:203–208.doi.org/10.1007/BF02850360

11. Adnaik RS. Bhagwat DA. Ruat ID. Mohite SK. Magdum CS. Laxative Potential of Cassia alata Leaves Extract. Research J. Pharm. and Tech. 2011; 4(1):98-100.

12. Wresdiyati T. Sadiah S. Winarto A. Febriyani V. Alpha-Glucosidase Inhibition and Hypoglycemic Activities of Sweitenia mahagoni Seed Extract. Hayati J. Biosci. 2015; 22(2): 73-78.

13. Fadholly A. Ansori ANM. Proboningrat A. Nugraha AP. Iskandar RPD. Rantam FA. Sudjarwo SA. Apoptosis of HeLa Cells via Caspase-3 Expression Induced by Chitosan-based Nanoparticles of Annona squamosa Leaf Extract: In Vitro Study. Indian J. Pharm. Educ. 2020; 54(2):416-421.doi.org/10.5530/ijper.54.2.47

14. Igbe I. Edosuyi O. Toxicity Proﬁle of Aqueous Extract of Cassia alata Flower in Wistar rats. Journal of Pharmacy & Bioresources. 2016;13(2):92-102.doi.org/10.4314/jpb.v13i2.5

15. Adnaik RS. Bhagwat DA. Raut ID. Mohite SK. Magdum CS. Laxative and Anthelmintic Potential of Cassia alata Flower Extract. Research J. Pharm. and Tech. 2011; 4(1): 98-100.

16. Shrivastava A. Parveen N. Dewangan G. Verma VS. Bhattacharya A. Sharma M. Evaluation of Antipyretic Potential of Cassia alata Leaves. Asian J. Pharm. Res. 2014; 4(4):195-197

17. Dewi R. Firza Y. Nashiry MA. Al-Sue-de FSR. Majid ASA. A Review on Cassia alata: Pharmacological, Traditional and Medicinal Aspects. Australian Herbal Insight. 2019; 2(1): E016-E021.doi.org/10.25163/ahi.110005

18. Turista DDR. Kharisma VD. Ansori ANM. Kardanova KA. Aslanov IR. Dotkulov IM. Asphev AZ et al Investigation of Cassia alata L. Bioactive Compounds for SARS-CoV-2 Mpro: In Silico Approach. Research J. Pharm. and Tech. 2023; 16(12): 5610-6.doi.org/10.52711/0974-360X.2023.00907

19. Anggraeni Y. Firdausi N. Randy A. Dewi RT. Kusumastuti SA. Sani Y. Yuliani T. et al. Formulation and Antibacterial Activity Test of Cream Containing Cassia alata Leaves Extract Against Propionibacterium acnes and Staphylococcus epidermidis. Research J. Pharm. and Tech. 2024; 17(3): 1356-3.doi.org/10.52711/0974-360X.2024.00214

20. Andrews CN. Storr M. The pathophysiology of Chronic Constipation. Can J. Gastroenterol. 2011; 25(Suppl B):16B-21B.doi.org/10.1155/2011/715858

21. Milosavljevic T. Popovic DD. Mijac DD. Milovanovic T. Krstic S. Krstic MN. Chronic Constipation: Gastroenterohepatology Approach. Dig. Dis. 2022; 40(2):175-180.doi.org/10.1159/000516976

22. Sujatha J. Asokan S. Rajeshkumar S. Phytochemical Analysis and Antioxidant Activity of Chloroform Extract of Cassia alata. Research J. Pharm. and Tech. 2018; 11(2): 439-444.doi.org/10.5958/0974-360X.2018.00081.1

23. Edegbo E. Okolo MLO. Adegoke AS. Omatola CA. Idache BM. Abraham JO. Akor ME et al Phytochemical Screening and Antifungal Activity of Cassia alata (Linn.) Crude Leaf Extracts. African Journal of Microbiology Research. 2023; 17(8):176-183.doi.org/10.5897/AJMR2023.9711

24. Megawati M. Ernawati T. Angelina M. Meilawati L. Antika LD. Supriadi D. Antioxidant Activity of Yellow Candle Bush (Cassia alata) Leaves Extract and Bioactive Fractions through LC-QTOF-MS/MS and Molecular Docking Approach. Research J. Pharm. and Tech. 2024; 17(4): 1599-5.doi.org/10.52711/0974-360X.2024.00253

25. Zhao L. Zheng L. A Review on Bioactive Anthraquinone and Derivatives as the Regulators for ROS. Molecules. 2023; 28(4): 8139. doi.org/10.3390/molecules28248139

26. Lombardi N. Bettiol A. Crescioli G. Maggini V. Gallo E. Sivelli F. Sofi F et al Associations between Anthraquinone Laxatives and Colorectal Cancer: Protocol for A Systematic Review and Meta Analysis. Phytother. Res. 2022; 36(3): 1093-1102. doi.org/10.1002/ptr.7373

27. Kongdang P. Pruksakorn D. Koonrungsesomboon N. Preclinical Experimental Models for Assessing Laxative Activities of Substance/ Products under Investigation: A Scoping Review of the Literature. Am. J. Transl. Res. 2022; 14(2): 698-717.

28. Rhie JK. Hayashi Y. Welage LS. Frens J. Wald RJ. Burnett JL. Amidon GE. Putcha L et al Drug Marker Absorption in Relation to Pellet Size, Gastric Motility and Viscous Meals in Humans. Pharmaceutical Research. 1998; 15(2): 233-238. doi.org/10.1023/A:1011962501270

29. Cummings JH. Sladen GE. James OFW. Sarner M. Misiewicz JJ. Laxative-Induced Diarrhoea: A Continuing Clinical Problem. The British Medical Journal. 1974; 1(5907): 537-541. doi.org/10.1136/bmj.1.5907.537

30. Keely SJ. Barret KE. Intestinal Secretory Mechanisms and Diarrhea. Am. J. Physiol. Gastrointest. Liver Physiol. 2022; 322(4): G405-G420.

31. Lee KJ. Pharmacologic Agents for Chronic Diarrhea. Intest Res. 2015; 13(4): 306-312. doi.org/10.1152/ajpgi.00316.2021

32. Bharucha AE. Lacy BE. Mechanisms, Evaluation, and Management of Chronic Constipation. Gastroenterology. 2020; 158: 1232.e3‐1249.e3.doi.org/10.5217/ir.2015.13.4.306

33. Corsetti M. Landes S. Lange R. Bisacodyl: A Review of Pharmacology and Clinical Evidence to Guide Use in Clinical Practice in Patients with Constipation. Neurogastroenterol Motil. 2021; 33(10): e14123. doi.org/10.1111/nmo.14123

Received on 07.07.2024 Revised on 13.11.2024

Accepted on 10.02.2025 Published on 01.07.2025

Available online from July 05, 2025

Research J. Pharmacy and Technology. 2025;18(7):2967-2970.

DOI: 10.52711/0974-360X.2025.00425

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.