In Vivo Antidiarrheal Potential of the Leaf Extract of Maytenus addat (Loes.) Sebsebe and Its Major Compound

Diarrhea continues to be one of the top causes of death in children under the age of five, particularly in developing nations. In Ethiopian traditional medicine, a variety of medicinal plants are used to treat diarrhea. One of these plants is Maytenus addat (Loes.) Sebsebe (fam. Celastraceae), which is endemic to the Afromontane forests, especially along forest margins, of Ethiopia. The air-dried powdered leaves of M. addat were macerated with 80% methanol to yield a crude extract. Additionally, the powdered plant material underwent sequential solvent extraction using chloroform, methanol, and water to obtain solvent fractions. The 80% methanol leaf extract, solvent fractions, and an isolated compound from M. addat were evaluated for their antidiarrheal activity using castor oil-induced diarrheal model, anti-enteropooling test, and charcoal meal test in mice. The results showed that the 80% methanolic leaf extract significantly reduced the onset of diarrhea, the weight of feces, and the frequency of defecation in all the tested doses. The methanol and water fractions of the hydroalcoholic extract also exhibited dose-dependent antidiarrheal activity, with the methanol fraction showing the highest activity at 400 mg/kg dose. Subsequently, the most active methanol fraction was subjected to C-18 solid phase extraction, resulting in the isolation of a 3-hydroxyflavone, identified as quercetin by ESI-qToF-MS, 1H, and 13C-NMR spectroscopic techniques. Quercetin demonstrated a strong antidiarrheal activity in a dose-dependent manner. Thus, the present study provided evidence that the leaves of M. addat possess genuine antidiarrheal activity upholding the traditional medicinal use of the plant for the treatment of diarrhea. The findings also suggest that quercetin is responsible, in full or in part, for the activity of the plant.


Introduction
Te problem of diarrhea is widespread globally, and it has high morbidity and mortality rates in developing countries, especially children under the age of 2 are particularly vulnerable due to limited access to clean water, sanitation conditions, and proper hygiene practices [1].Tis combined with worsening nutritional and overall health conditions contributes to high morbidity and mortality rates in these countries [2].Childhood diarrhea is a signifcant concern worldwide, with approximately 1.7 billion cases occurring each year.It is responsible for one in nine child deaths, resulting in a prevalence rate of 4.9 episodes per child per year.Shockingly, diarrhea is the second leading cause of death in children under the age of fve [1].It claims the lives of 525,000 children annually and greatly contributes to malnutrition in this age group [3].Overall, diarrhea accounts for 21% of deaths in children under the age of fve [4].Particularly in Africa and South Asia, this illness is responsible for a staggering 82% of children under-fve [5].In Ethiopia, diarrhea has been identifed as the cause of 20% of child mortality [6], and 12% of children under the age of fve sufered from diarrhea in 2016 [7].
To address diarrhea, the United Nations International Children's Emergency Fund (UNICEF) and the WHO recommend the use of reduced osmolality oral rehydration solution (ORS) to reduce stool output and vomiting in patients with acute noncholera diarrhea [8].Zinc supplementation is also advised as it has been shown to decrease the severity, duration, and recurrence of diarrhea within the following 2-3 months [9].Antimotility drugs like loperamide, diphenoxylate, paregoric, and codeine can efectively reduce the frequency of diarrhea episodes in adults.However, due to potential side efects and the possibility of worsening disease progression in specifc cases, these drugs are not recommended for infants or children [10].
Maytenus addat (Loes.)Sebsebe is a shrub or large tree which grows up to 30 m in height [15].It is endemic to Ethiopia where it is known by various vernacular names such as Atata (Amharic), Shamene (Guragigna) [16], and Kombolcha (Afaan Oromoo) [17].In Ethiopian traditional medicine, the aqueous leaf extract of M. addat has a history of being used to treat diarrheal diseases [17].Terefore, this study aims to investigate the antidiarrheal activity of the active constituent(s) from M. addat leaves, known for their reputation in managing diarrhea.

General.
A mixture of methanol-water (2 : 1) was used as a solvent system for RP-TLC.Solid phase extraction utilized Isolute C-18 (EC) columns (10 g, IST, Hengoed, UK).NMR spectra were recorded on a Bruker Avance DMX 400 FT-NMR spectrometer operating at 400 MHz for 1 H and 100 MHz for 13 C at room temperature with tetramethylsilane (TMS) as an internal standard.Chemical shifts are reported in ppm, and coupling constants (J) in Hz.Mass spectrum of the isolated compound was generated using an AB SCIEX Triple TOF 5600 mass spectrometer (Concord, ON, Canada) equipped with ESI (electro spray ionization) in the negative-ion mode time of fight mass spectrometry (−ve mode ESI-qTOF-MS).

Plant Material.
Leaves of M. addat were collected from the Gullele Botanic Garden, Addis Ababa, in November 2021.Te plant was authenticated by Mr. Melalku Wondafrash at the National Herbarium, Department of Plant Biology and Biodiversity Management, College of Natural and Computational Sciences, Addis Ababa University (AAU), where a voucher specimen (Collection number: MA01) was deposited for future reference.

Preparation of Hydroalcoholic Extract.
Te leaves of M. addat were cleaned and air-dried under shade at room temperature.After drying they were powdered using a mortar and pestle.Te powdered leaves (500 g) were then subjected to maceration with 80% methanol (2.5 L) at room temperature for three days, during which regular shaking and stirring were performed.After three days, the extract was fltered using Whatman No. 1 flter paper, and the marc was remacerated with the same volume of solvent for an additional three days.Te fltrates were combined, and the methanol was removed under reduced pressure (below 40 °C) using a Rota vapor (Heidolph, Germany).Te remaining aqueous solution was dried in an oven at a temperature not exceeding 40 °C.Te dried extract was transferred in to an amber-colored vial, labeled, and kept in a refrigerator at 4 °C until use.

Preparation of Solvent
Fractions.Te powdered plant material underwent successive solvent extraction.First, it was exhaustively extracted with chloroform, and the solvent was evaporated to dryness under reduced pressure.Te marc was then allowed to dry in an open air and sequentially extracted with methanol and distilled water.Te resulting extracts were dried in a vacuum oven at 40 °C.Te extracts were weighed, transferred into an amber-colored vails, labeled, and kept in a refrigerator at 4 °C until use. .Of these, fractions 31-60 gave a single spot on a reversed phase TLC using diferent solvent systems.Tese fractions were combined to obtain a yellow solid substance, coded MA-3.MA-3 was transferred into an amber-colored vial and stored in a refrigerator at 4 °C until further use.
Percent of fecal output � Mean weight of wet feces of treatment group Mean weight of wet feces of negative control group × 100, Percent inhibition of defecation � Mean wet feces defecation of (−ve control − test) Mean wet feces defecation of negative control × 100. (1) 2.8.3.Castor Oil-Induced Enteropooling Test.Te method of Oghenesuvwe et al. [22] was adopted with slight modifcations to establish the intraluminal liquid collection.Te mice were fasted for 18 h and treated with the respective substances as mentioned before.After 1 h of treatment, each animal received 0.5 ml of castor oil by the oral route.One hour later, the mice were sacrifced by cervical dislocation and both ends of the small intestine of each animal were tied with thread.Te mass of the tied intestine was weighed before and after removing the gut contents, and the colonic content was drained into a graduated cylinder and the volume measured.Te percentage of intestinal secretion and weight of intestinal contents reduction were calculated using the formulas given below [23].

Percent inhibition by using MVSIC
where MVSIC is the mean volume of small intestinal content; MVICC is the mean volume of the intestinal content of the negative control group; and MVICT is the mean volume of the intestinal content of the test group.

Journal of Tropical Medicine
where MWSIC is the mean weight of small intestinal content; MWICC is the mean weight of intestinal content of the control; and MWICT is the mean weight of intestine content of the test/standard drug group.

Charcoal Meal (Gastrointestinal Motility)
Test.In this model, the mice were fasted for 18 h.Te negative and positive control groups received 10 ml/kg of distilled water and 3 mg/kg of loperamide, respectively.Te treatment groups received their respective graded doses of the extract or fractions.After one hour, all the mice received a 0.5 ml of castor oil, followed by 1 ml of 5% activated charcoal suspension after another hour.Te mice were then sacrifced by cervical dislocation after 30 min, and the small intestine was removed and placed lengthwise on a piece of paper.Te length passed by the activated charcoal meal and the entire length of the intestine were determined to calculate the percentage of inhibition and peristaltic index as shown below [23].(4)

In Vivo Antidiarrheal Index (ADI).
Te ADI of the 80% methanol extract, solvent fractions, and standard drug loperamide was determined by combining three parameters from the above models using the formula presented below [24,25].
where Dfreq is the delay in excretion time as a percentage of vehicle treated group; Pfreq is the drop in purging frequency in the number of wet feces as a percentage of the vehicle treated group; and Gmeq is the gut meal travel decrease as a percentage of vehicle treated group.
2.9.Data Analysis.Te data were analyzed using SPSS (Statistical Package for Social Science) software version 26.A one-way analysis of variance (ANOVA) was conducted, followed by Tukey post hoc multiple comparison tests to compare the test groups.Te results were presented as mean ± standard error of the mean (SEM) and p < 0.05 was considered statistically signifcant.

Yields.
Maceration of 500 g of the dried leaves of M. addat with 80% methanol aforded 125 g dark green extract (25% (w/w)).A solid phase extraction of the active methanol fraction over C-18 column yielded 1.24 g favonoid labeled as MA-3.

Structural Elucidation of the Isolated Compound.
MA-3 was isolated from the methanol fraction of M. addat leaves as a yellow solid substance.It gave an R f value of 0.51 on a reversed-phase analytical TLC using methanol-water (2 : 1) as a solvent system.Te negative-mode ESI-qTOF-mass spectrum of MA-3 (Figure S1) exhibited a pseudomolecular ion at m/z 301.0350 [M-H] − (exact calculated mass � m/z 301.0348 mu [M-H] − ), indicating a molecular formula of C 15 H 10 O 7 .Te presence of 15 carbons was also evident from the 13 C-NMR spectrum of MA-3, with one carbonyl carbon, seven oxygenated quaternary sp 2 carbons, and two nonoxygenated sp 2 quaternary carbons.Tis along with 1 H-NMR spectrum as well as comparing its spectral data with previously reported data [19] for the same compound led to characterization of MA-3 as the 3hydroxyfavone, quercetin (Figure 1).

Acute Oral Toxicity Study.
None of the mice died during the acute oral toxicity study with the 80% methanol extract and solvent fractions of M. addat leaves, and no sign of toxicity was observed till the end of the 14 th day.Terefore, the LD 50 of the plant is greater than 2000 mg/kg.

Efects on Castor
Oil-Induced Diarrhea.Efects of the 80% methanol extract, solvent fractions, and quercetin isolated from the leaves of M. addat on castor oil-induced diarrhea are depicted in Table 1.Te results indicate that all the test samples signifcantly decreased the frequency and quantity of castor oil-induced diarrhea, as well as the total weight of feces produced.Te onset of diarrhea was also signifcantly (p < 0.05) delayed at all doses of the 80% methanol extract, with the highest efect observed at a dose of 400 mg/kg.Furthermore, the hydroalcoholic extract demonstrated dose-dependent inhibition of diarrhea frequency, with the 400 mg/kg dose showing the maximum efect.Te positive control loperamide inhibited defection by 66.66% at a dose of 3 mg/kg, while inhibition caused by the 80% methanol extract at a dose of 400 mg/kg was 55.55%.Te solvent fractions also signifcantly (p < 0.05) delayed the onset of diarrhea compared to the negative control with the methanol fraction showing the highest activity (delaying the onset of diarrhea by 125.2 ± 1.43 min (p < 0.05) at a dose of 400 mg/kg).Both the aqueous and methanol fractions demonstrated dose-dependent reductions in the number of 4 Journal of Tropical Medicine wet feces by 28.80%, 42.22%, and 60.00% for the aqueous fraction and 37.77%, 46.70%, and 62.20% for the methanol fraction at doses of 100, 200, and 400 mg/kg, respectively.However, the chloroform fraction showed a weaker efect compared to the other fractions.Te antidiarrheal activity of quercetin was also examined in this study, and the results showed that it signifcantly reduced the frequency and quantity of castor oil-induced diarrhea, as well as the total weight of feces produced.Quercetin also signifcantly (p < 0.05) delayed the onset of diarrhea in a dose-dependent manner.At a dose of 40 mg/ kg, percent inhibition of defecation, percent inhibition of feces output, and the delay in the onset of diarrhea caused by quercetin were comparable to those of loperamide (Table 1).

Efects on Castor Oil-Induced Enteropooling in Mice.
Te hydroalcoholic extract of M. addat, at all doses, signifcantly reduced intraluminal fuid accretion in mice compared to the vehicle-treated group (Table 2).Te percentage volume of small intestinal content decreased by 32.9%, 60.5%, and 65.8% at doses of 100, 200, and 400 mg/kg, respectively.Also, the extract decreased the weight of the intestinal contents in a dose-dependent manner with the 400 mg/kg dose achieving a 58.2% reduction.
Both the aqueous and methanol fractions of the 80% methanol extract of M. addat signifcantly (p < 0.05) reduced the quantity of the intestinal contents compared to the vehicle-treated group (Table 2).Te highest doses of these fractions resulted in the highest percentage reduction in both volume and weight of the intestinal contents, demonstrating 57.0% and 56.7% for the aqueous fraction and 68.4 and 60.2% for the methanol fraction, respectively.At a dose of 400 mg/kg, the activity of the methanol fraction in reducing both volume and weight of the small intestinal contents was comparable to that of loperamide (3 mg/kg).Again, the chloroform fraction did not show signifcant activity at any of the tested doses.
In the present study, quercetin was shown to reduce the volume and mass of intestinal content increased by the administration of castor oil.In mice, all evaluated doses of quercetin signifcantly reduced intraluminal fuid deposit compared to the vehicle-treated group (Table 2).Te percentage volume of small intestinal content was reduced by 40.8%, 61.8%, and 71.1% at doses of 10, 20, and 40 mg/kg, respectively.Quercetin also dose-dependently decreased the weight of intestinal contents compared to the negative control, with the 40 mg/kg dose achieving a 61.22% reduction, similar to the positive control loperamide, which inhibited 61.2% at 3 mg/kg.

Efects on Castor Oil-Induced Intestinal Transit in Mice.
Table 3 provides data on the inhibitory efects of the 80% methanol extract of M. addat leaves, solvent fractions, and quercetin on the movement of a charcoal meal in the small intestine.Te hydroalcoholic extract demonstrated percentage inhibition of 37.66, 45.71, and 52.52 on gastrointestinal transit time of charcoal meal at doses of 100, 200 and 400 mg/kg, respectively, in comparison to the control.On the other hand, the positive control, loperamide, displayed 66.76% (3 mg/kg) inhibition compared to the vehicle-treated group.Furthermore, the hydroalcoholic extract decreased movement of the charcoal meal by 46.48%, 40.70%, and 35.73% at doses of 100, 200 and 400 mg/kg, respectively, while the decrease caused by loperamide was 25.13%.
Similarly, the aqueous and methanol fractions exhibited dose-dependent inhibition of gastrointestinal motility.Te aqueous fraction showed 44.23%, 47.95%, and 59.95% inhibition, while the methanol fraction displayed inhibition of 45.33%, 54.48%, and 64.33% at doses of 100, 200, and 400 mg/kg, respectively.In contrast, the chloroform fraction did not decrease intestinal motility (Table 3).Te methanol fraction at a dose of 400 mg/kg signifcantly (p < 0.01) suppressed movement of the charcoal meal within the small intestine and reduced the peristaltic index compared to the negative control.Tese efects were comparable to those observed for loperamide at a dose of 3 mg/kg.Tus, the plant extract inhibited gastrointestinal contractions and slowed down intestinal transits, allowing more time for water and electrolyte absorption.
Te isolated compound quercetin also demonstrated antimotility activity, inhibiting the movement of charcoal meal in a dose-dependent manner.It showed percentage inhibition of 55.71%, 61.42%, and 66.66% at doses of 10, 20, and 40 mg/kg, respectively, while the positive control, loperamide, exhibited 66.76% (3 mg/kg) inhibition compared to the vehicle-treated group (Table 3).Additionally, quercetin reduced the mean percentage movement of the charcoal meal in the small intestine by 32.40%, 28.62%, and 24.91% at doses of 10, 20, and 40 mg/kg, respectively.At the highest dose employed, quercetin showed comparable activity with that of loperamide.Loperamide decreased movement of the charcoal meal in the small intestine by 25.13%.

3.4.4.
In Vivo Antidiarrheal Index.In this study, the total extract showed ADI values of 38.06, 57.79, and 70.91 at doses of 100, 200, and 400 mg/kg, respectively.Among the solvent fractions tested, the methanol fraction was the most efective demonstrating an ADI value of 79.42 at a dose of 400 mg/kg.On the other hand, the chloroform fraction had the lowest

Discussion
In Ethiopian traditional medicine, the crushed leaves of M. addat mixed with water are used for the treatment of diarrhea [18].In this study, 80% methanol was chosen as an extracting solvent as it has been shown to be more efective in extracting both polar and nonpolar compounds from plant materials [26].
In the current study, the castor oil-induced diarrheal model was used to evaluate the antidiarrheal activity of M. addat leaves.Tis model was intended to evaluate the overall antidiarrheal activity of the test substances.Castor oil causes diarrhea through various ways.One of the mechanisms is that it produces the active metabolite ricinoleic acid by intestinal lipases.Ricinoleic acid stimulates the secretion of liquid and electrolytes and increases intestinal motility due to irritation and infammation of the intestinal mucosa that leads to the release of prostaglandins [27,28].Castor oil also inhibits intestinal Na + /K + -ATP-ase activity, which induces diarrhea by reducing normal fuid absorption [29].Te other mechanism is activation of adenylate cyclase or mucosal cAMP-mediated active secretion as well as nitric oxide that induce diarrhea by hypersecretory response [27,29].Loperamide was used as a standard medication due to its antimotility and antisecretory properties, which effectively counteract the efects of castor oil [23].Loperamide acts on the smooth muscle of the intestine similar to opiate antagonists, reducing propulsive motor activity primarily in the jejunum [30].
In the castor oil-induced diarrheal model, the 80% methanol extract of the leaves of M. addat signifcantly delayed the time of diarrheal onset and decreased the frequency of defecation and weight of feces in a dosedependent manner.Terefore, this extract was further fractionated to determine whether the active components of the plant reside in the polar or nonpolar solvents.As shown in Table 1, the overall activity of the methanol and aqueous fractions was superior to those of the chloroform fraction suggesting that polar compound(s) could be responsible for the antidiarrheal activity of M. addat leaves.Moreover, in the castor oil-induced enteropooling test, the efect of the methanol fraction in reducing accumulation of fuid was signifcantly higher than the relatively nonpolar chloroform fraction, which was demonstrated by the drop of both volume and weight of intestinal contents (Table 2).In this model, the secreted fuid is accumulated in the lumen of the intestine as a result of inhibition of absorption caused by castor oil.Terefore, lesser volume of the intestinal content is an indication of antidiarrheal activity produced by a test substance.Similarly, in the castor oil-induced Journal of Tropical Medicine gastrointestinal motility model, the methanol fraction demonstrated a greater efect of reduction in the intestinal propulsive movement of charcoal meal than the aqueous and chloroform fractions (Table 3).Te efectiveness of the methanol fraction in treating diarrhea was confrmed by the determination of its ADI.Unsurprisingly, the methanol fraction exhibited the highest ADI value compared to either the total extract or the other solvent fractions.As ADI is the combined efects of three diarrheal parameters, namely, purging frequency in the number of wet stools, delay in onset of diarrheal stool, and intestinal motility, a high value indicates a more successful treatment of diarrhea [27].
From the foregoing, it was deduced that the active antidiarrheal compounds reside mainly in the polar methanol fraction.Tus, phytochemical analysis of the methanol fraction was undertaken, which resulted in the isolation of quercetin as a major compound.In the present study, quercetin was shown to delay diarrheal onset and decrease stool frequency and weight of feces.It also showed dosedependent decline in the weight and volume of intestinal contents and produced strong antimotility efect.More importantly, quercetin demonstrated a dose-dependent increase in in vivo antidiarrheal index.At a dose of 40 mg/kg, the ADI of quercetin (85.25%) was similar to the standard antidiarrheal agent loperamide (84.28%) revealing its efectiveness to cure diarrhea.Although quercetin was previously isolated from several plants including Maytenus buchananii [31], this is the frst report on the isolation of quercetin from M. addat.
A previous study by Lozoya et al. [32] found that extracts of Psidium guajava leaves, traditionally used as herbal remedy for acute diarrhea in Mexico, inhibit peristalsis of guinea pig ileum in vitro.Te active methanolic extract of the leaf extract was identifed to be rich in favanol glycosides, primarily based on quercetin.It was discovered that these glycosides are hydrolyzed by gastrointestinal fuid to active quercetin, which contributes to the antidiarrheal activity of Psidium guajava.Similarly, Zhang et al. [33] demonstrated that quercetin inhibits peristaltic motion in the mouse small intestine, decreases intestinal movement, and reduces capillary permeability in the abdominal cavity, ofering a potential mechanism for the antidiarrheal efects of P. guajava extract.Te present fndings are also consistent with Carlo et al. [34] who reported that quercetin reduces intestinal transit and intraluminal accumulation of fuid in mice.Terefore, it is highly plausible that the antidiarrheal efect of M. addat is due to the presence of quercetin, which was previously shown to inhibit peristalsis by facilitating inhibitory enteric pathways [35].Terefore, inhibition of the intestinal movement and reduction of capillary permeability in the abdominal activity could be the antidiarrheal mechanism of M. addat leaf extract.All values are articulated as mean ± standard error of the mean (SEM) (n � 5).Data were analyzed by one-way ANOVA followed by Tukey post hoc test.p.o: peroral; NC: negative control; MA100: Maytenus addat 80% methanol leaf extract (100 mg/kg); MA200: Maytenus addat 80% methanol leaf extract (200 mg/ kg); MA400: Maytenus addat 80% methanol leaf extract (400 mg/kg); CF100: chloroform fraction (100 mg/kg); CF200: chloroform fraction (200 mg/kg); CF400: chloroform fraction (400 mg/kg); AF100: aqueous fraction (100 mg/kg); AF200: aqueous fraction (200 mg/kg); AF400: aqueous fraction (400 mg/kg); MF100: methanol fraction (100 mg/kg); MF200: methanol fraction (200 mg/kg); MF400: methanol fraction (400 mg/kg); a: compared to the negative control; b: compared to loperamide; c: compared to 100 mg/kg of MA; d: compared to 200 mg/kg of MA; e: compared to 400 mg/kg of MA; f: compared to 100 mg/kg CF; g: compared to 200 mg/kg of CF; h: compared to 400 mg/kg of CF; i: compared to 100 mg/kg of AF; j: compared to 200 mg/kg of AF; k: compared to 400 mg/kg of AF; l: compared to 100 mg/kg of MF; m: compared to 200 mg/kg of MF; n: compared to 400 mg/kg MF; 1: p < 0.01; 2: p < 0.05; mice in the control group received distilled water (10 ml/kg).

Conclusions
Te present study revealed that both the hydroalcoholic extract and solvent fractions of M. addat leaves possess in vivo antidiarrheal action in mice.Notably, the methanol fraction exhibited the strongest antidiarrheal efects.Phytochemical investigation of the methanol fraction led to the identifcation of 3-hydroxyfavone identifed as quercetin.
Tese fndings provide scientifc support for the traditional use of the M. addat leaves as an antidiarrheal medicine.Te fndings also furnished evidence that quercetin is responsible, in full or in part, for the antidiarrheal activity of the plant [36].

�
Intestinal transit by charcoal meal(control − treated) Intestinal transit by charcoal meal in the control group × 100, Peristaltic index(PI) � Mean distance travelled by charcoal meal Mean length of small intestine × 100.
Castor Oil-Induced Diarrhea.Te mice were fasted for 18 h with access to water only.Animals in each group received their respective doses of the test substances: vehicle, 10 ml/kg of distilled water for negative control; loperamide 3 mg/kg for positive control.Similarly, the treatment groups received their respective doses of the extract or fractions.

Table 1 :
Efects of the 80% methanol leaf extract, solvent fractions, and quercetin isolated from Maytenus addat on castor oil-induced diarrhea.

Table 2 :
Efects of the 80% methanolic leaf extract, solvent fractions, and quercetin isolated from Maytenus addat on castor oil-induced enteropooling in mice.All values are articulated as mean ± standard error of the mean (SEM) (n � 5).Data were analyzed by one-way ANOVA followed by Tukey post hoc test.NC: negative control; MVSIC: mean volume of small intestinal contents; MWSIC: mean weight of small intestinal contents; MA100: MF400: methanol fraction (400 mg/kg); a: compared to the negative control; b: compared to loperamide; c: compared to 100 mg/kg of MA; d: compared to 200 mg/kg of MA; e: compared to 400 mg/kg of MA; f: compered to 100 mg/kg CF; g: compared to 200 mg/kg of CF; h: compared to 400 mg/kg of CF; i: compared to 100 mg/kg of AF; j: compared to 200 mg/kg of AF; k: compared to 400 mg/kg of AF; l: compared to 100 mg/kg of MF; m: compared to 200 mg/kg of MF; n: compared to 400 mg/kg of MF; 1: p < 0.01; 2: p < 0.05; mice in the control group received distilled water (10 ml/kg).

Table 3 :
Efect of 80% methanolic leaf extract, solvent fractions, and quercetin isolated from Maytenus addat on charcoal meal transit in castor oil-induced motility in mice.