Pharmacon: Jurnal Farmasi Indonesia Vol.
21 No.
, pp.
DOI: 10.
23917/pharmacon.
p-ISSN: 1411-4283, e-ISSN: 2685-5062 Stimulant Activity of White Pepper (Piperis albi Fructu.
Ethanol Extract In Vivo Arini Khaerunnisa1*.
Dhyneu Dwi Jayantie2.
Sutihat3.
Nurul Hida4.
Nani Suryani5 1-4Program Sarjana Farmasi.
Fakultas Sains.
Farmasi dan Kesehatan.
Universitas MathlaAoul Anwar.
Pandeglang.
Banten.
Indonesia 5Program Sarjana Kimia.
Fakultas Sains.
Farmasi dan Kesehatan.
Universitas MathlaAoul Anwar.
Pandeglang.
Banten.
Indonesia *Corresponding author: arinikhaerunnisa1@gmail.
ARTICLE HISTORY:
Submitted : 2023-08-01 Accepted : 2024-06-17 Published : 2024-06-30 KEYWORDS:
In vivo.
Natatory exhaustion.
Stimulant.
White pepper Citation:
Khaerunnisa.
Jayantie.
Hida.
, & Suryani.
Stimulant Activity of White Pepper (Piper nigrum L.
Ethanol Extract In Vivo.
Pharmacon: Jurnal Farmasi Indonesia, 21.
, 1Ae10.
https://doi.
org/10.
23917/pha ABSTRACT Caffeine is a stimulant substances that can stimulate the central nervous system (CNS) increasing concentration, and reducing drowsiness.
The use of caffeine generally comes from coffee plants which can increase gastrin secretion.
Long-term use of caffeine can cause side effects such as feelings of anxiety, irritability, insomnia and faster heart rate.
alternative stimulant that has limited side effects is needed.
White pepper (Piperis albi fructu.
is potential as stimulant.
The extract of White pepper contained piperine compound.
Piperine can potentially be a stimulant because it can stimulate the formation of energy in the body.
The purpose of this study was to determine the in vivo stimulant activity of ethanol extract White pepper in male white mice.
The method used in this research is Natatory exhaustion.
25 test animals were divided into 5 groups.
The doses used are white pepper extract 0.
65 and 1.
3 mg/20 g BW, 26 mg/20 g BW and 0.
5% CMC-Na.
Data analysis with SPSS 16 with the Kruskal-Wallis test and the Mann-Withney test.
The results of the stimulant activity test of white pepper ethanol extract at a dose of 0.
65 and 1.
3 mg/20 g BW for male white mice with the DDY strain with an average % increase in stamina of 63.
81 and 179.
31%,mean while in the positive control of caffeine by 232.
55% and the negative control of CMC-Na by 21.
White pepper ethanol extract dose of 1.
3 mg/20 g BW has stimulant activity which is not significantly different from caffeine positive control.
INTRODUCTION
Energy is needed by human to carry out physical activities.
Energy needs increase with heavy physical activity, so it requires a lot of energy to eliminate the feeling of fatigue that occurs (Setyowati et al.
, 2.
Physical activity can occur due to muscle concentrations.
Energy in the form of adenosine triphosphate (ATP) is required for muscle contraction.
triphosphate is then hydrolyzed to adenosine diphosphate (ADP) and used for muscle The limited amount of adenosine triphosphate in the body causes short muscle contractions and causes fatigue (Herwana et al.
Fatigue is a condition where the body experiences a lack of energy.
To eliminate fatigue a person needs to consume stimulants (Mustopo.
Setyowati et al.
, 2.
Stimulants can cause a person to increase enthusiasm, reduce fatigue and increase alertness.
Stimulants work by speeding up the central nervous system (CNS) as the controller of all body activities and the center for regulating information Central nervous system stimulation by stimulants can increase physical and mental abilities, concentration, so that it can make a person more prepared and minimize fatigue (Katzung, 2014.
Tary & Sujono, 2018.
Wade & Travis, 2.
The substance that is widely used by people as a stimulant is caffeine which comes from A 2022 The Author.
This work is licensed under a Creative Common Attribution 4.
0 (CC-BY) International .
ttps://creativecommons.
org/licenses/by/4.
Pharmacon: Jurnal Farmasi Indonesia.
Vol.
21 No.
, pp.
coffee, which can reduce fatigue and drowsiness.
However, long-term use of caffeine can cause side effects, feelings of anxiety, restlessness, irritability, insomnia and a faster heart rate.
the gastrointestinal system, caffeine can increase gastrin secretion, increasing gastric acid High inflammation and erosion of gastric mucosa and cause dyspepsia so that not everyone can consume coffe.
Therefore, alternative stimulants are needed that have minimal side effects (Fithriyana, 2018.
Rahmi et al.
, 2.
White pepper (Piper albi fructu.
is a member of the Piperaceae family which has potential as a Based on previous research.
White pepper has antihypertensive, antiasthmatic, antimicrobial, antioxidant, anticancer, antiinflamatory, hepato-protective, antidiarrheal, anticonvulsant and analgesic properties (Damanhouri, 2.
White pepper contains essential oils .
2%),
5%) and piperine alkaloids .
(Boangmanalu & Zahrotun, 2.
The piperine compound in black pepper has antiinflammatory activity (Levita et al.
, 2.
anti-microbial, antitumor, cytotoxicity.
Piperine stimulates a dose-dependent increase in the secretion of gastric acid and interruption of gastrointestinal The oral administration of piperine activates the liver, pancreas and digestive enzymes in the small intestinal mucosa.
The addition of piperine in food materials as food flavours may increase the protease, lipase and pancreatic amylase activities (Ashokkumar et al.
The piperine compound is reported to have four isomers namely piperine, isopiperine, chavicin and isochavicin (Damanhouri, 2.
The piperine compound in black pepper has the potential as a stimulant and the chavicin compound has the potential to stimulate enthusiasm (Gorgani et al.
, 2.
There are differences in piperine levels in black pepper and white pepper.
The 96% ethanol extract of black pepper and white pepper contain piperine levels 97 A 11.
95% and 38.
72 A 8.
respectively (Hikmawanti et al.
, 2.
Based on the description above, there is no information regarding the stimulant activity of white pepper ethanol extract, so research was carried out on the potential stimulant activity of white pepper extract which can reduce fatigue due to work activities METHODS Materials White pepper was collected from Cigeulis Pandeglang, 96% ethanol.
HCl.
Mg Powder, amyl alcohol, ammonia, chloroform.
H2SO4.
Mayer reagent.
Wagner reagent.
FeCl3, anhydrous acetic acid, 25 male white mice of the Deutschland Denken Yoken (DDY) strain.
Caffein.
CMC-Na, distilled water.
Plant Determination Twenty .
kg of white pepper was collected from Cigeulis Pandeglang.
Banten.
Plants were determined at the Herbarium Bogoriense.
Directorate of Scientific Collection Management at BRIN Cibinong.
Sample Preparation and Extraction White pepper is prepared by soaking in water, so that the skin peels off.
Then the samples were cleaned, dried and ground.
The powder of white pepper was sieved using mesh No.
White pepper was macerated using 96% ethanol solvent in a ratio of 1:2 w/v for 3 x 24 The macerate was concentrated using a vacuum rotary evaporator until a concentrated extract was obtained.
Phytochemical Screening Flavonoid identification As much as 1 g of simplicia white pepper was added to 10 mL of hot distilled water, then heated for 10 minutes and filtered.
2 mL of filtrate was added with 1 mL of concentrated HCl, and 0.
1 g of Mg Powder and 2 mL of amyl The color change in the amyl alcohol layer to yellow, red or orange indicates that the white pepper contains flavonoid compounds (Hasibuan & Edrianto, 2.
Alkaloid Identification As much as 1 g of simplicia was added with 10 mL chloroform and a few drops of ammonia.
The chloroform fraction was separated then concentrated H2SO4 was added.
5 mL of the fraction was taken and 2 drops were added to each Mayer and Wagner reagent tube.
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indicates that white pepper contains alkaloid compound (Syafitri et al.
, 2.
days for environmental adjustment, supervision and uniformity of food (Isnenia, 2.
Saponin Identification Stimulant Test As much as 1 g simplicia white pepper was diluted with 10 mL of hot distilled water, then shaken vigorously for 15 minutes.
If the foam dose not dissapear with the addition of 1 drop of HCl, this indicates the presence of saponin (Syhadat & Siregar, 2.
Experimental animals were fasted for 3-4 hours, aimed at emptying the stomach to speed up drug absorption.
The mice were then swam in an aquarium filled with water.
Then the mouseAos tired time was recorded using a stopwatch.
Mice were tired when they lower their heads or experience struggling phase until they felt below the water surface for 7 seconds.
Next, the mice were rested for 15 minutes.
After that, the mice were treated according (Table .
After 30 minutes of diving the sample, the mice swam back into the aquarium and the miceAos fatigue time was recorded.
The % increase in mice stamina was calculated (Sidrotullah et al.
, 2.
Tannin Identification As much as 1 g of simplicia white pepper was dissolved in distilled water, filtered.
2 mL of filtrate was added with 2 drops of 1% FeCl3 Positive results were indicated by green or blue-black color change (Hasibuan & Edrianto, 2.
Terpenoid and Steroid Identification As much as 1 g of simplicia white pepper was dissolved in chloroform, then filtered.
The filtrate was added with 1 mL of anhydrous acetic acid and 2 mL of concentrated H2SO4 (Lieberman Bucard tes.
Terpenoid positive if a red or purple color forms and steroid positive if a green or blue color forms (Rahimah et al.
In Vivo Stimulant Activity Test Review the Ethics of Experimental Animals The ethical review was carried out the Medical and Health Research Ethics Commission.
Muhammadiyah University.
Prof.
Dr.
Hamka (KEPKK-UHAMKA).
Ethical reviews were carried out to test the feasibility of research and to find out the reason for using test animals by considering the suffering that will be experienced by the test animals and the benefits that will be obtained for human (Ridwan, 2.
Preparation of Experimental Animals The sample size for experimental animals used the Federer formula, namely .
Ou 15 .
n = repetition % yeOyeayeEyeeyeIyeCyeiyeI yeOyea yeiyeiyeCyeayeOyeayeC = yeiyaOeyeiya
t1 = fatigue time before being given the test
t2 = fatigue time after being given the test
RESULT AND DISCUSION
Table 1.
Stimulant test treatment of ethanol extract of P.
Treat Sample Control ( ) Control (-) White papper extract White papper extract White papper extract Caffein CMC-Na 0.
Dose .
g/20 g BW) Determination results The determination results showed that the plant specimen was indeed the Piperis albi fructus plant from Piperaceae family.
Determination is the stage of determining the name of a specific type of plant.
Carried out to determine the correctness of sample to be used (Soemarie et al.
, 2.
t = treatment .
umber of treatments was .
The number of experimental animals that will be used is 25 male white mice of the Deutschland Denken Yoken (DDY) strain (Uthia et al.
, 2.
Before the research, mice were acclimatized for 7 https://journals2.
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Table 2.
Identification results of P.
nigrum fruit simplicia phytochemical screening Reagent HCl Mg powder amyl Wagner Mayer Hot distilled water HCl 2 N FeCl3 1% Liebermann-Burchard Liebermann-Burchard Sample Results Preparation Observation Results Red color Description Positive flavonoid Brown precipitate White precipitate Foam that didnAot disappear Blackish blue color No green or blue color formed Purple color Positive alkaloid Positive alkaloid Positive saponin Positive tannin Negative steroids Positive triterpenoids Extraction White pepper originating from Cigeulis.
Pandeglang.
Banten.
White pepper fruit was made into simplicia, then the samples were blended into powder and sieved using a mesh sieve No.
Refining aims to reduce the size of simplicia particles, thereby maximizing the extraction process by expanding the surface contact between the filter liquid and the active compounds contained in white pepper (Ahwan.
White pepper simplicia powder was extracted using the maceration method with 96% ethanol solvent.
Maceration aims to extract active substances that are not resistant to The reason for choosing the 96% ethanol solvent was that the extraction of piperine compounds can be done with polar solvents (Wendersteyt et al.
, 2.
The results of making 1000 g of white pepper extract from simplicia with 6000 mL of solvent resulted in a thick extract of 90.
747 g with a yield percentage of 9.
Phytochemical Screening The results of the phytochemical screening identification carried out on the white pepper simplicia to determine the class of secondary metabolite compounds contained in white The result showed that it positively contained flavonoids, alkaloids, saponins, tannins and triterpenoids which can be seen in Table 2.
Results of In vivo Stimulant Activity The results of the ethical review showed that the in vivo research protocol could be approved for implementation and passed ethical review (Ethical approval number: 03/22.
08/02.
Acclimatization Results The male white mice of the DDY strain had an average weight before acclimatization .
and after acclimatization for 7 days the average weight increased .
(Table .
Table 3.
Body weight of acclimatized mice Body weight of mice .
in various Average weight of mice: 28.
Coefficient Varians (CV): 4.
Terms of (CV): <15% The experinmental animals used in this research were male mice.
Before testing, 30 mice were grouped into 6 groups, where each group consisted of 5 mice.
Mice that have just arrived are weighed first to determine the initial Coefficient of Variance (CV).
The initial CV results obtained were 5.
77% eith an average body weight of 20.
3 g.
Then the animals were acclimatized for 7 days.
Acclimatization aims to enable the experimental animals to adapt to the new environment and to obtain a homogeneous mouse weight.
The homogeny of experimental animals can be determined by calculating the CV with a tolerance standard of <15%.
The CV aims to observe data variations or the distribution of If the CV is smaller, the more diverse .
the data (Efia, 2.
After acclimatization, the weight of the mice incerased with a CV value 4.
46% .
ulfilling the requirement.
with an average body weight of 1 g.
Results of Stimulant Activity In this test, mice will experience two phases.
In the first phase the mice will swim their head https://journals2.
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and both legs up .
truggling phas.
and after that the mice will experience a phase where the body position is no longer horizontal and the miceAos four legs do not move in the water .
loating phas.
The floating phase ends when the mouse begins to sink and the mice is immediately lifted.
The results of the histogram data can be seen Table 4 showing that all treatment doses have a stimulant effect.
The dose of white pepper extract at a dose of 1.
3 mg/20 g BW provided the highest stimulant effect with a % increase of The results of caffeine control showed a % increase of 232.
White pepper extract doses of 0.
32 and 0.
65 mg/20 gBW showed a % increase in stamina of 63.
92 and 120.
Based on data analysis using the KruskalWallis test, results were obtained that were significantly different between treatments at all doses before administration of the extract with an Asymp.
Sig value obtained of 0.
000 (<0.
The Mann-Whitney further test was carried out to see the differences between the treatment group and the control group.
The results showed that at a dose 1.
3 mg/20 g BW, white pepper extract had no significant difference with positive control caffeine with an Asmp.
Sig value 347 (>0.
The piperine compound found in black papper is an alkaloid which is efficacious for increasing stamina (Sumarny et al.
, 2.
The mechanism of action of alkaloid compounds as stimulants is by inhibiting the phosphodiesterase enzyme.
Inhibition of the posphodiesterase enzyme can increase the synthesis of 3Ao5Ao-adenosine monophosphate .
yclic AMP) (Febrianasari et al.
, 2.
An additional source of energy for the body is glucose 6 phosphate which is formed through cyclic AMP activating the phosphorylakinase enzyme, and converting glycogen in the body into glucose 1 phosphate, then with the enzyme glucophosphomutase, glucose 1 phosphate is converted into glucose 6 Glucose 6 phosphate makes the body more active or has a stimulant effect (Ferreira et , 2.
The mechanism of action of caffein in increasing stamina is by inhibiting the phosphodiesterase enzyme and can also block adenosine receptors which work in the opposite way to caffeine.
Adenosine has great influence on nerve cell activity (Winata, 2.
Secondary metabolite compounds in pepper include alkaloids, flavonoids, tannins, saponins, glycosides and essential oils.
Physiologically, they can increase blood circulation by improving body activity so that it will indirectly improve organ function by increasing the motor activity of experimental animals and fatigue threshold value (Sumarny et al.
, 2.
Flavonoids can provide a tonic effect by working as adenosine A1 receptor antagonists which play a role in sleep regulation.
Flavonoids such as isoflavones will eliminate drowsiness and fatigue, thereby producing freshness and enthusiasm in the body (Annisa et al.
, 2.
Table 4.
Results of the stimulant activity test of white paper extract Treatment Control ( ) Control (-) .
<0.
>0.
Sample White pepper extract .
32 mg/20 g BW) White pepper extract .
65 mg/20 g BW) White pepper extract .
3 mg/20 g BW) Caffein .
26 g/20 g BW) CMC-Na 0.
CONCLUSIONS
Simplicia of white pepper was positive for containing secondary metabolism of flavonoids, alkaloids, saponins, tannins and triterpenoids.
Average Increase in stamina (%) 92 A 26.
81 A 24.
21 A 25.
55 A 85.
10 A 2.
The 96% ethanol extract of white pepper fruit at a dose of 1.
3 mg/20 g BW had the most active stimulant activity with an average value % increase in stamina of 179.
31% which was not https://journals2.
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significanly different from the positive control
ACKNOWLEDGMENT