Ethanol Extract of Pansit-pansitan Leaves (Peperomia pellucida

Linn.) as an Alternative Antipyretic Medicine

Researchers:

Renz Albert Villanueva

Alliah Cyrelle Mendoza

Kezia May Fadriquela

 Chapter I

Problem and Its Background

Introduction

Fever is the increase of body temperature that is beyond

normal. As a parent, it can be extremely worrying if one of your

children has fever. Most fever cases are caused by infection or

other illnesses like Dengue, Influenza, etc. Fever remains the

most common concern all over the world that prompts parents to

bring their children, and even grown-up relatives, to the

hospital. Fever has traditionally been identified as rectal

temperature over 100.4OF or 38OC. Temperatures that are measured

from other body sites are usually lower from the rectal region.

The threshold for defining a fever does vary significantly among

individuals, since body temperature can vary by as much as 1OF.

Low-grade fevers are usually less than 102.2OF (39OC). Fever

itself is not considered to be life-threatening unless it is

extremely and persistently high, such as greater that 107 OF

(41.6OC) when measured rectally. Risk factors for worrisome fever

includes infants and toddlers less than 2 years of age, or

recurrent fevers that last for more than one week. Fever may

indicate the presence of a serious illness, but is usually caused

by infections, most of which are not serious. The part of the

brain called the hypothalamus controls body temperature. The

hypothalamus increase the body’s temperature as a way to fight

micro-organisms in the body that cause infection. However, many

conditions other than fever may cause a fever.

Peperomia pellucida (Linn.) or also known as Pansit-pansitan

is an erect, branched, annual herb, shallow rooted, reaching up

to 40 centimeters high, with very succulent stems. Stems are

round that is usually around 5mm thick. Leaves are alternate,

heart-shaped and turgid, as transparent and smooth as candle wax.

Spikes are green, erect, very slender and is 1 to 6 centimeters

long. This plant is considered as an anti-inflammatory,

antibacterial, refrigerant, analgesic, antifungal and anticancer.

Preliminary phytochemical screening of methanol extracts of stems

yielded carbohydrates, alkaloids, tannins, flavonoids, steroids,

triterpenoids, with the absence of saponins and proteins.

Proximate analysis of leaves yielded a high ash content, a higher

crude fiber content, and a still higher carbohydrate content.

Mineral analysis showed low manganese, iron, zinc and copper,

with high sodium content. Phytochemical screening yielding

alkaloids, cardenolides, saponins and tannins. Proximate analysis

showed P. pellucida to be rich in crude protein, carbohydrate and

total ash contents. The high ash content (31.22%) suggest a high-

value of mineral composition of potassium, calcium, and iron.

 Antipyretic is an agent or drug that reduces fever. As

pancit- pansitan leaves are natural and traditional medicine used

in fever, the leaves of this plant will provide a cost effective

alternative antipyretic agent. Hence, the present study was

designed to determine the antipyretic effect of ethanol extract

from Peperomia pellucida leaves. We can save money because it

will provide a cost effective alternative antipyretic agent. For

the environment, it will not be a harm because the study is

environmental-friendly.

Statement of the Problem:

The main objective of this study is to determine he

antipyretic effect of ethanol extract from Pansit-pansitan

(Peperomia pellucida) leaves and to produce a cost effective

alternative antipyretic agent.

Specifically, this study will seek to answer the following

research questions:

1. What is the active component of pansit-pansitan that can be

made as an alternative antipyretic agent?

2. What is the effect of using ethanol extract of pansit-

pansitan leaves in terms of:

 2.1 Rectal temperature of rats?

3. Are there significant difference between the experimental

product and the commercial product in terms of:

3.1 Color; and

3.2 Odor?

Null Hypothesis:

The researcher will be guided by the following

hypothesis:

1. The Pansit-pansitan has no active component that can be

made as an alternative antipyretic agent.

2. Using the ethanol extract of pansit-pansitan leaves has

no effect in terms of:

2.1 Rectal Temperature of Rats

3. There are no significant difference between the

experimental and commercial product in terms of :

3.1 Color; and

3.2 Odor.
Significance of the Study

The significance of the study is that, people can save money

because it will provide a cost-effective alternative antipyretic

agent. For the environment, it will not be a harm because this

study is environment-friendly.
 Chapter II

Review of Related Literature

Related Literature
A fever is a temporary increase in your body temperature, often

due to an illness. Having a fever is a sign that something out of the

ordinary is going on in your body. For an adult, a fever may be

uncomfortable, but usually isn't a cause for concern unless it

reaches 103 F (39.4 C) or higher. For infants and toddlers, a

slightly elevated temperature may indicate a serious infection.

Fevers generally go away within a few days. A number of over-the-

counter medications lower a fever, but sometimes it's better left

untreated. Fever seems to play a key role in helping your body

fight off a number of infections (Mayo Clinic, 2017).

Fever occurs when an area in your brain called the

hypothalamus, also known as your body's "thermostat", shifts the

set point of your normal body temperature upward. When this

happens, you may feel chilled and add layers of clothing or wrap

up in a blanket, or you may shiver to generate more body heat,

eventually resulting in an elevated body temperature. Normal body

temperature varies throughout the day, it's lower in the morning

and higher in the late afternoon and evening. Although most

people consider 98.6 F (37 C) normal, your body temperature can

vary by a degree or more, from about 97 F (36.1 C) to 99 F (37.2

C), and still be considered normal (Mayo Clinic, 2017)

Fever is a complex physiologic response triggered by

infectious or aseptic stimuli. Elevations in body temperature

occur when concentrations of prostaglandin E2 (PGE2) increase

within certain areas of the brain. These elevations alter the

firing rate of neurons that control thermoregulation in the

hypothalamus. Although fever benefits the nonspecific immune

response to invading microorganisms, it is also viewed as a

source of discomfort and is commonly suppressed with antipyretic

medication. Antipyretics such as aspirin have been widely used

since the late 19th century, but the mechanisms by which they

relieve fever have only been characterized in the last few

decades. It is now clear that most antipyretics work by

inhibiting the enzyme cyclooxygenase and reducing the levels of

PGE2 within the hypothalamus. Recently, other mechanisms of

action for antipyretic drugs have been suggested, including their

ability to reduce pro-inflammatory mediators, enhance anti-

inflammatory signals at sites of injury, or boost antipyretic

messages within the brain. Although the complex biologic actions

of antipyretic agents are better understood, the indications for

their clinical use are less clear. They may not be indicated for

all febrile conditions because some paradoxically contribute to

patient discomfort, interfere with accurately assessing patients

receiving antimicrobials, or predispose patients to adverse

effects from other medications. The development of more selective

fever-relieving agents and their prudent use with attention to

possible untoward consequences are important to the future

quality of clinical medicine (David M Aronoff, et, al., 2001).

Fever is a prominent feature of disease since antiquity. The febrile

response is orchestrated by the central nervous system through

endocrine, neurological, immunological and behavioural mechanisms.

Other than a regulated rise in body temperature, fever is often

accompanied by various sickness behaviours, changes in metabolic and

physiological characteristics of body systems and alterations in

immune responses. Fever and the febrile response, therefore, remain

significant contributors to the pathogenesis, clinical presentation

and outcome of many illnesses and diseases. This review highlights

the pathophysiology of the febrile response and describes the

fever types and patterns, including their clinical significance.

The various medical illnesses called “fever” are also listed and

the origins of their appellations discussed (Dimie Ogoina, 2011)

Both external cooling and pharmacotherapy have been used to

treat fever since time immemorial. In the past century such

treatments have proliferated at an astonishing rate. The COX-2

inhibitors are the most recent additions to the antipyretic

pharmacopoeia. Additional research is needed to determine whether

they represent an important new chapter in antipyretic therapy's

long history or, for that matter, if the benefits of any

currently available treatment for fever outweigh its cost. The

origin of antipyretic therapy is not known. When Alexander the

Great was stricken with the mysterious febrile illness that would

take his life in 323 BC, the Babylonian physicians who cared for

him prescribed cool baths as treatment for his unremitting fever.

Preceding generations almost certainly used similar external

cooling measures to relieve fever, as we still do to the present

day (Philip A. Mackowiak, October 2001). By the early 1900s an

expanding array of antipyretic compounds had been discovered and

incorporated into the clinical pharmacopoeia. These included

antipyrine (1884), antifebrin (1886), phenacetin (1887),

acetaminophen (1888), and pyramidon (1896). These were followed

shortly thereafter by phenylbutazone (1949), the fenamates

(1950s), and indomethacin (1963). Before 1971 little was known of

the mechanisms by which drugs such as aspirin exerted their

antipyretic and anti-inflammatory effects. Early theories held

that such drugs functioned in some way by stabilizing cell

membranes or by inhibiting certain proteases involved in the

inflammatory process. Eventually research into the mechanism of

action of aspirin-like drugs focused on the effects of these

agents on prostaglandin synthesis (Philip A. Mackowiak, Clinical

Infectious Diseases, Volume 31, Issue Supplement_5, October

2000).
 Relieving discomfort and reducing body temperature to a

normal level are both goals in treating fever, but it is also

important to identify and treat the fever’s underlying cause.

Fever treatment includes the use of various OTC antipyretics as

well as a host of non-pharmacologic measures. Available OTC

antipyretics include acetaminophen and the non-steroidal anti-

inflammatory drugs aspirin, ibuprofen, and naproxen.

Acetaminophen and ibuprofen are the 2 most widely used

antipyretics. Ibuprofen is only approved for fever reduction in

patients 6 months and older, however. These products are

available as single-entity or combination products in extended

release versions and come in a variety of forms, including

tablets, capsules, gel capsules, liquid gels, enteric coated,

liquids, suspensions, and chewable tablets for adult and

pediatric patients (Yvette C. Terrie, BSPharm, RPH, 2012).

Related Study

The main objective of the current study is to investigate

the potential of Carica papaya leaves extracts against Dengue

fever in 45 year old patient bitten by carrier mosquitoes. For

the treatment of Dengue fever the extract was prepared in water.

25 mL of aqueous extract of C. papaya leaves was administered to

patient infected with Dengue fever twice daily i.e. morning and

evening for five consecutive days. Before the extract

administration the blood samples from patient were analyzed.

Platelets count (PLT), White Blood Cells (WBC) and Neutrophils

(NEUT) decreased from 176 × 103/μL, 8.10 × 103/μL, 84.0% to 55 ×

103/μL, 3.7 × 103/μL and 46.0%. Subsequently, the blood samples

were rechecked after the administration of leaves extract. It was

observed that the PLT count increased from 55 × 103/μL to 168 ×

103/μL, WBC from 3.7 × 103/μL to 7.7 × 103/μL and NEUT from 46.0%

to 78.3%. From the patient feelings and blood reports it showed

that Carica papaya leaves aqueous extract exhibited potential

activity against Dengue fever. Furthermore, the different parts

of this valuable specie can be further used as a strong natural

candidate against viral diseases (Nisar Ahmad, et, al., Asian

Pacific Journal of Tropical Biomedicine, Volume 1, Issue

4, August 2011)

The objective is to study the antipyretic effect of three

different drugs used to treat fever in children paracetamol

(Cetal® syrup), metamizole sodium (Novalgin® syrup) and

diclofenac potassium (Catafly® syrup). Fever is a common symptom,

the most frequent causes of fever are infections. Although it is

necessary to treat the cause of fever, fever management is also

important, we wanted to study the patients' discomfort

accompanying fever and the beneficial effects of the fever

management. The fever discomfort can be an important reason for

the antipyretic treatment. Three antipyretics were tested in

three groups of patients, The study included 60 patients with

axillary temperature at least 37.60C, patients were divided into

three equal groups each group of 20 patients, group A received

paracetamol at dose of 15mgkg4hrs, group B received metamizole

sodium at dose of 15mgkg6hrs, and group C received diclofenac

potassium at dose of 1mgkg8hrs, we asked the first 30 study

subjects to fill in a questionnaire concerning their opinions

about fever, fever-associated discomfort, and relief upon

antipyretic therapy. All study medications had a significant

antipyretic effect. Diclofenac potassium at the dose 1 mgkg was

considered as the most effective as that of metamizole sodium

which is more effective than paracetamol. All tested antipyretics

significantly improved comfort in fevered children (Naglaa A.

Elmaghraby, et, al., The Journal of American Science, Volume 10,

2014).
 Chapter III

Methodology

Materials and Equipment

The researcher prepared the following materials and

equipment for the conduct of the study: 425 grams of Pansit-

pansitan leaves, 3 Liters of 95 percent ethanol, beaker, amber

bottle, stirring rod, strainer and cheesecloth. The equipment

used is Rotary Evaporator.

General Procedure

A. Collection of plant samples

Collect Pansit-pansitan plant in the same region or place to

ensure the uniformity among the plant samples. Gather 1 kilogram

of pansit-pansitan.

B. Collection of Pansit-pansitan leaves

Remove and separate the unnecessary parts of the pansit-

pansitan like stem and roots.

C. Extraction of Pansit-pansitan leaves

In the extraction process, macerate four hundred twenty-five

grams (425g) of pansit-pansitan leaves in three liters (3L) of

ninety-five percent (95%) ethanol. Macerate the mixture for

twenty-four (24) hours. After macerating the leaves, filter the

mixture using the strainer and cheese cloth. Put the extract in

the rotary evaporator and evaporate it under reduced pressure.

Separate the ethanol solution and keep the pansit-pansitan leaves

extract in a sealed, clean amber bottle. It will serve as the

experimental anti-pyretic medicine solution.

Testing Procedure

A. Rectal Temperature

The experiment will be carried out on Sprague Dawley Rats.

Keep the rats in iron cages to adjust to the environment. Feed

them with apple, rabbit pellet, and tap water for 40 days before

the experiment. Food and water will be withdrawn 6h prior to the

experiment. The animals will be grouped into two: the

experimental and control group. The experimental group will

receive the pansit-pansitan leaves extract and the control group

receiving the standard antipyretic agent solution. Before

starting the experiment, measure and record the rectal

temperatures of the rats using a rectal temperature probe

inserted into the rectum (Note: make sure to insert it with care

and the same depth each time). Inject the rats with boiled milk

at room temperature at the dose of 0.5.

Data Analysis

Use randomized block ANOVA for the comparison between the

experimental group who will receive the ethanol extract of

pansit-pansitan leaves, and control group who will receive the

standard antipyretic agent solution.