CHAPTER 2

Review of Related Literature and Studies

Piper betle from the family of Piperaceae is a tropical, shade-loving, perennial

evergreen climbing vine whose height reaches 2 to 4 meters. Piper betle leaves, more

commonly known as “Ikmo” or “Buyo”, is very popular in the Philippines where it is

used as a masticatory with nga-nga (Areca catechu) and apog (lime).

Piper betle contains secondary metabolites such as volatile oils, alkaloid called

arakene whose properties are very similar to cocaine, and phenols. In addition to those

mentioned above, Piper betle also yields active compounds like hydroxychavicol,

hydroxychavicol acetate, allypyrocatechol, chavibetol, piperbetol, methylpiperbetol,

piperol A, and piperol B. These constituents are responsible for the therapeutic uses of

Ikmo which is used in traditional medicine as antitussive, carminative, astringent,

stimulant, expectorant, antiseptic, anti-inflammatory, anti-fungal, anti-bacterial.

Bacteria was one of the most common cause of deadly diseases but with the

discovery of antibiotics, this problem was slowly resolved. However, due to inadequate

use of antibiotics, multidrug resistance developed and continues to be a challenge to the

healthcare sector.

Multidrug resistance is often described as decreased in vitro biological activity to

multiple class of drugs without considering remaining effective therapies. This leads to

bacterial strains being resistant to antibiotics. Some of the bacterial strains that are
resistant to multiple drugs are Staphylococcus aureus, Methicillin-resistant

Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes.

Staphylococcus aureus is a golden spherical bacterium frequently found in the

nose, throat, intestine, vagina, and skin of human body. It is a round and bunched

together pathogen and has the ability to cause different kinds of mild to severe infections

and it is capable to adapt fast to the different environmental conditions.

Methicillin-Resistant Staphylococcus aureus occurs due to the extensive use of

antimicrobial agents, coupled with the transmission of an appreciable proportion of the

organism by person-to-person contacts. MRSA are common in both community-onset

infections caused by circulating clones and in hospital-acquired infections. (Onanuga and

Temedie, 2011)

Pseudomonas aeruginosa is the most common pathogen isolated from patients

who have been hospitalized longer than 1 week, frequently causing nosocomial

infections.

Streptococcus pyogenes is a gram-positive, β-hemolytic streptococcus that is

catalase negative. It is a group A streptococcus based on its carbohydrate structure,

according to Lancefield typing of β-hemolytic strains. This bacterium is responsible for a

wide array of infections such as streptococcal pharyngitis, impetigo, erysipelas, cellulitis,

scarlet fever, bacteremia, and pneumonia. (Bryant et. al., 2015)

Medical practitioners may use alternative drug or a combination therapy for the

infections caused by these bacterial strains but the use of synthetic drugs may subject the

patient to higher risk because of harmful side effects. To overcome this problem, the use
of natural products from natural sources is emerging. Traditional medicinal plants are

responsible for a variety of therapeutic properties known, one of which is antimicrobial.

Among the traditional medicinal plants used, the ethanolic crude extract of Piper

betle leaves showed the highest antibacterial activity against the Gram-positive

methicillin-resistant Staphylococcus aureus and Vancomycin-resistant Enterococcus in

the disk diffusion (16-33 mm inhibition diameter), minimum inhibitory concentration

(19-156 μg/mL) and minimum bactericidal concentration (312 μg/mL) assays. Piper betle

leaf extracts showed remarkable antibacterial activity for all the Gram-negative

multidrug-resistant bacteria (extended spectrum β-lactamase-producing, carbapenem-

resistant enterobacteriaceae and metallo-β-lactamase-producing) in the disk diffusion (17-

21 mm inihibition diameter), minimum inhibitory concentration (312-625 μg/mL) and

minimum bactericidal concentration (312-625 μg/mL) assays. Piper betle had the greatest

potential value against both gram negative and gram positive multi-drug resistant

bacteria. (D.L. Valle Jr. et. al., 2015).

Drugs intended for skin infections are usually formulated into ointments for

topical application. Ointments are greasy and they stay on the surface of the skin and are

not well absorbed, thus are “occlusive”. They are best used on dry skin and they trap

moisture that’s why they are able to keep the skin moist for longer periods of time. They

have lesser chance of causing allergy because of few preservatives. Ointments allow

better penetration of the active ingredient in the topical medication and they are better

used on sensitive skin.

According to Pawar and Nabar, hydrophilic ointment, petroleum jelly and oil

base did not exhibit any zone of inhibition towards the resistant organism due to reduced
diffusible property of the formulated ointment. Ointments prepared in water soluble

exhibited good antibacterial activity. Base A, polyethylene glycol base, carbopol base and

honey showed good antibacterial property which are water-soluble and water-washable.