CHAPTER 2

REVIEW OF RELATED LITERATURE

Medicinal plants are discovered and are being used in different medicine practices over a

hundred of years for the treatment of different types of ailments. They are said to be one of the

oldest product for treatment. They are also the richest source of different drugs of traditional

medicine and modern time medicine that are being used today and they evolved over the period

of time because of different researches and further studies. Medicinal plants are still widely used

because drugs that are produced naturally are better than synthetic drugs and can be tolerated by

the body. This chapter includes complete study about different literatures related to the topic.

Corchorus capsularis Linn. Leucosyke capitellata Wedd.

Botonical Hierarchy

Kingdom: Plantae Kingdom: Plantae

Division: Tracheophyta Division: Tracheophyta

Class: Magnoliopsida Class: Magnoliopsida

Order: Malvales Order: Rosales

Family: Maluaceae Family: Urticaceae

Genus: Corchorus L. Genus: Leucosyke

 Species: Corchorus olitorius L. Species: Leucosyke capitellta

Angiogenesis

Cancer is a major cause of death worldwide and angiogenesis is critical in cancer

progression. (Kadioglu et al., 2013) Angiogenesis is a normal and vital process in growth and

development, as well as in wound healing and in the formation of granulation tissue. This is a

physiological process of new blood vessel development from pre-existing capillaries. (Salas et

al., 2015) Chemical signals in the body helps in the formation and repair of the blood vessels.

However these signals are well balanced in such a way that blood vessels are formed only when

they are needed. (A. L. Magdalin Joy et al., 2016) Angiogenesis happens all over lifetime in

health as well as illness, starting from utero and ongoing throughout adulthood. (Abd et al.,

2017) In the adult, except for a few physiological processes such as menses, wound healing, and

placental formation, all angiogenic processes are pathologic. By blocking the development of

new blood vessels, one hopes to cut off the tumor’s supply of oxygen and nutrients and,

therefore, its growth and spread to other parts of the body. (Kota et al., 2018) The formation of

new blood vessels needs to be highly regulated because blood vessels that grow too exuberantly

can have detrimental effects. Diseases that are related to excessive angiogenesis include

retinopathy, liver cirrhosis, psoriasis and cancer. Since the process plays an important role in

these pathological conditions, inhibition of angiogenesis is one promising approach in their

therapy and management. (Camposano et al., 2016) In 1994, The Angiogenesis Foundation

declared angiogenesis as a ‘common denominator’ in the most important diseases of society. In

many serious diseases states, the body loses control of angiogenesis. (Tai-Ping Fan et al., 2006)

In the Philippines, however, there were few studies being conducted among our herbal plants

with regards to their potentials as angiogenesis inhibitors. (Salas et al., 2015)

 The process of angiogenesis can be simply described into three major steps including:

I. Initiation of the angiogenic response

Angiogenesis is initiated in response to hypoxia, by the release of hypoxia inducible factors

(HIF), which facilitate the release of angiogenic stimulators, which in turn lead to EC activation.

In both physiological and pathological angiogenesis, EC activation is the first process that takes

place. Activated EC secrete proteases, which degrade the extracellular tissue to facilitate

endothelial penetration. Proteases may be broadly divided into matrix metalloproteases (MMPs)

and the plasminogen activator (PA) / plasmin system. The MMPs are capable of degrading

different protein types. PAs activate the plasminogen into plasmin, which degrades several

components of extracellular matrix (ECM). Both PAs and MMPs are secreted together with their

inhibitors, plasminogen activator inhibitors, and tissue inhibitors of metalloproteases,

respectively, ensuring a stringent control of local proteolytic activity. (Bisht et al., 2010)

II. Endothelial cell migration, proliferation, and tube formation

Extracellular matrix degradation results in an increased concentration of various growth factors,

which stimulate EC migration and proliferation. The ‘leader’ EC, followed by more EC, starts to

migrate through the degraded matrix, thus forming small sprouts. After the initial period of

migration, rapid EC proliferation begins, thus increasing the rate of sprout elongation. These

processes are also mediated by cell adhesion molecules. Cell adhesion molecules can be

classified into four families and neovascularization is facilitated by the member of each family.

Integrin αvβ3and αvβ5, vascular endothelial cadherin, vascular cell adhesion molecule-1, P-

selectin, and E-selectin are implicated in angiogenesis. (Bisht et al., 2010)

III. Maturation of the neovasculature

The final phase of the angiogenic process involves maturation of the neovasculature. The new

basement membrane is synthesized by the newly forming capillaries. During this process

extracellular proteolysis is locally inhibited to permit the deposition and assembly of the ECM

components. After the formation of the capillary sprout, degradation of the newly formed ECM

occurs again at the tip of the sprout, to allow further invasion. Interaction between the EC and

ECM and the mesenchymal cells is a prerequisite for the formation of a stable vasculature. The

polarity of the endothelial cells is established by cell adhesion molecules in order to form a

lumen. The platelet-derived growth factor (PDGF) regulates the recruitment of pericytes and

smooth muscle cells required for further stabilization of the new capillaries. Finally, when

sufficient neovascularization has occurred, the angiogenic factors are downregulated or the local

concentration of the inhibitors increases. As a result, the endothelial cells become quiescent.

(Bisht et al., 2010)

Antiangiogenic

In 1971, it was hypothesized that inhibition of angiogenesis (anti-angiogenesis) would be

an effective strategy to treat human cancer, and an active search for angiogenesis inducers and

inhibitors began. Extensive research has led to the identification and isolation of several

regulators of angiogenesis, some of which represent therapeutic targets. (Ferrara et al., 2005)

Antiangiogenic compounds including herbal ingredients, nonherbal alkaloids, and microRNAs

can be used for the control and treatment of cancers. Several lines of evidence indicate that

alkaloid-rich plants have several interesting features that effectively inhibit angiogenesis.

(Alasvand at al., 2019)