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ABSTRACT

Fatty seed extracts of Vitellaria paradoxa (Sapotaceae), an indigenous plant of West Africa is
a popular remedy for arthritis and swellings. This study investigated the knowledge,
prevalence and pattern of use of the fatty extract also known as shea butter in clinically
diagnosed arthritic patients as well as its effects on acute (topical and systemic) and chronic
inflammation in rodents. The knowledge, prevalence and pattern of use were determined
using pretested questionnaire in clinically diagnosed patients. The antiinflammatory activity
was studied using xylene-induced edema of the mouse ear, carragennan-induced edema of the
rat paw, formaldehyde-induced arthritis and cotton pellet granuloma test in rats. The result
showed that of the 164 respondents, 94.1% know about shea butter and 59.6% have used it
mainly as a massage ointment once or twice daily. However, 73.7% of the users combine this
remedy with analgesics to achieve relief. The pharmacological tests showed that topical
application of shea butter inhibited the acute edema of the mouse ear. Oral administration
also inhibited the development of systemic acute edema of the rat paw in a non-dose related
manner. The inhibitory effect was significant (p<0.05) within 1 h post administration of
irritant. Twice daily topical application of shea butter inhibited the global edematous
response to formaldehyde arthritis whereas once daily administration was not effective. Shea
butter also caused a significant (P<0.05) non-dose related inhibition of granuloma tissue
growth on implanted cotton pellets. These findings showed that shea butter possesses
antinflammatory action for both acute and chronic inflammations and thus provide a
scientific rationale for its use in treatment of disorders of inflammation in traditional
medicine.

 

 

TABLE OF CONTENTS

Title page……………………………………………………………………………………….. i
Certification …………………………………………………………………………………….. ii
Dedication ……………………………………………………………………………………… iii
Acknowledgement …………………………………………………………………………….. iv
Table of Content……………………………………………………………………………….. vi
List of Abbreviations………………………………………………………………………….. ix
List of Figures …………………………………………………………………………………. xi
List of Tables…………………………………………………………………………………… xii
Abstract ……………………………………………………………………………………….. xiii
CHAPTER ONE: INTRODUCTION
1.1 Inflammation……………………………………………………………………… 1
1.2 Causes of Inflammation…………………………………………………………… 2
1.3 Types of Inflammation…………………………………………………………… 2
1.3.1 Acute Inflammation……………………………………………………………… 3
1.3.2 Chronic Inflammation…………………………………………………………….. 4
1.4 The Inflammatory Response……………………………………………………… 5
1.5 Mediators of Inflammation……………………………………………………….. 7
1.5.1 Plasma Derived Mediators………………………………………………………… 7
1.5.2
1.5.2.1
Cell Derived Mediators…………………………………………………………….
Lipid Derived Mediators…………………………………………………………
8 10
1.6 Biomarkers of Inflammation……………………………………………………… 12
1.7 Disorders of Acute Inflammation…………………………………………………. 13
1.8 Disorders of Chronic Inflammation………………………………………………. 13
1.8.1 Arthritis …………………………………………………………………………… 14
1.8.1.1 Types of Arthritis………………………………………………………………….. 14
1.8.1.1.1 Non-inflammatory Arthritis………………………………………………………. 14
1.8.1.1.2 Inflammatory Arthritis……………………………………………………………. 15
1.9 Agents Used in Management of Inflammation/ Arthritis……………………….. 16
1.9.1 Non-steroidal Antiinflammatory Drugs………………………………………….. 17
1.9.1.1 Non selective COX Inhibitors……………………………………………………….. 18
1.9.1.2 Selective COX -2 Inhibitors……………………………………………………. 20
1.9.2 Corticosteroids…………………………………………………………………… 21
1.9.3
1.9.4
Disease Modifying Anti-Rheumatic Drugs……………………………………….
Biological Disease Modifying anti-rheumatic drugs (bDMARDs)……………….
21
23
1.9.5 Medicinal Plants………………………………………………………………….. 24
1.10 Botanical Profile of Vitellaria paradoxa……………………………………….. 26
1.10.1 Plant Taxonomy…………………………………………………………………. 26
1.10.2 Plant Description………………………………………………………………… 27
1.10.3 Geographical Distribution…………………………………………………………. 28
1.10.4 Ethnomedicinal Uses………………………………………………………………. 28
1.10.5 Literature Review………………………………………………………………………. 29
1.11 Aim and Scope of Study……………………………………………………… 30
CHAPTER TWO: MATERIALS AND METHODS
2.0 Materials and methods…………………………………………………………….. 31
2.1 Materials…………………………………………………………………………… 31
2.1.1 Animals……………………………………………………………….…………… 31
2.1.2 Chemical and Solvents…………………………………………………………….. 31
2.1.3 Drugs………………………………………………………………………………. 31
2.1.4 Equipment…………………………………………………………………………. 31
2.1.5 Patients…………………………………………………………………………….. 32
2.1.6 Shea butter…………………………………………………………………………. 32
2.2 Methods……………………………………………………………………………. 32
2.2.1 Data collection…………………………………………………………………….. 32
2.2.2 Pharmacological tests…………………………………………………………… 33
2.2.2.1 Systemic acute inflammation of the rat paw…………………………………….. 33
2.2.2.2 Topical acute edema of the mouse ear…………………………………………. 33
2.2.2.3 Formaldehyde induced arthritis in rats………………………………………….. 34
2.2.2.4 Cotton pellet induced granuloma in rats……………………………………………… 35
2.2.3 Statistical analysis………………………………………………………………. 36
CHAPTER THREE: RESULTS
3.0 Results……………………………………………………………………………… 37
3.1 Demographic characteristics of respondents……………………………………… 37
3.2 Respondents’ knowledge of their disease Condition………………………………. 37
3.3 Respondents’ knowledge and use of shea butter………………………………….. 37
3.4 Effects of shea butter on systemic acute inflammation………………………… 48
3.5 Effects of shea butter on topical acute inflammation…………………………………. 48
3.6 Effects of shea butter on experimental arthritis………………………………… 48
3.2.4 Effects of shea butter granuloma formation…………………………………………. 48
CHAPTER FOUR: DISCUSSION AND CONCLUSION
4.0 Discussion and conclusion………………………………………………………………. 53
4.1 Discussion……………………………………………………………………………….. 53
4.2 Conclusion……………………………………………………………………………….. 56
References………………………………………………………………………………………. 57
Appendix 1……………………………………………………………………………………… 67
Appendix 2……………………………………………………………………………………… 69

 

 

CHAPTER ONE

INTRODUCTION
1.1 Inflammation
Inflammation is a defensive response that begins after cellular injury which may be caused by
microbes, physical agents (burns, radiation, and trauma), chemicals (toxins, caustic
substances), necrotic tissues and/or immunological reaction (Villarreal et al., 2001). It is also
defined as a reactive state of hyperemia and exudation from blood vessels with consequent
redness, heat, swelling and pain which a tissue manifests in response to physical or chemical
injury or bacterial invasion (Macdonald, 1988). It is a condition involving localized increase
in the number of leucocytes and variety of complex mediator molecules (Santosh et al.,
2010).
The history of inflammation is as old as man’s existence in this planet. Today, it is
recognized that inflammation is far more complex than might first appear from the simple
definitions given above. It is a major response of the immune system to tissue damage and
infection, although not all infection gives rise to inflammation (Punchard et al., 2004).
Therefore, inflammation is also the innate immune system response to attack on the body and
a major and complex reaction of the body against infection upon tissue injury (Khan et al.,
2010).
Inflammation is diverse, ranging from the acute inflammation associated with Staphylococcus
aureus infection of the skin (the humble boil), through to chronic inflammatory processes
resulting in remodeling of the artery wall in atherosclerosis; the bronchial wall in asthma and
chronic bronchitis, and the debilitating destruction of the joints associated with rheumatoid
arthritis (Punchard et al., 2004).
However, inflammation is a protective attempt by the body to remove the injurious
agent/stimuli and initiate a healing process although the complex events and mediators
involved in the inflammatory reaction can induce, maintain or aggravate many diseases (Sosa
et al., 2002). Hence, the control of inflammation is of great relevance in the treatment of
such pathologies.
Inflammation serves no useful purpose in certain disorders like rheumatoid arthritis and
becomes actually a component of the disease rather than part of the healing process.
1.2 Causes of inflammation
As derived from the first definition, the causes of inflammation include;
1. Physical agents: These include trauma, ultraviolet radiation, ionizing radiation, burn
and excessive cooling.
2. Irritants and corrosive chemicals: Acids, alkali and oxidizing agents.
3. Microbial infections: This is a common cause of inflammation. Some organisms cause
immunologically mediated inflammation through hypersensitivity reactions as is
obtained with parasitic infections and tuberculosis inflammation. While viruses cause
death of individual cells by intracellular multiplication, bacteria release exotoxins and
endotoxins which result in inflammatory reactions.
4. Tissue necrosis: Tissue necrosis could be the result of lack of oxygen or nutrient
resulting to inadequate blood flow to tissues. This leads to tissue death causing a
potent inflammatory stimulus.
5. Hypersensitivity reactions: hypersensitivity occurs when an altered state of
immunological response causes an inappropriate or excessive immune reaction with
damages to tissues. These reactions have cellular or chemical mediators similar to
those involved in inflammation (Hiley and Barber, 2000).
1.3 Types of inflammation
Inflammation can be variously classified;
Based on causative agent: Inflammation can said to be aseptic (sterile) or septic.
Based on histological features: It can be specific or non-specific (Heymer, 1985).
Based on exudates: It can be granulomatous, ulcerative, hermorrhagic, necrotizing,
pseudomembranous, fibrinous, catarrhal, serous or suppurative (Porth, 2007).
Based on onset/duration: It is classified as per acute, acute, sub-acute or chronic.
Clinically, however, depending on the defense capacity of the host and duration of response,
there are two major types of inflammation
(a) Acute inflammation
(b) Chronic inflammation (Mohan,2006).
This also largely depends on extent of injury, type of injury and vascularity of tissue involved
(Khan et al., 2010).
1.3.1 Acute inflammation
Acute inflammation occurs at the time scale of hours to days and represents an initial effort to
eliminate the injury. It is characterized by the cardinal signs of inflammation which are pain,
redness, swelling, heat and loss of function. The first four (classical signs) were described by
Celsius (30 BC-38 AD), while loss of function was added later by Galen even though this
attribute is disputed and the fifth sign has also been ascribed to Thomas Sydenham and
Virchow (Cotran et al., 1998; Chandrasoma and Taylor, 2005). The more the cardinal signs
present, the more acute an inflammation is said to be.
The process of acute inflammation is initiated by cells already present in all tissues, mainly
resident macrophages, dendritic cells, histocytes, Kupffer cells and mastocytes. At the onset
of an infection, burn or other injuries, these cells undergo activation and release inflammatory
mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting
increased blood flow cause the redness (rubor) and increased heat (calor). Increased
permeability of the blood vessels results in exudation (leakage) of plasma proteins and fluids
in the tissue (edema), which manifests itself as swelling (tumor). Some of the released
mediators such as bradykinin increase sensitivity to pain (hyperalgesia, dolor). The mediator
molecules also alter the blood vessels to permit the migration of leukocytes, mainly
neutrophils, outside of the blood vessels (extravasation) into the tissue. The neutrophils
migrate along a chemotactic gradient created by the local cells to reach the site of injury. The
loss of function (function laesa) is probably the fault of a neurological reflex in the response
to pain.
In addition to cell-derived mediators, several acellular biochemical cascade systems
consisting of preformed plasma protein act in parallel to initiate and propagate the
inflammatory response. These include the complement system activated by bacteria, and the
coagulation and fibrinolysis systems activated by necrosis, e.g. a burn or a trauma.
Finally, downregulation of the inflammatory response concludes acute inflammation.
Removal of the injurious stimuli halts the response of the inflammatory mechanism, which
requires constant stimulation to propagate the process. Additionally, many inflammatory
mediators have short half-lives and are quickly degraded in the tissue. Hence, inflammation
ceases once the stimulus has been removed (Cotran et al., 1998).
1.3.2 Chronic inflammation
Chronic inflammation is a prolonged and persistent acute inflammation usually due to the
presence of non-degradable pathogens, persistent foreign bodies and autoimmune reactions.
The prolongation leads to, a progressive shift in the type of cells present at the site of
inflammation and is characterized by simultaneous destruction and healing of the tissue for
the inflammation process. It is usually delayed in onset and may last up to several weeks,
many months or years and primarily mediated by interferon γ (IFN-γ)and other cytokines,
growth factors IL-1, IL-6, TNF-α, reactive oxygen species and hydrolytic enzymes (Ferrero-
Miliani et al., 2007). Chronic inflammation may arise following acute inflammation (e.g.
pneumonia) and also without acute inflammation (e.g. tuberculosis, viral infection and
rheumatoid arthritis). It is generally irreversible (Howarth et al., 1991). Chronic
inflammation may result in either tissues destruction (fibrosis) or a host of diseases such as
hay fever, atherosclerosis, and rheumatoid arthritis. The mononuclear cells: monocytes,
macrophages, lymphocytes, plasma cells and fibroblasts are usually involved in chronic
inflammation. It is characterized by a dominating presence of macrophages in the injured
tissue (Chandrosoma and Taylor, 2005).
1.4 The Inflammatory Response
Generally, the process of inflammation involves a series of events and each type of stimuli
provokes a characteristic pattern of response. Three distinct phases mediated by different
mechanisms are recognized in inflammatory response;
1. An acute transient phase characterized by local vasodilation and increased
capillary permeability;
2. A delayed subacute phase, most prominently characterized by infiltration of
leukocytic and phagocytic cells and;
3. A chronic proliferative phase in which tissue degeneration and fibrosis occur
(Robert and Morrow, 2001).
The mechanisms of host defense involve mainly the antibodies and leukocytes which are
found in bloodstream. This explains why vascular phenomenon plays a key role in
inflammation. During inflammation, blood vessels undergo series of changes that are
designed to maximize the movement of plasma proteins and circulating cells out of the
circulation and into the site of injury or infection.
Vasodilation is one of the earliest manifestations of acute phase of inflammation; sometimes,
it follows a transient constriction of arterioles, lasting a few seconds. Vasodilation is quickly
followed by increased permeability of the microvasculature, with the outpouring of proteinrich
fluid into the extravascular tissues.
The hallmark of acute phase of inflammation is increased vascular permeability which leads
to the escape of a protein-rich fluid (exudate) into the extravascular tissue. This loss of fluid
results in increased viscosity of blood and stasis.
Subsequently, the hemodynamic condition changes, and more white cells assume a peripheral
position along the endothelial surface. This process of leukocyte accumulation is called
margination. As a result, individual and then rows of leukocytes tumble slowly along the
endothelium and adhere transiently (a process called rolling), finally coming to rest at some
point where they adhere firmly. In time, the endothelium can be virtually lined by white cells,
an appearance called pavementing. After firm adhesion, leucocytes insert pseudopods into the
junctions between the endothelial cells, squeeze through inter endothelial junctions and
assume a position between the endothelial cell and the basement membrane. Eventually, they
traverse the basement membrane and escape into the extravascular space. Neutrophils,
monocytes, lymphocytes, eosinophils, and basophils all use the same pathway to migrate
from the blood into tissues. The process of margination, rolling, adhesion and transmigration
of leukocytes serve to deliver the leukocytes to the site of injury or infection (Khan and
Khan, 2010).
The following adhesion molecules are involved in the recruitment of circulating blood cells
and consequent transmigration:
1. The integrins,
2. Immunoglobulin-like proteins known as intercellular adhesion molecule (ICAM) 1
and 2, and vascular cell adhesion molecule (VCAM),
3. The selectins (L-, P- and E-selectin) and
4. The mucin-like selectin ligands (Villareal et al., 2001).
The ultimate function of cellular events in inflammation is to deliver leukocytes to the site of
injury or infection. Because resident tissue macrophages, mast cells, and endothelial cells
respond to injurious agents by secreting the cytokines TNF, IL-1, and chemokines
(chemoattractant cytokines), leukocytes migrate to tissues toward the site of injury by the
process of chemotaxis, defined simply as locomotion oriented along a chemical gradient.
Leukocytes ingest offending agents, kill bacteria and other microbes, and get rid of necrotic
tissue and foreign substances (Nairn, 2004).
1.5 Mediators of inflammation
Inflammatory mediators are soluble, diffusible molecules that act locally at the site of tissue
damage and infection, and at more distant sites. A variety of substances are released upon
damage to cells while others are synthesized during the events that follow tissue injury
(Dray, 1995).
1.5.1 Plasma derived mediators
Mediators derived from plasma include complements, complement-derived peptides and
kinins.
(a). The complement and complement derived peptides
The complement system is made up of serum and membrane bound proteins named due to
their ability to augment the effect of other components of the immune system. Their
functions include;
i. Lysis of cell
ii. Production of mediators that participate in inflammation and attract phagocytes,
iii. Opsonisation of organisms and immune complexes for clearance by phagocytosis
and
iv. Enhancement of antibody-mediated immune responses (Nairn, 2004).
Released through the classic or alternative pathways of the complement cascade,
complement-derived peptides (C3a, C3b, and C5a) increase vascular permeability, cause
smooth muscle contraction, activate leukocytes, and induce mast-cell degranulation. C5a is
a potent chemotactic factor for neutrophils and mononuclear phagocytes (Edward,2014).
Mast cell degranulation triggered by complements is independent of IgE (Delves, 2014).
(b). The kinin system
The kinins are important inflammatory mediators. The most important kinin is bradykinin, a
vasoactive protein which increases vascular permeability and vasodilation and, importantly,
activates phospholipase A2 (PLA2) to liberate arachidonic acid (AA). The vasodilatory
effect of bradykinin is largely mediated through stimulated release of endothelium derived
nitric oxide, prostacyclin and EDHF (endothelium derived hyperpolarizing factor)
(Mombouli et al., 1992). Bradykinin causes smooth muscle contraction and is a major
mediator involved in the pain response (Dray and Perkins, 1993).
1.5.2 Cell derived mediators
These mediators are derived from injured tissue cells or leukocytes recruited to the site of
inflammation. Mast cells, platelets, and basophils produce the vasoactive amines- serotonin
and histamine while macrophages and lymphocytes produce the cytokines.
(a) Histamine
Histamine causes arteriolar dilation, increased capillary permeability (Meager, 1999),
contraction of nonvascular smooth muscle, and eosinophil chemotaxis. It can stimulate
nociceptors responsible for the pain response. Its release is stimulated by the complement
components C3a and C5a and by lysosomal proteins released from neutrophils. Histamine
activity is mediated through the activation of one of four specific histamine receptors,
designated H1, H2, H3, or H4, in target cells. Most histamine-induced vascular effects are
mediated by H1 receptors. H2 receptors mediate some vascular effects but are more important
for their role in histamine-induced gastric secretion. Less is understood about the role of H3
receptors, which may be localized to the central nervous system. H4 receptors are located on
cells of hematopoietic origin, and H4 antagonists are promising drug candidates to treat
inflammatory conditions involving mast cells and eosinophils (allergic conditions) (Edward,
2014).
(b) Serotonin
Serotonin (5-hydroxytryptamine) is a vasoactive mediator similar to histamine found in mast
cells and platelets in the gastrointestinal tract and central nervous system. Serotonin also
increases vascular permeability, dilates capillaries, and causes contraction of nonvascular
smooth muscles (Edward, 2014).
(c) Cytokines
Cytokines, including interleukins 1–10, tumor necrosis factor α (TNF-α), and interferon γ
(IFN-γ) are produced predominantly by macrophages and lymphocytes but can be
synthesized by other cell types as well (Burke et al., 2006). Their role in inflammation is
complex. These polypeptides modulate the activity and function of other cells to coordinate
and control the inflammatory response. Two of the more important cytokines, interleukin-1
(IL-1) and TNF-α, mobilize and activate leukocytes, enhance proliferation of B and T cells
and natural killer cell cytotoxicity, and are involved in the biologic response to endotoxins.
IL-1, IL-6, and TNF-α mediate the acute phase response and pyrexia that may accompany
infection and can induce systemic clinical signs, including sleep and anorexia. In the acute
phase response, interleukins stimulate the liver to synthesize acute-phase proteins, including
complement components, coagulation factors, protease inhibitors, and metal-binding proteins.
By increasing intracellular Ca2+ concentrations in leukocytes, cytokines are also important in
the induction of phospholipase A2 (PLA2). Colony-stimulating factors (GM-CSF, G-CSF, and
M-CSF) are cytokines that promote expansion of neutrophil, eosinophil, and macrophage
colonies in bone marrow. In chronic inflammation, cytokines IL-1, IL-6, and TNF-α
contribute to the activation of fibroblasts and osteoblasts and to the release of enzymes such
as collagenase and stromelysin that can cause cartilage and bone resorption. Experimental
evidence also suggests that cytokines stimulate synovial cells and chondrocytes to release
pain-inducing mediators (Edward, 2014). Chemokines are chemoattrractant cytokines
(Meager, 1999).
1.5.2.1 Lipid derived mediators
Lipid-derived autacoids play important roles in the inflammatory response and are a major
focus of research into new antiinflammatory drugs. These compounds include the eicosanoids
such as prostaglandins, prostacyclin, leukotrienes, and thromboxane A and the modified
phospholipids such as platelet activating factor (PAF).
(a). Eicosanoids
Eicosanoids are synthesized from 20-carbon polyunsaturated fatty acids by many cells,
including activated leukocytes, mast cells, and platelets and are therefore widely distributed.
Hormones and other inflammatory mediators (TNF-α, bradykinin) stimulate eicosanoid
production either by direct activation of PLA2, or indirectly by increasing intracellular Ca2+
concentrations, which in turn activate the enzyme. Cell membrane damage can also cause an
increase in intracellular Ca2+. Activated PLA2 directly hydrolyzes AA, which is rapidly
metabolized via one of two enzyme pathways—the cyclooxygenase (COX) pathway leading
to the formation of prostaglandin and thromboxanes, or the 5-lipoxygenase (5-LOX) pathway
that produces the leukotrienes (Samuelsson, 1983)
(i). Prostaglandins
Cyclooxygenase catalyzes the oxygenation of AA to form the cyclic endoperoxide
prostaglandin G2 (PGG2), which is converted to the closely related PGH2. Both PGG2 and
PGH2 are inherently unstable and rapidly converted to various prostaglandins, thromboxane
A2 (TXA2), and prostacyclin (PGI1). In the vascular beds of most animals, PGE1, PGE2, and
PGI1 are potent arteriolar dilators and enhance the effects of other mediators by increasing
small vein permeability. Other prostaglandins, including PGF2α and thromboxane, cause
smooth muscle contraction and vasoconstriction. Prostaglandins sensitize nociceptors to painprovoking
mediators such as bradykinin and histamine and, in high concentrations, can
directly stimulate sensory nerve endings. TXA2 is a potent platelet-aggregating agent
involved in thrombus formation (Edward, 2014).
(ii). Leukotrienes
Found predominately in platelets, leukocytes, and the lungs, 5-lipoxygenase (5-LOX)
catalyzes the formation of unstable hydroxyperoxides from AA. These hydroxyperoxides are
subsequently converted to the peptide leukotrienes. Leukotriene B4 (LTB4) and 5-
hydroxyeicosatetranoate (5-HETE) are strong chemoattractants stimulating
polymorphonuclear leukocyte movement (Pelletier, 2003). LTB4 also stimulates production
of cytokines in neutrophils, monocytes, and eosinophils and enhances the expression of C3b
receptors. Other leukotrienes facilitate the release of histamine and other autacoids from mast
cells and stimulate bronchiolar constriction and mucous secretion. In some species,
leukotrienes C4 and D4 are more potent than histamine in contracting bronchial smooth
muscle (Edward, 2014).
(iii). Platelet activating factor (PAF)
Platelet activating factor (PAF) is also derived from cell membrane phospholipids by the
action of PLA2. PAF, synthesized by mast cells, platelets, neutrophils, and eosinophils,
induces platelet aggregation and stimulates platelets to release vasoactive amines and
synthesize thromboxanes. PAF also increases vascular permeability and causes neutrophils to
aggregate and degranulate (Vane et al., 1998).
(b). Nitric oxide
The role of the free radical gas nitric oxide (NO) in inflammation is well established. NO is
an important cell-signaling messenger in a wide range of physiologic and pathophysiologic
processes. Small amounts of NO play a role in maintaining resting vascular tone,
vasodilation, and anti-aggregation of platelets. In response to certain cytokines (TNF-α, IL-1)
and other inflammatory mediators, the production of relatively large quantities of NO
is stimulated. In larger quantities, NO is a potent vasodilator, facilitates macrophage-induced
cytotoxicity, and may contribute to joint destruction in some types of arthritis (Willoughby
and Flower, 1993; Edward, 2014).
(c). Substance P
This is a neuropeptide that works hand in hand with cytokines to mediate vascular
permeability and stimulate immune cell secretion. It also transmits pain and regulates blood
pressure (Burke et al., 2006).
1.6 Biomarkers of inflammation
Biomarker is anything that can be used as an indicator of a particular disease state or some
other physiological state of an organism. Inflammation is known to induce high levels of
acute phase proteins which include C-reactive protein, serum amyloid A, serum amyloid P,
fibrinogen and vasopressin. These proteins mediate a range of systemic effects including
fever, malaise and somnolence (Cotran and Kumar, 1998).Apart from acute phase reactant
proteins, other biomarkers include increases in white cell count, ESR, albumin (Hiley and
Barber, 2000) and increases in cytokines especially interleukin1-6 and TNFα. Also the
adhesion molecules are increased especially E-selectin, P-selectin, intercellular and vascular
cell adhesion molecules.
Plasma levels of circulating biomarkers of inflammation are believed to reflect the severity of
inflammation and extent of underlying condition. C-reactive protein (CRP) – the acute phase
protein synthesized primarily by the liver that is stable and readily measured – is currently the
most widely used biomarker of inflammation. Albumin, the most abundant protein in the
body is also employed (Khan et al., 2010).
1.7 Disorders of Acute Inflammation
Disorders associated with acute inflammation comprise of large, unrelated abnormalities that
underlie a vast variety of human diseases. Acute inflammation has been said to underlie skin
inflammation/blisters, myocardial infarction, appendicitis, prostatitis, bronchopneumonia and
gastric ulcer (Beck, 2014).
1.8 Disorders of Chronic Inflammation
Chronic inflammatory diseases are defined by long-term inflammatory processes directed at a
particular endogenous or exogenous antigen. However, some non-immune diseases have their
etiological origin in inflammatory processes e.g. cancer, atherosclerosis and ischaemic heart
disease (Cotran et al., 1998). Classical chronic inflammatory disorders include; arthritis,
inflammatory bowel disease, idiopathic pulmonary fibrosis. Within them however, there is
considerable overlap with autoimmune conditions such as Multiple Sclerosis and Type 1
diabetes (Heap, 2009).
More contemporary revelations show chronic inflammation to be a major factor in the
development of degenerative diseases and loss of youthful functions. Human aging is
characterized by a chronic, low-grade inflammation, and this phenomenon has been termed
“inflammaging.” Inflammaging is a highly significant risk factor for both morbidity and
mortality in elderly people, as most if not all age-related diseases share an inflammatory
pathogenesis (Franceschi and Campisi, 2014).
1.8.1 Arthritis
Arthritis (which literally means inflammation of the joint) is defined as inflammation of the
intra-articular tissue of one or more joints and characterized by an increased volume of intraarticular
fluid with specific features that vary depending on the cause. Features that may have
diagnostic significance include color, turbidity, hemorrhage, or exudate. In addition, arthritis
may be classified according to the cause, duration (acute or chronic), or the components of
the exudates (serous, fibrinous, purulent, macrophagic or lymphoplasmacytic) (Weisbrode
and Doige, 2001).It often results in stiffness, soreness, and in many cases, swelling. It is a
common disease with peak incidence in third to fourth decades of life and 3 to 5 times higher
in females (Mohan, 2000).
1.8.1.1 Types of arthritis
Inflammatory and non-inflammatory arthritis are the two most common forms of arthritic
condition. However, there are dozens of different arthritis types (Godman, 2013).
1.8.1.1.1 Non-inflammatory arthritis
(a). Osteoarthritis
Non-inflammatory arthritis refers mainly to osteoarthritis (OA). Though it still results in
inflammation of the joints, this inflammation is the result of wear and tear. In particular, OA
results from the breakdown of cartilage which allows the bones to rub together. This can be
painful. It usually occurs later in life. Injuring the joint can accelerate the progression of OA,
but even everyday activities can contribute to OA later in life. Being overweight and putting
extra strain on the joints can also cause OA. Non-inflammatory arthritis is most commonly
found in the knees, hips, spine, and hands (Godman, 2013). It can also cause problem in
shoulder or any other joint.
(b). Gout (metabolic arthritis)
This occurs when uric acid crystals form in and around joints, causing sudden and intense
pain, redness and swelling.
1.8.1.1.2 Inflammatory arthritis
Inflammatory arthritis is a term used to describe a group of conditions which affects the
immune system.
(a). Septic arthritis
This is as a result of infection in a joint that causes pain, redness, heat and swelling of the
affected joint. The patient may also have a fever and feel unwell. The most commonly
affected joint is the knee, but it can also occur in the ankle, hip or wrist. This is a serious
condition that needs treatment with antibiotics and an operation in which the joint is washed
out.
(b). Rheumatoid arthritis (RA)
Rheumatoid arthritis is an autoimmune disease in which there is joint inflammation, synovial
proliferation and destruction of articular cartilage (Tripathi, 2003). It is a typical example of
inflammatory arthritis. It is a chronic disorder that affects about 1% of the population
globally with females 3 times more prone to attack than males (Shikha, 2010). The condition
is associated with progressive disability, systemic complications, early death and
socioeconomic costs (Firestein, 2003).This type of arthritis is less common but more severe.
It occurs when the immune system attacks the tissue lining the joints, and can lead to pain,
swelling, stiffness and joint deformity. The joints most affected are the hands, wrists,
shoulders, knees or feet. The cause is not known.
Various leucocyte populations, orchestrated by several cytokines, chemokines, growth factors
and hormones, infiltrate rheumatoid tissues and increase injury (Montecucco and Mach,
2009). The lipid mediator PGE2 is produced during inflammatory responses and is thought to
be a major PG species working in RA pathogenesis, since a high level of PGE2 is detected in
the synovial fluid and tissues of RA patients (Sano, 2011) and PGE2 exhibits pleiotropic
biological actions. For example, PGE2 mediates pain and inflammatory responses (Walsh et
al., 2005).
Rheumatoid arthritis is said to be characterized by synovial inflammation and hyperplasia
(“swelling”), autoantibody production (rheumatoid factor and anti–citrullinated protein
antibody [ACPA]), cartilage and bone destruction (“deformity”), and systemic features,
including cardiovascular, pulmonary, psychological, and skeletal disorders (Mclnnes and
Schett, 2011).
It is diagnosed by rheumatoid factor, which are abnormal antibodies (IgG) which are present
in blood. These are reacted with antigen and form antigen-antibody complex that leads to
pain and inflammation of synovial membrane (Kaur et al., 2012). The American College of
Rheumatology requires at least four of the following seven criteria to confirm the diagnosis
(Rindflisch and Muller, 2005).
i. Morning stiffness around the joint that lasts at least 1 hour
ii. Arthritis of three or more joints for at least 6 weeks
iii. Arthritis of hand joints for at least 6 weeks
iv. Arthritis on both sides of the body for at least 6 weeks
v. Rheumatoid nodules under the skin
vi. Rheumatoid factor present in blood testing
vii. Evidence of rheumatoid arthritis on X-rays
1.9 Agents used in management of inflammation/ arthritis
Ideally, antiinflammatory drugs should have;
1) Effect on the prime causative factor,
2) Inhibitory or blocking effect on initial reaction set in a biological model by the prime
cause and thereby inhibit the established inflammation and
3) Effect on end result of established inflammation which probably modifies nonspecifically
the underlying symptoms of inflammation or enhances the repair process.
(Naik and Shett, 1976).
The goals of treatment of rheumatoid arthritis are to alleviate pain, control inflammation,
preserve and improve activities of daily living, and prevent progressive joint destruction.
Treatment of rheumatoid arthritis is characterized by a steady evolution of new agents and
new approaches. For over 50 years, medical treatment has been based on the use of nonsteroidal
anti-inflammatory drugs (NSAIDs), corticosteroids and synthetic disease-modifying
antirheumatic drugs (sDMARDs) (Favalli et al., 2014). Equally important in the management
of RA is nonmedical treatment, including patient education, physical therapy, occupational
therapy, orthotics, and rarely, surgery (Jisna et al., 2014).
1.9.1 Non- sterodial anti-inflammatory drugs
The non-steroidal antiinflammatory drugs (NSAIDs) are chemically heterogeneous groups of
compounds, which though chemically unrelated, share certain therapeutic actions and adverse
effects (Burke et al., 2006). They alleviate pain by counteracting the cycloxygenase (COX)
enzyme which synthesizes prostaglandins, creating inflammation. Most of these drugs have
in addition to their antiinflammatory property, analgesic and antipyretic activities. However,
these drugs cause adverse gastric reactions, inhibit renal function, reduce the efficacy of
diuretics and retard the angiotensin converting enzyme inhibitors (Dobrilla et al., 1997; Gaddi
et al., 2004). Some long term use of NSAIDs can cause gastric erosions leading to stomach
ulcers and in extreme cases, severe hemorrhage resulting in death (Hayliyar et al., 1992;
Ament and Childers, 1997). Other adverse effects of NSAIDs are exacerbation of asthma and
kidney damage (Rang et al., 2007).NSAIDs are among the most frequently prescribed drugs
in modern medicine. They are very effective in the alleviation of pain, fever and
inflammation, and millions of patients worldwide have found relief in their use since the
discovery of the soothing properties of willow bark more than 3,500 years ago (Meek et al.,
2010). In 1963, indomethacin was introduced to treat rheumatoid arthritis, and this was
followed by the development of many other antiinflammatory agents.
NSAIDs can be broadly grouped into the non-selective COX inhibitors and selective COX-2
inhibitors. Some drugs, notably pyrazolones and acetaminophen, were previously not
classified into this group because they did not inhibit COX enzymes. In recent years, new
COX isoenzymes have been described, such as COX-2b and COX-3 that can be selectively
antagonized by these drugs, and therefore would fit into the NSAID category
(Chandrasekharan et al., 2002).
1.9.1.1Non-selective COX inhibitors
The non-selective COX inhibitors affect both COX-1 and COX-2 enzymes. They include the
salicylic acid derivatives, indole and indene acetic acids, arylpropionic acids, anthranillic
acids, heteroaryl acetic acids, enolic acids and the alkanones (Burke et al., 2006).
(a) Salicylic acid derivatives
These comprise esters of salicylic acids and salicylate esters of organic acids and salt of
salicylic acid (Burke et al., 2006). They have antipyretic, analgesic and anti-inflammatory
properties. A typical one is aspirin which is widely consumed and is the standard for
comparison and evaluation of the others (Amann and Peskar, 2002).
Apart from their effect on biosynthesis of prostaglandins, it has been observed that salicylates
have the capacity to suppress a variety of antigen-antibody reactions e.g. inhibition of antibody
production, for antigen-antibody aggregation and of antigen-induced release of
histamine (Guyton and Hall, 2007). At high dose, salicylates also inhibit the activation of NF-
κB in vitro (Yin et al., 1998).
(b). Indole and indene acetic acids
Indomethacin is a methylated indole derivative with prominent antiinflammatory property.
Others include sulindac, a prodrug whose antiinflammatory activity resides in its sulfide
metabolite (Haanen, 2001).
(c). Oxicams
Oxicams inhibit COX-I and II and possess good antiinflammatory properties. Oxicams
include piroxicam, meloxicam and tenoxicam (Nilsen, 1994; Burke et al., 2006).Meloxicam,
has a lower frequency for gastrointestinal side effects than piroxicam and several other
NSAIDs (Karen and Knox, 2007).
(d). Alkanones
Nabumetone was approved in 1991 and has substantial efficacy in treatment of rheumatoid
arthritis and osteoarthritis (Davies, 1997). It is principally 6-methoxy-2-naphythyl acetic acid,
potent non-selective inhibitor of COX enzyme (Patrignani et al., 2003).
(e). Heteroaryl acetic acids
These include tolmetin and ketorolac which are structurally related but with different
pharmacological features. Tolmetin was introduced in 1976 in the USA possessing typical
NSAID properties with strong antiinflammatory effects (Morely et al., 1982). Ketorolac has
moderately effective antiinflammatory effect with more potent analgesic property (Buckley
and Brodgan, 1990). Diclofenac on the other hand is a phenylacetic acid derivative
specifically developed as an antiinflammatory agent which also reduces intracellular
concentration of free arachidonate in leucocytes (Ebadi, 1997).
(f).Arylpropionic acids
These are approved for use in symptomatic treatment of rheumatoid arthritis, ankylosing
spondylitis, acute gouty arthritis and osteoarthritis. Ibuprofen is the most commonly used and
first member of the class to come into general use. Others include naproxen, ketoprofen,
flurbiprofen, fenoprofen and oxaprozin (Burke et al., 2006).
(g).Anthranillic acids
The phenylanthranillic acid was discovered in the 1950s as derivatives of N-phenylacetic
acids. They comprise the fenamates such as mefenamic acid, meclofenamic acid and
flufenamic acid (Burke et al., 2006; Guyton and Hall, 2007). They show no clear superiority
in antiinflammatory activity and may produce more adverse effects than other NSAIDs
(Karen and Knox, 2007).
1.9.1.2Selective COX-2 inhibitors
These are agents that selectively inhibit COX-2 while sparing COX-1 enzymes. They include
the diaryl substituted pyrazole (celecoxib) analogous to diclofenac, the diaryl substituted
furanone (rofecoxib), the indole acetic acid (etodolac), the sulphonanilide (Nimesulide)
(Robert and Morrow, 2001) and the new agents valdecoxib, peracoxib, lumiracoxib and
etoricoxib. Valdecoxib and rofecoxib have been withdrawn from the market in view of their
adverse event profile. The relative degree of selectivity for COX-2 inhibition by these agents
is shown below with the first approved member having the lowest degree of COX-2
selectivity. Lumiracoxib=Etoricoxib>Valdecoxib=Rofecoxib>>Celecoxib (Brune and Hinz,
2004). Actually, COX-2 inhibitors are effective for decreasing pain in RA with less
gastrointestinal side effects (Sano, 2011), although some concerns of risk of cardiovascular
events have been expressed (Mukherjee and Topol, 2003).
1.9.2 Steroidal antiinflammatory drugs (corticosteroids)
Glucocorticoids reduce inflammation or swelling by binding to cortisol receptors. These
drugs are often referred to as corticosteroids. They suppress inflammation rather than address
its underlying causes by inhibiting phospholipase A2 and suppressing expression of COX II
and the prostaglandin production it mediates. Corticosteroids also inhibit the transcription of
many genes coding for pro-inflammatory proteins like the cytokines (Newton et al., 1998).
The glucocorticoids are the most potent antiinflammatory drugs available (Ukwe, 2004).
Examples are prednisolone and dexamethasone.
1.9.3 Disease modifying anti-rheumatoid drugs (DMARDs)
The disease-modifying anti-rheumatic drugs are a category of unrelated drugs defined by
their use in rheumatoid arthritis to slow down disease progression. The term is often used in
contrast to non-steroidal antiinflammatory which refers to agents that treat the inflammation
but not the underlying cause. Although their use was first propagated in rheumatoid arthritis
(hence their name), the term has come to pertain to many other diseases, such as Crohn’s
disease, systemic lupus erythematosus (SLE), idiopathic thrombocytopenic purpurea (ITP),
myasthenia gravis and various others. Many of these are autoimmune disorders (Laurence et
al., 2006). The DMARDs include hydroxychloroquine, tumor necrotic factor (TNF) inhibitors
such as adalimumab, etanercept and golimumab; gold salts like sodium aurothiomalate and
auranofin; methotrexate, azathioprine, cyclophosphamide, biologics (infliximab), leflunomide
and D-penicillamine.
Some DMARDs are mild chemotherapeutic agents but use immunosuppression, a side-effect
of chemotherapy as its main therapeutic benefit. The term was originally introduced to
indicate drugs that reduce evidence of processes thought to underlie inflammatory diseases,
such as a raised erythrocyte sedimentation rate, reduced haemoglobin level, raised
rheumatoid factor level and more recently, raised C-reactive protein level. More recently, the
term has been used to indicate a drug that reduces the rate of damage to bone and cartilage.
DMARDs can be further subdivided into traditional small molecular mass drugs synthesized
chemically and newer ‘biological’ agents produced through genetic engineering (Nandi et al.,
2008).
DMARDs work by curbing the underlying processes that cause certain forms of
inflammatory arthritis including rheumatoid arthritis (RA), ankylosing spondylitis and
psoriatic arthritis. These drugs not only treat arthritis symptoms, but they can also slow down
progressive joint destruction. Some of these medications have been used to treat other
conditions, such as cancer or inflammatory bowel disease, or to reduce the risk of rejection of
a transplanted organ. Although these agents operate by different mechanism, many of them
can have similar impact on the course of a condition (Nandi et al., 2008).
Combinations of DMARDs are often used together, because each drug in the combination
can be used in smaller dosage than if it were given alone, thus reducing the risk of side
effects (Capell et al., 2007). DMARDs help control arthritis but do not cure the disease or
cause a “rebound flare” with no assurance that disease control will be reestablished upon
resumption of the medication (Nandi et al., 2008). They have varied mechanisms of action.
For instance, sulfasalazine suppresses IL-1 and TNF-alpha, induces apoptosis of
inflammatory cells and increases chemotactic factors. The gold salt inhibits macrophage
activation; cyclosporine inhibits calcineurin while methotrexate and azathiopurine have
antifolate and purine synthesis inhibitory activities (Capell et al., 2007) respectively.
Methotrexate (MTX) has long been considered the ‘gold standard’ disease modifying antirheumatic
drug (DMARD) for RA (McGeough et al., 2011). Methotrexate was first
introduced in rheumatology in 1962 for treatment of psoriatic arthritis (Black et al., 1964)
based on the wrong assumption of a possible interference with proliferation of connective
tissue. Its mode of action was not clear but the increase in adenosine levels and reduction in
proinflammatory cytokines seems to play a more predominant role than inhibition of cell
proliferation (Cutollo et al., 2002). Methotrexate has been recognized as the DMARD with
the most long term effectiveness and safety for RA before the introduction of biologic agents
(Sokka and Pincus, 2002).
With the identification of TNF as a key player in inflammatory and destructive pathway of
the disease, interest was shifted away from agents with poorly understood mechanism of
action towards therapies targeted to key molecules and cells involved in RA pathogenesis
(Feldmann et al., 1996). The first biological agents that were registered were tumour necrosis
factor alpha (TNFα) inhibitors: etanercept (FDA approved 1998) and infliximab (1999),
followed by adalimumab (2002). Infliximab is a chimeric monoclonal antibody, administered
intravenously. Etanercept is a fusion protein consisting of two identical chains of the
recombinant human TNF-receptor p75 monomer fused with the Fc domain of human IgG1,
and adalimumab is a human monoclonal antibody against TNFα. The latter 2 drugs are both
administered subcutaneously. Advances in understanding the role of T cells, B cells and
cytokines such as IL-6 has paved way to development of additional biologic drugs beyond
TNF inhibitors.
1.9.4 Biologic disease modifying anti-rheumatic drugs (bDMARDs)
These biologic agents(bDMARDs) include: Anakinra, a recombinant form of the IL1 receptor
antagonist (IL1-RA, administered subcutaneously); Rituximab, a β-cell depleting agent;
Abatacept, a recombinant dimerized form of cytotoxic T-lymphocyte antigen 4 (CTLA4) that
blocks T-cell co-stimulation, administered intravenously; Tocilizumab, a human monoclonal
antibody against the IL-6 receptor administered intravenously; and two recent TNFα
blockers, which are both administered subcutaneously: certulizumab pegol, a pegylated Fab
fragment from a humanized monoclonal antibody; and golimumab, a human monoclonal
antibody (2009)) (Bugatti et al., 2007; Fonseca et al., 2009; Hetland, 2011 ). They have
shown good efficacy and safety in patients with RA and are now widely used in clinical
practice (Favalli et al., 2009; Atzeni et al., 2013).
1.9.5 Medicinal plants with antiinflammatory activity
Since time immemorial, indigenous plants have been a major source of medicine because the
different constituents present in them have immense therapeutic value (Meher et al., 2011).
About 80%of people in developing countries still rely on traditional medicines of both plant
and animal origin. Side effects remain one of the problems of the long term use of medicines
as required in inflammatory rheumatoid arthritis and other inflammatory conditions. Thus
there is need for anti-arthritic drug with less severe side effects. Interest in alternative
treatment of arthritis (Gaby, 1999; Jacobs et al., 2001) has promoted use of alternative
medicine in western world but scientific evidence of anti-arthritic efficacy is lacking in some
cases. Also, there is growing realization that apart from being safer, economical and easily
available, herbs, phytochemicals and herbal products can influence the course of
inflammatory diseases and may provide an amalgamation of nutritional substances, which
help in restoring and maintaining wear and tear of tissues (Santosh et al., 2010). The use of
herbal medicine is becoming popular due to toxicity and side effect of allopathic medicine
and potential benefit of herbs.
Plants are important source of new therapeutic agents. Some medicinal plants that have been
studied for antiinflammatory activity include Aspila africana (Okoli et al., 2006b),
Schewenckia americana. L. (Solancaceae) (Nwabunike et al., 2014), Securidaca
longipedunculata Fres. (Polygalaceae) (Okoli et al., 2006a), Culcasia scadens P. Beauv
(Okoli and Akah, 2000), Acanthus monthanus (Okoli et al., 2008), Polygonum cuspidatum
(Bralley et al., 2008) and Sphaeranthus indius (Asteraceae) (Meher et al., 2011).A
comprehensive review on antiinflamatory activity of plants has shown medicinal plants as
reservoir for development of potent and safer drugs (Okoli et al., 2003). On the other hand,
plants used in rheumatoid arthritis include Piper nigrum L. (Piperaceae), Calotropis procera
L. (Asclepiadaceae) and Mangifera indica L. (Anacardiaceae) (Kaur et al., 2012).
Plant constituents that can modulate the expression of pro-inflammatory signals have
potential against arthritis. They include flavonoids, terpenoids, quinines, catechins, alkaloid,
anthocyanins and anthoxanthins.
Flavonoids are known to have anti-inflammatory activity (Bellik and Laid, 2013). It has been
elucidated that flavonoids are major anti-inflammatory agents. Some of them act as
phospholipase inhibitors while others act as TNF-α inhibitors in different inflammatory
conditions. Biochemical investigations have also shown that flavonoids can inhibit both
cyclooxygenase and lipoxygenase pathways of arachidonic metabolism depending upon their
chemical structures (Jang et al., 2002).Terpenoids significantly inhibit the development of
chronic joint swelling. Terpenoids may affect different mechanisms relevant to inflammation
arising in response to varied etiological factors (Changa et al., 2008). Antiinflammatory and
antinociceptive activity of terpenoids has been reported (Santos and Rao, 2000).It has also
been reported that terpenoids are natural inhibitors of NF-kB signaling with both
antiinflammatory and anticancer potentials (Salminen et al., 2008). The topical
antiinflammatory action of sesquiterpene is caused by inhibition of arachidonic acid
metabolism (Kumar et al., 2013). Phenolic compounds are reported to have antiinflammatory
and antioxidant activities (Frautschy et al., 2001).Alkaloids based on pyridine ring system
have been reported to have striking anti-inflammatory activity, e.g Berberine from Berberis is
a traditional remedy against rheumatism (Kupeli et al., 2002).
Plants commonly used to treat arthritis include Allium sativum, Allium cepa (Liliaceae), Aloe
vera (Liliaceae), Zingiber officinale (Zingiberaceae), Ginkgo biloba (Ginkgobaceae) and
Ananas comosus (Bromeliaceae) amongst others (Vikrant et al., 2011).
Moreover, scientific studies on anti-arthriticactivity have been carried out with significant
positive result in a lot of the medicinal plants; e.g.Costus speciousus koen (Costaceae) (Shruti
et. al., 2012), Strychnos potatorum (Longiniaceae) (Ekambaram et. al., 2010) and bark extract
of Alangium salvifolium Wang (Alangiaceae) (Jubie et al, 2008). Carpolobia lutea was
reported to possess both antiinflammatory and anti-arthritic properties (Iwu and Anyanwu,
1982) and has also been studied for analgesic action (Jackson et al., 2011). However, many
herbal medicines for inflammation and rheumatism have not undergone thorough scientific
investigations.
1.10 Botanical profile of Vitellaria paradoxa
1.10.1 Plant Taxonomy
Kingdom – Plantae
Division – Tracheophyta
Class – Angiospermae
Sub-class – Eudicots
Orders – Ericales
Family – Sapotaceae
Genus – Vitellaria (C.F Gaertn)
Specie – Vitellaria paradoxa
Subspecie – Vitellaria paradoxa nolitica
Synonyms – Butyrospemum parkii (Kotschy) and Butyrospemum paradoxum
(Henry and Nair, 1983).
Vernacular names – “Shea tree” (English),
“Dan ka’raye”, “K’awara” and “Ka’danya” (Hausa),
“Aku makpa” or “Emi-emi” (Yoruba),
“Okwuma” (Igbo) (Hall et al., 1996).
1.10.2 Plant description
The shea tree, which resembles an oak (Quercus species) in its general size and form, grows
up to 20 m (65 ft) tall and 1 m (3 ft) in diameter, with a dense, many-branched crown. It is
deciduous, but appears evergreen, because new leaves emerge as the old ones fall.
The bark is thick and corky, deeply fissured both horizontally and longitudinally, and fireresistant.
It is slash pale pink, secreting white latex when cut as do the broken twigs or
petioles (Orwa et al., 2009)
The leaves are tough, leathery and elliptical to oblong, with entire margins, and are clustered
at the branch tips or twig (alternate to whorled). Juvenile leaves rust-red and pubescent, later
coriaceous, glabrous and shiny dark green. The leave is 12-25 cm long and 4-7 cm wide.
The flowers are cream to brown, in dense terminal clusters, and are insect-pollinated. The
flowers develop in the axils of scale leaves, at the extremities of dormant twigs, from buds
formed 2 years previously. Each inflorescence usually contains 30-40 flowers, though 80-100
have been recorded. Individual flowers are subtended by scarious, brown, ovate or lanceolate
bracteoles, which are abscised before flower opening (Orwa et al., 2009).
The fruits are round to elliptical drupes, 3 to 6 cm (1.1-2.25 in) long, borne on peduncles
(fruit stalks) 1 to 3 cm (0.5 to 1.25 in) long. The fruits are drupes, with fleshy greenish yellow
pulp surrounding a hard- but thin-shelled seed, an egg-shaped kernel that weighs around 3g
(about 1/10 of an ounce) (Kar and Mital, 1981).The shea nut is surrounded by a fragile
shining shell with a large, round, rough hilum on a broad base (Orwa et al., 2009).
1.10.3 Geographical distribution
The shea tree is an indigenous plant to West Africa occupying Mali, Cameroon, Cote d’voire,
Ghana, Guinea, Togo, Nigeria, Sudan, Senegal and Ethiopia (Okullo et al., 2004) Burkina
Faso and Uganda (Lovett and Haq, 2000). However, the genus Vitellaria is considered by
botanical authorities as monospecific. The subspecie V. Paradoxa is restricted to Western
Africa while V. nilotica to Eastern Africa.
1.10.4 Ethnomedicinal uses
The fruit pulp of V. paradoxa is edible and is said to have a laxative effect (Soladoye, et al.,
1989). Its roots and barks are ground to paste and administered orally to cure jaundice
(Ampofo, 1983). Over the years, the fatty extract of the seeds of V. paradoxa (shea butter)
has been used in cosmetology and confectionary. The shea bark has been employed to treat
minor cuts and scratches. The leaves can be eaten raw while extracts of the leaves are used to
relieve headache and as an eyebath. The nut shell has in-built mosquito repellant and the
butter is used as moisturizing creams and lotions and for soap and chocolate manufacturing
(Abidemi et al., 2009; George et al., 2011). It has been claimed to have antiinflammatory,
emollient and humectant properties (Akihisia et al., 2010).
The main use of shea butter in the Western world is in chocolate manufacturing where the
similarity in composition and crystallisation properties between shea butter and cocoa butter
is utilized. Shea butter has served as an antiinflammation balm and used to heal bruises,
dermatitis and all forms of massage therapy. Shea butter is used as a base for medicinal and
cosmetic ointment, as pomade, as a hair cream, for soap production and as an illuminant
(Abbiw, 1990).
Unrefined shea butter is claimed to be good for dry skin, skin rashes, skin peeling after
tanning, sunburn, blemishes, cracked heels and skin, itchy skin, frost bite, stretch marks,
scars, chapped lips, eczema, small wounds or scrapes, diaper rash, hair moisturizer, burns,
athlete’s foot, insect bites and stings, arthritis, muscle fatigue, pets’ (dogs and horses) dry
skin, sunburn, scrapes, and as a natural mechanics lubricant (Wan and Wakilyn, 1997).
In southeast Nigeria, shea butter is a common remedy for swellings. It is used as massage
ointment in arthritis, as cough remedy and nasal decongestant in children. It is also used to
enhance hair growth in women.
1.10.5 Literature review
Studies on V. paradoxa have ranged from domestication of shea tree (Yidana, 2003), increase
in yield efficiency and purification of shea butter to morphological character variation studies
of shea tree (Djekota et al., 2014). Because of its role in combating food insecurity and
sustaining rural livelihoods, an assessment of the nutritional composition of shea fruit pulp
was carried out in Uganda. It was found to be rich in vitamin C, total carbohydrates and crude
fiber (Okullo et al., 2010). Phytochemical screening of the plant parts revealed the presence
of carbohydrates (free reducing sugars, ketoses, pentoses and starch), saponins, steroids,
tannins and alkaloids (Ndukwe et al., 2007).A unique healing property has been ascribed to
shea tree which justifies the name ‘tree of life’ though there is limited scientific backing to
the healing claims. Its fatty extract (shea butter) has been shown to be efficacious in nasal
congestion as decongestant (Tella, 1979). The bioactive substance in shea butter resides in
the unsaponifiable fraction and includes vitamin E, catechins and triterpenes (cinnamic acid
esters, alpha- and beta-amyrin, parkeol, buytospermol, and lupeol) (Badifu, 1989).Shea butter
is composed of five principal fatty acids: palmitic, stearic, oleic, linoleic, and arachidic. The
fatty acid composition is dominated by stearic and oleic acids, which together account for 85-
90% of the fatty acids. The relative proportions of these two fatty acids produces differences
in shea butter consistency (Maranz et al., 2004).
1.11Aim and scope of study
This study was to investigate the antiinflammatory activity of the fatty extract of V. paradoxa
(shea butter), to ascertain the basis for its use in inflammatory disorders. The study involved
the determination of the prevalence of use of shea butter amongst clinically diagnosed
arthritic patients using pre-tested questionnaire and investigation of the antiinflammatory
activity using rodent models of acute and chronic inflammation.

 

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